[Studies on Extraction Process of Radix Platycodi]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Jun, 2002  |  Pubmed ID: 12583340

The orthogonal design was used to optimize the extraction process of Radix Platycodi with content of total saponin and yield of the extract as markers. Factors that have been chosen were alcohol concentration, alcohol consumption, extraction times and extraction time. Each factor has three levels. The result showed that the optimum extraction condition obtained was 70% alcohol, 3 times the amount of material, refluxing for 5 times, 60 minutes each time, the optimized process was stable and workable.

Sensitivity Function-based Model Reduction: A Bacterial Gene Expression Case Study

Biotechnology and Bioengineering. Oct, 2002  |  Pubmed ID: 12209775

Mathematical models used to predict the behavior of genetically modified organisms require 1). a (rather) large number of state variables, and 2). complicated kinetic expressions containing a large number of parameters. Since these models are hardly identifiable and of limited use in model-based optimization and control strategies, a generic methodology based on sensitivity function analysis is presented to reduce the model complexity at the level of the kinetics, while maintaining high prediction power. As a case study to illustrate the method and results obtained, the influence of the dissolved oxygen concentration on the cytN gene expression in the bacterium Azospirillum brasilense Sp7 is modeled. As a first modeling approach, available mechanistic knowledge is incorporated into a mass balance equation model with 3 states and 14 parameters. The large differences in order of magnitude of the model parameters identified on the available experimental data indicate 1). possible structural problems in the kinetic model and, associated with this, 2). a possibly too high number of model parameters. A careful sensitivity function analysis reveals that a reduced model with only seven parameters is almost as accurate as the original model.

Cutting Edge: Salmonella AvrA Effector Inhibits the Key Proinflammatory, Anti-apoptotic NF-kappa B Pathway

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2002  |  Pubmed ID: 12218096

Secreted prokaryotic effector proteins have evolved to modulate the cellular functions of specific eukaryotic hosts. Generally, these proteins are considered virulence factors that facilitate parasitism. However, in certain plant and insect eukaryotic/prokaryotic relationships, effector proteins are involved in the establishment of commensal or symbiotic interactions. In this study, we report that the AvrA protein from Salmonella typhimurium, a common enteropathogen of humans, is an effector molecule that inhibits activation of the key proinflammatory NF-kappaB transcription factor and augments apoptosis in human epithelial cells. This activity is similar but mechanistically distinct from that described for YopJ, an AvrA homolog expressed by the bacterial pathogen Yersinia. We suggest that AvrA may limit virulence in vertebrates in a manner analogous to avirulence factors in plants, and as such, is the first bacterial effector from a mammalian pathogen that has been ascribed such a function.

Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-beta-selective Ligand, Diarylpropionitrile

Molecular Endocrinology (Baltimore, Md.). Feb, 2003  |  Pubmed ID: 12554752

Although the two subtypes of the human estrogen receptor (ER), ERalpha and ERbeta, share only 56% amino acid sequence identity in their ligand binding domain (LBD), the residues that surround the ligand are nearly identical; nevertheless, subtype-selective ligands are known. To understand the molecular basis by which diarylpropionitrile (DPN), an ERbeta-selective ligand, is able to discriminate between the two ERs, we examined its activity on ER mutants and chimeric constructs generated by DNA shuffling. The N-terminal region of the ERbeta LBD (through helix 6) appears to be fully responsible for the ERbeta selectivity of DPN. In fact, a single ERalpha point mutation (L384M) was largely sufficient to switch the DPN response of this ER to that of the ERbeta type, but residues in helix 3 are also important in achieving the full ERbeta selectivity of DPN. Using molecular modeling, we found an energetically favorable fit for the S-DPN enantiomer in ERbeta, in which the proximal phenol mimics the A ring of estradiol, and the nitrile engages in stabilizing interactions with residues in the ligand-binding pocket of ERbeta. Our findings highlight that a limited number of critical interactions of DPN with the ERbeta ligand-binding pocket underlie its ER subtype-selective character.

[Structural Characteristics of Phytoplankton Community During Harmful Algae Bloom in Jiaozhou Bay]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Nov, 2003  |  Pubmed ID: 14997657

Based on two days survey in August, 2001 in Jiaozhou Bay, the structural characteristics of phytoplankton community during harmful algae bloom was studied. The results showed that phytoplankton community was composed mainly by the coastal warm species, which were dominated by the diatom including 37 species. Only 7 Pyrrorophya and 1 Chlorophyta species were identified. The highest value of species number appeared in the central of Jiaozhou Bay, which included 37 species, but the lowest value in the edge of Jiaozhou Bay was only 10 species. The highest value of cell abundance appeared in the eastern waters of Jiaozhou Bay, being 6.96 x 10(3) cell.m-3, and the lowest value appeared in the mouth of Jiaozhou Bay, being 3.18 x 10(6) cell.m-3. The diversity and eveness of phytoplankton was the lowest in the eastern waters of Jiaozhou bay, but was higher in the mouth and the central of Jiaozhou Bay. Water mass movement and eutrophication were the main factors affecting the distribution of phytoplankton community in Jiaozhou Bay.

Cloning of Chicken Anemia Virus Vp3 Gene and Apoptosis Inductive Effect of Vp3 Gene in Vitro

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. 2003  |  Pubmed ID: 15015627

Using PCR technique, the vp3 gene of chicken anemia virus (CAV) was cloned into the eukaryotic expression vector pcDNA3 to construct a recombinant pcDNA-vp3. Restriction enzyme digestion and sequencing analysis revealed that CAV vp3 gene was correctly inserted into the blank vector pcDNA3. After LipofectAMINE-mediated transfection in vitro with pcDNA-vp3 and pcDNA3 respectively, the total mRNA was extracted from liver carcinoma cell lines HepG2 and diploid cell line L-02, and RT-PCR was performed afterward. The results of RT-PCR suggested that vp3 gene was expressed in these two cell lines. At the same time, using in situ apoptotic detection assay, TUNEL kits, the apoptotic cells were found in pcDNA-vp3 transfected HepG2, but not in mock transfected cell lines. VP3 could induce cell death by apoptosis in cancer cell lines, but not in diploid cell lines. All the results indicated that CAV vp3 gene, a potential therapeutic agents, has the potential of being used for cancer treatment.

DNA Shuffling Method for Generating Estrogen Receptor Alpha and Beta Chimeras in Yeast

BioTechniques. Feb, 2003  |  Pubmed ID: 12613251

To facilitate our study of the molecular basis for the estrogen receptor (ER) subtype selectivity of novel ligands, we used DNA shuffling to construct chimeric ERs having ligand binding domains derived from both ER alpha and ER beta. The efficiency of chimera generation was low with traditional DNA shuffling protocols. Furthermore, ER ligand binding domain sequences lack convenient restriction sites for introducing chimeric ligand binding domain sequences into expression vectors. To overcome these problems, we developed a modified strategy whereby chimeric sequences were exclusively amplified from among the reassembled products from DNA shuffling using a special pair of PCR primers whose 3' ends specifically match the alpha and beta sequences, respectively, and whose 5' ends match sequences outside the ER beta ligand binding domain. When chimeric ligand binding domain DNA sequences, amplified with these primers, were co-transformed into a yeast strain with a linearized expression vector for ER beta, an active expression vector was produced by homologous recombination. Twenty-two different crossover sites were found; most occurred when there was a stretch of eight or more identical base pairs in both sequences, and many were concentrated in the regions important for studying ligand binding and transactivation. This method should prove to be useful for generating chimeric gene products from parent templates that share relatively low sequence identity.

Genetic Diversity of Microsatellite Loci in Fifty-six Chinese Native Pig Breeds

Yi Chuan Xue Bao = Acta Genetica Sinica. Mar, 2003  |  Pubmed ID: 12812088

The genetic diversity of fifty-six indigenous pig breeds in China, and three introduced pig breeds (Duroc, Landrace and Large White) was surveyed using twenty-seven microsatellites recommended by the International Society for Animal Genetics (IS-AG) and Food and Agriculture Organization (FAO). By means of the allele frequencies, mean heterozygosity, effective number of alleles, estimator of gene differentiation, polymorphism information content, genetic distance and dendrogram analysis, the genetic variability and population structure of native pig breeds were estimated. Genetic variabilities within native pig breeds are as follows: Effective number of alleles vary from 2.12 to 9.03, from 0.44 to 0.87 for mean heterozygosity, from 0.39 to 0.86 for polymorphism information content. Nei's genetic distance and Nei's standard genetic distance were estimated and used to construct UPGMA and NJ dendrograms, which were evaluated by the bootstrap test. Fifty-six Chinese indigenous pig breeds were clustered into twelve groups based on the dendrogram. Compared with the classification in Pig Breeds in China, I, II and III groups in the study are equivalent to North-China type, IV group basically accords with Lower-Changjiang River Basin type, V, VI, VII, VIII and IX groups quite correspond with Central-China type, X and XI group largely correspond to South-China type, the last group, XII is equal to South-west type at large. Suggestions that the conservation farms together with conservation areas are appropriate methods for the preservation of native pig breeds in our country were proposed. The results could provide basic molecular data for the research on the germplasm characteristics of local breeds in our country and scientific basis for the conservation and utilization of those breeds.

Nuclear Remodelling and the Developmental Potential of Nuclear Transferred Porcine Oocytes Under Delayed-activated Conditions

Zygote (Cambridge, England). May, 2003  |  Pubmed ID: 12828416

It is still unclear whether nuclear envelope breakdown and premature chromosome condensation are essential for the reprogramming of the donor nucleus following somatic nuclear transfer. To address this, we determined the ability of delayed-activated or simultaneously activated porcine oocytes to undergo nuclear remodelling and development following somatic cell nuclear transfer. A small microtubule aster was observed in association with decondensed chromatin following nuclear transfer, suggesting the introduction of a somatic cell centrosome. In the delayed-activated condition, most fibroblast nuclei divided into two chromosome masses and two pronuclear-like structures following transfer into oocytes. In contrast, fibroblast nuclei in the simultaneously activated condition formed a large, swollen, pronuclear-like structure. Microtubule asters were organised in the vicinity of the nucleus regardless of the number of nuclei. More reconstructed oocytes developed to the blastocyst stage in the delayed-activated condition than in the simultaneously activated condition (p < 0.05). Nine piglets were born from two recipient sows following transfer of delayed-activated reconstructed oocytes, while none developed to full term in the simultaneously activated condition. Fingerprint analysis showed that the PCR-RFLP patterns of the nine offspring were identical to that of the donor pig. These results suggest that the activation of recipient oocytes during nuclear transfer probably relates to the nuclear remodelling process, which can affect the ability of embryos created by somatic cell nuclear transfer to develop.

Spiral CT in Gastric Carcinoma: Comparison with Barium Study, Fiberoptic Gastroscopy and Histopathology

World Journal of Gastroenterology : WJG. Jul, 2003  |  Pubmed ID: 12854130

To evaluate spiral computed tomography (CT) including virtual gastroscopy for diagnosis of gastric carcinoma in comparison with upper gastrointestinal series (UGI), fiberoptic gastroscopy (FG) and histopathology.

Preventive Effect of Hydrotalcite on Gastric Mucosal Injury in Rats Induced by Taurocholate

World Journal of Gastroenterology : WJG. Jul, 2003  |  Pubmed ID: 12854134

To study the preventive effect of hydrotalcite on gastric mucosal injury in rat induced by taurocholate, and to investigate the relationship between the protective mechanism of hydrotalcite and the expression of trefoil factor family 2 (TFF2) mRNA and c-fos protein.

Plasma Membrane Phospholipid Scramblase 1 Promotes EGF-dependent Activation of C-Src Through the Epidermal Growth Factor Receptor

The Journal of Biological Chemistry. Sep, 2003  |  Pubmed ID: 12871937

Phospholipid scramblase (PLSCR1) is a multiply palmitoylated, calcium-binding endofacial membrane protein proposed to mediate transbilayer movement of plasma membrane phospholipids. PLSCR1 is a component of membrane lipid rafts and has been shown to both physically and functionally interact with activated epidermal growth factor (EGF) receptors and other raft-associated cell surface receptors. Cell stimulation by EGF results in Tyr phosphorylation of PLSCR1, its association with both Shc and EGF receptors, and rapid cycling of PLSCR1 between plasma membrane and endosomal compartments. We now report evidence that upon EGF stimulation, PLSCR1 is phosphorylated by c-Src, within the tandem repeat sequence 68VYNQPVYNQP77. The in vivo interaction between PLSCR1 and Shc requires the Src-mediated phosphorylation on tyrosines 69 and 74. In in vitro pull down studies, phosphorylated PLSCR1 was found to bind directly to Shc through the phosphotyrosine binding domain. Consistent with the potential role of PLSCR1 in growth factor signaling pathways, granulocyte precursors derived from mice deficient in PLSCR1 show impaired proliferation and maturation under cytokine stimulation. Using PLSCR1-/- embryonic fibroblasts and kidney epithelial cells, we now demonstrate that deletion of PLSCR1 from the plasma membrane reduces the activation of c-Src by EGF, implying that PLSCR1 normally facilitates receptor-dependent activation of this kinase. We propose that PLSCR1, through its interaction with Shc, promotes Src kinase activation through the EGF receptor.

[Microzooplankton Herbivory During Red Tide-frequent-occurrence Period in Spring in the East China Sea]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jul, 2003  |  Pubmed ID: 14587325

Five typical stations in the Changjiang River estuary and adjacent waters of the East China Sea, were chosen as the sites to study phytoplankton growth and microzooplankton ingestion by on-deck-incubation dilution experiment from 25th April to 25th May 2002. The results showed that microzooplankton ingestion was a key process for controlling red tide event. Strombidium sulcatum, Noctiluca scintillans and Mesodinium robudium were dominant microzooplankton species. In this study, the ingestion rate of microzooplankton ranged from 0.28 to 1.13 d-1; ingestion pressure on percentage of phytoplankton standing crop ranged from 35.14% to 811.69%; ingestion pressure on percentage of potential production ranged from 74.04% to 203.25%; and ingestion rate of phytoplankton carbon ranged from 9.58 to 97.91 C.L-1.d-1. The microzooplankton grazing rate, ingestion pressure on percentage of phytoplankton standing crop, and ingestion rate of phytoplankton carbon were higher near coastal area, but lower at open sea, and the microzooplankton ingestion pressure on percentage of phytoplankton potential production was no the contrary. Compared with the similar studies around the world, the ingestion pressure of microzooplankton in the East China Sea was at a higher level. The primary deduction was that Strombidium was the key microzooplankton species on controlling Prorocentrum dentatum, the most important red tide species in the East China Sea.

Effects of a Collective Spin Resonance Mode on the Scanning Tunneling Microscopy Spectra of D-wave Superconductors

Physical Review Letters. Jan, 2004  |  Pubmed ID: 14754011

A high-energy spin resonance mode is known to exist in many high-temperature superconductors. Motivated by recent scanning tunneling microscopy experiments in superconducting Bi(2)Sr(2)CaCu(2)O(8+delta), we study the effects of this resonance mode on the local density of states (LDOS). The coupling between the electrons in a d-wave superconductor and the resonance mode produces high-energy peaks in the LDOS, which displays a two-unit-cell periodic modulation around a nonmagnetic impurity. This suggests a new means to not only detect the dynamical spin collective mode but also study its coupling to electronic excitations.

Bacterial Activation of Beta-catenin Signaling in Human Epithelia

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jul, 2004  |  Pubmed ID: 14764450

The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being nonpathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect proinflammatory pathways but also influence beta-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoP(c) activates the beta-catenin signaling pathway of human epithelia via a blockade of beta-catenin degradation. Normal beta-catenin ubiquitination necessary for constitutive beta-catenin degradation is abolished, allowing the accumulation and translocation of beta-catenin to the nucleus. Transcriptional activation mediated by the beta-catenin/T cell factor complex increases c-myc expression and enhances cell proliferation. We also show that the Salmonella effector protein AvrA is involved in modulating this beta-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence beta-catenin signaling and cell growth control in a manner previously unsuspected.

Allosteric Control of Ligand Selectivity Between Estrogen Receptors Alpha and Beta: Implications for Other Nuclear Receptors

Molecular Cell. Feb, 2004  |  Pubmed ID: 14967140

Allosteric communication between interacting molecules is fundamental to signal transduction and many other cellular processes. To better understand the relationship between nuclear receptor (NR) ligand positioning and the formation of the coactivator binding pocket, we investigated the determinants of ligand selectivity between the two estrogen receptor subtypes ERalpha and ERbeta. Chimeric receptors and structurally guided amino acid substitutions were used to demonstrate that distinct "hot spot" amino acids are required for ligand selectivity. Residues within the ligand binding pocket as well as distal secondary structural interactions contribute to subtype-specific positioning of the ligand and transcriptional output. Examination of other NRs suggests a mechanism of communication between the ligand and coactivator binding pockets, accounting for partial agonist and dimer-specific activity. These results demonstrate the importance of long-range interactions in the transmission of information through the ligand binding domain as well as in determining the ligand selectivity of closely related NR receptor subtypes.

[Growth of Platymonas Helgolandica Var. Tsingtaoensis, Cylindrotheca Closterium and Karenia Mikimotoi and Their Survival Strategies Under Different N/P Ratios]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Nov, 2004  |  Pubmed ID: 15707326

In this study, laboratory culture experiments were carried out in a batch culture system, with the focus on the effect of different N/P ratios (1:1, 4:1, 16:1, 80:1 and 160:1) on the growth of Platymonas helgolandica var. tsingtaoensis, Cylindrotheca closterium and Karenia mikimotoi. The cell abundance, growth rate, and chlorophyll a and protein contents were measured every 24 h for one week. The results showed that N/P ratio significantly affected the growth of three kinds of algae. Cylindrotheca closterium grew fastest under 160:1 N/P ratio, while Platymonas helgolandica var. tsingtaoensis and Karenia mikimotoi grew fastest under 4:1 and 80:1 N/P ratio, respectively. The maximum cell density of the phytoplankton was mainly influenced by cell size and specific growth rate, the synthesis of chlorophyll a was mainly affected by nitrogen, and high N/P ratio benefited the increase of chlorophyll a content. The protein concentration in cells correlated significantly with N/P ratio, cell size and cell period. As for survival strategy, Cylindrotheca closterium showed obvious features of fast-reproductioned r-selective species, whereas Platymonas helgolandica var. tsingtaoensis and Karenia mikimotoi were most likely to be the more competitive K-selected species.

CDw75 is a Significant Histopathological Marker for Gastric Carcinoma

World Journal of Gastroenterology : WJG. Jun, 2004  |  Pubmed ID: 15162552

To study the expression of CDw75 in patients with gastric carcinoma and to correlate CDw75 expression with progression of the tumor.

Microzooplankton Grazing on Phytoplankton in Summer in the Jiaozhou Bay, China

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jul, 2004  |  Pubmed ID: 15506108

With dilution method, this paper studied the microzooplankton grazing on phytoplankton inside, outside and in a harbor area of the Jiaozhou Bay during June and July 2002. The dominant phytoplankton species outside and inside the bay were Cylindrotheca closterium and Skeletonema costatum, while the samples in the harbor had Skeletonema costatum, Eucampia zodiacus, and Chaetoceros curvisetus as the dominant species. The dominant microzooplankton species outside and inside the Jiaozhou Bay were Tintinnopsis beroidea and unidentified Strombidium sp., while in the harbor, Strombidium sp. was the predominant microzooplankton species coexisted with few T. beroidea. The grazing rate of microzooplankton was 0.96 and 1.20 d(-1) outside the bay, 1.33 d(-1) inside the bay, and 0.36 d(-1) in the harbor. The grazing rates of microzooplankton and the consumption percentages of potential primary production increased in turn from harbor area, outside the bay, to inside the bay. They were 74% and 84% outside the bay, 93% inside the bay, and 53% in the harbor. The ingestion rate of phytoplankton carbon by microzooplankton was the highest in the harbor, with a value of 281 mgC x m(-3) x d(-1), the next was inside the bay, with a value of 102 mgC x m(-3) x d(-1), and the lowest was outside the bay, ranged from 31 to 49 mgC x m(-3) x d(-1). It seems that the phytoplankton community size structure and grazing behaviors of dominant microzooplankton species are the causes for these grazing differences. Compared with the similar studies in other bays around the world, the grazing pressure of microzooplankton in the Jiaozhou Bay is at the middle levels.

Phytoplankton Succession During a Red Tide of Skeletonema Costatum in Jiaozhou Bay of China

Marine Pollution Bulletin. Jan, 2005  |  Pubmed ID: 15664038

Experimental Study and Clinical Observation of Minimum-contact Plate in Long Bone Fracture

Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi / Chinese Medical Association. Apr, 2005  |  Pubmed ID: 15769310

To study the mechanical properties and the clinical results of minimum-contact plate in the treatment of fractures.

Crosstalk Between NF-kappaB and Beta-catenin Pathways in Bacterial-colonized Intestinal Epithelial Cells

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jul, 2005  |  Pubmed ID: 15790758

Salmonella-epithelial cell interactions are known to activate the proinflammatory NF-kappaB signaling pathway and have recently been found to also influence the beta-catenin signaling pathway, an important regulator of epithelial cell proliferation and differentiation. Here, using polarized epithelial cell models, we demonstrate that these same bacteria-mediated effects also direct the molecular crosstalk between the NF-kappaB and beta-catenin signaling pathways. Convergence of these two pathways is a result of the direct interaction between the NF-kappaB p50 subunit and beta-catenin. We show that PhoP(c), the avirulent derivative of a wild-type Salmonella strain, attenuates NF-kappaB activity by stabilizing the association of beta-catenin with NF-kappaB. In cell lines expressing constitutively active beta-catenin, IkappaBalpha protein was indirectly stabilized and NF-kappaB activity was repressed after wild-type Salmonella colonization. Accordingly, constitutively active beta-catenin was found to inhibit the secretion of IL-8. Thus our findings strongly suggest that the crosstalk between the beta-catenin and NF-kappaB signaling pathways is an important regulator of intestinal inflammation.

Global Proteome Discovery Using an Online Three-dimensional LC-MS/MS

Journal of Proteome Research. May-Jun, 2005  |  Pubmed ID: 15952726

We have developed a proteomics technology featuring on-line three-dimensional liquid chromatography coupled to tandem mass spectrometry (3D LC-MS/MS). Using 3D LC-MS/MS, the yeast-soluble, urea-solubilized peripheral membrane and SDS-solubilized membrane protein samples collectively yielded 3019 unique yeast protein identifications with an average of 5.5 peptides per protein from the 6300-gene Saccharomyces Genome Database searched with SEQUEST. A single run of the urea-solubilized sample yielded 2255 unique protein identifications, suggesting high peak capacity and resolving power of 3D LC-MS/MS. After precipitation of SDS from the digested membrane protein sample, 3D LC-MS/MS allowed the analysis of membrane proteins. Among 1221 proteins containing two or more predicted transmembrane domains, 495 such proteins were identified. The improved yeast proteome data allowed the mapping of many metabolic pathways and functional categories. The 3D LC-MS/MS technology provides a suitable tool for global proteome discovery.

The Hydroxyurea-induced Small GTP-binding Protein SAR Modulates Gamma-globin Gene Expression in Human Erythroid Cells

Blood. Nov, 2005  |  Pubmed ID: 15985540

Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identified an HU-induced small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR) protein, in adult erythroid cells using differential display. Stable SAR expression in K562 cells increased gamma-globin mRNA expression and resulted in macrocytosis. The cells appeared immature. SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing arrest in G1/S, apoptosis, and delay of maturation, cellular changes consistent with the previously known effects of HU on erythroid cells. SAR also enhanced both gamma- and beta-globin transcription in primary bone marrow CD34+ cells, with a greater effect on gamma-globin than on beta-globin. Although up-regulation of GATA-2 and p21 was observed both in SAR-expressing cells and HU-treated K562 cells, phosphatidylinositol 3 (PI3) kinase and phosphorylated ERK were inhibited specifically in SAR-expressing cells. These data reveal a novel role of SAR distinct from its previously known protein-trafficking function. We suggest that SAR may participate in both erythroid cell growth and gamma-globin production by regulating PI3 kinase/extracellular protein-related kinase (ERK) and GATA-2/p21-dependent signal transduction pathways.

