Insulin-producing Cells Are Bi-potential and Differentiatorsprior to Proliferation in Early Human Development

World Journal of Diabetes. Apr, 2011  |  Pubmed ID: 21537461

To investigate the differentiation and migration of endocrine cells to form the pancreatic islets of Langer-hans in early human development.

The Directive of the Protein: How Does Cytochrome P450 Select the Mechanism of Dopamine Formation?

Journal of the American Chemical Society. May, 2011  |  Pubmed ID: 21539368

Dopamine can be generated from tyramine via arene hydroxylation catalyzed by a cytochrome P450 enzyme (CYP2D6). Our quantum mechanical/molecular mechanical (QM/MM) results reveal the decisive impact of the protein in selecting the 'best' reaction mechanism. Instead of the traditional Meisenheimer-complex mechanism, the study reveals a mechanism involving an initial hydrogen atom transfer from the phenolic hydroxyl group of the tyramine to the iron-oxo of the compound I (Cpd I), followed by a ring-π radical rebound that eventually leads to dopamine by keto-enol rearrangement. This mechanism is not viable in the gas phase since the O-H bond activation by Cpd I is endothermic and the process does not form a stable intermediate. By contrast, the in-protein reaction has a low barrier and is exothermic. It is shown that the local electric field of the protein environment serves as a template that stabilizes the intermediate of the H-abstraction step and thereby mediates the catalysis of dopamine formation at a lower energy cost. Furthermore, it is shown that external electric fields can either catalyze or inhibit the process depending on their directionality.

Factors Affecting the Long-term Renal Allograft Survival

Chinese Medical Journal. Apr, 2011  |  Pubmed ID: 21542992

In the past decades, the one-year graft survival of cadaveric renal allografts has been markedly improved, but their long-term survival has not kept pace. The attrition rate of renal allografts surviving after one year remains almost unchanged. The causes for late graft loss are multiple. The aim of this study was to analyze the predictive factors that impact long-term survival of grafts after kidney transplantation.

NOA: a Novel Network Ontology Analysis Method

Nucleic Acids Research. Jul, 2011  |  Pubmed ID: 21543451

Gene ontology analysis has become a popular and important tool in bioinformatics study, and current ontology analyses are mainly conducted in individual gene or a gene list. However, recent molecular network analysis reveals that the same list of genes with different interactions may perform different functions. Therefore, it is necessary to consider molecular interactions to correctly and specifically annotate biological networks. Here, we propose a novel Network Ontology Analysis (NOA) method to perform gene ontology enrichment analysis on biological networks. Specifically, NOA first defines link ontology that assigns functions to interactions based on the known annotations of joint genes via optimizing two novel indexes 'Coverage' and 'Diversity'. Then, NOA generates two alternative reference sets to statistically rank the enriched functional terms for a given biological network. We compare NOA with traditional enrichment analysis methods in several biological networks, and find that: (i) NOA can capture the change of functions not only in dynamic transcription regulatory networks but also in rewiring protein interaction networks while the traditional methods cannot and (ii) NOA can find more relevant and specific functions than traditional methods in different types of static networks. Furthermore, a freely accessible web server for NOA has been developed at http://www.aporc.org/noa/.

Copper-catalyzed Intramolecular Dehydrogenative Aminooxygenation: Direct Access to Formyl-substituted Aromatic N-heterocycles

Angewandte Chemie (International Ed. in English). Jun, 2011  |  Pubmed ID: 21544911

The Prevalence of Canine Leishmania Infantum Infection in Western China Detected by PCR and Serological Tests

Parasites & Vectors. 2011  |  Pubmed ID: 21554677

Canine leishmaniasis (CanL) is endemic in western China, resulting in important public health problem. It is essential to evaluate the prevalence of canine Leishmania infantum infection for designing control policy. In the present study we report for the first time prevalence of Leishmania infection in dogs living in Jiuzhaigou County (Sichuan Provence, China), which is not only an important endemic area of CanL but also a tourism scenic spot, detected by PCR, ELISA and dipstick test. The results could provide key information for designing control programs against canine and human leishmaniasis. In addition, the complete sequence of the Leishmania isolate from Sichuan Province has not been reported to date and we present the sequences of 116 base-pair (bp) fragment of the conserved region in the minicircle kinetoplast DNA (kDNA) and the results of phylogenetic analyses based on the sequence of the amplified fragment.

Mn(III) Meso-tetrakis-(N-ethylpyridinium-2-yl) Porphyrin Mitigates Total Body Irradiation-induced Long-term Bone Marrow Suppression

Free Radical Biology & Medicine. Jul, 2011  |  Pubmed ID: 21565268

Our recent studies showed that total body irradiation (TBI) induces long-term bone marrow (BM) suppression in part by induction of hematopoietic stem cell (HSC) senescence through reactive oxygen species (ROS). In this study, we examined if Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin (MnTE), a superoxide dismutase mimetic and potent antioxidant, can mitigate TBI-induced long-term BM injury in a mouse model. Our results showed that post-TBI treatment with MnTE significantly inhibited the increases in ROS production and DNA damage in HSCs and the reduction in HSC frequency and clonogenic function induced by TBI. In fact, the clonogenic function of HSCs from irradiated mice after MnTE treatment was comparable to that of HSCs from normal controls on a per-HSC basis, suggesting that MnTE treatment inhibited the induction of HSC senescence by TBI. This suggestion is supported by the finding that MnTE treatment also reduced the expression of p16(Ink4a) (p16) mRNA in HSCs induced by TBI and improved the long-term and multilineage engraftment of irradiated HSCs after transplantation. Therefore, the results from this study demonstrate that MnTE has the potential to be used as a therapeutic agent to mitigate TBI-induced long-term BM suppression by inhibiting ionizing radiation-induced HSC senescence through the ROS-p16 pathway.

Reactive Oxygen Species and Hematopoietic Stem Cell Senescence

International Journal of Hematology. Jul, 2011  |  Pubmed ID: 21567162

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure to exogenous stress. At physiological levels, ROS function as signal molecules which can regulate a variety of cellular functions, including HSC proliferation, differentiation, and mobilization. However, an abnormal increase in ROS production occurs under various pathological conditions, which can inhibit HSC self-renewal and induce HSC senescence, resulting in premature exhaustion of HSCs and hematopoietic dysfunction. This review aims to provide a summary of a number of recent findings regarding the cellular sources of ROS in HSCs and the mechanisms of action whereby ROS induce HSC senescence. In particular, we highlight the roles of the p38 mitogen-activated protein kinase (p38)-p16(Ink4a) (p16) pathway in mediating ROS-induced HSC senescence.

A Study of Cycling Induced Degradation Mechanisms in Si Nanocrystal Memory Devices

Nanotechnology. Jun, 2011  |  Pubmed ID: 21572215

The endurance of Si nanocrystal memory devices under Fowler-Nordheim program and erase (P/E) cycling is investigated. Both threshold voltage (V(th)) and subthreshold swing (SS) degradation are observed when using a high program or erase voltage. The change of SS is found to be proportional to the shift of V(th), indicating that the generation of interface traps plays a dominant role. The charge pumping and the mid-gap voltage methods have been used to analyze endurance degradation both qualitatively and quantitatively. It is concluded that high erase voltage causes severe threshold voltage degradation by generating more interface traps and trapped oxide charges.

A Formation Mechanism of Oxygen Vacancies in a MnO2 Monolayer: a DFT + U Study

Physical Chemistry Chemical Physics : PCCP. Jun, 2011  |  Pubmed ID: 21573308

Recently we reported the oxygen vacancy induced structural variations of the monolayer of manganese dioxide (MnO(2)) under the electronic irradiation. In this report, we further studied the formation mechanism of oxygen vacancies in a MnO(2) monolayer under the framework of density functional theory plus Hubbard model. The effect of injected electrons on the formation of oxygen vacancies has been investigated. It is believed that oxygen is most likely leaving in the form of neutral atoms or molecules. The origination of the role of negative charges has been particularly discussed.

[Diversity of Culturable Actinomycetes in Sea Deposit of Tiger Beach at Bohai Bay, Dalian, China]

Wei Sheng Wu Xue Bao = Acta Microbiologica Sinica. Feb, 2011  |  Pubmed ID: 21574389

To study the diversity of culturable actinomycetes isolated from the sea deposit of Tiger beach at Bohai bay, Dalian, China.

Short-term Plasticity and Auditory Processing in the Ventral Cochlear Nucleus of Normal and Hearing-impaired Animals

Hearing Research. Sep, 2011  |  Pubmed ID: 21586317

The dynamics of synaptic transmission between neurons plays a major role in neural information processing. In the cochlear nucleus, auditory nerve synapses have a relatively high release probability and show pronounced synaptic depression that, in conjunction with the variability of interspike intervals, shapes the information transmitted to the postsynaptic cells. Cellular mechanisms have been best analyzed at the endbulb synapses, revealing that the recent history of presynaptic activity plays a complex, non-linear, role in regulating release. Emerging evidence suggests that the dynamics of synaptic function differs according to the target neuron within the cochlear nucleus. One consequence of hearing loss is changes in evoked release at surviving auditory nerve synapses, and in some situations spontaneous release is greatly enhanced. In contrast, even with cochlear ablation, postsynaptic excitability is less affected. The existing evidence suggests that different modes of hearing loss can result in different dynamic patterns of synaptic transmission between the auditory nerve and postsynaptic neurons. These changes in dynamics in turn will affect the efficacy with which different kinds of information about the acoustic environment can be processed by the parallel pathways in the cochlear nucleus.

Steroidogenic Factor-1 is Required for TGF-beta3-mediated 17beta-estradiol Synthesis in Mouse Ovarian Granulosa Cells

Endocrinology. Aug, 2011  |  Pubmed ID: 21586554

The TGF-β superfamily members are indicated to play key roles in ovarian follicular development, such as granulosa cell proliferation, estrogens, and progesterone production. However, little is known about the roles of TGF-β3 in follicular development. In this study, we found that TGF-β3 was predominantly expressed in granulosa cells of mouse ovarian follicles, and it significantly promoted 17β-estradiol (E(2)) release in a dose-dependent manner. The orphan nuclear receptor steroidogenic factor-1 (SF-1) was required in TGF-β3-induced Cyp19a1 (a key rate-limiting enzyme for estrogen biosynthesis) expression and E(2) release. Additionally, TGF-β3 enhanced the binding of SF-1 to endogenous ovary-specific Cyp19a1 type II promoter, as evidenced by chromatin immunoprecipitation assays. The enhanced effect of SF-1 by TGF-β3 may be mediated through functional interactions between SF-1 and mothers against decapentaplegic homolog (Smad)3 (a mediator of TGF-β signaling pathway), because disruption of the interaction abolished the synergistic effects of SF-1, Smad3, and TGF-β3 on Cyp19a1 mRNA expression. RNA interference and chromatin immunoprecipitation studies also demonstrated that Smad3 was required for SF-1 binding to Cyp19a1 type II promoter and activation of Cyp19a1. Smad3 thus acts as a point of convergence that involves integration of SF-1 and TGF-β signaling in affecting E(2) production. Taken together, our data provide mechanistic insights into the roles of SF-1 in TGF-β3-mediated E(2) synthesis. Understanding of potential cross-points between extracellular signals affecting estrogen production will help to discover new therapeutic targets in estrogen-related diseases.

[Effect of Particulate Allogeneic Acellular Dermal Matrix (PADM) Combined with Autologous Split-thickness Skin (STS) on Wound Healing in Rats]

Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns. Feb, 2011  |  Pubmed ID: 21591334

To evaluate the effects of mixed grafting of allogeneic PADM and autologous STS on wound healing of full-thickness defect in rats.

Collagen Cross Linking Increases Its Biodegradation Resistance in Wet Dentin Bonding

The Journal of Adhesive Dentistry. May, 2011  |  Pubmed ID: 21594232

Purpose: The biodegradation of exposed dentin collagen within the adhesive/dentin (a/d) interface is one of the main reasons for composite restoration failures and seriously affects the durability of dental restorations. In the present study, the objective was to investigate whether the inclusion of the cross-linking reagent (glutaraldehyde, GA) in the adhesive would increase collagen biodegradation resistance within the a/d interface. Materials and Methods: The model adhesive consisted of ~60 % monomers (HEMA/bis-GMA, 45/55 wt/wt) and ~ 40 % ethanol as a solvent. 5% GA was added to the above formulation. After the dentin surfaces were etched for 15 s with 35% phosphoric acid, rinsed with water and blotted dry, adhesives both with and without GA were applied and polymerized by visible light for 20 s. These a/d specimens were immersed in the biodegradation solution (prepared by adding 160 mg collagenase in 1 liter of TESCA buffer solution) for up to 30 days after proceeding with the sectioning/fracture to expose the a/d interfaces. The specimens were analyzed using SEM and micro-Raman spectroscopy. Results: SEM results indicated that for the adhesive without GA, there were many voids and a loss of collagen fibrils in the a/d interface after being challenged by the biodegradation solution. The Raman spectra collected from the interface showed that the amide I of collagen at 1667 cm-1 obviously decreased, indicating a removal of collagen fibrils during the degradation process. For the adhesive containing GA, the collagen fibrils within the interface did not degrade at all, which was also confirmed by the Raman results. Conclusion: The results corroborate the previous findings that by using the current adhesive system and wet bonding, the collagen fibrils in the a/d interface are largely unprotected and easily undergo biodegradation. Directly including cross-linking agents in the adhesive could protect collagen fibrils from degradation in situ within the a/d interface.

Surgical Treatment and Prognosis of Acetabular Fractures Associated with Ipsilateral Femoral Neck Fractures

Orthopedics. May, 2011  |  Pubmed ID: 21598880

Combined ipsilateral acetabular and femoral neck fractures are the result of high-energy trauma. Satisfactory treatment for this injury pattern remains a challenge, since traditional open reduction and internal fixation (ORIF) is always accompanied by a high prevalence of posttraumatic arthritis and avascular necrosis of the femoral head. Eight of 502 acetabular fractures from 1990 to 2008 were diagnosed with combined ipsilateral femoral neck fracture, in which 5 patients' fractures were associated with hip dislocation. These patients were injured from falls, traffic accidents, or crushing accidents. Radiographs and computed tomography scans were taken to check acetabular and femoral neck fractures. All of the patients underwent surgery using appropriate approaches and techniques. Postoperative radiographs demonstrated anatomic or satisfactory reduction for acetabular fractures as well as excellent or good reduction for femoral neck fractures in all of the patients. Follow-up radiographs showed femoral head necrosis in the 5 patients with femoral head dislocations, but not in the other 3 patients. We have seen few patients with this injury pattern, which makes us unable to detect significant differences between the patients associated with femoral head dislocation and those without femoral head dislocation. But by considering the results of our study and those reported in the literature, we believe that for patients with ipsilateral acetabular and femoral neck fractures without hip dislocation, satisfactory results could be expected after ORIF. But for those cases associated with hip dislocation, alternative methods such as acute THR as primary treatment are worthy of consideration.

Colonization Pressure Adjusted by Degree of Environmental Contamination: a Better Indicator for Predicting Methicillin-resistant Staphylococcus Aureus Acquisition

American Journal of Infection Control. Nov, 2011  |  Pubmed ID: 21600671

Colonization pressure has been confirmed as an important risk factor for methicillin-resistant Staphylococcus aureus (MRSA) acquisition among inpatients, but their precise relationship has not been well investigated. Because MRSA carriers can disperse MRSA into their immediate environment with different abilities, the relationship among colonization pressure, the degree of MRSA contamination in environment surrounding MRSA carriers, and MRSA transmission should be explored to facilitate efficient implementation of infection control measures.

Production of Feruloyl Esterase from Aspergillus Niger by Solid-State Fermentation on Different Carbon Sources

Enzyme Research. 2011  |  Pubmed ID: 21603274

A mixture of wheat bran with maize bran as a carbon source and addition of (NH(4))SO(4) as nitrogen source was found to significantly increase production of feruloyl esterase (FAE) enzyme compared with wheat bran as a sole carbon and nitrogen source. The optimal conditions in conical flasks were carbon source (30 g) to water 1 : 1, maize bran to wheat bran 1 : 2, (NH(4))SO(4) 1.2 g and MgSO(4) 70 mg. Under these conditions, FAE activity was 7.68 mU/g. The FAE activity on the mixed carbon sources showed, high activity against the plant cell walls contained in the cultures.

Transcatheter Closure of Perimembranous Ventricular Septal Defects (VSD) with VSD Occluder: Early and Mid-term Results

Heart and Vessels. May, 2011  |  Pubmed ID: 21618026

Results of perimembranous ventricular septal defects (pmVSD) transcatheter closure have been reported in the literature, mostly with the Amplatzer VSD device (muscular or eccentric) (AGA Medical Corp., Golden Valley, MN, USA). However, the data of percutaneous closure of pmVSD with VSD occluder (VSD-O) made in China are still limited. We sought to analyze the safety, efficacy, and follow-up results of percutaneous closure of pmVSD with VSD-O made in China. Seventy-eight patients underwent percutaneous closure of pmVSD at our institution between February 2005 and June 2007. A VSD device made in china (Huayishengjie Medical Corp., Beijing, China) was used in all subjects. The mean age at closure was 11 years (range 2.5-44 years). The attempt to place the device was successful in 74 patients (94.9%). The median device size used was 8 mm (range 5-16 mm). No deaths occurred. Total occlusion rate was 62.8% at completion of the procedure, rising to 87.2% at discharge and 99% during the follow-up. A total of eight early complications occurred (10.3%), but in all subjects these were transient. The median follow-up was 32 months. The most significant complication was complete atrioventricular block (cAVB) in the early phase (five subjects, 6.4%) and during the follow-up (one subject, 1.3%), and there was no need for pacemaker implantation in six subjects. Logistic regression analysis showed that the only variable significantly associated with the occurrence of this complication was age at the time of the procedure (p = 0.025; OR 0.22). All subjects experiencing this problem were <5 years old. Percutaneous pmVSD closure used VSD-O made in China is associated with excellent success and closure rates, no mortality, and low morbidity. Nowadays, pmVSD percutaneous closure is a valuable alternative to surgery. Longer follow-up data and improvements in device characteristics are needed to reduce the risk of cAVB.

Folate-functionalized Unimolecular Micelles Based on a Degradable Amphiphilic Dendrimer-like Star Polymer for Cancer Cell-targeted Drug Delivery

Biomacromolecules. Jul, 2011  |  Pubmed ID: 21619062

A folate-functionalized degradable amphiphilic dendrimer-like star polymer (FA-DLSP) with a well-defined poly(L-lactide) (PLLA) star polymer core and six hydrophilic polyester dendrons based on 2,2-bis(hydroxymethyl) propionic acid was successfully synthesized to be used as a nanoscale carrier for cancer cell-targeted drug delivery. This FA-DLSP hybrid formed unimolecular micelles in the aqueous solution with a mean particle size of ca. 15 nm as determined by dynamic light scattering and transmission electron microscopy. To study the feasibility of FA-DLSP micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, doxorubicin (DOX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 4 wt %. The DOX-loaded FA-DLSP micelles demonstrated a sustained release of DOX due to the hydrophobic interaction between the polymer core and the drug molecules. The hydrolytic degradation in vitro was monitored by weight loss and proton nuclear magnetic resonance spectroscopy to gain insight into the degradation mechanism of the FA-DLSP micelles. It was found that the degradation was pH-dependent and started from the hydrophilic shell gradually to the hydrophobic core. Flow cytometry and confocal microscope studies revealed that the cellular binding of the FA-DLSP hybrid against human KB cells with overexpressed folate-receptors was about twice that of the neat DLSP (without FA). The in vitro cellular cytotoxicity indicated that the FA-DLSP micelles (without DOX) had good biocompatibility with KB cells, whereas DOX-loaded micelles exhibited a similar degree of cytotoxicity against KB cells as that of free DOX. These results clearly showed that the FA-DLSP unimolecular micelles could be a promising nanosize anticancer drug carrier with excellent targeting property.

Clinicopathologic Correlations Between Human Papillomavirus 16 Infection and Beclin 1 Expression in Human Cervical Cancer

International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. Jul, 2011  |  Pubmed ID: 21623196

Our earlier study showed that the autophagy gene Beclin 1 could affect cell proliferation in a cervical cancer HeLa cell line. In this study, we examined Beclin 1 protein expression in 81 specimens of cervical squamous carcinoma by immunohistochemistry. Meanwhile, we detected E6 and E7 genes of human papillomavirus 16 in these tissues by polymerase chain reaction. Beclin 1 expression significantly decreased in samples of malignant cervical cancer tissues than in those of normal or cervical intraepithelial neoplasia tissues. The expression of Beclin 1 was associated with pelvic lymph node metastasis and histological grade, but did not correlate with International Federation of Gynecology and Obstetrics stage, age, depth of cervical infiltration, tumor size, and gross type of cervical lesion. The expression of Beclin 1 was not obviously correlated with E6 and E7 genes statistically. Therefore, decreased expression of Beclin 1 may be related to tumorigenesis and the development of cervical cancer, but is not significantly relevant with human papillomavirus 16 infection.

Alterations of Emotion, Cognition and Firing Activity of the Basolateral Nucleus of the Amygdala After Partial Bilateral Lesions of the Nigrostriatal Pathway in Rats

Brain Research Bulletin. Jul, 2011  |  Pubmed ID: 21624440

Although increasing evidence indicates that psychiatric symptoms are crucial characteristic of the early stage of Parkinson's disease (PD) and precede motor impairments, the neuronal firing activity of the basolateral nucleus of the amygdala (BLA) in the psychiatric symptom of PD and the involved mechanism are still unclear. In the present study, we examined the changes in emotional and cognitive tests not focused on motor fluency and firing activity of projection neurons in the BLA rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum, and the effects of apomorphine and the medial prefrontal cortex (mPFC) on these changes. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 18-22% and 26-30% loss of tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area and substantia nigra pars compacta of rats, respectively. The striatal lesions induced anxiety-like responses in the rats but did not result in depressive-like behavior or cognitive impairments. In the lesioned rats, the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and the firing pattern of BLA projection neurons was not changed. No significant differences were observed either in behaviors or firing activity of BLA projection neurons by further ibotenic acid lesions of the mPFC in the lesioned rats. Systemic administration of cumulative apomorphine (10-160 μg/kg) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA-lesioned and combined 6-OHDA- and mPFC-lesioned rats, but the latter needed more apomorphine stimulation. These data suggest that the anxiety in early stage of PD is possibly related to the decrease in firing activity of BLA projection neurons, which may be regulated by the activation of dopamine receptor in the mPFC.

