Highlights • A new understanding has emerged of links between human physiology and skin microbiota. • Microbial diversity is governed by genetics and diverse skin environments. • Host and microbe ...interactions shape and influence skin health. • Commensal microorganisms exhibit unique behaviors that permit tolerance.
To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up.
The Multicenter AIDS ...Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification.
The frequency of HAND for the 364 HIV+ individuals seen in 2007-2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007-2008, 2009-2010, and 2011-2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009-2010 to 2011-2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition.
HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.
Two important challenges need to be addressed to realize a practical biorefinery for the conversion of biomass to fuels and chemicals: (i) effective methods for the degradation and fractionation of ...lignocelluloses and (ii) efficient and robust chemical methods for the conversion of bio-feeds to target products via highly selective catalytic reactions. Ultrasonic energy promotes the pretreatment and conversion process through its special cavitational effects. In this review, recent progress and methods for combining and integrating sonication into biomass pretreatment and conversion for fuels and chemicals are critically assessed. Ultrasonic energy combined with proper solvents allows destruction of the recalcitrant lignocellulosic structure, fractionation of biomass components, and then assists many thermochemical and biochemical reactions, with increased equilibrium yields of sugars, bio-ethanol and gas products by 10–300%. Sonication promotes hydrolysis, esterification and transesterification in biodiesel synthesis and leads to reduced reaction time by 50–80%, lower reaction temperature, less amounts of solvent and catalyst than comparable unsonicated reaction systems. For algal biomass, sonication benefits the disruption, lysis and content release of macro and microalgae cells, and reduces the time required for subsequent extraction and chemical/biochemical reactions, with efficiencies typically being improved by 120–200%. High-frequency ultrasound of 1–3 MHz allows harvesting of microalgae, liquid product separation and in-situ process monitoring of biomass reactions, while high-intensity ultrasound at 20–50 kHz activates heterogeneous and enzymatic catalysis of the biomass reactions. The use of ultrasound in conversion of biomass to biofuels provides a positive process benefit.
The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a ...property that has clinical manifestations and alters muscle function. Here we review the structure, composition, and mechanical properties of skeletal muscle ECM; describe the cells that contribute to the maintenance of the ECM; and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure–function relationships. Detailed structure–function relationships of the ECM have yet to be defined and, as a result, we propose areas for future study. Muscle Nerve 44: 318–331, 2011
The ability to interpret the predictions made by quantitative structure-activity relationships (QSARs) offers a number of advantages. While QSARs built using nonlinear modeling approaches, such as ...the popular Random Forest algorithm, might sometimes be more predictive than those built using linear modeling approaches, their predictions have been perceived as difficult to interpret. However, a growing number of approaches have been proposed for interpreting nonlinear QSAR models in general and Random Forest in particular. In the current work, we compare the performance of Random Forest to those of two widely used linear modeling approaches: linear Support Vector Machines (SVMs) (or Support Vector Regression (SVR)) and partial least-squares (PLS). We compare their performance in terms of their predictivity as well as the chemical interpretability of the predictions using novel scoring schemes for assessing heat map images of substructural contributions. We critically assess different approaches for interpreting Random Forest models as well as for obtaining predictions from the forest. We assess the models on a large number of widely employed public-domain benchmark data sets corresponding to regression and binary classification problems of relevance to hit identification and toxicology. We conclude that Random Forest typically yields comparable or possibly better predictive performance than the linear modeling approaches and that its predictions may also be interpreted in a chemically and biologically meaningful way. In contrast to earlier work looking at interpretation of nonlinear QSAR models, we directly compare two methodologically distinct approaches for interpreting Random Forest models. The approaches for interpreting Random Forest assessed in our article were implemented using open-source programs that we have made available to the community. These programs are the rfFC package ( https://r-forge.r-project.org/R/?group_id=1725 ) for the R statistical programming language and the Python program HeatMapWrapper https://doi.org/10.5281/zenodo.495163 for heat map generation.
National space agencies and private corporations aim at an extended presence of humans in space in the medium to long term. Together with currently suboptimal technology, microgravity and cosmic rays ...raise health concerns about deep-space exploration missions. Both of these physical factors affect the cardiovascular system, whose gravity-dependence is pronounced. Heart and vascular function are, therefore, susceptible to substantial changes in weightlessness. The altered cardiovascular function in space causes physiological problems in the postflight period. A compromised cardiovascular system can be excessively vulnerable to space radiation, synergistically resulting in increased damage. The space radiation dose is significantly lower than in patients undergoing radiotherapy, in whom cardiac damage is well-documented following cancer therapy in the thoracic region. Nevertheless, epidemiological findings suggest an increased risk of late cardiovascular disease even with low doses of radiation. Moreover, the peculiar biological effectiveness of heavy ions in cosmic rays might increase this risk substantially. However, whether radiation-induced cardiovascular effects have a threshold at low doses is still unclear. The main countermeasures to mitigate the effect of the space environment on cardiac function are physical exercise, antioxidants, nutraceuticals, and radiation shielding.
Cancer chemotherapy is in evolution from non-specific cytotoxic drugs that damage both tumour and normal cells to more specific agents and immunotherapy approaches. Targeted agents are directed at ...unique molecular features of cancer cells, and immunotherapeutics modulate the tumour immune response; both approaches aim to produce greater effectiveness with less toxicity. The development and use of such agents in biomarker-defined populations enables a more personalized approach to cancer treatment than previously possible and has the potential to reduce the cost of cancer care.
Sleep is an essential process that supports learning and memory by acting on synapses through poorly understood molecular mechanisms. Using biochemistry, proteomics, and imaging in mice, we find that ...during sleep, synapses undergo widespread alterations in composition and signaling, including weakening of synapses through removal and dephosphorylation of synaptic AMPA-type glutamate receptors. These changes are driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors mGluR1/5. Homer1a serves as a molecular integrator of arousal and sleep need via the wake- and sleep-promoting neuromodulators, noradrenaline and adenosine, respectively. Our data suggest that homeostatic scaling-down, a global form of synaptic plasticity, is active during sleep to remodel synapses and participates in the consolidation of contextual memory.
PDF
