Mechanism of Intermolecular Hydroacylation of Vinylsilanes Catalyzed by a Rhodium(I) Olefin Complex: a DFT Study

Journal of Molecular Modeling. Jun, 2011  |  Pubmed ID: 21713414

Density functional theory (DFT) was used to investigate the Rh(I)-catalyzed intermolecular hydroacylation of vinylsilane with benzaldehyde. All intermediates and transition states were optimized completely at the B3LYP/6-31G(d,p) level (LANL2DZ(f) for Rh). Calculations indicated that Rh(I)-catalyzed intermolecular hydroacylation is exergonic, and the total free energy released is -110 kJ mol(-1). Rh(I)-catalyzed intermolecular hydroacylation mainly involves the active catalyst CA2, rhodium-alkene-benzaldehyde complex M1, rhodium-alkene-hydrogen-acyl complex M2, rhodium-alkyl-acyl complex M3, rhodium-alkyl-carbonyl-phenyl complex M4, rhodium-acyl-phenyl complex M5, and rhodium-ketone complex M6. The reaction pathway CA2 + R2 → M1b → T1b → M2b → T2b1 → M3b1 → T4b → M4b → T5b → M5b → T6b → M6b → P2 is the most favorable among all reaction channels of Rh(I)-catalyzed intermolecular hydroacylation. The reductive elimination reaction is the rate-determining step for this pathway, and the dominant product predicted theoretically is the linear ketone, which is consistent with Brookhart's experiments. Solvation has a significant effect, and it greatly decreases the free energies of all species. The use of the ligand Cp' (Cp' = C(5)Me(4)CF(3)) decreased the free energies in general, and in this case the rate-determining step was again the reductive elimination reaction.

[Comparison of Short-term Postoperative Outcomes Between Hand-assisted Laparoscopic and Conventional Sigmoidectomy]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Jun, 2011  |  Pubmed ID: 21713711

To compare the safety and efficacy perioperatively between hand-assisted laparscopic surgery (HALS) and conventional open sigmoidectomy.

Metformin Induces G1 Cell Cycle Arrest and Inhibits Cell Proliferation in Nasopharyngeal Carcinoma Cells

Anatomical Record (Hoboken, N.J. : 2007). Aug, 2011  |  Pubmed ID: 21717584

It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP-activated protein kinase (AMPK). But its role in nasopharyngeal carcinoma (NPC) is not known. Here, we reported for the first time that 1-50 mM of metformin in a dose- and time-dependent manner suppressed cell proliferation and colony formation in NPC cell line, C666-1. Further studies revealed that the protein level of cyclin D1 decreased and the percentage of the cells in G0/G1 phase increased by 5 mM metformin treatment. Metformin also induced the phosphorylation of AMPK (T172) in a time-dependent manner. Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells. In a summary, metformin prevents proliferation of C666-1 cells by down-regulating cyclin D1 level and inducing G1 cell cycle arrest. AMPK-mediated inhibition of mTORC1 signaling may be involved in this process.

Methamphetamine-Associated Psychosis

Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology. Jul, 2011  |  Pubmed ID: 21728034

Methamphetamine (METH) is a frequent drug of abuse in U.S. populations and commonly associated with psychosis. This may be a factor in frequent criminal justice referrals and lengthy treatment required by METH users. Persecutory delusions and auditory hallucinations are the most consistent symptoms of METH-associated psychosis (MAP). MAP has largely been studied in Asian populations and risk factors have varied across studies. Duration, frequency and amount of use as well as sexual abuse, family history, other substance use, and co-occurring personality and mood disorders are risk factors for MAP. MAP may be unique with its long duration of psychosis and recurrence without relapse to METH. Seven candidate genes have been identified that may be associated with MAP. Six of these genes are also associated with susceptibility, symptoms, or treatment of schizophrenia and most are linked to glutamatergic neurotransmission. Animal studies of pre-pulse inhibition, attenuation of social interaction, and stereotypy and alterations in locomotion are used to study MAP in rodents. Employing various models, rodent studies have identified neuroanatomical and neurochemical changes associated with METH use. Throughout this review, we identify key gaps in our understanding of MAP and suggest potential directions for future research.

[Relation of GSTP1 and CYP2E1 Polymorphisms with Susceptibility to Acute Leukemia]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jun, 2011  |  Pubmed ID: 21729529

This study was aimed to investigate the relation of glutathione S-transferase pI (GSTP1) and cytochrome P450 enzyme 2E1 (CYP2E1) gene polymorphisms with the susceptibility to acute leukemia (AL) in Chinese population. The GSFP1 and CTP2E1 gene polymorphisms in 150 patients with AL and 150 patients with non-hematological diseases or non-tumor as controls were detected by means of case-control paired 1:1 method and ligase detection reaction (LDR) techniques. The results indicated that the frequently of G allele and Ile/Val + Val/Val of GSTP1 gene (26.7%and 44% respectively) in AL group were higher than those in control group (10% and 16% respectively); the AL risk for persons with Ile/Val + Val/Val was 3.260-fold (95%CI = 1.527 - 5.236) of persons with Ile/Ile. The further stratified analysis showed the frequency of Ile/Val + Val/Val in AML group was higher than that in control group (55% vs 16%, p < 0.05); the AML risk for persons with Ile/Val + Val/Val was 2.214-fold (95% CI = 1.009-3.260) as persons with Ile/Ile. The frequencies of C2 allele (16.7%) and C1C2/C2C2 of CYP2E1 gene (30%) in AL group seemed higher than those in control groups (13.9% and 26%), but the difference between them was not statistical significant (p > 0.05). The further stratified analysis showed that C1C2/C2C2 of CYP2E1 gene occurred more frequently in AML group (36%) than that in control group (32%), but there was no statistical difference between them (p > 0.05). Combined genotype analysis showed that the AML risk for persons in combination of lle/Val + Val/Val of GSTP1 gene with C1C2 + C2C2 of CYP2E1 gene increased by 3.208-fold. It is concluded that the GSTP1 gene is related with susceptibility to AML, the AL risk for persons with lle/Val + Val/Val of GSTP1 gene decreased, while CYP2E1 gene is not related with susceptibility to AL, the AML risk for persons in combination of GSTP1 wildtype with CYP2E1 hybrid and mutant genotype can be further decreased.

[Apoptosis-inducing Effect of Clostridium Difficile Toxin A on K562 Cells and Its Mechanism]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jun, 2011  |  Pubmed ID: 21729540

This study was purposed to investigate the growth inhibition and apoptosis-inducing effect of Clostridium difficile toxin A (TcdA) on the leukemia cell line K562. The proliferative activity of K562 cells exposed to Tcd A was tested by MTT assay, cell apoptosis was detected by flow cytometry; immunocytochemistry and colorimetric assay were employed to detect the protein expressions of BCL-2/BAX and the activity of Caspase-3, respectively. The results indicated that the proliferation of K562 cells was inhibited in a time-and dose-dependent manner after exposure to Tcd A for 24, 48 and 72 hours, the cells displayed the typical apoptotic, morphological changes, the expression of BCL-2 protein was down-regulated but the expression of BAX protein was signficantly increased, compared with control group (p < 0.05). In addition, caspase-3 was activated in a concentration-dependent manner. It is concluded that Tcd A inhibits cell growth of K562 by inducing apoptosis, and the up-regulation of BAX protein and activation of caspase-3 may play important roles in these processes.

[New Advance of Research on Therapy of Severe Acute Radiation Sickness with Mesenchymal Stem Cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jun, 2011  |  Pubmed ID: 21729581

Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress. In this review, the biological characteristics and new research advance on MSC in treatment of severe acute radiation sickness are summarized and discussed.

Genome Sequence and Global Sequence Variation Map with 5.5 Million SNPs in Chinese Rhesus Macaque

Genome Biology. 2011  |  Pubmed ID: 21733155

Rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate animal in biomedical research. A global map of genetic variations in rhesus macaque is valuable for both evolutionary and functional studies.

In Situ Intestinal Perfusion of Irinotecan: Application to P-gp Mediated Drug Interaction and Introduction of an Improved HPLC Assay

Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques. 2011  |  Pubmed ID: 21733405

To determine experimentally the intestinal permeability of the anticancer prodrug irinotecan, and to quantify the amount of its cytotoxic metabolite SN-38 that is intestinally excreted (exsorped) as a predictor of intestinal toxicity, and to assess the effect of p-glycoprotein (p-gp) inhibitors (verapamil as a model) on the permeability and toxicity of irinotecan.

Epitopes Immediately Below the Base of the V3 Loop of Gp120 As Targets for the Initial Autologous Neutralizing Antibody Response in Two HIV-1 Subtype B-infected Individuals

Journal of Virology. Sep, 2011  |  Pubmed ID: 21734041

Epitopes that drive the initial autologous neutralizing antibody response in HIV-1-infected individuals could provide insights for vaccine design. Although highly strain specific, these epitopes are immunogenic, vulnerable to antibody attack on infectious virus, and could be involved in the ontogeny of broadly neutralizing antibody responses. To delineate such epitopes, we used site-directed mutagenesis, autologous plasma samples, and autologous monoclonal antibodies to map the amino acid changes that led to escape from the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals. Additional mapping of the epitopes was accomplished by using alanine scanning mutagenesis. Escape in the two individuals occurred by different pathways, but the responses in both cases appeared to be directed against the same region of gp120. In total, three amino acid positions were identified that were independently associated with autologous neutralization. Positions 295 and 332 are located immediately before and after the N- and C-terminal cysteines of the V3 loop, respectively, the latter of which affected an N-linked glycan that was critical to the neutralization epitope. Position 415 affected an N-linked glycan at position 413 in the C terminus of V4 that might mask epitopes near the base of V3. All three sites lie in close proximity on a four-stranded antiparallel sheet on the outer domain of gp120. We conclude that a region just below the base of the V3 loop, near the coreceptor binding domain of gp120, can be a target for autologous neutralization.

Direct Detection of Native Proteins in Biological Matrices Using Extractive Electrospray Ionization Mass Spectrometry

The Analyst. Sep, 2011  |  Pubmed ID: 21734987

The high-throughput and sensitive characterization of native proteins in biological samples is of increasing interest in multiple disciplines. Extractive electrospray ionization (EESI) forms ions of native proteins including lysozyme, α-chymotrypsin, myoglobin, human serum albumin, RNAse A and blood hemoglobin in extremely complex biosamples or PBS buffer solutions by softly depositing charges on the protein molecules. This method produces no significant conformational changes of the proteins in the ion formation process, and features direct detection of trace proteins present in biological matrices. The detection limit of low pmol L(-1) for lysozyme in untreated biological liquids such as human urine and tears was demonstrated using EESI mass spectrometry (MS), showing an attractive MS platform for the direct analysis of native proteins in actual biological samples.

Analysis of Common Genetic Variants Identifies RELN As a Risk Gene for Schizophrenia in Chinese Population

The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry. Jul, 2011  |  Pubmed ID: 21745129

Abstract Objectives. Several lines of evidence have shown that both RELN mRNA and protein are possibly down-regulated in the brain of schizophrenia patients. Recent association studies in European populations suggested RELN as a risk gene for schizophrenia. In this study, we test if RELN contributes to the risk of schizophrenia in Chinese population. Methods. We conducted case-control association analysis of 19 representative single nucleotide polymorphisms (SNPs) spanning the entire region of RELN in two independent Han Chinese samples from southwestern China (the Kunming sample and the Yuxi sample). Results. We identified six SNPs significantly associated with schizophrenia in the Kunming sample and four of them remained significant in the combined samples (the P values range from 0.006 to 4.0 ? 10(?5)). Haplotype analysis also suggested significant associations for the haplotypes incorporating the six significant SNPs (global P < 1.0 ? 10(?5)). Additionally, we also observed several other haplotypes (defined by a different set of SNPs) significantly associated with schizophrenia in the Kunming sample. However, the reported association of rs7341475 in Ashkenazi Jews was not significant in Han Chinese. Conclusions: Our findings demonstrate that RELN is a susceptibility gene for schizophrenia in Chinese population, and it is likely a common risk gene for schizophrenia in major populations worldwide.

Electrical Bistability in Self-assembled Hybrid Multilayers of Phospholipid and Nanoparticles

Nanotechnology. Aug, 2011  |  Pubmed ID: 21747161

A novel kind of biomolecule-based electrical bistable device composed of phospholipid-CdTe nanoparticle multilayered films was demonstrated. The composite film was fabricated by a facile solution-cast method. X-ray reflectivity and transmission electron microscopy measurements showed the homogeneous distribution of nanoparticles within the lamellar lipid matrix with long-range ordering. Current-voltage scans on the Al/(lipid-nanoparticle composite film)/ITO/glass structures at room temperature exhibited an obvious current bistable phenomenon. Further investigation of such bionanoparticle composite film promises to show its importance for applications in future memory nanodevices with tailored performance.

Transverse Wave Propagation in Photonic Crystal Based on Holographic Polymer-dispersed Liquid Crystal

Optics Express. Jul, 2011  |  Pubmed ID: 21747498

This study investigates the transversely propagating waves in a body-centered tetragonal photonic crystal based on a holographic polymer-dispersed liquid crystal film. Rotating the film reveals three different transverse propagating waves. Degeneracy of optical Bloch waves from reciprocal lattice vectors explains their symmetrical distribution.

Associations Between Body Mass and the Outcome of Surgery for Scoliosis in Chinese Adults

PloS One. 2011  |  Pubmed ID: 21747941

In this study we intended to prove that being overweight has an unfavorable impact on the surgical treatment outcome of adult idiopathic scoliosis (AdIS).

Dr. Chen-lu Tsou: a Tireless Advocate for Advancement in the Standards of Scientific Research in China

Protein & Cell. Jun, 2011  |  Pubmed ID: 21748592

A Novel Mechanism of V-type Zinc Inhibition of Glutamate Dehydrogenase Results from Disruption of Subunit Interactions Necessary for Efficient Catalysis

The FEBS Journal. Sep, 2011  |  Pubmed ID: 21749647

Bovine glutamate dehydrogenase is potently inhibited by zinc and the major impact is on V(max) suggesting a V-type effect on catalysis or product release. Zinc inhibition decreases as glutamate concentrations decrease suggesting a role for subunit interactions. With the monocarboxylic amino acid norvaline, which gives no evidence of subunit interactions, zinc does not inhibit. Zinc significantly decreases the size of the pre-steady state burst in the reaction but does not affect NADPH binding in the enzyme-NADPH-glutamate complex that governs the steady state turnover, again suggesting that zinc disrupts subunit interactions required for catalytic competence. While differential scanning calorimetry suggests zinc binds and induces a slightly conformationally more rigid state of the protein, limited proteolysis indicates that regions in the vicinity of the antennae regions and the trimer-trimer interface become more flexible. The structures of glutamate dehydrogenase bound with zinc and europium show that zinc binds between the three dimers of subunits in the hexamer, a region shown to bind novel inhibitors that block catalytic turnover, which is consistent with the above findings. In contrast, europium binds to the base of the antenna region and appears to abrogate the inhibitory effect of zinc. Structures of various states of the enzyme have shown that both regions are heavily involved in the conformational changes associated with catalytic turnover. These results suggest that the V-type inhibition produced with glutamate as the substrate results from disruption of subunit interactions necessary for efficient catalysis rather than by a direct effect on the active site conformation.

Temperature Effect on the Shear-induced Cell Damage in Biofabrication

Artificial Organs. Jul, 2011  |  Pubmed ID: 21752034

Biofabrication that incorporates living cells to manufacture various bioproducts is often carried out at different temperatures as the process demands. In the process, cells are subjected to mechanical forces, which may damage cells if the forces reach a certain level. Previous studies have shown that the cell damage is mainly caused by shear stress; however, none of them looked at the temperature effect on cell damage. In the present work, the influence of temperature on shear-induced cell damage was investigated experimentally by using a cone-and-plate rheometer, and based on the experimental results, a cell damage law was established to quantitatively describe the relationship between the cell damage percent and temperature. The so-established cell damage law was then applied to the modeling of the cell damage percent that occurs in the biofabrication process in which pressurized air was applied to dispense Schwann cells suspended in the alginate solution at different temperatures. The agreement between the model predictions and the experimental results suggests that the method presented in this article is effective for use in the investigation of the temperature effect, thereby providing a cue to preserve cell viability in the biofabrication processes.

[Angiotensin II-induced Monocyte/macrophage Inflammatory Effects and Drug Intervention]

Sheng Li Ke Xue Jin Zhan [Progress in Physiology]. Apr, 2011  |  Pubmed ID: 21770263

Comment on "Brighter Light Sources from Black Metal: Significant Increase in Emission Efficiency of Incandescent Light Sources"

Physical Review Letters. Jun, 2011  |  Pubmed ID: 21770609

Highly Flexible Frontside-illuminated Dye-sensitized Solar Cells Using Three-dimensional Network TiO2 Nanowires

Journal of Nanoscience and Nanotechnology. May, 2011  |  Pubmed ID: 21780380

Here we report a highly flexible frontside-illuminated dye-sensitized solar cell (FIDSSC) using Ti foils as the substrates. The laser-drilled microhole arrays (LDMAs) on Ti foil substrates as the photoanode provided an efficient pathway for the diffusion of liquid electrolyte, which would be particularly favorable for frontside illumination of FIDSSC designs. The three-dimensional (3D) network TiO2 nanowires (NWs) were directly grown on the Ti substrate with LDMAs via a simple hydrothermal method. Platinized Ti sheet was used as the counter electrode in the FIDSSC. The mechanical properties of the novel structured device were measured. It was shown that as-synthesized large-scale 3D network TiO2 NWs with a diameter of about 20-30 nm and a length of about 6 microm can prevent crack from generating efficiently when bended to an extreme angle of 120 degree. Furthermore, we demonstrated that the effects of the different bending angles on the performance of the 3D network TiO2 NWs-based FIDSSCs were slight, indicating NWs preferable advantages for the fabrication of flexible DSSCs. The results showed that the FIDSSC achieved an efficiency of 0.72% under front illumination of AM 1.5 simulated one sun light (100 mWcm(-2)).

[Myocardial Regeneration and Repair of Infarcted Heart by a New Composition Isolated from Geum Japonicum]

Zhonghua Xin Xue Guan Bing Za Zhi. May, 2011  |  Pubmed ID: 21781595

To isolate the cardiogenic fraction, which can enhance cardiogenic differentiation of bone marrow-derived mesenchymal stem cells (MSC) from Geum japonicum. The therapeutic effect of the isolated cardiogenic fraction was further tested in a rat myocardial infarction (MI) model.

Synthesis, Crystal Structures, and Biological Evaluation of Manganese(II) and Nickel(II) Complexes of 4-cyclohexyl-1-(1-(pyrazin-2-yl)ethylidene)thiosemicarbazide

European Journal of Medicinal Chemistry. Sep, 2011  |  Pubmed ID: 21784563

4-Cyclohexyl-1-(1-(pyrazin-2-yl)ethylidene)thiosemicarbazide (HL) and its transition metal complexes formulated as [Mn(L)(2)] (1) and [Ni(L)(2)] (2) have been prepared in 55-75% yield and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological activities of the synthesized compounds have been evaluated against selected Gram positive bacteria Bacillus subtilis, Gram negative bacteria Pseudomonas aeruginosa and the K562 leukemia cell line, respectively. The cytotoxicity data suggest that these compounds may be endowed with important biological properties, especially the nickel complex 2 with MIC = 31.2 μg/mL and IC(50) = 0.53 μM, respectively. Effect of the free ligand and its two complexes on Mitochondria membrane potential (MMP) and PI-associated fluorescence intensity as well as their effect on cell apoptosis in K562 leukemia cell line was also studied. The tested compounds may exert their cytotoxicity activity via induced loss of MMP.

A Novel Point Mutation at Donor Splice-site in Intron 18 of ATP2A2 Gene Resulting in the Insertion of 27 Nucleotides into the Mature MRNA in a Chinese Patient with Severe Darier's Disease

Journal of Dermatological Science. Oct, 2011  |  Pubmed ID: 21784620

RhG-CSF Improves Radiation-induced Myelosuppression and Survival in the Canine Exposed to Fission Neutron Irradiation

Journal of Radiation Research. 2011  |  Pubmed ID: 21785235

Fission-neutron radiation damage is hard to treat due to its critical injuries to hematopoietic and gastrointestinal systems, and so far few data are available on the therapeutic measures for neutron-radiation syndrome. This study was designed to test the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in dogs which had received 2.3 Gy mixed fission-neutron-γ irradiation with a high ratio of neutrons (~90%). Following irradiation, rhG-CSF treatment induced 100% survival versus 60% in controls. Only two of five rhG-CSF-treated dogs experienced leukopenia (white blood cells [WBC] count < 1.0 × 10(9)/L) and neutropenia (neutrophil [ANC] count < 0.5 × 10(9)/L), whereas all irradiated controls displayed a profound period of leukopenia and neutropenia. Furthermore, administration of rhG-CSF significantly delayed the onset of leukopenia and reduced the duration of leucopenia as compared with controls. In addition, individual dogs in the rhG-CSF-treated group exhibited evident differences in rhG-CSF responsiveness after neutron-irradiation. Finally, histopathological evaluation of the surviving dogs revealed that the incidence and severity of bone marrow, thymus and spleen damage decreased in rhG-CSF-treated dogs as compared with surviving controls. Thus, these results demonstrated that rhG-CSF administration enhanced recovery of myelopoiesis and survival after neutron-irradiation.

Stretchable, Transparent Graphene Interconnects for Arrays of Microscale Inorganic Light Emitting Diodes on Rubber Substrates

Nano Letters. Sep, 2011  |  Pubmed ID: 21790143

This paper describes the fabrication and design principles for using transparent graphene interconnects in stretchable arrays of microscale inorganic light emitting diodes (LEDs) on rubber substrates. We demonstrate several appealing properties of graphene for this purpose, including its ability to spontaneously conform to significant surface topography, in a manner that yields effective contacts even to deep, recessed device regions. Mechanics modeling reveals the fundamental aspects of this process, as well as the use of the same layers of graphene for interconnects designed to accommodate strains of 100% or more, in a completely reversible fashion. These attributes are compatible with conventional thin film processing and can yield high-performance devices in transparent layouts. Graphene interconnects possess attractive features for both existing and emerging applications of LEDs in information display, biomedical systems, and other environments.

Optimal Time-Resource Allocation for Energy-Efficient Physical Activity Detection

IEEE Transactions on Signal Processing : a Publication of the IEEE Signal Processing Society. 2011  |  Pubmed ID: 21796237

The optimal allocation of samples for physical activity detection in a wireless body area network for health-monitoring is considered. The number of biometric samples collected at the mobile device fusion center, from both device-internal and external Bluetooth heterogeneous sensors, is optimized to minimize the transmission power for a fixed number of samples, and to meet a performance requirement defined using the probability of misclassification between multiple hypotheses. A filter-based feature selection method determines an optimal feature set for classification, and a correlated Gaussian model is considered. Using experimental data from overweight adolescent subjects, it is found that allocating a greater proportion of samples to sensors which better discriminate between certain activity levels can result in either a lower probability of error or energy-savings ranging from 18% to 22%, in comparison to equal allocation of samples. The current activity of the subjects and the performance requirements do not significantly affect the optimal allocation, but employing personalized models results in improved energy-efficiency. As the number of samples is an integer, an exhaustive search to determine the optimal allocation is typical, but computationally expensive. To this end, an alternate, continuous-valued vector optimization is derived which yields approximately optimal allocations and can be implemented on the mobile fusion center due to its significantly lower complexity.