New Insight into the Antifibrotic Effects of Praziquantel on Mice in Infection with Schistosoma Japonicum

PloS One. 2011  |  Pubmed ID: 21629648

Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required.

Effects of the Removal of Cytoplasm on the Development of Early Cloned Bovine Embryos

Animal Reproduction Science. Jun, 2011  |  Pubmed ID: 21632190

Oocyte cytoplasm plays a prominent role in cloned embryonic development. To investigate the influence of oocyte cytoplasmic amount on cloned embryo development, we generated bovine somatic cell nuclear transfer (SCNT) embryos containing high (30-40% of the cytoplasm was removed), medium (15-25% of the cytoplasm was removed) and low (<10% of the cytoplasm was removed) nucleocytoplasmic volume ratios (N/C) using enucleated metaphase II oocyte as recipient, and fibroblast as donor nucleus, and analyzed the expression levels of ND1, Cytb and ATPase6, as well as the embryonic quality. The results indicated: (1) the process of embryonic development was not influenced by <40% of cytoplasm removal; (2) the rate of blastocyst formation, the total number of blastomere and the ratio of ICM to TE were inversely proportional to the N/C; (3) SCNT embryos with reduced volume equal to 75-85% or >90% of an intact oocyte volume showed similar karyotype structure of the donor cells; (4) the number of mtDNA copy was larger in low N/C embryos than that in medium or high N/C embryos, and the expression levels of each gene hardly varied from the 2-cell to 8-cell stage, while the expression levels increased dramatically at the blastocyst stage; (5) from 16-cell to the blastocyst stage, the change of the expression level of each gene was not significant between low N/C embryos and IVF embryos, but it was more significant than those of high or medium N/C embryos. The results suggest that the decrease of mtDNA copy number and mitochondrial gene expression may be related to the impairment in early embryonic development, and removal of <10% adjacent cytoplasm volume may be optimal for bovine SCNT embryo development.

An Easy Way to Apply Orthodontic Extraction for Impacted Lower Third Molar Compressing to the Inferior Alveolar Nerve

Journal of Cranio-maxillo-facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. Jun, 2011  |  Pubmed ID: 21641229

PURPOSE: To study the results of an easy orthodontic extraction method for impacted lower third molar removal which had roots compressing to the inferior alveolar nerve (IAN). PATIENTS AND METHODS: Forty patients were divided into two groups according to their desire. Orthodontic traction group (n=20) had brackets or mini bone screws on the antagonist maxillary molars as anchorage for orthodontic traction from 3 to 10 weeks until the roots' tip was away from the IAN, the tooth was then removed. Traditional extraction group (n=20) had the tooth removed immediately by the same surgeon. Post-operative results were compared between the two groups. RESULTS: All 20 patients in the orthodontic extraction group had their lower impacted third molar removed easily without lower lip numbness after surgery, while 5 patients in the traditional extraction group had transient IAN injury and went away 1 week later. There were no anchorage teeth and adjacent mandibular second molar loose or displacement. CONCLUSION: Application of orthodontic brackets or mini bone screws on the antagonist maxillary molars is an easy way for orthodontic extraction of impacted lower third molar with roots' tip compressed to the IAN. It is an effective way to avoid IAN injury during tooth extraction.

Effects of Obstructive Sleep Apnea and Its Treatment on Cardiovascular Risk in CAD Patients

Respiratory Medicine. Oct, 2011  |  Pubmed ID: 21646006

This study, in optimally treated CAD patients with newly diagnosed OSA, focused on (1) The relationships between OSA and serum biomarkers of four potential pathways of cardiovascular injury in OSA: high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), N terminal pro B type natriuretic peptide (NT-proBNP) and fibrinogen; and (2) The effect of continuous positive airway pressure (CPAP) therapy on these markers. 151 Chinese patients with proven CAD and standard medication were enrolled. After polysomnography, patients were classified into four groups according to apnea-hypopnea index (AHI): no OSA (n = 25); mild OSA (n = 50); moderate OSA (n = 43); severe OSA (n = 33). Morning levels of hs-CRP, ET-1, NT-proBNP and fibrinogen were assayed and repeated in severe OSA patients after 3-months CPAP treatment. Hs-CRP was greater in patients with severe OSA than those with no OSA or mild OSA (P = 0.001, P = 0.003; respectively). After adjustment for confounders, the hs-CRP levels correlated most strongly with AHI and oxygen desturation index (ODI) (r = 0.439, P < 0.001; r = 0.445, P < 0.001; respectively). In stepwise multiple linear regressions, the strongest predictor of hs-CRP levels was ODI (P < 0.001). After 3 months of CPAP treatment, the hs-CRP levels deceased (P = 0.005) in CAD patients with severe OSA. In CAD patients on current optimal medications, hs-CRP is significantly correlated with the severity of OSA, and the elevated hs-CRP levels can be decreased by CPAP. This suggests that OSA could activate vascular inflammation in CAD patients despite current best practice medications.

Differential Expression of the Wnt/β-catenin Pathway in the Genital Tubercle (GT) of Fetal Male Rat Following Maternal Exposure to Di-n-butyl Phthalate (DBP)

Systems Biology in Reproductive Medicine. Oct, 2011  |  Pubmed ID: 21657945

Di-n-butyl phthalate (DBP) is one of the most abundantly produced endocrine disruptors that leaches out from polyvinyl chloride plastics and can cause hypospadias in male rats during maternal exposure. The objective of this study was to first explore the roles of Wnt/β-catenin pathway in the fetal rat genital tubercle (GT) following in-utero exposure to DBP. Timed-pregnant rats were given DBP by gastric intubation at a dose of 750 mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a rat model of hypospadias. On GD19, genital tubercle down-regulation of β-catenin, Phospho-GSK-3β, and up-regulation of GSK-3β (glycogen synthase kinase-3β), NFκB in fetal male rats was observed by western blot analysis. β-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of β-catenin decreased in the DBP-treated fetal rat GT compared to the normal control. These findings, for the first time, indicate that DBP may affect the development of GT by down-regulating the Wnt/β-catenin pathway in fetal male rats.

Antioxidant Treatment with Quercetin Ameliorates Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

Journal of Bioscience and Bioengineering. Sep, 2011  |  Pubmed ID: 21664865

Oxidative stress is demonstrated to be involved in the pathophysiological mechanism of erectile dysfunction (ED). Quercetin, a potent bioflavonoid, has been reported to have the antioxidant role. In the present study, we examined the effect of quercetin on ED and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ. The diabetic rats were then randomized to diabetic group and quercetin therapy groups which were treated with quercetin at different doses of 5, 20 and 50mg/kg per day respectively. At the end of the 8th week, erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Superoxide dismutase (SOD) activity, thiobarbituric acid-reacting substance (TBARS) and nitrite and nitrate (NOx) levels were measured in cavernosum tissue. Endothelial NO synthase (eNOS) expression was determined using Western blot method. ICP in diabetic rats was significantly decreased than that in controls. After treatment with quercetin at the doses of 20 and 50mg/kg, ICP was significantly increased compared to that in untreated diabetic rats. Decreased levels of SOD activity, NOx and eNOS expression, as well as elevated levels of TBARS were found in diabetic group compared with control group. Treatment with 20 and 50mg/kg quercetin improved SOD activity, NOx and TBARS levels in corpus cavernosum of diabetic rats. Decreased expression of eNOS in diabetic rats was only ameliorated by 50mg/kg quercetin treatment. Quercetin could ameliorate ED in diabetic rats by inhibiting oxidative stress.

A Survey of the Cellular Responses in Pseudomonas Putida KT2440 Growing in Sterilized Soil by Microarray Analysis

FEMS Microbiology Ecology. Nov, 2011  |  Pubmed ID: 21671961

Genome-wide scanning of gene expression by microarray techniques was successfully performed on RNA extracted from sterilized soil inoculated with Pseudomonas putida KT2440/pSL1, which contains a chloroaromatic degrading plasmid, in the presence or absence of 3-chlorobenzoic acid (3CB). The genes showing significant changes in their expression in both the triplicate-microarray analysis using amplified RNA and the single-microarray analysis using unamplified RNA were investigated. Pathway analysis revealed that the benzoate degradation pathway underwent the most significant changes following treatment with 3CB. Analysis based on categorization of differentially expressed genes against 3CB revealed new findings about the cellular responses of the bacteria to 3CB. Genes specifically involved in the transport of 3CB were upregulated, including a K(+)/H(+) antiporter complex, a universal stress protein, two cytochrome P450 proteins and an efflux transporter. The downregulated expression of several genes involved in carbon metabolism and the genes belonging to a prophage in the presence of 3CB was observed. This study demonstrated the applicability of the method of soil RNA extraction for microarray analysis of gene expression in bacteria growing in sterilized soil.

Synthesis of Quinazolin-4(3H)-ones Via Pd(II)-catalyzed Intramolecular C(sp2)-H Carboxamidation of N-arylamidines

The Journal of Organic Chemistry. Aug, 2011  |  Pubmed ID: 21675775

An efficient synthesis of quinazolin-4(3H)-ones from N-arylamidines, through palladium-catalyzed intramolecular C(sp(2))-H carboxamidation, has been developed. The reaction, carried out in the presence of 1.0 equiv of CuO as oxidant under atmospheric pressure of CO, provides diversified 2-aryl(alkyl)quinazolin-4(3H)-ones in reasonable to good yields from N-arylamidines, which are readily derived from anilines and nitriles. Compared with existing approaches to quinazolin-4(3H)-ones, the current strategy features atom-economy and step-efficiency.

Bariatric Surgery Reduces Visceral Adipose Inflammation and Improves Endothelial Function in Type 2 Diabetic Mice

Arteriosclerosis, Thrombosis, and Vascular Biology. Sep, 2011  |  Pubmed ID: 21680898

Bariatric surgery is emerging as an effective method to alleviate a multitude of medical conditions associated with morbid obesity and type 2 diabetes. However, little is known about the effects and mechanisms of bariatric surgery on visceral fat inflammation and endothelial dysfunction in type 2 diabetes. We hypothesize that bariatric surgery ameliorates interferon-γ-mediated adipose tissue inflammation/oxidative stress and improves endothelial function in type 2 diabetic mice.

Direct Conversion of Bio-ethanol to Isobutene on Nanosized Zn(x)Zr(y)O(z) Mixed Oxides with Balanced Acid-base Sites

Journal of the American Chemical Society. Jul, 2011  |  Pubmed ID: 21682296

We report the design and synthesis of nanosized Zn(x)Zr(y)O(z) mixed oxides for direct and high-yield conversion of bio-ethanol to isobutene (~83%). ZnO is addded to ZrO(2) to selectively passivate zirconia's strong Lewis acidic sites and weaken Brönsted acidic sites, while simultaneously introducing basicity. As a result, the undesired reactions of bio-ethanol dehydration and acetone polymerization/coking are suppressed. Instead, a surface basic site-catalyzed ethanol dehydrogenation to acetaldehyde, acetaldehyde to acetone conversion via a complex pathway including aldol-condensation/dehydrogenation, and a Brönsted acidic site-catalyzed acetone-to-isobutene reaction pathway dominates on the nanosized Zn(x)Zr(y)O(z) mixed oxide catalyst, leading to a highly selective process for direct conversion of bio-ethanol to isobutene.

Affinity Hydrogels for Controlled Protein Release Using Nucleic Acid Aptamers and Complementary Oligonucleotides

Biomaterials. Oct, 2011  |  Pubmed ID: 21684002

Biomaterials for the precise control of protein release are important to the development of new strategies for treating human diseases. This study aimed to fundamentally understand aptamer--protein dissociation triggered by complementary oligonucleotides, and to apply this understanding to develop affinity hydrogels for controlled protein release. The results showed that the oligonucleotide tails of the aptamers played a critical role in inducing intermolecular hybridization and triggering aptamer--protein dissociation. In addition, the attachment of the oligonucleotide tails to the aptamers and the increase of hybridizing length could produce a synergistic effect on the dissociation of bound proteins from their aptamers. More importantly, pegylated complementary oligonucleotides could successfully trigger protein release from the aptamer-functionalized hydrogels at multiple time points. Based on these results, it is believed that aptamer-functionalized hydrogels and complementary oligonucleotides hold great potential of controlling the release of protein drugs to treat human diseases.

Surface-mediated Four-wave Mixing of Nanostructures with Counterpropagating Surface Plasmon Polaritons

Optics Letters. Jun, 2011  |  Pubmed ID: 21686016

We demonstrate that four-wave mixing (FWM) signals from individual Si nanoparticles can be generated by the surface fields of traveling surface plasmon polariton modes. We have chosen a counterpropagating excitation scheme in which the nanoparticle is exposed only to surface excitation fields and not to direct laser illumination. We show that background-free, surface-mediated FWM of nanoparticles can be acquired, and that the resulting nonlinear radiation is coherent.

Selective Hydrogenation of Trans,trans-muconic Acid to Adipic Acid over a Titania-supported Rhenium Catalyst

ChemSusChem. Aug, 2011  |  Pubmed ID: 21688400

[Comparative Study of Intertrochanteric Fractures Treated with Proximal Femur Locking Compress Plate in Aged]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. May, 2011  |  Pubmed ID: 21688530

To compare the clinic outcomes of dynamic hip screw (DHS), intramedullary fixation (IF) and proximal femur locking plate (PF-LCP) in the treatment of intertrochanteric fractures in the elderly patients.

Computational Systems Biology: Integration of Sequence, Structure, Network, and Dynamics

BMC Systems Biology. 2011  |  Pubmed ID: 21689468

A report of the 4nd International Conference on Computational Systems Biology, 9-11 September 2010, Suzhou, China.

Support Vector Machine Prediction of Enzyme Function with Conjoint Triad Feature and Hierarchical Context

BMC Systems Biology. 2011  |  Pubmed ID: 21689481

Enzymes are known as the largest class of proteins and their functions are usually annotated by the Enzyme Commission (EC), which uses a hierarchy structure, i.e., four numbers separated by periods, to classify the function of enzymes. Automatically categorizing enzyme into the EC hierarchy is crucial to understand its specific molecular mechanism.

Spectral Clustering on Multiple Manifolds

IEEE Transactions on Neural Networks / a Publication of the IEEE Neural Networks Council. Jul, 2011  |  Pubmed ID: 21690009

Spectral clustering (SC) is a large family of grouping methods that partition data using eigenvectors of an affinity matrix derived from the data. Though SC methods have been successfully applied to a large number of challenging clustering scenarios, it is noteworthy that they will fail when there are significant intersections among different clusters. In this paper, based on the analysis that SC methods are able to work well when the affinity values of the points belonging to different clusters are relatively low, we propose a new method, called spectral multi-manifold clustering (SMMC), which is able to handle intersections. In our model, the data are assumed to lie on or close to multiple smooth low-dimensional manifolds, where some data manifolds are separated but some are intersecting. Then, local geometric information of the sampled data is incorporated to construct a suitable affinity matrix. Finally, spectral method is applied to this affinity matrix to group the data. Extensive experiments on synthetic as well as real datasets demonstrate the promising performance of SMMC.

Nematocidal Flavone-C-glycosides Against the Root-knot Nematode (Meloidogyne Incognita) from Arisaema Erubescens Tubers

Molecules (Basel, Switzerland). 2011  |  Pubmed ID: 21694672

A screening of several Chinese medicinal herbs for nematicidal properties showed that Arisaema erubescens (Wall.) Schott tubers possessed significant nematicidal activity against the root-knot nematode (Meloidogyne incognita). From the ethanol extract, two nematicidal flavone-C-glycosides were isolated by bioassay-guided fractionation. The compounds were identified as schaftoside and isoschaftoside on the basis of their phytochemical and spectral data. Schaftoside and isoschaftoside possessed strong nematicidal activity against M. incognita (LC(50) = 114.66 μg/mL and 323.09 μg/mL, respectively) while the crude extract of A. erubescens exhibited nematicidal activity against the root-knot nematode with a LC(50) value of 258.11 μg/mL.

Fluorescence in Situ Hybridization on Plant Extended Chromatin DNA Fibers for Single-copy and Repetitive DNA Sequences

Plant Cell Reports. Sep, 2011  |  Pubmed ID: 21695528

The compactness of plant chromosomes and the structure of the plant cell wall and cytoplasm provide a great obstacle to fluorescence in situ hybridization (FISH) for single-copy or low-copy DNA sequences. Consequently, many new methods for improving spatial resolution via chromosomal stretching have been employed to overcome this technical challenge. In this article, a technique for extracting cell-wall free nuclei at mitotic interphase, then using these nuclei to prepare extended DNA fibers (EDFs) by the method of a receding interface, whereby slide-mounted chromatin produces EDFs in concert with gravity-assisted buffer flow, was adopted as a result of the low frequency of EDF damage produced by this procedure. To examine the quality of these EDFs, we used single-copy gene encoding S-locus receptor kinase and multi-copy 5S rDNA (ribosomal DNA) as probes. The resulting EDFs proved suitable for high-resolution FISH mapping for repetitive DNA sequences, and the localization of a single-copy locus.

Does the Aminopeptidase a Have Prognostic and Diagnostic Value in Chagas Disease and Other Dilated Cardiomyopathies?

Journal of Cardiovascular Pharmacology. Oct, 2011  |  Pubmed ID: 21697726

Chagas disease (CD), which is caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. We investigated if plasma activity of one of the enzymes being part of the renin-angiotensin system, aminopeptidase A (APA), has diagnostic and prognostic potency in patients with CD and dilated cardiomyopathies (DCMs) due to other causes. Blood samples were taken from 94 patients with CD, 46 patients with DCM, and 34 healthy control subjects. Plasma APA activity was determined by fluorometry assays. The average follow-up time was 39 months; by the end of study, 33 patients had died and another 13 received heart transplant. There was no significant alteration in plasma APA activity in the patients with CD or DCM, as compared with that in controls. The Pearson correlation of echocardiographic data with plasma APA activity in patients with CD and DCM did not reveal any significant correlation with left-ventricular ejection fraction or other echocardiographic parameters. APA activity was unable to predict mortality or the need for heart transplant. Detection of APA activity in plasma may not prove suitable for prognosis in patients with heart failure and is unable to screen or diagnose asymptomatic patients with CD for early therapy.

Graphene Flash Memory

ACS Nano. Oct, 2011  |  Pubmed ID: 21854056

Graphene's single atomic layer of sp(2) carbon has recently garnered much attention for its potential use in electronic applications. Here, we report a memory application for graphene, which we call graphene flash memory (GFM). GFM has the potential to exceed the performance of current flash memory technology by utilizing the intrinsic properties of graphene, such as high density of states, high work function, and low dimensionality. To this end, we have grown large-area graphene sheets by chemical vapor deposition and integrated them into a floating gate structure. GFM displays a wide memory window of ∼6 V at significantly low program/erase voltages of ±7 V. GFM also shows a long retention time of more than 10 years at room temperature. Additionally, simulations suggest that GFM suffers very little from cell-to-cell interference, potentially enabling scaling down far beyond current state-of-the-art flash memory devices.

Changes in the Inositol Lipid Signal System and Effects on the Secretion of TNF-α by Macrophages in Severely Scalded Mice

Burns : Journal of the International Society for Burn Injuries. Dec, 2011  |  Pubmed ID: 21855216

In order to study the mechanism of abnormal macrophage (Mϕ) function in pro-inflammatory cytokine changes after burn, the inositol lipid signal system and its role in tumour necrosis factor-alpha (TNF-α) secretion by peritoneal Mϕs was observed in severely scalded mice.

Deconvoluting Subensemble Chemical Reaction Kinetics of Platinum-sulfur Ligand Exchange Detected with Single-molecule Fluorescence Microscopy

Inorganic Chemistry. Oct, 2011  |  Pubmed ID: 21863905

The subensemble kinetics of a platinum-sulfur covalent chemical reaction at the solution/surface interface of a model industrial catalyst support was examined using single-molecule fluorescence microscopy (SMFM) and was found to exhibit biexponential first-order kinetic behavior. The observed kinetics was a convolution of the observation probability and chemical reaction rate. These results suggest that deconvolution strategies may be broadly important for obtaining accurate chemical reaction kinetics with SMFM.

[Feasibility of Peptide Mass Fingerprinting for Differential Diagnosis of IgA and Non-IgA Nephropathy]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Aug, 2011  |  Pubmed ID: 21868311

To investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).?

A Pilot Study of the Efficacy and Safety of Paroxetine Augmented with Risperidone, Valproate, Buspirone, Trazodone, or Thyroid Hormone in Adult Chinese Patients with Treatment-resistant Major Depression

Journal of Clinical Psychopharmacology. Oct, 2011  |  Pubmed ID: 21869688

To compare the efficacy and safety of augmenting paroxetine with risperidone, buspirone, valproate, trazodone, or thyroid hormone in patients with treatment-resistant depression (TRD), 225 patients with retrospectively and/or prospectively identified stage II TRD were randomly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45), sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100 mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study. Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study, response rate based on 17-item Hamilton Rating Scale for Depression total score of 50% improvement or greater from baseline, and the change in scores of Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey, and the Life Satisfaction Rating Scale. The remission rates were 26.7% for risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and 37.5% for thyroid hormone. There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events. Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD. Large-sample studies are warranted to support or refute these findings.

[Experimental Studies on the Early Treatment of Soft Tissue Explosion Injury by Vacuum-assisted Closure]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jul, 2011  |  Pubmed ID: 21870402

To investigate the effect on early treatment with vacuum-assisted closure(VAC) to wound healing of acute explosion injury in pigs, and provide a new way for early treatment of battle wounds.

