Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I/M154I catalytic domain

HIV-1 integrase (IN) is an essential enzyme for the viral replication and an interesting target for the design of new pharmaceuticals for multidrug therapy of AIDS. Single and multiple mutations of IN at residues T66, S153, or M154 confer degrees of resistance to several inhibitors that prevent the enzyme from performing its normal strand transfer activity. Four different conformations of IN were chosen from a prior molecular dynamics (MD) simulation on the modeled IN T66I/M154I catalytic core domain as starting points for additional MD studies. The aim of this article is to understand the dynamic features that may play roles in the catalytic activity of the double mutant enzyme in the absence of any inhibitor. Moreover, we want to verify the influence of using different starting points on the MD trajectories and associated dynamical properties. By comparison of the trajectories obtained from these MD simulations we have demonstrated that the starting point does not affect the conformational space explored by this protein and that the time of the simulation is long enough to achieve convergence for this system.     

Proposed standard nomenclature for the alpha- and beta-globin gene families

The globin family of genes and proteins has been a recurrent object of study for many decades. This interest has generated a vast amount of knowledge. However it has also created an inconsistent and confusing nomenclature, due to the lack of a systematic approach to naming genes and failure to reflect the phylogenetic relationships among genes of the gene family. To alleviate the problems with the existing system, here we propose a standardized nomenclature for the alpha and beta globin family of genes, based on a phylogenetic analysis of vertebrate alpha and beta globins, and following the Guidelines for Human Gene Nomenclature.     

Antioxidant activity,acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum extracts

In this study several investigations and tests were performed to determine the antioxidant activity and the acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum aqueous extracts (10% mass) and ethanolic extracts (10% mass and 70% ethanol), respectively. Moreover, for each type of the prepared extracts of P. officinalis and of C. umbellatum the content in the biologically active compounds – polyphenols, flavones and proanthocyanidins was determined. The antioxidant activity was assessed using two methods, namely the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and reducing power assay. The analyzed plant extracts showed a high acetylcholinesterase and tyrosinase inhibitory activity in the range of 72.24–94.24% (at the highest used dose – 3 mg/mL), 66.96% and 94.03% (at 3 mg/mL), respectively correlated with a high DPPH radical inhibition – 70.29–84.9% (at 3 mg/mL). These medicinal plants could provide a potential natural source of bioactive compounds and could be beneficial to the human health, especially in the neurodegenerative disorders and as sources of natural antioxidants in food industry.     

Capsaicin Modulates Proliferation,Migration, and Activation of Hepatic Stellate Cells

Capsaicin, the active component of chili pepper, has been reported to have antiproliferative and anti-inflammatory effects on a variety of cell lines. In the current study, we aimed to investigate the effects of capsaicin during HSC activation and maintenance. Activated and freshly isolated HSCs were treated with capsaicin. Proliferation was measured by incorporation of EdU. Cell cycle arrest and apoptosis were investigated using flow cytometry. The migratory response to chemotactic stimuli was evaluated by a modified Boyden chamber assay. Activation markers and inflammatory cytokines were determined by qPCR, immunocytochemistry, and flow cytometry. Our results show that capsaicin reduces HSC proliferation, migration, and expression of profibrogenic markers of activated and primary mouse HSCs. In conclusion, the present study shows that capsaicin modulates proliferation, migration, and activation of HSC in vitro.     

Effects of topographic variability on the scaling of plant species richness in gradient dominated landscapes

