3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors.

Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave r (cv) (2) values of 0.

3D-QSAR and molecular docking studies on fused pyrazoles as p38α mitogen-activated protein kinase inhibitors.

The p38α mitogen-activated protein kinase (MAPK) has become an attractive target for the treatment of many diseases such as rheumatoid arthritis, inflammatory bowel disease and Crohn's disease. In this paper, 3D-QSAR and molecular docking studies were performed on 59 p38α MAPK inhibitors. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to determine the structural requirements for potency in inhibiting p38α MAPK.

The effects of stimulation at acupoint ST36 points against hemorrhagic shock in dogs.

The aim of this study is to investigate the effects of electroacupuncturing (EA) zusanli points on levels of basic hemodynamics, lactate, and cytokines in dogs with hemorrhagic shock. Thirty healthy dogs were randomly divided into 5 groups: sham hemorrhagic shocked group, hemorrhagic shocked group, EA group, nonacupuncturing group, and EA after vagotomy group. Zusanli points were electroacupunctured with constant voltage (10-15 V, 30 Hz) for 30 minutes immediately after the shock models were established.

Robust relationship inference in genome-wide association studies.

Motivation: Genome-wide association studies (GWASs) have been widely used to map loci contributing to variation in complex traits and risk of diseases in humans. Accurate specification of familial relationships is crucial for family-based GWAS, as well as in population-based GWAS with unknown (or unrecognized) family structure. The family structure in a GWAS should be routinely investigated using the SNP data prior to the analysis of population structure or phenotype.

3D-QSAR and docking studies on pyrazolo[4,3-h]qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors.

3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. The CoMFA and CoMSIA models using 54 molecules in the training set, gave r(cv)(2) values of 0.644 and 0.

Molecular modelling studies on d-annulated benzazepinones as VEGF-R2 kinase inhibitors using docking and 3D-QSAR.

Chemotypes comprising the d-annulated 1,3-dihydro-2H-1-benzazepin-2-one scaffold derived from the paullone structure were found to be potent vascular endothelial growth factor receptor 2 (VEGF-R2) kinase inhibitors. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and docking studies were performed on a series of d-annulated benzazepinones with VEGF-R2 kinase inhibition activities. The comparative molecular field analysis and comparative molecular similarity indices analysis models using 32 molecules in the training set gave r(2)(cv) values of 0.

3D-QSAR and molecular docking studies of azaindole derivatives as Aurora B kinase inhibitors.

The Aurora kinases have been regarded as attractive targets for the development of new anticancer agents. Recently a series of azaindole derivatives with Aurora B inhibitory activities were reported. To explore the relationship between the structures of substituted azaindole derivatives and their inhibition of Aurora B, 3D-QSAR and molecular docking studies were performed on a dataset of 41 compounds.

Identification of the residues in the extracellular domain of thrombopoietin receptor involved in the binding of thrombopoietin and a nuclear distribution protein (human NUDC).

Thrombopoietin (TPO) and its receptor (Mpl) have long been associated with megakaryocyte proliferation, differentiation, and platelet formation. However, studies have also shown that the extracellular domain of Mpl (Mpl-EC) interacts with human (h) NUDC, a protein previously characterized as a human homolog of a fungal nuclear migration protein. This study was undertaken to further delineate the putative binding domain on the Mpl receptor.

[A novel near-infrared spectra detection system based on MEMS grating light modulators].

A novel near-infrared spectrum detection system based on grating light modulators is proposed in the present paper. A new spectrum detection method that combines MEMS grating light modulators with a single near infrared detector is applied in the system, which can avoid using costly near infrared detector array. Firstly, the optical structure of the spectra detection system was designed.

Mesorhizobium camelthorni sp. nov., isolated from Alhagi sparsifolia.

Nine strains isolated from symbiotic root nodules on Alhagi sparsifolia were previously designated as representing genospecies I. Phylogenetic analyses indicated that genospecies I was related closely to Mesorhizobium alhagi (genospecies II), and clearly formed a new lineage within the genus Mesorhizobium. In this study, we differentiated genospecies I from recognized species of the genus Mesorhizobium based on phylogenetic analyses of additional core genes (recA, glnA), levels of DNA-DNA relatedness (<43.

[Cloning of the fimA gene of Porphyromonas gingivalis and its expression and purification in Escherichia coli].

Unlabelled: OBJECTIVE; To clone the fimA gene of Porphyromonas gingivalis (P. gingivalis) and detect its expression in Escherichia coli (E. coli).

Mesorhizobium robiniae sp. nov., isolated from root nodules of Robinia pseudoacacia.

Previously, five rhizobial strains isolated from root nodules of Robinia pseudoacacia were assigned to the same genospecies on the basis of identical 16S rRNA gene sequences and phylogenetic analyses of the nodA, nodC and nifH genes, in which the five isolates formed a well-supported group that excluded other sequences found in public databases. In this study, the 16S rRNA gene sequence similarities between the isolates and Mesorhizobium mediterraneum UPM-Ca36(T) and Mesorhizobium temperatum SDW018(T) were 99.5 and 99.

