Spatiotemporal model of cellular mechanotransduction via Rho and YAP

How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies

Marshall Space Flight Center Electromagnetic Compatibility Design and Interference Control (MEDIC) handbook

The purpose of the MEDIC Handbook is to provide practical and helpful information in the design of electrical equipment for electromagnetic compatibility (EMS). Included is the definition of electromagnetic interference (EMI) terms and units as well as an explanation of the basic EMI interactions. An overview of typical NASA EMI test requirements and associated test setups is given. General design techniques to minimize the risk of EMI and EMI suppression techniques at the board and equipment interface levels are presented. The Handbook contains specific EMI test compliance design techniques and retrofit fixes for noncompliant equipment. Also presented are special tests that are useful in the design process or in instances of specification noncompliance

Applicability and sensitivity of PCR-SSCP method for milk species identification in cheese

Species identification in food has become a prominent issue in recent years as the importance of consumer protection has increased. DNA-based species identification methods were developed by researchers in the last two decades, as these are reliable, accurate, and low-cost techniques for species identification in raw and processed food products as well. In our study, universal primers were designed to conserved regions of mitochondrial 12S rRNA. Amplicons were heat-denatured and a PCR single strand conformation polymorphism (SSCP) method was developed to identify cattle, buffalo, sheep, and goat DNA. Sensitivity of this technique was tested on DNA mixtures of cattle-sheep, cattle-goat, and cattle-buffalo and the threshold limit of cattle DNA was 5%, 5%, and 3%, respectively. One hundred and five cheeses were purchased and collected from Bosnian and Hungarian farmers, retails, and supermarkets to reveal fraud, 32 percent of them (34 cheeses) were found to be mislabelled by species

Reproduction Efficiency and Health Traits in Dorper, White Dorper, and Tsigai Sheep Breeds under Temperate European Conditions

The objective of the current pilot study was to evaluate the reproductive performance and health indicators in Dorper, White Dorper, and Tsigai breed ewes managed semi-intensively under European temperate conditions. A total of 544 ewe-year units were observed, with ewes (ranging from 1.5 to 8 years of age) managed under identical rearing conditions for a period of two consecutive production cycles (2012 through 2013 and 2013 through 2014). In general, significant (p≤0.001) genotype-related disparities were found in occurrence rates for all health parameters taken into study. Clinical mastitis incidence was significantly lower (p≤0.05) in Dorper (9.4%) and White Dorper (10.8%) breeds compared to that of Tsigai ewes (17.4%). Significant differences (p≤0.05) for lameness were found between Dorper and Tsigai breeds, with occurrence rates of 8.0% and 2.9%, respectively. Incidence for pneumonia and abortion was not influenced (p>0.05) by the ewes’ genotype. Litter size was significantly lower (p≤0.05) in White Dorper breed than for Dorper and Tsigai ewes, of 1.21, 1.40, and 1.45, respectively. Conception rates and lambs survival were not affected (p>0.05) by genotype. Results suggest that South African Dorper and White Dorper sheep breeds have adapted well to the specific rearing conditions

Sinteza i antihipoksično djelovanje alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline

The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by microanalyses, IR- and 1H NMR data. Values of acute p.o. and i.p. toxicity in mice show lower toxicity compared to caffeine. Declines in spontaneous locomotor activity support the idea of depressive CNS activity of the compounds. Two compounds exhibited brain antihypoxic activity (5a and 5b against haemic and circulatory hypoxia, respectively).U radu je opisana sinteza alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline i njihova karakterizacija elementarnom analizom, IR- i 1H NMR spektroskopijom. Testiranja na miševima pokazuju da su sintetizirani spojevi primijenjeni p.o. i i.p. manje toksični od kofeina. Smanjenje lokomotoričke aktivnosti podupire ideju o njihovom depresivnom djelovanju na SŽS. Spojevi 5a i 5b djeluju antihipoksički u uvjetima krvne i cirkulacijske hipoksije u mozgu

Metagenomic Comparison of Two Thiomicrospira Lineages Inhabiting Contrasting Deep-Sea Hydrothermal Environments

Background: The most widespread bacteria in oxic zones of carbonate chimneys at the serpentinite-hosted Lost City hydrothermal field, Mid-Atlantic Ridge, belong to the Thiomicrospira group of sulfur-oxidizing chemolithoautotrophs. It is unclear why Thiomicrospira-like organisms thrive in these chimneys considering that Lost City hydrothermal fluids are notably lacking in hydrogen sulfide and carbon dioxide. Methodology/Principal Findings: Here we describe metagenomic sequences obtained from a Lost City carbonate chimney that are highly similar to the genome of Thiomicrospira crunogena XCL-2, an isolate from a basalt-hosted hydrothermal vent in the Pacific Ocean. Even though T. crunogena and Lost City Thiomicrospira inhabit different types of hydrothermal systems in different oceans, their genomic contents are highly similar. For example, sequences encoding the sulfur oxidation and carbon fixation pathways (including a carbon concentration mechanism) of T. crunogena are also present in the Lost City metagenome. Comparative genomic analyses also revealed substantial genomic changes that must have occurred since the divergence of the two lineages, including large genomic rearrangements, gene fusion events, a prophage insertion, and transposase activity. Conclusions/Significance: Our results show significant genomic similarity between Thiomicrospira organisms inhabiting different kinds of hydrothermal systems in different oceans, suggesting that these organisms are widespread and highl

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life

Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study

<p>Abstract</p> <p>Background</p> <p>The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype.</p> <p>Methods</p> <p>We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model.</p> <p>Results</p> <p>Univariate analysis showed: 1) <it>TNF</it>-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, <it>p </it>= 0.005, population attributable risk, PAR 5.2%); 2) carriers of the <it>IL6</it>-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, <it>p </it>= 0.007, PAR = 31.5%); 3) the carriage of <it>IL2</it>-330*G allele was associated with protection from severe osteolysis (OR = 0.55, <it>p </it>= 0.043). Based on logistic regression, the alleles <it>TNF</it>-238*A and <it>IL6</it>-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of <it>TNF</it>-238*A had increased cumulative hazard of THA failure according to Cox model (<it>p </it>= 0.024). In contrast, <it>IL2</it>-330*G allele predicted lower cumulative hazard of THA failure (<it>p </it>= 0.019).</p> <p>Conclusion</p> <p>Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor <it>TNF </it>allele could increase the cumulative risk of THA failure. Conversely, SNP in the <it>IL2 </it>gene may protect carriers from the above THA complications.</p