Metalloporphyrin Mixed-valence π-cation Radicals: [Fe(oxoOEC(•/2))(Cl)]2SbCl6, Structure, Magnetic Properties, and Near-IR Spectra

Inorganic Chemistry. Sep, 2011  |  Pubmed ID: 21809820

The preparation and characterization of a mixed-valence π-cation radical derivative of an iron(III) oxochlorinato complex is reported. The new complex has been synthesized by the one-electron oxidation of a pair of [Fe(oxoOEC)(Cl)] molecules to form the dimeric cation [Fe(oxoOEC)(Cl)]₂⁺. The cation has been characterized by X-ray analysis, Mössbauer spectroscopy, UV-vis and near-IR spectroscopy, and magnetic susceptibility measurements from 6-300 K. The crystal structure shows that the two rings have a smaller overlap area than those of the formally related nickel and copper octaethylporphinate derivatives, reflecting the larger steric congestion at the periphery in part of the oxochlorin rings. The Mössbauer data is consistent with two equivalent iron(III) centers. The unpaired electron is delocalized over the two oxochlorin rings and mediates a strong antiferromagnetic interaction between the high-spin iron(III) centers.

Green Tea Polyphenols Control Dysregulated Glutamate Dehydrogenase in Transgenic Mice by Hijacking the ADP Activation Site

The Journal of Biological Chemistry. Sep, 2011  |  Pubmed ID: 21813650

Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition cause the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic β-cell responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) inhibit GDH in vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyperresponse to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding, and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product or some derivative thereof may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown that restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in vivo.

Autosomal Interactions and Mechanisms of Pyrethroid Resistance in House Flies, Musca Domestica

International Journal of Biological Sciences. 2011  |  Pubmed ID: 21814485

Five BC₁ lines and 16 house fly mass-cross homozygous lines were generated from crosses of the pyrethroid resistant ALHF (wild-type) and susceptible aabys (bearing recessive morphological markers on each of five autosomes) strains. Each of the resulting homozygous lines had different combinations of autosomes from the resistant ALHF strain. Levels of resistance to permethrin were measured for each line to determine the autosomal linkage, interaction and, possibly, regulation in pyrethroid resistance of house flies. Results indicated that factors on autosome 4 are not involved in the development of resistance in house flies, while factors on autosomes 1, 2, 3 and 5 play important roles in pyrethroid resistance. The sodium channel gene has been mapped on autosome 3 and multiple cytochrome P450 genes overexpressed in resistant ALHF house flies have been genetically mapped on autosome 5, suggesting that P450 mediated detoxification and sodium channel-mediated target site insensitivity located on autosomes 3 and 5, respectively, are major factors related to resistance development in house flies. However, neither the factors on autosome 3 or 5 alone, nor the factors from both autosomes 3 and 5 combined could confer high levels of resistance to pyrethroid. In addition, strong synergistic effects on resistance was obtained when autosomes 1 and 2 interact with autosome 3 and/or 5, suggesting that the trans factors on autosomes 1 and 2 may interact with factors on autosomes 3 and 5, therefore, playing regulatory roles in the development of sodium channel insensitivity- and P450 detoxification-mediated resistance.

[Developing a Risk Appraisal Model for Gestational Diabetes Mellitus]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. May, 2011  |  Pubmed ID: 21826998

To identify risk factors associated with gestational diabetes mellitus (GDM) and establish a risk appraisal model for GDM.

Heterogeneity of Aberrant Immunoglobulin Expression in Cancer Cells

Cellular & Molecular Immunology. Nov, 2011  |  Pubmed ID: 21860405

Accumulating evidence has shown that immunoglobulin (Ig) is 'unexpectedly' expressed by epithelial cancer cells and that it can promote tumor growth. The main purpose of this study was to explore the components of the cancerous Ig and its possible function. The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence, indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells. Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction. The cancerous Ig consists of an α heavy chain and a κ light chain. Finally, by analyzing the Ig components pulled down by protein A beads, the cancerous Ig was found to be structurally distinct from normal Ig. The cancerous Ig was truncated or aberrant. Although the underlying mechanism that causes the abnormalities has not been determined, our current discoveries strengthen our previous findings and promise fruitful future explorations.

[Energy Zero Balance Study on the Energy Intake of Healthy Adults Engaged in Light Physical Activities in Southern China]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Jul, 2011  |  Pubmed ID: 21861345

Using an energy zero balance method to investigate and analyze the level of dietary energy intake of healthy adults in southern China, in order to provide basic data for revising Chinese energy DRIs.

Early Results of Left Carotid Chimney Technique in Endovascular Repair of Acute Non-a-non-B Aortic Dissections

Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. Aug, 2011  |  Pubmed ID: 21861733

To report our early experience with endovascular repair of acute non-A-non-B aortic dissections using chimney grafts to preserve blood flow to a left common carotid artery (LCCA) located in the proximal landing zone.

Effects of Intrabone Marrow-Bone Marrow Transplantation Plus Adult Thymus Transplantation on Survival of Mice Bearing Leukemia

Stem Cells and Development. Oct, 2011  |  Pubmed ID: 21861761

We recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor is effective in mice bearing solid tumors. In the current study, we examined the effects of this strategy on the survival of mice with leukemia. One week after intravenous injection of 1×10(6) leukemic cells (EL-4, H-2(b)) into 8-week-old B6 (H-2(b)) mice, the mice were 8 Gy irradiated and transplanted with 1×10(7) bone marrow cells (BMCs) from 8-week-old BALB/c mice (H-2(d)) by IBM-BMT with or without donor lymphocyte infusion (DLI) or ATT. All the mice without treatment died within 70 days after injection of EL-4. About 40% of those treated with IBM-BMT alone died within 100 days due to tumor relapse. In contrast, those treated with IBM-BMT+DLI or ATT showed the longest survival rate without relapse of leukemia. In addition, the former showed less graft versus host disease (GVHD) than the latter. The mice treated with IBM-BMT+ATT also showed an intermediate percentage of effector memory (EM) and central memory (CM) cells between those treated with BMT alone and those treated with IBM-BMT+DLI. The numbers and functions of T cells increased in those treated with IBM-BMT+ATT with interleukin-2 and interferon-γ production. These results suggest that IBM-BMT+ATT is effective in the treatment of leukemia with strong graft versus leukemia without increased risk of GVHD.

Single-particle Reconstruction Using L(2)-gradient Flow

Journal of Structural Biology. Dec, 2011  |  Pubmed ID: 21864687

In this paper, we present an iterative algorithm for reconstructing a three-dimensional density function from a set of two dimensional electron microscopy images. By minimizing an energy functional consisting of a fidelity term and a regularization term, an L(2)-gradient flow is derived. The flow is integrated by a finite element method in the spatial direction and an explicit Euler scheme in the temporal direction. Our method compares favorably with those of the weighted back projection, Fourier method, algebraic reconstruction technique and simultaneous iterative reconstruction technique.

[Effects of Clostridium Difficile Toxin a on Proliferation of K562 Cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Aug, 2011  |  Pubmed ID: 21867609

This study was aimed to investigate the effect of clostridium difficile toxin A (Tcd A) on proliferation of K562 cells and its mechanism. The proliferative activity of K562 cells exposed to Tcd A was tested by MTT assay; cell cycle distribution and mitochondrial membrane potential were analyzed by flow cytometry; the protein expression of cytochrome C and DNA fragmentation were observed by immunohistochemistry staining and agarose gel electrophoresis respectively. The results indicated that Tcd A inhibited proliferation of K562 cells in a time-and concentration-dependent manner. Cells were arrested at G(0)/G(1) phase. Peak of apoptosis appeared. The protein expression of cytochrome C increased as compared with control group (p < 0.05). Agarose gel electrophoresis of DNA from K562 treated with Tcd A revealed a "ladder" pattern. It is concluded that clostridium difficile toxin A can inhibit proliferation and induce apoptosis of K562 cells. The mechanism may be in relation to decrease of mitochondrial membrane potential and the release of cytochrome C from mitochondria matrix.

High Dose Granulocyte Colony-stimulating Factor Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated by 2.3 Gy Mixed Fission Neutron and Gamma Ray

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Aug, 2011  |  Pubmed ID: 21867631

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.

Labelled Antibody-based One-step Time-resolved Fluoroimmunoassay for Measurement of Free Thyroxine in Serum

Annals of Clinical Biochemistry. Nov, 2011  |  Pubmed ID: 21885471

Valid assays measuring free thyroxine (FT4) must perform without bias despite large variations in the concentrations and affinities of serum thyroxine-binding proteins in the population. We developed a new, rapid one-step labelled-antibody time-resolved fluoroimmunoassay (TRFIA) for FT4.

Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association with Schizophrenia

The American Journal of Psychiatry. Dec, 2011  |  Pubmed ID: 21890790

ZNF804A is a schizophrenia risk gene that was recently identified by genome-wide association studies as well as subsequent replications. Although the results are consistent among studies in European populations, there have been conflicting reports in Chinese populations. The authors conducted both association and functional analyses to test whether ZNF804A is a risk gene for schizophrenia in Chinese populations.

Tear Menisci After Overnight Contact Lens Wear

Optometry and Vision Science : Official Publication of the American Academy of Optometry. Dec, 2011  |  Pubmed ID: 21892112

To determine the effect of overnight wear of contact lenses (CL) on tear meniscus, tear film stability, and subjective comfort.

Role of a Type IV-like Secretion System of Streptococcus Suis 2 in the Development of Streptococcal Toxic Shock Syndrome

The Journal of Infectious Diseases. Jul, 2011  |  Pubmed ID: 21673039

Streptococcus suis serotype 2 (S. suis 2) has evolved into a highly invasive pathogen that was found to be the cause of 2 large-scale outbreaks of streptococcus toxic shock syndrome (STSS) in China. However, the mechanism of action of this non-group A streptococcal (GAS) S. suis-caused STSS is still unknown. Previously, we identified a unique pathogenicity island (PAI) designated 89K that is specific to the STSS-causing epidemic strains of S. suis 2. In this study, we further report a functional type IV-like secretion system (T4SS-like system) harbored in the 89K PAI that contributes to the development of STSS. Knockout of the 2 key components (VirD4-89K and VirB4-89K) of the T4SS-like system eliminated the lethality of the highly virulent strain and impaired its ability to trigger host immune response in experimental infection of mice. Our findings provide a new insight into the pathogenesis of STSS caused by the highly pathogenic S. suis 2 isolates.

Randomized, Controlled, Multicenter, Clinical Trial Comparing BRYAN Cervical Disc Arthroplasty with Anterior Cervical Decompression and Fusion in China

Spine. Jun, 2011  |  Pubmed ID: 21673620

ABSTRACT: Study Design: Prospective, randomized, controlled, multicenter clinical trial.Objective: To compare outcomes of cervical disc arthroplasty with those of anterior cervical decompression and fusion (ACDF) in a Chinese population.Summary of Background Data: Cervical disc arthroplasty has been found to be superior to ACDF for maintaining range of motion (ROM) at the index spinal segment and possibly will avoid abnormal stress to adjacent segments.Methods: A total of 120 patients from three large hospitals in China were randomly assigned to treatment with cervical disc arthroplasty (n = 60) using the BRYAN prosthesis or ACDF (n = 60) and were followed up postoperatively for 24 months.Results: The two groups had similar preoperative demographics and baseline characteristics including ROM, Neck Disability Index (NDI), and Visual Analog Scale for neck and arm pain. The total disc replacement (TDR) group had a significantly longer operation time than the ACDF group (P<0.001). Outcome data obtained after 24 months revealed a significant difference between the groups in mean change from baseline in ROM at the index level (P<0.001); ROM was maintained in the TDR group, but reduced in the ACDF group. There were no significant between group differences in the baseline changes in NDI or Visual Analog Scale scores for pain. One patient in the TDR group and four patients in the ACDF group required re-operations.Conclusion: At 24 months after surgery, the cervical disc prosthesis yielded good clinical results while maintaining ROM at the index level. Cervical disc arthroplasty appears to be a viable alternative to ACDF.

Glycogen Synthase Kinase 3 Beta (GSK3β) Phosphorylates the RNAase III Enzyme Drosha at S300 and S302

PloS One. 2011  |  Pubmed ID: 21674040

The canonical microRNA (miRNA) pathway commences with the enzymatic cleavage of the primary gene transcript (pri-miRNA) by the RNAase III enzyme Drosha in the nucleus into shorter pre-miRNA species that are subsequently exported to the cytoplasm for further processing into shorter, mature miRNA molecules. Using a series of reporter constructs, we have previously demonstrated that phosphorylation of Drosha at Ser 300 and 302 was required for its nuclear localization. Here, we identify GSK3β as the culprit kinase. We demonstrate that Drosha is unable to selectively localize to the nucleus in cells deficient in GSK3β. These findings expand the substrate base of GSK3β to include a central component of the miRNA biogenesis pathway.

Metformin Inhibits Renal Cell Carcinoma in Vitro and in Vivo Xenograft

Urologic Oncology. Jun, 2011  |  Pubmed ID: 21676631

OBJECTIVE: To evaluate the effects of metformin on renal cell carcinoma (RCC) and its underlying mechanisms. MATERIALS AND METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays to investigate the effects of metformin on RCC cell growth. Flow cytometry was used to evaluate the cell cycle changes after metformin treatment. We further determined the possible signaling molecules involved in this process by immunoblot analysis of various proteins. Furthermore, a xenograft model was used to study the effects of metformin on RCC tumor growth. RESULTS: We demonstrated that metformin effectively inhibits cell proliferation in 786-O and OS-RC-2 RCC cell lines. Moreover, metformin down-regulated cyclin D1 expression and induced G(0)/G(1) cell cycle arrest in these cells. Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Most importantly, daily treatment of mice with metformin prevented RCC tumor growth in a xenograft model. CONCLUSIONS: Metformin was able to induce G(0/)G(1) cell cycle arrest and inhibit RCC growth in vitro and in vivo. These results suggest that metformin may be a potential therapeutic agent for the treatment of RCC.

No Association Between APOE Epsilon 4 Allele and Multiple Sclerosis Susceptibility: a Meta-analysis from 5472 Cases and 4727 Controls

Journal of the Neurological Sciences. Sep, 2011  |  Pubmed ID: 21679970

Apolipoprotein E (APOE) gene ε4, 2 alleles have been reported to be associated with multiple sclerosis (MS), but results were conflicting. In order to derive a more precise estimation of the associations, a meta-analysis was performed.

Endovascular Stenting for Treatment of Nutcracker Syndrome: Report of 61 Cases with Long-term Followup

The Journal of Urology. Aug, 2011  |  Pubmed ID: 21683388

We report the efficacy and safety of endovascular stenting for nutcracker syndrome at long-term followup.

[Chromosome Recombination in Rice Meiosis]

Yi Chuan = Hereditas / Zhongguo Yi Chuan Xue Hui Bian Ji. Jun, 2011  |  Pubmed ID: 21684871

Meiosis is a highly conservative process, which plays important role in the life cycles of all sexually reproductive organisms, while the pairing, synapsis, and recombination are the key events in this process and have become the hotspots in meiosis studies. At present, we cannot observe the process of cross and recombination of chromosomes directly in plant meiosis, and generally conclude the process by analysis the genetic population. In the present study, we analyzed 32 DH lines using graphical genotypes, and found 4 chromosomes out of 32 DH lines had regional heterozygosis, which was further confirmed using STS markers. We suggested that it may cause by repair incompletion or mis-repair of chromsome. These results provid some directly evidence for explaining the mechanism of plant meiosis.

Knockdown of Akt Sensitizes Osteosarcoma Cells to Apoptosis Induced by Cisplatin Treatment

International Journal of Molecular Sciences. 2011  |  Pubmed ID: 21686164

Akt plays an important role in the inhibition of apoptosis induced by chemotherapy and other stimuli. We therefore investigated if knockdown of Akt2 promoted drug-induced apoptosis in cultured osteosarcoma cells in vitro. SAOS-2 cells were transfected with Akt2 siRNA. The sensitivity of the transformed cell line to the chemotherapeutic drug cisplatin was assessed. Reduced expression of Akt2 did not directly inhibit the growth rate of the transfected cells; however, it significantly increased their sensitivity to cisplatin. Knockdown of Akt2, together with cisplatin treatment, promoted the expression of p53 up-regulated modulator of apoptosis (PUMA). It is possible that the augmentation of cisplatin cytotoxicity may be mediated by PUMA activation. The results of this study suggest that knockdown of Akt2 expression may have therapeutic applications in enhancing the efficacy of chemotherapy in patients with osteosarcoma.

Cerebral Artery-vein Separation Using 0.1-Hz Oscillation in Dual-wavelength Optical Imaging

IEEE Transactions on Medical Imaging. Dec, 2011  |  Pubmed ID: 21693415

We present a novel artery-vein separation method using 0.1-Hz oscillation at two wavelengths with optical imaging of intrinsic signals (OIS). The 0.1-Hz oscillation at a green light wavelength of 546 nm exhibits greater amplitude in arteries than in veins and is primarily caused by vasomotion, whereas the 0.1-Hz oscillation at a red light wavelength of 630 nm exhibits greater amplitude in veins than in arteries and is primarily caused by changes of deoxyhemoglobin concentration. This spectral feature enables cortical arteries and veins to be segmented independently. The arteries can be segmented on the 0.1-Hz amplitude image at 546 nm using matched filters of a modified dual Gaussian model combining with a single Gaussian model. The veins are a combination of vessels segmented on both amplitude images at the two wavelengths using multiscale matched filters of single Gaussian model. Our method can separate most of the thin arteries and veins from each other, especially the thin arteries with low contrast in raw gray images. In vivo OIS experiments demonstrate the separation ability of the 0.1-Hz based segmentation method in cerebral cortex of eight rats. Two validation studies were undertaken to evaluate the performance of the method by quantifying the arterial and venous length based on a reference standard. The results indicate that our 0.1-Hz method is very effective in separating both large and thin arteries and veins regardless of vessel crossover or overlapping to great extent in comparison with previous methods.

MicroRNA-138 Modulates DNA Damage Response by Repressing Histone H2AX Expression

Molecular Cancer Research : MCR. Aug, 2011  |  Pubmed ID: 21693595

Precise regulation of DNA damage response is crucial for cellular survival after DNA damage, and its abrogation often results in genomic instability in cancer. Phosphorylated histone H2AX (γH2AX) forms nuclear foci at sites of DNA damage and facilitates DNA damage response and repair. MicroRNAs (miRNA) are short, nonprotein-encoding RNA molecules, which posttranscriptionally regulate gene expression by repressing translation of and/or degrading mRNA. How miRNAs modulate DNA damage response is largely unknown. In this study, we developed a cell-based screening assay using ionizing radiation (IR)-induced γH2AX foci formation in a human osteosarcoma cell line, U2OS, as the readout. By screening a library of human miRNA mimics, we identified several miRNAs that inhibited γH2AX foci formation. Among them, miR-138 directly targeted the histone H2AX 3'-untranslated region, reduced histone H2AX expression, and induced chromosomal instability after DNA damage. Overexpression of miR-138 inhibited homologous recombination and enhanced cellular sensitivity to multiple DNA-damaging agents (cisplatin, camptothecin, and IR). Reintroduction of histone H2AX in miR-138 overexpressing cells attenuated miR-138-mediated sensitization to cisplatin and camptothecin. Our study suggests that miR-138 is an important regulator of genomic stability and a potential therapeutic agent to improve the efficacy of radiotherapy and chemotherapy with DNA-damaging agents.

Age-related Changes in Tear Menisci Imaged by Optical Coherence Tomography

Optometry and Vision Science : Official Publication of the American Academy of Optometry. Oct, 2011  |  Pubmed ID: 21705939

To determine age-related changes of tear menisci in healthy subjects and to compare tear variables between age-matched normals and dry eye subjects.

Metabolic Syndrome and Incident Coronary Heart Disease in Australian Indigenous Populations

Obesity (Silver Spring, Md.). Jun, 2011  |  Pubmed ID: 21660075

This report aims to compare the prediction of the metabolic syndrome (MetS) and its components for morbidity and mortality of coronary heart disease (CHD) in a cohort of Australian Aboriginal and Torres Strait Islander adults (TSIs). A total of 2,100 adults (1,283 Aborigines and 817 TSIs) was followed up for 6 years from 2000. Outcome measures were all CHD events (deaths and hospitalizations). Baseline anthropometric measurements, blood pressure (BP), fasting blood lipids and glucose were collected. Smoking and alcohol intake was self-reported. We found MetS was more prevalent in TSI (50.3%) compared to Aborigines (33.0%). Baseline MetS doubled the risk of a CHD event in Aborigines. Increased fasting triglycerides was stronger in predicting CHD (hazard ratio (HR): 2.8) compared with MetS after adjusted for age, sex, tobacco and alcohol consumption, and baseline diabetes and albuminuria for Aborigines but not among TSIs. MetS was not more powerful than its components in predicting CHD event. In Australian Aborigines, the "triglyceridemic waist" phenotype strongly predicts CHD event, whereas among TSI, baseline diabetes mediated the prediction of increased fasting glucose for CHD event.

A Comparison of Anterior and Posterior Instrumentation for Restoring and Retaining Sagittal Balance in Patients With Idiopathic Adolescent Scoliosis

Journal of Spinal Disorders & Techniques. Jun, 2011  |  Pubmed ID: 21666508

STUDY DESIGN: Retrospective, comparative study. OBJECTIVE: To compare the effects of anterior rod-screw instrumentation and posterior pedicle screw instrumentation on sagittal balance in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Lenke type 5 AIS is treated by anterior or posterior spinal fusion surgery. Most studies comparing anterior and posterior fusion surgery have focused on assessing improvement in coronal balance. Studies comparing the effects of anterior and posterior surgery on sagittal balance are lacking. METHODS: The records of 49 patients diagnosed with Lenke type 5 AIS were examined. A total of 21 patients underwent anterior surgery between 2000 and 2003, while 26 underwent posterior surgery between 2004 and 2006. Preoperative, postoperative, and follow-up thoracic kyphosis (T5-T12 and T2-T12), lumbar lordosis, thoracolumbar junction kyphosis, and spinal vertical axis measurements were made by examining radiographs. Quality of life was assessed using the Scoliosis Research Society-22 questionnaire. All patients were followed up for at least 2 years. RESULTS: There were no significant between group differences in coronal alignment, thoracic kyphosis, or T11-L2 alignment after surgery. Sagittal alignment improvement was significantly more pronounced in the anterior surgery group compared with the posterior surgery group. The fusion segment was also significantly shorter in the anterior surgery compared with the posterior surgery group. Quality of life scores were significantly higher in the anterior surgery group compared with the posterior surgery group. CONCLUSION: Anterior solid rod-screw instrumentation results in shorter fusion segments, and better sagittal alignment and quality of life than posterior pedicle screw instrumentation in patients with Lenke type 5 AIS.

