Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells

The pHs of extracellular fluids (ECFs) in normal tissues are commonly maintained at 7.35 to 7.45. The acidification of the ECF is one of the major characteristics of tumour microenvironment. In this study, we report that decreased extracellular pH promotes the transformation of mesenchymal stem cells (MSCs) into cancer-associated fibroblasts (CAFs), termed CAF activation. Furthermore, we demonstrate that GPR68, a proton-sensing G-protein-coupled receptor (GPCR), is required for the pH-dependent regulation of the differentiation of MSCs into CAFs. We then identify Yes-associated protein 1 (YAP) as a downstream effector of GPR68 for CAF activation. Finally, we show that knockdown of GPR68 in MSCs can prevent the CAF activation under cancer microenvironment. Systemic transplantation of GPR68-silenced MSCs suppresses in-situ tumour growth and prolong life span after cancer graft.     

The Mbam drainage system and onchocerciasis transmission post ivermectin mass drug administration (MDA) campaign,Cameroon

BackgroundThe impact of large scale Mass Drug Adminstration (MDA) of ivermectin on active onchocerciasis transmission by Simulium damnosum, which transmits the parasite O. volvulus is of great importance for onchocerciasis control programmes. We investigated in the Mbam river system area, the impact of MDA of ivermectin on entomological indices and also verify if there are river system factors that could have favoured the transmission of onchocerciasis in this area and contribute to the persistence of disease. We compared three independent techniques to detect Onchocerca larvae in blackflies and also analyzed the river system within 9 months post-MDA of ivermectin.MethodSimulium flies were captured before and after 1, 3, 6 and 9months of ivermectin-MDA. The biting rate was determined and 41% of the flies dissected while the rest were grouped into pools of 100 flies for DNA extraction. The extracted DNA was then subjected to O-150 LAMP and real-time PCR for the detection of infection by Onchocerca species using pool screening. The river system was analysed and the water discharge compared between rainy and dry seasons.Principal findingsWe used human landing collection method (previously called human bait) to collect 22,274 adult female Simulium flies from Mbam River System. Of this number, 9,134 were dissected while 129 pools constituted for molecular screening. Overall biting and parous rates of 1113 flies/man/day and 24.7%, respectively, were observed. All diagnostic techniques detected similar rates of O. volvulus infection (P = 0.9252) and infectivity (P = 0.4825) at all monitoring time points. Onchocerca ochengi larvae were only detected in 2 of the 129 pools. Analysis of the river drainage revealed two hydroelectric dams constructed on the tributaries of the Mbam river were the key contributing factor to the high-water discharge during both rainy and dry seasons.ConclusionResults from fly dissection (Microscopy), real-time PCR and LAMP revealed the same trends pre- and post-MDA. The infection rate with animal Onchocerca sp was exceptionally low. The dense river system generate important breeding sites that govern the abundance of Simulium during both dry and rainy seasons.     

Consistent estimation of the number of communities via regularized network embedding

The network analysis plays an important role in numerous application domains including biomedicine. Estimation of the number of communities is a fundamental and critical issue in network analysis. Most existing studies assume that the number of communities is known a priori, or lack of rigorous theoretical guarantee on the estimation consistency. In this paper, we propose a regularized network embedding model to simultaneously estimate the community structure and the number of communities in a unified formulation. The proposed model equips network embedding with a novel composite regularization term, which pushes the embedding vector toward its center and pushes similar community centers collapsed with each other. A rigorous theoretical analysis is conducted, establishing asymptotic consistency in terms of community detection and estimation of the number of communities. Extensive numerical experiments have also been conducted on both synthetic networks and brain functional connectivity network, which demonstrate the superior performance of the proposed method compared with existing alternatives.     

A purely green synthesis of silver nanoparticles using Carica papaya,Manihot esculenta,and Morinda citrifolia: synthesis and antibacterial evaluations

Bioprocess and Biosystems Engineering - Green procedure for synthesizing silver nanoparticles (AgNPs) is currently considered due to its economy and toxic-free effects. Several existing works on...     