The Basic Helix-loop-helix Transcription Factor Family in the Pea Aphid, Acyrthosiphon Pisum

Journal of Insect Science (Online). 2011  |  Pubmed ID: 21870970

The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, and human. This study identified 54 bHLH family members in the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae), genome. Phylogenetic analyses revealed that they belong to 37 bHLH families with 21, 13, 9, 1, 9, and 1 members in group A, B, C, D, E, and F, respectively. Through in-group phylogenetic analyses, all of the identified A. pisum bHLH members were assigned into their correspondent bHLH families with confidence, among which 51 were defined according to phylogenetic analyses with orthologs from Drosophila melanogaster Meigen (Diptera: Drosophilidae), and 3 of them were defined according to phylogenetic analyses with orthologs from Bombyx mori L. (Lepidoptera: Bombycidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Analyses on genomic coding regions revealed that the number and average length of introns in A. pisum bHLH motifs are higher than those in other insects. The present study provides useful background information for future studies on structure and function of bHLH proteins in the regulation of A. pisum development.

The Higher Barrier of Darunavir and Tipranavir Resistance for HIV-1 Protease

Biochemical and Biophysical Research Communications. Sep, 2011  |  Pubmed ID: 21871444

Darunavir and tipranavir are two inhibitors that are active against multi-drug resistant (MDR) HIV-1 protease variants. In this study, the invitro inhibitory efficacy was tested against a MDR HIV-1 protease variant, MDR 769 82T, containing the drug resistance mutations of 46L/54V/82T/84V/90M. Crystallographic and enzymatic studies were performed to examine the mechanism of resistance and the relative maintenance of potency. The key findings are as follows: (i) The MDR protease exhibits decreased susceptibility to all nine HIV-1 protease inhibitors approved by the US Food and Drug Administration (FDA), among which darunavir and tipranavir are the most potent; (ii) the threonine 82 mutation on the protease greatly enhances drug resistance by altering the hydrophobicity of the binding pocket; (iii) darunavir or tipranavir binding facilitates closure of the wide-open flaps of the MDR protease; and (iv) the remaining potency of tipranavir may be preserved by stabilizing the flaps in the inhibitor-protease complex while darunavir maintains its potency by preserving protein main chain hydrogen bonds with the flexible P2 group. These results could provide new insights into drug design strategies to overcome multi-drug resistance of HIV-1 protease variants.

Discovery of Diagnosis Pattern of Coronary Heart Disease with Qi Deficiency Syndrome by the T-test-based Adaboost Algorithm

Evidence-based Complementary and Alternative Medicine : ECAM. 2011  |  Pubmed ID: 21876710

Coronary heart disease (CHD) is still the leading cause of death for adults worldwide. Traditional Chinese medicine (TCM) has a history of 1000 years fighting against the disease and provides a complementary and alternative treatment to it. Syndrome is the core of TCM diagnosis and it is traditionally diagnosed based on macroscopic symptoms as well as tongue and pulse recognitions of patients. Establishment of the diagnosis method in the microcosmic level is an urgent and major problem in TCM. The aim of this study was to establish characteristic diagnosis pattern for CHD with Qi deficiency syndrome (QDS). Thirty-four biological parameters were detected in 52 patients having unstable angina (UA) with or without QDS. Then, we presented a novel data mining method, t-test-based Adaboost algorithm, to establish highest prediction accuracy with the least number of biological parameters for UA with QDS. We gained a pattern composed of five biological parameters that distinguishes UA with QDS patients from non-QDS patients. The diagnosis accuracy of the patterns could reach 84.5% based on a 3-fold cross validation technique. Moreover, we included 85 UA cases collected from hospitals located in the north and south of China to further verify the association between the pattern and QDS. The classification accuracy is 83.5%, which keeps consistent with the accuracy obtained by the cross-validation technique. The association between a symptom and the five biological parameters was established by the data mining method and it reached an accuracy of ∼80%. These results showed that the t-test-based Adaboost algorithm might be a powerful technique for diagnosing syndrome in TCM in the context of CHD.

Carbon Nanotubes Grown in Situ on Graphene Nanosheets As Superior Anodes for Li-ion Batteries

Nanoscale. Oct, 2011  |  Pubmed ID: 21879120

Graphene and carbon nanotubes are intriguing alternative anode materials for lithium ion batteries. The prevention of graphene restacking and facilitation of lithium diffusion into CNTs with large aspect ratio are highly desirable for the performance enhancements including capacity, cycliability and rate capability. In this work, we demonstrated that a multilayered graphene-CNT hybrid nanostructure was able to hold such merits. GNS were separated and stabilized by CNTs grown in situ on GNS surface. The length of CNTs was found to be a key factor to the electrochemical performances. The GNS-CNT composite with the shortest CNT decoration displayed highly reversible capacities of 573 mAh g(-1) at a small current of 0.2C and 520 mAh g(-1) at a large current of 2C. The growth and lithium storage mechanism for graphene-CNT composite was also proposed.

Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging

Science Translational Medicine. Aug, 2011  |  Pubmed ID: 21885406

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.

Assessment of Nanomaterial Cytotoxicity with SOLiD Sequencing-based MicroRNA Expression Profiling

Biomaterials. Dec, 2011  |  Pubmed ID: 21889204

The cytotoxicity of nanomaterials has become a major concern in the field of nanotechnology. The key challenge is the lack of reliable methods to examine the overall cellular effects of nanomaterials. Here, a new method is developed to assess the cytological effects of nanomaterial basing on miRNA expression profiling. The SOLiD sequencing is used to acquire the miRNAs expression profiling in NIH/3T3 cells after exposure to Fe(2)O(3) NPs, CdTe QDs and MW-CNTs, respectively. The systematic analysis of miRNAs expression profiling is established by taking account of all miRNAs into their regulatory networks. By affecting the output of targeted mRNAs, miRNAs widely regulated the KEGG pathways and GO biological processes in nanomaterial treated cells. Therefore, the miRNA expression profiling can well reflect the characteristic of nanomaterials, and the method not only provide more evidences to assess biocompatibility of nanomaterials and but also clues to discover new biological effects of nanomaterials.

Tbx20 Transcription Factor is a Downstream Mediator for Bone Morphogenetic Protein-10 in Regulating Cardiac Ventricular Wall Development and Function

The Journal of Biological Chemistry. Oct, 2011  |  Pubmed ID: 21890625

Bone morphogenetic protein 10 (BMP10) belongs to the TGFβ-superfamily. Previously, we had demonstrated that BMP10 is a key regulator for ventricular chamber formation, growth, and maturation. Ablation of BMP10 leads to hypoplastic ventricular wall formation, and elevated levels of BMP10 are associated with abnormal ventricular trabeculation/compaction and wall maturation. However, the molecular mechanism(s) by which BMP10 regulates ventricle wall growth and maturation is still largely unknown. In this study, we sought to identify the specific transcriptional network that is potentially mediated by BMP10. We analyzed and compared the gene expression profiles between α-myosin heavy chain (αMHC)-BMP10 transgenic hearts and nontransgenic littermate controls using Affymetrix mouse exon arrays. T-box 20 (Tbx20), a cardiac transcription factor, was significantly up-regulated in αMHC-BMP10 transgenic hearts, which was validated by quantitative RT-PCR and in situ hybridization. Ablation of BMP10 reduced Tbx20 expression specifically in the BMP10-expressing region of the developing ventricle. In vitro promoter analysis demonstrated that BMP10 was able to induce Tbx20 promoter activity through a conserved Smad binding site in the Tbx20 promoter proximal region. Furthermore, overexpression of Tbx20 in myocardium led to dilated cardiomyopathy that exhibited ventricular hypertrabeculation and an abnormal muscular septum, which phenocopied genetically modified mice with elevated BMP10 levels. Taken together, our findings demonstrate that the BMP10-Tbx20 signaling cascade is important for ventricular wall development and maturation.

Nanopore-based Detection of Circulating MicroRNAs in Lung Cancer Patients

Nature Nanotechnology. Oct, 2011  |  Pubmed ID: 21892163

MicroRNAs are short RNA molecules that regulate gene expression, and have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, detecting microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the α-haemolysin protein can selectively detect microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labels or amplification of the microRNA. The sensor, which uses a programmable oligonucleotide probe to generate a target-specific signature signal, can quantify subpicomolar levels of cancer-associated microRNAs and can distinguish single-nucleotide differences between microRNA family members. This approach is potentially useful for quantitative microRNA detection, the discovery of disease markers and non-invasive early diagnosis of cancer.

Do All the Protic Ionic Liquids Exist As Molecular Aggregates in the Gas Phase?

Physical Chemistry Chemical Physics : PCCP. Oct, 2011  |  Pubmed ID: 21897972

According to an EI-MS study of 1,1,3,3-tetramethylguanidium-based protic ionic liquids (PILs), it has been concluded that not all PILs exist as molecular aggregates in the gas phase. The detection of both ions of m/z 115.0 and m/z 116.0 for the 1,1,3,3-tetramethylguanidinium trifluoromethylsulfonate (TMGS) protic ionic liquid indicates that both the molecular and ionic aggregates co-exist in the gas phase, which is to say that the TMGS may also evaporate via the ionic aggregates just like aprotic ionic liquids. Furthermore, investigation on triethylamine-based and 1-methylimidazole-based PILs confirmed that the gas phase structure of PILs depends on both the acidity and basicity of the corresponding acid and base.

Plasma MicroRNAs As Novel Biomarkers for Early Detection of Lung Cancer

International Journal of Clinical and Experimental Pathology. Aug, 2011  |  Pubmed ID: 21904633

A diagnosis of lung cancer at its early stages is vital for improving the survival rate of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide non-coding small RNAs, are frequently dysregulated in lung cancer. The objective of this study was to investigate the potential of circulating miRNAs for early detection of lung cancer. We searched the published literature for the miRNA microarray data of primary lung cancer and selected 15 miRNAs that were most frequently up-regulated in lung cancer tissues. Total plasma RNA including miRNAs was isolated, polyadenylated and reverse-transcribed into cDNAs. The levels of miRNAs were determined by real-time RT-PCR in 74 lung cancer patients and 68 age-matched cancer-free controls. We found that the levels of miR-155, miR-197, and miR-182 in the plasma of lung cancer including stage I patients were significantly elevated compared with controls (P<0.001). The combination of these 3 miRNAs yielded 81.33% sensitivity and 86.76% specificity in discriminating lung cancer patients from controls. The levels of miR-155 and miR-197 were higher in the plasma from lung cancer patients with metastasis than in those without metastasis (P<0.05) and were significantly decreased in responsive patients during chemotherapy (P<0.001). These results indicate that miR-155, miR-197, and miR-182 can be potential non-invasive biomarkers for early detection of lung cancer.

A B3LYP and MP2(full) Theoretical Investigation into Explosive Sensitivity Upon the Formation of the Molecule-cation Interaction Between the Nitro Group of 3,4-dinitropyrazole and H(+), Li (+), Na (+), Be (2+) or Mg (2+)

Journal of Molecular Modeling. Sep, 2011  |  Pubmed ID: 21904813

The explosive sensitivity upon the formation of molecule-cation interaction between the nitro group of 3,4-dinitropyrazole (DNP) and H(+), Li(+), Na(+), Be(2+) or Mg(2+) has been investigated using the B3LYP and MP2(full) methods with the 6-311++G** and 6-311++G(2df,2p) basis sets. The bond dissociation energy (BDE) of the C3-N7 trigger bond has also been discussed for the DNP monomer and the corresponding complex. The interaction between the oxygen atom of nitro group and H(+) in DNP…H(+) is partly covalent in nature. The molecule-cation interaction and bond dissociation energy of the C3-N7 trigger bond follow the order of DNP…Be(2+) > DNP…Mg(2+) > DNP…Li(+) > DNP…Na(+). Except for DNP…H(+), the increment of the trigger bond dissociation energy in comparison with the DNP monomer correlates well with the molecule-cation interaction energy, natural charge of the nitro group, electron density ρ (BCP(C3-N7)), delocalization energy E ((2)) and NBO charge transfer. The analyses of atoms in molecules (AIM), natural bond orbital (NBO) and electron density shifts have shown that the electron density of the nitro group shifts toward the C3-N7 trigger bond upon the formation of the molecule-cation interaction. Thus, the trigger bond is strengthened and the sensitivity of DNP is reduced.

[Evaluation of Efficacy of the Anticoagulation and Thrombolysis for Deep Venous Thrombosis Via Local Vein Approach and Peripheral Vein Approach]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Jun, 2011  |  Pubmed ID: 21914299

To investigate the efficacy of anticoagulation and thrombolysis for deep venous thrombosis via local vein approach and peripheral vein approach to guide clinical treatment.

The Effect of Zinc Addition on the Oxidation State of Cobalt in Co/ZrO2 Catalysts

ChemSusChem. Nov, 2011  |  Pubmed ID: 21919212

The effect of zinc promotion on the oxidation state of cobalt in Co/ZrO(2) catalysts was investigated and correlated with the activity and selectivity for ethanol steam reforming (ESR). Catalysts were synthesized by applying incipient wetness impregnation and characterized by using Brunauer-Emmett-Teller (BET), temperature-programmed reduction (TPR) measurements, X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Higher ethanol conversion and lower CH(4) selectivity are observed for the Co/ZrO(2) catalyst promoted with Zn as compared to the Co/ZrO(2) catalyst alone. Addition of Zn inhibits the oxidation of metallic cobalt (Co(0) ) particles and results in a higher ratio of Co(0) /Co(2+) in the Zn-promoted Co/ZrO(2) catalyst. These results suggest that metallic cobalt (Co(0) ) is more active than Co(2+) in the ethanol conversion through dehydrogenation and that Co(2+) may play a role in the CH(4) formation. TPR measurements, on the other hand, reveal that Zn addition inhibits the reduction of Co(2+) and Co(3+) , which would lead to the false conclusion that oxidized Co is required to reduce the CH(4) formation. Therefore, TPR measurements may not be appropriate to correlate the degree of metal reducibility (in this case Co(0)) with the catalyst activity for reactions, such as ESR, where oxidizing conditions exist.

Sub-2μm Porous Silica Materials for Enhanced Separation Performance in Liquid Chromatography

Journal of Chromatography. A. Sep, 2011  |  Pubmed ID: 21925665

Fully or partially sub-2μm porous silica materials have garnered strong interests as column packing materials in separation and analytical technologies due to the promise of rapid separation, enhanced efficiency and separation resolution. Silica support materials of different morphology and sub-2μm size have been developed to improve separation performances in liquid chromatography (LC) and capillary electrochromatography (CEC). The current review highlights the recent development of sub-2μm fully/partially porous silica materials and the demonstrations of their enhanced performance in achiral and chiral chromatography.

Differential Gene Expression Between Wild-type and Gulo-deficient Mice Supplied with Vitamin C

Genetics and Molecular Biology. Jul, 2011  |  Pubmed ID: 21931508

The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (≥ twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.

Fragment-based Prediction of Skin Sensitization Using Recursive Partitioning

Journal of Computer-aided Molecular Design. Sep, 2011  |  Pubmed ID: 21932057

Skin sensitization is an important toxic endpoint in the risk assessment of chemicals. In this paper, structure-activity relationships analysis was performed on the skin sensitization potential of 357 compounds with local lymph node assay data. Structural fragments were extracted by GASTON (GrAph/Sequence/Tree extractiON) from the training set. Eight fragments with accuracy significantly higher than 0.73 (p<0.1) were retained to make up an indicator descriptor fragment. The fragment descriptor and eight other physicochemical descriptors closely related to the endpoint were calculated to construct the recursive partitioning tree (RP tree) for classification. The balanced accuracy of the training set, test set I, and test set II in the leave-one-out model were 0.846, 0.800, and 0.809, respectively. The results highlight that fragment-based RP tree is a preferable method for identifying skin sensitizers. Moreover, the selected fragments provide useful structural information for exploring sensitization mechanisms, and RP tree creates a graphic tree to identify the most important properties associated with skin sensitization. They can provide some guidance for designing of drugs with lower sensitization level.

Value of Ultrasound Elastography in Detecting Small Breast Tumors

Chinese Medical Journal. Aug, 2011  |  Pubmed ID: 21933573

Detecting small breast tumors is difficult for conventional ultrasound. The goal of this study was to assess the value of ultrasound elastography in characterizing small breast tumors and to compare its sensitivity, specificity and accuracy with conventional ultrasound.

Endovascular Repair of a Tuberculous Aneurysm of Descending Thoracic Aorta

Chinese Medical Journal. Jul, 2011  |  Pubmed ID: 21933632

Tuberculous aortic aneurysm (TBAA) is an extremely rare clinical event with life-threatening implication. Management for this condition is challenging and its therapeutic option has not been yet established. A few recent reports described endovascular repair rather than open surgery as the method for treatment. Although this remains controversial, endovascular exclusion has been gaining acceptance for some surgeons. We present a case of TBAA who was treated by endovascular stent grafting for a descending thoracic aortic aneurysm with simultaneous anti-tuberculous medication. The outcome was favorable.

BisGMA/TEGDMA Dental Composite Containing High Aspect-ratio Hydroxyapatite Nanofibers

Dental Materials : Official Publication of the Academy of Dental Materials. Nov, 2011  |  Pubmed ID: 21937098

The objectives of this study are to investigate the properties of high aspect-ratio hydroxyapatite (HAP) nanofibers and the reinforcing effect of such fibers on bisphenol A glycidyl methacrylate (BisGMA)/triethylene glycol dimethacrylate (TEGDMA) dental resins (without silica microparticle filler) and dental composites (with silica microparticle filler) with various mass fractions (loading rates).

Sn@CNT Nanostructures Rooted in Graphene with High and Fast Li-storage Capacities

ACS Nano. Oct, 2011  |  Pubmed ID: 21939228

Development of materials with carefully crafted nanostructures has been an important strategy for the next-generation lithium-ion batteries to achieve higher capacity, longer cycle life, and better rate capability. Graphene-based and Sn-based anode materials are promising anodes with higher capacities than graphite; however, most of them exhibit fast capacity fading at prolonged cycling and poor rate capability. This paper reports a hierarchical Sn@CNT nanostructure rooted in graphene, which exhibits larger than theoretical reversible capacities of 1160-982 mAh/g in 100 cycles at 100 mA/g and excellent rate capability (828 mAh/g at 1000 mA/g and 594 mAh/g at 5000 mA/g). The excellent electrochemical performances compared to graphene/Sn-based anodes have been attributed to the efficient prevention of graphene agglomeration by Sn@CNT decoration and the increased electrochemical activities of Sn by CNT shell protection and GNS support.

An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

Science (New York, N.Y.). Oct, 2011  |  Pubmed ID: 21940856

We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.

Assembly of Colloidal Nanoparticles Directed by the Microstructures of Polycrystalline Ice

ACS Nano. Oct, 2011  |  Pubmed ID: 21942743

We show that the microstructures of polycrystalline ice can serve as a confining template for one-dimensional assembly of colloidal nanoparticles. Upon simply freezing an aqueous colloid, the nanoparticles are excluded from ice grains and form chains in the ice veins. The nanoparticle chains are transferable and can be strengthened by polymer encapsulation. After coating with polyaniline shells, simple sedimentation is used to remove large aggregates, enriching single-line chains of 40 nm gold nanoparticles with a total length of several micrometers. When gold nanorods were used, they formed one-dimensional aggregates with specific end-to-end conformation, indicating the confining effects of the nanoscale ice veins at the final stage of freezing. The unbranched and ultralong plasmonic chains are of importance for future study of plasmonic coupling and development of plasmonic waveguides.

Decreased Expression of Dual-specificity Phosphatase 9 is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

BMC Cancer. 2011  |  Pubmed ID: 21943117

The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs.

Custom-molded Foot-orthosis Intervention and Multisegment Medial Foot Kinematics During Walking

Journal of Athletic Training. 2011  |  Pubmed ID: 21944067

Foot-orthosis (FO) intervention to prevent and treat numerous lower extremity injuries is widely accepted clinically. However, the results of quantitative gait analyses have been equivocal. The foot models used, participants receiving intervention, and orthoses used might contribute to the variability.

Oral Sildenafil Treatment for Eisenmenger Syndrome: a Prospective, Open-label, Multicentre Study

Heart (British Cardiac Society). Nov, 2011  |  Pubmed ID: 21948962

Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear.

Controllable Formation and TEM Spatial Visualization of Cross-linked Gold Nanoparticle Spherical Aggregates

Nanoscale. Nov, 2011  |  Pubmed ID: 21952917

Gold nanoparticles (NPs) were assembled and cross-linked into spherical aggregates by colloidal emulsion evaporation and ligand exchanging. The optical absorption, conventional transmission electron microscopy (TEM) and bright field (BF) TEM tomography confirm that the cross-linking of the pre-condensed aggregates generates high stability and compactness.

Association of Elevated NTproBNP with Recurrent Thromboembolic Events After Acute Pulmonary Embolism

Thrombosis Research. Sep, 2011  |  Pubmed ID: 21955395

INTRODUCTION: N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor of adverse short-term clinical outcomes in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined. The aim of this study was to assess the value of plasma NTproBNP with regard to recurrent venous thromboembolism (VTE). MATERIALS AND METHODS: NTproBNP levels were measured in 224 consecutive patients with the first episode of acute pulmonary embolism occurring from January 2005 through October 2010. Patients were categorized into two groups by NTproBNP reference range. Follow-ups were performed at 3, 6, and 12months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. RESULTS: NTproBNP was elevated in 158 (70.5%) patients and not elevated in 66 (29.5%) patients. After a mean follow-up period of 31.0±19.4months, patients with elevated NTproBNP showed an increased risk of recurrent VTE (20 patients, 12.7%) compared to those without elevated NTproBNP (only 1 patient, 1.5%) (P=0.009). Of the 7 deaths related to pulmonary embolism, 6 occurred in patients with elevated NTproBNP compared to patients with normal NTproBNP (1 of 7 deaths). In a multivariate analysis stratified by oral anticoagulant treatment duration, elevated NTproBNP was an independent predictor of recurrent VTE (hazard ratio, 9.32; P=0.02). CONCLUSIONS: Elevated NTproBNP is associated with recurrent VTE in acute pulmonary embolism patients.