[Effect of Thickness and Shade of Porcelain of Ceramometal Restorations on Color of Gingival Porcelain]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Jun, 2005  |  Pubmed ID: 16078471

The purpose of this study was to evaluate the color changes of gingival porcelain through varying thickness and shade of porcelain of ceramometal restorations.

[Analysis of Chromatic Value of Gingival Porcelain]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Aug, 2005  |  Pubmed ID: 16178183

To study the distribution of the chromatic value of gingival porcelains.

Feasibility on Systemic Delivery of Asialoorosomucoid Complex to Hepatic Origin Cells Mediated by Asialoglycoprotein Receptor

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. 2005  |  Pubmed ID: 16201257

Receptor mediated gene delivery is a new gene transfer strategy. Asialoglycoprotein receptor (ASGP-R), the receptor of asialoorosomucoid (Asor), is specially expressed on the surface of hepatocyte. In this paper, the nuclide 131I was combined with Asor to form a kind of soluble nuclide-protein complex, which can be specifically endocytosed into hepatocyte by ASGP-R. After in travenous injection of the complex into experimental animals, the deposition of Asor in vivo and the targeting quality of hepatocyte was detected by ECT. This research testified the feasibility of targeting Asor complex delivery to hepatocyte mediated by ASGP-R in vivo, and provided foundation for the genetic diagnosis and gene therapy of hepatic cell-related diseases.

Interactions Between Coilin and PIASy Partially Link Cajal Bodies to PML Bodies

Journal of Cell Science. Nov, 2005  |  Pubmed ID: 16219678

The eukaryotic nucleus contains a variety of dynamic structures, yet studies into the functional relationship of one type of subnuclear domain to another have been limited. For example, PML bodies and Cajal bodies associate, but the functional consequence of this association and the mediating factors are unknown. Here we report that an associated PML body/Cajal body can co-localize to an snRNA gene locus, with the Cajal body invariably situated between the PML body and the snRNA locus. Binding studies demonstrate that coilin (a Cajal body protein) directly interacts with PIASy (a PML body protein). Cell biological experiments using coilin and PIASy knockout cell lines demonstrate that interactions between coilin and PIASy account in part for the observed association of Cajal bodies with PML bodies. When the PIASy interaction region on coilin is deleted, the frequency of the association between Cajal bodies and PML bodies is reduced. These studies provide another example of coilin's role in the functional organization of the nucleus.

Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

Physical Review Letters. Sep, 2005  |  Pubmed ID: 16241696

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.

Chitosan-glycerol Phosphate/blood Implants Improve Hyaline Cartilage Repair in Ovine Microfracture Defects

The Journal of Bone and Joint Surgery. American Volume. Dec, 2005  |  Pubmed ID: 16322617

Microfracture is a surgical procedure that is used to treat focal articular cartilage defects. Although joint function improves following microfracture, the procedure elicits incomplete repair. As blood clot formation in the microfracture defect is an essential initiating event in microfracture therapy, we hypothesized that the repair would be improved if the microfracture defect were filled with a blood clot that was stabilized by the incorporation of a thrombogenic and adhesive polymer, specifically, chitosan. The objectives of the present study were to evaluate (1) blood clot adhesion in fresh microfracture defects and (2) the quality of the repair, at six months postoperatively, of microfracture defects that had been treated with or without chitosan-glycerol phosphate/blood clot implants, using a sheep model.

[Relationship Between Trauma Score and Complications and Interventions of Traumatic Patients in Department of Emergency Medicine]

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue = Chinese Critical Care Medicine = Zhongguo Weizhongbing Jijiuyixue. Jan, 2006  |  Pubmed ID: 16464385

To investigate the relationship between trauma score (TS) and complications and interventional strategies in trauma patients in the Emergency Department.

Increased NF-kappaB Activity in Fibroblasts Lacking the Vitamin D Receptor

American Journal of Physiology. Endocrinology and Metabolism. Aug, 2006  |  Pubmed ID: 16507601

1,25-Dihydroxyvitamin D [1,25(OH)2D3] is known to have anti-inflammatory activity; however, the molecular mechanism remains poorly defined. Here we show that the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-kappaB activation, a pathway essential for inflammatory response. In mouse embryonic fibroblasts (MEFs) derived from VDR-/- mice, the basal level of kappaB inhibitor (IkappaB) alpha protein was markedly decreased compared with VDR+/- MEFs; however, degradation of IkappaBalpha and its phosphorylation in response to TNF-alpha treatment or Salmonella infection were not altered in VDR-/- cells, neither were the levels of IkappaB kinase-alpha and IkappaB kinase-beta proteins. Consistent with IkappaBalpha reduction, p65 accumulation in the nucleus was markedly increased in unstimulated VDR-/- cells. In addition, the physical interaction between VDR and p65 was absent in VDR-/- MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in nuclear p65 DNA binding and NF-kappaB transcriptional activity; consistently, induction of IL-6 by TNF-alpha or IL-1beta was much more robust in VDR-/- than in VDR+/- cells, indicating that VDR-/- cells are more susceptible to inflammatory stimulation. Therefore, cells lacking VDR appear to be more proinflammatory due to the intrinsic high NF-kappaB activity. The reduction of IkappaBalpha in VDR-/- MEFs may be partially explained by the lack of VDR-mediated stabilization of IkappaBalpha by 1,25(OH)2D3. This is supported by the observation that IkappaBalpha degradation induced by TNF-alpha was inhibited by 1,25(OH)2D3 in VDR+/- cells, but not in VDR-/- cells. Taken together, these data suggest that VDR plays an inhibitory role in the regulation of NF-kappaB activation.

High-silica Ferrierite Zeolite Self-transformed from Aluminosilicate Gel

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Jun, 2006  |  Pubmed ID: 16673433

Salt Stress in Desulfovibrio Vulgaris Hildenborough: an Integrated Genomics Approach

Journal of Bacteriology. Jun, 2006  |  Pubmed ID: 16707698

The ability of Desulfovibrio vulgaris Hildenborough to reduce, and therefore contain, toxic and radioactive metal waste has made all factors that affect the physiology of this organism of great interest. Increased salinity is an important and frequent fluctuation faced by D. vulgaris in its natural habitat. In liquid culture, exposure to excess salt resulted in striking elongation of D. vulgaris cells. Using data from transcriptomics, proteomics, metabolite assays, phospholipid fatty acid profiling, and electron microscopy, we used a systems approach to explore the effects of excess NaCl on D. vulgaris. In this study we demonstrated that import of osmoprotectants, such as glycine betaine and ectoine, is the primary mechanism used by D. vulgaris to counter hyperionic stress. Several efflux systems were also highly up-regulated, as was the ATP synthesis pathway. Increases in the levels of both RNA and DNA helicases suggested that salt stress affected the stability of nucleic acid base pairing. An overall increase in the level of branched fatty acids indicated that there were changes in cell wall fluidity. The immediate response to salt stress included up-regulation of chemotaxis genes, although flagellar biosynthesis was down-regulated. Other down-regulated systems included lactate uptake permeases and ABC transport systems. The results of an extensive NaCl stress analysis were compared with microarray data from a KCl stress analysis, and unlike many other bacteria, D. vulgaris responded similarly to the two stresses. Integration of data from multiple methods allowed us to develop a conceptual model for the salt stress response in D. vulgaris that can be compared to those in other microorganisms.

Alterations in Oxidative Phosphorylation Complex Proteins in the Hearts of Transgenic Mice That Overexpress the P38 MAP Kinase Activator, MAP Kinase Kinase 6

American Journal of Physiology. Heart and Circulatory Physiology. Nov, 2006  |  Pubmed ID: 16766635

Ischemia-reperfusion (I/R) has critical consequences in the heart. Recent studies on the functions of I/R-activated kinases, such as p38 mitogen-activated protein kinase (MAPK), showed that I/R injury is reduced in the hearts of transgenic mice that overexpress the p38 MAPK activator MAPK kinase 6 (MKK6). This protection may be fostered by changes in the levels of many proteins not currently known to be regulated by p38. To examine this possibility, we employed the multidimensional protein identification technology MudPIT to characterize changes in levels of proteins in MKK6 transgenic mouse hearts, focusing on proteins in mitochondria, which play key roles in mediating I/R injury in the heart. Of the 386 mitochondrial proteins identified, the levels of 58 were decreased, while only 2 were increased in the MKK6 transgenic mouse hearts. Among those that were decreased were 21 mitochondrial oxidative phosphorylation complex proteins, which was unexpected because p38 is not known to mediate such decreases. Immunoblotting verified that proteins in each of the five oxidative phosphorylation complexes were reduced in MKK6 mouse hearts. On assessing functional consequences of these reductions, we found that MKK6 mouse heart mitochondria exhibited 50% lower oxidative respiration and I/R-mediated reactive oxygen species (ROS) generation, both of which are predicted consequences of decreased oxidative phosphorylation complex proteins. Thus the cardioprotection observed in MKK6 transgenic mouse hearts may be partly due to decreased electron transport, which is potentially beneficial, because damaging ROS are known to be generated by mitochondrial complexes I and III during reoxygenation.

WW Domain Binding Protein-2, an E6-associated Protein Interacting Protein, Acts As a Coactivator of Estrogen and Progesterone Receptors

Molecular Endocrinology (Baltimore, Md.). Oct, 2006  |  Pubmed ID: 16772533

WW domain binding protein-2 (WBP-2) was cloned as an E6-associated protein interacting protein, and its role in steroid hormone receptors functions was investigated. We show that WBP-2 specifically enhanced the transactivation functions of progesterone receptor (PR) and estrogen receptor (ER), whereas it did not have any significant effect on the androgen receptor, glucocorticoid receptor, or the activation functions of p53 and VP-16. Depletion of endogenous WBP-2 with small interfering RNAs indicated that WBP-2 was required for the proper functioning of PR and ER. We also demonstrated that WBP-2 contains an intrinsic activation domain. Moreover, chromatin immunoprecipitation assays demonstrate the hormone-dependent recruitment of WBP-2 onto an estrogen-responsive promoter. Mutational analysis suggests that one of three polyproline (PY) motifs of WBP-2 is essential for its coactivation and intrinsic activation functions. We show that WBP-2 and E6-associated protein each enhance PR function, and their effect on PR action are additive when coexpressed, suggesting a common signaling pathway. In this study, we also demonstrate that the WBP-2 binding protein, Yes kinase-associated protein (YAP) enhances PR transactivation, but YAP's coactivation function is absolutely dependent on WBP-2. Taken together, our data establish the role of WBP-2 and YAP as coactivators for ER and PR transactivation pathways.

Burden of Abnormal Hematopoietic Clone in Patients with Myelodysplastic Syndromes

Chinese Medical Sciences Journal = Chung-kuo I Hsüeh K'o Hsüeh Tsa Chih / Chinese Academy of Medical Sciences. Jun, 2006  |  Pubmed ID: 16845796

To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS).

Rational Selection of Small Molecules That Increase Transcription Through the GAA Repeats Found in Friedreich's Ataxia

FEBS Letters. Oct, 2006  |  Pubmed ID: 16989817

Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat disease with no effective therapy. Expanded GAA repeats in the first intron of the FRDA gene are thought to form unusual non-B DNA conformations that decrease transcription and subsequently reduce levels of the encoded protein, frataxin. Frataxin plays a crucial role in iron metabolism and detoxification. To discover small molecules that increase transcription through the GAA repeat region in FRDA, we have made stable cell lines containing a portion of expanded intron 1 fused to a GFP reporter. Small molecules identified using the competition dialysis method were found to increase FRDA-intron 1-reporter gene expression. One of these compounds, pentamidine, increases frataxin levels in patient cells. Thus our approach can be used to detect small molecules of potential therapeutic value in FRDA.

[Study on Different Thickness and Chromatics of Various Opaques]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Dec, 2006  |  Pubmed ID: 17334070

To study the effect existed in the course of adopting different thickness and chromatics of various opaques so that a good methods can be provided for clinical care in prosthodontics.

Simultaneous Determination of First-line Anti-tuberculosis Drugs and Their Major Metabolic Ratios by Liquid Chromatography/tandem Mass Spectrometry

Rapid Communications in Mass Spectrometry : RCM. 2007  |  Pubmed ID: 17340570

Monitoring of anti-tuberculosis drug concentrations and dose adjustment can be helpful in cases that show poor response to treatment. Here, we describe a method that can rapidly and simultaneously measure the blood concentrations of four anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) and two major metabolic ratios (acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin) using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A C18 reversed-phase column and gradients of methanol in 0.3% formic acid and water were used for HPLC separation. The drug concentrations were determined by multiple reaction monitoring in positive ion mode and the assay performance was evaluated. We determined peak concentration ranges for each drug and acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin ratios by analyzing 2-h post-dose samples in patients treated with standard dosing as a first-line treatment. The preparation of 20 samples including two steps of deproteinization with 50% and 100% methanol was performed within 20 min and chromatographic separation was achieved within 4 min/sample. Interassay calibration variability data obtained over concentrations of 0-8 microg/mL for isoniazid and ethambutol and 0-80 microg/mL for rifampicin and pyrazinamide showed a linear and reproducible curve. Within-run and between-run imprecision (CVs) were 1.9-5.5% and 3.5-10.5% and the lower limits of detection and quantification were 0.01-0.5 microg/mL and 0.05-1.0 microg/mL, respectively. The isoniazid concentration was found to be inversely correlated to the acetylisoniazid/isoniazid ratio (R=-0.739, P<0.001). The devised method allows for the simple, rapid, sensitive and reproducible quantification of isoniazid, rifampicin, pyrazinamide, ethambutol and their two metabolic ratios and should be helpful for therapeutic drug monitoring in tuberculosis patients.

Beta-Catenin Activity Negatively Regulates Bacteria-induced Inflammation

Laboratory Investigation; a Journal of Technical Methods and Pathology. Jun, 2007  |  Pubmed ID: 17384665

Wild-type (WT) Salmonella typhimurium causes acute intestinal inflammation by activating the nuclear factor kappa B (NF-kappaB) pathway. Interestingly, WT Salmonella infection also causes degradation of beta-catenin, a regulator of cellular proliferation. Regulation of beta-catenin and the inhibitor of NF-kappaB, IkappaBalpha, is strikingly similar, involving phosphorylation at identical sites, ubiquitination by the same E3 ligase, and subsequent proteasomal degradation. However, how beta-catenin directly regulates the NF-kappaB pathway during bacteria-induced inflammation in vivo is unknown. Using streptomycin-pretreated mice challenged with Salmonella, we demonstrated that WT Salmonella stimulated beta-catenin degradation and decreased the physical association between NF-kappaB and beta-catenin. Accordingly, WT Salmonella infection decreased the expression of c-myc, a beta-catenin-regulated target gene, and increased the levels of IL-6 and TNF-alpha, the NF-kappaB-regulated target genes. Bacterial infection directly stimulated phosphorylation of beta-catenin, both in vivo and in vitro. Closer examination revealed that glycogen synthase kinase 3beta (GSK-3beta) kinase activity was increased in response to WT Salmonella, whereas non-virulent Salmonella had no effect. siRNA of GSK-3beta was able to stabilize IkappaBalpha in response to WT Salmonella. Pretreatment for 24 h with LiCl, an inhibitor of GSK-3beta, reduced WT Salmonella induced IL-8 secretion. Additionally, cells expressing constitutively active beta-catenin showed IkappaBalpha stabilization and inhibition of NF-kappaB activity not only after WT Salmonella infection but also after commensal bacteria (Escherichia coli F18) and TNF-alpha treatment. This study suggests a new role for beta-catenin as a negative regulator of inflammation.

[Selective Feeding of Calanus Sinicus on Harmful Algal Blooms Species in East China Sea in Spring]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jan, 2007  |  Pubmed ID: 17396516

From April 27th to June 5th 2005, the selective feeding of Calanus sinicus on harmful algal blooms (HABs) species was studied by in situ feeding experiments at six typical stations in a high frequency red tide occurring region of East China Sea. The results showed that the selective feeding behavior of C. sinicus was dependent on food density. It had an obvious food selectivity when the abundance of phytoplankton cell was low, but the selectivity changed from preference to discrimination at high phytoplankton cell abundance, with a threshold value of 329 cells ml. The selective feeding of C. sinicus was also dependent on food composition. It showed no selective feeding or discrimination on microzooplankton at most stations, but preferred to P. delicatissima and disliked Karenia mikimotoi at HABs occurring station, which induced the succession of phytoplankton community to K. mikimotoi blooming.

Nanostructured Biosensor for Measuring Neuropathy Target Esterase Activity

Analytical Chemistry. Jul, 2007  |  Pubmed ID: 17555296

Neuropathy target esterase (NTE) is a membrane protein found in human neurons and other cells, including lymphocytes. Binding of certain organophosphorus (OP) compounds to NTE is believed to cause OP-induced delayed neuropathy (OPIDN), a type of paralysis for which there is no effective treatment. Mutations in NTE have also been linked with serious neurological diseases, such as motor neuron disease. This paper describes development of the first nanostructured biosensor interface containing a catalytically active fragment of NTE known as NEST. The biosensor was fabricated using the layer-by-layer assembly approach, by immobilizing a layer of NEST on top of multilayers consisting of a polyelectrolyte (poly-L-lysine) and an enzyme (tyrosinase). The biosensor has a response time on the order of seconds and gives a concentration-dependent decrease in sensor output in response to a known NEST (and NTE) inhibitor. Potential applications of the biosensor include screening OP compounds for NTE inhibition and investigating the enzymology of wild-type and mutant forms of NTE. Although the development of a NEST biosensor was the primary purpose of this study, we found that the approach developed for NEST could also be extended to measure the activity of other esterases involved in neural processes, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). On the basis of measured sensitivities, phenyl valerate was the preferred substrate for NEST and BChE, whereas phenyl acetate was better for AChE.

Src Promotes Estrogen-dependent Estrogen Receptor Alpha Proteolysis in Human Breast Cancer

The Journal of Clinical Investigation. Aug, 2007  |  Pubmed ID: 17627304

Estrogen drives both transcriptional activation and proteolysis of estrogen receptor alpha (ER alpha; encoded by ESR1). Here we observed variable and overlapping ESR1 mRNA levels in 200 ER alpha-negative and 50 ER alpha-positive primary breast cancers examined, which suggests important posttranscriptional ER alpha regulation. Our results indicate that Src cooperates with estrogen to activate ER alpha proteolysis. Inducible Src stimulated ligand-activated ER alpha transcriptional activity and reduced ER alpha t(1/2). Src and ER alpha levels were inversely correlated in primary breast cancers. ER alpha-negative primary breast cancers and cell lines showed increased Src levels and/or activity compared with ER alpha-positive cancers and cells. ER alpha t(1/2) was reduced in ER alpha-negative cell lines. In both ER alpha-positive and -negative cell lines, both proteasome and Src inhibitors increased ER alpha levels. Src inhibition impaired ligand-activated ER alpha ubiquitylation and increased ER alpha levels. Src siRNA impaired ligand-activated ER alpha loss in BT-20 cells. Pretreatment with Src increased ER alpha ubiquitylation and degradation in vitro. These findings provide what we believe to be a novel link between Src activation and ER alpha proteolysis and support a model whereby crosstalk between liganded ER alpha and Src drives ER alpha transcriptional activity and targets ER alpha for ubiquitin-dependent proteolysis. Oncogenic Src activation may promote not only proliferation, but also estrogen-activated ER alpha loss in a subset of ER alpha-negative breast cancers, altering prognosis and response to therapy.

On the Predictability of Protein Database Search Complexity and Its Relevance to Optimization of Distributed Searches

Journal of Proteome Research. Sep, 2007  |  Pubmed ID: 17663575

We discuss several aspects related to load balancing of database search jobs in a distributed computing environment, such as Linux cluster. Load balancing is a technique for making the most of multiple computational resources, which is particularly relevant in environments in which the usage of such resources is very high. The particular case of the Sequest program is considered here, but the general methodology should apply to any similar database search program. We show how the runtimes for Sequest searches of tandem mass spectral data can be predicted from profiles of previous representative searches, and how this information can be used for better load balancing of novel data. A well-known heuristic load balancing method is shown to be applicable to this problem, and its performance is analyzed for a variety of search parameters.

Long-range Activation of GREB1 by Estrogen Receptor Via Three Distal Consensus Estrogen-responsive Elements in Breast Cancer Cells

Molecular Endocrinology (Baltimore, Md.). Nov, 2007  |  Pubmed ID: 17666587

The estrogen receptor (ER) binds to estrogen-responsive elements (EREs) to activate gene transcription. The best characterized EREs are located in proximal gene promoters, but recent data indicate that only a minority of ER binding sites lie within proximal promoter regions. GREB1 (gene regulated by estrogen in breast cancer 1) is an ER target gene that regulates estrogen-induced proliferation in breast cancer cells. We identified three consensus EREs, located at -21.2, -9.5, and -1.6 kb upstream of the closest GREB1a transcription start site that appear to mediate long-range GREB1 gene activation by ER. All three ERE sites nucleate ER, steroid receptor coactivator-3 (SRC-3), and RNA polymerase II (Pol II) and undergo histone acetylation in response to estradiol. Estrogen-stimulated ER binding at all three EREs was cyclic and synchronous. SRC-3 and Pol II recruitment to all three EREs was activated by estrogen but not tamoxifen. In contrast, estrogen stimulated only Pol II and not ER or SRC-3 recruitment to the GREB1 core promoter regions. Long-range histone acetylation, centered on the three ERE motifs and the GREB1 core promoters, was observed in response to estrogen but not to tamoxifen. These data suggest that estrogen-stimulated GREB1 transcription may involve coordinated ER binding to all three distal consensus ERE motifs. Long-range activation by ER acting at multiple EREs may be more common than previously appreciated.

Salmonella Effector AvrA Regulation of Colonic Epithelial Cell Inflammation by Deubiquitination

The American Journal of Pathology. Sep, 2007  |  Pubmed ID: 17690189

AvrA is a newly described bacterial effector existing in Salmonella. Here, we test the hypothesis that AvrA is a deubiquitinase that removes ubiquitin from two inhibitors of the nuclear factor-kappaB (NF-kappaB) pathway, IkappaBalpha and beta-catenin, thereby inhibiting the inflammatory responses of the host. The role of AvrA was assessed in intestinal epithelial cell models and in mouse models infected with AvrA-deficient and -sufficient Salmonella strains. We also purified AvrA and AvrA mutant proteins and characterized their deubiquitinase activity in a cell-free system. We investigated target gene and inflammatory cytokine expression, as well as effects on epithelial cell proliferation and apoptosis induced by AvrA-deficient and -sufficient bacterial strains in vivo. Our results show that AvrA blocks degradation of IkappaBalpha and beta-catenin in epithelial cells. AvrA deubiquitinates IkappaBalpha, which blocks its degradation and leads to the inhibition of NF-kappaB activation. Target genes of the NF-kappaB pathway, such as interleukin-6, were correspondingly down-regulated during bacterial infection with Salmonella expressing AvrA. AvrA also deubiquitinates and thus blocks degradation of beta-catenin. Target genes of the beta-catenin pathway, such as c-myc and cyclinD1, were correspondingly up-regulated with AvrA expression. Increased beta-catenin further negatively regulates the NF-kappaB pathway. Our findings suggest an important role for AvrA in regulating host inflammatory responses through NF-kappaB and beta-catenin pathways.