Climatic influences on needle cohort survival mediated by Swiss needle cast in coastal Douglas-fir

Swiss needle cast (SNC) severity in Douglas-fir (Pseudotsuga menziesii) has been shown to vary spatially and temporally in response to climatic factors both within its native range and in regions where it has been planted as an exotic species. Survival models were developed for different Douglas-fir needle cohorts to enhance our understanding of how climatic influences on needle longevity are mediated by SNC in the Oregon Coast Range. The climate-based models were based on repeated measurement of 100 plots between 1998 and 2005 coupled with downscaled PRISM climate data. Potential predictors of needle survival by annual cohort were selected from numerous climatic variables at annual, seasonal, and monthly scales. Needle survival probability was positively associated with maximum summer temperature, and negatively associated with minimum winter temperature and spring precipitation. Seasonal climate variables associated with needle longevity are consistent with current epidemiological understanding of Phaeocyrptopus gaeumannii, as well as with previous analyses of climatic influences on SNC severity as measured by average years of foliage retention and frequency of fungal fruiting bodies, or pseudothecia, in stomates.     

The disruption ofSaccharomyces cerevisiae cells and release of glucose 6-phosphate dehydrogenase (G6PDH) in a horizontal dyno bead mill operated in continuous recycling mode

Baker’s yeast was disrupted in a 1.4-L stainless steel horizontal bead mill under a continuous recycle mode using 0.3 mm diameter zirconia beads as abrasive. A single pass in continuous mode bead mill operation liberates half of the maximally released protein. The maximum total protein release can only be achieved after passaging the cells 5 times through the disruption chamber. The degree of cell disruption was increased with the increase in feeding rate, but the total protein release was highest at the middle range of feeding rate (45 L/h). The total protein release was increased with an increase in biomass concentration from 10 to 50% (w/v). However, higher heat dissipation as a result of high viscosity of concentrated biomass led to the denaturation of labile protein such as glucose 6-phosphate dehydrogenase (G6PDH). As a result the highest specific activity of G6PDH was achieved at biomass concentration of 20% (ww/v). Generally, the degree of cell disruption and total protein released were increased with an increase in impeller tip speed, but the specific activity of G6PDH was decreased substantially at higher impeller tip speed (14 m/s). Both the degree of cell disruption and total protein release increased, as the bead loading increased from 75 to 85% (v/v). Hence, in order to obtain a higher yield of labile protein such as G6PDH, the yeast cell should not be disrupted at biomass concentration and impeller tip speed higher than 20% (w/v) and 10 m/s, respectively.     

DegU调控单核细胞增生李斯特菌感染宿主细胞及适应高温的机制研究

【目的】本研究旨在探究孤儿调节因子DegU在介导单核细胞增生李斯特菌(Listeria monocytogenes)宿主感染和高温环境适应性方面的调控机制。【方法】本研究以单增李斯特菌参考菌株EGD-e、degU基因缺失菌株ΔdegU和回补菌株CΔdegU为研究材料，通过细胞模型、实时荧光定量聚合酶链式反应和凝胶阻滞试验等方法探究DegU对单增李斯特菌感染宿主细胞和适应高温的调控机制。【结果】研究结果表明：缺失degU后，单增李斯特菌在Caco-2上的黏附和侵袭能力显著降低，在RAW264.7中的增殖能力显著降低，在L929中的空斑形成能力也显著降低；进一步通过实时荧光定量聚合酶链式反应检测degU基因缺失后引起的单增李斯特菌毒力因子转录水平变化，发现多个重要毒力因子转录水平均显著下调；该试验结果还发现与毒力相关的热应激基因clpE(受CtsR抑制的ATP依赖蛋白水解酶编码基因)转录水平显著升高，而在43℃高温条件下，clpE转录水平显著降低；进一步通过凝胶阻滞试验结果表明DegU能够与clpE的启动子直接结合。【结论】综上所述，degU基因缺失能够降低单增李斯特菌在宿主感染过程中的细...