It is commonly assumed that variation in abiotic site conditions influences the number of niches, which in turn affects the potential species richness in an area. Based on theoretical considerations, abiotic variation is often used as an estimator of species richness at broad scales, while at finer landscape scales the diversity of habitat types is used. However, habitat estimators assume the landscape to be composed of discrete, homogeneous patches with sharp boundaries, and such a concept is hard to apply in gradient-dominated landscapes. The aim of this study was therefore to investigate the influence of topographic variability (TV) on species richness at the landscape level (gamma (γ) diversity) and on its components (alpha (α) and beta (β) diversity) at microsite and habitat group levels. Using floristic data from 12 "landscapes" of 1 km² we investigated the influence on diversity components of two simple and one complex measures of TV. While the standard deviation (SD) of altitude explained a high proportion of the variation in γ diversity (linear regression model, R²=0.63), the complex measure, SD of solar radiation explained it even better (R²=0.82). There were strong effects of TV on α and β diversity components at the microsite level, but only marginal increases of the diversity components at the habitat level. Further analyses revealed that the missing increase of the habitat level components was caused by differences between habitat groups and that only grassland diversity components increased significantly with TV. We conclude that TV at a landscape scale has strong effects on niche or microsite diversity and is an appropriate estimator of relative species richness in landscapes that are topographically heterogeneous and gradient dominated.     

Cooperation of Aspergillus nidulans enzymes increases plant polysaccharide saccharification

Efficient polysaccharide degradation depends on interaction between enzymes acting on the main chain and the side chains. Previous studies demonstrated cooperation between several enzymes, but not all enzyme combinations have been explored. A better understanding of enzyme cooperation would enable the design of better enzyme mixtures, optimally profiting from synergistic effects. In this study, we analyzed the cooperation of several enzymes involved in the degradation of xylan, glucan, xyloglucan and crude plant biomass from Aspergillus nidulans by single and combined incubations with their polymeric substrate. Positive effects were observed between most enzymes, although not always to the same extent. Moreover, the tailor made cocktails formulated in this study resulted in efficient release of glucose from plant biomass. This study also serves as an example for the complex cooperation that occurs between enzymes in plant biomass saccharification and how expression in easily‐accessible hosts, such as Pichia pastoris, can help in revealing these effects.     

Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring

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Exploring context dependency in eco‐evolutionary patterns with the stick insect Timema cristinae

Rapid evolution can influence the ecology of populations, communities, and ecosystems, but the importance of evolution for ecological dynamics remains unclear, largely because the contexts in which evolution is powerful are poorly resolved. Here, we carry out a large observational study to test hypotheses about context dependency of eco‐evolutionary patterns previously identified on the stick insect Timema cristinae. Experiments and observations conducted in 2011 and 2012 documented predator‐mediated negative effects of camouflage maladaptation (i.e., evolutionary dynamics) on: (a) T. cristinae abundance and, (b) species richness and abundance of other arthropods. Here we show that camouflage maladaptation does not correlate with T. cristinae abundance and, instead, is associated with increased abundance and species richness of cohabitating arthropods. We furthermore find that plants with high levels of Timema maladaptation tend to have higher foliar nitrogen, that is, higher nutritional value, and more positive mass‐abundance slopes in the coexisting arthropod communities. We propose explanations for the observed contrasting results, such as negative density‐ and frequency‐dependent selection, feedbacks between herbivore abundance and plant nutritional quality, and common effects of predation pressure on selection and prey abundance. Our results demonstrate the utility of observational studies to assess the context dependency of eco‐evolutionary dynamics patterns and provide testable hypotheses for future work.     

Effects of captivity,diet, and relocation on the gut bacterial communities of white‐footed mice

Microbes can have important impacts on their host's survival. Captive breeding programs for endangered species include periods of captivity that can ultimately have an impact on reintroduction success. No study to date has investigated the impacts of captive diet on the gut microbiota during the relocation process of generalist species. This study simulated a captive breeding program with white‐footed mice (Peromyscus leucopus) to describe the variability in gut microbial community structure and composition during captivity and relocation in their natural habitat, and compared it to wild individuals. Mice born in captivity were fed two different diets, a control with dry standardized pellets and a treatment with nonprocessed components that reflect a version of their wild diet that could be provided in captivity. The mice from the two groups were then relocated to their natural habitat. Relocated mice that had the treatment diet had more phylotypes in common with the wild‐host microbiota than mice under the control diet or mice kept in captivity. These results have broad implications for our understanding of microbial community dynamics and the effects of captivity on reintroduced animals, including the potential impact on the survival of endangered species. This study demonstrates that ex situ conservation actions should consider a more holistic perspective of an animal's biology including its microbes.