Rationales for Expression and Altered Expression of Apoptotic Protease Activating Factor-1 Gene in Gastric Cancer

World Journal of Gastroenterology : WJG. Oct, 2007  |  Pubmed ID: 17876870

To elucidate the relationship between apoptotic protease activating factor-1 (Apaf-1) gene and gastric cancer.

Flagellin-induced Tolerance of the Toll-like Receptor 5 Signaling Pathway in Polarized Intestinal Epithelial Cells

American Journal of Physiology. Gastrointestinal and Liver Physiology. Mar, 2007  |  Pubmed ID: 17138965

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render immune cells tolerant to subsequent challenges by TLR ligands. Accordingly, we examined whether prior exposure to purified flagellin would render human intestinal epithelial cells insensitive to future contact. We found that flagellin-induced tolerance is common to polarized epithelial cells and prevents further activation of proinflammatory signaling cascades by both purified flagellin and Salmonella bacteria but does not affect TNF-alpha stimulation of the same pathways. Flagellin tolerance is a rapid process that does not require protein synthesis, and that occurs within 1 to 2 h of flagellin exposure. Prolonged flagellin exposure blocks activation of the NF-kappaB, MAPK, and phosphoinositol 3-kinase signaling pathways and results in the internalization of a fraction of the basolateral TLR5 without affecting the polarity or total expression of TLR5. After removal of flagellin, cells require more than 24 h to fully recover their ability to mount a normal proinflammatory response. We have found that activation of phosphoinositol 3-kinase and Akt by flagellin has a small damping effect in the early stages of flagellin signaling but is not responsible for tolerance. Our study indicates that inhibition of TLR5-associated IL-1 receptor-associated kinase-4 activity occurs during the development of flagellin tolerance and is likely to be the cause of tolerance.

P27 Phosphorylation by Src Regulates Inhibition of Cyclin E-Cdk2

Cell. Jan, 2007  |  Pubmed ID: 17254967

The kinase inhibitor p27Kip1 regulates the G1 cell cycle phase. Here, we present data indicating that the oncogenic kinase Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Src inhibitors increase cellular p27 stability, and Src overexpression accelerates p27 proteolysis. Src-phosphorylated p27 is shown to inhibit cyclin E-Cdk2 poorly in vitro, and Src transfection reduces p27-cyclin E-Cdk2 complexes. Our data indicate that phosphorylation by Src impairs the Cdk2 inhibitory action of p27 and reduces its steady-state binding to cyclin E-Cdk2 to facilitate cyclin E-Cdk2-dependent p27 proteolysis. Furthermore, we find that Src-activated breast cancer lines show reduced p27 and observe a correlation between Src activation and reduced nuclear p27 in 482 primary human breast cancers. Importantly, we report that in tamoxifen-resistant breast cancer cell lines, Src inhibition can increase p27 levels and restore tamoxifen sensitivity. These data provide a new rationale for Src inhibitors in cancer therapy.

Involvement of the Vitamin D Receptor in the Regulation of NF-kappaB Activity in Fibroblasts

The Journal of Steroid Biochemistry and Molecular Biology. Mar, 2007  |  Pubmed ID: 17298882

We have used mouse embryonic fibroblasts (MEFs) derived from VDR(+/-) and VDR(-/-) mice to determine whether the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-kappaB activation. We found that the basal IkappaBalpha protein level was markedly decreased in VDR(-/-) MEFs compared to VDR(+/-) MEFs; however, degradation of IkappaBalpha and its phosphorylation were not altered in VDR(-/-) cells, neither were the levels of IKKalpha and IKKbeta proteins. Consistently, p65 nuclear translocation was increased in unstimulated VDR(-/-) cells. The physical interaction between VDR and p65 was absent in VDR(-/-) MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in NF-kappaB transcriptional activity. Consistently, induction of IL-6 by TNFalpha or IL-1beta was much more robust in VDR(-/-) than in VDR(+/-) cells, indicating that VDR(-/-) cells are more susceptible to inflammatory stimulation. Therefore, fibroblasts lacking VDR appear to be more pro-inflammatory due to the intrinsic high NF-kappaB activity. The reduction of IkappaBalpha in VDR(-/-) MEFs may be partially explained by the lack of VDR-mediated stabilization of IkappaBalpha by 1,25(OH)(2)D(3). These data suggest that VDR plays an inhibitory role in the regulation of NF-kappaB activation.

Developmentally Regulated Tumor Necrosis Factor-alpha Induced Nuclear Factor-kappaB Activation in Intestinal Epithelium

American Journal of Physiology. Gastrointestinal and Liver Physiology. May, 2007  |  Pubmed ID: 17307728

Premature infants are susceptible to many conditions that are inflammatory in nature. For this patient population, which is expecting the intrauterine environment, pathways necessary for fetal life and development may not have completed the transitions necessary for extrauterine life. In this study, responses to tumor necrosis factor-alpha were compared in human fetal and adult intestinal epithelial cell lines along with preweaned and postweaned mouse intestinal sections to identify a potential developmental difference that may explain the heightened inflammatory response of preterm infants. The nuclear factor-kappaB (NF-kappaB) pathway regulates a wide variety of genes involved in immune and inflammatory processes. We report that, compared with adult intestinal epithelial cells, immature intestinal epithelial cells have increased NF-kappaB activity associated with increased NF-kappaB-DNA binding and transcriptional activity. This increased activity appears due to inadequate inhibition of signaling leading to NF-kappaB activation since there is also increased phosphorylation, ubiquitination, and degradation of the inhibitor of NF-kappaB in conjunction with decreased baseline expression and delayed resynthesis of this inhibitor. Thus we demonstrate a potential mechanism for the heightened inflammatory response of immature intestinal epithelial cells.

[Study on Color Matching of Equal Volume in Dental Ceramic Prothesis Materials]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Oct, 2007  |  Pubmed ID: 18072563

To study the color changes on brightness and hue in dental ceramic prothesis materials.

[Clinical Study on Treatment of Chronic Simple Lichen by Qiangyue Cream]

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. Dec, 2007  |  Pubmed ID: 18198650

To explore the efficacy and safety of Qiangyue Cream (QYC) for treatment of chronic simple lichen (CSL).

Spontaneous Emergence of Modularity in a Model of Evolving Individuals

Physical Review Letters. Nov, 2007  |  Pubmed ID: 18233336

We investigate the selective forces that promote the emergence of modularity in nature. We demonstrate the spontaneous emergence of modularity in a population of individuals that evolve in a changing environment. We show that the level of modularity correlates with the rapidity and severity of environmental change. The modularity arises as a synergistic response to the noise in the environment in the presence of horizontal gene transfer. We suggest that the hierarchical structure observed in the natural world may be a broken-symmetry state, which generically results from evolution in a changing environment.

[Phytoplankton Assemblage in Yangtze River Estuary and Its Adjacent Waters in Winter Time]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Nov, 2007  |  Pubmed ID: 18260464

Water samples were collected from Yangtze River Estuary and its adjacent waters in 28th February-10th March, 2005, and the species composition of phytoplankton was analyzed by Utermöhl method. A total of 130 taxa (including 25 uncertain species) which belong to 67 genera of 5 phyla were identified. The phytoplankton community was mainly composed of Bacillariophyta, followed by Dinophyta. There were also a few species belonging to Chrysophyceae, Cyanophyceae and Chlorophyceae. The dominant species were Paralia sulcata, Skeletonema costatum, Thalassiosira rotula, Bleakeleya notata, Coscinodiscus radiatus and Thalassiosira excentrica. The cell abundance of phytoplankton ranged from 0.1 to 90.0 cells x ml(-1), with an average of 10.1 cells x ml(-1). Horizontally, the cell abundance was relatively high in inshore and low in offshore; while vertically, it was high in surface water and decreased slightly with increasing water depth. The cell abundance and chl a concentration of phytoplankton positively correlated with the concentrations of nitrate, nitrite, ammonium, phosphate and silicate in water, but negatively correlated with water salinity. The Shannon-Wiener diversity index and Pielou evenness index were higher in the center of survey area but lower in northeast part and inshore area.

Mixed Epithelial and Stromal Tumor of Kidney with Malignant Transformation: Report of Two Cases and Review of Literature

Human Pathology. Mar, 2008  |  Pubmed ID: 18261632

We present 2 cases of mixed epithelial and stromal tumor of the kidney with sarcomatous transformation. One patient was a 53-year-old woman who presented with macroscopic hematuria. The resected tumor involved the right renal parenchyma, measuring 13.0 x 8.0 x 4.0 cm, and extended to perirenal adipose tissue. The second patient was a 56-year-old woman who presented with right flank colic pain. The tumor measured 6.0 x 5.5 x 4.0 cm, with an intact capsule at the upper pole. Both tumors showed a well-circumscribed, multilocular, cystic, and focally solid mass. Sections of both tumors revealed benign and malignant components. The benign component consisted of multilocular cysts and fibrous stroma with a focally ovarian stromalike component. The malignant component in both cases was predominantly composed of undifferentiated cellular spindle cell sarcoma with frequent mitoses. One case showed additional heterologous malignant elements, including rhabdomyosarcomatous, chondrosarcomatous, and focal carcinomatous components. We report 2 additional cases of sarcomatous transformation in mixed epithelial and stromal tumor of the kidney.

Platelet-activating Factor-induced Chloride Channel Activation is Associated with Intracellular Acidosis and Apoptosis of Intestinal Epithelial Cells

American Journal of Physiology. Gastrointestinal and Liver Physiology. May, 2008  |  Pubmed ID: 18339705

Platelet-activating factor (PAF) is a phospholipid inter- and intracellular mediator implicated in intestinal injury primarily via induction of an inflammatory cascade. We find that PAF also has direct pathological effects on intestinal epithelial cells (IEC). PAF induces Cl(-) channel activation, which is associated with intracellular acidosis and apoptosis. Using the rat small IEC line IEC-6, electrophysiological experiments demonstrated that PAF induces Cl(-) channel activation. This PAF-activated Cl(-) current was inhibited by Ca(2+) chelation and a calcium calmodulin kinase II inhibitor, suggesting PAF activation of a Ca(2+)-activated Cl(-) channel. To determine the pathological consequences of Cl(-) channel activation, microfluorimetry experiments were performed, which revealed PAF-induced intracellular acidosis, which is also inhibited by the Cl(-) channel inhibitor 4,4'diisothiocyanostilbene-2,2'disulfonic acid and Ca(2+) chelation. PAF-induced intracellular acidosis is associated with caspase 3 activation and DNA fragmentation. PAF-induced caspase activation was abolished in cells transfected with a pH compensatory Na/H exchanger construct to enhance H(+) extruding ability and prevent intracellular acidosis. As ClC-3 is a known intestinal Cl(-) channel dependent on both Ca(2+) and calcium calmodulin kinase II phosphorylation, we generated ClC-3 knockdown cells using short hairpin RNA. PAF induced Cl(-) current; acidosis and apoptosis were all significantly decreased in ClC-3 knockdown cells. Our data suggest a novel mechanism of PAF-induced injury by which PAF induces intracellular acidosis via activation of the Ca(2+)-dependent Cl(-) channel ClC-3, resulting in apoptosis of IEC.

Enhanced Hyaluronic Acid Production by a Two-stage Culture Strategy Based on the Modeling of Batch and Fed-batch Cultivation of Streptococcus Zooepidemicus

Bioresource Technology. Nov, 2008  |  Pubmed ID: 18397825

This study aimed to enhance hyaluronic acid (HA) production by a two-stage culture strategy based on the modeling of batch and fed-batch culture of Streptococcus zooepidemicus. Batch culture had higher specific HA synthesis rate while fed-batch culture had higher specific cell growth rate. The lower specific HA synthesis rate in fed-batch culture resulted from the competition of cell growth for the common precursors at a low substrate concentration. Based on the modeling of batch and fed-batch culture of S. zooepidemicus, a two-stage culture strategy was proposed to enhance HA production. S. zooepidemicus were cultured in a fed-batch mode with sucrose concentration maintained at 1.0+/-0.2g/L during 0-8h and then batch culture was performed during 8-20h with an initial sucrose concentration of 15g/L. With the proposed two-stage culture strategy, HA production was increased to 6.6g/L compared with 5.0g/L in batch culture with the same total sucrose. The enhanced HA production by the proposed two-stage culture strategy resulted from the decreased inhibition of cell growth and the increased transformation rate of sucrose to HA.

The Cost of Treating Skeletal-related Events in Patients with Prostate Cancer

The American Journal of Managed Care. May, 2008  |  Pubmed ID: 18471035

To examine the economic burden of skeletal-related events (SREs) and to assess the frequency of different types of SREs in this population.

Lithocholic Acid Down-regulation of NF-kappaB Activity Through Vitamin D Receptor in Colonic Cancer Cells

The Journal of Steroid Biochemistry and Molecular Biology. Jul, 2008  |  Pubmed ID: 18515093

Lithocholic acid (LCA), a secondary bile acid, is a vitamin D receptor (VDR) ligand. 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the hormonal form of vitamin D, is involved in the anti-inflammatory action through VDR. Therefore, we hypothesize that LCA acts like 1,25(OH)(2)D(3) to drive anti-inflammatory signals. In present study, we used human colonic cancer cells to assess the role of LCA in regulation of the pro-inflammatory NF-kappaB pathway. We found that LCA treatment increased VDR levels, mimicking the effect of 1,25(OH)(2)D(3). LCA pretreatment inhibited the IL-1beta-induced IkappaBalpha degradation and decreased the NF-kappaB p65 phosphorylation. We also measured the production of IL-8, a well-known NF-kappaB target gene, as a read-out of the biological effect of LCA expression on NF-kappaB pathway. LCA significantly decreased IL-8 secretion induced by IL-1beta. These LCA-induced effects were very similar to those of 1,25(OH)(2)D(3.) Thus, LCA recapitulated the effects of 1,25(OH)(2)D(3) on IL-1beta stimulated cells. Mouse embryonic fibroblast (MEF) cells lacking VDR have intrinsically high NF-kappaB activity. LCA pretreatment was not able to prevent TNFalpha-induced IkappaBalpha degradation in MEF VDR (-/-), whereas LCA stabilized IkappaBalpha in MEF VDR (+/-) cells. Collectively, our data indicated that LCA activated the VDR to block inflammatory signals in colon cells.

Salmonella Type III Effector AvrA Stabilizes Cell Tight Junctions to Inhibit Inflammation in Intestinal Epithelial Cells

PloS One. 2008  |  Pubmed ID: 18523661

Salmonella Typhimurium is a major cause of human gastroenteritis. The Salmonella type III secretory system secretes virulence proteins, called effectors. Effectors are responsible for the alteration of tight junction (TJ) structure and function in intestinal epithelial cells. AvrA is a newly described bacterial effector found in Salmonella. We report here that AvrA expression stabilizes cell permeability and tight junctions in intestinal epithelial cells. Cells colonized with an AvrA-deficient bacterial strain (AvrA-) displayed decreased cell permeability, disruption of TJs, and an increased inflammatory response. Western blot data showed that TJ proteins, such as ZO-1, claudin-1, decreased after AvrA- colonization for only 1 hour. In contrast, cells colonized with AvrA-sufficient bacteria maintained cell permeability with stabilized TJ structure. This difference was confirmed in vivo. Fluorescent tracer studies showed increased fluorescence in the blood of mice infected with AvrA- compared to those infected with the AvrA-sufficient strains. AvrA- disrupted TJ structure and function and increased inflammation in vivo, compared to the AvrA- sufficient strain. Additionally, AvrA overexpression increased TJ protein expression when transfected into colonic epithelial cells. An intriguing aspect of this study is that AvrA stabilized TJs, even though the other TTSS proteins, SopB, SopE, and SopE2, are known to disrupt TJs. AvrA may play a role in stabilizing TJs and balancing the opposing action of other bacterial effectors. Our findings indicate an important role for the bacterial effector AvrA in regulation of intestinal epithelial cell TJs during inflammation. The role of AvrA represents a highly refined bacterial strategy that helps the bacteria survive in the host and dampen the inflammatory response.

[Size-fractionated Biomass of Phytoplankton in the Yangtze River Estuary and Its Adjacent Waters in Winter and Spring]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Mar, 2008  |  Pubmed ID: 18533541

Based on the multi-discipline investigation in 28th February-10th March and 30th May-4th June, 2005, this paper studied the distribution of size-fractionated phytoplankton in the Yangtze River estuary and its adjacent waters, and the environmental factors that affected this distribution. The results showed that in winter, the average chlorophyll a concentration was 1.28 mg X m(-3), and the region with high concentration chlorophyll a was located near the river mouth. Small-sized phytoplankton (SSP, <20 microm) contributed 66.7% to the total phytoplankton biomass, but big-sized phytoplankton (BSP, >20 microm) was dominant in the plume system. In spring, the average chlorophyll a concentration in inner river and outer estuary was 0.67 and 6.03 mg x m(-3), respectively, and the maximum of chlorophyll a concentration appeared in the waters between 122.5 degrees E and 123.0 degrees E. The SSP dominated in the plume system, especially in the algal bloom frequently occurring area which located at south of survey area, contributed 83.5% to the total phytoplankton biomass. The vertical profile of size-fractionated chlorophyll a showed that with the increase of water depth, the SSP and BSP became equal in the offshores. Among the environmental factors in the Yangtze River estuary and its adjacent waters, salinity and nutrients were the main factors affecting the distribution and composition of size-fractioned phytoplankton biomass in winter and spring.

Optimizing the Codon Usage of Synthetic Gene with QPSO Algorithm

Journal of Theoretical Biology. Sep, 2008  |  Pubmed ID: 18579159

Molecular Biology makes it possible to express foreign genes in microorganism, plants and animals. To improve the heterologous expression, it is important that the codon usage of sequence be optimized to make it adaptive to host organism. In this paper, a novel method based on Quantum-behaved Particle Swarm Optimization (QPSO) algorithm is developed to optimize the codon usage of synthetic gene. Compared to the existing probability methods, QPSO is able to generate better results when DNA/RNA sequence length is less than 6Kb which is the commonly used range. While the software or web service based on probability method may not exclude all defined restriction sites when there are many undesired sites in the sequence, our proposed method can remove the undesired site efficiently during the optimization process.

Flagellin is Required for Salmonella-induced Expression of Heat Shock Protein Hsp25 in Intestinal Epithelium

American Journal of Physiology. Gastrointestinal and Liver Physiology. Mar, 2008  |  Pubmed ID: 18202113

Flagellin is a bacterial protein responsible for activation of Toll-like receptor 5 (TLR5), which we hypothesize is involved in Salmonella's induction of cytoprotective heat shock proteins in intestinal epithelial cells. Flagellin induces the cytoprotective heat shock protein Hsp25 in different intestinal epithelial cell lines and in mouse intestine. Flagellin induces Hsp25 expression in a time-dependent manner in vitro. This effect is transcriptional, as confirmed by luciferase reporter assays and actinomycin D treatment. In addition, Hsp25 induction requires p38 MAPK activation and is only observed when flagellin is added to the basolateral side of polarized intestinal epithelial cells, consistent with the known location of TLR5. Flagellin-mediated Hsp25 induction is associated with increased protective effects against oxidant stress, an effect that is at least partially mediated by p38 MAPK. Use of small interfering RNA against Hsp25 demonstrates that flagellin-mediated protection against oxidant stress is to some degree mediated through Hsp25 induction. This suggests that, by protecting against oxidant injury, the induction of Hsp25 expression by flagellin may contribute to intestinal homeostasis. In a coculture cell model and in a mouse model of Salmonella enterica Serovar Typhimurium infection, not only does infection with wild-type and a flagellin-deletion mutant strain of Salmonella show that flagellin induces Hsp25 in vivo, but it also demonstrates that in the case of live Salmonella infection, flagellin serves as a major stimulus for the induction of Hsp25 expression. These data provide evidence that flagellin is required for Salmonella-mediated induction of Hsp25 expression in intestinal epithelium.

[Phytoplankton Assemblages on the Continental Shelf of East China Sea in Autumn 2006]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Nov, 2008  |  Pubmed ID: 19238843

Based on the survey from November 19 to December 24, 2006, the species composition, assemblage structure, and cell abundance of phytoplankton on the continental shelf of East China Sea (24.0 degrees N- 32.0 degrees N, 120.0 degrees - 128.0 degrees E) were studied. The phytoplankton flora in the survey area included 145 taxa, belonging to 64 genera of 4 classes (including uncertain species). Bacillariophyta was the dominant functional group, followed by Pyrrophyta. The dominant species in turn were Thalassionema nitzschioides, Thalassiosira rotula, Leptocylindrus danicus, Guinardia striata, Pseudo-nitzschia pungens, and Trichodesmium thiebautii. The cell abundance of the phytoplankton ranged from 0.09 to 35.11 cells x ml(-1), with an average of 4.92 cells x ml(-1). In the autumn, Bacillariophyta abundance discriminated the surface pattern of the phytoplankton, and the higher abundance area was located at the northeast part of offshore regions, with the cell abundance reached 30 cells x ml(-1). On the whole, the cell abundance of Bacillariophyta and Pyrrophyta was concentrated in surface water, and it reduced rapidly from surface layer down to the bottom. According to the section distribution, the phytoplankton mainly concentrated in surface water, and also, in the middle and bottom layers for some stations. The average of Shannon-Wiener indices of phytoplankton assemblage was 2.80, with the higher values occurred in the northeast and southeast of the survey area. The average of Pielou' s evenness of phytoplankton assemblage was 0.81, and the higher value was located at the middle of the survey area. The surface horizontal distribution of Shannon-Wiener indices was coincided with that of phytoplankton cell abundance. According to the Pearson correlation analysis, the factors that significantly affected the growth of the phytoplankton were nitrite, dissolved organic nitrogen (DON), and temperature.

Novel Role of the Vitamin D Receptor in Maintaining the Integrity of the Intestinal Mucosal Barrier

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jan, 2008  |  Pubmed ID: 17962355

Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.

Influence of Clay Minerals on the Reduction of Cr6+ by Citric Acid

Chemosphere. Mar, 2008  |  Pubmed ID: 18022670

The influence of clay minerals on the reduction of Cr6+ by citric acid was investigated at pH values 4.0, 4.5 and 5.0 at 25 degrees C. The results indicate that montmorillonite and illite greatly accelerate the reduction reactions at pH 4.0 and 4.5, but their effects are dramatically reduced at pH 5.0. The role of clay minerals in accelerating the reactions is in the order: illite>montmorillonite>kaolinite, which has a positive correlation with the amount of Mn2+ adsorbed on the surfaces of these minerals. With light, Fe(3+) also significantly increases reaction rates. Ethylenediaminetetraacetic acid (EDTA) greatly suppresses the acceleration of the reduction reactions by these minerals, indicating that EDTA competes with citric acid for Mn2+. Thus, the formation of complexes between Mn(2+) and citric acid could be a prerequisite for the acceleration of the reductions of Cr6+ by clay minerals. In addition, there is no relationship between the specific surface area of clay minerals and the reduction rate of Cr6+ by citric acid.

Expression of Kv1.2 in Microglia and Its Putative Roles in Modulating Production of Proinflammatory Cytokines and Reactive Oxygen Species

Journal of Neurochemistry. Sep, 2008  |  Pubmed ID: 18627436

Microglial cells are endowed with different potassium ion channels but their expression and specific functions have remained to be fully clarified. This study has shown Kv1.2 expression in the amoeboid microglia in the rat brain between 1 (P1) and 10 (P10) days of age. Kv1.2 expression was localized in the ramified microglia at P14 and was hardly detected at P21. In postnatal rats exposed to hypoxia, Kv1.2 immunoreactivity in microglia was markedly enhanced. Quantitative RT-PCR analysis confirmed Kv1.2 mRNA expression in microglial cells in vitro. It was further shown that Kv1.2 and protein expression coupled with that of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) was significantly increased when the cells were subjected to hypoxia. The same increase was observed in cells exposed to adenosine 5'-triphosphate (ATP) and lipopolysaccharide (LPS). Concomitantly, the intracellular potassium concentration decreased significantly. Blockade of Kv1.2 channel with rTityustoxin-Kalpha (TsTx) resulted in partial recovery of intracellular potassium concentration accompanied by a reduced expression of IL-1beta and TNF-alpha mRNA and protein expression and intracellular reactive oxygen species (ROS) production. We conclude that Kv1.2 in microglia modulates IL-1beta and TNF-alpha expression and ROS production probably by regulating the intracellular potassium concentration.