Genome-wide Association Study Identifies Two New Susceptibility Loci for Atopic Dermatitis in the Chinese Han Population

Nature Genetics. Jul, 2011  |  Pubmed ID: 21666691

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

Fine Tuning of Emission Color of Iridium(III) Complexes from Yellow to Red Via Substituent Effect on 2-phenylbenzothiazole Ligands: Synthesis, Photophysical, Electrochemical and DFT Study

Dalton Transactions (Cambridge, England : 2003). Jul, 2011  |  Pubmed ID: 21666891

Four novel iridium(III) complexes bearing biphenyl (7a-7c) or fluorenyl (7d) modified benzothiazole cyclometallate ligands are synthesized. In comparison with the yellow parent complex, bis(2-phenylbenzothiozolato-N,C(2')) iridium(III) (acetylacetonate) [(pbt)(2)Ir(acac)] (λ(PLmax) = 557 nm, φ(PL) = 0.26), 7a-7d show 20-43 nm bathochromic shifted orange or red phosphorescence in solution, with maximum photoluminescence (PL) quantum yield of 0.62, and PL lifetime of 1.8-2.0 μs. Meanwhile, the resulting complexes also exhibit intense orange or red phosphorescence of λ(PLmax) = 588-611 nm in solid films. The complex 7c with two tert-butyl substituents possesses the highest phosphorescent efficiency both in dilute solution and thin solid films, therefore may be a prospective candidate for both doping and host emitting electrophosphorescent material. Furthermore, despite the observation of severe oxygen quenching for 7a-7d in solution, 7a and 7c even show efficient emission intensity quenching by oxygen in their solid state due to the existence of void channels in crystals; consequently, they are promising molecular oxygen sensor reagents. Electrochemical measurement and DFT calculation results suggest that all these chelates own declined LUMOs of 0.1 eV relative to that of (pbt)(2)Ir(acac) owing to the contribution of the phenyl substituents; whereas only 7d shows a more destabilized HOMO (∼0.1 eV) compared with the parent chelate.

Synthesis, Field-emission and Electric Properties of Metastable Phase VO2 (A) Ultra-long Nanobelts

Dalton Transactions (Cambridge, England : 2003). Nov, 2011  |  Pubmed ID: 21918759

High quality single crystalline metastable phase VO(2) (A) ultra-long nanobelts were synthesized by hydrothermal method using inorganic V(2)O(5) sol as precursor and polyethylene glycol (PEG) as both surfactant and reducing agent. It was found that the oriented attach growth mechanism is responsible for the formation of VO(2) (A) nanobelts. In addition to an endothermic peak, an unusual exothermic peak was detected in DSC curve of the nanobelts. The temperature dependence of the lattice parameters have been studied, and it was found that the a-axis expands while the c-axis contracts in the high-temperature XRD test. The VO(2) (A) nanobelt has a low turn-on field of 3.8 V μm(-1) and a high field enhancement factor of 1739 in the field emission measurement. Electrical transport measurement of a single VO(2) (A) nanobelt gives a relative low hoping activation energy of 0.28 eV.

Amelioration of 2,4,6-trinitrobenzene Sulfonic Acid-induced Colitis in Mice by Immunoregulatory Dendritic Cells

Journal of Gastroenterology. Dec, 2011  |  Pubmed ID: 21922185

Dendritic cells (DCs) are widely distributed throughout the lymphoid and nonlymphoid tissues, and are important initiators of acquired immunity. They also serve as regulators by inducing self-tolerance. However, it has not been thoroughly clarified whether DCs are somehow involved in the regulation or treatment of inflammatory bowel diseases.

T Cell Surveillance of Oncogene-induced Prostate Cancer is Impeded by T Cell-derived TGF-β1 Cytokine

Immunity. Jul, 2011  |  Pubmed ID: 21757379

Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune system, which was associated with heightened TGF-β signaling in T cells from the tumor-draining lymph nodes. Blockade of TGF-β signaling in T cells enhanced tumor antigen-specific T cell responses and inhibited tumor development. Surprisingly, T cell- but not Treg cell-specific ablation of TGF-β1 was sufficient to augment T cell cytotoxic activity and blocked tumor growth and metastases. These findings reveal that T cell production of TGF-β1 is an essential requirement for tumors to evade immunosurveillance independent of TGF-β produced by tumors.

Weight of the IDSA/ATS Minor Criteria for Severe Community-acquired Pneumonia

Respiratory Medicine. Oct, 2011  |  Pubmed ID: 21764276

The 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines defined severe community-acquired pneumonia (CAP) when patients fulfilled three out of nine minor criteria. Whether each of the criteria is of equal weight is not clear. The purpose of this study was to determine the weight of the minor criteria.

Intracellular ATP Levels Affect Secondary Metabolite Production in Streptomyces Spp

Bioscience, Biotechnology, and Biochemistry. 2011  |  Pubmed ID: 21821936

The addition of extracellular ATP (exATP) to four Streptomyces strains had similar effects: low exATP levels stimulated antibiotic production and high levels reduced it. Compared with antibiotic production, the concentrations of intracellular ATP (inATP) in the tested strains were opposite, which suggests a role of inATP in regulating secondary metabolite production. Under inactivation of the polyphosphate kinase gene (ppk) in Streptomyces lividans, we observed the same results: when the inATP level in the mutant strain was lower than in the parent strain, more antibiotic was produced. Combining all the results, a strong inverse relationship between [inATP] and the secondary metabolite production is suggested by this study.

Counting Citations in Texts Rather Than Reference Lists to Improve the Accuracy of Assessing Scientific Contribution: Citation Frequency of Individual Articles in Other Papers More Fairly Measures Their Scientific Contribution Than Mere Presence in Reference Lists

BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology. Oct, 2011  |  Pubmed ID: 21826692

Epidermal Electronics

Science (New York, N.Y.). Aug, 2011  |  Pubmed ID: 21836009

We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.

[Preliminary Clinical Study on the Treatment of Severe Infantile Hemangioma with High-dose Propranolol in China]

Zhonghua Zheng Xing Wai Ke Za Zhi = Zhonghua Zhengxing Waike Zazhi = Chinese Journal of Plastic Surgery. May, 2011  |  Pubmed ID: 21837992

To investigate the clinical results of the treatment of severe infantile hemangioma with high-dose propranolol in Chinese.

Detection of Mercury(II) by Quantum Dot/DNA/gold Nanoparticle Ensemble Based Nanosensor Via Nanometal Surface Energy Transfer

Analytical Chemistry. Sep, 2011  |  Pubmed ID: 21842845

An ultrasensitive fluorescent sensor based on the quantum dot/DNA/gold nanoparticle ensemble has been developed for detection of mercury(II). DNA hybridization occurs when Hg(II) ions are present in the aqueous solution containing the DNA-conjugated quantum dots (QDs) and Au nanoparticles. As a result, the QDs and the Au nanoparticles are brought into the close proximity, which enables the nanometal surface energy transfer (NSET) from the QDs to the Au nanoparticles, quenching the fluorescence emission of the QDs. This nanosensor exhibits a limit of detection of 0.4 and 1.2 ppb toward Hg(II) in the buffer solution and in the river water, respectively. The sensor also shows high selectivity toward the Hg(II) ions.

Genes and Pathways Co-associated with the Exposure to Multiple Drugs of Abuse, Including Alcohol, Amphetamine/methamphetamine, Cocaine, Marijuana, Morphine, And/or Nicotine: a Review of Proteomics Analyses

Molecular Neurobiology. Dec, 2011  |  Pubmed ID: 21922273

Drug addiction is a chronic neuronal disease. In recent years, proteomics technology has been widely used to assess the protein expression in the brain tissues of both animals and humans exposed to addictive drugs. Through this approach, a large number of proteins potentially involved in the etiology of drug addictions have been identified, which provide a valuable resource to study protein function, biochemical pathways, and networks related to the molecular mechanisms underlying drug dependence. In this article, we summarize the recent application of proteomics to profiling protein expression patterns in animal or human brain tissues after the administration of alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine/heroin/butorphanol, or nicotine. From available reports, we compiled a list of 497 proteins associated with exposure to one or more addictive drugs, with 160 being related to exposure to at least two abused drugs. A number of biochemical pathways and biological processes appear to be enriched among these proteins, including synaptic transmission and signaling pathways related to neuronal functions. The data included in this work provide a summary and extension of the proteomics studies on drug addiction. Furthermore, the proteins and biological processes highlighted here may provide valuable insight into the cellular activities and biological processes in neurons in the development of drug addiction.

Incorporation of the HIV-1 Microbicide Cyanovirin-N in a Food Product

Journal of Acquired Immune Deficiency Syndromes (1999). Dec, 2011  |  Pubmed ID: 21926631

An urgent need exists for HIV-1 microbicides. Here, we describe the in vivo testing of lactic acid bacteria bioengineered to secrete cyanovirin-N. We fed pigtail macaques a yogurt formulation that used bioengineered strains as a starter culture. Cyanovirin-N expression could be detected in the rectal vault during and immediately after feeding. Ex vivo viral challenge of rectal tissue biopsies revealed that peak viral burden was significantly lower in tissue obtained from experimental animals compared with control animals. Formulation of candidate compounds in lactic acid bacteria and their oral administration seems to be a feasible strategy for mucosal delivery of microbicides.

Study of Luan-Pao-Prescription on Ovarian Dysfunction in Rats

Journal of Ethnopharmacology. Sep, 2011  |  Pubmed ID: 21933702

ETHNOPHARMACOLOGICAL RELEVANCE: Luan-Pao-Prescription (LPP) has been clinically proven to be effective on infertility. In the present study we explored the improvement and underlying mechanism of LPP on ovarian dysfunction in rats. MATERIALS AND METHODS: 13month old female rats were randomly divided into 4 groups: the Saline group, the LPP groups treated by low (1.67g/kg), and high-dose (5g/kg) LPP respectively, and the hormone group treated by pregnant mare gonadotrophin serum and chorionic gonadotrophin (PMSG/hCG). The estrous cycle was determined by daily observation of vaginal smears; serum estradiol and testosterone were estimated by enzyme-linked immunosorbent assay; ovarian morphology, ovary volume and fertility of female rats were all detected during the study. RESULTS: During 21days of LPP treatment, about 20% increase of rats with regular estrous cycle of 4-6days was found, but no change was detected on serum estradiol and testosterone at the dose of 1.67g/kg and 5g/kg LPP. Both ovary index and uterus index were up-regulated significantly at the dose of 5g/kg LPP, but no regulation on oviduct index, adrenal gland index, pancreatic gland index and spleen index was observed at the two LPP groups. 5g/kg LPP increased total number of pregnant mothers and the offspring; however there are no offspring in PMSG/hCG group. The offspring exhibited similar body weight in each treatment, and no apparent malformation was found for the cubs. While PMSG/hCG treatment increased the ovary index, serum estradiol and testosterone concentration considerably, but no improvement was found on estrous cycle, oviduct index, uterus index, and reproduction. CONCLUSION: Administration of LPP may have comparable benefits for ovarian dysfunction, but with fewer side effects. Oral LPP have a better overall influence on rats than PSMG/hCG; it may be more effective in improvement of estrous cycle, ovary function and reproduction.

Recognition of Physical Activities in Overweight Hispanic Youth Using KNOWME Networks

Journal of Physical Activity & Health. May, 2011  |  Pubmed ID: 21934162

BACKGROUND: KNOWME Networks is a wireless body area network with two tri-axial accelerometers, a heart rate monitor, and mobile phone that acts as the data collection hub. One function of KNOWME Networks is to detect physical activity (PA) in overweight Hispanic youth. The purpose of this study was to evaluate the in-lab recognition accuracy of KNOWME. METHODS: Twenty overweight Hispanic participants (10 males; age 14.6±1.8 years), underwent four data collection sessions consisting of nine activities/session: lying down, sitting, sitting fidgeting, standing, standing fidgeting, standing playing an active video game, slow walking, brisk walking, and running. Data was used to train activity recognition models. The accuracy of personalized and generalized models is reported. RESULTS: Overall accuracy for personalized models was 84%. The most accurately detected activity was running (96%). The models had difficulty distinguishing between the static and fidgeting categories of sitting and standing. When static and fidgeting activity categories were collapsed, the overall accuracy improved to 94%. Personalized models demonstrated higher accuracy than generalized models. CONCLUSIONS: KNOWME Networks can accurately detect a range of activities. KNOWME has the ability to collect and process data in real-time, building the foundation for tailored, real-time interventions to increase PA or decrease sedentary time.

[Effect of Metformin on Apoptosis of Renal Cell Carcinoma Cells in Vitro and Its Mechanisms]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Sep, 2011  |  Pubmed ID: 21945753

To evaluate the effect of metformin on the apoptosis of renal cell carcinoma (RCC) cells in vitro and its mechanisms.

[Development of a Time-resolved Fluoroimmunoassay for Detecting S1 Subunit of Pertussis Toxin and Its Application]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Sep, 2011  |  Pubmed ID: 21945754

To develop a time-resolved fluoroimmunoassay (TRFIA) for detection of pertussis toxin (PT) S1 subunit for quality control of human PT vaccine.

[Correlation of CD82 and HTERT Expressions and HPV Infection with Penile Cancer]

Zhonghua Nan Ke Xue = National Journal of Andrology. Sep, 2011  |  Pubmed ID: 21961244

To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease.

Gamma-secretase Inhibitor Enhances the Cytotoxic Effect of Bortezomib in Multiple Myeloma

Cellular Oncology (Dordrecht). Dec, 2011  |  Pubmed ID: 21965140

Targeting of Notch signaling with γ-secretase inhibitors (GSIs) has been considered a promising strategy for the treatment of hematological malignancies including multiple myeloma (MM). Here we investigated whether the cytotoxic effect of bortezomib, an agent commonly used in MM, could be enhanced by the addition of a GSI.

Critical Roles of Chemokine Receptor CCR10 in Regulating Memory IgA Responses in Intestines

Proceedings of the National Academy of Sciences of the United States of America. Nov, 2011  |  Pubmed ID: 21969568

Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper IgA production to maintain intestinal homeostasis and protect against infection. However, interfering with CCR10 or its ligand did not impair intestinal IgA production under homeostatic conditions or during infection, and the in vivo function of CCR10 in the intestinal IgA response remains unknown. We found that an enhanced generation of IgA(+) cells in isolated lymphoid follicles of intestines offset defective intestinal migration of IgA(+) cells in CCR10-KO mice, resulting in the apparently normal IgA production under homeostatic conditions and in primary response to pathogen infection. However, the compensatorily generated IgA(+) cells in CCR10-KO mice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA-producing plasma cells and IgA(+) memory B cells generated against the pathogen infection could not be maintained properly in intestines. Consequently, IgA memory responses to the pathogen reinfection were severely impaired in CCR10-KO mice. These findings elucidate critical roles of CCR10 in regulating the intestinal IgA response and memory maintenance and could help in design of vaccines against intestinal and possibly other mucosal pathogens.

Evaluation of Apparent Diffusion Coefficient Mappings in Amnestic Mild Cognitive Impairment Using an Image Analysis Software Brain Search

Acta Radiologica (Stockholm, Sweden : 1987). Dec, 2011  |  Pubmed ID: 21969707

The apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can quantify alterations in water diffusivity resulting from microscopic structural changes from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).

Coupling Corona Discharge for Ambient Extractive Ionization Mass Spectrometry

The Analyst. Dec, 2011  |  Pubmed ID: 21971289

Unlike the extractive electrospray ionization (EESI) technique described elsewhere, a corona discharge instead of electrospray ionization has been utilized to charge a neutral solvent spray under ambient conditions for the generation of highly charged microdroplets, which impact a neutral sample plume for the extractive ionization of the analytes in raw samples without any sample pretreatment. Using the positive ion mode, molecular radical cations were easily generated for the detection of non-polar compounds (e.g., benzene, cyclohexane, etc.), while protonated molecular ions of polar compounds (e.g., acetonitrile, acetic ether) were readily produced for the detection. By dispensing the matrix in a relatively large space, this method tolerates highly complex matrices. For a given sample such as lily fragrances, more compounds were detected by the method established here than the EESI technique. An acceptable relative standard deviation (RSD 8.9%, n = 11) was obtained for the direct measurement of explosives (10 ppb) in waste water samples. The experimental data demonstrate that this method could simultaneously detect both polar and non-polar analytes with high sensitivity, showing promising applications for the rapid detection of a wide variety of compounds present in complex matrices.

A Successful International Cooperation with a Bumpy Start

Protein & Cell. Sep, 2011  |  Pubmed ID: 21976059

Treatment of Bone Nonunion and Bone Defects Associated with Unsuccessful Humeral Condylar Fracture Repair with Autogenous Iliac Bone Reconstruction

Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons ... [et Al.]. Oct, 2011  |  Pubmed ID: 21982349

BACKGROUND: Our preliminary study retrospectively assessed outcomes after the use of autogenous iliac bone grafts combined with internal fixation to repair refractory bone nonunions and bone defects associated with supracondylar or intracondylar humeral fractures, or both. MATERIALS AND METHODS: We identified 22 patients (14 men and 8 women) with a mean age of 33.8 years (range, 17-60 years) with bone nonunion and severe bone defects associated with supracondylar or intercondylar humerus fractures, or both. The humeral condyle in each patient was anatomically reconstructed using autologous iliac bone grafts and internal fixation. Active functional exercise was initiated 3 to 4 weeks after surgery. The following variables were assessed: preoperative and postoperative elbow range of motion, Mayo Elbow Performance Score (MEPS), and postoperative complications. RESULTS: Mean follow-up was 38.6 months. Mean duration until bone union was 5.6 months. Preoperatively, 16 patients had a fair or poor MEPS (<75). At final follow-up MEPS was excellent (>90) in 8, good (75-90) in 9, fair (60-74) in 4, and poor (<60) in 1 patient. Postoperative heterotopic ossification anterior to the elbow joint occurred in 2 patients. CONCLUSIONS: Our preliminary results suggest that anatomic reconstruction of the humeral condyle using autogenous iliac bone grafting with internal fixation can improve elbow joint function in patients with bone nonunion and bone defects associated with supracondylar or intracondylar humeral fractures, or both. Larger scale studies are warranted to confirm our findings and compare the efficacy of this vs other surgical approaches.

Clozapine, but Not Olanzapine, Disrupts Conditioned Avoidance Response in Rats by Antagonizing 5-HT(2A/2C) Receptors

Journal of Neural Transmission (Vienna, Austria : 1996). Oct, 2011  |  Pubmed ID: 21986871

The present study was designed to assess the role of 5-HT(2A/2C) receptors in the acute and repeated effect of clozapine and olanzapine in a rat conditioned avoidance response model, a validated model of antipsychotic activity. Male Sprague-Dawley rats that were previously treated with either phencyclidine (0.5-2.0 mg/kg, sc), amphetamine (1.25-5.0 mg/kg, sc), or saline and tested in a prepulse inhibition of acoustic startle study were used. They were first trained to acquire avoidance response to a white noise (CS1) and a pure tone (CS2) that differed in their ability to predict the occurrence of footshock. Those who acquired avoidance response were administered with clozapine (10.0 mg/kg, sc) or olanzapine (1.0 mg/kg, sc) together with either saline or 1-2,5-dimethoxy-4-iodo-amphetamine (DOI, a selective 5-HT(2A/2C) agonist, 1.0 or 2.5 mg/kg, sc), and their conditioned avoidance responses were tested for four consecutive days. After two drug-free retraining days, the long-term repeated effect was assessed in a challenge test during which all rats were injected with a low dose of clozapine (5 mg/kg, sc) or olanzapine (0.5 mg/kg). Results show that pretreatment of DOI dose-dependently reversed the acute disruptive effect of clozapine on both CS1 and CS2 avoidance responses, whereas it had little effect in reversing the acute effect of olanzapine. On the challenge test, pretreatment of DOI did not alter the clozapine-induced tolerance or the olanzapine-induced sensitization effect. These results confirmed our previous findings and suggest that clozapine, but not olanzapine, acts on through 5-HT(2A/2C) receptors to achieve its acute avoidance disruptive effect and likely its therapeutic effects. The long-term clozapine tolerance and olanzapine sensitization effects appear to be mediated by non-5-HT(2A/2C) receptors.

School Environment Factors Were Associated with BMI Among Adolescents in Xi'an City, China

BMC Public Health. 2011  |  Pubmed ID: 21988882

School environment influences students' behaviours. The purpose of this research was to identify school environment factors associated with BMI.

Mental Health System in China: History, Recent Service Reform and Future Challenges

World Psychiatry : Official Journal of the World Psychiatric Association (WPA). Oct, 2011  |  Pubmed ID: 21991281

This paper summarizes the history of the development of Chinese mental health system; the current situation in the mental health field that China has to face in its effort to reform the system, including mental health burden, workforce and resources, as well as structural issues; the process of national mental health service reform, including how it was included into the national public health program, how it began as a training program and then became a treatment and intervention program, its unique training and capacity building model, and its outcomes and impacts; the barriers and challenges of the reform process; future suggestions for policy; and Chinese experiences as response to the international advocacy for the development of mental health.

Large-scale Genome-wide Association Study of Asian Population Reveals Genetic Factors in FRMD4A and Other Loci Influencing Smoking Initiation and Nicotine Dependence

Human Genetics. Oct, 2011  |  Pubmed ID: 22006218

Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p value(meta) = 6.40 × 10(-6); rs2349433, p value(meta) = 5.57 × 10(-6)), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p value(meta) = 2.30 × 10(-6)) and the other at 7q31.1 (rs848353, p value(meta) = 9.16 × 10(-8)). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples.

Disorders in Angiogenesis and Redox Pathways Are Main Factors Contributing to the Progression of Rheumatoid Arthritis: a Comparative Proteomic Study

Arthritis and Rheumatism. Oct, 2011  |  Pubmed ID: 22006448

OBJECTIVES: To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in FLS of RA patients and normal subjects using proteomics analysis. METHODS: Proteins extracted from primary culture of FLS of 50 RA patients and 10 normal subjects were analyzed by automated 2D-Nano-LC-ESI-MS/MS. Differential expressed proteins were screened by 2-sample t-test (p<0.05) and fold change (fold>1.5), based on the bioinformatics analysis. Vasculature development-related proteins (THY-1, CTGF and THBS1) and oxidation reduction-related proteins (SOD2) in synovial tissue were confirmed by real-time PCR and Western blot. The effect of THY-1 and CTGF expression on THY-1, CTGF, THBS1 and VEGF was analyzed also by RNA interference experiments. RESULTS: According to the criteria of having more than one unique peptide per protein present and a false discovery rate ≤5%, 1060 proteins were identified from RA and 1292 proteins from normal subjects, from which 100 differential proteins were screened out in RA. Of them, 46 proteins were up-regulated and the remaining 54 proteins were down-regulated. GO and pathway analyses showed that 6 vasculature development-related proteins were up-regulated including THY-1, CTGF and THBS1, while 11 oxidation reduction-related proteins were down-regulated, including SOD2. The results were consistent with those obtained by mass spectrometry. THY-1, VEGF, CTGF and THBS1 were down-regulated after THY-1 knockdown, and VEGF and CTGF were down-regulated after CTGF knockdown. rhCTGF could enhance proliferation and transwell migration of HUVEC cells. CONCLUSIONS: Up-regulation of vasculature development-related protein and down-regulation of oxidation reduction-related protein in FLS are predominant factors which may be contributing to the pathogenesis of RA. © 2011 American College of Rheumatology.