Total enteral nutrition in prevention of pancreatic necrotic infection in severe acute pancreatitis.

Objective: This study was designed to evaluate the effects of total enteral nutrition and total parenteral nutrition in prevention of pancreatic necrotic infection in severe acute pancreatitis.

Methods: One hundred seven patients were enrolled in the study between 2003 and 2007. In the first week of hospitalization, they were randomized to feeding by either total parenteral nutrition (54 patients) or total enteral nutrition (53 patients).

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR).

We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.

Planning and executing a genome wide association study (GWAS).

In recent years, genome-wide association approaches have proven a powerful and successful strategy to identify genetic contributors to complex traits, including a number of endocrine disorders. Their success has meant that genome wide association studies (GWAS) are fast becoming the default study design for discovery of new genetic variants that influence a clinical trait or phenotype. This chapter focuses on a number of key elements that require consideration for the successful conduct of a GWAS.

A generalized family-based association test for dichotomous traits.

Recent advances in genotyping technology make it possible to utilize large-scale association analysis for disease-gene mapping. Powerful and robust family-based association methods are crucial for successful gene mapping. We propose a family-based association method, the generalized disequilibrium test (GDT), in which the genotype differences of all discordant relative pairs are utilized in assessing association within a family.

Mesorhizobium alhagi sp. nov., isolated from wild Alhagi sparsifolia in north-western China.

Eleven strains that formed symbiotic root nodules on Alhagi sparsifolia, designated previously as genospecies II, were identified as a new lineage of Mesorhizobium (Alphaproteobacteria) that could be differentiated from all previously recognized species of the genus Mesorhizobium by using 16S rRNA gene sequences (<97.8 % similarity), DNA-DNA hybridization (<45 %), dnaJ, dnaK, recA, glnA, nifH, nodA and nodC gene sequences, fatty acid profiles (C(18 : 1)omega7c, 35 %;11-methyl C(18 : 1)omega7c, 30 %) and numerical taxonomy. These strains are therefore considered to represent a novel species, for which the name Mesorhizobium alhagi sp.

Dobutamine enhances alveolar fluid clearance in a rat model of acute lung injury.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain leading factors for morbidity and mortality in critically ill patients. A significant aspect of ALI and ARDS is impaired alveolar fluid clearance (AFC). Improvements in therapies for these types of respiratory illnesses will require an understanding of the mechanisms that control AFC.

[Preventive effect of endothelial nitric oxide synthase gene transfer on chronic hypoxic pulmonary hypertension in rats].

Objective: To investigate the preventive effect of endothelial nitric oxide synthase (eNOS) gene transfer on chronic hypoxic pulmonary hypertension (CHPH) in rats.

Methods: Twenty-four male Wistar rats were randomly divided into four groups with 6 rats in each group: normoxia group (group N), hypoxia group (group H), hypoxia with LacZ group (group H-LacZ) and hypoxia with eNOS group (group H-eNOS). AdCMVceNOS, AdCMVLacZ or normal saline (NS) was injected intratracheally 3 days before the beginning of exposure to normoxia or hypoxia.

Variance components linkage analysis with repeated measurements.

Background: When subjects are measured multiple times, linkage analysis needs to appropriately model these repeated measures. A number of methods have been proposed to model repeated measures in linkage analysis. Here, we focus on assessing the impact of repeated measures on the power and cost of a linkage study.

Genome-wide scan for linkage to type 1 diabetes in 2,496 multiplex families from the Type 1 Diabetes Genetics Consortium.

Objective: Type 1 diabetes arises from the actions of multiple genetic and environmental risk factors. Considerable success at identifying common genetic variants that contribute to type 1 diabetes risk has come from genetic association (primarily case-control) studies. However, such studies have limited power to detect genes containing multiple rare variants that contribute significantly to disease risk.

Apolipoprotein E and functional motor severity in cerebral palsy.

Cerebral palsy is attributed to non-progressive disturbances in the developing fetal or infant brain. The APOE ε4 allele has been associated with poor outcome after brain injury in adults but may be protective among very young children. We conducted this study to explore the hypothesis that the APOE ε4 is associated with lowered severity of cerebral palsy.

Positive and negative regulatory mechanisms in high-affinity IgE receptor-mediated mast cell activation.

Mast cells are important effector cells in allergic inflammatory reactions. The aggregation of the high-affinity IgE receptor (FcepsilonRI) on the surface of mast cells initiates a complex cascade of signaling events that ultimately leads to the release of various mediators involved in allergic inflammation and anaphylactic reactions. The release of these mediators is tightly controlled by signaling pathways that are propagated through the cell by specific phosphorylation and dephosphorylation events.

Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.

Effects of cardiopulmonary bypass on tight junction protein expressions in intestinal mucosa of rats.

Aim: To investigate the tight junction protein expressions of intestinal mucosa in an experimental model of cardiopulmonary bypass (CPB) in rats.

Methods: Thirty anesthetized rats were randomly divided into two groups: Group S (n = 10) served as sham operation and group C (n = 20) served as CPB which underwent CPB for 1 h. Expression of occludin and zonula occludens-1 (ZO-1) were determined by Western blotting and immunotochemistry, respectively.