Geobacter Sulfurreducens Strain Engineered for Increased Rates of Respiration

Metabolic Engineering. Sep, 2008  |  Pubmed ID: 18644460

Geobacter species are among the most effective microorganisms known for the bioremediation of radioactive and toxic metals in contaminated subsurface environments and for converting organic compounds to electricity in microbial fuel cells. However, faster rates of electron transfer could aid in optimizing these processes. Therefore, the Optknock strain design methodology was applied in an iterative manner to the constraint-based, in silico model of Geobacter sulfurreducens to identify gene deletions predicted to increase respiration rates. The common factor in the Optknock predictions was that each resulted in a predicted increase in the cellular ATP demand, either by creating ATP-consuming futile cycles or decreasing the availability of reducing equivalents and inorganic phosphate for ATP biosynthesis. The in silico model predicted that increasing the ATP demand would result in higher fluxes of acetate through the TCA cycle and higher rates of NADPH oxidation coupled with decreases in flux in reactions that funnel acetate toward biosynthetic pathways. A strain of G. sulfurreducens was constructed in which the hydrolytic, F(1) portion of the membrane-bound F(0)F(1) (H(+))-ATP synthase complex was expressed when IPTG was added to the medium. Induction of the ATP drain decreased the ATP content of the cell by more than half. The cells with the ATP drain had higher rates of respiration, slower growth rates, and a lower cell yield. Genome-wide analysis of gene transcript levels indicated that when the higher rate of respiration was induced transcript levels were higher for genes involved in energy metabolism, especially in those encoding TCA cycle enzymes, subunits of the NADH dehydrogenase, and proteins involved in electron acceptor reduction. This was accompanied by lower transcript levels for genes encoding proteins involved in amino acid biosynthesis, cell growth, and motility. Several changes in gene expression that involve processes not included in the in silico model were also detected, including increased expression of a number of redox-active proteins, such as c-type cytochromes and a putative multicopper outer-surface protein. The results demonstrate that it is possible to genetically engineer increased respiration rates in G. sulfurreducens in accordance with predictions from in silico metabolic modeling. To our knowledge, this is the first report of metabolic engineering to increase the respiratory rate of a microorganism.

Lymphoma Involving the Ulnar Nerve: Sonographic Findings

Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. Oct, 2008  |  Pubmed ID: 18809966

[Role of Phospholipase C-gamma1 Signaling Pathway in H(2)O(2)-induced Apoptosis of PC12 Cells]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Nov, 2008  |  Pubmed ID: 19033097

To explore the role of phospholipase C-gamma1 (PLC-gamma1) signaling pathway in H(2)O(2)-induced apoptosis of PC12 cells.

Identification and Characterization of Novel MicroRNAs from Schistosoma Japonicum

PloS One. 2008  |  Pubmed ID: 19107204

Schistosomiasis japonica remains a major public health problem in China. Its pathogen, Schistosoma japonicum has a complex life cycle and a unique repertoire of genes expressed at different life cycle stages. Exploring schistosome gene regulation will yield the best prospects for new drug targets and vaccine candidates. MicroRNAs (miRNAs) are a highly conserved class of noncoding RNA that control many biological processes by sequence-specific inhibition of gene expression. Although a large number of miRNAs have been identified from plants to mammals, it remains no experimental proof whether schistosome exist miRNAs.

Differential Selection on Gene Translation Efficiency Between the Filamentous Fungus Ashbya Gossypii and Yeasts

BMC Evolutionary Biology. 2008  |  Pubmed ID: 19111070

The filamentous fungus Ashbya gossypii grows into a multicellular mycelium that is distinct from the unicellular morphology of its closely related yeast species. It has been proposed that genes important for cell cycle regulation play central roles for such phenotypic differences. Because A. gossypii shares an almost identical set of cell cycle genes with the typical yeast Saccharomyces cerevisiae, the differences might occur at the level of orthologous gene regulation. Codon usage patterns were compared to identify orthologous genes with different gene regulation between A. gossypii and nine closely related yeast species.

[Effects of Mineralization Liquid on Rat's Osteoblast Proliferation and Differentiation]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Dec, 2008  |  Pubmed ID: 19186865

To compare the rat osteoblast proliferation and differentiation in the mineralization condition and non-mineralization condition, and to prove the feasible time of adding the mineralization liquid to the cell surroundings.

Comparative Study on the Influence of Dissolved Oxygen Control Approaches on the Microbial Hyaluronic Acid Production of Streptococcus Zooepidemicus

Bioprocess and Biosystems Engineering. Oct, 2009  |  Pubmed ID: 19205747

Three different dissolved oxygen (DO) control approaches were proposed to improve hyaluronic acid (HA) production: a three-stage agitation speed control approach, a two-stage DO control approach, and an oxygen vector perfluorodecalin (PFC) applied approach. In the three-stage agitation speed control approach, agitation speed was 200 rpm during 0-8 h, 400 rpm during 8-12 h, and 600 rpm during 12-20 h. In the two-stage DO control strategy, DO was controlled at above 10% during 0-8 h and at 5% during 8-20 h. In the PFC applied approach, PFC (3% v/v) was added at 8 h. HA production reached 5.5 g/L in the three-stage agitation speed control culture model, and 6.3 g/L in two-stage DO control culture model, and 6.6 g/L in the PFC applied culture model. Compared with the other two DO control approaches, the PFC applied approach had a lower shear stress and thus a higher HA production was achieved.

Molecular Momentum Transport at Fluid-solid Interfaces in MEMS/NEMS: A Review

International Journal of Molecular Sciences. Nov, 2009  |  Pubmed ID: 20087458

This review is focused on molecular momentum transport at fluid-solid interfaces mainly related to microfluidics and nanofluidics in micro-/nano-electro-mechanical systems (MEMS/NEMS). This broad subject covers molecular dynamics behaviors, boundary conditions, molecular momentum accommodations, theoretical and phenomenological models in terms of gas-solid and liquid-solid interfaces affected by various physical factors, such as fluid and solid species, surface roughness, surface patterns, wettability, temperature, pressure, fluid viscosity and polarity. This review offers an overview of the major achievements, including experiments, theories and molecular dynamics simulations, in the field with particular emphasis on the effects on microfluidics and nanofluidics in nanoscience and nanotechnology. In Section 1 we present a brief introduction on the backgrounds, history and concepts. Sections 2 and 3 are focused on molecular momentum transport at gas-solid and liquid-solid interfaces, respectively. Summary and conclusions are finally presented in Section 4.

[Effects of Different Titanium-treated Surfaces on Rat's Osteoblast Function and Cell Cycle]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Oct, 2009  |  Pubmed ID: 19947482

This study is designed to compare the distribution, function and cell cycle of rat osteoblast cultured on sandblasting and acid-alkali base titanium surface versus that cultured on carbonated hydroxyapatite titanium surface; the aim is to probe the influences of different surfaces on the function of osteoblasts. SD rat's osteoblasts were primary-cultured, passaged to the 4th generation and then cultured on the two kinds of surfaces. The cellular modality was observed using an inverted microscopy analyzing system. Proliferation was examined by MTT chromatometry and depicted by growth curve. Expression of alkaline phosphatase (ALP) was detected by Enzyme-Linked Immunosorbent Assay. The cell apoptosis and proliferation were examined by flow cytometry. The proliferation curve and index of the osteoblasts on the two kinds of surfaces were almost the same. However, on the carbonated hydroxyapatite group, the level of alkaline phosphatase expression of osteoblasts was higher and kept longer than the other one. In conclusion, the elements on the titanium surface influence the cell function, and the surface with rich PO4(3-) and Ga2+ can enhance the mineralization function of rat osteoblast.

Metabolic Flux Estimation Using Particle Swarm Optimization with Penalty Function

Rivista Di Biologia. May-Aug, 2009  |  Pubmed ID: 20077391

Metabolic flux estimation through 13C trace experiment is crucial for quantifying the intracellular metabolic fluxes. In fact, it corresponds to a constrained optimization problem that minimizes a weighted distance between measured and simulated results. In this paper, we propose particle swarm optimization (PSO) with penalty function to solve 13C-based metabolic flux estimation problem. The stoichiometric constraints are transformed to an unconstrained one, by penalizing the constraints and building a single objective function, which in turn is minimized using PSO algorithm for flux quantification. The proposed algorithm is applied to estimate the central metabolic fluxes of Corynebacterium glutamicum. From simulation results, it is shown that the proposed algorithm has superior performance and fast convergence ability when compared to other existing algorithms.

Genome-scale Constraint-based Modeling of Geobacter Metallireducens

BMC Systems Biology. 2009  |  Pubmed ID: 19175927

Geobacter metallireducens was the first organism that can be grown in pure culture to completely oxidize organic compounds with Fe(III) oxide serving as electron acceptor. Geobacter species, including G. sulfurreducens and G. metallireducens, are used for bioremediation and electricity generation from waste organic matter and renewable biomass. The constraint-based modeling approach enables the development of genome-scale in silico models that can predict the behavior of complex biological systems and their responses to the environments. Such a modeling approach was applied to provide physiological and ecological insights on the metabolism of G. metallireducens.

Mosaicplasty Associated with Gene Enhanced Tissue Engineering for the Treatment of Acute Osteochondral Defects in a Goat Model

Archives of Orthopaedic and Trauma Surgery. Jun, 2009  |  Pubmed ID: 18839189

To compare single mosaicplasty, mosaicplasty associated with gene enhanced tissue engineering and mosaicplasty associated with the gels of non-gene transduced bone mesenchymal stem cells (BMSCs) in alginate for the treatment of acute osteochondral defects in a goat model.

Which Physicians Have Access to Electronic Prescribing and Which Ones End Up Using It?

Health Policy (Amsterdam, Netherlands). Mar, 2009  |  Pubmed ID: 18715669

This study examines the availability of electronic prescription and the utilization of e-prescribing by physicians in the US.

Binary Particle Swarm Optimization Algorithm with Mutation for Multiple Sequence Alignment

Rivista Di Biologia. Jan-Apr, 2009  |  Pubmed ID: 19718624

Multiple sequence alignment (MSA) is a fundamental and challenging problem in the analysis of biologic sequence. The MSA problem is hard to be solved directly, for it always results in exponential complexity with the scale of the problem. In this paper, we propose mutation-based binary particle swarm optimization (M-BPSO) for MSA solving. In the proposed M-BPSO algorithm, BPSO algorithm is conducted to provide alignments. Thereafter, mutation operator is performed to move out of local optima and speed up convergence. From simulation results of nucleic acid and amino acid sequences, it is shown that the proposed M-BPSO algorithm has superior performance when compared to other existing algorithms. Furthermore, this algorithm can be used quickly and efficiently for smaller and medium size sequences.

Cholesterol Overloading Leads to Hepatic L02 Cell Damage Through Activation of the Unfolded Protein Response

International Journal of Molecular Medicine. Oct, 2009  |  Pubmed ID: 19724885

Reported data indicate that cholesterol loading in the liver can cause hepatic injury. To explore the possible mechanisms of cell damage resulting from cholesterol overloading in hepatocytes, cell apoptosis, the unfolded protein response (UPR) and the correlation between them were assessed in the cholesterol-overloaded normal human hepatic cell line L02. L02 cells were incubated with 200 microg/ ml of low density lipoprotein (LDL) for 24 h with or without 20 microg/ml 58035, an inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT). In the LDL+58035 group, the intracellular cholesterol level was dramatically increased, which was measured by an enzymatic combined high performance liquid chromatography assay. Expression of immunoglobulin-binding protein, X-box binding protein 1, activating transcription factor 6, activating transcription factor 4, CCAAT/enhancer-binding protein homologous protein-10, markers of endoplasmic reticulum stress (ERS)/ UPR, were up-regulated as determined using reverse transcription-polymerase chain reaction (RT-PCR) or Western blot analysis. The rate of cell apoptic death increased 21.3+/-2.4%. Meanwhile, the active caspase-3 protein expression was increased 8.4-fold compared to the active caspase-3 protein expression in the controls. Furthermore, 4-phenylbutyric acid, an inhibitor of UPR, partly reduced cell apoptosis and activation of caspase-3. This study suggests that cholesterol overloading in hepatic L02 cells induces ERS and activates the UPR which, in part, leads to the apoptotic damage of cells.

Safety of Chronic Low-dose Capecitabine As Maintenance Therapy in Gastrointestinal Cancers

Gastrointestinal Cancer Research : GCR. Jul, 2009  |  Pubmed ID: 19742139

Maintenance chemotherapy is not routinely used in gastrointestinal (GI) cancers. Capecitabine is an oral formulation that is enzymatically converted to 5-fluorouracil preferentially in tumor tissue. We hypothesize that capecitabine could be used as a long-term maintenance therapy to improve outcomes in patients with high-risk GI cancers following standard chemotherapy regimens.

A Case of Compressive Optic Neuropathy Caused by Sphenoid Sinus Cholesterol Granuloma

Japanese Journal of Ophthalmology. Jul, 2009  |  Pubmed ID: 19763767

[Medical Devices Adverse Events and Its Preventive Measures]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Mar, 2009  |  Pubmed ID: 19771899

The text analyzes the reasons of medical devices adverse events occurrence from manufacturers, medical institutions and patients. To guard against the events, the medical institutions should put emphasis on check of purchasing, informed consent, technical permission, SOP performing, the safe of medical and enhance monitoring etc.

Genome-scale Comparison and Constraint-based Metabolic Reconstruction of the Facultative Anaerobic Fe(III)-reducer Rhodoferax Ferrireducens

BMC Genomics. 2009  |  Pubmed ID: 19772637

Rhodoferax ferrireducens is a metabolically versatile, Fe(III)-reducing, subsurface microorganism that is likely to play an important role in the carbon and metal cycles in the subsurface. It also has the unique ability to convert sugars to electricity, oxidizing the sugars to carbon dioxide with quantitative electron transfer to graphite electrodes in microbial fuel cells. In order to expand our limited knowledge about R. ferrireducens, the complete genome sequence of this organism was further annotated and then the physiology of R. ferrireducens was investigated with a constraint-based, genome-scale in silico metabolic model and laboratory studies.

Pathogenic Bacterial Proteins and Their Anti-Inflammatory Effects in the Eukaryotic Host

Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry. Sep, 2009  |  Pubmed ID: 20090866

Bacteria use multiple strategies to bypass the inflammatory responses in order to survive in the host cells. In this review, we discuss the mechanism of the bacerial proteins in inhibiting inflammation. We highlight the anti-inflammatory roles of the type three secretion proteins including Salmonella AvrA, Enteropathogenic Escherichia coli Cif, and Yersinia YopJ, Staphylococcus aureus extracellular adherence protein, and Chlamydia proteins. We also discuss the research progress on the structures of these anti-inflammatory bacterial proteins. The current therapeutic methods for diseases, such as inflammatory bowel diseases, sclerosis, lack influence on the course of chronic inflammation and infection. Therefore, based on the molecular mechanism of the anti-inflammatory bacterial proteins and their 3-Dimension structure, we can design new peptides or non-peptidic molecules that serve as anti-inflammatory drugs without the possible side effect of promoting bacterial infection.

Reconstruction of Defects with the Posterior Femoral Fasciocutaneous Flap After Resection of Malignant Tumours of the Femoral Greater Trochanter, Sacrococcygeal Region and Knee

Journal of Plastic, Reconstructive & Aesthetic Surgery : JPRAS. Feb, 2009  |  Pubmed ID: 18054531

To determine the vascular anatomy and clinical application of superiorly and inferiorly based posterior thigh fasciocutaneous flaps.

Numerical Bias Estimation for Mass Spectrometric Mass Isotopomer Analysis

Analytical Biochemistry. May, 2009  |  Pubmed ID: 19275875

Mass spectrometric (MS) isotopomer analysis has become a standard tool for investigating biological systems using stable isotopes. In particular, metabolic flux analysis uses mass isotopomers of metabolic products typically formed from (13)C-labeled substrates to quantitate intracellular pathway fluxes. In the current work, we describe a model-driven method of numerical bias estimation regarding MS isotopomer analysis. Correct bias estimation is crucial for measuring statistical qualities of measurements and obtaining reliable fluxes. The model we developed for bias estimation corrects a priori unknown systematic errors unique for each individual mass isotopomer peak. For validation, we carried out both computational simulations and experimental measurements. From stochastic simulations, it was observed that carbon mass isotopomer distributions and measurement noise can be determined much more precisely only if signals are corrected for possible systematic errors. By removing the estimated background signals, the residuals resulting from experimental measurement and model expectation became consistent with normality, experimental variability was reduced, and data consistency was improved. The method is useful for obtaining systematic error-free data from (13)C tracer experiments and can also be extended to other stable isotopes. As a result, the reliability of metabolic fluxes that are typically computed from mass isotopomer measurements is increased.

Photoreceptor IFT Complexes Containing Chaperones, Guanylyl Cyclase 1 and Rhodopsin

Traffic (Copenhagen, Denmark). Jun, 2009  |  Pubmed ID: 19302411

Intraflagellar transport (IFT) provides a mechanism for the transport of cilium-specific proteins, but the mechanisms for linkage of cargo and IFT proteins have not been identified. Using the sensory outer segments (OS) of photoreceptors, which are derived from sensory cilia, we have identified IFT-cargo complexes containing IFT proteins, kinesin 2 family proteins, two photoreceptor-specific membrane proteins, guanylyl cyclase 1 (GC1, Gucy2e) and rhodopsin (RHO), and the chaperones, mammalian relative of DNAJ, DnajB6 (MRJ), and HSC70 (Hspa8). Analysis of these complexes leads to a model in which MRJ through its binding to IFT88 and GC1 plays a critical role in formation or stabilization of the IFT-cargo complexes. Consistent with the function of MRJ in the activation of HSC70 ATPase activity, Mg-ATP enhances the co-IP of GC1, RHO, and MRJ with IFT proteins. Furthermore, RNAi knockdown of MRJ in IMCD3 cells expressing GC1-green fluorescent protein (GFP) reduces cilium membrane targeting of GC1-GFP without apparent effect on cilium elongation.

PTD4-apoptin Protein Therapy Inhibits Tumor Growth in Vivo

International Journal of Cancer. Journal International Du Cancer. Jun, 2009  |  Pubmed ID: 19326452

Apoptin protein harbors tumor-selective cell death activity, which makes it a potential anticancer therapy candidate. This study reports an apoptin therapy approach based on protein transduction domain 4 (PTD4)-mediated transduction of recombinant apoptin protein. In vitro, the PTD4-apoptin fusion protein is located in the nucleus and induces cell death in, e.g., human hepatocarcinoma HepG2 cells. In normal human L-02 hepatocytes, PTD4-apoptin protein retained mainly cytoplasmic and did not induce detectable levels of cell death, illustrating that the PTD4 domain does not affect apoptin's tumor-selective characteristics. In vivo, liver, cervix and gastric carcinoma xenografts treated with PTD4-apoptin protein for 6 days via the tumor epidermis exhibited a significant tumor growth inhibition because of apoptin-mediated cell death. In addition, treatment of human hepatocarcinoma xenografts during 3 weeks showed that PTD4-apoptin protein has significant anticancer activity, whereas control treatment with PTD4-enhanced green fluorescence protein or saline did not. Cell death and disruption of the tumor integrity were apparent in the PTD4-apoptin transduced xenografted tumors. As important, although PTD4-apoptin protein could be detected in the epidermal tissue covering the subcutaneous tumor tissue and in several organs, such as liver and brain, of the treated mice, no tissue disruption or signs of cell death could be detected. Our in vivo data reveal that apoptin protein delivery constitutes a novel powerful and safe anticancer therapy.

16S RRNA Gene-based Analysis of Fecal Microbiota from Preterm Infants with and Without Necrotizing Enterocolitis

The ISME Journal. Aug, 2009  |  Pubmed ID: 19369970

Neonatal necrotizing enterocolitis (NEC) is an inflammatory intestinal disorder affecting preterm infants. Intestinal bacteria have an important function; however no causative pathogen has been identified. The purpose of this study was to determine if there are differences in microbial patterns that may be critical to the development of this disease. Fecal samples from 20 preterm infants, 10 with NEC and 10 matched controls (including 4 twin pairs) were obtained from patients in a single site level III neonatal intensive care unit. Bacterial DNA from individual fecal samples was PCR-amplified and subjected to terminal restriction fragment length polymorphism analysis and library sequencing of the 16S rRNA gene to characterize diversity and structure of the enteric microbiota. The distribution of samples from NEC patients distinctly clustered separately from controls. Intestinal bacterial colonization in all preterm infants was notable for low diversity. Patients with NEC had even less diversity, an increase in abundance of Gammaproteobacteria, a decrease in other bacteria species, and had received a higher mean number of previous days of antibiotics. Our results suggest that NEC is associated with severe lack of microbiota diversity that may accentuate the impact of single dominant microorganisms favored by empiric and widespread use of antibiotics.

Fe(III) Photocatalytic Reduction of Cr(VI) by Low-molecular-weight Organic Acids with Alpha-OH

Journal of Hazardous Materials. Sep, 2009  |  Pubmed ID: 19372002

The photochemical reduction of Cr(VI) by four low-molecular-weight organic acids (tartaric acid, citric acid, malic acid, and n-butyric acid) in the presence of either dissolved Fe(III) in dilute aqueous solution or adsorbed Fe(III) on clay mineral surfaces (kaolinite, montmorillonite and illite) was investigated using batch reactors at a pH range from 3.5 to 4.5 at 25 degrees C. The results indicate that Fe(III) photocatalytic reduction of Cr(VI) by organic acids with alpha-OH is extremely fast. During a reaction period when less than 80% initial Cr(VI) was consumed, the reaction can be described as pseudo-first-order with respect to Cr(VI) when organic acid in excess. By plotting ln[Cr(VI)] as a function of reaction time, rate constants of Cr(VI) reduction by organic acids are obtained. The rate constants involving the four acids are in the order: tartaric acid (with 2 carboxylic groups and 2 alpha-OH groups)>citric acid (with 3 carboxylic groups and 1 alpha-OH group) approximately malic acid (with 2 carboxylic groups and 1 alpha-OH group)>n-butyric acid (with 1 carboxylic group and no alpha-OH group). This order suggests that the number of alpha-OH but not the number of carboxylic groups is an important determinant of kinetics. With light, the reduction of Cr(VI) by citric acid is accelerated by clay minerals. The enhancement of Cr(VI) reduction is attributed to the catalysis of Fe(III) adsorbed on clay mineral surfaces. However, such an acceleration is markedly suppressed by introducing NaF into the reaction system since NaF forms a complex with Fe(III). It is concluded that the complex formation between Fe(III) and organic acid is a key step for the photocatalytic reduction of Cr(VI) in the presence of Fe(III) and organic acids with alpha-OH.

Bacteria-free Solution Derived from Lactobacillus Plantarum Inhibits Multiple NF-kappaB Pathways and Inhibits Proteasome Function

Inflammatory Bowel Diseases. Oct, 2009  |  Pubmed ID: 19373789

Bacteria play a role in inflammatory bowel disease and other forms of intestinal inflammation. Although much attention has focused on the search for a pathogen or inciting inflammatory bacteria, another possibility is a lack of beneficial bacteria that normally confer anti-inflammatory properties in the gut. The purpose of this study was to determine whether normal commensal bacteria could inhibit inflammatory pathways important in intestinal inflammation.