[Association of RELN SNP Rs7341475 with Schizophrenia in the Chinese Population]

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Oct, 2011  |  Pubmed ID: 22006801

Schizophrenia is a common and complex psychiatric disorder. Significant evidence has suggested that genetic factors play pivotal roles in the etiology of schizophrenia. More than 100 schizophrenia candidate genes have been reported; however, many of them do not have satisfactory replications among different populations. Among these genes, RELN is thought to be associated with schizophrenia in many populations, suggesting it is a real risk gene for this disorder. Identified in the GWAS study, single nucleotide polymorphism (SNP) rs7341475, located in intron 4 of RELN, has been successfully replicated in subsequent investigations, implying its potential contribution to schizophrenia susceptibility. To investigate the association of rs7341475 with schizophrenia in Chinese populations, a case-control association analysis was conducted with samples from Yuxi (400 cases and 400 controls) in southwestern China. The results do not indicate any association of rs7341475 with schizophrenia, which suggests it is not a risk SNP for schizophrenia in Han Chinese.

Association of RELN Promoter SNPs with Schizophrenia in the Chinese Population

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Oct, 2011  |  Pubmed ID: 22006802

Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations. Based on the reported down-regulation of RELN in schizophrenia patients compared with normal subjects, we speculated that variants in the RELN promoter region may confer risk for schizophrenia. In this study, we investigated the associations of three SNPs in the promoter region of RELN with schizophrenia in a case-control sample from southwestern China (940 cases and 1 369 controls). The results suggested that none of the SNPs showed significant associations in our sample, indicating the risk variants for schizophrenia in RELN may not be located in the promoter region. We also performed meta-analysis by combining our data with previously reported data on the Chinese population with a total sample size of 2 843 individuals, and the result remained non-significant. Collectively, our results suggested variants in the RELN promoter may not harbor risk SNPs associated with schizophrenia in the Chinese population.

Excited State Ab Initio and Franck-Condon Simulation of S1 †� S0 Fluorescence Excitation Spectra of P-, M-, and O-difluorobenzenes

The Journal of Physical Chemistry. A. Dec, 2011  |  Pubmed ID: 22017741

Although difluorobenzenes (DFBs) are well-known organic molecules to understand the electronic structure and spectroscopy of benzene and its derivatives, few theoretical investigations have been performed to simulate their fine spectra and assign their vibrational bands. In this work, the fluorescence excitation (FEX) spectra of the first excited singlet states for three DFBs molecules (para-, meta- and ortho-difluorobenzene) were simulated by the Franck-Condon calculations with the displaced harmonic oscillator approximation plus the distorted correction. The calculated results indicated that the spectral profiles of three DFBs are primarily described by the Franck-Condon progression of their totally symmetric vibrational modes. Specifically, it is found that modes v(3) and v(5) of para-DFB, v(8) and v(9) of meta-DFB, and ortho-DFB play the most important roles in the fluorescence spectra. By taking into account the contributions of the distorted effect, we could assign most of the dominant overtones from the nontotally symmetric vibrational modes, and the results agree well with the experimental assignments. Some inferred and unassigned vibrational transitions in experiment were confirmed according to the present calculated results. In addition, in the simulated fluorescence spectra, we tentatively assigned several combination bands with relative moderate intensity and weak vibrational lines which appeared in the experimental observations but the corresponding assignments were not given. The present work reproduced satisfactorily the experimental FEX spectra of p-, m-, and o-DFBs derivatives and provided a useful method to simulate the FEX spectra of dihalogenated benzene molecules.

Epitope-tagged Pkhd1 Tracks the Processing, Secretion, and Localization of Fibrocystin

Journal of the American Society of Nephrology : JASN. Dec, 2011  |  Pubmed ID: 22021705

Mutations in the PKHD1 gene, which encodes fibrocystin, cause autosomal recessive polycystic kidney disease (ARPKD). Unfortunately, the lack of specific antibodies to the mouse protein impairs the study of splicing, post-translational processing, shedding, and temporal and spatial expression of endogenous fibrocystin at the cellular and subcellular level. Here, we report using a knock-in strategy to generate a null Pkhd1 strain and a strain that expresses fibrocystin along with two SV5-Pk epitope tags engineered in-frame into the third exon, immediately C-terminal to the signal-peptide cleavage site in a poorly conserved region. By 6 mo of age, the Pkhd1-null mouse develops massive cystic hepatomegaly and proximal tubule dilation, whereas the mouse with epitope-tagged fibrocystin has histologically normal liver and kidneys at 14 mo. Although Pkhd1 was believed to generate many splice forms, our western analysis resolved fibrocystin as a 500 kD product without other forms in the 15-550 kD range. Western analysis also revealed that exosome-like vesicles (ELVs) secrete the bulk of fibrocystin in its mature cleaved form, and scanning electron microscopy identified that fibrocystin on ELVs attached to cilia. Furthermore, the addition of ELVs with epitope-tagged fibrocystin to wild-type cells showed that label transferred to primary cilia within 5 min. In summary, tagging of the endogenous Pkhd1 gene facilitates the study of the glycosylation, proteolytic cleavage, and shedding of fibrocystin.

Historical Geographic Dispersal of the Golden Snub-nosed Monkey (Rhinopithecus Roxellana) and the Influence of Climatic Oscillations

American Journal of Primatology. Oct, 2011  |  Pubmed ID: 22025257

Current understanding of historic climate oscillations that have occurred over the past few million years has modified scientific views on evolution. Major climatic events have caused local and global extinction of plants and animals and have impacted the spatial distribution of many species. The endangered golden snub-nosed monkey (Rhinopithecus roxellana) currently inhabits three isolated regions of China: the Sichuan and Gansu provinces (SG), the Qinling Mountains in Shaanxi province (QL), and the Shennongjia Forestry District in Hubei province (SNJ). However, considerable uncertainty still exists about their historical dispersal routes under the influence of environment change. To date, two dispersal routes have been proposed: (1) the QL and SNJ populations originated from the SG population; and (2) the SG population recolonized from the QL and SNJ populations. We used the mitochondrial DNA complete control region to perform statistical assessments of the relative probability of alternative migration scenarios and the role of environmental change on the geographic dispersal of Rhinopithecus roxellana. Thirty haplotypes were identified from the three geographic regions and a high degree of genetic structure was observed. The most recent common ancestor among the mitochondrial DNA haplotypes was estimated to live around 0.47-1.88 million years ago and five notable haplotype clusters were found. Phylogenetic analysis and historical gene flow estimates suggested that the QL and SNJ populations originated from the SG population, with at least two dispersal events from the SG population occurring during the Pleistocene (1.17±0.70 and 0.53±0.30 Ma). Composite dispersal history of the golden snub-nosed monkey can be explained by both environmental change inducing global climate change and the influence of the Tibetan Plateau uplift. Such range shifts involved considerable demographic changes, as revealed in the dramatic decreases in population size during the last 25,000 years. Am. J. Primatol. 73:1-11, 2011.  © 2011 Wiley Periodicals, Inc.

Clustering 100,000 Protein Structure Decoys in Minutes

IEEE/ACM Transactions on Computational Biology and Bioinformatics / IEEE, ACM. Oct, 2011  |  Pubmed ID: 22025764

Ab initio protein structure prediction methods first generate large sets of structural conformations as candidates (called decoys), and then select the most representative decoys through clustering techniques. Classical clustering methods are inefficient due to the pairwise distance calculation, and thus become infeasible when the number of decoys is large. In addition, the existing clustering approaches suffer from the arbitrariness in determining a distance threshold for proteins within a cluster: a small distance threshold leads to many small clusters, while a large distance threshold results in the merging of several independent clusters into one cluster. In this paper, we propose an efficient clustering method through fast estimating cluster centroids and efficient pruning rotation spaces. The number of clusters is automatically detected by information distance criteria. A package named ONION, which can be downloaded freely, is implemented accordingly. Experimental results on benchmark data sets suggest that ONION is 14 times faster than existing tools, and ONION obtains better selections for 31 targets, and worse selection for 19 targets compared to SPICKER's selections. On an average PC, ONION can cluster 100,000 decoys in around 12 minutes.

Complete Genome Sequence of Haloarcula Hispanica, a Model Haloarchaeon for Studying Genetics, Metabolism, and Virus-host Interaction

Journal of Bacteriology. Nov, 2011  |  Pubmed ID: 21994921

Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid.

Genetic Association and Identification of a Functional SNP at GSK3β for Schizophrenia Susceptibility

Schizophrenia Research. Dec, 2011  |  Pubmed ID: 21996267

GSK3β is a key gene in neurodevelopment, and also an important target of antipsychotics. Several lines of evidence including association and gene expression studies have suggested GSK3β as a susceptibility gene for schizophrenia, but the underlying genetic mechanism is still unknown. In this study, we test whether the genetic variants in GSK3β contribute to the risk of schizophrenia in Chinese population.

Single Nucleotide Polymorphism WRN Leu1074Phe is Associated with Prostate Cancer Susceptibility in Chinese Subjects

Acta Medica Okayama. Oct, 2011  |  Pubmed ID: 22037268

Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR＝0.58, 95%CI:0.35-0.97, p＝0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age ≤ 72 yr (OR＝0.27, 95%CI:0.12-0.61, p＝0.002) and in patients with localized diseases (OR＝0.36, 95%CI:0.19-0.70, p＝0.003). However, no statistically significant difference was found in the subgroup with age ＞72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects.

Genetics of GABAergic Signaling in Nicotine and Alcohol Dependence

Human Genetics. Nov, 2011  |  Pubmed ID: 22048727

Both nicotine and alcohol addictions are common chronic brain disorders that are of great concern to individuals and society. Although genetics contributes significantly to these disorders, the susceptibility genes and variants underlying them remain largely unknown. Many years of genome-wide linkage and association studies have implicated a number of genes and pathways in the etiology of nicotine and alcohol addictions. In this communication, we focus on current evidence, primarily from human genetic studies, supporting the involvement of genes and variants in the GABAergic signaling system in the etiology of nicotine dependence and alcoholism based on linkage, association, and gene-by-gene interaction studies. Current efforts aim not only to replicate these findings in independent samples, but also to identify which variant contributes to the detected associations and through what molecular mechanisms.

Prenatal Expression of Purinergic Receptor P2X3 in Human Dorsal Root Ganglion

Purinergic Signalling. Nov, 2011  |  Pubmed ID: 22052556

The dorsal root ganglion (DRG) is consisted of neurons that relay multiple types of spinal sensory stimuli to the central nervous system. Several neuroactive molecules may be involved in sensory modulation especially pain processing at the DRG, including the purinergic receptor P2X3 and calcitonin-gene-related peptide (CGRP). P2X3 receptor has been considered a promising pharmaceutical target for the development of new pain medicine. Currently, litter is known about the expression of P2X3 in the human DRG. The present study characterized the localization of P2X3 in prenatal human DRG obtained from fetuses at 4-8 gestational months, by comparing to CGRP expression as well as binding pattern of isolectin-B4 (IB4), a marker of small DRG neurons presumably relevant to nociception. P2X3 immunoreactivity (IR) appeared in most neuron-like perikarya, with their numerical density reduced during the gestational period studied. P2X3 IR was co-labeled very commonly with IB4 binding and infrequently with CGRP IR and was not colocalized with IR for the gliocyte marker glutamine synthetase. Together, the data show an early and broad expression of P2X3 in prenatal human DRG neurons, pointing to a biological role of purinergic signaling during the development of spinal sensory system.

Association of TGF-beta1, IL-4 and IL-13 Gene Polymerphisms with Asthma in a Chinese Population

Asian Pacific Journal of Allergy and Immunology / Launched by the Allergy and Immunology Society of Thailand. Sep, 2011  |  Pubmed ID: 22053598

Asthma is a common respiratory disease caused by genetic and environmental factors. It has been suggested that TGF-beta1, IL-4 and IL-13 play important roles in asthma.

Removal of Methylene Blue from Aqueous Solution with Magnetite Loaded Multi-wall Carbon Nanotube: Kinetic, Isotherm and Mechanism Analysis

Journal of Hazardous Materials. Dec, 2011  |  Pubmed ID: 22040800

In this study, we have demonstrated the efficient removal of cationic dye, methylene blue (MB), from aqueous solution with the one-pot solvothermal synthesized magnetite-loaded multi-walled carbon nanotubes (M-MWCNTs). The as-prepared M-MWCNTs were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The effects of contact time, initial dye concentration, and solution pH on the adsorption of MB onto M-MWCNTs were systematically studied. It was shown that the MB adsorption was pH-dependent. Adsorption kinetics was best described by the pseudo-second-order model. Equilibrium data were well fitted to the Langmuir isotherm model, yielding maximum monolayer adsorption capacity of 48.06 mg g(-1). FTIR analysis suggested that the adsorption mechanism was possibly attributed to the electrostatic attraction and π-π stacking interactions between MWCNTs and MB.

Scavenging Effect of Naoerkang on Amyloid Beta-peptide Deposition in the Hippocampus in a Rat Model of Alzheimer's Disease

Chinese Journal of Integrative Medicine. Nov, 2011  |  Pubmed ID: 22057414

To observe the effect of a Chinese medicine compound, Naoerkang (NEK), on amyloid-beta peptide (1-42; Aβ(1-42)) and matrix metalloproteinase-9 (MMP-9) expressions in the hippocampus of Alzheimer's disease (AD) model rats.

[Therapeutic Effectiveness of Intra-knee-articular Injection of Platelet-rich Plasma on Knee Articular Cartilage Degeneration]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Oct, 2011  |  Pubmed ID: 22069972

Platelet-rich plasma (PRP) can enhance the chondrocyte proliferation and repair of cartilage defects. To explore the safety and efficacy of intra-knee-articular injection of PRP to treat knee articular cartilage degeneration by comparing with injecting sodium hyaluronate (SH).

[Effectiveness of in Situ Subtalar Arthrodesis with Bone Graft for Subtalar Traumatic Arthritis and Gait Analysis]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Oct, 2011  |  Pubmed ID: 22069975

To evaluate the effects of in situ subtalar arthrodesis with bone graft for subtalar traumatic arthritis, and to analyse the plantar pressure distribution so as to provide the evidence for effectiveness evaluation.

Predictors of Suicidal Ideation with Sub-optimal Health Status and Anxiety Symptom Among Chinese Adolescents

Journal of Tropical Pediatrics. Nov, 2011  |  Pubmed ID: 22071377

Evidences in respect to the predictors of suicide ideation are uncertain and most associations only have been identified in cross-sectional studies. More information is needed to identify whether these predictors are true risk factors and can predict the development of suicidal ideation independently. Using the data from a prospective, longitudinal study (n = 2348), we examined the predictors of suicide ideation with demographic variety and psychological well-being of adolescents. Positive items of sub-optimal health status and anxiety symptom at baseline could strongly predict the incidence of self-reported suicidal ideation on a 1-year follow-up study. These results have implications for programs aimed at identifying school students at risk for suicide.

The Structure and Allosteric Regulation of Mammalian Glutamate Dehydrogenase

Archives of Biochemistry and Biophysics. Nov, 2011  |  Pubmed ID: 22079166

Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine, while the most important inhibitors include GTP, palmitoyl CoA, and ATP. Recently, spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds were found to block the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

Replicated Associations of TNFAIP3, TNIP1 and ETS1 with Systemic Lupus Erythematosus in a Southwestern Chinese Population

Arthritis Research & Therapy. Nov, 2011  |  Pubmed ID: 22087647

ABSTRACT: INTRODUCTION: Recent genome-wide and candidate gene association studies in large numbers of systemic lupus erythematosus (SLE) patients have suggested approximately 30 susceptibility genes. These genes are involved in three types of biological processes, including immune complex processing, toll-like receptor function and type I interferon production, and immune signal transduction in lymphocytes, and they may contribute to the pathogenesis of SLE. To better understand the genetic risk factors of SLE, we investigated the associations of seven SLE susceptibility genes in a Chinese population, including FCGR3A, FCGR2A, TNFAIP3, TLR9, TREX1, ETS1 and TNIP1. METHODS: A total of 20 single nucleotide polymorphisms (SNPs) spanning the seven SLE susceptibility genes were genotyped in a sample of 564 unrelated SLE patients and 504 unrelated healthy controls recruited from Yunnan, southwestern China. The associations of SNPs with SLE were assessed by statistical analysis. RESULTS: Five SNPs in two genes (TNFAIP3 and ETS1) were significantly associated with SLE (corrected P values ranging from 0.03 to 5.5 x 10-7). Through stratified analysis, TNFAIP3 and ETS1 showed significant associations with multiple SLE subphenotypes (such as malar rash, arthritis, hematologic disorder and anti-nuclear antibody) while TNIP1 just showed relatively weak association with onset age. The associations of the SNPs in the other four genes were not replicated. CONCLUSIONS: The replication analysis indicates that TNFAIP3, ETS1 and TNIP1 are likely common susceptibility genes for SLE in Chinese populations, and they may contribute to the pathogenesis of multiple SLE subphenotypes.

Development of the Simplified Chinese Version of the Spinal Appearance Questionnaire (SAQ): Cross-Cultural Adaptation and Psychometric Properties Evaluation

Spine. Nov, 2011  |  Pubmed ID: 22089401

ABSTRACT: Study Design. Cross-cultural adaptation and psychometric testing of the Spinal Appearance Questionnaire (SAQ).Objective. To evaluate the reliability and validity of simplified Chinese version of the SAQ (SC-SAQ).Summary of Background Data. The SAQ is widely used to assess the perception of spinal appearance in patients with adolescent idiopathic scoliosis (AIS). However, there is no culturally adapted, reliable, and validated SAQ for mainland China.Methods. The cross-cultural adaptation of the original SAQ was performed following international guidelines. The SC-SAQ was administered concurrently with the simplified Chinese version of the Scoliosis Research Society-22 questionnaire (SC-SRS-22) to 223 patients with AIS. A total of 92 patients were randomly selected to complete the questionnaires again 4-7 days after the first completion. Psychometric testing included reliability by internal consistency and test-test reliability, convergent validity by comparing the SC-SAQ with the SC-SRS-22 appearance domain, and discriminant validity by analyzing the relationship between SC-SAQ scores and patients' characteristics.Results. Internal consistency for the SC-SAQ was satisfactory with intradomain correlations ranging from r = 0.526 to r = 0.808(P <0.0001). The test-retest reliability for the SC-SAQ was excellent with intraclass correlation coefficient of 0.933 (95% confidence interval [CI] = 0.903-0.956) and good Bland-Altman agreement (no systematic bias was found in the Bland-Altman plot). Convergent validity test demonstrated a moderate correlation between the overall SC-SAQ and SC-SRS-22 appearance domain with ρ = -0.401 (p<0.0001). Correlation between the overall SC-SAQ and the major curve magnitude was significant with r = 0.827(p<0.0001). Discriminant validity was confirmed by significant differences of overall SC-SAQ and individual domain scores among the 6 subgroups categorized by the major curve magnitude (P<0.0001) and among patients requiring exercise, bracing, or surgery (P<0.0001).Conclusion. The SC-SAQ showed satisfactory reliability and validity in the evaluation of spinal deformity appearance for AIS patients in mainland China.

[Genotyping for CYP2C19 with Multiplex PCR Point Mutation Screening Technology]

Zhonghua Yi Xue Za Zhi. Aug, 2011  |  Pubmed ID: 22094099

To establish a multiplex PCR point mutation screening technique for the genotyping of CYP2C19.

Diffuse Polymorphic Eosinophilic Cellulitis in a Patient with Metallic Alloy Implants: a Possible Association?

International Journal of Dermatology. Dec, 2011  |  Pubmed ID: 22098002

Molecular Cloning and Functional Characterization of MdSOS2 Reveals Its Involvement in Salt Tolerance in Apple Callus and Arabidopsis

Plant Cell Reports. Nov, 2011  |  Pubmed ID: 22108717

Plants respond to various environmental stresses by activating "stress genes". CIPKs (CBL-interacting protein kinases) family genes play an important role in the process of stress response. In this study, a CIPK gene MdSOS2 was isolated from apple (Malus × Domestica). Sequence alignment and phylogenetic analysis showed that it is highly similar with Arabidopsis AtSOS2 and contained the conserved domains and motifs. Expression analysis demonstrated that MdSOS2 expressed in all tested organs at different levels, and positively in response to salt stress. Furthermore, the ectopic expression of MdSOS2 complemented the function of Arabidopsis sos2 mutant, and conferred enhanced salt tolerance to the transgenic Arabidopsis. Yeast two-hybrid assay indicated that the N-terminal of MdSOS2 protein physically interacted with MdSOS3 and AtSOS3, respectively, suggesting that SOS pathway operates in apple tree. Finally, MdSOS2 overexpression enhanced, while its suppression reduced the tolerance to salt in transgenic apple calluses, indicating that MdSOS2 acts as a positive regulator in response to salt stress in apple.

Photorefractive Two-wave Mixing for Image Amplification in Digital Holography

Optics Express. Oct, 2011  |  Pubmed ID: 22109051

We use photorefractive two-wave mixing for coherent amplification of the object beam in digital holographic recording. Both amplitude and phase reconstruction benefit from the prior amplification as they have an increased SNR. We experimentally verify that the amplification process does not affect the phase of the wavefield. This allows for digital holographic phase analysis after amplification. As the grating formation in photorefractive crystals is just driven by coherent light, the crystal works as a coherence gate. Thus the proposed combination allows for applying digital holography for imaging through scattering media, after the image bearing light is coherence gated and filtered out of scattered background. We show experimental proof-of principle results.

A Novel Micelle of Coumarin Derivative Monoend-functionalized PEG for Anti-tumor Drug Delivery: in Vitro and in Vivo Study

Journal of Drug Targeting. Nov, 2011  |  Pubmed ID: 22118403

In this paper, a novel micelle for anti-tumor drug delivery was reported. Two 7-carboxymethoxy coumarin molecules were immobilized on the terminal group of a methoxy poly(ethylene glycol) chain via l-lysine as linker. The amphiphilic 7-carboxymethoxy coumarin monoend-functionalized methoxy poly(ethylene glycol) (mPEG-Lys-DCOU) chains were self-assembled micelles. Anti-tumor drug doxorubicin was loaded in the mPEG-Lys-DCOU micelles and the release profile was studied. The cytotoxicity of mPEG-Lys-DCOU was evaluated by NIH 3T3 fibroblasts. The drug-loaded micelles were incubated with HepG2 tumor cells to investigate the in vitro anti-tumor effect. The in vivo inhibition efficacy of drug-loaded micelles was carried out on 4T1 breast cancer animal model. The results showed that both hydrophobic and π-π stacking interactions within mPEG-Lys-DCOU amphiphiles were contributed to the self-assembly. Both blank and drug loaded micelles were monodisperse nanoparticles with the average diameters around 300 nm. The release profile exhibited certain pH dependence. The drug release rate at pH = 5.5 was much faster than that at pH = 7.4. mPEG-Lys-DCOU amphiphiles were non-toxic to NIH 3T3 fibroblasts. Both in vitro and in vivo studies demonstrated that the inhibition efficacy of drug-loaded micelles were comparable to that of doxorubicin hydrochloride. mPEG-Lys-DCOU micelles are promising carriers for anti-tumor drug delivery.