Hepatocellular Necrosis, Apoptosis, and Proliferation After Transcatheter Arterial Embolization or Chemoembolization in a Standardized Rabbit Model

Journal of Vascular and Interventional Radiology : JVIR. Nov, 2011  |  Pubmed ID: 21959058

To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model.

Classification of 5-HT(1A) Receptor Agonists and Antagonists Using GA-SVM Method

Acta Pharmacologica Sinica. Nov, 2011  |  Pubmed ID: 21963891

To construct a reliable computational model for the classification of agonists and antagonists of 5-HT(1A) receptor.

Fast Synthesis of 1,3-DAG by Lecitase® Ultra-catalyzed Esterification in Solvent-free System

European Journal of Lipid Science and Technology : EJLST. Aug, 2011  |  Pubmed ID: 21966255

Lecitase® Ultra, a phospholipase, was explored as an effective biocatalyst for direct esterification of glycerol with oleic acid to produce 1,3-DAG. Experiments were carried out in batch mode, and optimal reaction conditions were evaluated. In comparison with several organic solvent mediums, the solvent-free system was found to be more beneficial for this esterification reaction, which was further studied to investigate the reaction conditions including oleic acid/glycerol mole ratio, temperature, initial water content, enzyme load, and operating time. The results showed that Lecitase® Ultra catalyzed a fast synthesis of 1,3-DAG by direct esterification in a solvent-free medium. Under the optimal reaction conditions, a short reaction time 1.5 h was found to achieve the fatty acid esterification efficiency of 80.3 ± 1.2% and 1,3-DAG content of 54.8 ± 1.6 wt% (lipid layer of reaction mixture mass). The reusability of Lecitase® Ultra was evaluated via recycling the excess glycerol layer in the reaction system. DAG in the upper lipid layer of reaction mixture was purified by molecular distillation and the 1,3-DAG-enriched oil with a purity of about 75 wt% was obtained.Practical applications: The new Lecitase® Ultra catalyzed process for production of 1,3-DAG from glycerol and oleic acid described in this study provides several advantages over conventional methods including short reaction time, the absence of a solvents and a high product yield.

Mitigation of Ionizing Radiation-induced Bone Marrow Suppression by P38 Inhibition and G-CSF Administration

Journal of Radiation Research. 2011  |  Pubmed ID: 21971035

p38 mitogen-activated protein kinases (p38) has been shown to be activated in hematopoietic stem and progenitors cells after exposure to ionizing radiation (IR) and its activation has been implicated in bone marrow (BM) suppression under various pathological conditions. Therefore, in the present study we investigated whether inhibition of p38 activity alone with SB203580 (SB, a specific p38 inhibitor) or in combination with granulocyte colony-stimulating factor (G-CSF) can mitigate total body irradiation (TBI)-induced BM damage and lethality. Our results showed that p38 inhibition with SB had no significant effect on the 30-day survival rates of the mice exposed to 7.2 Gy TBI when it was used alone but increased the survival of the mice when it was combined with G-CSF. This combined effect may be attributable to a better preservation or stimulation of hematopoietic stem and progenitor cells, because BM cells from SB and G-CSF-treated mice produced more colony forming units-granulocyte-macrophage (CFU-GM) and 4-week cobblestone area forming cells (CAFCs) than the cells from either SB or G-CSF-treated mice after TBI in a colony forming cell assay and a CAFC assay, respectively. These findings suggest that the combined therapy with SB and G-GSF is more effective in mitigating TBI-induced acute BM injury than either agent alone.

Coherent Magnetic Semiconductor Nanodot Arrays

Nanoscale Research Letters. 2011  |  Pubmed ID: 21711627

ABSTRACT: In searching appropriate candidates of magnetic semiconductors compatible with mainstream Si technology for future spintronic devices, extensive attention has been focused on Mn-doped Ge magnetic semiconductors. Up to now, lack of reliable methods to obtain high-quality MnGe nanostructures with a desired shape and a good controllability has been a barrier to make these materials practically applicable for spintronic devices. Here, we report, for the first time, an innovative growth approach to produce self-assembled and coherent magnetic MnGe nanodot arrays with an excellent reproducibility. Magnetotransport experiments reveal that the nanodot arrays possess giant magneto-resistance associated with geometrical effects. The discovery of the MnGe nanodot arrays paves the way towards next-generation high-density magnetic memories and spintronic devices with low-power dissipation.

Preparation of Cyclodextrin Chiral Stationary Phases by Organic Soluble Catalytic 'click' Chemistry

Nature Protocols. Jul, 2011  |  Pubmed ID: 21720308

We describe an effective and simple protocol that uses click chemistry to attach native β-cyclodextrin (β-CD) to silica particles, resulting in a chiral stationary phase (CCNCSP) that can be used for the enantioseparation of chiral drugs by high-performance liquid chromatography (HPLC). Starting from β-CD, the CCNCSP is prepared in several steps: (i) reaction of β-CD with 1-(p-toluenesulfonyl)-imidazole to afford mono-6-toluenesulfonyl-β-CD; (ii) azidolysis of mono-6-toluenesulfonyl-β-CD in dimethylformamide to give mono-6-azido-β-CD (N(3)-CD); (iii) reaction of cuprous iodide with triphenylphosphine to form an organic soluble catalyst CuI(PPh(3)); (iv) preparation of alkynyl-modified silica particles; and (v) click chemistry immobilization of N(3)-CD onto alkynyl-modified silica to afford the desired chiral stationary phase. Synthesis of the stationary phase and column packing takes ∼1 week.

Cyclin T2: a Novel MiR-15a Target Gene Involved in Early Spermatogenesis

FEBS Letters. Aug, 2011  |  Pubmed ID: 21740905

MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression that play important roles in various biological processes. Spermatogenesis is a highly regulated process in which diploid spermatogonia eventually differentiate into haploid spermatozoa. In this study, we identified four differentially expressed miRNAs between two premeiotic male germ cells, made predictions about their putative targets, and confirmed cyclin T2 (Ccnt2) as a direct target of miR-15a. We also report that miR-15a inhibited muscle differentiation at least in part by targeting Ccnt2, which represents a novel interaction. Subsequently, miR-15a and Ccnt2 were profiled in developing mice testes to observe their inverse correlations in the postnatal 3-week period to understand their roles in spermatogenesis.

Genome Sequence of Mycoplasma Ovipneumoniae Strain SC01

Journal of Bacteriology. Sep, 2011  |  Pubmed ID: 21742877

Mycoplasma ovipneumoniae is associated with chronic nonprogressive pneumonia in both sheep and goats. Studies concerning its molecular pathogenesis, genetic analysis, and vaccine development have been hindered due to limited genomic information. Here, we announce the first complete genome sequence of this organism.

Remote Multi-color Excitation Using Femtosecond Propagating Surface Plasmon Polaritons in Gold Films

Optics Express. Jul, 2011  |  Pubmed ID: 21747501

We demonstrate dual-color nonlinear excitation of quantum dots positioned onto a gold film at distances up to 40 μm away from a micrometer sized focused laser spot. We attribute the observed remote nonlinear signal to the excitation of two independent surface plasmon polariton (SPP) modes excited at the laser spot in the gold film, which subsequently propagate in a collinear fashion to a distant site and provide the surface field required for nonlinear excitation of the target. This scheme decouples the illuminating photon flux from surface plasmon mediated nonlinear excitation of the target, which provides more control of unwanted heating effects at the target site and represents an attractive approach for surface-mediated femtosecond nonlinear examinations of molecules.

3,3'-Dinitro-4,4'-bipyridine

Acta Crystallographica. Section E, Structure Reports Online. May, 2011  |  Pubmed ID: 21754493

In the title compound, C(10)H(6)N(4)O(4), the pyridine rings are oriented at a dihedral angle of 67.8 (1)°. The O-atom pairs are trans, each displaced by a similar distance [average = 0.2331 (2) Å] out of the attached pyridine ring plane. In the crystal, inter-molecular C-H⋯O and C-H⋯N inter-actions link the mol-ecules into a three-dimensional network.

Oxidative DNA Damage Induced by a Copper(II)-1,10-phenanthroline-L-serine Complex in the Presence of Rutin

Chemistry & Biodiversity. Jul, 2011  |  Pubmed ID: 21766454

The capacity of the ternary complex copper(II)-1,10-phenanthroline-L-serine ([Cu-Phen-Ser]) to induce double-strand scission of DNA was explored by agarose-gel electrophoresis. It was found that the complex exhibited remarkable activity to damage DNA in the presence of rutin. Analysis of the UV and fluorescence spectra clearly demonstrated that the complex was bound to DNA by intercalation. Further, the occurrence of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, after the treatment of DNA by the complex in presence of rutin was evidenced by an electrochemical method. Finally, the mechanism of oxidative damage to double-stranded DNA by the [Cu-Phen-Ser] complex in the presence of rutin was discussed.

Proteomic Study on Sodium Selenite-induced Apoptosis of Human Cervical Cancer HeLa Cells

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). Jul, 2011  |  Pubmed ID: 21767938

Sodium selenite can induce the apoptosis of cancer cells, however its mechanism has seldom been studied via proteomics. In this paper, human cervical cancer HeLa cells were investigated by MTT assay and morphological observation to get appropriate selenite concentrations for proteomic study. Results showed that selenite at concentrations larger than 10 μmol/L significantly inhibited the viability of HeLa cells. 40 μmol/L selenite was in the appropriate range for proteomic study. After 24 h treatment with 40 μmol/L selenite, total proteins were extracted from the cells and applied to two-dimensional gel electrophoresis (2DE). Those proteins with their expression levels altered at least 2-fold comparing to the control were picked up for protein identification via MALDI-TOF mass spectrometry and further confirmed by Western blot analysis. About 1000 spots were detected by the software in each 2DE gel, among which 13 differentially expressed proteins were identified by mass spectrometry and most of them are relevant to oxidative stress, such as peroxiredoxins, superoxide dismutase, quinolinate phosphoribosyl transferase, and D-dopachrome tautomerase. Meanwhile, reactive oxygen species (ROS) and mitochondrial membrane potential were also detected by flow cytometry and laser confocal scanning microscope. An increase in ROS generation and a decrease in mitochondrial membrane potential were detected in the selenite-treated cells compared with the control, which are consistent with the down-expression of antioxidative proteins in proteomics. Those results indicate that selenite induces the apoptosis of HeLa cells via ROS-mediated mitochondrial pathway. The present study also implies the potentiality of selenium in cervical cancer treatment.

Effects of Chronic, Systemic Treatment with the Dopamine Receptor Agonist R-apomorphine in Partially Lesioned Rat Model of Parkinson's Disease: an Electrophysiological Study of Substantia Nigra Dopamine Neurons

The Chinese Journal of Physiology. Apr, 2011  |  Pubmed ID: 21789890

Previous studies have suggested that R-apomorphine (R-APO), a non-selective dopamine (DA) receptor agonist, has neuroprotective effects in the experimental models of Parkinson's disease (PD). In this study, we investigated the effects of chronic, systemic treatment with R-APO in the firing activity of substantia nigra pars compacta (SNc) DA neurons in 6-hydroxydopamine (6-OHDA) partially lesioned rats. In the 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (20.1 microg) into the striatum produced a partial lesion causing 41% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the SNc. In the partially lesioned rats, chronic, systemic treatment of R-APO (10 mg/kg/day, s.c., 11 days) attenuated loss of TH-ir neurons in the SNc. The partial lesion of the nigrostriatal pathway and R-APO treatment did not change the firing rate and firing pattern of DA neurons in the SNc of rats. In contrast, the R-APO treatment increased the number of spontaneously active DA neurons of the SNc in the partially lesioned rats, while the lesion decreased the number of spontaneously active DA neurons. In addition, the chronic R-APO treatment decreased the responsiveness of the DA neurons to intravenously administrated R-APO in the partially lesioned rats. These results indicate that chronic, systemic R-APO treatment has the neuroprotective effect, and reverses the decrease in the number of spontaneously active DA neurons in the SNc whereas the treatment induces a reduction in the sensitivity of DA receptors in the SNc to R-APO stimulation in this model.

Cardioprotective Effect of Liposomal Prostaglandin E1 on a Porcine Model of Myocardial Infarction Reperfusion No-reflow

Journal of Zhejiang University. Science. B. Aug, 2011  |  Pubmed ID: 21796804

To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).

Rigorous Assessment and Integration of the Sequence and Structure Based Features to Predict Hot Spots

BMC Bioinformatics. 2011  |  Pubmed ID: 21798070

Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need.

Comparative MRNA and MicroRNA Expression Profiling of Three Genitourinary Cancers Reveals Common Hallmarks and Cancer-specific Molecular Events

PloS One. 2011  |  Pubmed ID: 21799901

Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.

Mapping a Region of Hepatitis C Virus E2 That is Responsible for Escape from Neutralizing Antibodies and a Core CD81-binding Region That Does Not Tolerate Neutralization Escape Mutations

Journal of Virology. Oct, 2011  |  Pubmed ID: 21813602

Understanding the interaction between broadly neutralizing antibodies and their epitopes provides a basis for the rational design of a preventive hepatitis C virus (HCV) vaccine. CBH-2, HC-11, and HC-1 are representatives of antibodies to overlapping epitopes on E2 that mediate neutralization by blocking virus binding to CD81. To obtain insights into escape mechanisms, infectious cell culture virus, 2a HCVcc, was propagated under increasing concentrations of a neutralizing antibody to isolate escape mutants. Three escape patterns were observed with these antibodies. First, CBH-2 escape mutants that contained mutations at D431G or A439E, which did not compromise viral fitness, were isolated. Second, under the selective pressure of HC-11, escape mutations progressed from a single L438F substitution at a low antibody concentration to double substitutions, L438F and N434D or L438F and T435A, at higher antibody concentrations. Escape from HC-11 was associated with a loss of viral fitness. An HCV pseudoparticle (HCVpp) containing the L438F mutation bound to CD81 half as efficiently as did wild-type (wt) HCVpp. Third, for HC-1, the antibody at a critical concentration completely suppressed viral replication and generated no escape mutants. Epitope mapping revealed contact residues for CBH-2 and HC-11 in two regions of the E2 glycoprotein, amino acids (aa) 425 to 443 and aa 529 to 535. Interestingly, contact residues for HC-1 were identified only in the region encompassing aa 529 to 535 and not in aa 425 to 443. Taken together, these findings point to a region of variability, aa 425 to 443, that is responsible primarily for viral escape from neutralization, with or without compromising viral fitness. Moreover, the region aa 529 to 535 is a core CD81 binding region that does not tolerate neutralization escape mutations.

Palladium-catalyzed Intramolecular C(sp2)-H Amidination by Isonitrile Insertion Provides Direct Access to 4-aminoquinazolines from N-arylamidines

Organic Letters. Sep, 2011  |  Pubmed ID: 21819077

An efficient method for the synthesis of 4-amino-2-aryl(alkyl)quinazolines from readily available N-arylamidines and isonitriles via palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion has been developed.

Frequent Mutations of Chromatin Remodeling Genes in Transitional Cell Carcinoma of the Bladder

Nature Genetics. Sep, 2011  |  Pubmed ID: 21822268

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.

A Novel Vaccine Delivery System: Biodegradable Nanoparticles in Thermosensitive Hydrogel

Growth Factors (Chur, Switzerland). Dec, 2011  |  Pubmed ID: 21981422

In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF-NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system.

Skin-specifically Transgenic Expression of Biologically Active Human Cytoxic T-lymphocyte Associated Antigen4-Immunoglobulin (hCTLA4Ig) in Mice Using Lentiviral Vector

Transgenic Research. Oct, 2011  |  Pubmed ID: 21983813

Xenogeneic skin, especially porcine skin, has already been used to cover large wounds in clinic practice of wound care. Our previous data showed that transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic burn wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong its survival in xenogeneic wounds for coverage. Lentiviral transgenesis provides an extremely efficient and cost-effective method to produce transgenic animals. However, tissue-targeted transgenic expression of biologically functional protein by lentiviral transgenesis is rarely reported. In this work, a recombinant lentiviral vector (LV), named FKCW in this article, was constructed by inserting a skin-specific hCTLA4Ig expression cassette consisting of keratin 14 (K14) promoter, hCTLA4Ig coding sequence and an intronic fragment. Its efficacy for transgenesis and skin-specific expression of bio-active hCTLA4Ig protein was tested using mice as models. The LV FKCW was readily to be packaged and concentrated to high titres (1.287-6.254 × 10(9) TU/ml) by conventional lentivirus package system. Using eggs collected from only five mated females having been subjected to conventional super-ovulation treatment, 8 hCTLA4Ig transgenic founder mice were generated with the concentrated FKCW vector, and transgenic founder per injected and transferred egg was 6.3%, which was nearly 9-fold higher than that for DNA micro-injection with a similar transgene construct in our previous work. The lentiviral transgenic hCTLA4Ig exhibited strictly skin-specific expression at a level comparable to or even slightly higher than that of transgenic hCTLA4Ig delivered by micro-injection in a similar cassette. Lentiviral transgenic hCTLA4Ig protein remarkably suppressed human lymphocyte proliferation in vitro to a degree comparable to that of commercially purchased purified hCTLA4Ig protein with defined activity at similar concentrations. Besides, lentiviral hCTLA4Ig transgenic mouse skin grafted into rat burn wounds exhibited remarkably extended survival compared to wild-type skin of the same strain (13.8 ± 3.8 vs. 6.8 ± 3.0 days), indicating that lentiviral transgenic hCTLA4Ig did inhibit immune rejection against xenogeneic skin graft in vivo. These results laid down the foundation to further efficiently generate transgenic pigs skin-specifically expressing bio-active hCTLA4Ig by lentiviral transgenesis, and provided a demonstration that transgenic animals with tissue-targeted expression of biologically functional protein can be efficiently produced using LV.

Risk Factors Related to Aneurysmal Rebleeding

World Neurosurgery. Sep-Oct, 2011  |  Pubmed ID: 21986427

Rebleeding from ruptured intracranial aneurysms is a major cause of death and disability. The aim of this study was to investigate the incidence of rebleeding and the risk factors related to rebleeding before early aneurysm repair.

Sleeve Gastrectomy Prevents Lipoprotein Receptor-1 Expression in Aortas of Obese Rats

World Journal of Gastroenterology : WJG. Aug, 2011  |  Pubmed ID: 21990956

To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas.

Chemical Composition and Structure of Peritubular and Intertubular Human Dentine Revisited

Archives of Oral Biology. Oct, 2011  |  Pubmed ID: 21996490

OBJECTIVE: Currently there is still a debate about whether peritubular dentine (PTD) is non-collageneous or collageneous tissue. The chemical composition and structure of human PTD and intertubular dentine (ITD) was re-visited in this study. DESIGN: The dentine tubular region including ITD and PTD prepared from human third molars was in situ detected by means of micro-Raman spectroscopy (μRs) and atomic force microscopy (AFM). RESULTS: From the μRs study, it was found that the mineral/matrix ratios (phosphate vs. CH(2)) in PTD were ∼3 times of those in ITD. For the mineral, the differences between PTD and ITD were small, but still detectable. For the organic matrix, the intensity ratios of amide III to CH(2) in ITD were ∼1.5 times of those in PTD, indicating the structural differences. In addition, there was a higher proline/hydroxyproline content in ITD than that in PTD. However, the overall Raman peak contour in the amide regions (I & III) was similar, indicating collagen might still exist in both the ITD and PTD. An in situ AFM observation of the dentinal tubular region during EDTA etching confirmed that dentine collagen ran across from the ITD into the PTD. CONCLUSION: A phenomenon similar to that observed in the dentine-enamel junction is proposed to explain the above results. It is demonstrated that the μRs-AFM approach can be used to provide an insight into the structure of small dental tissues at the micron or sub-micron scale.

Rapid Dynamics of Contrast Responses in the Cat Primary Visual Cortex

PloS One. 2011  |  Pubmed ID: 21998655

The visual information we receive during natural vision changes rapidly and continuously. The visual system must adapt to the spatiotemporal contents of the environment in order to efficiently process the dynamic signals. However, neuronal responses to luminance contrast are usually measured using drifting or stationary gratings presented for a prolonged duration. Since motion in our visual field is continuous, the signals received by the visual system contain an abundance of transient components in the contrast domain. Here using a modified reverse correlation method, we studied the properties of responses of neurons in the cat primary visual cortex to different contrasts of grating stimuli presented statically and transiently for 40 ms, and showed that neurons can effectively discriminate the rapidly changing contrasts. The change in the contrast response function (CRF) over time mainly consisted of an increment in contrast gain (CRF shifts to left) in the developing phase of temporal responses and a decrement in response gain (CRF shifts downward) in the decay phase. When the distribution range of stimulus contrasts was increased, neurons demonstrated decrement in contrast gain and response gain. Our results suggest that contrast gain control (contrast adaptation) and response gain control mechanisms are well established during the first tens of milliseconds after stimulus onset and may cooperatively mediate the rapid dynamic responses of visual cortical neurons to the continuously changing contrast. This fast contrast adaptation may play a role in detecting contrast contours in the context of visual scenes that are varying rapidly.