Spontaneous Emergence of Modularity in a Model of Evolving Individuals and in Real Networks

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Mar, 2009  |  Pubmed ID: 19391971

We investigate the selective forces that promote the emergence of modularity in nature. We demonstrate the spontaneous emergence of modularity in a population of individuals that evolve in a changing environment. We show that the level of modularity correlates with the rapidity and severity of environmental change. The modularity arises as a synergistic response to the noise in the environment in the presence of horizontal gene transfer. We suggest that the hierarchical structure observed in the natural world may be a broken symmetry state, which generically results from evolution in a changing environment. To support our results, we analyze experimental protein interaction data and show that protein interaction networks became increasingly modular as evolution proceeded over the last four billion years. We also discuss a method to determine the divergence time of a protein.

Drilling and Microfracture Lead to Different Bone Structure and Necrosis During Bone-marrow Stimulation for Cartilage Repair

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. Nov, 2009  |  Pubmed ID: 19402150

Bone marrow stimulation is performed using several surgical techniques that have not been systematically compared or optimized for a desired cartilage repair outcome. In this study, we investigated acute osteochondral characteristics following microfracture and comparing to drilling in a mature rabbit model of cartilage repair. Microfracture holes were made to a depth of 2 mm and drill holes to either 2 mm or 6 mm under cooled irrigation. Animals were sacrificed 1 day postoperatively and subchondral bone assessed by histology and micro-CT. We confirmed one hypothesis that microfracture produces fractured and compacted bone around holes, essentially sealing them off from viable bone marrow and potentially impeding repair. In contrast, drilling cleanly removed bone from the holes to provide access channels to marrow stroma. Our second hypothesis that drilling would cause greater osteocyte death than microfracture due to heat necrosis was not substantiated, because more empty osteocyte lacunae were associated with microfracture than drilling, probably due to shearing and crushing of adjacent bone. Drilling deeper to 6 mm versus 2 mm penetrated the epiphyseal scar in this model and led to greater subchondral hematoma. Our study revealed distinct differences between microfracture and drilling for acute subchondral bone structure and osteocyte necrosis. Additional ongoing studies suggest these differences significantly affect long-term cartilage repair outcome.

[Comparative Research on Repairing Acute Osteochondral Defect by Mosaicplasty and the Combination of Mosaicplasty with Tissue Engineering Methods]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Apr, 2009  |  Pubmed ID: 19431993

To compare the effect of mosaicplasty, mosaicplasty with gene enhanced tissue engineering and mosaicplasty with the gels of non-gene transduced BMSCs in alginate on the treatment of acute osteochondral defects.

HCV NS5B Polymerase Inhibitors 1: Synthesis and in Vitro Activity of 2-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene Derivatives

Bioorganic & Medicinal Chemistry Letters. Aug, 2009  |  Pubmed ID: 19502055

2-(1,1-Dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives as potential anti-HCV drugs targeting NS5B polymerase have been investigated. Their synthesis, HCV NS5B polymerase inhibition and replicon activity are discussed.

Enhancement of Hyaluronic Acid Production by Batch Culture of Streptococcus Zooepidemicus with N-dodecane As an Oxygen Vector

Journal of Microbiology and Biotechnology. Jun, 2009  |  Pubmed ID: 19597318

This study aimed to examine the influence of adding an oxygen vector, n-dodecane, on hyaluronic acid (HA) production by batch culture of Streptococcus zooepidemicus. Owing to the high viscosity of culture broth, microbial HA production during 8-16 h was limited by the oxygen transfer coefficient K(L)a, which could be enhanced by adding n-dodecane. With the addition of n-dodecane to the culture medium to a final concentration of 5% (v/v), the average value of K(L)a during 8-16 h was increased to 36+/-2 h(-1), which was 3.6 times that of the control without n-dodecane addition. With the increased K(L)a and dissolved oxygen (DO) by adding 5% (v/v) of n-dodecane, a 30% increase of HA production was observed compared with the control. Furthermore, the comparison of the oxygen mass transfer in the absence and presence of n-dodecane was conducted with two proposed mathematical models. The use of n-dodecane as an oxygen vector, as described in this paper, provides an efficient alternative for the optimization of other aerobic biopolymer productions,where K(L)a is usually a limiting factor.

Cell Adhesion to Fibronectin Induces Mitomycin C Resistance in Bladder Cancer Cells

BJU International. Dec, 2009  |  Pubmed ID: 19624598

To investigate whether cell adhesion to fibronectin induces drug resistance in human bladder cancer cells, and to study the survival signalling pathway in cell adhesion to fibronectin-mediated chemotherapy resistance in vitro.

Genome-wide Analysis of the RpoN Regulon in Geobacter Sulfurreducens

BMC Genomics. 2009  |  Pubmed ID: 19624843

The role of the RNA polymerase sigma factor RpoN in regulation of gene expression in Geobacter sulfurreducens was investigated to better understand transcriptional regulatory networks as part of an effort to develop regulatory modules for genome-scale in silico models, which can predict the physiological responses of Geobacter species during groundwater bioremediation or electricity production.

Overexpression of Tissue Inhibitors of Metalloproteinase 2 Up-regulates NF-kappaB Activity in Melanoma Cells

Journal of Molecular Signaling. 2009  |  Pubmed ID: 19627587

Matrix Metalloproteinase functions in the remodeling of the extracellular matrix that is integral for many normal and pathological processes such as morphogenesis, angiogenesis, tissue repair, and tumor invasion. The tissue inhibitor of the metalloproteinase family including the tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates the activity of multifunctional metalloproteinase. It is known that IL-8, the target gene of NF-kappaB pathway, increases in the melanoma cells. However, it is not clear whether the TIMP-2 expression regulates the NF-kappaB pathway. In this study, we have used stable melanoma cell lines, parental A2058, A2058T2-1 overexpressing TIMP-2, and A2058T2R-7 underexpressing TIMP-2, to determine the TIMP-2 regulation of the NF-kappaB activity.

Hydrogen Peroxide Induces the Activation of the Phospholipase C-gamma1 Survival Pathway in PC12 Cells: Protective Role in Apoptosis

Acta Biochimica Et Biophysica Sinica. Aug, 2009  |  Pubmed ID: 19657563

It has been reported that phospholipase C-gamma1 (PLC-gamma1) plays an important protective role in hydrogen peroxide (H(2)O(2))-induced pheochromocytoma (PC) 12 cells death. However, most studies have used high doses of H2O2 and the downstream targets of PLC-gamma1 activation remain to be identified. The present study was designed to examine the roles of PLC-gamma1 signaling pathway in the apoptosis of PC12 cells induced by low dose of H(2)O(2), as well as the downstream factors involved in this pathway. Low-dose treatment of H(2)O(2) resulted in PLC-gamma1 tyrosine phosphorylation in a time-dependent manner and H(2)O(2) killed the PC12 cells by inducing necrosis. In contrast, pretreatment of PC12 cells with U73122, a specific inhibitor of PLC, markedly increased the percentage of dead cells. The mode of cell death was converted to apoptosis as determined by Hoechst/PI nuclear staining and fluorescence microscopy. Western blot analysis demonstrated that the expression of Bcl-2 protein and the activation of pro-caspase-3 were not significantly affected by low dose of H(2)O(2) alone. However, after pretreatment with U73122, Bcl-2 protein expression was dramatically decreased and the activation of pro-caspase-3 was significantly increased. We concluded that PLC-gamma1 plays an important protective role in H(2)O(2)-induced PC12 cells death. Bcl-2 and caspase-3 probably participate in the signaling pathway as downstream factors.

Modeling and Optimization of Microbial Hyaluronic Acid Production by Streptococcus Zooepidemicus Using Radial Basis Function Neural Network Coupling Quantum-behaved Particle Swarm Optimization Algorithm

Biotechnology Progress. Nov-Dec, 2009  |  Pubmed ID: 19691123

Hyaluronic acid (HA) is a natural biopolymer with unique physiochemical and biological properties and finds a wide range of applications in biomedical and cosmetic fields. It is important to increase HA production to meet the increasing HA market demand. This work is aimed to model and optimize the amino acids addition to enhance HA production of Streptococcus zooepidemicus with radial basis function (RBF) neural network coupling quantum-behaved particle swarm optimization (QPSO) algorithm. In the RBF-QPSO approach, RBF neural network is used as a bioprocess modeling tool and QPSO algorithm is applied to conduct the optimization with the established RBF neural network black model as the objective function. The predicted maximum HA yield was 6.92 g/L under the following conditions: arginine 0.062 g/L, cysteine 0.036 g/L, and lysine 0.043 g/L. The optimal amino acids addition allowed HA yield increased from 5.0 g/L of the control to 6.7 g/L in the validation experiments. Moreover, the modeling and optimization capacity of the RBF-QPSO approach was compared with that of response surface methodology (RSM). It was indicated that the RBF-QPSO approach gave a slightly better modeling and optimization result compared with RSM. The developed RBF-QPSO approach in this work may be helpful for the modeling and optimization of the other multivariable, nonlinear, time-variant bioprocesses.

Microbial Production of Low Molecular Weight Hyaluronic Acid by Adding Hydrogen Peroxide and Ascorbate in Batch Culture of Streptococcus Zooepidemicus

Bioresource Technology. Jan, 2009  |  Pubmed ID: 18619838

Microbial production of low molecular weight hyaluronic acid (HA) by the addition of hydrogen peroxide and ascorbate during the batch culture of Streptococcus zooepidemicus was investigated. Hydrogen peroxide (1.0 mmol/g HA) and ascorbate (0.5 mmol/g HA) were added at 8h and 12h to degrade HA. With the redox depolymerization of HA, the HA molecular weight decreased from 1,300 kDa for the control to 80 kDa, and the average broth viscosity during 8-16 h decreased from 360 mPa s for the control to 290 mPa s. The average oxygen mass transfer coefficient K(L)a increased from 10h(-1) for the control to 35 h(-1) and the average dissolved oxygen level increased from 1% of air saturation in the control to 10%. HA production increased from 5.0 g/L for the control to 6.5 g/L, and contributed to the increased redox potential and energy charge. This novel process not only significantly enhanced production of low molecular weight HA, but also improved purification efficiency due to a decreased broth viscosity. Low molecular weight HA finds applications in biomedical and healthcare fields.

High-yield Hypocrellin A Production in Solid-state Fermentation by Shiraia Sp. SUPER-H168

Applied Biochemistry and Biotechnology. Apr, 2010  |  Pubmed ID: 19697160

Hypocrellin A production by Shiraia sp. SUPER-H168 was studied under solid-state fermentation. Corn was found to be the best substrate after evaluating eight kinds of agro-industrial crops and residues. The optimized solid-state fermentation conditions were as follows: inoculum size 3 x 10(6) spores, substrate particle size 0.8-1 mm, initial moisture content 50%, and temperature 30 degrees C. Six kinds of external carbon source and seven kinds of external nitrogen source were evaluated, respectively, for HA production. Glucose and NaNO(3) were the best. The combination of them was optimized by the response surface method. The optimum compositions of the supplementary glucose and NaNO(3) were 1.65 g/100 g and 0.43 g/L, respectively. Hypocrellin A production reached 4.7 mg/g.

An "in-depth" Description of the Small Non-coding RNA Population of Schistosoma Japonicum Schistosomulum

PLoS Neglected Tropical Diseases. 2010  |  Pubmed ID: 20161724

Parasitic flatworms of the genus Schistosoma are the causative agents of schistosomiasis, which afflicts more than 200 million people yearly in tropical regions of South America, Asia and Africa. A promising approach to the control of this and many other diseases involves the application of our understanding of small non-coding RNA function to the design of safe and effective means of treatment. In a previous study, we identified five conserved miRNAs from the adult stage of Schistosoma japonicum. Here, we applied Illumina Solexa high-throughput sequencing methods (deep sequencing) to investigate the small RNAs expressed in S. japonicum schistosomulum (3 weeks post-infection). This has allowed us to examine over four million sequence reads including both frequently and infrequently represented members of the RNA population. Thus we have identified 20 conserved miRNA families that have orthologs in well-studied model organisms and 16 miRNA that appear to be specific to Schistosoma. We have also observed minor amounts of heterogeneity in both 3' and 5' terminal positions of some miRNA as well as RNA fragments resulting from the processing of miRNA precursor. An investigation of the genomic arrangement of the 36 identified miRNA revealed that seven were tightly linked in two clusters. We also identified members of the small RNA population whose structure indicates that they are part of an endogenously derived RNA silencing pathway, as evidenced by their extensive complementarities with retrotransposon and retrovirus-related Pol polyprotein from transposon.

Gene Duplication in the Genome of Parasitic Giardia Lamblia

BMC Evolutionary Biology. 2010  |  Pubmed ID: 20163721

Giardia are a group of widespread intestinal protozoan parasites in a number of vertebrates. Much evidence from G. lamblia indicated they might be the most primitive extant eukaryotes. When and how such a group of the earliest branching unicellular eukaryotes developed the ability to successfully parasitize the latest branching higher eukaryotes (vertebrates) is an intriguing question. Gene duplication has long been thought to be the most common mechanism in the production of primary resources for the origin of evolutionary novelties. In order to parse the evolutionary trajectory of Giardia parasitic lifestyle, here we carried out a genome-wide analysis about gene duplication patterns in G. lamblia.

Functional Characterization and High-throughput Proteomic Analysis of Interrupted Genes in the Archaeon Sulfolobus Solfataricus

Journal of Proteome Research. May, 2010  |  Pubmed ID: 20192274

Sequenced genomes often reveal interrupted coding sequences that complicate the annotation process and the subsequent functional characterization of the genes. In the past, interrupted genes were generally considered to be the result of sequencing errors or pseudogenes, that is, gene remnants with little or no biological importance. However, recent lines of evidence support the hypothesis that these coding sequences can be functional; thus, it is crucial to understand whether interrupted genes are expressed in vivo. We addressed this issue by experimentally demonstrating the existence of functional disrupted genes in archaeal genomes. We discovered previously unknown disrupted genes that have interrupted homologues in distantly related species of archaea. The combination of a RT-PCR strategy with shotgun proteomics demonstrates that interrupted genes in the archaeon Sulfolobus solfataricus are expressed in vivo. In addition, the sequence of the peptides determined by LCMSMS and experiments of in vitro translation allows us to identify a gene expressed by programmed -1 frameshifting. Our findings will enable an accurate reinterpretation of archaeal interrupted genes shedding light on their function and on archaeal genome evolution.

Salmonella Typhimurium Infection Increases P53 Acetylation in Intestinal Epithelial Cells

American Journal of Physiology. Gastrointestinal and Liver Physiology. May, 2010  |  Pubmed ID: 20224008

The ability of Salmonella typhimurium to enter intestinal epithelial cells constitutes a crucial step in pathogenesis. Salmonella invasion of the intestinal epithelium requires bacterial type three secretion system. Type three secretion system is a transport device that injects virulence proteins, called effectors, to paralyze or reprogram the eukaryotic cells. Avirulence factor for Salmonella (AvrA) is a Salmonella effector that inhibits the host's inflammatory responses. The mechanism by which AvrA modulates host cell signaling is not entirely clear. p53 is situated at the crossroads of a network of signaling pathways that are essential for genotoxic and nongenotoxic stress responses. We hypothesized that Salmonella infection activates the p53 pathway. We demonstrated that Salmonella infection increased p53 acetylation. Cells infected with AvrA-sufficient Salmonella have increased p53 acetylation, whereas cells infected with AvrA-deficient Salmonella have less p53 acetylation. In a cell-free system, AvrA possessed acetyltransferase activity and used p53 as a substrate. AvrA expression increased p53 transcriptional activity and induced cell cycle arrest. HCT116 p53-/- cells had less inflammatory responses. In a mouse model of Salmonella infection, intestinal epithelial p53 acetylation was increased by AvrA expression. Our studies provide novel mechanistic evidence that Salmonella modulates the p53 pathway during intestinal inflammation and infection.

High-efficiency Mechanical Energy Storage and Retrieval Using Interfaces in Nanowires

Nano Letters. May, 2010  |  Pubmed ID: 20369897

By molecular dynamics simulations, we demonstrate a new concept for mechanical energy storage and retrieval using surface energy as reservoir in body-centered cubic (bcc) tungsten nanowire, achieving a combination of unique features such as large and constant actuation stress (>3 GPa), exceptionally large actuation strain (>30%) and energy density, and >98% energy storage efficiency. The underlying mechanism is a shear-dominant diffusionless transformation akin to martensitic transformation, but driven by surface rather than bulk free energies, and enabled by motion of coherent twin boundary, whose migration has been shown to possess ultralow friction in bcc metals. Aside from energy storage, such surface-energy driven displacive transformations are important for phase transformation and energy-matter control at the nanoscale.

[Validity and Reliability of the Nonalcoholic Fatty Liver Diseases Activity Score (NAS) in Korean NAFLD Patients and Its Correlation with Clinical Factors]

The Korean Journal of Hepatology. Mar, 2010  |  Pubmed ID: 20375640

Nonalcoholic steatohepatitis (NASH) is commonly diagnosed using the semi-quantitative grading and staging system proposed by Brunt et al. in 1999. The Pathology Committee of the NASH established the nonalcoholic fatty liver diseases (NAFLD) activity score (NAS) in 2005. The aim of this study was to elucidate the validity and reliability of the NAS in Korean NAFLD patients.

The Study of Distraction Osteogenesis with Nitinol Shape Memory Alloy Spring Controlled by Infrared Light

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. Aug, 2010  |  Pubmed ID: 20382048

The objective of this study was to investigate the feasibility of distraction osteogenesis with a nitinol shape memory alloy spring controlled by infrared light.

[Recent Research Advances on Function of CD4+T Lymphocytes]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Apr, 2010  |  Pubmed ID: 20416207

Cellular immunity is an important component of human immune system and plays a crucial role in the fight against tumor cell or invasive pathogens. Researches on cell-based immunotherapy have long been focused on eliciting tumor-specific CD8+ cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. However, the resulting treatments have been surprisingly poor at inducing complete tumor rejection, in both the experimental models and clinical trials. The CD4+ T cells has been studied mainly for their role as helpers for CD8+ CTL, even suggesting that the tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. Recent studies indicated that CD4+T cells are not a pure cell lineage with single function, but a cell population with complex functions. Moreover CD4+ T cells may not only be helper cells, but also act as potent effector cells or partners with NK cells that can clear a wide variety of tumors. In a word, the antitumor potential of effector CD4+ T cells might have been underestimated. In this article, the classification and differentiation of CD4+ T cells, the function and secreted cytokines of CD4+ T cells, the CD4+ T cells and tumor immune, the tumor-immuno regulatory effects of CD4+ T cells, and clinical researches of CD4+ T cells are reviewed.

[Research on Signal Detection Methods Based on Data Mining in Adverse Drug Reaction of Shuanghuanglian Injection]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Feb, 2010  |  Pubmed ID: 20422995

This paper is aimed to explore the adverse reaction condition of Shuanghuangli an injection with three common used signal detecting methods based on SRS database of Jiangsu province, and to evaluate the performance of three methods.

Chronic Effects of a Salmonella Type III Secretion Effector Protein AvrA in Vivo

PloS One. 2010  |  Pubmed ID: 20463922

Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host.

Scaffold-guided Subchondral Bone Repair: Implication of Neutrophils and Alternatively Activated Arginase-1+ Macrophages

The American Journal of Sports Medicine. Sep, 2010  |  Pubmed ID: 20522834

Microfracture and drilling elicit a cartilage repair whose quality depends on subchondral bone repair. Alternatively activated (AA) macrophages express arginase-1, release angiogenic factors, and could be potential mediators of trabecular bone repair.

Vitamin D Receptor Negatively Regulates Bacterial-stimulated NF-kappaB Activity in Intestine

The American Journal of Pathology. Aug, 2010  |  Pubmed ID: 20566739

Vitamin D receptor (VDR) plays an essential role in gastrointestinal inflammation. Most investigations have focused on the immune response; however, how bacteria regulate VDR and how VDR modulates the nuclear factor (NF)-kappaB pathway in intestinal epithelial cells remain unexplored. This study investigated the effects of VDR ablation on NF-kappaB activation in intestinal epithelia and the role of enteric bacteria on VDR expression. We found that VDR(-/-) mice exhibited a pro-inflammatory bias. After Salmonella infection, VDR(-/-) mice had increased bacterial burden and mortality. Serum interleukin-6 in noninfected VDR(+/+) mice was undetectable, but was easily detectable in VDR(-/-) mice. NF-kappaB p65 formed a complex with VDR in noninfected wild-type mouse intestine. In contrast, deletion of VDR abolished VDR/P65 binding. P65 nuclear translocation occurred in colonic epithelial cells of untreated VDR(-/-) mice. VDR deletion also elevated NF-kappaB activity in intestinal epithelia. VDR was localized to the surface epithelia of germ-free mice, but to crypt epithelial cells in conventionalized mice. VDR expression, distribution, transcriptional activity, and target genes were regulated by Salmonella stimulation, independent of 1,25-dihydroxyvitamin D3. Our study demonstrates that commensal and pathogenic bacteria directly regulate colonic epithelial VDR expression and location in vivo. VDR negatively regulates bacterial-induced intestinal NF-kappaB activation and attenuates response to infection. Therefore, VDR is an important contributor to intestinal homeostasis and host protection from bacterial invasion and infection.

Study on the Relationship Between Cyclodextrin Glycosyltransferase's Thermostability and Salt Bridge by Molecular Dynamics Simulation

Protein and Peptide Letters. Nov, 2010  |  Pubmed ID: 20594159

Cyclodextrin glycosyltransferase (EC 2.4.1.19, CGTase) is an important industrial enzyme in the production of cyclodextrins. Thermal stability is of great importance for this enzyme. Rational design of thermostable variants of mesophilic proteins is well motivated. In this work, molecular dynamics simulations have been performed to study thermal stabilization of CGTase protein via electrostatic interactions of salt bridges. To predict behaviors of the salt bridges engineered into a mesophilic protein to increase stability, in silico mutant of CGTase from the mesophilic Bacillus macerans is generated. Dynamic motions of salt bridges in thermal unstable regions are monitored during the simulations. Among the five salt bridges, Lys88-Glu91, Asp296-Arg335 and Arg336-Asp370 are found to be more important for stability than the others. Especially, the region C is stabilized by a well-organized strong multiple salt bridge interactions. The results reveal that salt bridges involved in thermal unstable regions are relatively strong and prone to be tightened at elevated temperature, which can hold the stable conformation of the spatial neighborhood. Meanwhile, we use the heat capacity and total energy as the measure of stability difference between the original and its mutant variant, and then, quantify the contribution of salt bridges in thermal unstable regions for the mutant protein. Therefore, the viable computational strategy has been demonstrated to improve thermal stability of the mesophilic CGTase by introducing stable salt bridge interactions into its thermal unstable regions and it can be universally applied to other enzymes.

Comparative Pharmacokinetics and Bioavailability Studies of Quercetin, Kaempferol and Isorhamnetin After Oral Administration of Ginkgo Biloba Extracts, Ginkgo Biloba Extract Phospholipid Complexes and Ginkgo Biloba Extract Solid Dispersions in Rats

Fitoterapia. Dec, 2010  |  Pubmed ID: 20603197

The aim of this study was to improve the oral bioavailability of Ginkgo biloba extract (GBE) through preparing G. biloba extract phospholipid complexes (GBP) and G. biloba extract solid dispersions (GBS). Firstly we prepared the GBP and GBS and studied their physicochemical properties by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and dissolution. Then we studied the pharmacokinetic characteristics and bioavailability in rats. The results showed that the bioavailability of quercetin, kaempferol and isorhamnetin in rats was increased remarkably after oral administration of GBP and GBS comparing with GBE. The bioavailabilities of GBP increased more than that of GBS.

MTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone Availability

The Journal of Biological Chemistry. Aug, 2010  |  Pubmed ID: 20605781

Balanced protein synthesis and degradation are crucial for proper cellular function. Protein synthesis is tightly coupled to energy status and nutrient levels by the mammalian target of rapamycin complex 1 (mTORC1). Quality of newly synthesized polypeptides is maintained by the molecular chaperone and ubiquitin-proteasome systems. Little is known about how cells integrate information about the quantity and quality of translational products simultaneously. We demonstrate that cells distinguish moderate reductions in protein quality from severe protein misfolding using molecular chaperones to differentially regulate mTORC1 signaling. Moderate reduction of chaperone availability enhances mTORC1 signaling, whereas stress-induced complete depletion of chaperoning capacity suppresses mTORC1 signaling. Molecular chaperones regulate mTORC1 assembly in coordination with nutrient availability. This mechanism enables mTORC1 to rapidly detect and respond to environmental cues while also sensing intracellular protein misfolding. The tight linkage between protein quality and quantity control provides a plausible mechanism coupling protein misfolding with metabolic dyshomeostasis.

Optimization and Scale-up of Propionic Acid Production by Propionic Acid-tolerant Propionibacterium Acidipropionici with Glycerol As the Carbon Source

Bioresource Technology. Nov, 2010  |  Pubmed ID: 20620054

Propionic acid production by Propionibacterium acidipropionici with glycerol as sole carbon source was studied in 7-L batch and 10m(3) bioreactor cultures. In batch cultures, propionic acid production increased and specific cell growth rate decreased with increasing glycerol concentrations. Maximum propionic acid production and productivity reached 44.62+/-1.12g/L and 0.20+/-0.0075gL(-1)h(-1)at 220h, respectively, when glycerol was fed at a constant rate of 0.01L/h from 72 to 120h with an initial glycerol concentration of 30g/L. In the 10m(3) bioreactor, maximum propionic acid production reached 47.28+/-0.12g/L at 240h. This glycerol feeding approach may be useful for propionic acid production on an industrial scale.

Vitamin D and Mucosal Immune Function

Current Opinion in Gastroenterology. Nov, 2010  |  Pubmed ID: 20639756

Significant advances have been made in the characterization of Vitamin D and the Vitamin D receptor (VDR) in immune function. The studies of signaling pathways involved in the response to infection and inflammation have led to a more detailed understanding of the cellular response to Vitamin D through VDR. This review summarizes recent progress in understanding how Vitamin D contributes to mucosal immune function, particularly in relation to the molecular mechanisms by which Vitamin D and VDR influence mucosal immunity, bacterial infection, and inflammation.

Right-sided Free Wall Accessory Pathway Refractory to Conventional Catheter Ablation: Lessons from 3-dimensional Electroanatomic Mapping

Journal of Cardiovascular Electrophysiology. Dec, 2010  |  Pubmed ID: 20653815

the aim of this study was to delineate the electroanatomic substrates of right-sided free wall (RFW) accessory pathways (APs) that were refractory to conventional catheter ablation utilizing 3-dimensional (3-D) mapping.

The Inflammatory Cytokine Tumor Necrosis Factor Modulates the Expression of Salmonella Typhimurium Effector Proteins

Journal of Inflammation (London, England). 2010  |  Pubmed ID: 20704730

Tumor necrosis factor alpha (TNF-alpha)is a host inflammatory factor. Bacteria increase TNF-alpha expression in a variety of human diseases including infectious diseases, inflammatory bowel diseases, and cancer. It is unknown, however, how TNF-alpha directly modulates bacterial protein expression during intestinal infection and chronic inflammation. In the current study, we hypothesize that Salmonella typhimurium senses TNF-alpha and show that TNF-alpha treatment modulates Salmonella virulent proteins (called effectors), thus changing the host-bacterial interaction in intestinal epithelial cells. We investigated the expression of 23 Salmonella effectors after TNF-alpha exposure. We found that TNF-alpha treatment led to differential effector expression: effector SipA was increased by TNF-alpha treatment, whereas the expression levels of other effectors, including gogB and spvB, decreased in the presence of TNF-alpha. We verified the protein expression of Salmonella effectors AvrA and SipA by Western blots. Furthermore, we used intestinal epithelial cells as our experimental model to explore the response of human intestinal cells to TNF-alpha pretreated Salmonella. More bacterial invasion was found in host cells colonized with Salmonella strains pretreated with TNF-alpha compared to Salmonella without TNF-alpha treatment. TNF-alpha pretreated Salmonella induced higher proinflammatory JNK signalling responses compared to the Salmonella strains without TNF-alpha exposure. Exposure to TNF-alpha made Salmonella to induce more inflammatory cytokine IL-8 in intestinal epithelial cells. JNK inhibitor treatment was able to suppress the effects of TNF-pretreated-Salmonella in enhancing expressions of phosphorylated-JNK and c-jun and secretion of IL-8. Overall, our study provides new insights into Salmonella-host interactions in intestinal inflammation.

Safety of Capecitabine: a Review

Expert Opinion on Drug Safety. Sep, 2010  |  Pubmed ID: 20722491

Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years.

Analysis and Characterization of the Genes Encoding the Dicer and Argonaute Proteins of Schistosoma Japonicum

Parasites & Vectors. 2010  |  Pubmed ID: 20849617

ABSTRACT:

Color Constancy Based on Texture Pyramid Matching and Regularized Local Regression

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. Oct, 2010  |  Pubmed ID: 20921999

Considering that no single algorithm available is universal in color constancy, we propose an effective combination approach using a texture-based matching strategy and a local regression with prior-knowledge regularization. To represent the images, we construct a texture pyramid using an integrated Weibull distribution. Then we define an image similarity measure to search for the K most similar images of the test image. To combine the single algorithms, we integrate prior knowledge into a regularized local regression in a decorrelated color space. Regression weights are obtained on these similar images, and the regularization is implemented by the frequency ratio of the best single algorithm. Experiments on two real world datasets show our approach outperforms the state-of-the-art single algorithms and popular combination approaches with a performance increase of at least 29% compared to the best-performing single algorithm w.r.t median angular error.

High Origin of Radial Arteries: a Report of Two Rare Cases

TheScientificWorldJournal. 2010  |  Pubmed ID: 20953550

Variations in the arterial supply of the upper limb are relatively common, with reported prevalence rates ranging from 11 to 24.4%. Of these, the most commonly encountered variation in the arm is a high origin of the radial artery. However, after consecutively dissecting and examining 600 Singaporean Chinese cadavers (1,200 upper limbs), we found only two cases of this. In both cases, the brachioradial artery originated from the upper one-third of the brachial artery and continued distally as the radial artery in the forearm. The local prevalence of 0.33% of this variation is significantly lower compared against populations from other geographical regions. Although rare, recognition of the variation is of fundamental importance to clinical practice.

[Preparation of Multivariant-phospholipid Complex of Ginkgo Biloba Extract]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Aug, 2010  |  Pubmed ID: 21046750

To prepare Ginkgo biloba extract multivariant-phospholipid complex(MGBP) and improve the vitro dissolution of ginkgo total flavonoids by adding another water-soluble carrier in phospholipid complex.

Metabolic Response of Geobacter Sulfurreducens Towards Electron Donor/acceptor Variation

Microbial Cell Factories. 2010  |  Pubmed ID: 21092215

Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen) and acceptors (Fe(III), fumarate) was investigated via (13)C-based metabolic flux analysis. We examined the (13)C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with (13)C-acetate.

Vitamin D Receptor Deletion Leads to Reduced Level of IkappaBalpha Protein Through Protein Translation, Protein-protein Interaction, and Post-translational Modification

The International Journal of Biochemistry & Cell Biology. Feb, 2010  |  Pubmed ID: 19931640

Vitamin D receptor plays an essential role in the regulation of inflammation. Previous studies demonstrate that vitamin D receptor negatively modulates the proinflammatory NF-kappaB pathway. However, it is unknown how vitamin D receptor regulates IkappaBalpha, the endogenous inhibitor of NF-kappaB. Here we investigated the molecular mechanism of vitamin D receptor deletion and IkappaBalpha expression. We found that cells lacking vitamin D receptor had significantly increased levels of IkappaBalpha mRNA and simultaneously decreased levels of IkappaBalpha protein. Lacking vitamin D receptor abolished its binding to the IkappaBalpha promoter. Moreover, the levels of protein translation regulators and the rate of protein synthesis were both decreased in cells lacking vitamin D receptor. At the post-translational level, IkappaBalpha ubiquitination was enhanced, indicating increased degradation of IkappaBalpha in the absence of vitamin D receptor. We further transfected cells with a plasmid carrying either wild-type or mutant IkappaBalpha. The expression of wild-type IkappaBalpha was much higher in the cells with vitamin D receptor than in the cells without vitamin D receptor, whereas the expression of exogenous IkappaBalpha was equally high in both cell lines. In summary, vitamin D receptor deletion affects IkappaBalpha through mRNA transcription, protein translation, protein-protein interaction, post-translational modification, and protein degradation, thus reducing the level of IkappaBalpha protein. Cells lacking vitamin D receptor are known in a proinflammatory state with activation of NF-kappaB. Our study provides new insight into vitamin D receptor regulation of an inhibitor of NF-kappaB in inflammation. Deletion of vitamin D receptor contributes to the activation of NF-kappaB on multiple levels.

Cytotoxicity and Cellular Uptake of Iron Nanowires

Biomaterials. Mar, 2010  |  Pubmed ID: 19945156

The toxicity of nanostructured materials and nanoparticles are very important considerations for many nanotechnology applications. Iron nanowires (NWs), as useful magnetic nanomaterials, may be good candidates for several biomedical applications. Here Fe NWs with an average diameter of about 50 nm were prepared by electrodeposition within the nanopores of anodic aluminum oxide (AAO) templates, and characterized by using scanning electron microcopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The cytotoxicity of the Fe NWs was studied at cell level. Specifically, the influence of concentration and size on the cytotoxicity of Fe NWs to HeLa cells was evaluated by MTT assay combined with direct morphology observations by TEM and phase contrast microscopy. The results clearly showed that the presence of Fe NWs had no significant effect on the cell proliferation and cell viability, even the HeLa cells exposed to Fe NWs at the high concentration of 10,000 per cell for 72 h still showed high cell viability of about 80%. From phase contrast microscopy, confocal laser scanning microscopy (CLSM) and TEM observations, it was found that Fe NWs were indeed internalized by HeLa cells. The cellular uptake process and results of Fe NWs demonstrated that as-prepared Fe NWs had not only a good biocompatibility but also a very low cytotoxicity.

Biodiversity of Brackish Water Amphipods (crustacean) in Two Estuaries, Southeast Coast of India

Environmental Monitoring and Assessment. Dec, 2010  |  Pubmed ID: 20082137

The present study about the gammarid amphipods of Vellar and Uppanar estuaries was performed during two seasons (pre-monsoon and post-monsoon, 2005-2006), respectively, in nine habitats: five in the Vellar estuary and four in the Uppanar estuary. Amphipod samples were collected from sediments, oyster beds, seaweeds, sea grass, and mangroves. A total of 29 species of gammarid amphipods were collected in each area. The surface water temperature ranged from 16°C to 26°C, the salinity from 20 to 32 psu, and the pH between 7.5 and 8.3. Dissolved oxygen ranged from 5.3 to 7.8 ml/l. The maximum abundance of amphipods was observed during the pre-monsoon (July to September) in Vellar mangrove, and it was minimum during the pre-monsoon in Uppanar sea grass. It was found that several physicochemical factors, such as salinity, temperature, dissolved oxygen, pH, and the substrate have a marked effect on the distribution and the relative abundance of amphipods. The ranges of species diversity, richness, dominance, and evenness in the Vellar and Uppanar estuaries were 1.58-4.15, 1.82-5.29, 0-0.11, and 0.96-1, respectively. Using multivariate analyses, in each estuary, it was possible to identify different communities of amphipod species according to their habitats.

Salmonella Regulation of Intestinal Stem Cells Through the Wnt/beta-catenin Pathway

FEBS Letters. Mar, 2010  |  Pubmed ID: 20083111

Recent studies have revealed that bacteria target stem cells for long-term survival in a Drosophila model. However, in mammalian models, little is known about bacterial infection and intestinal stem cells. Our study aims at understanding bacterial regulation of the intestinal stem cell in a Salmonella colitis mouse model. We found that Salmonella activates the Wnt/beta-catenin signaling pathway that is known to regulate stem cells. We identified Salmonella protein AvrA that modulates Wnt signaling including upregulating Wnt expression, modifying beta-catenin, increasing total beta-catenin expression, and activating Wnt/beta-catenin transcriptional activity in the intestinal epithelial cells. The numbers of stem cells and proliferative cells increased in the intestine infected with Salmonella expressing AvrA. Our study provides insights into bacterial infection and stem cell maintenance.

Hemozoin from Schistosoma Japonicum Does Not Affect Murine Myeloid Dendritic Cell Function

Parasitology Research. Feb, 2010  |  Pubmed ID: 20087747

Hemozoin (Hz) formation is a byproduct of hemoglobin digestion in some hematophagous organisms. Although Hz produced by Plasmodium falciparum (PfHz) has been shown to affect development and activities of human dendritic cells (DCs), the effects of Schistosoma Hz on DCs have not been elucidated. Our data presented in this report demonstrated that native Schistosoma japonica Hz (SjHz) did not affect the differentiation of murine bone marrow cells into immature DCs (imDCs). Maturation and stimulatory activities to T cells by imDCs induced by LPS were not altered in the presence of SjHz; whereas purified PfHz induced a slight increase in CD40 expression and enhanced IL-12p40 secretion. Lastly, SjHz treatment did not significantly affect the phagocytic activities of DCs. These data suggested that SjHz failed to exert any significant effects on the development and activities of murine myeloid DCs. The mechanisms of different effects on DCs by SjHz and PfHz remain to be elucidated.

Strong Crystal Size Effect on Deformation Twinning

Nature. Jan, 2010  |  Pubmed ID: 20090749

Deformation twinning in crystals is a highly coherent inelastic shearing process that controls the mechanical behaviour of many materials, but its origin and spatio-temporal features are shrouded in mystery. Using micro-compression and in situ nano-compression experiments, here we find that the stress required for deformation twinning increases drastically with decreasing sample size of a titanium alloy single crystal, until the sample size is reduced to one micrometre, below which the deformation twinning is entirely replaced by less correlated, ordinary dislocation plasticity. Accompanying the transition in deformation mechanism, the maximum flow stress of the submicrometre-sized pillars was observed to saturate at a value close to titanium's ideal strength. We develop a 'stimulated slip' model to explain the strong size dependence of deformation twinning. The sample size in transition is relatively large and easily accessible in experiments, making our understanding of size dependence relevant for applications.

Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases Are Essential for the Inflammatory Response in Cancer Cells

Journal of Signal Transduction. 2010  |  Pubmed ID: 21152266

Inflammation plays a critical role in the development of cancer. Matrix Metalloproteinase (MMP) functions in the remodeling of the extracellular matrix that is integral for many normal and pathological processes such as morphogenesis, angiogenesis, tissue repair, and tumor invasion. The tissue inhibitor of metalloproteinases (TIMPs) family regulates the activity of multifunctional metalloproteinases. In this paper, we discuss the role and mechanism of MMP and TIMP in regulating inflammation responses in solid tumors. We discuss the mechanism of MMP and inflammation in melanoma, colon cancer, breast cancer, and prostate cancer. We highlight the roles of the TIMP-2 in modulating the proinflammatory NF-κB pathway in melanoma and lung caner cells. Based on the molecular mechanisms of TIMPs and MMPs in inflammation and cancer, we can design new strategies for cancer therapy.

Global Analysis of the Eukaryotic Pathways and Networks Regulated by Salmonella Typhimurium in Mouse Intestinal Infection in Vivo

BMC Genomics. 2010  |  Pubmed ID: 21172007

Acute enteritis caused by Salmonella is a public health concern. Salmonella infection is also known to increase the risk of inflammatory bowel diseases and cancer. Therefore, it is important to understand how Salmonella works in targeting eukaryotic pathways in intestinal infection. However, the global physiological function of Salmonella typhimurium in intestinal mucosa in vivo is unclear. In this study, a whole genome approach combined with bioinformatics assays was used to investigate the in vivo genetic responses of the mouse colon to Salmonella. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) after Salmonella infection.

[Expression of Human Papillomavirus Type 16/18 in Human Cervical Carcinomas by the Quantum Dot Fluorescent In-situ Hybridization]

Zhonghua Bing Li Xue Za Zhi Chinese Journal of Pathology. Oct, 2010  |  Pubmed ID: 21176533

To investigate fluorescence in situ hybridization labeled with quantum dots (QDs) for the detection of human papillomavirus 16/18 (HPV16/18) infection in cervical carcinoma patients.

Eukaryotic Signaling Pathways Targeted by Salmonella Effector Protein AvrA in Intestinal Infection in Vivo

BMC Microbiology. 2010  |  Pubmed ID: 21182782

The Salmonella AvrA gene is present in 80% of Salmonella enterica serovar strains. AvrA protein mimics the activities of some eukaryotic proteins and uses these activities to the pathogen's advantage by debilitating the target cells, such as intestinal epithelial cells. Therefore, it is important to understand how AvrA works in targeting eukaryotic signaling pathways in intestinal infection in vivo. In this study, we hypothesized that AvrA interacts with multiple stress pathways in eukaryotic cells to manipulate the host defense system. A whole genome approach combined with bioinformatics assays was used to investigate the in vivo genetic responses of the mouse colon to Salmonella with or without AvrA protein expression in the early stage (8 hours) and late stage (4 days). Specifically, we examined the gene expression profiles in mouse colon as it responded to pathogenic Salmonella stain SL1344 (with AvrA expression) or SB1117 (without AvrA expression).

Constraint-based Modeling Analysis of the Metabolism of Two Pelobacter Species

BMC Systems Biology. 2010  |  Pubmed ID: 21182788

Pelobacter species are commonly found in a number of subsurface environments, and are unique members of the Geobacteraceae family. They are phylogenetically intertwined with both Geobacter and Desulfuromonas species. Pelobacter species likely play important roles in the fermentative degradation of unusual organic matters and syntrophic metabolism in the natural environments, and are of interest for applications in bioremediation and microbial fuel cells.

Seasonal Variations in Physico-chemical Parameters and Heavy Metals in Water and Sediments of Uppanar Estuary, Nagapattinam, India

Journal of Environmental Biology / Academy of Environmental Biology, India. Sep, 2010  |  Pubmed ID: 21387922

The present study was carried out to determine the physico-chemical characteristics and heavy metals in water and sediments in Uppanar Estuary, Nagapattinam, Southeast coast of India during January to December 2007. The minimum and maximum values of atmospheric and surface water temperatures (degrees C), salinity (per thousand), pH and dissolved oxygen (ml l(-1)) were: 26.0-35.0; 25.0-33.5; 8.0-35.0; 7.2-8.2 and 2.8-5.5 respectively. The ranges of nitrate, nitrite, phosphate and silicate were: 7.05-24.23; 0.82-3.15; 0.31-2.18 and 40.0-198.0 (microM) respectively. The ranges of heavy metals in water (microg 1(-1)) and sediment (microg g(-1)) copper zinc, cadmium and mercury were: 2.45-18.25; 26.43-101.24; 1.23-24.35 and 0.01-0.22 and 5.02-81.27; 22.47-75.42; 2.25-10.06 and 0.01-0.16 respectively.

Enteric Bacteria and Cancer Stem Cells

Cancers. 2010  |  Pubmed ID: 21297903

Intestinal bacteria can contribute to cell proliferation and cancer development, particularly in chronic infectious diseases in which bacteria and/or bacterial components might interfere with cell function. The number of microbial cells within the gut lumen is estimated to be 100 trillion, which is about 10-times larger than the number of eukaryotic cells in the human body. Because of the complexity of the gut flora, identifying the specific microbial agents related to human diseases remains challenging. Recent studies have demonstrated that the stemness of colon cancer cells is, in part, orchestrated by the microenvironment and is defined by high Wnt activity. In this review article, we will discuss recent progress with respect to intestinal stem cells, cancer stem cells, and the molecular mechanisms of enteric bacteria in the activation of the Wnt pathway. We will also discuss the roles of other pathways, including JAK-STAT, JNK, and Notch, in regulating stem cell niches during bacterial infections using Drosophila models. Insights gained from understanding how host-bacterial interaction during inflammation and cancer may serve as a paradigm for understanding the nature of self-renewal signals.

Deletion of Vitamin D Receptor Leads to Premature Emphysema/COPD by Increased Matrix Metalloproteinases and Lymphoid Aggregates Formation

Biochemical and Biophysical Research Communications. Mar, 2011  |  Pubmed ID: 21300024

Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.

Photodynamic Antimicrobial Activity of Hypocrellin A

Journal of Photochemistry and Photobiology. B, Biology. Apr, 2011  |  Pubmed ID: 21300554

Antimicrobial photodynamic therapy is a recently developed therapeutic option that combines a non-toxic photosensitizer with harmless visible light to damage the microbial cell. Hypocrellin A (HA), a natural occurring lipid-soluble perylenequinone pigment, has gained considerable interest since its anticancer and antiviral activities have been reported. Here, we examined the antimicrobial activity of HA against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Salmonella typhimurium). The results indicate that HA has a photodynamic antimicrobial activity against both Gram-positive and Gram-negative bacteria when CaCl(2) or MgCl(2) was employed. A loose binding has been established between HA and the organisms. Molecular oxygen is significantly involved in the photodynamic action of HA. Furthermore, HA maintains a photodynamic activity in terms of both types I and II reactions. Our results confirm the potential of HA to be used as a photosensitizer in antimicrobial photodynamic therapy.

Transmission of New CRF07_BC Strains with 7 Amino Acid Deletion in Gag P6

Virology Journal. 2011  |  Pubmed ID: 21306651

A 7 amino acid deletion in Gag p6 (P6delta7) emerged in Chinese prevalent HIV-1 strain CRF07_BC from different epidemic regions. It is important to determine whether this mutation could be transmitted and spread. In this study, HIV-1 Gag sequences from 5 different epidemic regions in China were collected to trace the transmission linkage and to analyze genetic evolution of P6delta7 strains. The sequence analysis demonstrated that P6delta7 is a CRF07_BC specific deletion, different P6delta7 strains could be originated from different parental CRF07_BC recombinants in different epidemic regions, and the transmission of P6delta7 strain has occurred in IDU populations. This is for the first time to identify the transmission linkage for P6delta7 strains and serves as a wake-up call for further monitoring in the future; In addition, P6delta7 deletion may represent an evolutionary feature which might exert influence on the fitness of CRF07_BC strain.

Induction of Hypocrellin Production by Triton X-100 Under Submerged Fermentation with Shiraia Sp. SUPER-H168

New Biotechnology. Oct, 2011  |  Pubmed ID: 21324385

Hypocrellins are important photodynamic therapy compounds for cancer disease. The effect of surfactants on hypocrellin production of Shiraia sp. SUPER-H168 was evaluated under submerged fermentation condition. The production of hypocrellins could reach 780.6 mg/l with the addition of Triton X-100, confirmed by color reaction, high performance liquid chromatography, electrospray ionization mass spectrometry and nuclear magnetic resonance experiments. According to our observation, treatment of the culture at the beginning of the fermentation was most effective, and the yield of hypocrellins was much lower with the addition of Triton X-100 during the log phase and stationary phase. Shiraia sp. SUPER-H168 could not produce hypocrellin with the addition of other tested surfactants, such as Tween 40, Triton X-114 and SDS. The experimental results indicated that Shiraia sp. SUPER-H168 could not produce hypocrellins without Triton X-100 under submerged fermentation condition.