A Canine Model of Multiple Organ Dysfunction Following Acute Type-A Aortic Dissection

Surgery Today. Nov, 2011  |  Pubmed ID: 22120508

PURPOSE: Despite recent advances in surgical techniques and perioperative management, the mortality rate in patients with type-A aortic dissection remains high. The establishment of an animal model that exhibits the clinical features of acute aortic dissection would facilitate investigations of the pathogenesis of aortic dissection and the development of appropriate treatments. METHODS: Twelve beagle dogs were divided into two groups: (1) an experimental group treated with the modified surgical procedure to generate an ascending aortic dissection (n = 6); and (2) a control group treated with a median sternotomy but without aortic dissection. All animals received continuous intravenous infusion of adrenaline to achieve controlled hypertension. The tearing length of the aortic intima, the pathological changes, the plasma levels of inflammatory mediators, and the organ functions were dynamically examined and compared. RESULTS: The modified surgical procedure plus controlled hypertension successfully established a novel canine model of acute type-A aortic dissection. In the experimental group, the tearing length of the aortic intima reached the abdominal aorta (average 17 cm), and a false lumen was formed in the aortic media. The lung and intestinal tract had obvious structural injuries. The plasma levels of all inflammatory mediators tested, including tumor necrosis factor-α, interleukin-6, interleukin-10, and endotoxin, were significantly higher in the experimental animals than in the control group. The functional examination of the liver and kidneys revealed substantial disturbances, as reflected by the elevated plasma levels of alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen in the experimental group. CONCLUSIONS: A novel canine model of acute Stanford type-A aortic dissection has been developed, which showed multiple organ dysfunction that mimicked the clinically relevant features observed in man. This aortic dissection model is unique, and may further improve our understanding of the underlying pathogenesis of aortic dissections.

EPO Improves the Proliferation and Inhibits Apoptosis of Trophoblast and Decidual Stromal Cells Through Activating STAT-5 and Inactivating P38 Signal in Human Early Pregnancy

International Journal of Clinical and Experimental Pathology. 2011  |  Pubmed ID: 22135724

The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot, respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the normal early pregnancy. This study suggests that HIF-1α may regulate the expression of EPO, which plays a favorable regulatory role in the proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.

Use of the Metabolomics Approach to Characterize Chinese Medicinal Material Huangqi

Molecular Plant. Dec, 2011  |  Pubmed ID: 22138859

Integration of the genetic and metabolic fingerprinting can provide a new approach to differentiate similar Traditional Chinese Medical (TCM) materials. Two leguminous plants, Mojia Huangqi and Menggu Huangqi, are important medical herbs and share great similarities in morphology, chemical constituent, and genomic DNA sequence. The taxonomy of Mojia Huangqi and Menggu Huangqi has been debated for more than 50 years and discrimination of TCM materials directly affects the pharmacological and clinical effects. AFLP based genetic fingerprinting and GC-TOF/MS-based metabolic fingerprinting were used to successfully discriminate the two species. The results of AFLP supported the opinion that Menggu Huangqi was a variant of Mojia Huangqi. The metabolic fingerprinting showed growth locations have greater impacts on the metabolite composition and quantity than the genotypes (cultivated versus wild) in Menggu Huangqi. The difference of some soluble sugars, fatty acids, proline, and polyamine reflected plant adaptation to different growth environments. Using multivariate and univariate statistical analysis, three AFLP markers and eight metabolites were identified as candidate DNA and metabolic markers to distinguish the two herb materials. The correlation network between AFLP markers and metabolites revealed a complex correlation network, which indicated the special metabolic pathways and the regulation networks of Huangqi.

Dengue Vector Surveillance Programs: a Review of Methodological Diversity in Some Endemic and Epidemic Countries

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Nov, 2011  |  Pubmed ID: 22144710

Vector surveillance is a cornerstone of dengue management yet there is a diversity of surveillance programs evident internationally. Such diversity is described in this review to enable a broader assessment of dengue vector surveillance methods. This review describes the diversity of surveillance programs for dengue vectors in several endemic and epidemic countries. Furthermore, strengths and weaknesses of vector surveillance methods, including larval surveys, BG-Sentinel trap, and autocidal and sticky ovitraps, are also discussed. The ability to compare and contrast these programs could contribute to the finding of better methods both locally and nationally and facilitate interregional technology transfer. Health authorities in both endemic and epidemic countries alike could benefit from adopting technologies and practices from other regions.

Postoperative Mortality and Morbidity in Octogenarians and Nonagenarians with Hip Fracture: an Analysis of Perioperative Risk Factors

Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi / Chinese Medical Association. Dec, 2011  |  Pubmed ID: 22152134

Objective: To evaluate the role of high risk factors in octogenarians and nonagenarians with hip trauma, which may lead to excessive mortality and morbi- dity postoperatively.Methods: Fifty-four octogenarians and nonagenarians patients were enrolled in the study, receiving surgical repair of hip fracture in our hospital from January 2006 to January 2010. High risk factors were recorded preoperatively in detail. Complications and survival state were followed up by telephone for 2 years postoperatively. All the data were analyzed by Chi-square test with SPSS 13.0.Results: Twenty-six males (48.1%), aged from 80 to 94 years with a mean age of 84.2 years, and twenty-eight females (51.9%), aged from 80 to 95 years with a mean age of 83.4 years, were presented in the cohort study. The hip traumas were caused by daily slight injuries (52 cases) and car accidents (2 cases), respectively. Twenty-eight patients (51.9%) with femoral neck fracture while 26 patients (48.1%) with intertrochanteric fracture were diagnosed through an anterior-posterior pelvic radiophotograph. In this series, 39 patients (72.2%) suffered from one or more comorbidities preoperatively. The morbidity was 48.1% and the major cause was urinary tract infection, while a significant difference was noted between females and males. The mortality was 20.4% with a predominant cause of acute renal failure.Conclusions: The gender should be considered as a critical high risk factor in octogenarians and nonagenarians with hip trauma postoperatively. Females are more likely to suffer complications postoperatively, which is especially obvious in senile patients over 80 years (P less than 0.05). Urinary tract infection is the most frequent complication after hip surgery, followed by low limb embolism and malnutrition. The mortality is dramatically greater in patients over 80 years old than those below, and major causes are acute renal failure, multiple organ dysfunction syndrome and mental deterioration. Multidisciplinary consultations and mental assessment are encouraged in patients over 80 years old after hip trauma and surgery. Hip fractures in octogenarians and nonagenarians deserve special attention because of their advanced age and comorbidities.

Forensically Informative Nucleotide Sequencing (FINS) for the Authentication of Chinese Medicinal Materials

Chinese Medicine. 2011  |  Pubmed ID: 22153058

ABSTRACT: Chinese medicinal materials may be authenticated by molecular identification. As a definitive approach to molecular identification of medicinal materials, forensically informative nucleotide sequencing (FINS) comprises four steps, namely (1) DNA extraction from biological samples, (2) selection and amplification of a specific DNA fragment, (3) determination of the sequence of the amplified DNA fragment and (4) cladistic analysis of the sample DNA sequence against a DNA database. Success of the FINS identification depends on the selection of DNA region and reference species. This article describes the techniques and applications of FINS for authenticating Chinese medicinal materials.

Guanylate Binding Protein 1 is a Novel Effector of EGFR-driven Invasion in Glioblastoma

The Journal of Experimental Medicine. Dec, 2011  |  Pubmed ID: 22162832

Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.

Mitochondrial Genome of Plateau Zokor Myospalax Baileyi

Mitochondrial DNA. Oct, 2011  |  Pubmed ID: 22165832

Plateau zokors Myospalax baileyi are subterranean rodents and endemic to the cold and hypoxic (2800-4300 m above sea level) climate of the farm, prairie, alpine prairie, and meadow habitats across the Tibetan plateau. The complete mitochondrial (mt) genome of M. baileyi has been determined. Our results showed that the total length of the mitogenome was 16,351 bp, and had a gene content of 13 protein coding, 22 tRNAs and 2 rRNAs. Except for the seven tRNA and Nd6 genes, all other mt genes are encoded on the heavy strand. The overall base composition of the heavy strand is 33.65% A, 29.65% T, 24.42% C, and 12.28% G, with an AT content of 63.3%.

Polymorphic Variations in Manganese Superoxide Dismutase (MnSOD), Glutathione Peroxidase-1 (GPX1), and Catalase (CAT) Contribute to Elevated Plasma Triglyceride Levels in Chinese Patients with Type 2 Diabetes or Diabetic Cardiovascular Disease

Molecular and Cellular Biochemistry. Dec, 2011  |  Pubmed ID: 22167619

Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case-control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (T→C), GPX1 Pro198Leu (C→T), and CAT -262C/T (C→T) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.

[History of Hot Spring Bath Treatment in China]

Zhonghua Yi Shi Za Zhi (Beijing, China : 1980). Jul, 2011  |  Pubmed ID: 22169492

As early as the 7th century B.C. (Western Zhou Dynasty), there is a recording as 'spring which contains sulfur could treat disease' on the Wentang Stele written by WANG Bao. Wenquan Fu written by ZHANG Heng in the Easten Han Dynasty also mentioned hot spring bath treatment. The distribution of hot springs in China has been summarized by LI Daoyuan in the Northern Wei Dynasty in his Shuijingzhu which recorded hot springs in 41 places and interpreted the definition of hot spring. Bencao Shiyi (by CHEN Cangqi, Tang Dynasty) discussed the formation of and indications for hot springs. HU Zai in the Song Dynasty pointed out distinguishing hot springs according to water quality in his book Yuyin Conghua. TANG Shenwei in the Song Dynasty noted in Jingshi Zhenglei Beiji Bencao that hot spring bath treatment should be combined with diet. Shiwu Bencao (Ming Dynasty) classified hot springs into sulfur springs, arsenicum springs, cinnabar springs, aluminite springs, etc. and pointed out their individual indications. Geologists did not start the work on distribution and water quality analysis of hot springs until the first half of the 20th century. There are 972 hot springs in Wenquan Jiyao (written by geologist ZHANG Hongzhao and published in 1956). In July 1982, the First National Geothermal Conference was held and it reported that there were more than 2600 hot springs in China. Since the second half of the 20th century, hot spring sanatoriums and rehabilitation centers have been established, which promoted the development of hot spring bath treatment.

Recent Advances in Single Molecule Studies of Nucleosomes

Current Opinion in Structural Biology. Dec, 2011  |  Pubmed ID: 22172540

As the fundamental packing units of DNA in eukaryotes, nucleosomes play a central role in governing DNA accessibility in a variety of cellular processes. Our understanding of the mechanisms underlying this complex regulation has been aided by unique structural and dynamic perspectives offered by single molecule techniques. Recent years have witnessed remarkable advances achieved using these techniques, including the generation of a detailed histone-DNA energy landscape, elucidation of nucleosome disassembly processes, and real-time monitoring of molecular motors interacting with nucleosomes. These and other highlights of single molecule nucleosome studies will be discussed in this review.

Modulation of Innate Immune-related Pathways in Nicotine-treated SH-SY5Y Cells

Amino Acids. Dec, 2011  |  Pubmed ID: 22187147

Although nicotine has a broad impact on both the central and peripheral nervous systems, the molecular mechanisms remain largely unknown, especially at the signaling pathway level. To investigate that aspect, we employed both conventional molecular techniques, such as quantitative real-time PCR and Western blotting analysis, and high-throughput microarray approach to identify the genes and signaling pathways that are modulated by nicotine. We found 14 pathways significantly altered in SH-SY5Y neuroblastoma cells. Of these, the Toll-like receptor pathway (TLR; p = 2.57 × 10(-4)) is one of the most important innate immune pathways. The death receptor pathway (DR; p = 8.71 × 10(-4)), whose transducers coordinate TLR signals and help conduct the host immune response to infection, was also significantly changed by nicotine. Furthermore, we found that several downstream pathways of TLR and DR signaling, such as PI3K/AKT signaling (p = 9.55 × 10(-6)), p38 signaling (p = 2.40 × 10(-6)), and ERK signaling (p = 1.70 × 10(-4)), were also significantly modulated by nicotine. Interestingly, most of the differentially expressed genes in these pathways leading to nuclear factor κB (NF-κB) activation and those important inhibitors of pathways leading to apoptosis, including FLIP and Bcl-2, were up-regulated by nicotine. Taken together, our findings demonstrate that nicotine can regulate multiple innate immune-related pathways, and our data thus provide new clues to the molecular mechanisms underlying nicotine's regulatory effects on neurons.

Correlation Between Morphologic Appearance and Function of Filtering Bleb in Vivo

Yan Ke Xue Bao = Eye Science / "Yan Ke Xue Bao" Bian Ji Bu. Dec, 2011  |  Pubmed ID: 22187303

Efficacy and long-term success of trabeculectomy largely depends on the postoperative development of a functioning filtering bleb. This study was designed to observe histological changes in filtering blebs after trabeculectomy using in vivo confocal microscopy (IVCM), and to investigate the correlation between morphologic appearance and function of filtering blebs.

Comparison Between Two Pedicle Screw Augmentation Instrumentations in Adult Degenerative Scoliosis with Osteoporosis

BMC Musculoskeletal Disorders. 2011  |  Pubmed ID: 22188765

ABSTRACT:

Broadband Superluminescent Diode-based Ultrahigh Resolution Optical Coherence Tomography for Ophthalmic Imaging

Journal of Biomedical Optics. Dec, 2011  |  Pubmed ID: 22191923

Spectral domain optical coherence tomography (SD-OCT) with ultrahigh resolution can be used to measure precise structures in the context of ophthalmic imaging. We designed an ultrahigh resolution SD-OCT system based on broadband superluminescent diode (SLD) as the light source. An axial resolution of 2.2 μm in tissue, a scan depth of 1.48 mm, and a high sensitivity of 93 dB were achieved by the spectrometer designed. The ultrahigh-resolution SD-OCT system was employed to image the human cornea and retina with a cross-section image of 2048 × 2048 pixels. Our research demonstrated that ultrahigh -resolution SD-OCT can be achieved using broadband SLD in a simple way.

A Genome-wide Association Study in Han Chinese Identifies Multiple Susceptibility Loci for IgA Nephropathy

Nature Genetics. 2011  |  Pubmed ID: 22197929

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

Functional Definition of LuxS, an Autoinducer-2 (AI-2) Synthase and Its Role in Full Virulence of Streptococcus Suis Serotype 2

Journal of Microbiology (Seoul, Korea). Dec, 2011  |  Pubmed ID: 22203565

Quorum sensing is a widespread chemical communication in response to fluctuation of bacterial population density, and has been implicated into bacterial biofilm formation and regulation of expression of virulence factors. The luxS gene product, S-ribosylhomocysteinase, catalizes the last committed step in biosynthetic pathway of autoinducer 2 (AI-2), a signaling molecule for inter-species quorum sensing. We found a luxS homologue in 05ZYH33, an epidemic strain of Streptococcus suis serotype 2 (SS2) in China. A luxS null mutant (ΔluxS) of 05ZYH33 strain was obtained using an approach of homologous recombination. LuxS was determined to be required for AI-2 production in 05ZYH33 strain of S. suis 2. Inactivation of luxS gene led to a wide range of phenotypic changes including thinner capsular walls, increased tolerance to H(2)O(2), reduced adherence capacity to epithelial cells, etc. In particular, loss of LuxS impaired dramatically its full virulence of SS2 in experimental model of piglets, and functional complementation restored it nearly to the level of parent strain. Genome-wide transcriptome analyses suggested that some known virulence factors such as CPS are down-regulated in the ΔluxS mutant, which might in part explain virulence attenuation by luxS deletion. Similarly, 29 of 71 genes with different expression level were proposed to be targets candidate regulated by LuxS/AI-2-dependent quorum sensing.

ACSL6 is Associated with the Number of Cigarettes Smoked and Its Expression is Altered by Chronic Nicotine Exposure

PloS One. 2011  |  Pubmed ID: 22205969

Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions.

CD4+CD25+Foxp3+ Regulatory T Cells Protect Endothelial Function Impaired by Oxidized Low Density Lipoprotein Via the KLF-2 Transcription Factor

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2011  |  Pubmed ID: 22178876

To investigate the regulation of CD4(+)CD25(+) Regulatory T cells (Tregs) on pro-inflammatory adhesion molecules, Krüppel-Like Factor-2 (KLF-2) and its downstream transcriptional targets in human umbilical vein endothelial cells (HUVECs) impaired by ox-LDL and the mechanisms of it.

Behind the Artemisinin, Efforts and Persistence from Numerous Scientists

Protein & Cell. Nov, 2011  |  Pubmed ID: 22180085

Topiramate for the Treatment of Methamphetamine Addiction: a Multi-center Placebo-controlled Trial

Addiction (Abingdon, England). Dec, 2011  |  Pubmed ID: 22221594

Aims: Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled outpatient trial tested topiramate for treating methamphetamine addiction. Design: Participants (N = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 6-12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting: The trial was conducted at eight medical centers in the United States. Participants: One hundred forty methamphetamine-dependent adults took part in the trial. Measurements: The primary outcome was abstinence from methamphetamine during weeks 6-12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. Findings: In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6-12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer-rated severity of dependence scores significantly. Subjects with negative urine before randomization (N = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 6-12. Topiramate was safe and well tolerated. Conclusions: Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.

[Modified Single-stage Transpedicular Decompression, Debridement, and Posterior Instrumentation in Treatment of Thoracic Tuberculosis]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Nov, 2011  |  Pubmed ID: 22229179

To investigate the effectiveness and feasibility of modified single-stage transpedicular decompression, debridement, and posterior instrumentation in treatment of thoracic tuberculosis.

Modeling High-level Descriptions of Real-life Physical Activities Using Latent Topic Modeling of Multimodal Sensor Signals

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22255715

We propose a new methodology to model high-level descriptions of physical activities using multimodal sensor signals (ambulatory electrocardiogram (ECG) and accelerometer signals) obtained by a wearable wireless sensor network. We introduce a two-step strategy where the first step estimates likelihood scores over the low-level descriptions of physical activities such as walking or sitting directly from sensor signals and the second step infers the high-level description based on the estimated low-level description scores. Assuming that a high-level description of a certain physical activity may consist of multiple low-level physical activities and a low-level physical activity can be observed in multiple high-level descriptions of physical activities, we introduce the statistical concept of latent topics in physical activities to model the high-level status with low-level descriptions. With an unsupervised approach using a database from unconstrained free-living settings, we show promising results in modeling high-level descriptions of physical activities.

T Cell- but Not Tumor Cell-produced TGF-β1 Promotes the Development of Spontaneous Mammary Cancer

Oncotarget. Dec, 2011  |  Pubmed ID: 22248703

During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development. Here, using a transgenic model of mammary cancer, we report that deletion of TGF-β1 from tumor cells did not protect mice from tumor development. However, ablation of TGF-β1 from T cells significantly inhibited mammary tumor growth. Additionally, absence of TGF-β1 in T cells prevented tumors from advancing to higher pathological grades and further suppressed secondary tumor development in the lungs. These findings reveal T cells but not tumor cells as a critical source of TGF-β1 that promotes tumor development.

[Diagnosis and Treatment of Occult Sacral Fracture]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Dec, 2011  |  Pubmed ID: 22276524

The occult sacral fracture has no symptoms of sacral nerves injuries and no severe pain. These occult sacral fractures have no significant fracture signs on plain X-ray film, which can be found only by spiral CT or MRI and be misdiagnosed easily. This article made a brief review on the diagnosis and treatment of this type of sacral fractures.

[Energy Expenditure of Healthy Adults Engaged in Light Activities in Southern China Measured by Energy Balance Method]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Nov, 2011  |  Pubmed ID: 22279664

To measure the energy expenditure of healthy adults engaged in light activities in southern China, and to provide reference database for revising Chinese RNI.

Knockdown of S100A4 Decreases Tumorigenesis and Metastasis in Osteosarcoma Cells by Repression of Matrix Metalloproteinase-9

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 22292654

Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is highly malignant. Metastases are the major cause of death, and patients with relapse have a poor prognosis. Given the associations of S100A4 with OS and tumor metastasis, we explored its potential roles in OS metastasis. Among 32 OS (16 metastatic and 16 non- metastatic) specimens examined, we found a significant increase of S100A4 mRNA in metastatic tissues, and more importantly, expression of S100A4 and MMP-9 to be strongly correlated in patients who had lymph node or distant metastasis. We observed that siRNA mediated suppression of the S100A4 gene significantly reduced the proliferative and invasive capability of highly invasive OS cells, with a reduced rate of tumor growth and metastasis under in vivo conditions. Matrix metalloproteinase 9 (MMP-9) proved highly responsive to S100A4 gene suppression, demonstrating significant reduction in proteolytic activity, while overexpression of S100A4 increased the expression and proteolytic activity of MMP-9. Links of S100A4 with cell motility were confirmed by depletion which resulted in reduced cell migration. Moreover, loss of cell metastatic potential was completely rescued by overexpression of MMP-9. Collectively, our findings indicate that S100A4 contributes to OS metastasis by stimulating MMP-9 expression, suggesting potential as a novel diagnostic biomarker for OS progression as well as a therapeutic target.

[The Combined Fixation with Splints and Plaster After Closed Reduction for the Treatment of Distal Fractures of Radius in Elderly Patients]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Nov, 2011  |  Pubmed ID: 22295482

To evaluate the effects of combined fixation with splints and plaster after closed reduction for the treatment of distal fractures of radius in elderly patients

[Endovascular Repair of Infrarenal Abdominal Aortic Aneurysm with the Complex Aortic Anatomy]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Oct, 2011  |  Pubmed ID: 22321680

To explore the safety and efficiency of endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) which have the complex aortic anatomy.

[Correlations of Serum Alanine Aminotransferase and Insulin Resistance, Pancreatic B-cell Function]

Zhonghua Yi Xue Za Zhi. Dec, 2011  |  Pubmed ID: 22333257

To explore the correlations of serum alanine aminotransferase (ALT), insulin resistance and pancreatic B-cell function.