Involvement of a Helix-loop-helix Transcription Factor CHC-1 in CO(2)-mediated Conidiation Suppression in Neurospora Crassa

Fungal Genetics and Biology : FG & B. Dec, 2011  |  Pubmed ID: 22001287

The morphological switch from vegetative growth to conidiation in filamentous fungi is highly regulated, but the understanding of the regulatory mechanisms is limited. In this study, by screening a set of knock-out mutants corresponding to 103 transcription factor encoding genes in Neurospora crassa, a mutant was found to produce abundant conidia in race tubes in which conidiation in the wild-type strain was suppressed. The corresponding gene NCU00749 encodes a protein containing a helix-loop-helix DNA binding region. Unlike enhanced conidiation in ras-1 and sod-1 mutants, which was completely suppressed by antioxidant N-acetyl cysteine, enhanced conidiation in the NCU00749 mutant was only slightly affected by N-acetyl cysteine. When grown on slants, the NCU00749 deletion mutant exhibited earlier conidial formation than the wild-type strain, and this was more evident at a higher (5%) CO(2) concentration. Therefore, we named NCU00749 as conidiation at high carbon dioxide-1 (chc-1). Genes that are highly expressed during conidial development, eas, con-6, con-8 and con-10, were transcribed at a higher rate in the chc-1 deletion mutant than the wild-type strain in response to conidiation induction. To determine the mechanisms by which CHC-1 regulates conidiation, we conducted a RNA sequencing analysis and found that 404 genes exhibited ≥ 2 fold changes in transcription in response to chc-1 deletion. Among them, fluffy and ada-6, two transcription factor genes that positively regulate conidiation in N. crassa, and rca-1, whose homolog flbD in Aspergillus nidulans is essential for conidiation, were upregulated in the chc-1 deletion mutant. Results of RNA sequencing also suggest that signal transduction via the cAMP and the MAK-2 mediated signal pathways, and ROS generation and removal, mechanisms known to regulate conidiation, are not involved in chc-1 mediated control of conidiation. In addition, chc-1 also influences expression of genes involved in other important biological processes besides conidiation such as carbon metabolism, sphingolipid synthesis, cell wall synthesis, and calcium signaling.

Upregulation of IRS-1 Expression in Goto-Kakizaki Rats Following Roux-en-Y Gastric Bypass Surgery: Resolution of Type 2 Diabetes?

The Tohoku Journal of Experimental Medicine. 2011  |  Pubmed ID: 22001674

Type 2 diabetes mellitus (T2DM) is an endocrine disorder that is rapidly growing in prevalence within China and throughout the world. Roux-en-Y gastric bypass (RYGB) surgery, widely used in the treatment of obesity, has been recognized as an effective and long-term treatment for T2DM in recent years. However, the underlying mechanisms responsible for glycemic control remain unclear. This study was designed to investigate the roles of insulin receptor substrates (IRSs) in glucose tolerance and insulin resistance following RYGB surgery. Goto-Kakizaki (GK) rats, a model of T2DM, were randomly allocated into three groups: RYGB surgery, sham surgery, and control (10 animals/group). Wistar rats were also used as non-diabetic control. Daily food intake, body weight, glucose and insulin were measured pre- and post-operatively. Insulin receptor substrate 1 (IRS-1) and insulin receptor substrate 2 (IRS-2) content, the main subtypes of IRSs, were measured in skeletal muscle, adipose tissue and liver using western immunoblot analyses on postoperative day 28. Following surgery, RYGB-treated rats showed markedly improved oral glucose tolerance, as judged by lower peak and area-under-the-curve glucose values (p < 0.01 vs. GK or GK sham). Improved insulin resistance was also observed in RYGB-treated rats. Western immunoblot analyses showed that IRS-1 and its phosphorylation levels were significantly increased in skeletal muscle and adipose tissues in RYGB group (p < 0.01 vs. GK or GK sham), whereas IRS-2 levels were downregulated in liver. These findings suggest that improvements in glucose tolerance and insulin resistance following RYGB surgery are associated with upregulation of IRS-1.

Affinity Maturation to Improve Human Monoclonal Antibody Neutralization Potency and Breadth Against Hepatitis C Virus

The Journal of Biological Chemistry. Dec, 2011  |  Pubmed ID: 22002064

A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.

Inhibition of P38 MAPK Attenuates Ionizing Radiation-induced Hematopoietic Cell Senescence and Residual Bone Marrow Injury

Radiation Research. Dec, 2011  |  Pubmed ID: 22014293

Exposure to a moderate or high total-body dose of radiation induces not only acute bone marrow suppression but also residual (or long-term) bone marrow injury. The induction of residual bone marrow injury is primarily attributed to the induction of hematopoietic cell senescence by ionizing radiation. However, the mechanisms underlying radiation-induced hematopoietic cell senescence are not known and thus were investigated in the present study. Using a well-established long-term bone marrow cell culture system, we found that radiation induced hematopoietic cell senescence at least in part via activation of p38 mitogen-activated protein kinase (p38). This suggestion is supported by the finding that exposure to radiation selectively activated p38 in bone marrow hematopoietic cells. The activation was associated with a significant reduction in hematopoietic cell clonogenic function, an increased expression of p16(INK4a) (p16), and an elevated senescence-associated β-galactosidase (SA-β-gal) activity. All these changes were attenuated by p38 inhibition with a specific p38 inhibitor, SB203580 (SB). Selective activation of p38 was also observed in bone marrow hematopoietic stem cells (HSCs) after mice were exposed to a sublethal total-body dose (6.5 Gy) of radiation. Treatment of the irradiated mice with SB after total-body irradiation (TBI) increased the frequencies of HSCs and hematopoietic progenitor cells (HPCs) in their bone marrow and the clonogenic functions of the irradiated HSCs and HPCs. These findings suggest that activation of p38 plays a role in mediating radiation-induced hematopoietic cell senescence and residual bone marrow suppression.

FoxM1 Promotes β-catenin Nuclear Localization and Controls Wnt Target-gene Expression and Glioma Tumorigenesis

Cancer Cell. Oct, 2011  |  Pubmed ID: 22014570

Wnt/β-catenin signaling is essential for stem cell regulation and tumorigenesis, but its molecular mechanisms are not fully understood. Here, we report that FoxM1 is a downstream component of Wnt signaling and is critical for β-catenin transcriptional function in tumor cells. Wnt3a increases the level and nuclear translocation of FoxM1, which binds directly to β-catenin and enhances β-catenin nuclear localization and transcriptional activity. Genetic deletion of FoxM1 in immortalized neural stem cells abolishes β-catenin nuclear localization. FoxM1 mutations that disrupt the FoxM1-β-catenin interaction or FoxM1 nuclear import prevent β-catenin nuclear accumulation in tumor cells. FoxM1-β-catenin interaction controls Wnt target gene expression, is required for glioma formation, and represents a mechanism for canonical Wnt signaling during tumorigenesis.

The Electrophysiological Cardiac Ventricular Substrate in Patients After Myocardial Infarction: Noninvasive Characterization with Electrocardiographic Imaging

Journal of the American College of Cardiology. Oct, 2011  |  Pubmed ID: 22018301

The aim of this study was to noninvasively image the electrophysiological (EP) substrate of human ventricles after myocardial infarction and define its characteristics.

A Highly Efficient Graphene Oxide Absorber for Q-switched Nd:GdVO4 Lasers

Nanotechnology. Nov, 2011  |  Pubmed ID: 22019939

We demonstrated that graphene oxide material could be used as a highly efficient saturable absorber for the Q-switched Nd:GdVO4 laser. A novel and low-cost graphene oxide (GO) absorber was fabricated by a vertical evaporation technique and high viscosity of polyvinyl alcohol (PVA) aqueous solution. A piece of GO/PVA absorber, a piece of round quartz, and an output coupler mirror were combined to be a sandwich structure passive component. Using such a structure, 104 ns pulses and 1.22 W average output power were obtained with the maximum pulse energy at 2 µJ and a slope efficiency of 17%.

Improving Accuracy of Protein-protein Interaction Prediction by Considering the Converse Problem for Sequence Representation

BMC Bioinformatics. 2011  |  Pubmed ID: 22024143

With the development of genome-sequencing technologies, protein sequences are readily obtained by translating the measured mRNAs. Therefore predicting protein-protein interactions from the sequences is of great demand. The reason lies in the fact that identifying protein-protein interactions is becoming a bottleneck for eventually understanding the functions of proteins, especially for those organisms barely characterized. Although a few methods have been proposed, the converse problem, if the features used extract sufficient and unbiased information from protein sequences, is almost untouched.

Construction and Evaluation of a Multistage Mycobacterium Tuberculosis Subunit Vaccine Candidate Mtb10.4-HspX

Vaccine. Nov, 2011  |  Pubmed ID: 22024175

To search for more effective vaccines to enhance the immunogenicity and protective efficacy of Mycobacterium bovis Bacille Calmette-Guerin (BCG) and to control or even eradicate Mycobacterium tuberculosis (M. tuberculosis) in all stages of infection including the persister bacteria, antigens of Mtb10.4 (Rv0288) expressed in replicating bacilli and HspX (also called Acr, Hsp16.3, Rv2031c) highly expressed in dormant bacilli were fused together to construct a multistage fusion protein Mtb10.4-HspX (MH for short) without affinity tag with potential advantage for clinical use. The human T-cell responses to MH were evaluated for its immunogenicity. Furthermore, MH was emulsified in an adjuvant composed of N,N'-dimethyl-N,N'-dioctadecylammonium bromide (DDA) and mycobacterial cord factor trehalose-6,6-dimycolate (TDM) to construct subunit vaccine, whose immunogenicity and potency to boost BCG primed immunity against M. tuberculosis infection were evaluated in mice. The results showed that the fusion protein MH without affinity tag was stably produced in Escherichia coli and was successfully purified by chromatography. MH was strongly recognized by human T cells from TB patients and persons latently infected with M. tuberculosis. In conclusion, MH in adjuvant DDA-TDM generated strong antigen-specific humoral and cell-mediated immunity, and had the capability to enhance BCG-primed immunity and the protective efficacy against M. tuberculosis in mice. These findings suggest that MH in DDA-TDM have the potential to be a good multistage tuberculosis vaccine candidate.

Specifically Colorimetric Recognition of Calcium, Strontium, and Barium Ions Using 2-mercaptosuccinic Acid-functionalized Gold Nanoparticles and Its Use in Reliable Detection of Calcium Ion in Water

The Analyst. Oct, 2011  |  Pubmed ID: 21829822

A colorimetric probe based on 2-mercaptosuccinic acid-functionalized gold nanoparticles has been developed to exhibit selectivity towards Ca(2+), Sr(2+), and Ba(2+) ions over other metallic cations under specified conditions and finds its practical application in detecting Ca(2+) levels in water.

Diaqua-bis-(4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ato-κN,O)manganese(II) N,N-dimethyl-formamide Disolvate

Acta Crystallographica. Section E, Structure Reports Online. Jul, 2011  |  Pubmed ID: 21836838

In the title compound, [Mn(C(7)H(7)N(2)O(4))(2)(H(2)O)(2)]·2C(3)H(7)NO, the central Mn(II) ion, located on an inversion center, is hexa-coordinated by four O atoms from two water mol-ecules and two carboxyl-ate groups, and two N atoms from two 4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ate anions in a slightly distorted octa-hedral environment. The complex mol-ecules and solvent mol-ecules are connected via N-H⋯O and O-H⋯O hydrogen bonds into a two-dimensional polymeric structure parallel to (001).

Diaqua-bis-(4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ato-κN,O)cadmium Dihydrate

Acta Crystallographica. Section E, Structure Reports Online. Jul, 2011  |  Pubmed ID: 21836881

The asymmetric unit of the title compound, [Cd(C(7)H(7)N(2)O(4))(2)(H(2)O)(2)]·2H(2)O, consists of one Cd(II) ion, one 4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ate anion, one coordinated water mol-ecule and one lattice water mol-ecule. The Cd(II) ion lies on a twofold axis, and is hexa-coordinated by four O atoms from water mol-ecules and carboxyl-ate groups and two N atoms from two imidazole rings, in a distorted octa-hedral arrangement. An extensive framework of N-H⋯O and O-H⋯O hydrogen bonds with the participation of coordinated and free water mol-ecules is found in the crystal structure, which contributes to the formation of a three-dimensional structure.

Laparoscopically Assisted Anorectal Pull-through for High Imperforate Anus in Infants: Intermediate Results

Journal of Pediatric Surgery. Aug, 2011  |  Pubmed ID: 21843727

The aim of this study was to evaluate the clinical outcomes and postoperative anal function in infants with congenital high imperforate anus treated with laparoscopically assisted anorectal pull-through (LAARP).

Predictive Value of D-dimer Test for Recurrent Venous Thromboembolism at Hospital Discharge in Patients with Acute Pulmonary Embolism

Journal of Thrombosis and Thrombolysis. Nov, 2011  |  Pubmed ID: 21847593

D-dimer can be used to exclude acute pulmonary embolism (PE) for its high negative predictive value (NPV). Also, it is a predictor of recurrent venous thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE when tested at hospital discharge. Plasma D-dimer levels were repeatedly measured at hospital discharge in 204 consecutive patients with the first episode of acute pulmonary embolism. Patients were categorized to two groups by D-dimer levels at hospital discharge and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. D-dimer levels were persistently abnormal in 66 patients (32%). After 31±19 months follow-up, patients with persistently abnormal D-dimer level levels showed a higher rate of of recurrent VTE (14 patients, 21%) compared to those with D-dimer regression (8 patients, 6%) (P = 0.001). At the multivariate analysis, after adjustment for other relevant factors, persistently abnormal D-dimer level levels were an independent predictor of recurrent VTE in all subjects investigated, (hazard ratio, 4.10; 95% CI, 1.61-10.39; P = 0.003), especially in those with unprovoked PE (hazard ratio, 4.61; 95% CI, 1.85-11.49; P = 0.001). The negative predictive value of D-dimer was 94.2 and 92.9% in all subjects or those with unprovoked PE, respectively. Persistently abnormal D-dimer level levels at hospital discharge have a high negative predictive value for recurrence in patients with acute pulmonary embolism, especially in subjects with an unprovoked previous event.

Dual Microfluidic Perifusion Networks for Concurrent Islet Perifusion and Optical Imaging

Biomedical Microdevices. Aug, 2011  |  Pubmed ID: 21850483

This study explores a new class of duplex microfluidic device which utilizes a dual perifusion network to simultaneously perform live-cell optical imaging of physiological activities and study insulin release kinetics on two islet populations. This device also incorporates on-chip staggered herringbone mixers (SHMs) to increase mixing efficiency and facilitate the generation of user-defined chemical gradients. Mouse islets are used to simultaneously measure dynamic insulin release, changes in mitochondrial potentials, and calcium influx in response to insulin secretagogues (glucose and tolbutamide), and show a high signal-to-noise ratio and spatiotemporal resolution of all measured parameters for both perifusion chambers. This system has many potential applications for studying β-cell physiology and pathophysiology, as well as for therapeutic drug screening. This dual perifusion device is not limited to islet studies and could easily be applied to other tissues and cells without major modifications.

Meeting Report: ACB-2011 Shanghai - "biotechnology for Better Life"

Biotechnology Journal. Nov, 2011  |  Pubmed ID: 22069092

Hemodynamic Effects and Safety of Pulmonary Angiography in Chinese Patients with Pulmonary Hypertension

Chinese Medical Journal. Oct, 2011  |  Pubmed ID: 22088513

Pulmonary angiography is widely performed in pulmonary hypertension patients, but its immediate effects on right heart hemodynamics and safety are not well known. The objective of this study was to investigate the right heart hemodynamic effects and safety of pulmonary angiography in Chinese patients with pulmonary hypertension.

Intraoperative Ultrasound Assistance in the Resection of Small, Deep-seated, or Ill-defined Intracerebral Lesions

Chinese Medical Journal. Oct, 2011  |  Pubmed ID: 22088526

Intraoperative ultrasound (IOUS) has been increasingly used as a guiding tool during neurosurgical procedures. In this study, we aimed to evaluate the potential application of intraoperative ultrasound assisted surgery in the resection of small, deep-seated, or ill-defined lesions.

Chiral Transformation: from Single Nanowire to Double Helix

Journal of the American Chemical Society. Dec, 2011  |  Pubmed ID: 22091894

We report a new type of water-soluble ultrathin Au-Ag alloy nanowire (NW), which exhibits unprecedented behavior in a colloidal solution. Upon growth of a thin metal (Pd, Pt, or Au) layer, the NW winds around itself to give a metallic double helix. We propose that the winding originates from the chirality within the as-synthesized Au-Ag NWs, which were induced to untwist upon metal deposition.

[Short-term Efficacy Comparison of Laparoscopic-assisted Versus Open Distal Gastrectomy]

Zhonghua Yi Xue Za Zhi. Jul, 2011  |  Pubmed ID: 22093785

To compare the short-term efficacy of laparoscopic-assisted verus open distal gastrectomy for gastric cancer.

Multifocal Intraparenchymal Langerhans' Cell Histiocytosis Concomitant With an Arachnoid Cyst in a Child: Case Report and Review of the Literature

Journal of Child Neurology. Nov, 2011  |  Pubmed ID: 22094914

Langerhans' cell histiocytosis is a disease usually found in children and characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system. Intracranial Langerhans' cell histiocytosis presenting as multifocal intraparenchymal lesions is very rare. In this article, the authors report on a 4-year-old boy diagnosed with multifocal intraparenchymal Langerhans' cell histiocytosis concomitant with an arachnoid cyst. After a series of laboratory examinations, the right frontal mass was surgically excised. Histological examinations confirmed the diagnosis of intracranial Langerhans' cell histiocytosis. The patient's intracranial hypertension symptoms were alleviated, and the remaining foci were treated by Langerhans' cell histiocytosis-directed standard chemotherapy. At the 8-month follow-up visit, no recurrence of the excised lesion was found, and no change in the size of other lesions was seen. Supratentorial intracerebral lesions with mass effect and enhancement have rarely been described; in this report, the histological features of and therapeutic options for such a case are discussed.

A Genome-wide Survey on Basic Helix-loop-helix Transcription Factors in Giant Panda

PloS One. 2011  |  Pubmed ID: 22096504

The giant panda (Ailuropoda melanoleuca) is a critically endangered mammalian species. Studies on functions of regulatory proteins involved in developmental processes would facilitate understanding of specific behavior in giant panda. The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, mouse and human. Our present study identified 107 bHLH family members being encoded in giant panda genome. Phylogenetic analyses revealed that they belong to 44 bHLH families with 46, 25, 15, 4, 11 and 3 members in group A, B, C, D, E and F, respectively, while the remaining 3 members were assigned into "orphan". Compared to mouse, the giant panda does not encode seven bHLH proteins namely Beta3a, Mesp2, Sclerax, S-Myc, Hes5 (or Hes6), EBF4 and Orphan 1. These results provide useful background information for future studies on structure and function of bHLH proteins in the regulation of giant panda development.

[Experimental Study on Metabonomics of Coronary Heart Disease Myocardlal Ischemia of Blood Stasis Syndrome Based on the NOESY Pulse NMR]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Oct, 2011  |  Pubmed ID: 22097206

To study changes of serum metabolite profiles in Ameriod ring induced coronary heart disease (CHD) chronic myocardial ischemia (CMI) mini-pigs by NMR.

Kernel-based Data Fusion Improves the Drug-protein Interaction Prediction

Computational Biology and Chemistry. Dec, 2011  |  Pubmed ID: 22099632

Proteins are involved in almost every action of every organism by interacting with other small molecules including drugs. Computationally predicting the drug-protein interactions is particularly important in speeding up the process of developing novel drugs. To borrow the information from existing drug-protein interactions, we need to define the similarity among proteins and the similarity among drugs. Usually these similarities are defined based on one single data source and many methods have been proposed. However, the availability of many genomic and chemogenomic data sources allows us to integrate these useful data sources to improve the predictions. Thus a great challenge is how to integrate these heterogeneous data sources. Here, we propose a kernel-based method to predict drug-protein interactions by integrating multiple types of data. Specially, we collect drug pharmacological and therapeutic effects, drug chemical structures, and protein genomic information to characterize the drug-target interactions, then integrate them by a kernel function within a support vector machine (SVM)-based predictor. With this data fusion technology, we establish the drug-protein interactions from a collections of data sources. Our new method is validated on four classes of drug target proteins, including enzymes, ion channels (ICs), G-protein couple receptors (GPCRs), and nuclear receptors (NRs). We find that every single data source is predictive and integration of different data sources allows the improvement of accuracy, i.e., data integration can uncover more experimentally observed drug-target interactions upon the same levels of false positive rate than single data source based methods. The functional annotation analysis indicates that our new predictions are worthy of future experimental validation. In conclusion, our new method can efficiently integrate diverse data sources, and will promote the further research in drug discovery.

A New Eudesmane Sesquiterpene Glucoside from Liriope Muscari Fibrous Roots

Molecules (Basel, Switzerland). 2011  |  Pubmed ID: 22031065

The screening of several Chinese medicinal herbs for nematocidal properties showed that the ethanol extract of Liriope muscari fibrous roots possessed significant nematocidal activity against the pine wood nematode (Bursaphelenchus xylophilus). From the ethanol extract, a new constituent (1,4-epoxy-cis-eudesm-6-O-β-D-glucopyranoside) and three known glycosides [1β,6α-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside (liriopeoside A), 1β,6β-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside, and 1α,6β-dihydroxy-5,10-bis-epi-eudesm-4(15)-ene-6-O-β D-glucopyranoside] were isolated by bioassay-guided fractionation. The structures were elucidated by 1D and 2D NMR and MS techniques. 1,4-Epoxy-cis-eudesm-6-O-β-D-glucopyranoside possessed moderate nemato-cidal activity against B. xylophilus with a LC(50 )value of 339.76 μg/mL, while liriopeoside A (LC(50) = 82.84 μg/mL) and 1β,6β-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside (LC(50) = 153.39 μg/mL) also exhibited nematocidal activity against B. xylophilus. The crude extract of L. muscari fibrous roots exhibited nematocidal activity against the pine wood nematode with a LC(50) value of 182.56 μg/mL.