Deep Sequencing of the Camellia Sinensis Transcriptome Revealed Candidate Genes for Major Metabolic Pathways of Tea-specific Compounds

BMC Genomics. 2011  |  Pubmed ID: 21356090

Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes.

High-efficiency Coaxial Relativistic Backward Wave Oscillator

The Review of Scientific Instruments. Feb, 2011  |  Pubmed ID: 21361620

This paper studies the coaxial relativistic backward wave oscillator (CRBWO) through analytical, numerical, and experimental methods. This new type of device is remarked by its high efficiency of more than 35%, which is predicted by the theoretical calculation and the numerical simulation and validated by experiment. The two primary hindrances preventing CRBWO from achieving the expected high efficiency, the poor coaxiality and the power capacity, are discussed in detail and some advanced methods are developed. The theoretical and numerical conclusions agree with the experiment results, which are obtained from the electric probe and the calorimeter simultaneously for each shot of CRBWO. Employing the electron beam pulse of the full width at half maximum 28 ns, a microwave pulse of the width about 20 ns is generated in the experiment; the power is 710 MW and the efficiency is higher than 33%.

Intrapulmonary Delivery of Human Umbilical Cord Mesenchymal Stem Cells Attenuates Acute Lung Injury by Expanding CD4+CD25+ Forkhead Boxp3 (FOXP3)+ Regulatory T Cells and Balancing Anti- and Pro-inflammatory Factors

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2011  |  Pubmed ID: 21691076

Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4(+)CD25(+) Foxp3(+)Treg cells and lead to an improvement in ALI.

[Umbilical Cord Mesenchymal Stem Cell Transplantation for Treatment of Experimental Autoimmune Myasthenia Gravis in Rats]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jun, 2011  |  Pubmed ID: 21729563

Umbilical cord mesenchymal stem cell (UCMSC) transplantation has been widely used in the treatment of a variety of diseases due to their advantages such as abundant resources, low immunogenicity and large ex vivo expansion capacity. This study was aimed to investigate the effects of UCMSC on experimental autoimmune myasthenia gravis (EAMG) rats. The distribution of human-derived cells was observed by immunofluorescence method, the effect of MSC on B-cell in situ-secreted antibodies was assayed by ELISPOT, the secreted IFN-γ level was detected by using Transwell test. The results showed that UCMSC were able to migrate to inflammation region and lymph nudes, moreover human-derived cells could be detected in medulla zone of lymph nudes. In vitro in situ detection of AchR specific antibody secretion revealed that the full contact of MSC with lymphnode-derived lymphocytes could effectively inhibit production of AchR antibody. Transwell test indicated that the direct contact of UCMSC with CD4 T cells could effectively decrease production of IFN-γ, which modulated the unbalance between Th1/Th2 to a certain extent. It is concluded that UCMSC can regulate the immune system by direct cell-cell contact or/and release of cytokines, which bring a new insight into knowledge about MSC-based therapy for EAMG.

Diversity and Distribution of Diazotrophic Communities in the South China Sea Deep Basin with Mesoscale Cyclonic Eddy Perturbations

FEMS Microbiology Ecology. Dec, 2011  |  Pubmed ID: 22066702

The South China Sea (SCS) is an oligotrophic subtropical marginal ocean with a deep basin and a permanently stratified central gyre. Upwelling and nitrogen fixation provide new nitrogen for primary production in the SCS. This study was aimed at an investigation of phylogenetic diversity and quantification of the diazotroph community in the SCS deep basin, which is characterized by frequent mesoscale eddies. The diazotroph community had a relatively low diversity but a distinct spatial heterogeneity of diversity in the SCS deep basin. The potential for nitrogen fixation consistently occurred during cyclonic eddies, although upwelling of nutrient-replete deep water might have alleviated nitrogen limitation in the SCS. However, diazotrophic proteobacteria were dominant, but neither Trichodesmium nor heterocystous cyanobacterial diatom symbionts. Quantitative PCR analysis using probe-primer sets developed in this study revealed that the nif H gene of the two dominant alpha- and gammaproteobacterial groups was at the highest abundance (up to 10(4) to 10(5)  copies L(-1) ). Trichodesmium thiebautii was detected with an average density of 10(2)  trichomes L(-1) in the euphotic waters, while Richelia intracellularis was observed sporadically under the microscope. The unicellular cyanobacterial groups A and B were not detected in our libraries. Our results suggested that diazotrophic proteobacteria were significant components potentially contributing to nitrogen fixation in this oligotrophic marginal ocean ecosystem.

A New Regime for Mechanical Annealing and Strong Sample-size Strengthening in Body Centred Cubic Molybdenum

Nature Communications. 2011  |  Pubmed ID: 22109521

Because of crystal symmetry, body centred cubic (BCC) metals have large differences in lattice friction between screw and edge dislocations, and manifest generally different mechanical behaviours from face centred cubic (FCC) metals. Although mechanical annealing (significant drop in stored dislocation density in response to applied stress) has been observed in FCC metals, it has not been observed in BCC metals so far. Here we show that significant mechanical annealing does occur in BCC Mo pillars, when their diameters decrease to hundreds of nanometers. In addition, there exists a critical diameter for focused ion beam milled pillars, below which the strengthening exponent increases dramatically, from ~0.3 to ~1. Thus, a new regime of size effects in BCC metals is discovered that converges to that of FCC metals, revealing deep connection in the dislocation dynamics of the two systems.

Simulation and Analysis of a Metamaterial Sensor Based on a Microring Resonator

Sensors (Basel, Switzerland). 2011  |  Pubmed ID: 22163933

Metamaterials are artificial media structured on a size scale smaller than the wavelength of external stimuli, that may provide novel tools to significantly enhance the sensitivity and resolution of the sensors. In this paper, we derive the dispersion relation of hollow cylindrical dielectric waveguide, and compute the resonant frequencies and Q factors of the corresponding Whispering-Gallery-Modes (WGM). A metamaterial sensor based on microring resonator operating in WGM is proposed, and the resonance intensity spectrum curves in the frequency range from 185 to 212 THz were studied under different sensing conditions. Full-wave simulations, considering the frequency shift sensitivity influenced by the change of core media permittivity, the thickness and permittivity of the adsorbed substance, prove that the sensitivity of the metamaterial sensor is more than 7 times that of the traditional microring resonator sensor, and the metamaterial layer loaded in the inner side of the microring doesn't affect the high Q performance of the microring resonator.

A Microring Resonator Based Negative Permeability Metamaterial Sensor

Sensors (Basel, Switzerland). 2011  |  Pubmed ID: 22164062

Metamaterials are artificial multifunctional materials that acquire their material properties from their structure, rather than inheriting them directly from the materials they are composed of, and they may provide novel tools to significantly enhance the sensitivity and resolution of sensors. In this paper, we derive the dispersion relation of a cylindrical dielectric waveguide loaded on a negative permeability metamaterial (NPM) layer, and compute the resonant frequencies and electric field distribution of the corresponding Whispering-Gallery-Modes (WGMs). The theoretical resonant frequency and electric field distribution results are in good agreement with the full wave simulation results. We show that the NPM sensor based on a microring resonator possesses higher sensitivity than the traditional microring sensor since with the evanescent wave amplification and the increase of NPM layer thickness, the sensitivity will be greatly increased. This may open a door for designing sensors with specified sensitivity.

Impact of Mineral Deposition on Shrimp, Penaeus Monodon in a High Alkaline Water

Journal of Environmental Biology / Academy of Environmental Biology, India. May, 2011  |  Pubmed ID: 22167938

This study compares water quality parameters, shrimp growth and mortality rates, and biomass at harvest in two ponds of equal size, seeded with the same density (7 m2) of White Spot Syndrome Virus (WSSV) and Monodon Baculo Virus (MBV) negative post-larvae (PL)-20 of shrimp, Penaeus monodon in the Vellar estuary of South India. The primary difference between the ponds was the water source; one was filled from the estuary and the second with water from bore wells with high alkalinity. Temperature in both ponds was similar and reached 320C after 185 days of culture. Dissolved oxygen (DO) levels were within the acceptable range although levels in the alkaline pond were near the lower limit for the last 90 days before harvest. Salinity levels were similar in both ponds, above optimal levels, and increased over the 185 days. Alkalinity in the estuarine water was typically <50 ppm and again 200-320 ppm in the alkaline pond. In the alkaline pond, beginning on the 75th day mineral deposits was observed covering all parts of the shrimp including the eye and the inner gill chambers, and by harvest, 42% of the shrimp showed this coating. Elemental analysis identified the major constituents as calcium, phosphorus and manganese. Survival rates in the estuarine-water-fed pond was 92% with a total pond biomass at harvest of 1.65 tons ha-1 compared to survival of 79% in the alkaline pond and a biomass at harvest of 1.020 tons ha-1. When well water must be used, its alkalinity should be monitored and diluted with water from other sources.

Confocal Laser Scanning Microscopic Observation on Adult Schistosoma Japonicum Harbored in Mice Following Treatment with Single-dose Mefloquine

Parasitology Research. Dec, 2011  |  Pubmed ID: 22200961

The aim of the present study is to assess the mefloquine-induced alteration of adult Schistosoma japonicum using confocal laser scanning microscopy (CLSM). Eight out of ten mice infected with 60-80 S. japonicum cercariae for 35 days were treated orally with mefloquine at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h and 3, 7, and 14 days post-treatment, and schistosomes were collected by perfusion from the liver and mesenteric veins, fixed in 70% alcohol, stained with acid carmine, and examined by CLSM. Worms obtained from untreated mice served as controls. Twenty-four hours post-treatment, focal tegument of adult male and female worms, which composed of fine and short villus-like materials, became thicker and longer, or disorder arrangement, while the musculatures beneath the tegument revealed in focal and irregular swelling with various degrees. In the gut of male and female schistosomes, severe dilatation accompanied by swelling, collapse, and peeling of gut mucosa was universal. In the reproductive organs, no apparent alteration in the testis structure of male worms was seen, while in female worms, slight damage to the ovary included loose arrangement of mature ovary cells accompanied by some of them degenerated and collapsed. As to vitelline glands, severe damage, such as swelling, indistinction, fusion or collapse of vitelline cells, and apparent swelling of parenchymal tissues in vitelline gland lobules, was seen. Meanwhile, abnormal ova emerged in the uterus at this time point. Three to 7 days post-treatment, the damage to the worms aggravated either in extent or in severity along with time. In some focally swollen worm body, the parenchymal tissues revealed in severe swelling. In addition, a large piece of degenerated and necrotic parenchymal tissues emerged closed to the severe destructed oral or ventral sucker. In the gut of male and female worms, the major alterations manifested by focal collapse or peeling of mucosa, and desquamation of gut epithelial cells. As to the reproductive organs, the testes of male worms revealed in reduction of size, decrease in number of germinative cells, and some of them showed degeneration and collapse, or destruction of the capsule around the testis. In female worms, some ovaries only showed degenerated and collapsed cells accompanied with many cell fragments. Meanwhile, almost all of the vitelline cells lost their definition, which revealed in indistinct cell structure, fusion of some cells, and formation of many cell fragments due to their collapse. Fourteen days post-treatment, only some male worms survived the treatment were collected. Their tegument and musculature showed prominent recovery, but severe damage to the gut and testes was still observed. Our results confirm that under the observation by CLSM, mefloquine exhibits destructive effect on adult S. japonicum, particularly the morphological structure of digestive system and reproductive system of the worms.

Crocin Inhibits Proliferation and Nucleic Acid Synthesis and Induces Apoptosis in the Human Tongue Squamous Cell Carcinoma Cell Line Tca8113

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 22320974

Background: Cancer chemoprevention is a proven effective strategy for oral squamous cell carcinoma (OSCC). The present study was designed to investigate the effects of crocin, a potential chemopreventive agent, on growth and DNA and RNA content in a human tongue squamous cell carcinoma cell line, Tca8113. Methods: Tca8113 cells were treated with crocin for 24, 48, 72, and 96 h at concentrations of 0.1, 0.2, 0.4, and 0.8 mM. Tumor cell viability was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. In addition, Tca8113 cells were treated with 0.4 mM crocin and cytotoxic effects as an inducer of apoptosis were analyzed using flow cytometry. Furthermore, acridine orange (AO) staining and observation using laser scanning confocal microscopy (LSCM) were used to determine the effects of the drug on nucleic acid synthesis. Results: Crocin decreased Tca8113 cell viability and growth remarkably at 24, 48, 72, and 96 h, in a concentration-dependent manner (P<0.05). In addition, 0.4 mM crocin significantly induced both early and late apoptosis of Tca8113 cells. Moreover, the cellular DNA and RNA content was significantly downregulated by 0.4 mM crocin compared with the negative control (P<0.01). Conclusions: Our observations support the feasibility of applying crocin as a chemoprophylactic agent and treatment for OSCCs.

Cloning, Soluble Expression, and Production of Recombinant Antihypertensive Peptide Multimer (AHPM-2) in Escherichia Coli for Bioactivity Identification

Protein and Peptide Letters. Jul, 2011  |  Pubmed ID: 21413919

Recombinant antihypertensive peptide multimer (AHPM-2, 8kDa/68AA), a new designed polypeptide with potential antihypertensive effect in vivo, is composed of 15 low-molecular-weight antihypertensive peptides tandemly linked up according to the restriction sites of gastrointestinal proteases. After gene optimization, the DNA fragment encoding AHPM-2 was chemically synthesized, cloned into the pET32a, and successfully expressed in E.coli, above 90% in a soluble form. After chromatographic purification, the expressed fusion protein Trx-AHPM-2 was subject to the simulated gastrointestinal digestion, and the hydrolysate showed potent ACE inhibitory activity with an IC50 value of 4.5±0.3 μg ml-1. The active fragments from the AHPM-2 were identified by UPLC-MS/MS. This method will be useful in obtaining an appreciable quantity of recombinant AHP at low cost, and the intact AHPM-2 is expected to be developed into functional food for preventing hypertension as well as for therapeutic.

Effects of Cigarette Smoke Condensate on Oral Squamous Cell Carcinoma Cells

Archives of Oral Biology. Oct, 2011  |  Pubmed ID: 21489402

Epidemiological studies have reported that tobacco use is a major etiological factor for oral cancer. Several matrix metalloproteinases (MMPs) have been shown to play important roles in the invasion and metastasis of oral squamous cell carcinomas, especially MMP-2 and MMP-9. This study examined the effects of cigarette smoke condensate (CSC) on oral cancer cells.

Vitamin D, Vitamin D Receptor, and Macroautophagy in Inflammation and Infection

Discovery Medicine. Apr, 2011  |  Pubmed ID: 21524386

Vitamin D is involved in mineral and bone homeostasis, immune responses, anti-inflammation, anti-infection, and cancer prevention. Vitamin D receptor (VDR) is a nuclear receptor that mediates most biological functions of 1,25(OH)(2)D(3) or vitamin D(3), the active form of vitamin D. Recently, vitamin D(3)-induced autophagy has been reported. Autophagy is a lysosome-mediated catabolic pathway classified into three different types: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy contributes to anti-aging, antimicrobial defense, and tumor suppression. The functions of autophagy overlap remarkably with those of vitamin D/VDR signaling. This review focuses on vitamin D(3), VDR, and macroautophagy in inflammation and infection. We place emphasis on the regulatory roles of vitamin D(3) on autophagy at different steps, including induction, nucleation, elongation to maturation, and degradation. We summarize the known molecular mechanisms of vitamin D/VDR signaling on autophagy homeostasis. The potential application of the insights gleaned from these research findings to anti-inflammation and anti-infection is also discussed.

[Phytoplankton in Yangtze River Estuary and Its Adjacent Waters in Spring in 2009: Species Composition and Size-fractionated Chlorophyll A]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jan, 2011  |  Pubmed ID: 21548314

Based on the multidisciplinary cruise investigation in the Yangtze River estuary and its adjacent waters in April 2009, the phytoplankton species and their abundance were analyzed by the Utermöhl method, and the size-fractionated chlorophyll a concentrations were determined. In the meantime, the relationships between the dominant phytoplankton species and environmental physicochemical factors were explored by Canonical Correspondence Analysis (CCA). A total of 3 phyla, 46 genera, and 64 species (not including uncertain species) were found, mostly diatoms and dinoflagellates, with diatoms dominant. Most of these species were temperate and coastal, but a few brackish and oceanic species also presented. There were 33 diatom genera including 45 species. The dominant species were Skeletonema dohrnii, Paralia sulcata, Thalassionema nitzschioides, Pseudo-nitzschia pungens, Melosira granulata var. angustissima, Pseudo-nitzschia delicatissima, and Guinardia delicatula. The phytoplankton cell abundance ranged from 0.3 to 13447.7 cells x ml(-1), with an average of 1142.385 cells x ml(-1). Concerning the horizontal distribution, cell abundance was the highest in the middle-northern part of the survey area, with S. dohrnii dominant. The phytoplankton cell abundance was high in the surface layer water, and decreased with increasing depth. The Shannon diversity index and Pielou evenness index were consistently low in the middle-northern part of the survey area, in contrast to the trend of phytoplankton cell abundance. The chlorophyll a concentrations ranged from 0.34 to 29 g x L(-1), with an average of 3.3 g x L(-1), consistent with the cell abundance distribution. Size-fractionated chlorophyll a results showed that the biomass in the middle-northern part of the survey area was mainly composed of microphytoplankton (> 20 microm), while that in offshore waters was mainly composed of nanophytoplankton (2-20 microm) and picophytoplankton (< 2 microm). The CCA showed that the distribution of predominant species S. dohrnii was mainly affected by the water nitrate content, pH value, and microzooplankton grazing. On the contrary, the distribution of other common species including dinoflagellates was mainly associated with water salinity, and phosphate and silicate contents. The paper also compared the differences in the methods of phytoplankton quantification used by the present study and by the previous studies based on net samples. It was suggested that in future work, the autecological study of genus Skeletonema in the Yangtze River estuary and its adjacent waters should be strengthened.

[Congenital Fibrosarcoma with Diffuse Metastases in Fetus: Report of a Case]

Zhonghua Bing Li Xue Za Zhi Chinese Journal of Pathology. Apr, 2011  |  Pubmed ID: 21616008

Characterization of Subchondral Bone Repair for Marrow-stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing

The American Journal of Sports Medicine. Aug, 2011  |  Pubmed ID: 21628638

Microfracture and drilling are bone marrow-stimulation techniques that initiate cartilage repair by providing access to cell populations in subchondral bone marrow. This study examined the effect of hole depth and of microfracture versus drilling on subchondral bone repair and cartilage repair in full-thickness chondral defects.

[Determination of Avermectin, Diclazuril, Toltrazuril and Metabolite Residues in Pork by High Performance Liquid Chromatography-tandem Mass Spectrometry]

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Mar, 2011  |  Pubmed ID: 21657050

A method for the determination of avermectin, ivermectin, doramectin, moxidectin, eprinomectin, diclazuril, toltrazuril and its two metabolite residues in pork was developed using QuEChERS method with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample was extracted with acetonitrile and purified through QuEChERS method using ODS as the sorbent. The target compounds were separated on a Venusil ASB C18 column (150 mm x 2.1 mm, 3.0 microm) and detected by HPLC-MS/MS. The linear ranges were 0.005 - 0.2 mg/L and the correlation coefficients were all above 0.990. The average recoveries and the relative standard deviations ranged from 73.2% to 91.5% and from 12% to 17% at the spiked levels of 0.005, 0.01 and 0.02 mg/kg for the 9 analytes in pork matrix. This method is reliable, and suitable for the determination of the residues of avermectin and related compounds in pork.

Depth of Subchondral Perforation Influences the Outcome of Bone Marrow Stimulation Cartilage Repair

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. Aug, 2011  |  Pubmed ID: 21671261

Subchondral drilling and microfracture are bone marrow stimulation techniques commonly used for the treatment of cartilage defects. Few studies to date have examined the technical variants which may influence the success of the cartilage repair procedures. This study compared the effect of hole depth (6 mm vs. 2 mm) and hole type (drill vs. microfracture) on chondral defect repair using a mature rabbit model. Results from quantitative histomorphometry and histological scoring showed that deeper versus shallower drilling elicited a greater fill of the cartilage defect with a more hyaline character in the repair matrix indicated by significant improvement (p = 0.021) in the aggregate measure of increased cartilage defect fill, increased glycosaminoglycan and type II collagen content and reduced type I collagen content of total soft repair tissue. Compared to microfracture at the same 2 mm depth, drilling to 2 mm produced a similar quantity and quality of cartilage repair (p = 0.120) according to the aggregate indicator described above. We conclude that the depth of bone marrow stimulation can exert important influences on cartilage repair outcomes.

Gastrodin Inhibits Expression of Inducible NO Synthase, Cyclooxygenase-2 and Proinflammatory Cytokines in Cultured LPS-stimulated Microglia Via MAPK Pathways

PloS One. 2011  |  Pubmed ID: 21765922

Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS).

[Phytoplankton Assemblages in Yangtze River Estuary in the First Sluice Discharge Duration of Three Gorges Dam in Late Spring]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Apr, 2011  |  Pubmed ID: 21774331

In June 15-25, 2003, the first sluice discharge duration of the Three Gorges Dam, water samples were taken from a grid of survey stations around the Yangtze River Estuary and its adjacent waters to analyze the characteristics of phytoplankton assemblages. In the survey area, the major phytoplankton groups were diatoms and dinoflagellates, and a few species belonging to Chrysophyceae and Chlorophyceae were observed. The cell abundance of the assemblages ranged from 0.2 to 1504.2 cells ml(-1), with an average of 72.7 cells ml(-1), and the dominant species were Skeletonema spp., Prorocentrum dentatum, and Scrippsiella trochoidea. The highest cell abundance was appeared in north diluted waters and southwest inshore waters. The cell abundance was the maximum in mid (10 m) water layer, and the minimum in bottom layer. In diluted waters, Skeletonema spp. was the dominant species, and mainly presented in surface water layer; while in the waters with the diluted water of Yangtze River and the mixed water of Taiwan Warmer Current and Yellow Sea, Prorocentrum dentatum dominated, and mainly distributed in surface and mid water layers.

[The Antagonistic Effect of the Oral Streptococcus on the Saccharomyces Albicans in Vitro]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Jun, 2011  |  Pubmed ID: 21776861

To investigate the antagonistic effects of three species of oral Streptococcus on the growth of oral Saccharomyces albicans in vitro.

[Influence of the Unevenness of Articular Surface on the Osteochondral Repair]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jun, 2011  |  Pubmed ID: 21786559

To investigate whether the unevenness of articular surface would affect the osteochondral repair.

Probiotics, Nuclear Receptor Signaling, and Anti-inflammatory Pathways

Gastroenterology Research and Practice. 2011  |  Pubmed ID: 21808643

There is increased investigation of the human microbiome as it relates to health and disease. Dysbiosis is implicated in various clinical conditions including inflammatory bowel disease (IBD). Probiotics have been explored as a potential treatment for IBD and other diseases. The mechanism of action for probiotics has yet to be fully elucidated. This paper discusses novel mechanisms of action for probiotics involving anti-inflammatory signaling pathways. We highlight recent progress in probiotics and nuclear receptor signaling, such as peroxisome-proliferator-activated receptor gamma (PPARγ) and vitamin D receptor (VDR). We also discuss future areas of investigation.