Insulin-Like Growth Factor 3 Regulates Expression of Genes Encoding Steroidogenic Enzymes and Key Transcription Factors in the Nile Tilapia Gonad

Biology of Reproduction. Feb, 2012  |  Pubmed ID: 22337331

Insulin-like growth factors (Igfs) are implicated in a wide variety of physiological roles in teleost gonadal development and reproduction. In the present study, igf3 mRNA expression in the tilapia ovary was found to be higher than in the testis from 5 to 40 days after hatching (dah), but was lower than the testis from 50 to 70 dah. Consistently, Igf3 protein signal was detected in the somatic cells of the XX and XY gonads from 10 dah till adulthood by immunohistochemistry using a specific Igf3 polyclonal antibody. Incubation of ovarian and testicular cells in primary culture with recombinant Igf3 significantly increased nr5a1, foxl2, dmrt1, cyp19a1a, cyp11a1, cyp11b2, hsd3b2 and cyp17a1 expression in time- and dose-dependent manners. Promoter analysis using luciferase assays in HEK293 cells revealed that igf3 promoter activity was directly activated by Nr5a1 (Sf1), and further enhanced by Foxl2, Nr0b1a (Dax1) and Nr0b1b (Dax2) but repressed by Dmrt1 and estrogen receptor (Esr1, Esr2a or Esr2b) along with 17beta-estradiol treatment. In addition, igf3 promoter activity was increased slightly by Forskolin treatment alone, but synergistically up-regulated by transfection with nr5a1. These in vitro results correlated well with the expression profile of igf3 during early gonad differentiation. Our results indicated that igf3 is involved in fish gonad steroidogenesis because of its ability to regulate the expression of foxl2, dmrt1, nr5a1 and steroidogenic enzymes. The expression of igf3 is in turn regulated by the transcription factors Foxl2, Dmrt1 and Nr5a1 as well as by 17beta-estradiol treatment.

Folate Status and Health Behaviours in Two Australian Indigenous Populations in North Queensland

Public Health Nutrition. Feb, 2012  |  Pubmed ID: 22321761

OBJECTIVE: To assess nutritional status using red-cell folate (RCF) and associated health behaviours including fruit and vegetable intake, smoking, drinking and physical activity in two Indigenous populations living in remote northern Australia. DESIGN: A cross-sectional survey conducted during 1998-2000. SETTING: Twenty-six rural communities in north Queensland, Australia. SUBJECTS: A total of 2524 Indigenous people aged 15 years and over was included in the study. Self-reported fruit and vegetable intake, tobacco smoking, alcohol intake and physical activity were recorded. RCF was measured using the Bayer Advia Centaur automated immunoassay system. The association between low RCF (RCF<295 nmol/l) and risk factors was analysed using general linear models adjusted for demographic factors and covariates, namely BMI, diabetes and dyslipidaemia. RESULTS: The prevalence of RCF deficiency was higher in Aboriginal participants compared with Torres Strait Islanders (25·6 % v. 14·8 %, P < 0·001). Young women of childbearing age were more likely to have low RCF. Among Aboriginal adults, smoking was strongly associated with low RCF (risk ratio = 1·9, 95 % CI 1·5, 2·5 in females and risk ratio = 2·9, 95 % CI 1·9, 4·2 in males). CONCLUSIONS: Indigenous Australians, especially women of childbearing age, had high prevalence of low RCF. Smoking was associated with insufficient folate independent of fruit and vegetable intake and alcohol consumption in the Aboriginal population. This population with an already higher risk of obesity and higher rate of tobacco smoking should be targeted to improve nutrition status to prevent ill health such as diabetes and CVD.

Cerebrospinal Fluid Aβ and Tau Level Fluctuation in an Older Clinical Cohort

Archives of Neurology. Feb, 2012  |  Pubmed ID: 22332192

To determine whether cerebrospinal fluid (CSF) biomarkers for Alzheimer disease fluctuate significantly over time in a cohort of older, mildly symptomatic individuals.

Theoretical Studies on the Mo-catalyzed Asymmetric Intramolecular Pauson-Khand-type [2 + 2 + 1] Cycloadditions of 3-allyloxy-1-propynylphosphonates

Journal of Molecular Modeling. Feb, 2012  |  Pubmed ID: 22297921

Density functional theory (DFT) was used to investigate the Mo-catalyzed intramolecular Pauson-Khand reaction of 3-allyloxy-1-propynylphosphonates. All intermediates and transition states were optimized completely at the B3LYP/6-31 G(d,p) level [LANL2DZ(f) for Mo]. In the Mo-catalyzed intramolecular Pauson-Khand reaction, the C-C oxidative cyclization reaction was the chirality-determining step, and the reductive elimination reaction was the rate-determining step. The carbonyl insertion reaction into the Mo-C(sp (3)) bond was easier than into the Mo-C = C bond. And the dominant product predicted theoretically was of (S)-chirality, which agreed with experimental data. This reaction was solvent dependent, and toluene was the best among the three solvents toluene, CH(3)CN, and THF.

Causes of Death After Hip Fracture in Senile Patients

Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi / Chinese Medical Association. Feb, 2012  |  Pubmed ID: 22300919

Hip trauma has been a leading cause of death in senile patients for more than a centenary. Although the mortality decreased due to the advanced technique in medication, surgery and nursing, the increasing mortality should not be neglected in elders after orthopedic operation nowadays. Many factors are considered to influence the causes of death after trauma, such as age, gender, personal customs, comorbidities, types of fracture, timing of surgery, procedure, anesthesia, complications, medical treatment, activity of daily living, or even marriage status. This article reviews these causes from the aspects of patient's own factors, iatrogenic factors, medical treatment and other factors and provides some clues for further clinical application according to the recent foreign and domestic researches. According to the present research, it is essential for surgeons to perform a comprehensive estimation for patients suffering from hip trauma.

Global Stability of Plasma Proteomes for Mass Spectrometry-based Analyses

Molecular & Cellular Proteomics : MCP. Feb, 2012  |  Pubmed ID: 22301387

Peptide-based mass spectrometry approaches, such as multiple reaction monitoring (MRM) provide a powerful means to measure candidate protein biomarkers in plasma. A potential confounding problem is the effect of preanalytical variables, which may affect the integrity of proteins and peptides. Although some blood proteins undergo rapid physiological proteolysis ex vivo, the stability of most plasma proteins to preanalytical variables remains largely unexplored. We applied liquid chomatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomics and MRM analyses to characterize the stability of proteins at the peptide level in plasma. We systematically evaluated the effects of delay in plasma preparation at different temperatures, multiple freeze-thaw cycles and erythocyte hemolysis on peptide and protein inventories in prospectively collected human plasma. Time course studies indicated few significant changes in peptide and protein identifications, semi-tryptic peptides and methionine-oxidized peptides in plasma from blood collected in EDTA plasma tubes and stored for up to a week at 4° C or room temperature prior to plasma isolation. Similarly, few significant changes were observed in similar analyses of plasma subjected to up to 25 freeze-thaw cycles. Hemolyzed samples produced no significant differences beyond the presence of hemoglobin proteins. Finally, paired comparisons of plasma and serum samples prepared from the same patients also yielded few significant differences, except for the depletion of fibrinogen in serum. Blood proteins thus are broadly stable to preanalytical variables when analyzed at the peptide level. Collection protocols to generate plasma for MRM-based analyses may have different requirements than for other analyses directed at intact proteins.

The Distribution Profile and Oxidation States of Biometals in APP Transgenic Mouse Brain: Dyshomeostasis with Age and As a Function of the Development of Alzheimer's Disease

Metallomics : Integrated Biometal Science. Feb, 2012  |  Pubmed ID: 22301945

The enrichment of transition metals in the brain and the dyshomeostasis of metals are thought to be important etiological factors for elderly people in a number of neurodegenerative diseases, including Alzheimer's disease (AD). However, the understanding of how biometals dynamically dysregulate in the stages of AD development, such as the exact time-dependent and site-dependent accumulation in the brain with AD progression, is still limited. Herein, by using the APP/V717I transgenic mouse model and age-matched mice as control, we offer distinctive in situ and quantitative images of metals (Cu, Fe, Zn and Ca) in brain sections by synchrotron radiation micro beam X-ray fluorescence (SR-μXRF). The images show that Fe and Ca increased with brain aging in both AD and control (CNT) mice, and Cu, Fe, Zn and Ca appeared significantly elevated in AD mice and showed an obvious age-dependent rise. Fe, Cu and Zn were obviously specifically enriched in the cortex and hippocampus, which were also the plaque-formation sensitive brain regions. Our results demonstrate that the enrichment of transition metals with age and metals' dyshomeostasis in specific regions may contribute together to the etiology and development of AD in elderly people. The XANES measurements of Cu and Fe show evidence that Cu may have redox properties in the AD brain.

RRM1 and ERCC1 Expression in Peripheral Blood Versus Tumor Tissue in Gemcitabine/carboplatin-treated Advanced Non-small Cell Lung Cancer

Cancer Chemotherapy and Pharmacology. Feb, 2012  |  Pubmed ID: 22302408

PURPOSE: To comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy. METHODS: A total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated. RESULTS: RRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (r = 0.332, 0.258; P = 0.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (r = 0.351; P = 0.013) and tumor tissue (r = 0.634; P < 0.001). Neither was correlated with clinical and pathological factors. Patients with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; P = 0.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0 months, 18.5 vs. 12.0 months, and 19.8 vs. 12.5 months; P = 0.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0 months, 7.8 vs. 3.9 months, and 5.8 vs. 3.8 months; P = 0.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival. CONCLUSIONS: Advanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy.

Reliability and Validity of Simplified Chinese Version of Roland-morris Questionnaire in Evaluating Rural and Urban Patients with Low Back Pain

PloS One. 2012  |  Pubmed ID: 22303457

The causes of low back pain in China and Western countries are extremely different. We attempted to analyze the risk factors of low back pain in urban and rural patients under the dual economy with the simplified Chinese version of Roland-Morris disability questionnaire (SC-RMDQ) to demonstrate that SC-RMDQ could evaluate patients with low back pain arising from different causes.

Comparison of Adaptive Statistical Iterative and Filtered Back Projection Reconstruction Techniques in Brain CT

European Journal of Radiology. Feb, 2012  |  Pubmed ID: 22304977

PURPOSE: To compare image quality and visualization of normal structures and lesions in brain computed tomography (CT) with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP) reconstruction techniques in different X-ray tube current-time products. MATERIALS AND METHODS: In this IRB-approved prospective study, forty patients (nineteen men, twenty-one women; mean age 69.5±11.2 years) received brain scan at different tube current-time products (300 and 200mAs) in 64-section multi-detector CT (GE, Discovery CT750 HD). Images were reconstructed with FBP and four levels of ASIR-FBP blending. Two radiologists (please note that our hospital is renowned for its geriatric medicine department, and these two radiologists are more experienced in chronic cerebral vascular disease than in neoplastic disease, so this research did not contain cerebral tumors but as a discussion) assessed all the reconstructed images for visibility of normal structures, lesion conspicuity, image contrast and diagnostic confidence in a blinded and randomized manner. Volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded. All the data were analyzed by using SPSS 13.0 statistical analysis software. RESULTS: There was no statistically significant difference between the image qualities at 200mAs with 50% ASIR blending technique and 300mAs with FBP technique (p>.05). While between the image qualities at 200mAs with FBP and 300mAs with FBP technique a statistically significant difference (p<.05) was found. CONCLUSION: ASIR provided same image quality and diagnostic ability in brain imaging with greater than 30% dose reduction compared with FBP reconstruction technique.

ApoA1: Mimetic Peptide Reverses Adipocyte Dysfunction in Vivo and in Vitro Via an Increase in Hemeoxygenase (HO-1) and Wnt10b

Cell Cycle (Georgetown, Tex.). Feb, 2012  |  Pubmed ID: 22306989

Insulin resistance is a risk factor in the development of type 2 diabetes and is a major cause of atherosclerosis. Reduction in heme oxygenase (HO-1) has been shown to exacerbate vascular dysfunction and insulin resistance in obese mice and involves a decrease in adiponectin levels. Adiponectin is released from mesenchymal stem cell (MSC)-derived adipocytes, its levels are decreased in type 2 diabetes. We hypothesized that the apoA1 mimetic peptide, L-4F, will target the expression of the HO-1-adiponectin axis and reverse adipocyte dysfunction both in vivo and in vitro. The administration of L-4F [2 mg/Kg/daily (i.p.) for 4-week to 8-week-old obese (ob) mice restored adipocyte function, increased adiponectin release (p < 0.05) and decreased the levels of IL-1 and IL-6 (p < 0.05)]. These perturbations were associated with an increase in insulin sensitivity (p < 0.01 vs. untreated ob mice) and decreased glucose levels (309 + 42 vs. 201 + 8 mg/d after L-4F treatment). Treatment of both mesenchymal stem cell (MSC)-derived adipocytes with L-4F (50 μg/ml) increased adiponectin (p < 0.05), decreased IL-1 and IL-6 (p < 0.05) levels and increased MSC-derived adipocyte cell numbers by 50% in S phase (p < 0.05). MSC-derived adipocytes treated with L-4F increased WNT10b and decreased Peg 1/Mest. Inhibition of HO activity reversed the decrease in the adipogenic response gene, Peg 1/Mest. An increase of HO-1 expression by L-4F increased insulin-receptor phosphorylation. These findings support the hypothesis that L-4F increases early adipocyte markers, HO-1-adiponectin, WNT10b and decreases Peg1/Mest, negative regulators of adipocyte differentiation.

A Highly Diastereoselective Three-component Tandem 1,4-conjugated Addition-cyclization Reaction to Multisubstituted Pyrrolidines

Organic & Biomolecular Chemistry. Mar, 2012  |  Pubmed ID: 22307730

A highly diastereoselective three-component tandem 1,4-conjugate addition-cyclization reaction of diazoacetophenones with anilines and unsaturated ketoesters was developed. The reaction provides general, easy, and highly efficient access to multisubstituted pyrrolidines in good yield with high diastereoselectivity.

Diet and Feeding Behavior of Rhinopithecus Brelichi at Yangaoping, Guizhou

American Journal of Primatology. Feb, 2012  |  Pubmed ID: 22311194

Expectations of increases in human population growth and accelerated habitat loss, along with the realization that efforts to provide protection for ecosystems that sustain primates have met with limited success, make it critical that conservation plans are grounded firmly in scientific observation. Studies of the diet breadth and feeding behavior of endangered species, therefore, are critical for understanding ecological adaptations and developing a conservation strategy. The diet and feeding ecology of gray snub-nosed monkeys (Rhinopithecus brelichi) were studied in the Fanjingshan National Nature Reserve, Guizhou, China. The monkeys were found to consume 107 different species of trees, shrubs, and ground plants from 58 genera and 28 families. Food items included young leaves, mature leaves, flowers, fruits/seeds, buds, and insects. Among these food items, there were at least 13 evergreen species of tree and liana, 3 species of grasses, and at least 2 kinds of invertebrates collected from decayed wood. Diet varied markedly throughout different seasons. Overall, diet composition (based on feeding records) was 15.3% buds, 25.5% young leaves, 21.8% mature leaves, 9.4% flowers, 21.6% fruits/seeds, and 6.3% other items. The monkeys feed mainly on young leaves and flowers in spring, unripe fruits/seeds and young leaves in summer, ripe fruits/seeds in autumn, and mature leaves and buds in winter. We propose that when inhabiting forests of lower elevation and greater vegetation complexity, R. brelichi is characterized by expanded diet breadth and includes a greater diversity of food types and plant species in its diet. One food type that appears critical to the diet of this species, especially during the winter, are the buds of Magnolia sprengeri. To protect this resource we advocate working with local communities to limit the collection of M. sprengeri, which is used in traditional Chinese medicine and has high economic value for people in the reserve.

Comparison of the Pedicle Screws Placement Between Electronic Conductivity Device and Normal Pedicle Finder in Posterior Surgery of Scoliosis

Journal of Spinal Disorders & Techniques. Feb, 2012  |  Pubmed ID: 22314520

STUDY DESIGN:: Prospective randomized clinical trial. OBJECTIVE:: To compare the accuracy and time using of pedicle screw placement between electronic conductivity device (ECD) and normal pedicle finder (NPF) in posterior surgery of scoliosis, through a randomized clinical trial. SUMMARY OF BACKGROUND DATA:: Pedicle screw insertion for scoliosis correction can be associated with increased pedicle perforations. The malposition rates using various techniques in different region of the spine have been reported to occur with a frequency of 3.3%-43%. An ECD has been reported in spine surgeries, but its accuracy and surgical time comparing with NPF in the presence of scoliosis has not been reported. METHODS:: The 42 patients of adolescent idiopathic scoliosis with average major Cobb angle of 55.3±7 degrees (range, 45-78 degrees), who received posterior correction surgeries using pedicle screws system only were divided into 2 groups by random: group NPF (22 patients); and group ECD (20 patients). NPF group had 332 screws and ECD group had 362 screws. The 2 groups were compared for accuracy of screw placement, time for screw insertion, and the number of times the C-arm had to be brought into the field. RESULTS:: There were 47 (14.2%) pedicle perforation in the NPF group as compared with only 15 (4.1%) in the ECD group (P<0.001). Although in different region of the spine, screw accuracy showed discrepant statistical result, with upper (T1-T3), middle (T4-T7), and lower thoracic (T8-T10) comparison showing significant statistical difference (P=0.010, 0.001, and 0.041, respectively) and thoracolumbar (T11-L2) and lower lumbar (L3-L5) comparison showing no significant statistical difference (P=0.278 and 0.292, respectively). Average screw insertion time in the NPF group was 241±61 seconds compared with 204±33 seconds in the ECD group (P=0.009). The C-arm had to be moved into the operation field on an average of 1.59±0.67 times in the NPF group compared with 1.20±0.52 in the ECD group (P=0.040). CONCLUSIONS:: ECD increases pedicle screw accuracy, especially in T1-T10, and reduces insertion time and radiation in posterior adolescent idiopathic scoliosis.

Somatic and Reproductive Cell Development in Rice Anther Is Regulated by a Putative Glutaredoxin

The Plant Cell. Feb, 2012  |  Pubmed ID: 22319054

The switch from mitosis to meiosis is one of the most pivotal events in eukaryotes undergoing sexual reproduction. However, the mechanisms orchestrating meiosis initiation remain elusive, particularly in plants. Flowering plants are heterosporous, with male and female spore genesis adopting different developmental courses. We show here that plant pollen mother cells contain a specific meiosis initiation machinery through characterization of a rice (Oryza sativa) gene, MICROSPORELESS1 (MIL1). The mil1 mutant does not produce microspores in anthers but has the normal female fertility. Detailed molecular and cytological investigations demonstrate that mil1 anthers are defective in the meiotic entry of sporogenous cell progenies and in the differentiation of surrounding somatic cell layers, resulting in locules filled with somatic cells instead of microspores. Furthermore, analysis of mil1 msp1 double mutants reveals that due to the absence of MIL1, the cells in their anther locule center do not activate meiotic cell cycle either, generating a similar anther phenotype to mil1. MIL1 encodes a plant-specific CC-type glutaredoxin, which could interact with TGA transcription factors. These results suggest meiotic entry in microsporocytes is directed by an anther-specific mechanism, which requires MIL1 activity, and redox regulation might play important roles in this process.

Aortic Regurgitation Caused by Behçet's Disease: Surgical Experience During an 11-Year Period

Journal of Cardiac Surgery. Jan, 2012  |  Pubmed ID: 22321112

Abstract  Background and Aim of the Study: Aortic regurgitation (AR) caused by Behçet's disease is a rare clinical condition and surgical experience is limited. Many patients undergoing simple aortic valve replacement (AVR) required a second or third operation as a result of prosthetic valve dehiscence. We analyze our experience with surgical management for AR in Behçet's disease during an 11-year period. Methods: From April 1997 through December 2008, 10 male patients (mean age, 38.4 ± 6.9 years) with AR caused by Behçet's disease underwent surgical treatment. The primary procedures were AVR in seven cases and aortic root replacement in three (two Bentall, one Cabrol). The duration of follow-up was 5.3 ± 3.6 years. Results: In the seven patients with simple AVR, valve dehiscence occurred in six after an interval of 2.9 ± 1.7 months, necessitating 11 reoperations (four redo AVRs, one redo redo-AVR, four aortic root replacements, and two heart transplants) with one early death. In aortic root replacement patients, two Bentall patients survived and required no reintervention, and the Cabrol patient died from electromechanical uncoupling one year postoperatively. Of the seven survivors, the definite procedure was aortic root replacement in four cases, heart transplantation in two, and AVR in one. Conclusions: The rate of valve dehiscence was high after isolated AVR in patients with AR caused by Behçet's disease. At the first operation, aortic root replacement should be the procedure of choice, preferably with a homograft. Heart transplantation might be a feasible alternative to aortic root replacement in selected patients. (J Card Surg 2012;27:39-44).

A Mutation in the Rice Chalcone Isomerase Gene Causes the Golden Hull and Internode 1 Phenotype

Planta. Jan, 2012  |  Pubmed ID: 22286805

The biosynthesis of flavonoids, important secondary plant metabolites, has been investigated extensively, but few mutants of genes in this pathway have been identified in rice (Oryza sativa). The rice gold hull and internode (gh) mutants exhibit a reddish-brown pigmentation in the hull and internode and their phenotype has long been used as a morphological marker trait for breeding and genetic study. Here, we characterized that the gh1 mutant was a mutant of the rice chalcone isomerase gene (OsCHI). The result showed that gh1 had a Dasheng retrotransposon inserted in the 5' UTR of the OsCHI gene, which resulted in the complete loss of OsCHI expression. gh1 exhibited golden pigmentation in hulls and internodes once the panicles were exposed to light. The total flavonoid content in gh1 hulls was increased threefold compared to wild type. Consistent with the gh1 phenotype, OsCHI transcripts were expressed in most tissues of rice and most abundantly in internodes. It was also expressed at high levels in panicles before heading, distributed mainly in lemmas and paleae, but its expression decreased substantially after the panicles emerged from the sheath. OsCHI encodes a protein functionally and structurally conserved to chalcone isomerases in other species. Our findings demonstrated that the OsCHI gene was indispensable for flux of the flavonoid pathway in rice.

PDIMs and PGLs Are Both Required for Virulence of Mycobacterium Marinum

Infection and Immunity. Jan, 2012  |  Pubmed ID: 22290144

Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of Mycobacterium tuberculosis (M. tb). This has been complicated by the natural deficiency of PGLs in many clinical strains of M. tb and the frequent loss of PDIMs in laboratory M. tb strains. In this study, we isolated seven mutants of Mycobacterium marinum deficient in PDIMs and/or PGLs, in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that M. marinum strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help to understand the role of PDIMs and PGLs in M. tb virulence.

Approximating Ideal Filters by Systems of Fractional Order

Computational and Mathematical Methods in Medicine. 2012  |  Pubmed ID: 22291851

The contributions in this paper are in two folds. On the one hand, we propose a general approach for approximating ideal filters based on fractional calculus from the point of view of systems of fractional order. On the other hand, we suggest that the Paley and Wiener criterion might not be a necessary condition for designing physically realizable ideal filters. As an application of the present approach, we show a case in designing ideal filters for suppressing 50-Hz interference in electrocardiogram (ECG) signals.