Design and Synthesis of Dual-ligand Modified Chitosan As a Liver Targeting Vector

Journal of Materials Science. Materials in Medicine. Nov, 2011  |  Pubmed ID: 22105225

Vector plays an important role in hepatic targeted drug delivery system. In this study, a novel material as a liver targeting vector, dual-ligand modified chitosan (GCGA) composed of chitosan (CTS), glycyrrhetinic acid (GA) and lactobionic acid (LA), was designed and synthesized by an orthogonal experiment with two-step synthesis under mild conditions. The synthesized final product was characterized and confirmed by FTIR and (1)H-NMR spectroscopy, and DS of GA and LA in CTS were measured to be 13.77 and 16.74 mol% using (1)H-NMR, respectively. The cytotoxicity of CTS and GCGA was concentration dependent which was inverse proportion to the cell viability by MTT assay using L929 cell line, and inhibitory concentration 50% (IC50) was 0.2 mg/ml for GCGA. The in vitro targeting efficiency and the in vitro cellular uptake were investigated. Compared with CTS NPs and GA-CTS NPs, GCGA NPs showed good cell specificity to BEL-7402 cells via the dual-ligand-receptor-mediated recognition, leading to a higher affinity to BEL-7402 cells. The results suggested that GCGA described here has the potential to be used as an effective vector for hepatic targeted drug therapy.

Engineering "Hot" Nanoparticles for Surface-Enhanced Raman Scattering by Embedding Reporter Molecules in Metal Layers

Small (Weinheim an Der Bergstrasse, Germany). Nov, 2011  |  Pubmed ID: 22125121

Ag is deposited on the surface of Au nanoparticles functionalized with 4-mercaptobenzoic acid (MBA). Exceptionally strong surface-enhanced Raman scattering (SERS) signals are observed from the resulting colloid. Using SERS as a tool, evidence is obtained for the embedding of MBA inside the nanoscale metal layer.

Variation in Sequences and MRNA Expression Levels of Inhibin Subunits α (INHA) and βA (INHBA) Genes Between Prolific and Nonprolific Goat Breeds

Molecular Reproduction and Development. Nov, 2011  |  Pubmed ID: 22128068

Genomic Sequence Analysis of Granulovirus Isolated from the Tobacco Cutworm, Spodoptera Litura

PloS One. 2011  |  Pubmed ID: 22132235

Spodoptera litura is a noctuid moth that is considered an agricultural pest. The larvae feed on a wide range of plants and have been recorded on plants from 40 plant families (mostly dicotyledons). It is a major pest of many crops. To better understand Spodoptera litura granulovirus (SpliGV), the nucleotide sequence of the SpliGV DNA genome was determined and analyzed.

Blockade of MGluR5 Reverses Abnormal Firing of Subthalamic Nucleus Neurons in 6-hydroxydopamine Partially Lesioned Rats

The Chinese Journal of Physiology. Oct, 2011  |  Pubmed ID: 22135908

Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic nucleus (STN) results in burst-firing activity of STN neurons, which is similar to that observed in Parkinson's disease (PD). We examined the effects of chronic and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, in firing activity of STN neurons in partially lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in vehicle-treated rats showed an increasing firing rate and a more irregular firing pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, 14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats. These data demonstrate that partial lesion of the nigrostriatal pathway increases firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment has the neuroprotective effect and reverses the abnormal firing activity of STN neurons, suggesting that MPEP has an important implication for the treatment of PD.

Highly Efficient Tm:YAG Ceramic Laser Resonantly Pumped at 1617 Nm

Optics Letters. Dec, 2011  |  Pubmed ID: 22139217

We report on a highly efficient polycrystalline Tm:YAG ceramic laser in-band pumped by an Er:YAG laser at 1617 nm. Lasing characteristics of 4.0 and 6.0 at.%Tm(3+)-doped YAG ceramics were investigated and compared. With an output coupler of 10% transmission, a maximum output power of 7.3 W was obtained at 2015 nm under 12.8 W of incident pump power, corresponding to a slope efficiency with respect to incident pump power of 62.3%.

A Systematic Analysis on DNA Methylation and the Expression of Both MRNA and MicroRNA in Bladder Cancer

PloS One. 2011  |  Pubmed ID: 22140553

DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported.

Carbon Monoxide Inhibits Fas Activating Antibody-induced Apoptosis in Endothelial Cells

Medical Gas Research. 2011  |  Pubmed ID: 22146483

ABSTRACT:

Electric-field Controlled Ferromagnetism in MnGe Magnetic Quantum Dots

Nano Reviews. 2011  |  Pubmed ID: 22110869

Electric-field control of ferromagnetism in magnetic semiconductors at room temperature has been actively pursued as one of the important approaches to realize practical spintronics and non-volatile logic devices. While Mn-doped III-V semiconductors were considered as potential candidates for achieving this controllability, the search for an ideal material with high Curie temperature (T(c)>300 K) and controllable ferromagnetism at room temperature has continued for nearly a decade. Among various dilute magnetic semiconductors (DMSs), materials derived from group IV elements such as Si and Ge are the ideal candidates for such materials due to their excellent compatibility with the conventional complementary metal-oxide-semiconductor (CMOS) technology. Here, we review recent reports on the development of high-Curie temperature Mn(0.05)Ge(0.95) quantum dots (QDs) and successfully demonstrate electric-field control of ferromagnetism in the Mn(0.05)Ge(0.95) quantum dots up to 300 K. Upon the application of gate-bias to a metal-oxide-semiconductor (MOS) capacitor, the ferromagnetism of the channel layer (i.e. the Mn(0.05)Ge(0.95) quantum dots) was modulated as a function of the hole concentration. Finally, a theoretical model based upon the formation of magnetic polarons has been proposed to explain the observed field controlled ferromagnetism.

Structural Evolution of GeMn/Ge Superlattices Grown by Molecular Beam Epitaxy Under Different Growth Conditions

Nanoscale Research Letters. Dec, 2011  |  Pubmed ID: 22151995

ABSTRACT: GeMn/Ge epitaxial 'superlattices' grown by molecular beam epitaxy with different growth conditions have been systematically investigated by transmission electron microscopy. It is revealed that periodic arrays of GeMn nanodots can be formed on Ge and GaAs substrates at low temperature (approximately 70degreesC) due to the matched lattice constants of Ge (5.656 A) and GaAs (5.653 A), while a periodic Ge/GeMn superlattice grown on Si showed disordered GeMn nanodots with a large amount of stacking faults, which can be explained by the fact that Ge and Si have a large lattice mismatch. Moreover, by varying growth conditions, the GeMn/Ge superlattices can be manipulated from having disordered GeMn nanodots to ordered coherent nanodots and then to ordered nanocolumns.

[Fluorescence in Situ Hybridization Study of Acute Myeloid Leukemia with Cryptic Chromosome Rearrangements]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Dec, 2011  |  Pubmed ID: 22161107

To detect specific chromosome rearrangements in acute myeloid leukemia (AML) using interphase-fluorescence in situ hybridization (FISH).

Effects of Matrine on Proliferation and Apoptosis in Gallbladder Carcinoma Cells (GBC-SD)

Phytotherapy Research : PTR. Dec, 2011  |  Pubmed ID: 22162124

Although matrine, a primary active component of dried Sophora flavescens root (ku shen), is known to induce apoptosis in a variety of tumor cells in vitro, the molecular mechanism of such apoptosis remains elusive. This analysis of the cell cycle and apoptosis in matrine-treated human gallbladder carcinoma cells (GBC-SD) showed that matrine can indeed inhibit cell proliferation and induce G1 cell cycle arrest and apoptosis in a dose- and time-dependent manner. An additional western blot analysis of matrine-treated cells also showed caspase-3 and Bcl-2 activation, as well as cyclinE down-regulation. Overall, the results indicate that matrine perturbs gallbladder cancer cell progression during the G1 phase by down-regulating cyclinE and induces apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and increasing expression of the proapoptotic protein Bax. Copyright © 2011 John Wiley & Sons, Ltd.

Neutralizing Antibody Response to Hepatitis C Virus

Viruses. Nov, 2011  |  Pubmed ID: 22163337

A critical first step in a "rational vaccine design" approach for hepatitis C virus (HCV) is to identify the most relevant mechanisms of immune protection. Emerging evidence provides support for a protective role of virus neutralizing antibodies, and the ability of the B cell response to modify the course of acute HCV infection. This has been made possible by the development of in vitro cell culture models, based on HCV retroviral pseudotype particles expressing E1E2 and infectious cell culture-derived HCV virions, and small animal models that are robust tools in studies of antibody-mediated virus neutralization. This review is focused on the immunogenic determinants on the E2 glycoprotein mediating virus neutralization and the pathways in which the virus is able to escape from immune containment. Encouraging findings from recent studies provide support for the existence of broadly neutralization antibodies that are not associated with virus escape. The identification of conserved epitopes mediating virus neutralization that are not associated with virus escape will facilitate the design of a vaccine immunogen capable of eliciting broadly neutralizing antibodies against this highly diverse virus.

[Effects of Excreted/secreted Antigens of Toxoplasma Gondii on CD4+ CD25+ Foxp3+ T Cells and NK Cells of Melanoma-bearing Mice]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Jun, 2011  |  Pubmed ID: 22164498

To explore the effects of excreted/secreted antigens (ESA) of Toxoplasma gondii on CD4+CD25+ Foxp3+ T cells and NK cells of melanoma-bearing mice, as well as the tumor growth.

Quantification of Increased Cellularity During Inflammatory Demyelination

Brain : a Journal of Neurology. Dec, 2011  |  Pubmed ID: 22171354

Multiple sclerosis is characterized by inflammatory demyelination and irreversible axonal injury leading to permanent neurological disabilities. Diffusion tensor imaging demonstrates an improved capability over standard magnetic resonance imaging to differentiate axon from myelin pathologies. However, the increased cellularity and vasogenic oedema associated with inflammation cannot be detected or separated from axon/myelin injury by diffusion tensor imaging, limiting its clinical applications. A novel diffusion basis spectrum imaging, capable of characterizing water diffusion properties associated with axon/myelin injury and inflammation, was developed to quantitatively reveal white matter pathologies in central nervous system disorders. Tissue phantoms made of normal fixed mouse trigeminal nerves juxtaposed with and without gel were employed to demonstrate the feasibility of diffusion basis spectrum imaging to quantify baseline cellularity in the absence and presence of vasogenic oedema. Following the phantom studies, in vivo diffusion basis spectrum imaging and diffusion tensor imaging with immunohistochemistry validation were performed on the corpus callosum of cuprizone treated mice. Results demonstrate that in vivo diffusion basis spectrum imaging can effectively separate the confounding effects of increased cellularity and/or grey matter contamination, allowing successful detection of immunohistochemistry confirmed axonal injury and/or demyelination in middle and rostral corpus callosum that were missed by diffusion tensor imaging. In addition, diffusion basis spectrum imaging-derived cellularity strongly correlated with numbers of cell nuclei determined using immunohistochemistry. Our findings suggest that diffusion basis spectrum imaging has great potential to provide non-invasive biomarkers for neuroinflammation, axonal injury and demyelination coexisting in multiple sclerosis.

Viscoelastic Transition and Yield Strain of the Folded Protein

PloS One. 2011  |  Pubmed ID: 22174767

For proteins, the mechanical properties of the folded state are directly related to function, which generally entails conformational motion. Through sub-Angstrom resolution measurements of the AC mechanical susceptibility of a globular protein we describe a new fundamental materials property of the folded state. For increasing amplitude of the forcing, there is a reversible transition from elastic to viscoelastic response. At fixed frequency, the amplitude of the deformation is piecewise linear in the force, with different slopes in the elastic and viscoelastic regimes. Effectively, the protein softens beyond a yield point defined by this transition. We propose that ligand induced conformational changes generally operate in this viscoelastic regime, and that this is a universal property of the folded state.

In Vitro Effects of Aqueous Extracts of Astragalus Membranaceus and Scutellaria Baicalensis GEORGI on Toxoplasma Gondii

Parasitology Research. Dec, 2011  |  Pubmed ID: 22179265

Toxoplasma gondii is a parasite that infects animals and humans worldwide. The standard treatment for toxoplasmosis is limiting due to toxic adverse effects, thus there is a need to identify new drugs that are less toxic. Both Astragalus membranaceus and Scutellaria baicalensis GEORGI are popular traditional Chinese herbs widely used for the treatment of various inflammatory diseases in Asia, and we have previously demonstrated that water extracts of A. membranaceus (AmE) and S. baicalensis GEORGI (SbE) have good efficacy in controlling T. gondii replication in mouse models. This study was designed to further evaluate their effects against developing tachyzoites of the RH strain of T. gondii in HeLa cell cultures. AmE, SbE, and TMP-SMX (trimethoprim-sulfamethoxazole) were added into the wells containing both HeLa cells and replicating T. gondii of green fluorescent protein (GFP)-expressing RH tachyzoites. The proliferation and morphous of the tachyzoites were observed, the fluorescence intensity expressed as the fluorescence gray scale value was measured, and the living tachyzoites were counted at different culture times after treatment. The results showed that, compared to untreated controls, parasites treated with either AmE or SbE had significantly decreased intracellular replication at 72, 96, and 120 h after treatment (P < 0.01); while compared to either AmE- or SbE-treated groups, SMX-treated groups had even significantly decreased replication (only a few living parasites were detected) at the above times (P < 0.01). Our data demonstrated that both AmE and SbE had remarkable in vitro activities against T. gondii.

Immobilization of Gene Vectors on Bisphosphonate-mediated Gene-eluting Metal Stents Using Antibody for Localized Gene Delivery

Journal of Controlled Release : Official Journal of the Controlled Release Society. Nov, 2011  |  Pubmed ID: 22195832

Novel PH-sensitive Zwitterionic Poly(amino Acid) Derivatives for Drug Delivery

Journal of Controlled Release : Official Journal of the Controlled Release Society. Nov, 2011  |  Pubmed ID: 22195952

Bis[2-(benzyl-idene-amino)-phen-yl] Disulfide

Acta Crystallographica. Section E, Structure Reports Online. Dec, 2011  |  Pubmed ID: 22199858

In the title mol-ecule, C(26)H(20)N(2)S(2), the two benzene rings connected by a disulfide chain form a dihedral angle of 84.9 (1)°, and the two benzene rings in the two benzyl-idene-amino-phenyl fragments form dihedral angles of 34.4 (1) and 32.8 (1)°. The crystal structure exhibits weak inter-molecular C-H⋯S hydrogen bonds, which link the mol-ecules into chains along [101].

[Efficacy of Gadobenate Dimeglumine Vs Gadopentetate Dimeglumine in Contrast- Enhanced Magnetic Resonance Imaging for Diagnosis of Solitary Brain Metastases]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Dec, 2011  |  Pubmed ID: 22200693

To compare gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) for their efficacy as contrast agents in contrast-enhanced magnetic resonance imaging (MRI) for diagnosis of solitary brain metastases (SBM).

The Validation of Complete Fourier Direct MR Method for Diffusion MRI Via Biological and Numerical Phantoms

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: 22255156

The equations of the Complete Fourier Direct (CFD) MR model are explicitly derived for diffusion weighted NMR experiments. The CFD-MR theory is validated by comparing a biological phantom constructed from nerve bundles and agar gel with its numerical implementation. The displacement integral distribution function estimated from the experimental data is in high agreement with the numerical phantom. CFD-MR's ability to estimate accurately and fully spin diffusion properties demonstrated here, provides the experimental validation of the theoretical CFD-MR model.

Periostin and Osteopontin Are Overexpressed in Chronically Inflamed Sinuses

International Forum of Allergy & Rhinology. Mar, 2011  |  Pubmed ID: 22287326

In chronic rhinosinusitis (CRS), the inflammation leads to a proliferative response in the extracellular matrix (ECM). Periostin and osteopontin are 2 ECM proteins which have received attention for their roles in tissue remodeling in inflammatory diseases of the upper and lower airways. Transforming growth factor beta-1 (TGFβ1) is an inflammatory cytokine that has been implicated in fibrotic conditions affecting virtually every organ. In this study we seek to evaluate the differential expression of periostin, osteopontin, and TGFβ1 in the ethmoid sinus and nasal floor of patients with CRS. Furthermore, we seek to determine if a correlation exists between their differential expression in the nose and sinuses of patients with CRS.

Comparison of Flexural Properties and Surface Roughness of Nanohybrid and Microhybrid Dental Composites

General Dentistry. Sep, 2011  |  Pubmed ID: 22313818

Recently introduced nanohybrid dental composites have promised a smoother surface finish and strength, comparable to that of microhybrid composites. This study compared the mechanical properties and surface finish of nanohybrid and microhybrid composites by measuring the flexural strength and modulus (four-point bend) and surface roughness after polishing (using atomic force microscopy) of six commercial dental composites (three nanohybrid, three microhybrid). Scanning electron microscopy (SEM) was used to qualitatively characterize filler morphology and size. The flexural strength and modulus were significantly higher among the microhybrid composites, while the nanohybrid composites exhibited significantly lower surface roughness. SEM characterization revealed differences in filler particle size and shape that could affect the flexural properties and surface roughness. Composites containing spherical filler particles exhibited higher flexural properties and lower roughness values compared to composites with irregular fillers. These results did not support the premise that nanohybrid composites offer similar mechanical properties to microhybrids in addition to a better surface finish.

Bacterial Niche-specific Genome Expansion is Coupled with Highly Frequent Gene Disruptions in Deep-sea Sediments

PloS One. 2011  |  Pubmed ID: 22216192

The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers) of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed.

Supramolecular Micellar Nanoaggregates Based on a Novel Chitosan/vitamin E Succinate Copolymer for Paclitaxel Selective Delivery

International Journal of Nanomedicine. 2011  |  Pubmed ID: 22228999

Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX), Cremophor EL(®) (BASF, Ludwigshafen, Germany) needs to be used as a solubilizer in its clinical formulation (Taxol(®), Bristol-Myers Squibb, New York, NY), although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element.

[Preliminary Study on Variations and Neural Generators of Error-related Negativity in First Episode Schizophrenics]

Zhonghua Yi Xue Za Zhi. Nov, 2011  |  Pubmed ID: 22333055

To explore the variations and their activated brain areas of error-related negativity (ERN) in first episode schizophrenics.

[Fine-needle Aspiration Cytology of Thyroid Nodules: a Clinical Evaluation]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery. Nov, 2011  |  Pubmed ID: 22335973

To investigate the clinical application of fine needle aspiration (FNA) cytology of thyroid nodules.

Regioselective and Stereospecific Cross-Coupling of Primary Allylic Amines with Boronic Acids and Boronates Through Palladium-Catalyzed CN Bond Cleavage

Angewandte Chemie (International Ed. in English). Feb, 2012  |  Pubmed ID: 22334495

The NH(2) group serves as an effective leaving group in the palladium-catalyzed regioselective and stereospecific title reaction. The reaction works well with aryl- and alkenylboronic acids and aryl-, alkenyl-, allyl-, and benzylboronates, and complete transfer of chirality has been achieved when using α-chiral primary allylic amines as the allylic electrophiles.

Systematic Prevention of Bubble Formation and Accumulation for Long-term Culture of Pancreatic Islet Cells in Microfluidic Device

Biomedical Microdevices. Jan, 2012  |  Pubmed ID: 22252566

Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability.

Surface-dominated Conduction in a 6 Nm-thick Bi2Se3 Thin Film

Nano Letters. Feb, 2012  |  Pubmed ID: 22316380

We report a direct observation of surface dominated conduction in an intrinsic Bi2Se3 thin film with a thickness of 6 quintuple layers (QLs) grown on lattice-matched CdS (0001) substrates by molecular beam epitaxy (MBE). Shubnikov-de Haas (SdH) oscillations from the topological surface states suggest that the Fermi level falls inside the bulk band gap and is 53 ± 5 meV above the Dirac point, in agreement with 70 ± 20 meV obtained from scanning tunneling spectroscopies (STS). Our results demonstrate a great potential of producing genuine topological insulator devices using Dirac Fermions of the surface states, when the film thickness is pushed to nano-meter range.

Murine CD8(+)T Cell Cytotoxicity Against Schistosomula Induced by Inoculation of Schistosomal 22.6/26GST Coupled Sepharose 4B Beads

Vaccine. Feb, 2012  |  Pubmed ID: 22326902

Schistosomasis is a world-wide parasitic disease. Although chemotherapy is the main treatment method for schistosomasis currently, it cannot prevent schistosome reinfection. Up to now no effective vaccine is available to prevent schistosomiasis. Dendritic cells (DCs) are one of the key players in the cellular immune response and play an important role in antigen presentation as antigen-presenting cells. Here we reported a novel large particulate antigen, in which Sepharose 4B beads were coated with Sj22.6/26GST. Our results showed that this particulate antigen could be cross-presented by DCs to CD8(+)T cells. Furthermore, CD8(+)T cells stimulated by particulate antigen directly exerted cytotoxicity against Schistosoma japonicum schistosomula. We also demonstrated that S. japonicum schistosomula acquired the MHC class I molecules from host blood serum and presented the molecules at the larval surface. While it may help them escape from the host immune surveillance, these MHC I-antigen complexes presented on the surface render schistosomula the potential targets of the CD8(+)T cell cytotoxicity induced by particulate antigen-based vaccine. Finally we evaluated the protective immunity of this particulate vaccine in a mouse infection challenge model. Our data clearly showed that the particulate vaccine induced a partial reduction in both worm burdens and egg loads. Taken together, these results suggest that this large particulate vaccine could be a potential vaccine for the prevention of schistosome infection.

Molecular Characterization, Polymorphism and Association of Porcine MYST2 Gene

Molecular Biology Reports. Feb, 2012  |  Pubmed ID: 22327654

MYST histone acetyltransferase 2 (MYST2) is an important reproduction related gene. In this study, we cloned the full-length cDNA sequence of porcine MYST2 gene through the rapid amplification of cDNA ends method. The porcine MYST2 gene encodes a protein of 611 amino acids which shares high homology with the MYST2 of six species: cattle (99%), rabbit (99%), human (99%), rat (99%), mouse (99%) and chicken (98%).The open reading frame of this gene is structured in 15 exons and 14 introns as revealed by computer-assisted analysis. The phylogenetic analysis revealed that the porcine MYST2 gene has a closer genetic distance with the MYST2 gene of cattle. PCR-RFLP was established to detect the GU373686:c.2872G > A substitution of porcine MYST2 gene mRNA and association of this mutation with litter size traits was assessed in Large White (n = 200) and Landrace (n = 200) pig populations. Results demonstrated that this polymorphic locus was significantly associated with the litter size of all parities in Large White sows and Landrace sows. These data serve as a foundation for further insight into this porcine gene.