[Structural Characteristics of Sophora Moorcroftiana Community on Wind-sandy Land in Middle Reaches of Yaluzangbu River]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. May, 2011  |  Pubmed ID: 21812283

Based on quadrat investigation and hierarchical cluster analysis, this paper studied the structural characteristics of Sophora moorcroftiana community at its different restoration succession stages on the wind-sandy land in middle reaches of Yaluzangbu River. The plant community on the wind-sandy land could be divided into 6 types, i.e., S. moorcroftiana community, Orinus thoroldii community, S. moorcroftiana < O. thoroldii community, S. moorcroftiana-O. thoroldii community, Artemisia weiibyii+S. moorcroftiana community, and S. moorcroftiana+A. weiibyii community. The restoration succession began with the sand-fixing S. moorcroftiana distributed on moving dune, followed by O. thoroldii invasion, and then, S. moorcroftiana-O. thoroldii community formed gradually. Another restoration succession approach began with O. thoroldii community, S. moorcroftiana occurred then, and finally, S. moorcroftiana-O, thoroldii community formed. On semi-fixed dune, A. weiibyi could invade the community, and S. moorcroftiana+A. weiibyi community formed. The climax community on the wind-sandy land was the shrub community dominated by S. moorcroftiana. With increasing slope grade, the coverage and height of S. moorcroftiana community tended to decrease. Biological crust had definite improvement effect on the soil physical and chemical properties. At the places with biological crust, surface soil water content was significantly higher, compared with that at the places with other restoration succession stages of S. moorcroftiana community. The crown diameter, plant height, and the sprouting branch number of S. moorcroftiana community were the highest on moving dune, followed by on fixed dune, and on semi-fixed dune. The dead branch number at different restoration succession stages indicated that S. moorcroftiana population had a declining trend after the sand was fixed.

Wingless Homolog Wnt11 Suppresses Bacterial Invasion and Inflammation in Intestinal Epithelial Cells

American Journal of Physiology. Gastrointestinal and Liver Physiology. Dec, 2011  |  Pubmed ID: 21903761

Wnt11 plays an essential role in gastrointestinal epithelial proliferation, and previous investigations have focused on development and immune responses. However, the roles of how enteric bacteria regulate Wnt11 and how Wnt11 modulates the host response to pathogenic bacteria remain unexplored. This study investigated the effects of Salmonella infection on Wnt activation in intestinal epithelial cells. We found that Wnt11 mRNA and protein expression were elevated after Salmonella colonization. Wnt11 protein secretion in epithelial cells was also elevated after bacterial infection. Furthermore, we demonstrated that pathogenic Salmonella regulated Wnt11 expression and localization in vivo. We found a decrease in Salmonella invasion in cells with Wnt11 overexpression compared with cells with normal Wnt11 level. IL-8 mRNA in Wnt11-transfected cells was low; however, it was enhanced in cells with a low level of Wnt11 expression. Functionally, Wnt11 overexpression inhibited Salmonella-induced apoptosis. AvrA is a known bacterial effector protein that stabilizes β-catenin, the downstream regulator of Wnt signaling, and inhibits bacterially induced intestinal inflammation. We observed that Wnt11 expression, secretion, and transcriptional activity were regulated by Salmonella AvrA. Overall, Wnt11 is involved in the protection of the host intestinal cells by blocking the invasion of pathogenic bacteria, suppressing inflammation, and inhibiting apoptosis. Wnt11 is a novel and important contributor to intestinal homeostasis and host defense.

Quantum-Behaved Particle Swarm Optimization: Analysis of Individual Particle Behavior and Parameter Selection

Evolutionary Computation. Sep, 2011  |  Pubmed ID: 21905841

Abstract Quantum-behaved particle swarm optimization (QPSO), motivated by quantum mechanics and the trajectory analysis of particle swarm optimization (PSO), is a probabilistic algorithm belonging to the bare-bones PSO family. Although it has been shown to perform well in finding the optimal solutions for optimization problems, there has so far been little explanation of how it works. This paper presents a comprehensive analysis of the QPSO algorithm. In the theoretical analysis, we analyze the behavior of a single particle in QPSO in terms of probability measure. Since the particle's behavior is influenced by the contraction-expansion (CE) coefficient, which is the most important parameter of the algorithm, the goal of the theoretical analysis is to find out the upper bound of the CE coefficient, within which the value of the CE coefficient selected can guarantee the convergence or boundedness of the particle's position. In the experimental analysis, the theoretical results are first validated by stochastic simulations for the particle's behavior. Then, based on the derived upper bound of the CE coefficient, we perform empirical studies on a suite of well-known benchmark functions to show how to control and select the value of the CE coefficient, in order to obtain generally good algorithmic performance in real world applications. Finally, a further performance comparison between QPSO and other variants of PSO on the benchmarks is made to show the efficiency of the QPSO algorithm with the proposed parameter control and selection methods.

[Relationship Between the Bone Mass and the Expressions of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Bone Morphogenetic Protein 2 MRNA in Avascular Necrosis of Femoral Head]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Aug, 2011  |  Pubmed ID: 21923031

To study the expression changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and bone morphogenetic protein 2 (BMP-2) in femoral neck fracture, traumatic, and non-traumatic avascular necrosis of femoral head (ANFH), and to study the relationship between the expressions of VEGF, bFGF, BMP-2 mRNA and bone mass so as to explore the pathogenesis of ANFH and provide the exprimental basis for individual treatment of ANFH.

Microdrilled Cartilage Defects Treated with Thrombin-Solidified Chitosan/Blood Implant Regenerate a More Hyaline, Stable, and Structurally Integrated Osteochondral Unit Compared to Drilled Controls

Tissue Engineering. Part A. Nov, 2011  |  Pubmed ID: 21942869

This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ∼24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled controls, chitosan implants solidified with thrombin elicited a more hyaline and structurally integrated osteochondral unit, features needed for long-term durability.

[Research on the Repair of Acute Large Osteochondral Defects with Mosaicplasty Associated with Genes-enhanced Tissue Engineering in Different Proportion]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Sep, 2011  |  Pubmed ID: 22007589

To investigate the optimum proportion of Mosaicplasty and genes-enhanced tissue engineering for the repair of acute osteochondral defects.

PTD4-apoptin Protein and Dacarbazine Show a Synergistic Antitumor Effect on B16-F1 Melanoma in Vitro and in Vivo

European Journal of Pharmacology. Mar, 2011  |  Pubmed ID: 21184754

PTD4-apoptin protein enters cells and harbors tumor-selective cell death activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose-dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of drug interaction<1) in all three different tumor cell lines. In vivo, PTD4-apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1 melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment significantly increased the antitumor effect in comparison to the single treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a 50% reduction of dacarbazine revealed similar antitumor activities, without detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine treatment represents a promising novel efficient and safe anticancer strategy.

Erythropoietin Protects Intestinal Epithelial Barrier Function and Lowers the Incidence of Experimental Neonatal Necrotizing Enterocolitis

The Journal of Biological Chemistry. Apr, 2011  |  Pubmed ID: 21262973

The impermeant nature of the intestinal barrier is maintained by tight junctions (TJs) formed between adjacent intestinal epithelial cells. Disruption of TJs and loss of barrier function are associated with a number of gastrointestinal diseases, including neonatal necrotizing enterocolitis (NEC), the leading cause of death from gastrointestinal diseases in preterm infants. Human milk is protective against NEC, and the human milk factor erythropoietin (Epo) has been shown to protect endothelial cell-cell and blood-brain barriers. We hypothesized that Epo may also protect intestinal epithelial barriers, thereby lowering the incidence of NEC. Our data demonstrate that Epo protects enterocyte barrier function by supporting expression of the TJ protein ZO-1. As immaturity is a key factor in NEC, Epo regulation of ZO-1 in the human fetal immature H4 intestinal epithelial cell line was examined and demonstrated Epo-stimulated ZO-1 expression in a dose-dependent manner through the PI3K/Akt pathway. In a rat NEC model, oral administration of Epo lowered the incidence of NEC from 45 to 23% with statistical significance. In addition, Epo treatment protected intestinal barrier function and prevented loss of ZO-1 at the TJs in vivo. These effects were associated with elevated Akt phosphorylation in the intestine. This study reveals a novel role of Epo in the regulation of intestinal epithelial TJs and barrier function and suggests the possible use of enteral Epo as a therapeutic agent for gut diseases.

PI3K-mTORC1 Attenuates Stress Response by Inhibiting Cap-independent Hsp70 Translation

The Journal of Biological Chemistry. Feb, 2011  |  Pubmed ID: 21177857

Protein synthesis is a key regulated cellular process that links nutrient availability and organismal growth. It has long been known that some cellular proteins continue to be synthesized under conditions where global translation is severely compromised. One prominent example is the selective translation of heat shock proteins (Hsps) under stress conditions. Although the transcriptional regulation of Hsp genes has been well established, neither the specific translation-promoting features nor the regulatory mechanism of the translation machinery have been clearly defined. Here we show that the stress-induced preferential translation of Hsp70 mRNA is negatively regulated by PI3K-mTORC1 signaling. Despite the transcriptional up-regulation, the translation of Hsp70 mRNA is deficient in cells lacking tuberous sclerosis complex 2. Conversely, Hsp70 synthesis is enhanced under the reduced PI3K-mTORC1 signaling. We found that the 5' UTR of Hsp70 mRNA contributes to cap-independent translation without exhibiting typical features of internal ribosome entry site. Our findings imply a plausible mechanism for how persistent PI3K-mTORC1 signaling favors the development of age-related pathologies by attenuating stress resistance.

Distributed Multiple Description Video Coding on Packet Loss Channels

IEEE Transactions on Image Processing : a Publication of the IEEE Signal Processing Society. Jun, 2011  |  Pubmed ID: 21138804

In this paper, we are to solve the drift problem of multiple description video coding on packet loss channels by using state-of-the-art distributed techniques. We first present an asymptotically optimal code design of multiple descriptions in the Wyner-Ziv (MDWZ) setting. Then we propose a distributed multiple description video coding (DMDVC) scheme, which performs MDWZ coding on each nonintra coded frame. Instead of the prediction loops used in traditional multiple description video coding, Slepian-Wolf based coding is used to exploit interframe correlations. A bitplane extraction scheme is proposed to improve the balance between two descriptions, so that side informations can be interchanged between the side decoders of DMDVC with negligible quality degradation, which is crucial to robust transmission over packet loss channels. Experiment results demonstrate the robustness of our scheme, especially at high packet loss rates.

Genome-wide Identification of SNPs in MicroRNA Genes and the SNP Effects on MicroRNA Target Binding and Biogenesis

Human Mutation. Jan, 2012  |  Pubmed ID: 22045659

MicroRNAs (miRNAs) are studied as key regulators of gene expression involved in different diseases. Several single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA-mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites, and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3' untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed seven loss-of-function SNPs and one gain-of-function SNP by luciferase assay. This is the first case of experimental validation of an SNP in an miRNA creating a novel miRNA target binding. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine.

Wnt2 Inhibits Enteric Bacterial-induced Inflammation in Intestinal Epithelial Cells

Inflammatory Bowel Diseases. Mar, 2012  |  Pubmed ID: 21674728

Wnt signaling plays an essential role in gastrointestinal epithelial proliferation. Most investigations have focused on developmental and immune responses. Bacterial infection can be chronic and increases the risk of inflammatory bowel disease and colitis-associated cancer. However, we lack studies on how bacteria regulate Wnt proteins and how Wnts modulate the host responses to enteric bacteria. This study investigated the effects of Salmonella and Escherichia coli on Wnt2, one of the Wnt family members, in intestinal epithelia cells.

Preparation, Characterization and Pharmacokinetic Studies of Tacrolimus-dimethyl-β-cyclodextrin Inclusion Complex-loaded Albumin Nanoparticles

International Journal of Pharmaceutics. Feb, 2012  |  Pubmed ID: 22326299

The purpose of the study is to develop a new formulation for clinically used anti-cancer agent tacrolimus (FK506) to minimize the severe side effects. Toward this end, a new formulation method has been developed by complexation of FK506 with an hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) using ultrasonic means. The resulting complex displays dramatically enhanced solubility of FK506. Then bovine serum albumin (BSA) nanoparticles were prepared directly from the preformed FK506/DM-β-CD inclusion complex by the desolvation-chemical crosslinking method, with the size of 148.4-262.9nm. Stable colloidal dispersions of the nanoparticles were formed with zeta potentials of the range of -24.9 to -38.4mV. The entrapment efficiency of FK506 was increased as high as 1.57-fold. Moreover, notably FK506 was released from the nanoparticles in a sustained manner. As demonstrated, pharmacokinetic studies reveal that, as compared with FK506-loaded BSA nanoparticles, the FK506/DM-β-CD inclusion complex-loaded BSA nanoparticles have significant increase at T(max), t(1/2), MRT and decrease at C(max). In summary, these results suggest that the drug/DM-β-CD inclusion complex-loaded BSA nanoparticles display significantly improved delivery efficiency for poorly soluble FK506 or its derivatives.

A Modified LC-MS/MS Method for Determination of Tetramethylpyrazine in Microdialysis Samples and Calibration of Home-made Linear Probes

Biomedical Chromatography : BMC. Feb, 2012  |  Pubmed ID: 22334234

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used for the treatment of cardiovascular diseases. Several factors may affect TMP exposure after topical administration, resulting in large variability and demanding further elucidation of drug distribution. This paper describes a new efficient reliable LC-MS/MS assay for the determination of TMP in dermal microdialysate, where TMP was separated on an Agilent C(18) column (3.5 µm, 100 mm × 2.1 mm i.d.) using a mixture of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow-rate of 0.3 mL/min. The retention time was 1.89 min for TMP and 1.17 min for the internal standard (caffeine). Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for TMP was not altered through the implant lifetime. The validation and sample analysis results showed that the method is precise, accurate and well suited to support dermal microdialysis experiments. Copyright © 2012 John Wiley & Sons, Ltd.

Approaching the Ideal Elastic Limit of Metallic Glasses

Nature Communications. 2012  |  Pubmed ID: 22215084

The ideal elastic limit is the upper bound to the stress and elastic strain a material can withstand. This intrinsic property has been widely studied for crystalline metals, both theoretically and experimentally. For metallic glasses, however, the ideal elastic limit remains poorly characterized and understood. Here we show that the elastic strain limit and the corresponding strength of submicron-sized metallic glass specimens are about twice as high as the already impressive elastic limit observed in bulk metallic glass samples, in line with model predictions of the ideal elastic limit of metallic glasses. We achieve this by employing an in situ transmission electron microscope tensile deformation technique. Furthermore, we propose an alternative mechanism for the apparent 'work hardening' behaviour observed in the tensile stress-strain curves.

Effects of Alendronate on Human Osteoblast-like MG63 Cells and Matrix Metalloproteinases

Archives of Oral Biology. Jan, 2012  |  Pubmed ID: 22251575

OBJECTIVE: The objective of this study was to examine the effects of alendronate on the expression and activity of matrix metalloproteinases (MMPs) and the expression of the tissue inhibitors of MMPs (TIMPs) from human osteoblast-like MG63 cells. MATERIALS AND METHODS: MG63 cells were exposed to various concentrations of alendronate. Cell proliferation and cytotoxicity were evaluated by water-soluble tetrazolium-1 and lactate dehydrogenase, respectively. MG63-mediated collagen degradation was assessed utilising Type I collagen assays. Conditioned media and membrane extracts were collected for Western blot analyses of select MMPs and TIMPs. Gelatin zymography gels were incubated with alendronate to assess its effects on MMP-2 activity. RESULTS: Alendronate affected MG63 proliferation and cytotoxicity at concentrations equal to/or greater than 10(-5)M (all p<0.05). There were no significant differences in the collagen degrading ability of treated cells at non-toxic levels vs. untreated cells. Alendronate had no effects on the expression of MMP-2 or MT1-MMP (membrane type-1 MMP) in the conditioned media or membrane extracts, and of MMP-1 or TIMP-2 in the conditioned media. TIMP-2 in the membrane extracts was not detectable. MMP-2 activity in the zymograms was inhibited by 10(-3) and 10(-2)M alendronate. CONCLUSION: Alendronate at 10(-5)M or higher was toxic to the cells. Alendronate at 10(-8) to 10(-6)M did not alter the expression of MMP-1, MMP-2, MT1-MMP or TIMP-2, as well as did not alter collagen degradation. Alendronate inhibited MMP-2 activity at 10(-3) and 10(-2)M in the zymograms. In conclusion, non-toxic levels of alendronate (10(-8) to 10(-6)M) did not alter MMP expression in MG63 cells or inhibit MMP-2 activity.

First Report on Co-Occurrence Knockdown Resistance Mutations and Susceptibility to Beta-Cypermethrin in Anopheles Sinensis from Jiangsu Province, China

PloS One. 2012  |  Pubmed ID: 22272229

The increasing prevalence of insecticide resistance in Anopheles sinensis, a major vector of malaria in Jiangsu province in eastern China, threatens to compromise the successful use of insecticides in malaria control strategies. It is therefore vital to understand the insecticide resistance status of An. sinensis in the region. This study examined the nucleotide diversity of the para-sodium channel and knockdown resistance (kdr) in five field populations of adult An. sinensis mosquitoes collected in Jiangsu province, identifying the L1014F and L1014C substitutions for the first time. Competitive polymerase chain reaction (PCR) amplification of specific allele (cPASA) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) for resistance diagnosis were developed and validated. Comparing the results with direct sequencing revealed that the PCR-RFLP method was more sensitive and specific whereas the cPASA method was more convenient and suitable. The significant positive correlation between kdr allele frequency and bioassay-based resistance phenotype demonstrates that the frequency of L1014F and L1014C substitutions in the kdr gene provides a useful molecular marker for monitoring beta-cypermethrin resistance in natural populations of An. sinensis. Our results point to the L1014F substitution as the key mutation associated with beta-cypermethrin resistance. The high resistance and mutation frequency detected in the five populations also suggest cross-resistance with other pyrethroids may occur in An. sinensis, highlighting the need for further surveys to map insecticide resistance in China and the adoption of a rational management of insecticide application for resistance management and mosquito vector control.

Chemical Composition of Five Wild Edible Mushrooms Collected from Southwest China and Their Antihyperglycemic and Antioxidant Activity

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Jan, 2012  |  Pubmed ID: 22300772

Evaluation of the chemical composition and antihyperglycemic and antioxidant activity of five wild edible mushrooms (Clitocybe maxima, Catathelasma ventricosum, Stropharia rugoso-annulata, Craterellus cornucopioides and Laccaria amethystea) from Southwest China. The chemical composition assay includes proximate analysis (moisture, ash, crude protein, crude fat, total carbohydrates and total energy), bioactive compounds analysis (total phenolic, flavonoid, ascorbic acid, ergosterol, tocopherol), fatty acid analysis, amino acid analysis, phenolic compounds analysis and mineral analysis of these mushrooms. Furthermore, assays of α-glucosidase inhibitory and α-amylase inhibitory activity were used for evaluating antihyperglycemic activity of the mushrooms, and assays of reducing power, chelating effect on ferrous ions, scavenging effect on hydroxyl free radicals and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were used for evaluating antioxidant activity of the mushrooms. Based on the results, ethanolic and aqueous extract of these mushroom all showed antihyperglycemic and antioxidant potential. In particular, the aqueous extract of C. ventricosum revealed the highest α-glucosidase inhibitory activity (EC50 value 2.74μg/mL), DPPH radical scavenging activity (EC50 value 2.86mg/mL) and reducing power (EC50 value 0.96mg/mL), while the aqueous extract of L. amethystea showed the highest α-amylase inhibitory activity (EC50 value 4.37μg/mL) and metal chelating activity (EC50 value 2.13mg/mL).

Camptothecin Fails to Induce Apoptosis in Tumor Necrosis Factor-Alpha-Treated HaCaT Cells

Pharmacology. Feb, 2012  |  Pubmed ID: 22301394

Camptothecin (CPT), a DNA topoisomerase I inhibitor, was originally isolated from the fruits of the Chinese Camptotheca acuminata tree. CPT and its derivatives have been used in the treatment of psoriasis and cancer in China for decades. It is well known that tumor necrosis factor-α (TNF-α) is a key proinflammatory cytokine in the pathogenesis of psoriasis. In this study, we investigated the effect of CPT on TNF-α-treated HaCaT cells. The results indicated that CPT in the concentration range of 0.5-2.0 μg·ml(-1) failed to show any proapoptotic effect in HaCaT cells. It was found that both CPT and TNF-α up-regulated the expression of TRAIL receptor 1/2 but not TRAIL in HaCaT cells. Furthermore, the expression of antiapoptotic proteins (IAP1, IAP2, and Bcl-X(L)) was up-regulated by TNF-α and suppressed by CPT in HaCaT cells. Because these gene products are known to be regulated by nuclear factor-kappa B (NF-κB), we examined the role of CPT on NF-κB activation. It was found that CPT not only failed to inhibit TNF-α-induced NF-κB activation but also contributed to NF-κB activation. In addition to these effects, CPT also promoted the production of interleukin-6, similar to TNF-α, in HaCaT cells. In conclusion, despite ample evidence supporting CPT-induced carcinoma cell apoptosis, our study clearly shows that CPT fails to show any proapoptotic effects in HaCaT cells, even though it enhanced TRAIL receptor 1/2 expression and inhibited the expression of TNF-α-induced antiapoptotic proteins. Taken together, this study demonstrates that CPT fails to block the activity of TNF-α. With respect to the NF-κB-activating role of CPT, we suggest that the benefit of CPT in the treatment of psoriasis should be reevaluated.

Inflammatory Response of Human Keratinocytes Triggered by Sporothrix Schenckii Via Toll-like Receptor 2 and 4

Journal of Dermatological Science. Jan, 2012  |  Pubmed ID: 22305616

Rapid Strain Evaluation Using Dynamic DO-stat Fed-batch Fermentation Under Scale-down Conditions

Methods in Molecular Biology (Clifton, N.J.). 2012  |  Pubmed ID: 22144363

While large amount of strains can be quickly generated via metabolic engineering, the speed/efficiency of evaluating each strain becomes the bottleneck in the process from strain development to final production. In this chapter, a method is introduced to rapidly evaluate strain performance in fed-batch fermentation mode by using dynamic dissolved oxygen stat feed back control with no additional advanced online measurement. In addition, a scale-down feature is integrated in the method to mimic the limitation of oxygen transfer in large-scale vessels, so that strains can be evaluated under the conditions close to that in large-scale bioreactors. The method has been implemented in several commercial standard benchtop scale fermentation systems with different fermentation control software.

Ultrastructural Alterations of Juvenile Schistosoma Japonicum Harbored in Mice Following Mefloquine Administration

Parasitology Research. Feb, 2012  |  Pubmed ID: 21750873

The aim of the present study was to assess the ultrastructural alterations of juvenile Schistosoma japonicum induced by mefloquine. Mice infected with 14-day-old S. japonicum were treated orally with mefloquine at a single dose of 400 mg/kg. Between 8 h and 7 days after treatment, groups of two mice were sacrificed, and schistosomula were recovered for transmission electron microscopic observations. Ultrastructural damage was seen in the tegument, subtegumental musculature, parenchymal tissues, and gut epithelial cell. It was already prominent 8 h after drug administration and increased in severity rapidly to reach a peak 3 days post-treatment. Tegumental alterations were characterized by emergence of irregular and elongated cytoplasmic processes, which further fused together accompanied by indistinction of matrix and roughness of external plasma membrane. Meanwhile, in the subtegument, damage to the syncytium, swelling, and lysis of muscle bundles and parenchymal tissues were universal, which further aggravated the lesion on the tegument, followed by collapse or disintegration of damaged tegument to form numerous fragment or debris of cytoplasmic process detached from the worm surface. Severe damage to the gut epithelial cell was also observed 8 h post-mefloquine treatment, which included focal lysis of cytoplasm accompanied by formation of vacuoles and degeneration of mitochondria, emergence of enlarged and contracted nucleus with indistinct or focal disrupted nuclear membrane, and decrease in microvilli. All these alterations further increased in severity and reached the peak 3 days post-treatment. The findings of our study indicate that mefloquine exhibits a fast and potent ability to cause extensive ultrastructural damage to juvenile S. japonicum, which correlates with its high efficacy against juvenile schistosomes.