Phaeosphaerins A-F, Cytotoxic Perylenequinones from an Endolichenic Fungus, Phaeosphaeria Sp

Journal of Natural Products. Jan, 2012  |  Pubmed ID: 22276650

Six novel phototoxins, phaeosphaerins A-F (1-6), together with six known perylenequinones were isolated from an endolichenic fungus Phaeosphaeria sp. Their structures were determined unequivocally on the basis of comprehensive analysis of MS and NMR data as well as electronic circular dichroism calculations. These toxins kill cancer cells in vitro with accumulation in lysosomes, and the killing effects were potently intensified in the presence of light.

All-pedicle-screw Versus Hybrid Hook-screw Instrumentation for Posterior Spinal Correction Surgery in Adolescent Idiopathic Scoliosis: a Curve Flexibility Matched-pair Study

Archives of Orthopaedic and Trauma Surgery. Jan, 2012  |  Pubmed ID: 22252852

INTRODUCTION: Comparisons of all-pedicle-screw (PS) and hybrid hook-screw (HS) instrumentation for the treatment of adolescent idiopathic scoliosis (AIS) have produced conflicting results. The aim of this study was to compare all-pedicle-screw and hybrid hook-screw instrumentation for the treatment of AIS using a matched-pair study design in which preoperative flexibility was matched. METHODS: In this retrospective study conducted at one medical center, 21 all-pedicle-screw/hybrid hook-screw pairs of Lenke type I AIS patients matched for age, height, weight, body mass index, sex, and preoperative curve flexibility who had been treated at our institution from January 2000 to October 2006 were selected. Postoperative and 2-year postoperative coronal curve correction, postoperative kyphosis, blood transfusion needs, operation time, and hospital cost were measured and analyzed statistically. RESULTS: The PS group compared with the HS group had better postoperative correction (P = 0.0231) and 2-year coronal curve correction (P = 0.016). While statistically significant (P = 0.0073), the postoperative Cobb angle was only 3° less in the PS group, Maintenance of correction after 2 years was better in the PS group (P = 0.0016). The PS group had less blood loss (P < 0.0001) and shorter operation time (P < 0.0001), but the hospital cost for the PS group was higher (P < 0.0001). CONCLUSIONS: All-pedicle-screw and hybrid hook-screw instrumentations are comparable with regard to curve correction, but all-pedicle screw instrumentation reduces blood loss during surgery and shortens the operation time, which may help shorten healing time.

Evidence of Allomaternal Nursing Across One-Male Units in the Yunnan Snub-Nosed Monkey (Rhinopithecus Bieti)

PloS One. 2012  |  Pubmed ID: 22253869

Allomaternal nursing, common in several species of social mammals, also has been reported in nonhuman primates. However, the function of this behavior in enhancing infant survivorship remains poorly understood.

Initial Hydrogenations of Pyridine on MoP(001): A Density Functional Study

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012  |  Pubmed ID: 22256950

The initial hydrogenations of pyridine on MoP(001) with various hydrogen species are studied using self-consistent periodic density functional theory (DFT). The possible surface hydrogen species are examined by studying interaction of H(2) and H(2)S with the surface, and the results suggest that the rational hydrogen source for pyridine hydrogenations should be surface hydrogen atoms, followed by adsorbed H(2)S and SH. On MoP(001), pyridine has two types of adsorption modes, i.e., side-on and end-on; and the most stable η(5)(N,C(α),C(β),C(β),C(α)) configuration of the side-on mode facilitates the hydrogenation of pyridine. The optimal hydrogenation path of pyridine with surface hydrogen atoms in the Langmuir-Hinshelwood mechanism is the formation of 3-monohydropyridine, followed by producing 3,5-dihydropyridine, in which the two-step hydrogenations take place on the C(β) atoms. When adsorbed H(2)S is considered as the source of hydrogen, slightly higher hydrogenation barriers are always involved, while the energy barriers for hydrogenations involving adsorbed SH are much lower. However, the hydrogenation of pyridine should be suppressed by the adsorption of H(2)S, and the promotion effect of adsorbed SH is limited.

Zan Ding: Founder of Medical Psychology in China

Protein & Cell. Jan, 2012  |  Pubmed ID: 22259123

Sensitivity of a Novel Model of Mammary Cancer Stem Cell-like Cells to TNF-related Death Pathways

Cancer Immunology, Immunotherapy : CII. Jan, 2012  |  Pubmed ID: 22270714

Cancer stem cells (CSC) are resistant to radiation and chemotherapy and play a significant role in cancer recurrence and metastatic disease. It is therefore important to identify alternative strategies, such as immunotherapies that can be used to control this refractory population. A CD44(+)CD24(-/low) subpopulation of cells within the B6 PyMT-MMTV transgenic mouse-derived AT-3 mammary carcinoma cell line was identified, which had CSC-like characteristics, including pluripotency and a resistance to chemo- and radiotherapy. Therefore, unlike xenograph models that require immunocompromised settings, this novel system may provide a means to study immune-mediated responses against CSC-like cells. The immunobiology of the AT-3 CSC-like cell population was studied by their surface molecule expression profile and their sensitivity to specified cell death pathways. Comparable levels of Rae-1, CD155, CD54 and higher levels of Fas and DR5 were expressed on the AT-3 CSC-like cells compared to non-CSC-like tumor cells. Expression correlated with an in vitro sensitivity to cell death by NK cells or through the ligation of the death receptors (Fas or DR5), by their ligands or anti-Fas and anti-DR5 mAbs. Indeed, compared to the rest of the AT-3 tumor cells, the CD44(+)CD24(-/low) subpopulation of cells were more sensitive to both Fas- and TRAIL-mediated cell death pathways. Therefore, despite the refractory nature of CSC to other conventional therapies, these CSC-like cells were not inherently resistant to specified forms of immune-mediated cell death. These results encourage the continued investigation into immunotherapeutic strategies as a means of controlling breast CSC, particularly through their cell death pathways.

Maternal Responses to Dead Infants in Yunnan Snub-nosed Monkey (Rhinopithecus Bieti) in the Baimaxueshan Nature Reserve, Yunnan, China

Primates; Journal of Primatology. Jan, 2012  |  Pubmed ID: 22274959

How a nonhuman primate mother responds to her dead infant is an indication of maternal behavior and perspectives on death. Here we describe three cases of a mother's response toward her dead infant in Yunnan snub-nosed monkeys (Rhinopithecus bieti) at Baimaxueshan Nature Reserve in Yunnan, China. The mother, whose infant died at 1 month of age, showed strong maternal affection to the corpse and carried it for 4 days. A mother with a stillborn infant showed similar maternal behavior to her dead offspring, but only held it for 1 day. The mother of an aborted infant abandoned the carcass without carrying it or displaying other forms of maternal behavior. Our results suggest that the mother-infant bond in the Yunnan snub-nosed monkey is strongly influenced by the infants' age. Postdeath infant-carrying behavior could be affected by the combined action of reproductive hormones and the emotional response of the mother. This manuscript represents the first detailed report of a mother carrying her dead infant in this endangered monkey species.

Side-to-side Neurorrhaphy for High-level Peripheral Nerve Injuries

Acta Neurochirurgica. Jan, 2012  |  Pubmed ID: 22231778

BACKGROUND: The results of peripheral nerve repair, especially for high-level peripheral nerve injuries, have been unsatisfactory. The method of side-to-side neurorrhaphy was developed in our laboratory from 1994 to 2002. This method involves suturing the injured nerve to a nearby donor nerve in a side-to-side manner. This study was performed to assess the clinical results of side-to-side neurorrhaphy in patients with high-level peripheral nerve injuries. METHODS: Twenty-five patients with various types of high-level peripheral nerve injuries who underwent side-to-side neurorrhaphy were studied. The British Medical Research Council (BMRC) scale was used to assess recovery of nerve function. RESULTS: Average follow-up duration was 3.2 years. Before surgery the patients had a nerve function of M0/S0 to M1/S1. After side-to-side neurorrhaphy, 7 patients had a score of M3/S4, 8 patients a score of M3/S3 and 10 patients a score of M2/S3. The total useful recovery rate (BMRC grade ≥3) was 60% for motor function and 100% for sensory function. Side-to-side neurorrhaphy did not result in any significant loss of donor nerve function. There was significant correlation between both the type of injury and the time interval between injury and surgery and motor nerve function. Age, gender and location of the injured nerve did not correlate with sensory or motor nerve function. CONCLUSION: Side-to-side neurorrhaphy appears to be promising as a feasible method for repair of high-level peripheral nerve injuries.

Identification and Characterization of Monoclonal Antibodies Against the ORFV059 Protein Encoded by Orf Virus

Virus Genes. Jan, 2012  |  Pubmed ID: 22237464

Recent outbreaks of orf in China have been attributed to a novel strain of Orf virus (ORFV) designated ORFV-Jilin. Currently, monoclonal antibodies (Mabs) have not yet been developed against this specific pathogen even though such entities could have potential applications regarding the diagnosis and characterization of ORFV-Jilin. Therefore, the current study was undertaken to generate Mab against the immunodominant ORFV059 protein of this virus. For this purpose, the ORFV-Jilin ORFV059 protein was expressed in Escherichia coli and subsequently used as an antigen to immunize mice and for the initial screening of hybridomas prepared from the mice for their ability to produce anti-ORFV059 protein Mabs via an indirect ELISA. Ten, positive hybridomas were identified in this manner and verified based on the ability of their released Mab to react specifically with both naturally and artificially expressed ORFV059 protein in Western blots. The two hybridomas with the greatest propensity to secrete Mab were subcloned three times before being introduced intraperitoneally into mice. Afterwards, both Mab were separately purified from the mice's ascetic fluids and found to successfully recognize the ORFV-Jilin ORFV059 protein in a variety of immunological assays. Thus, the widespread utility of these Mab as a diagnostic core reagent should prove invaluable for further investigations regarding the mechanisms of orf pathogenesis and the control of this disease. In this regard, it should be noted that Mab A3 was used to confirm the predicted late expression of the ORFV-Jilin ORFV059 protein during virus replication.

MCPH1/BRIT1 Represses Transcription of the Human Telomerase Reverse Transcriptase Gene

Gene. Mar, 2012  |  Pubmed ID: 22240313

MCPH1, a repressor of human telomerase reverse transcriptase (hTERT) function, is implicated in cellular immortalization. But little is known about how MCPH1 represses telomerase activity. In this study, to determine the mechanism by which MCPH1 regulates hTERT gene expression, we examined the role of MCPH1 in regulating the hTERT promoter in vitro. Co-transfection of the hTERT promoter with MCPH1 in Hela cells could inhibit the hTERT promoter activity. The EMSA assay demonstrated that MCPH1 could bind to the proximal hTERT promoter. Overexpression of MCPH1 could repress telomerase activity, and the repression was abolished by knocking down the MCPH1 expression using siRNA in U2OS cells. We propose that MCPH1 functions as a transcriptional repressor of hTERT in vitro. Since the activation of telomerase, widely observed in human tumor cell lines, is a critical step in tumorigenesis, our findings provide new insights into delineating the tumor-suppressing function of MCPH1 through its down-regulation of hTERT/telomerase expression.

Immunotherapeutic Potential of Anti-human Endogenous Retrovirus-k Envelope Protein Antibodies in Targeting Breast Tumors

Journal of the National Cancer Institute. Feb, 2012  |  Pubmed ID: 22247020

Background The envelope (env) protein of the human endogenous retrovirus type K (HERV-K) family is commonly expressed on the surface of breast cancer cells. We assessed whether HERV-K env is a potential target for antibody-based immunotherapy of breast cancer. Methods We examined the expression of HERV-K env protein in various malignant (MDA-MB-231, MCF-7, SKBR3, MDA-MB-453, T47D, and ZR-75-1) and nonmalignant (MCF-10A and MCF-10AT) human breast cell lines by immunoblot, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry. Anti-HERV-K env monoclonal antibodies (mAbs; 6H5, 4D1, 4E11, 6E11, and 4E6) were used to target expression of HERV-K, and antitumor effects were assessed by quantifying growth and apoptosis of breast cancer cells in vitro, and tumor growth in vivo in mice (n = 5 per group) bearing xenograft tumors. The mechanisms responsible for 6H5 mAb-mediated effects were investigated by microarray assays, flow cytometry, immunoblot, and immunofluorescence staining. The expression of HERV-K env protein was assessed in primary breast tumors (n = 223) by immunohistochemistry. All statistical tests were two-sided. Results The expression of HERV-K env protein in malignant breast cancer cell lines was substantially higher than nonmalignant breast cells. Anti-HERV-K-specific mAbs inhibited growth and induced apoptosis of breast cancer cells in vitro. Mice treated with 6H5 mAb showed statistically significantly reduced growth of xenograft tumors compared with mice treated with control immunoglobulin (control [mIgG] vs 6H5 mAb, for tumors originating from MDA-MB-231 cells, mean size = 1448.33 vs 475.44 mm(3); difference = 972.89 mm(3), 95% CI = 470.17 to 1475.61 mm(3); P < .001). Several proteins involved in the apoptotic signaling pathways were overexpressed in vitro in 6H5 mAb-treated malignant breast cells compared with mIgG-treated control. HERV-K expression was detected in 148 (66%) of 223 primary breast tumors, and a higher rate of lymph node metastasis was associated with HERV-K-positive compared with HERV-K-negative tumors (43% vs 23%, P = .003). Conclusion Monoclonal antibodies against HERV-K env protein show potential as novel immunotherapeutic agents for breast cancer therapy.

Effect of Preeclampsia Serum on Human Uterine Spiral Artery Smooth Muscle Cell Apoptosis in a Coculture Model with Cytotrophoblasts

Gynecologic and Obstetric Investigation. Jan, 2012  |  Pubmed ID: 22248491

Background/Aims: To investigate cytotrophoblast (CTB) invasive ability and human uterine spiral artery smooth muscle cell (HUSASMC) apoptosis in a coculture model with serum from preeclamptic pregnancies. Methods: Transwell migration assay was used to detect the invasive ability of CTBs. Cocultured CTBs and HUSASMCs were incubated with normal or preeclamptic serum for 24 h. Monocultures of CTBs and HUSASMCs were treated identically to the cocultures and served as controls. HUSASMC viability and apoptosis rates were determined by MTT and annexin V-FITC assays. The expressions of Fas ligand (FasL) mRNA in CTBs and Fas mRNA in HUSASMCs were detected by RT-PCR. The expression of the Fas protein in HUSASMCs was detected by Western blotting. Results: In a model of CTBs cocultured with HUSASMCs, preeclamptic serum effectively decreased the invasive ability and FasL mRNA expression of the CTBs. Preeclampsia serum also increased HUSASMC viability, decreased their apoptotic rate, and decreased the expression of Fas mRNA and protein. Conclusion: The abnormal invasive ability of CTBs and decreased expression of the Fas/FasL system may be directly involved in the defective remodeling of the uterine spiral arteries during preeclampsia. Furthermore, the decrease in HUSASMC apoptosis may be related to the abnormal expression of Fas/FasL.

Analysis of the Effectiveness of Visual Inspection with Acetic Acid/Lugol's Iodine in One-time and Annual Follow-up Screening in Rural China

Archives of Gynecology and Obstetrics. Jan, 2012  |  Pubmed ID: 22222723

PURPOSE: Via a large population-based survey conducted in rural, southwestern China, we aim to evaluate the effect of visual inspection with acetic acid/Lugol's iodine (VIA/VILI) on diagnosing cases of cervical cancer and of pre-cancerous lesions while exploring the mode of cervical prevention and control in low-resource settings in China. METHODS: Women aged 30-59 years from Chongqing, China were recruited from 2006 to 2009. Participants underwent VIA/VILI, and, if positive, received colposcopy-directed or random biopsies. Women with negative VIA/VILI or biopsy-confirmed cervical intraepithelial neoplasia (CIN) 1 lesions diagnosed in the first round of screening were re-screened in the following year with the same procedure. RESULTS: In total, 10,269 women received VIA/VILI. The average age of participants was 40.9 ± 7.6 years. Overall, 0.85% (87/10,269) of women were diagnosed via pathology-confirmed biopsy with CIN1, 0.25% (26/10,269) with CIN2, 0.27% (28/10,269) with CIN3, and 0.02% (2/10,269) with cervical cancer. Over half (57.7%) of CIN2 lesions, the majority of CIN3 lesions (89.3%), and all cancer cases (100%) were detected in the first round of screening. CONCLUSION: In a rural, low-resource setting in China, one-time VIA/VILI screening detected more than a half of CIN2 cases, most CIN3 cases and all the cervical cancer cases. Detection rates of CIN2 lesions significantly increased with a 1-year follow-up VIA/VILI screen. Therefore, if multiple cervical cancer screenings are not feasible logistically or financially, a one-time VIA/VILI may be the most efficient strategy to detect cervical cancer and most CIN3 lesions in women in low-resource settings.

First-In-Class Small Molecule Inhibitors of the Single-Strand DNA Cytosine Deaminase APOBEC3G

ACS Chemical Biology. Jan, 2012  |  Pubmed ID: 22181350

APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions C321-to-L, F, Y, or W mimicked chemical inhibition. A strong specificity for APOBEC3G was evident, as most compounds failed to inhibit the related APOBEC3A enzyme or the unrelated enzymes E. coli uracil DNA glycosylase, HIV-1 RNase H, or HIV-1 integrase. Partial, but not complete, sensitivity could be conferred to APOBEC3A by introducing the entire C321 loop from APOBEC3G. Thus, a structural model is presented in which the mechanism of inhibition is both specific and competitive, by binding a pocket adjacent to the APOBEC3G active site, reacting with C321, and blocking access to substrate DNA cytosines.

High PH Solubilization and Chromatography-Based Renaturation and Purification of Recombinant Human Granulocyte Colony-Stimulating Factor from Inclusion Bodies

Applied Biochemistry and Biotechnology. Jan, 2012  |  Pubmed ID: 22212394

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a very efficient therapeutic protein drug which has been widely used in human clinics to treat cancer patients suffering from chemotherapy-induced neutropenia. In this study, rhG-CSF was solubilized from inclusion bodies by using a high-pH solution containing low concentration of urea. It was found that solubilization of the rhG-CSF inclusion bodies greatly depended on the buffer pH employed; alkalic pH significantly favored the solubilization. In addition, when small amount of urea was added to the solution at high pH, the solubilization was further enhanced. After solubilization, the rhG-CSF was renatured with simultaneous purification by using weak anion exchange, strong anion exchange, and hydrophobic interaction chromatography, separately. The results indicated that the rhG-CSF solubilized by the high-pH solution containing low concentration of urea had much higher mass recovery than the one solubilized by 8 M urea when using anyone of the three refolding methods employed in this work. In the case of weak anion exchange chromatography, the high pH solubilized rhG-CSF could get a mass recovery of 73%. The strategy of combining solubilization of inclusion bodies at high pH with refolding of protein using liquid chromatography may become a routine method for protein production from inclusion bodies.

Retrospective Analysis on the Impact of Tuberculosis on Patients with Systemic Lupus Erythematosus (SLE)

Rheumatology International. Jan, 2012  |  Pubmed ID: 22212413

Up to now, there have been few reports concerning changes in lupus activity and immune indices of tuberculosis in patients with systemic lupus erythematosis (SLE). A retrospective investigation was given to survey the case data of SLE patients companied with tuberculosis that were treated in our hospital from 2001 to 2010 and compared with that of sex- and age-matched patients with single SLE. Changes in autoantibodies, lupus activity, inflammatory indices, positive rates of tuberculin (PPD) test and tuberculosis antibody (TB-Ab) of both groups were observed. It was indicated by results that ANA antibody level and positive rates of anti-Sm, anti-SSA and anti-SSB antibodies were significantly lower in the TB group than those in the control group (P < 0.05); C3 and C4 levels were significantly higher in the TB group than those in the control group; damage of hematological system (predominantly platelet) was less severe in the TB group than that in the control group (P < 0.05); no significant differences in IgG, IgM and IgA were noted between two groups (P > 0.05); ESR, C-reactive protein and LDH levels were significantly higher in the TB group than those in the control group (P < 0.05); PPD-IgG were significantly higher in the TB group than those in the control group (P < 0.05). These results suggested that after SLE patients were infected with tuberculosis, immune function was altered and lupus activity was inhibited as well.

Dermatofibrosarcoma Protuberans

Ophthalmology. Jan, 2012  |  Pubmed ID: 22214941

Vif Hijacks CBF-β to Degrade APOBEC3G and Promote HIV-1 Infection

Nature. Jan, 2012  |  Pubmed ID: 22190037

Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication. The AIDS virus, human immunodeficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation. Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-β to this ubiquitin ligase complex. CBF-β, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-β is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-β to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-β-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.

Adsorption Equilibria of Binary Gas Mixtures on Graphitized Carbon Black

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012  |  Pubmed ID: 22191667

Adsorption equilibria for binary gas mixtures (methane-carbon dioxide, methane-ethane, and carbon dioxide-ethane) on the graphitized carbon black STH-2 were measured by the open flow method at 293.2 K. The experimental pressure range was (0 to 1.6) MPa. The extended Langmuir (EL) model and the ideal adsorption solution theory (IAST) have been adopted to predict the equilibria of binary gas mixtures. The results indicate that gas mixtures adsorbed on the homogeneous surface of STH-2 exhibit the nonideal behavior, which is mainly induced by adsorbate-adsorbate interactions. The real adsorption solution theory (RAST) has been used to analyze the property of the adsorbed mixtures. The activity coefficients have been correlated with the Wilson equation. The investigation demonstrates that the nonideality of adsorbed phase is completely dissimilar with the bulk liquid phase. The adsorption of the heavier component would benefit the adsorption of the lighter component.

The Neck Linker of Kinesin 1 Seems Optimally Designed to Approach the Largest Stepping Velocity: a Simulation Study of an Ideal Model

Journal of Physics. Condensed Matter : an Institute of Physics Journal. Jan, 2012  |  Pubmed ID: 22173184

The neck linker is widely believed to play a critical role in the hand-over-hand walking of conventional kinesin 1. Experiments have shown that change of the neck linker length will significantly change the stepping velocity of the motor. In this paper, we studied this length effect based on a highly simplified chemically powered ratchet model. In this model, we assume that the chemical steps (ATP hydrolysis, ADP and P(i) release, ATP binding, neck linker docking) are fast enough under conditions far from equilibrium and the mechanical steps (detachment, diffusional search and re-attachment of the free head) are rate-limiting in kinesin walking. According to this model, and regarding the neck linker as a worm-like-chain polypeptide, we can calculate the steady state stepping velocity of the motor for different neck linker lengths. Our results show, under the actual values of binding energy between kinesin head and microtubule (~15k(B)T) and the persistence length of neck linker (~0.5 nm), that there is an optimal neck linker length (~14-16 a.a.) corresponding to the maximal velocity, which implies that the length of the wild-type neck linker (~15 a.a.) might be optimally designed for kinesin 1 to approach the largest stepping velocity.