Dual-functional Click-triazole: a Metal Chelator and Immobilization Linker for the Construction of a Heterogeneous Palladium Catalyst and Its Application for the Aerobic Oxidation of Alcohols

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22331347

A novel SBA-15 supported catalyst PdL(n)@SBA-15 containing a 2-pyridyl-1,2,3-triazole ligand framework was prepared via a "click" route, in which the click-triazole acted as both a stable linker and a good chelator. The catalyst was characterized and applied for the aerobic oxidation of alcohols, and the product was obtained in up to 98% yield.

Cu-Catalyzed Oxidative C(sp(2))-H Cycloetherification of O-Arylphenols for the Preparation of Dibenzofurans

Organic Letters. Jan, 2012  |  Pubmed ID: 22288878

A new process involving copper-catalyzed aerobic C(sp(2))-H activation, followed by cycloetherification, has been developed. This reaction serves as a direct method for the preparation of multisubstituted dibenzofurans starting with o-arylphenols. The presence of a strong para-electron-withdrawing group (e.g., NO(2)) on the phenol is essential for the success of the reaction.

Lentiviral Transgenic MicroRNA-Based ShRNA Suppressed Mouse Cytochromosome P450 3A (CYP3A) Expression in a Dose-Dependent and Inheritable Manner

PloS One. 2012  |  Pubmed ID: 22291988

Cytochomosome P450 enzymes (CYP) are heme-containing monooxygenases responsible for oxidative metabolism of many exogenous and endogenous compounds including drugs. The species difference of CYP limits the extent to which data obtained from animals can be translated to humans in pharmacodynamics or pharmacokinetics studies. Transgenic expression of human CYP in animals lacking or with largely reduced endogenous CYP counterparts is recognized as an ideal strategy to correct CYP species difference. CYP3A is the most abundant CYP subfamily both in human and mammals. In this study, we designed a microRNA-based shRNA (miR-shRNA) simultaneously targeting four members of mouse CYP3A subfamily (CYP3A11, CYP3A16, CYP3A41 and CYP3A44), and transgenic mice expressing the designed miR-shRNA were generated by lentiviral transgenesis. Results showed that the CYP3A expression level in transgenic mice was markedly reduced compared to that in wild type or unrelated miR-shRNA transgenic mice, and was inversely correlated to the miR-shRNA expression level. The CYP3A expression levels in transgenic offspring of different generations were also remarkably lower compared to those of controls, and moreover the inhibition rate of CYP3A expression remained comparable over generations. The ratio of the targeted CYP3A transcriptional levels was comparable between knockdown and control mice of the same gender as detected by RT-PCR DGGE analysis. These data suggested that transgenic miR-shRNA suppressed CYP3A expression in a dose-dependent and inheritable manner, and transcriptional levels of the targeted CYP3As were suppressed to a similar extent. The observed knockdown efficacy was further confirmed by enzymatic activity analysis, and data showed that CYP3A activities in transgenic mice were markedly reduced compared to those in wild-type or unrelated miR-shRNA transgenic controls (1.11±0.71 vs 5.85±1.74, 5.9±2.4; P<0.01). This work laid down a foundation to further knock down the remaining murine CYP3As or CYPs of other subfamilies, and a basis to generate CYP knockdown animals of other species.

Islet Preconditioning Via Multimodal Microfluidic Modulation of Intermittent Hypoxia

Analytical Chemistry. Feb, 2012  |  Pubmed ID: 22296179

Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues.

A Novel Sulfonamide Agent, MPSP-001, Exhibits Potent Activity Against Human Cancer Cells in Vitro Through Disruption of Microtubule

Acta Pharmacologica Sinica. Feb, 2012  |  Pubmed ID: 22301862

Aim:To evaluate the anti-cancer effects of a new sulfonamide derivative, 2-(N-(3-chlorophenyl)-4-methoxyphenylsulfonamido)-N-hydroxypropanamide (MPSP-001).Methods:Human cancer cell lines (HepG2, THP-1, K562, HGC-27, SKOV3, PANC-1, SW480, Kba, HeLa, A549, MDA-MB-453, and MCF-7) were examined. The cytotoxicity of MPSP-001 was evaluated using the WST-8 assay. Cell cycle distribution was examined with flow cytometry. Mitotic spindle formation was detected using immunofluorescence microscopy. Apoptosis-related proteins were examined with Western blot using specific phosphorylated protein antibodies. Competitive tubulin-binding assay was performed to test whether the compound competitively bound to the colchicine site. Molecular docking was performed to explore the possible binding conformation.Results:MPSP-001 potently inhibited the growth of the 12 different types of human cancer cells with the IC(50) values ranging from 1.9 to 15.7 μmol/L. The compound exerted potent inhibition on the drug-resistant Kb/VCR and MCF-7/ADR cells, as on Kba and MCF-7 cells. In HeLa, HGC-27, A549, and other cells, the compound (5 μmol/L) caused cell cycle arrest at the G(2)/M phase, and subsequently induced cell apoptosis. In Hela cells, it prevented the mitotic spindle formation. Furthermore, the compound dose-dependently inhibited polymerization of tubulin in vitro, and directly bound to the colchicine-site of β-tubulin. Molecular docking predicted that the compound may form two hydrogen bonds to the binding pocket. The compound showed synergistic effects with colchicine and taxol in blocking mitosis of HeLa cells.Conclusion:MPSP-001 shows a broad-spectrum of anti-tumor efficacy in vitro and represents a novel structure with anti-microtubule activity.

Improvement in T-Staging of Rectal Carcinoma: Using a Novel Endorectal Ultrasonography Technique with Sterile Coupling Gel Filling the Rectum

Ultrasound in Medicine & Biology. Feb, 2012  |  Pubmed ID: 22305079

Our purpose was to study the accuracy of using endorectal ultrasonography (ERUS) with sterile coupling gels filling the rectum in the preoperative T-staging of rectal carcinoma. A total of 189 patients with confirmed rectal carcinoma were recruited. All underwent ERUS and surgery within the week following sonography. EURS was performed by introducing sterile coupling gel into the rectum. Two radiologists looked at the images at the same time and agreed upon staging. Rectal carcinoma was staged from Tis to T4. The accuracy of T-staging by ERUS was 89.95%. The sensitivity, specificity, PPV and NPV for ERUS at different stages were calculated. For early stage (Tis and T1), these values were 93.62%, 97.89%, 93.62% and 97.89%, respectively. ERUS filling with sterile coupling gel in the rectum overcomes the pressure effect from a water bath and the restriction caused by tumor stenosis, thus, greatly improving the accuracy of T-staging. The examination is real-time, safe and inexpensive.

"One-stop-shop" Cardiac MRI at 3.0T for the Detection of Coronary Artery Disease

International Journal of Cardiology. Feb, 2012  |  Pubmed ID: 22305773

Content Determination of Benzyl Glucosinolate and Anti-cancer Activity of Its Hydrolysis Product in Carica Papaya L

Asian Pacific Journal of Tropical Medicine. Mar, 2012  |  Pubmed ID: 22305790

To determine the content of benzyl glucosinolate (BG) in the pulp and the seed and investigate the anti-cancer activity of its hydrolysis product in Carica papaya L.

Dual Polarisation Interferometry for Real-time, Label-free Detection of Interaction of Mercury(ii) with Mercury-specific Oligonucleotides

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22310380

A real-time, label-free dual polarisation interferometry technique was used to investigate the interaction of Hg(2+) with a 21-mer T-rich oligonucleotide and further construct a Hg(2+) biosensor based on thymine-Hg(2+)-thymine coordination chemistry.

Gate-Controlled Surface Conduction in Na-Doped Bi(2)Te(3) Topological Insulator Nanoplates

Nano Letters. Feb, 2012  |  Pubmed ID: 22313251

Exploring exciting and exotic physics, scientists are pursuing practical device applications for topological insulators. The Dirac-like surface states in topological insulators are protected by the time-reversal symmetry, which naturally forbids backscattering events during the carrier transport process, and therefore offers promising applications in dissipationless spintronic devices. Although considerable efforts have been devoted to controlling their surface conduction, limited work has been focused on tuning surface states and bulk carriers in Bi(2)Te(3) nanostructures by external field. Here we report gate-tunable surface conduction in Na-doped Bi(2)Te(3) topological insulator nanoplates. Significantly, by applying external gate voltages, such topological insulators can be tuned from p-type to n-type. Our results render a promise in finding novel topological insulators with enhanced surface states.

Serotonin-mediated Modulation of Na+/K+ Pump Current in Rat Hippocampal CA1 Pyramidal Neurons

BMC Neuroscience. Jan, 2012  |  Pubmed ID: 22257758

ABSTRACT: BACKGROUND: The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na+/K+ pump in rat hippocampal CA1 pyramidal neurons. RESULTS: 5-HT (0.1, 1 mM) showed Na+/K+ pump current (Ip) densities of 0.40+/-0.04, 0.34+/-0.03 pA/pF contrast to 0.63+/-0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT3 receptor (5-HT3R) antagonist, not by WAY100635, a 5-HT1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT3R specific agonist, mimicked the effect of 5-HT on Ip. CONCLUSION: 5-HT inhibits neuronal Na+/K+ pump activity via 5-HT3R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.

Inhibition of P38 MAPK Activity Promotes Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells

Annals of Hematology. Jan, 2012  |  Pubmed ID: 22258328

Ex vivo expansion of hematopoietic stem cells (HSCs) depends on HSC self-renewing proliferation and functional maintenance, which can be negatively affected by HSC differentiation, apoptosis, and senescence. Therefore, inhibition of HSC senescence may promote HSC expansion. To test this hypothesis, we examined the effect of inhibition of p38 mitogen-activated protein kinase (p38) on the expansion of human umbilical cord blood (hUCB) CD133(+) cells because activation of p38 has been implicated in the induction of HSC senescence under various physiological and pathological conditions. Our results showed that ex vivo expansion of hUCB CD133(+) cells activated p38, which was abrogated by the p38 specific inhibitor SB203580 (SB). Inhibition of p38 activity with SB promoted the expansion of CD133(+) cells and CD133(+)CD38(-) cells. In addition, hUCB CD133(+) cells expanded in the presence of SB for 7 days showed about threefold increase in the clonogenic function of HSCs and engraftment in non-obese diabetic/severe combined immunodeficient mice after transplantation compared to the input cells. In contrast, the cells expanded without SB exhibited a significant reduction in these HSC functions. The enhancement of ex vivo expansion of hUCB HSCs is primarily attributable to SB-mediated inhibition of HSC senescence. In addition, inhibition of HSC apoptosis and upregulation of CXCR4 may also contribute to the enhancement. However, p38 inhibition had no significant effect on HSC differentiation and proliferation. These findings suggest that inhibition of p38 activation may represent a novel strategy to promote ex vivo expansion of hUCB HSCs.

Elevated Admission Microalbuminuria Predicts Poor Myocardial Blood Flow and 6-Month Mortality in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Clinical Cardiology. Jan, 2012  |  Pubmed ID: 22262165

BACKGROUND: Microalbuminuria (MA) is considered a major risk factor predisposing to cardiovascular morbidity and mortality. Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by MA have been well described. However, data regarding admission MA and coronary and myocardial flow are scant. The aims of this study were to evaluate the effects of admission MA on coronary blood flow and prognosis in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. HYPOTHESIS: Did elevated admission microalbuminuria predict poor myocardial blood flow and 6-month mortality in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention? METHODS: A total of 247 patients undergoing primary PCI for STEMI within 12 hours after symptom onset were studied. Patients were divided into 2 groups according to admission urinary albumin extraction rate (UAER): (1) an MA group (UAER 20-200 µg/min), and (2) a normoalbuminuria (NA) group (UAER < 20 µg/min). RESULTS: Microalbuminuria was observed in 108 patients. Univariate analyses showed statistical differences between the NA and MA groups in serum creatine level, plasma glucose level, and peak creatine kinase level on presentation. Thrombolysis In Myocardial Infarction (TIMI) flow grades (TFGs) 0-2 in the MA group were more frequent (9.4% vs 21.2%, P < 0.05) than in the NA group, and corrected TIMI frame count was higher (23.9 ± 18.5 vs 29.8 ± 23.5, P < 0.05). Admission MA was an independent predictor of poor myocardial perfusion (adjusted relative risk: 3.14, 95% confidence interval: 0.99-6.78) and a higher rate of 6-month mortality in STEMI patients undergoing primary PCI (adjusted relative risk: 1.58, 95% confidence interval: 0.74-3.39). CONCLUSIONS: Admission MA levels are associated with impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI. © 2012 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Myocardial Perfusion Magnetic Resonance Imaging Using Sliding-Window Conjugate-Gradient Highly Constrained Back-Projection Reconstruction for Detection of Coronary Artery Disease

The American Journal of Cardiology. Jan, 2012  |  Pubmed ID: 22264595

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD.

Down-Regulation of Pm4CL1 Gene Expression in E. Coli Model by Antisense MRNA

Biochemical Genetics. Jan, 2012  |  Pubmed ID: 22273846

The coumarate:coenzyme A ligase 1 gene (4CL1) was isolated from secondary developing xylem tissues of Pinus massoniana Lamb (Pm4CL1). The Pm4CL1 gene was inserted into a pQE30 expression vector in both sense and antisense orientations to form a pQE30-4CL1-anti4CL1. The expression level of the Pm4CL1 gene in Escherichia coli cells was inhibited by the antisense mRNA of the Pm4CL1 gene. The results of reverse transcriptase polymerase chain reaction and sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the average mRNA and protein expression levels of the Pm4CL1 gene in E. coli cells were decreased by 43 and 46%, respectively. These results are an important basis for further investigation.

Chemical Characterization of Etched Dentin in Non-Carious Cervical Lesions

The Journal of Adhesive Dentistry. Jan, 2012  |  Pubmed ID: 22282761

Purpose: Bonding to non-carious cervical lesion (NCCL) sclerotic dentin that involves acid etching continues to be a challenging problem due to its altered chemical structure. In the present study, the objective was to investigate the chemical response of NCCL sclerotic dentin to the different acid etching times. Materials and Methods: Extracted human premolars affected with NCCLs were selected, and a cavity matching the natural lesion with respect to size and location was prepared on the lingual surface of each tooth to serve as the control. The dentin surfaces were treated for 15 s and 30 s using 37% phosphoric acid and then analyzed by Raman microspectroscopic mapping/imaging. Results: NCCL dentin substrates had dramatic effects on the chemical profile of dentin demineralization. The spectral comparison showed that the demineralized layer generated by the acid treatment was highly irregular in terms of depth and mineral component retained, especially when NCCL sclerotic dentin was etched for 15 s. When the etching time was increased to 30 s, the demineralization of NCCL sclerotic dentin was more effective and comparable to the nonsclerotic control that was treated for 15 s. Different etching times affected the depth, degree, and profile of the dentin demineralization. Conclusion: The shorter etching time (ie, 15 s) might not be adequate for NCCL sclerotic dentin. However, the longer etching time (ie, 30 s) would induce much deeper demineralized dentin for nonsclerotic substrates. Thus, although extended etching times can be used to remove the hypermineralized layer, further studies are required to analyze the impact this might have on the dentin bonding.

AT1 Receptor Blockade Delays Postlactational Mammary Gland Involution: a Novel Role for the Renin Angiotensin System

The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Jan, 2012  |  Pubmed ID: 22286690

Angiotensin II (AngII), the main effector peptide of the renin-angiotensin system (RAS), participates in multiple biological processes, including cell growth, apoptosis, and tissue remodeling. Since AngII activates, in different cell types, signal transducing pathways that are critical for mammary gland postlactational regression, we investigated the role of the RAS during this process. We found that exogenous administration of AngII in mammary glands of lactating Balb/c mice induced epithelium apoptosis [2.9±0.5% (control) vs. 9.6±1.1% (AngII); P < 0.001] and activation of the proapoptotic factor STAT3, an effect inhibited by irbesartan, an AT(1) receptor blocker. Subsequently, we studied the expression kinetics of RAS components during involution. We found that angiotensin-converting enzyme (ACE) mRNA expression peaked 6 h after weaning (5.7-fold; P<0.01), while induction of angiotensinogen and AT(1) and AT(2) receptors expression was detected 96 h after weaning (6.2-, 10-, and 6.2-fold increase, respectively; P<0.01). To assess the role of endogenously generated AngII, mice were treated with losartan, an AT(1) receptor blocker, during mammary involution. Mammary glands from losartan-treated mice showed activation of the survival factors AKT and BCL-(XL), significantly lower LIF and TNF-α mRNA expression (P<0.05), reduced apoptosis [12.1±2.1% (control) vs. 4.8±0.7% (losartan); P<0.001] and shedding of epithelial cells, inhibition of MMP-9 activity in a dose-dependent manner (80%; P<0.05; with losartan IC(50) value of 6.9 mg/kg/d] and lower collagen deposition and adipocyte invasion causing a delayed involution compared to vehicle-treated mice. Furthermore, mammary glands of forced weaned AT(1A)- and/or AT(1B)-deficient mice exhibited retarded apoptosis of epithelial cells [6.3±0.95% (WT) vs. 3.3±0.56% (AT(1A)/AT(1B) DKO); P<0.05] with remarkable delayed postlactational regression compared to wild-type animals. Taken together, these results strongly suggest that AngII, via the AT(1) receptor, plays a major role in mouse mammary gland involution identifying a novel role for the RAS.-Nahmod, K. A., Walther, T., Cambados, N., Fernandez, N., Meiss, R., Tappenbeck, N., Wang, Y., Raffo, D., Simian, M., Schwiebs, A., Pozner, R. G., Fuxman Bass, J. I., Pozzi, A. G., Geffner, J. R., Kordon, E. C., Schere-Levy, C. AT(1) receptor blockade delays postlactational mammary gland involution: a novel role for the renin angiotensin system.

Estradiol Directly Attenuates Sodium Currents and Depolarizing Afterpotentials in Isolated Gonadotropin-releasing Hormone Neurons

Brain Research. Feb, 2012  |  Pubmed ID: 22209345

The gonadotropin-releasing hormone (GnRH) neuron is the pivotal control center in a tightly regulated reproductive axis. The release of GnRH controls estradiol production by the ovary, and estradiol acts at the hypothalamus to regulate GnRH release. However, the mechanisms of estradiol feedback are just beginning to be understood. We have previously shown that estradiol administered to the female mouse modulates sodium currents in fluorescently-labeled GnRH neurons. In the current studies, estradiol (1nM) was applied directly, for 16-24h, to hypothalamic cultures from young or aged female ovariectomized mice. The direct application of estradiol modulated a tetrodotoxin-sensitive sodium current in isolated GnRH neurons from both young and aged animals. Estradiol, and the specific estrogen receptor-β agonist DPN, decreased current amplitude measured in the morning (AM), but had no effect on afternoon currents. These compounds also decreased the rise and decay slope of the current response, increased the width of the current, and increased action potential width in AM recordings. In addition, estradiol decreased the amplitude of the depolarizing afterpotential (DAP); this effect was not time-of-day dependent. The ER-β agonist DPN did not mimic the effect of estradiol on DAPs, and the modulation of DAPs by estradiol was no longer present in cells from postreproductive animals. These results indicate that estradiol can affect the physiology of GnRH neurons via multiple pathways that are differentially regulated during the transition to reproductive senescence, suggesting that estradiol regulation of GnRH neuronal output is modulated during the aging process.

Water-dispersible, Uniform Nanospheres by Heating-enabled Micellization of Amphiphilic Block Copolymers in Polar Solvents

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012  |  Pubmed ID: 22211314

Uniform nanospheres with tunable size down to 30 nm were prepared simply by heating amphiphilic block copolymers in polar solvents. Unlike reverse micelles prepared in nonpolar, oily solvents, these nanospheres have a hydrophilic surface, giving them good dispersibility in water. Furthermore, they are present as individual, separated, rigid particles upon casting from the solution other than continuous thin films of merged micelles cast from micellar solution in nonpolar solvents. These nanospheres were generated by a heating-enabled micellization process in which the affinity between the solvent and the polymer chains as well as the segmental mobility of both hydrophilic and hydrophobic blocks was enhanced, triggering the micellization of the glassy copolymers in polar solvents. This heating-enabled micellization produces purely well-defined nanospheres without interference of other morphologies. The micelle sizes and corona thickness are tunable mainly by changing the lengths of the hydrophobic and hydrophilic blocks, respectively. The heating-enabled micellization route for the preparation of polymeric nanospheres is extremely simple, and is particularly advantageous in producing rigid, micellar nanospheres from block copolymers with long glassy, hydrophobic blocks which are otherwise difficult to prepare with high efficiency and purity. Furthermore, encapsulation of hydrophobic molecules (e.g., dyes) into micelle cores could be integrated into the heating-enabled micellization, leading to a simple and effective process for dye-labeled nanoparticles and drug carriers.

Estimating Population Divergence Time and Phylogeny from Single-nucleotide Polymorphisms Data with Outgroup Ascertainment Bias

Molecular Ecology. Feb, 2012  |  Pubmed ID: 22211450

The inference of population divergence times and branching patterns is of fundamental importance in many population genetic analyses. Many methods have been developed for estimating population divergence times, and recently, there has been particular attention towards genome-wide single-nucleotide polymorphisms (SNP) data. However, most SNP data have been affected by an ascertainment bias caused by the SNP selection and discovery protocols. Here, we present a modification of an existing maximum likelihood method that will allow approximately unbiased inferences when ascertainment is based on a set of outgroup populations. We also present a method for estimating trees from the asymmetric dissimilarity measures arising from pairwise divergence time estimation in population genetics. We evaluate the methods by simulations and by applying them to a large SNP data set of seven East Asian populations.

