3D-QSAR studies of checkpoint kinase 1 inhibitors based on molecular docking and CoMFA

Three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on a series of substituted 1,4-dihydroindeno[1,2-c]pyrazoles inhibitors, using molecular docking and comparative molecular field analysis (CoMFA). The docking results from GOLD 3.0.1 provide a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA model was built with cross-validated q ² value of 0.534 and non-cross-validated partial least-squares analysis with the optimum components of six showed a conventional r ² value of 0.911. The predictive ability of this model was validated by the testing set with a conventional r ² value of 0.812. Based on the docking and CoMFA, we have identified some key features of the 1,4-dihydroindeno[1,2-c]pyrazoles derivatives that are responsible for checkpoint kinase 1 inhibitory activity. The analyses may be used to design more potent 1,4-dihydroindeno[1,2-c]pyrazoles derivatives and predict their activity prior to synthesis.     

Applications of functional gene microarrays for profiling microbial communities

Functional gene arrays (FGAs) have been considered as a specific, sensitive, quantitative, and high throughput metagenomic tool to detect, monitor and characterize microbial communities. Especially GeoChips, the most comprehensive FGAs have been applied to analyze the functional diversity, composition, structure, and metabolic potential or activity of a variety of microbial communities from different habitats, such as aquatic ecosystems, soils, contaminated sites, extreme environments, and bioreactors. FGAs are able to address fundamental questions related to global change, bioremediation, land use, human health, and ecological theories, and link the microbial community structure to environmental properties and ecosystem functioning. This review focuses on applications of FGA technology for profiling microbial communities, including target preparation, hybridization and data processing, and data analysis. We also discuss challenges and future directions of FGA applications.     

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

OBJECTIVE--To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN--Open randomised multicentre trial with three year follow up. SETTING--Outpatient departments of six French hospitals. PATIENTS--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS--Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.     

Metabolic engineering of Clostridium tyrobutyricum for enhanced butyric acid production with high butyrate/acetate ratio

Applied Microbiology and Biotechnology - Butyric acid fermentation by Clostridium couples with the synthesis of acetic acid. But the presence of acetic acid reduces butyric acid yield and increases...     

MicroRNA profiles in Sorghum exposed to individual drought or heat or their combination

Sorghum is largely grown for food, fodder and for biofuel production in semi-arid regions where the drought or high temperature or their combination co-occur. Plant microRNAs (miRNAs) are integral to the gene regulatory networks that control almost all biological processes including adaptation to stress conditions. Thus far, plant miRNA profiles under separate drought or heat stresses have been reported but not under combined drought and heat. In this study, we report miRNA profiles in leaves of sorghum exposed to individual drought or heat or their combination. Approximately 29 conserved miRNA families represented by 80 individual miRNAs, 26 families represented by 47 members of less conserved or sorghum-specific miRNA families as well as 8 novel miRNA families have been identified. Of these, 25 miRNAs were found to be differentially regulated in response to stress treatments. The comparative profiling revealed that the miRNA regulation was stronger under heat or combination of heat and drought compared to the drought alone. Furthermore, using degradome sequencing, 48 genes were confirmed as targets for the miRNAs in sorghum. Overall, this study provides a framework for understanding of the miRNA-guided gene regulations under combined stresses.

     

OSMRβ mutants enhance basal keratinocyte differentiation via inactivation of the STAT5/KLF7 axis in PLCA patients

Dear Editor, Primary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized by deposition of amyloid material in the superficial dermis.According to clinical characteristics,PLCA is divided into lichen,macular,and nodular amyloidosis.PLCA is found worldwide but has a higher incidence in South America and Southeast Asia,such as in Brazil and China (Chang et al.,2014;Tey et al.,2016).     

Loss of Heterozygosity Drives Clonal Diversity of Phytophthora capsici in China

Phytophthora capsici causes significant loss to pepper (Capsicum annum) in China and our goal was to develop single nucleotide polymorphism (SNP) markers for P. capsici and characterize genetic diversity nationwide. Eighteen isolates of P. capsici from locations worldwide were re-sequenced and candidate nuclear and mitochondrial SNPs identified. From 2006 to 2012, 276 isolates of P. capsici were recovered from 136 locations in 27 provinces and genotyped using 45 nuclear and 2 mitochondrial SNPs. There were two main mitochondrial haplotypes and 95 multi-locus genotypes (MLGs) identified. Genetic diversity was geographically structured with a high level of genotypic diversity in the north and on Hainan Island in the south, suggesting outcrossing contributes to diversity in these areas. The remaining areas of China are dominated by four clonal lineages that share mitochondrial haplotypes, are almost exclusively the A1 or A2 mating type and appear to exhibit extensive diversity based on loss of heterozygosity (LOH). Analysis of SNPs directly from infected peppers confirmed LOH in field populations. One clonal lineage is dominant throughout much of the country. The overall implications for long-lived genetically diverse clonal lineages amidst a widely dispersed sexual population are discussed.     

Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia

Transient global ischemia (which closely resembles clinical situations such as cardiac arrest, near drowning or severe systemic hypotension during surgical procedures), often induces delayed neuronal death in the brain, especially in the hippocampal CA1 region. The mechanism of ischemia/reperfusion (I/R) injury is not fully understood. In this study, we have shown that the P2X7 receptor antagonist, BBG, reduced delayed neuronal death in the hippocampal CA1 region after I/R injury; P2X7 receptor expression levels increased before delayed neuronal death after I/R injury; inhibition of the P2X7 receptor reduced I/R-induced microglial microvesicle-like components, IL-1β expression, P38 phosphorylation, and glial activation in hippocampal CA1 region after I/R injury. These results indicate that antagonism of the P2X7 receptor and signaling pathways of microglial MV shedding, such as src-protein tyrosine kinase, P38 MAP kinase and A-SMase, might be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.