The Pathological Characteristics of Glioma Stem Cell Niches

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Jan, 2012  |  Pubmed ID: 22178090

Brain tumor stem cells (BTSC) are predicted to be critical drivers of tumor progression due to their self-renewal capacity and limitless proliferative potential. Recent studies suggest that stem cells are controlled by a particular microenvironment known as a "niche". We therefore analysed human glioma tissues and found that the CD133(+) and nestin(+) niches are perivascularly localized in all glioma tissues. Furthermore, there is a positive correlation between the CD133(+) niches and CD133(+) blood vessels, which is similar to the correlation between the nestin(+) niches and nestin(+) blood vessels. We demonstrate that both CD133(+) blood vessels and nestin(+) blood vessels have an important role in maintaining the structure of the glioma stem cell niche. Moreover, the abundance of CD133(+) niches and nestin(+) niches increases significantly as tumor grade increases. These findings provide a new insight into the biology of BTSC and open a new perspective for targeted therapy against the brain tumors.

Design and Optimization of Photo Bioreactor for O2 Regulation and Control by System Dynamics and Computer Simulation

Bioresource Technology. Jan, 2012  |  Pubmed ID: 22153599

In this paper, a valid kinetic model of photo bioreactor (PBR) used for highly-effective cultivation of blue algae, Spirulina platensis, was developed for fully describing the dynamic characteristics of O(2) concentration, then a closed-loop PBR with Linear-Quadratic Gaussian (LQG) servo controller was established and optimized via digital simulation and dynamic response optimization, and the effectiveness of the closed-loop PBR was further tested and accredited by real-time simulation. The result showed that the closed-loop PBR could regulate and control the O(2) concentration in its gas phase according to the reference with desired dynamic response performance, hence microalgae with unique characteristic could be selected as a powerful tool for O(2) regulation and control whenever O(2) concentration in Bioregenerative Life Support System (BLSS) deviates from the nominal level in emergencies, and greatly enhance safety and reliability of BLSS on space and ground missions.

Contextual and Behavioral Control of Antipsychotic Sensitization Induced by Haloperidol and Olanzapine

Behavioural Pharmacology. Feb, 2012  |  Pubmed ID: 22157143

Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical effects of antipsychotic treatment, understanding the neurobiological mechanisms of antipsychotic sensitization and its contextual control would greatly enhance our understanding of the psychological and neurochemical nature of antipsychotic treatment in the clinic.

Design, Synthesis and Biological Evaluation of Novel Glycosylated Diphyllin Derivatives As Topoisomerase II Inhibitors

European Journal of Medicinal Chemistry. Jan, 2012  |  Pubmed ID: 22119124

Recently, a novel glycosylated diphyllin derivative 11 which exhibiting potent anticancer activity by targeting topoisomerase IIα was reported by our group. In order to provide more molecules for structure-activity relationship (SAR) studies, 12 new glycosylated diphyllin analogs have been designed, synthesized, and evaluated for their biological activities. The SAR analysis revealed that (i) the sugar moiety on the diphyllin is essential for the anticancer activity; (ii) equatorial C4'-OH on the sugar is superior to the axial one, and (iii) a proper cyclic lipophilic group at the C4' and C6' of sugar might enhance the anticancer activity.

Synthesis, Crystal Structures, and Biological Evaluation of Cu(II) and Zn(II) Complexes of 2-benzoylpyridine Schiff Bases Derived from S-methyl- and S-phenyldithiocarbazates

Journal of Inorganic Biochemistry. Jan, 2012  |  Pubmed ID: 22112848

Two NNS tridentate Schiff base ligands of 2-benzoylpyridine S-methyldithiocarbazate (HL(1)) and 2-benzoylpyridine S-phenyldithiocarbazate (HL(2)) and their transition metal complexes [Cu(2)(L(1))(2)(CH(3)COO)](ClO(4)) (1), [Zn(2)(L(1))(2)(ClO(4))(2)] (2), [Zn(L(2))(2)](3) have been prepared and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. In the solid state, each of two Schiff bases remains in its thione tautomeric form with the thione sulfur atom trans to the azomethine nitrogen atom. Under similar prepared conditions, three new complexes showed distinctly different coordination modes depending on their coordinating preferences. Each copper atom in S-bridged dinuclear complex [Cu(2)(L(1))(2)(CH(3)COO)](ClO(4)) (1) is surrounded by five donor atoms in a square-pyramidal fashion (4+1). [Zn(2)(L(1))(2)(ClO(4))(2)] (2) is a dimer in which each zinc atom adopts a seven-coordinate distorted pentagonal bipyramidal geometry, while mononuclear [Zn(L(2))(2)] (3) has octahedral coordination geometry. Biological studies, carried out in vitro against selected bacteria, fungi, and K562 leukaemia cell line, respectively, have shown that different substituted groups attached at the dithiocarbazate moieties and metals showed distinctive differences in the biological property. Zinc(II) complexes 2 and 3 could distinguish K562 leukaemia cell line from normal hepatocyte QSG7701 cell line. Effect of the title compounds on Mitochondria membrane potential (MMP) and PI-associated fluorescence intensity in K562 leukaemia cell line are also studied. The title compounds may exert their cytotoxicity activity via induced loss of MMP.

A Natural Compound Induced Cardiogenic Differentiation of Endogenous MSCs for Repair of Infarcted Heart

Differentiation; Research in Biological Diversity. Jan, 2012  |  Pubmed ID: 22099171

An intra-myocardial injection of a cardiogenic factor (cardiogenin) was reported to induce myocardial regeneration of exogenous mesenchymal stem cell (MSCs) origin. In this study, replacement of the dangerous intra-myocardial injection with a safe method and whether the endogenous MSCs contribute to the cardiogenin-mediated myocardial regeneration were investigated. Bone marrow transplantation with labeled MSCs was performed in rats, which were subsequently subject to a permanent ligation of left anterior descending coronary artery one week after the transplantation. The rats were then treated with the cardiogenin through oral administration for 2 weeks. We not only demonstrated the substantial therapeutic effects of cardiogenin on myocardial infarction through an oral administration, but also provided direct evidences that the bone marrow derived endogenous MSCs are the major cellular source of the regenerating myocardium. Preliminary mechanistic studies suggested that miR-9 and its target E-cadherin may be required for intercalated disc formation.

Class II ADP-ribosylation Factors Are Required for Efficient Secretion of Dengue Viruses

The Journal of Biological Chemistry. Jan, 2012  |  Pubmed ID: 22105072

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.

Multiple End Joining Mechanisms Repair a Chromosomal DNA Break in Fission Yeast

DNA Repair. Feb, 2012  |  Pubmed ID: 22093869

Non-homologous end joining (NHEJ) is an important mechanism for repairing DNA double-strand breaks (DSBs). The fission yeast Schizosaccharomyces pombe has a conserved set of NHEJ factors including Ku, DNA ligase IV, Xlf1, and Pol4. Their roles in chromosomal DSB repair have not been directly characterized before. Here we used HO endonuclease to create a specific chromosomal DSB in fission yeast and examined the imprecise end joining events allowing cells to survive the continuous expression of HO. Our analysis showed that cell survival was significantly reduced in mutants defective for Ku, ligase IV, or Xlf1. Using Sanger sequencing and Illumina sequencing, we have characterized in depth the repair junction sequences in HO survivors. In wild type cells the majority of repair events were one-nucleotide insertions dependent on Ku, ligase IV, and Pol4. Our data suggest that fission yeast Pol4 is important for gap filling during NHEJ repair and can extend primers in the absence of terminal base pairing with the templates. In Ku and ligase IV mutants, the survivors mainly resulted from two types of alternative end joining events: one used microhomology flanking the HO site to delete sequences of hundreds to thousands of base pairs, the other rejoined the break using the HO-generated overhangs but also introduced one- or two-nucleotide base substitutions. The chromosomal repair assay we describe here should provide a useful tool for further exploration of the end joining repair mechanisms in fission yeast.

Multifunctional Nanoprobes for Upconversion Fluorescence, MR and CT Trimodal Imaging

Biomaterials. Feb, 2012  |  Pubmed ID: 22061493

Early diagnosis probes that combine fluorescence, X-ray computed tomography (CT) and magnetic resonance (MR) imagings are anticipated to give three dimensional (3D) details of tissues and cells of high resolution and sensitivity. However, how to combine these three modalities together within a sub-50 nm sized structure is technically challenging. Here we report a trimodal imaging probe of PEGylated NaY/GdF(4): Yb, Er, Tm @SiO(2)-Au@PEG(5000) nanopaticles of uniform size of less than 50 nm. The as-designed nanoprobes showed (1) strong emissions ranging from the visible (Vis) to near infrared (NIR) for fluorescent imaging, (2) T(1)-weighted MRI by shorting T(1) relaxation time and (3) enhanced HU value as a CT contrast agent. The structure was optimized based on a comprehensive investigation on the influence of the distance between the NaY/GdF(4): Yb, Er, Tm core and Au nanoparticles (NPs) at the surface. The potential of trimodal imaging for cancerous cells and lesions was further demonstrated both in vitro and in vivo.

Conditioned Response Evoked by Nicotine Conditioned Stimulus Preferentially Induces C-Fos Expression in Medial Regions of Caudate-Putamen

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Mar, 2012  |  Pubmed ID: 22048468

Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS). Rats were injected (SC) in an intermixed fashion with saline or nicotine (16 sessions of each) and placed in conditioning chambers where they were given one of the three conditions depending on group assignment: (a) nicotine paired 100% of the time with intermittent access to sucrose (nicotine-CS condition), (b) nicotine and saline each paired 50% of the time with sucrose (chamber-CS condition), or (c) no sucrose US control (CS-alone condition). Rats in the nicotine-CS condition acquired the discrimination as evidenced by goal-tracking (ie, increased dipper entries before initial sucrose delivery) only on nicotine sessions. The chamber-CS condition showed goal-tracking on all sessions; no goal-tracking was seen in the CS-alone condition. On the test day, rats in each condition were challenged with saline or nicotine and later assessed for c-Fos immunoreactivity. In concordance with previous reports, nicotine induced c-Fos expression in the majority of areas tested; however, learning-dependent expression was specific to dorsomedial and ventromedial regions of caudate-putamen (dmCPu, vmCPu). Only rats in the nicotine-CS condition, when challenged with nicotine, had higher c-Fos expression in the dmCPu and vmCPu. These results suggest that medial areas of CPu involved in excitatory conditioning with an appetitive nicotine CS.

Analysis of Microsatellite Mutations in Buccal Cells from a Case-control Study for Lung Cancer

Cancer Epidemiology. Feb, 2012  |  Pubmed ID: 22056752

Exposure to tobacco carcinogens is the major cause of human lung cancer, but even heavy smokers have only about a 10% life-time risk of developing lung cancer. Currently used screening processes, based largely on age and exposure status, have proven to be of limited clinical utility in predicting cancer risk. More precise methods of assessing an individual's risk of developing lung cancer are needed. Because of their sensitivity to DNA damage, microsatellites are potentially useful for the assessment of somatic mutational load in normal cells. We assessed mutational load using hypermutable microsatellites in buccal cells obtained from lung carcinoma cases and controls to test if such a measure could be used to estimate lung cancer risk. There was no significant association between smoking status and mutation frequency with any of the markers tested. No significant association between case status and mutation frequency was observed. Age was significantly related to mutation frequency in the microsatellite marker D7S1482. These observations indicate that somatic mutational load, as measured using mutation frequency of microsatellites in buccal cells, increases with increasing age but that subjects who develop lung cancer have a similar mutational load as those who remain cancer free. This finding suggests that mutation frequency of microsatellite mutations in buccal cells may not be a promising biomarker for lung cancer risk.

PPE38 Modulates the Innate Immune Response and is Required for Mycobacterium Marinum Virulence

Infection and Immunity. Jan, 2012  |  Pubmed ID: 22038915

The proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) family proteins are prevalent in pathogenic mycobacteria and play a diverse role in mycobacterial pathogenesis. While some members have been studied, the function of most PE/PPE proteins remains unknown. In this study, we isolated a transposon-inactivated PPE38 mutant of Mycobacterium marinum and characterized its phenotype. We found that the PPE38 protein is associated with the cell wall and exposed on the cell surface. The inactivation of PPE38 altered the bacterial cell surface properties and led to deficiencies in cord formation, sliding motility, and biofilm formation. The PPE38 mutant was defective in phagocytosis by macrophages and exhibited reduced virulence in adult zebrafish. We also found that PPE38 is involved in the induction of proinflammatory cytokines in infected macrophages. Together, our results indicate that PPE38, a previously uncharacterized protein, plays a role in mycobacterial virulence, presumably by modulating the host innate immune response.

A Facile Strategy for Obtaining Fresh Ag As SERS Active Substrates

Journal of Colloid and Interface Science. Jan, 2012  |  Pubmed ID: 21999955

A facile strategy has been reported to obtain on-line fresh Ag as surface-enhanced Raman scattering (SERS) active substrates by making AgCl nanoparticles exposed to the laser beam of Raman spectrometer. The composition and morphology of AgCl nanoparticles were characterized by X-ray diffraction (XRD), UV-visible (UV-vis) spectroscopy and scanning electron microscopy (SEM). The laser-driven evolvement and possible formation mechanism of cubic AgCl nanoparticles to Ag/AgCl composites were also investigated by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and high-resolution transmission electron microscopy (HRTEM). Raman measurements demonstrate that the fresh Ag nanoparticles with a few defects have a prominent SERS sensitivity to probe molecules, such as the 4-mercaptopyridine (4-Mpy) and 4-aminothiophenol (PATP) molecules. The SERS intensity of 4-Mpy and PATP increases up to the maximum when the laser irradiation time is prolonged to 50s, which corresponds to the defect extent and the proportion of fresh Ag in the Ag/AgCl composites. This work provides a simple, efficient and feasible approach for obtaining on-line fresh Ag as SERS substrates.

Promotion of Cell Proliferation and Inhibition of ADCC by Cancerous Immunoglobulin Expressed in Cancer Cell Lines

Cellular & Molecular Immunology. Jan, 2012  |  Pubmed ID: 22036905

To explore the significance of cancerous immunoglobulin (Ig) in cancer cell growth, HeLa cervical cancer cells were stably transfected with small interfering RNA (siRNA) that specifically, efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes. This stable cell line was used to examine cell viability, colony formation and tumor growth in athymic nude mice. The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo. Similarly, this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells. Furthermore, the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity (ADCC) induced by an anti-human epithelial growth factor receptor (EGFR) antibody in a dose-dependent manner, suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell (or NK cell) effector function. The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers.

A Genetic Epidemiological Survey of Idiopathic Epilepsy in the Chinese Han Population

Epilepsy Research. Feb, 2012  |  Pubmed ID: 21993360

Idiopathic epilepsy (IE) is a syndrome that comprises epilepsy only, with no underlying structural brain lesion or other neurological signs or symptoms. Numerous studies have shown that genetic factors play an important role in IE. IE is a common disease in the Chinese Han population. However, the genetic epidemiological characteristics of IE in the Chinese population, such as its heritability and genetic models remain unclear.

Let-7c Functions As a Metastasis Suppressor by Targeting MMP11 and PBX3 in Colorectal Cancer

The Journal of Pathology. Feb, 2012  |  Pubmed ID: 21984339

Accumulating evidence shows that microRNAs, functioning as either oncogenes or tumour suppressors by negatively regulating downstream target genes that are actively involved in tumour initiation and progression, may be promising biomarkers and therapy targets. Data mining through a microRNA chip database indicated that let-7c may be associated with tumour metastasis. Here, we confirmed that down-regulation of let-7c in primary cancer tissues was significantly associated with metastases, advanced TNM stages and poor survival of colorectal cancer patients. Moreover, ectopic expression of let-7c in a highly metastatic Lovo cell line remarkably suppressed cell migration and invasion in vitro by the down-regulation of K-RAS, MMP11 and PBX3, as well as tumour growth and metastases in vivo, whereas inhibition of let-7c in low-metastatic HT29 cells increased cell motility and invasion by the enhanced gene expression of K-RAS, MMP11 and PBX3. Interestingly, the luciferase reporters' activities with the 3'-UTRs of K-RAS, MMP11 and PBX3 were inhibited significantly by let-7c. Importantly, rescue experiments involving the over-expression of these genes without their 3'-UTRs completely reversed the effects of let-7c on tumour metastasis, both in vitro and in vivo. Finally, the levels of let-7c were inversely correlated with those of MMP11 and PBX3, but not with those of K-RAS. Taken together, these results demonstrate that let-7c, apart from its tumour growth suppression role, also functions as a tumour metastasis suppressor in colorectal cancer by directly destabilizing the mRNAs of MMP11 and PBX3 at least. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Pharmacokinetics, Tissue Distribution, Excretion, and Antiviral Activity of Pegylated Recombinant Human Consensus Interferon-α Variant in Monkeys, Rats and Guinea Pigs

Regulatory Peptides. Jan, 2012  |  Pubmed ID: 21985916

The study aims to characterize the pharmacokinetic, tissue distribution, excretion, and antiviral activity properties of a novel pegylated recombinant human consensus interferon-α variant (PEG-IFN-SA) following a single subcutaneous administration to monkeys, rats and guinea pigs. Studies included: (1) pharmacokinetic properties of PEG-IFN-SA and comparison with those of non-pegylated IFN-SA in rhesus monkeys and rats; (2) tissue distribution and urinary, fecal, and biliary excretion patterns of (125)I-PEG-IFN-SA in guinea pigs; and (3) antiviral activity assessment of PEG-IFN-SA in cynomolgus monkeys. The pegylated protein exhibited improved pharmacokinetic properties compared to IFN-SA in both monkeys and rats, with a 12-fold and 15-fold increase in elimination half-life, and a 100-fold and 10-fold decrease in serum clearance, as well as a 2.5-fold and 10-fold increase in the time to reach peak serum concentration, respectively. (125)I-PEG-IFN-SA was found to be distributed to most of the tissues examined and has character of targeting special distribution, and urinary appeared to be a major route for the excretion of PEG-IFN-SA in guinea pigs. Serum sample analysis from PEG-IFN-SA-treated monkeys showed dose-dependent antiviral activity for one week. These findings demonstrate that pegylation of IFN-SA results in more desirable pharmacokinetic properties, enhanced drug exposure and sustained-efficacy of in vivo antiviral action.

Correlation Between Glioblastoma Stem-like Cells and Tumor Vascularization

Oncology Reports. Jan, 2012  |  Pubmed ID: 21971709

Glioblastoma multiforme (GBM) is the most lethal type of brain tumor. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the inability to treat these tumors effectively. We analyzed 70 glioblastoma samples by immunohistochemistry and double immunofluorescence staining. The immunohistochemical expression of the putative brain tumor stem cell markers CD133 and Nestin in paraffin sections was analyzed using morphometry. In all GBM samples, CD133 or Nestin was expressed in tumor and endothelial cells. Double immunofluorescence stainings showed that the two different marked GSCs were found accumulated around the CD31+ blood vessels and CD133/CD31 or Nestin/CD31 co-expression was found in the endothelial cells and GSCs. Furthermore, the vascular endothelial growth factor (VEGF) and the endothelial marker CD31 were co-expressed in GSCs. Therefore, GSCs not only showed distinct perivascular distribution but were capable of differentiating into endothelial cells. We demonstrate that GSCs contribute directly to the tumor vasculature by endothelial cell differentiation. GSCs and tumor vascularization are closely related to each other, not only in the regional distribution but also in biological function. These findings describe a new mechanism for tumor vasculo-genesis and may provide new insights for targeted therapy against brain tumors.

Asymptotic Identity in Min-plus Algebra: a Report on CPNS

Computational and Mathematical Methods in Medicine. 2012  |  Pubmed ID: 21822446

Network calculus is a theory initiated primarily in computer communication networks, especially in the aspect of real-time communications, where min-plus algebra plays a role. Cyber-physical networking systems (CPNSs) are recently developing fast and models in data flows as well as systems in CPNS are, accordingly, greatly desired. Though min-plus algebra may be a promising tool to linearize any node in CPNS as can be seen from its applications to the Internet computing, there are tough problems remaining unsolved in this regard. The identity in min-plus algebra is one problem we shall address. We shall point out the confusions about the conventional identity in the min-plus algebra and present an analytical expression of the asymptotic identity that may not cause confusions.

DJ-1 May Contribute to Metastasis of Non-small Cell Lung Cancer

Molecular Biology Reports. Mar, 2012  |  Pubmed ID: 21670963

Lung cancer is a leading cause of cancer-related death, about 40% human non-small cell lung cancer (NSCLC) patients showed lymph node involvements. However, the precise mechanism for the metastasis is still not fully understood. This study was to analyze the potential molecular mechanism for lung cancer metastasis. In the current study, proteomics analysis by two-dimensional electrophoresis (2-DE) was performed first to identify the differentially expressed protein between the higher metastasis lung adenocarcinoma cell line Anip973 and the lower metastasis lung adenocarcinoma cell line AGZY83-a. We confirmed the result by RT-PCR, immunoblotting and immunocytochemistry analyses in these two cell lines. Then we examined the expression of the differentially expressed protein in tumor tissues of NSCLC patients by immunoblotting and immunohistochemistry analyses. Using 2-DE analysis, we have identified DJ-1 was expressed higher in the higher metastasis Anip973 compared to the parental cell line AGZY83-a, that was confirmed by RT-PCR, immunoblotting and immunocytochemistry analyses. In NSCLC patients' tumor tissues study, immunoblotting data showed that, DJ-1 expression level was significantly higher in 72.2% (13/18) of NSCLC tissue samples compared to that in paired normal lung tissues (P = 0.044). Immunohistochemistry analysis demonstrated increased DJ-1 expression in 85 NSCLC tumor tissue samples compared with 7 normal lung tissue samples (P = 0.044). DJ-1 expression was also found to be significantly correlated with cancer lymphatic metastasis (P = 0.039). DJ-1 might contribute to the metastasis of NSCLC.

Association Between OCTN1/2 Gene Polymorphisms (1672C-T, 207G-C) and Susceptibility of Crohn's Disease: a Meta-analysis

International Journal of Colorectal Disease. Jan, 2012  |  Pubmed ID: 21706137

Although a number of genetic studies have attempted to link organic cation transporter 1/2 (OCTN1/2) polymorphisms to susceptibility of Crohn's disease (CD), the results were often inconsistent. The present study aimed at investigating the associations.

Efficient Expression of an Alkaline Pectate Lyase Gene from Bacillus Subtilis and the Characterization of the Recombinant Protein

Biotechnology Letters. Jan, 2012  |  Pubmed ID: 21915717

The gene encoding a novel alkaline pectate lyase (Apel) from Bacillus subtilis was cloned and expressed in B. subtilis WB600. Apel contained an ORF of 1,260 bp, encoding a signal peptide of 21 amino acids and a mature protein of 399 amino acids with a calculated molecular mass of 45497.9 Da. The mature Apel was structurally related to the enzymes in the polysaccharide lyase family 1. After purification, the recombinant Apel had a specific activity of 445 U mg(-1). The enzyme was optimally active at 50°C and pH 9.

Dual-energy Computed Tomography Imaging of Thyroid Nodule Specimens: Comparison with Pathologic Findings

Investigative Radiology. Jan, 2012  |  Pubmed ID: 21788907

To quantitatively assess the imaging characteristics of thyroid nodules in dual-energy computed tomography (CT) imaging for differentiation of benign and malignant lesions.