Ionic Liquids with Metal Chelate Anions

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22215209

A series of stable (air, water stable and with good thermal stability) and hydrophobic ionic liquids based upon metal chelate anions were synthesized, which were shown to be effective, mild, and easy to recycle catalysts at the same time stable solvents for the oxidation of cyclohexene.

Synthesis of the Pyridinyl Analogues of Dibenzylideneacetone (pyr-dba) Via an Improved Claisen-Schmidt Condensation, Displaying Diverse Biological Activities As Curcumin Analogues

Organic & Biomolecular Chemistry. Feb, 2012  |  Pubmed ID: 22179573

An efficient and easy procedure to synthesize the pyridinyl analogues of dibenzylideneacetone (pyr-dba) was developed by the condensation of substituted nicotinaldehyde and acetone in the presence of K(2)CO(3) in toluene-EtOH-H(2)O solvent system. Structurally diverse pyr-dba, including quinolinyl dba, can be prepared conveniently in moderate to excellent yields under mild conditions with this method. The resulting pyr-dba functioned as the enone analogs of curcumin and efficiently inhibited the activation of NF-κB and the growth of colorectal carcinoma HCT116 p53+/+ cells as well as the HIV-1 IN-LEDGF/p75 interaction.

Acetic Acid-induced Programmed Cell Death and Release of Volatile Organic Compounds in Chlamydomonas Reinhardtii

Plant Physiology and Biochemistry : PPB / Société Française De Physiologie Végétale. Feb, 2012  |  Pubmed ID: 22153255

Acetic acid widely spreads in atmosphere, aquatic ecosystems containing residues and anoxic soil. It can inhibit aquatic plant germination and growth, and even cause programmed cell death (PCD) of yeast. In the present study, biochemical and physiological responses of the model unicellular green algae Chlamydomonas reinhardtii were examined after acetic acid stress. H(2)O(2) burst was found in C. reinhardtii after acetic acid stress at pH 5.0 for 10 min. The photosynthetic pigments were degraded, gross photosynthesis and respiration were disappeared gradually, and DNA fragmentation was also detected. Those results indicated that C. reinhardtii cells underwent a PCD but not a necrotic, accidental cell death event. It was noticed that C. reinhardtii cells in PCD released abundant volatile organic compounds (VOCs) upon acetic acid stress. Therefore, we analyzed the VOCs and tested their effects on other normal cells. The treatment of C. reinhardtii cultures with VOCs reduced the cell density and increased antioxidant enzyme activity. Therefore, a function of VOCs as infochemicals involved in cell-to-cell communication at the conditions of applied stress is suggested.

Loperamide, an Antidiarrhea Drug, Has Antitumor Activity by Inducing Cell Apoptosis

Pharmacological Research : the Official Journal of the Italian Pharmacological Society. Mar, 2012  |  Pubmed ID: 22119769

Loperamide, an antidiarrhea drug, is a peripheral opiate agonist. Some other opiate agonists have been shown to promote cell apoptosis. In this research, we studied the apoptosis-inducing and cytotoxic activities of loperamide. MTT assay was used to determine its cytotoxicity on nine established human tumor cell lines. Cell apoptosis was detected by flow cytometry. Hypodiploid cells and cell cycles were analyzed by propidium iodide (PI) staining, while early apoptotic cells were detected by annexin V-FITC/PI staining. It was found that loperamide could inhibit the proliferation of the tested tumor cell lines. The IC(50) values for SMMC7721, MCF7, SPC-A1, SKOV3-DDP, H460, HepG2, SGC7901, U2OS, and ACHN cells were 24.2±2.1μM, 23.6±2.5μM, 25.9±3.1μM, 27.1±2.5μM, 41.4±2.1μM, 23.7±1.3μM, 35.4±3.5μM, 11.8±2.8μM, and 28.5±3.4μM, respectively. Loperamide was more effective to the human osteosarcoma U2OS cells with an IC(50) value of 11.8±2.8μM. Meanwhile, it could induce cell apoptosis and cause G2/M-phase cell cycle arrest. The apoptotic cells could be found when treating with loperamide for 6h and most of them belonged to early apoptosis. In loperamide-treated cells, activation of caspase-3 was found, namely that caspase-3 was involved in the loperamide-induced apoptosis. The results of these studies indicate that loperamide is a potential antitumor agent. To our knowledge, this is the first report on antitumor activity of loperamide.

Revelation of Topological Surface States in Bi(2)se(3) Thin Films by in Situ Al Passivation

ACS Nano. Jan, 2012  |  Pubmed ID: 22147687

Topological insulators (TIs) are extraordinary materials that possess massless, Dirac-like topological surface states in which backscattering is prohibited due to the strong spin-orbit coupling. However, there have been reports on degradation of topological surface states in ambient conditions, which presents a great challenge for probing the original topological surface states after TI materials are prepared. Here, we show that in situ Al passivation inside a molecular beam epitaxy (MBE) chamber could inhibit the degradation process and reveal the pristine topological surface states. Dual evidence from Shubnikov-de Hass (SdH) oscillations and weak antilocalization (WAL) effect, originated from the π Berry phase, suggests that the helically spin-polarized surface states are well preserved by the proposed in situ Al passivation. In contrast, we show the degradation of surface states for the unpassivated control samples, in which the 2D carrier density is increased 39.2% due to ambient n-doping, the SdH oscillations are completely absent, and a large deviation from WAL is observed.

Probing Biomolecular Interactions with Dual Polarization Interferometry: Real-time and Label-free Coralyne Detection by Use of Homoadenine DNA Oligonucleotide

Analytical Chemistry. Jan, 2012  |  Pubmed ID: 22148232

We incorporated the specific recognition of adenine-rich singled-stranded DNA (ssDNA) into dual polarization interferometry (DPI) measurements for direct, selective, and sensitive detection of the small molecule coralyne, and we simultaneously employed the real-time and label-free technique for detailed investigation of the interaction between coralyne and adenine-rich ssDNA. Data from UV-visible spectroscopy, circular dichroism (CD) spectroscopy, and DNA melting firmly confirmed that 48-mer homoadenine ssDNA oligonucleotide (A(48)) had highly specific recognition for coralyne, whereas 48-mer homothymine ssDNA oligonucleotide (T(48)) as the control had no such recognition. The immobilization of ssDNA (A(48) or T(48)) on a silicon oxynitride chip could be achieved through a preadsorbed poly(ethylenimine) (PEI) layer. Mass, thickness, and refractive index (RI) changes resolved by DPI during the whole process of ssDNA immobilization suggested that most ssDNA molecules were likely to lie on the PEI surface mainly in the form of a flat monolayer and insert themselves partly into the PEI layer. Qualitative and quantitative analysis of mass, thickness, and RI changes in A(48)/PEI layer upon addition of different concentrations of coralyne revealed that A(48) most likely underwent a conformational change from single-stranded to double-stranded structure. By evaluation of the binding curves from changes in mass, the association rate constant (k(a)), dissociation rate constant (k(d)), and association constant (K(A)) between coralyne and A(48) were determined to be 4.95 × 10(3) M(-1) s(-1), 0.031 s(-1), and 1.6 × 10(5) M(-1), respectively. Good linear correlations between coralyne concentrations ranging from 0.5 to 12 μM and three parameters (mass, thickness, and RI) resolved by the response to coralyne binding were obtained. The detection limits were 0.22 μM for mass calibration, 0.14 μM for thickness calibration, and 0.32 μM for RI calibration. The high selectivity of the biosensor to coralyne at the A(48)/PEI interface was successfully confirmed by using the other two interfaces (T(48)/PEI and PEI) and three typical intercalators (ethidium bromide, daunomycin, and methylene blue). It is expected that the biosensing platform may be extended to simultaneously detect and characterize the interactions of a variety of target molecules with functional DNA molecules with high sensitivity.

Frequent Mutations of Genes Encoding Ubiquitin-mediated Proteolysis Pathway Components in Clear Cell Renal Cell Carcinoma

Nature Genetics. Jan, 2012  |  Pubmed ID: 22138691

We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1α and HIF2α in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.

Polymeric Graphitic Carbon Nitride As a Heterogeneous Organocatalyst: from Photochemistry to Multipurpose Catalysis to Sustainable Chemistry

Angewandte Chemie (International Ed. in English). Jan, 2012  |  Pubmed ID: 22109976

Polymeric graphitic carbon nitride materials (for simplicity: g-C(3)N(4)) have attracted much attention in recent years because of their similarity to graphene. They are composed of C, N, and some minor H content only. In contrast to graphenes, g-C(3)N(4) is a medium-bandgap semiconductor and in that role an effective photocatalyst and chemical catalyst for a broad variety of reactions. In this Review, we describe the "polymer chemistry" of this structure, how band positions and bandgap can be varied by doping and copolymerization, and how the organic solid can be textured to make it an effective heterogenous catalyst. g-C(3)N(4) and its modifications have a high thermal and chemical stability and can catalyze a number of "dream reactions", such as photochemical splitting of water, mild and selective oxidation reactions, and--as a coactive catalytic support--superactive hydrogenation reactions. As carbon nitride is metal-free as such, it also tolerates functional groups and is therefore suited for multipurpose applications in biomass conversion and sustainable chemistry.

The Effect of Hydroxyapatite Presence on the Degree of Conversion and Polymerization Rate in a Model Self-etching Adhesive

Dental Materials : Official Publication of the Academy of Dental Materials. Mar, 2012  |  Pubmed ID: 22032933

The effect of hydroxyapatite (HAp) content on photopolymerization of a model self-etching adhesive was studied by using attenuated total reflectance Fourier transform infrared (ATR/FT-IR) spectroscopy.

Cloning and MRNA Expression Levels of GDF9, BMP15, and BMPR1B Genes in Prolific and Non-prolific Goat Breeds

Molecular Reproduction and Development. Jan, 2012  |  Pubmed ID: 22102530

Synthesis and Herbicidal Activities of Novel 3-(substituted Benzyloxy or Phenoxy)-6-methyl-4-(3-trifluoromethylphenyl)pyridazine Derivatives

Pest Management Science. Feb, 2012  |  Pubmed ID: 22076665

4-(3-Trifluoromethylphenyl)pyridazine represents a new series of compounds with bleaching and herbicidal activities.

Cell Adhesion on an Artificial Extracellular Matrix Using Aptamer-functionalized PEG Hydrogels

Biomaterials. Feb, 2012  |  Pubmed ID: 22079002

The development of an artificial extracellular matrix (ECM) is important to regenerative medicine because the ECM plays complex and dynamic roles in the regulation of cell behavior. In this study, nucleic acid aptamers were applied to functionalize hydrogels for mimicking the adhesion sites of the ECM. The results showed that nucleic acid aptamers could be incorporated into polyethylene glycol (PEG) hydrogels via free radical polymerization. The incorporation of the aptamers produced only a moderate effect on the mechanical properties of the PEG hydrogels. Importantly, the results also showed that the aptamers effectively induced cell type-specific adhesion to the PEG hydrogels without affecting cell viability. The cell adhesion was a function of the aptamer concentration, the spacer length and the cell seeding time. In addition, cell adhesion to the aptamer-functionalized hydrogel could be attenuated by means of aptamer inactivation in a physiological condition. Thus, aptamer-functionalized hydrogels are promising biomaterials for the development of artificial ECMs.

RROP2(186-533): a Novel Peptide Antigen for Detection of IgM Antibodies Against Toxoplasma Gondii

Foodborne Pathogens and Disease. Jan, 2012  |  Pubmed ID: 22085219

Toxoplasma gondii infections are prevalent in a wide range of mammalian hosts including humans. Infection in pregnant women may cause the transmission of parasite to the fetus that makes serious problems. IgM antibodies against Toxoplasma (Toxo-IgM) have been believed to be significant indicators for both recently acquired and congenital toxoplasmosis. So far, however, there has not been any recognized protein of T. gondii that specifically reacts to IgM antibodies. Here, an antigen exclusively for detection of IgM antibodies screened by two-dimensional electrophoresis and mass spectrometry has been reported. The study identified 13 Toxoplasma proteins probed by IgG antibodies and one (rhpotry protein 2 [ROP2]) by IgM antibodies with human sera of Toxo-IgM(-)-IgG(+) and -IgM(+)-IgG(-), respectively, which had been prescreened by Toxo-IgM and -IgG commercial kits from the suspected cases. Following cloning, expression, and purification of the fragment of ROP2(186-533), an enzyme-linked immunosorbent assay with rROP2(186-533) to measure IgM and IgG antibodies was developed. As a result, 100%(48/48) of sera with Toxo-IgM(+)-IgG(-)showed positive Toxo-IgM but none of them (0%) showed positive Toxo-IgG when rROP2(186-533) was used as antigen. Neither Toxo-IgG nor Toxo-IgM antibodies were found when tested with 59 sera of Toxo-IgM(-)-IgG(+). These results indicate that rROP2(186-533) could be used as an antigen that specifically capture Toxo-IgM antibodies and may have a high potential in the serological diagnosis of both acute acquired and congenital toxoplasmosis.

NFBD1/MDC1 is a Protein of Oncogenic Potential in Human Cervical Cancer

Molecular and Cellular Biochemistry. Jan, 2012  |  Pubmed ID: 21853275

A large nuclear protein of 2089 amino acids, NFBD1/MDC1 has recently been implicated in tumorigenesis and tumor growth. In this study, we investigated its expression in cervical cancers and explored its function using gene knockdown approaches. We report here that NFBD1 expression is substantial increased in 24 of 39 cases (61.5%) of cervical cancer tissues at the mRNA level and in 35 of 60 cases (58.3%) at the protein level compared with the case matched normal tissues. Tumors with higher grade of malignancy tend to have higher levels of NFBD1 expression. By infecting cells with retroviruses expressing NFBD1 shRNA, we successfully knocked down NFBD1 expression in cervical cancer cell lines HeLa, SiHa, and CaSki. NFBD1 knockdown cells display significant growth inhibition, cell cycle arrest, higher apoptotic rate, and enhanced sensitivity to adriamycin. Furthermore, NFBD1 knockdown also inhibits the growth of HeLa cells in nude mice. Western blot analyses further revealed that NFBD1 knockdown induced Bax, Puma, and Noxa while down-regulating Bcl-2; it also up-regulated cytochrome C and activated caspases 3 and 9. Therefore, the function of NFBD1 may be involved in the CDC25C-CyclinB1/CDC2 pathway at the G2/M checkpoint, and the cytochrome C/caspase 3 apoptotic pathway. Since expression of NFBD1 seems to be related to the oncogenic potential of cervical cancer, and suppression of its expression can inhibit cancer cell growth both in vitro and in vivo, NFBD1 may be a potential therapeutic target in human cervical cancer.

Improved Degree of Conversion of Model Self-etching Adhesives Through Their Interaction with Dentine

Journal of Dentistry. Jan, 2012  |  Pubmed ID: 22024375

To investigate the correlation of the chemical interaction between model self-etching adhesives and dentine with the degree of conversion (DC) of the adhesives.

A Large Sample Volume Magic Angle Spinning Nuclear Magnetic Resonance Probe for in Situ Investigations with Constant Flow of Reactants

Physical Chemistry Chemical Physics : PCCP. Feb, 2012  |  Pubmed ID: 22025270

A large-sample-volume constant-flow magic angle sample spinning (CF-MAS) NMR probe is reported for in situ studies of the reaction dynamics, stable intermediates/transition states, and mechanisms of catalytic reactions. In our approach, the reactants are introduced into the catalyst bed using a fixed tube at one end of the MAS rotor while a second fixed tube, linked to a vacuum pump, is attached at the other end of the rotor. The pressure difference between both ends of the catalyst bed inside the sample cell space forces the reactants flowing through the catalyst bed, which improves the diffusion of the reactants and products. This design allows the use of a large sample volume for enhanced sensitivity and thus permitting in situ(13)C CF-MAS studies at natural abundance. As an example of application, we show that reactants, products and reaction transition states associated with the 2-butanol dehydration reaction over a mesoporous silicalite supported heteropoly acid catalyst (HPA/meso-silicalite-1) can all be detected in a single (13)C CF-MAS NMR spectrum at natural abundance. Coke products can also be detected at natural (13)C abundance and under the stopped flow condition. Furthermore, (1)H CF-MAS NMR is used to identify the surface functional groups of HPA/meso-silicalite-1 under the condition of in situ drying. We also show that the reaction dynamics of 2-butanol dehydration using HPA/meso-silicalite-1 as a catalyst can be explored using (1)H CF-MAS NMR.

Fusion of Human Umbilical Cord Mesenchymal Stem Cells with Esophageal Carcinoma Cells Inhibits the Tumorigenicity of Esophageal Carcinoma Cells

International Journal of Oncology. Feb, 2012  |  Pubmed ID: 22002183

Prior studies on the biology and therapeutic application of human stem cells in human malignancies have reported mixed results. Some evidence shows the use of stem cell transplantation is an important tool in the treatment of several hematologic and non-hematologic malignancies while some others suggest both human stem cells and mature stromal cells can contribute to the development and growth of human malignancies. Aiming to provide more evidence on this controversial issue, we investigated the effect of cell fusion of mesenchymal stem cells with esophageal carcinoma cells on tumorigenesis. Results suggest that artificial fusion of human umbilical cord mesenchymal stem cells with esophageal carcinoma cells resulted in hybrids with declined cell growth, increased apoptosis and suppressed tumorigenicity. The comparison of gene expression profiles of human mesenchymal stem cells, esophageal carcinoma cells and hybrids indicated that fusion induced activation of apoptosis. Furthermore, the expression of DUSP6/MKP3 in MAPK pathway increased strikingly and the exogenous overexpression confirmed the growth suppression. Our results demonstrate fusion of human mesenchymal stem cells with esophageal carcinoma cells induced apoptosis and benign transdifferentiation rather than reprogramming to cancer stem cells.

A Dynamic Hybrid Framework for Constrained Evolutionary Optimization

IEEE Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the IEEE Systems, Man, and Cybernetics Society. Feb, 2012  |  Pubmed ID: 21824851

Based on our previous work, this paper presents a dynamic hybrid framework, called DyHF, for solving constrained optimization problems. This framework consists of two major steps: global search model and local search model. In the global and local search models, differential evolution serves as the search engine, and Pareto dominance used in multiobjective optimization is employed to compare the individuals in the population. Unlike other existing methods, the above two steps are executed dynamically according to the feasibility proportion of the current population in this paper, with the purpose of reasonably distributing the computational resource for the global and local search during the evolution. The performance of DyHF is tested on 22 benchmark test functions. The experimental results clearly show that the overall performance of DyHF is highly competitive with that of a number of state-of-the-art approaches from the literature.

Crystal Structure of the Extracellular Domain of Human Myelin Protein Zero

Proteins. Jan, 2012  |  Pubmed ID: 21971831

SNP Rs2470152 in CYP19 is Correlated to Aromatase Activity in Chinese Polycystic Ovary Syndrome Patients

Molecular Medicine Reports. Jan, 2012  |  Pubmed ID: 21972004

CYP19 encodes aromatase, a key enzyme essential for estrogen biosynthesis. Single nucleotide polymorphism (SNP) rs2470152 in CYP19 is associated with serum estradiol (E2) level and the E2/T (estradiol/testosterone) ratio. A case‑control study including 661 individuals [364 polycystic ovary syndrome (PCOS) patients and 297 controls] was conducted to assess the association of SNP rs2470152 with PCOS. The subjects were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Hormone levels were analyzed among various genotypes. The genotypic distributions of rs2470152 did not differ in PCOS patients when compared to the controls. However, differences in the E2/T ratio were detected, exhibiting a lower ratio in the heterozygous TC genotype in PCOS patients (p=0.01036) and controls (p=0.000). Testosterone levels also differed between the three genotypes of PCOS patients (p=0.00625), with a higher level in the TC genotype. Therefore, rs2470152 in CYP19 was not a major etiological factor for PCOS; however, the heterozygous TC genotype may inhibit aromatase activity, resulting in hyperandrogenism, particularly in PCOS patients.

P38 MAPK Regulates Calcium Signal-mediated Lipid Accumulation Through Changing VDR Expression in Primary Preadipocytes of Mice

Molecular Biology Reports. Mar, 2012  |  Pubmed ID: 21701827

In the present study we have examined whether p38 mitogen activated protein kinase (p38 MAPK) signal pathway interacts with calcium signal on lipid accumulation in primary preadipocytes of mice. The primary preadipocytes were treated with p38 MAPK inhibitor SB203580, blockers and excitomotors of calcium channel for 24 h, respectively. Intracellular triglyceride (TG) content was measured by triglyceride kit and lipid accumulation was determined by Oil Red O staining. Meanwhile, the mRNA expressions of peroxisome proliferators-activated receptor gamma (PPARγ) gene, fatty acid synthetase (FAS) gene, lipoprotein lipase (LPL) gene, vitamin D receptor (VDR) gene and extracellular Ca(2+)-sensing receptor (CaSR) gene were analyzed with real-time PCR. The protein content and phosphorylation of VDR and p38 were tested with Western Blotting. The data showed that intracellular TG content and the mRNA expression levels of PPARγ, FAS, LPL in N group and L group as well as FAS, LPL in C group were increased significantly (P < 0.01) compared to the control. On the contrary, intracellular TG content and the mRNA expression levels of PPARγ, FAS in B group as well as intracellular TG content and PPARγ, FAS, LPL in SB group and B+SB group were decreased significantly (P < 0.01). VDR mRNA expression and protein content were decreased in B, C, and SB added groups (P < 0.01). In addition, p38 phosphorylation levels increased in N and L groups (P < 0.01) and decreased in SB added groups (P < 0.01). These findings suggest that p38 MAPK pathway through regulating VDR mRNA expression participates in mediation of calcium signal and affects calcium signal regulating lipid accumulation in mice preadipocytes through changing PPARγ, FAS and LPL mRNA expression. In addition, calcium signal have a feedback effect in phosphorylation of p38.