Recent developments in fluorescence in situ hybridization (FISH) methods allow the detection and visualization of the genes/genomic regions of bacteria, archaea and infecting viruses at the single cell level. These methods use mixtures of polynucleotides as probes to specifically detect the target of interest. Gene-PROBER enables the design of polynucleotide mixtures for targeting genes or genomic regions in microorganisms. It has four workflows, depending on the availability of non-target sequences and the choice of probe synthesis, either by chemical synthesis or by PCR. It outputs polynucleotides that are spread along the target sequence and have similar melting properties. Therefore, such a polynucleotide mixture can be used as a single probe, in a single hybridization reaction. Gene-PROBER is a freely available web service that can be accessed at http//gene-prober.icbm.de/, and is implemented in the R language using the Shiny package.Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking scores and interaction profile analyses exhibited strong binding affinity of eleven FDA approved drugs and five nucleoside analogues NA1 (-13.84), nadide (-13.65), citicholine (-13.54), NA2 (-12.42), and NA3 (-12.27). The lead compound NA1 exhibited significant hydrogen bonding and hydrophobic interaction at the natural substrate binding site. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface (SASA), hydrogen bond formation, principle component analysis, and free energy landscape calculations for NA1 bound protein displayed stable complex formation in 100 ns molecular dynamics simulation, compared to unbound macro domain and natural substrate adenosine-5-diphosphoribose bound macro domain that served as a positive control. The molecular mechanics Poisson-Boltzmann surface area analysis of NA1 demonstrated binding free energy of -175.978 ± 0.401 kJ/mol in comparison to natural substrate which had binding free energy of -133.403 ± 14.103 kJ/mol. In silico analysis by modelling tool ADMET and prediction of biological activity of these compounds further validated them as putative therapeutic molecules against SARS-CoV-2. Taken together, this study offers NA1 as a lead SARS-CoV-2 A1pp domain inhibitor for future testing and development as therapeutics against human coronavirus.
This study reviewed systematically the effects of sleep extension on sports performance.
Systematic review.
The systematic review was conducted in November 2020. Articles published in English were searched in PubMed, Virtual Health Library, SPORTDiscus, and Web of Science and Scopus databases. The search terms used were "sleep extension" AND athlete. The measures of interest were sports performance. Studies were included if they were a) original articles, b) published in English and peer-reviewed article, c) had only athletes as participants, d) experimental protocol whose objective was to investigate the effects of sleep extension on sports performance, including randomized (RCT) and non-randomized controlled trial (nRCT), and e) at least a sports performance measure as a dependent variable.
The primary search revealed that a total of 5 out of 74 articles were considered eligible and 2 studies were subsequently included. The studies used different strategies to extend time in bed or total sleep time (extending 26-106min). From fifteen sports measures, six presented a large effect size, and the others ranged from trivial to medium. Overall, the risk of bias was high to RCT and low to nRCT and the quality of evidence ranged from very low quality to moderate quality in ten outcomes.
The limited evidence suggests that sleep extension interventions may be beneficial to improve sports performance in athletes where the magnitude is dependent on the variable assessed, although such conclusions are tentative because of the quality of the evidence and risk of bias.
The limited evidence suggests that sleep extension interventions may be beneficial to improve sports performance in athletes where the magnitude is dependent on the variable assessed, although such conclusions are tentative because of the quality of the evidence and risk of bias.This prospective, observational study investigated changes in sleep and the effect on energy intake, gestational weight gain, and cardiometabolic health across pregnancy in 52 healthy pregnant women with obesity. Habitual sleep was assessed by wrist-worn actigraphy (time spent in bed; TIB, total sleep time; TST, and sleep efficiency) in early (130-156 weeks) and late (350-366) pregnancy. A change to habitual sleep was defined as change of one-half of the standard deviation of TIB and TST across six consecutive nights from early pregnancy. Energy intake and changes in weight, fasting glucose, insulin, and lipids across pregnancy were compared between women who changed sleep. During early pregnancy, TIB was 924 ± 008 h and varied by 137 ± 007 h across the six nights. TST and sleep efficiency significantly declined from early to late pregnancy (703 ± 008 h to 628 ± 009 h, p less then 0.001) and (76 ± 0.1% to 71 ± 0.2%, p less then 0.001), respectively. For women who increased TIB (n = 11), fasting glucose decreased (-11.6 ± 4.3%, p less then 0.01) across pregnancy and they had a trend towards decreased insulin (-57.8 ± 33.5%; p = 0.09) and HOMA-IR (-72.4 ± 37.3%; p = 0.06) compared to women who decreased TIB (n = 13). https://www.selleckchem.com/products/milademetan.html Women who increased TIB had a significantly lower daily energy intake across pregnancy (-540 ± 163 kcal; p less then 0.01) and tended to have less gestational weight gain (-147 ± 88 g/week; p = 0.10). Changes in TST did not affect plasma markers, energy intake or weight gain. The positive relationship between sleep and cardiometabolic health during pregnancy is explained in part by lower energy intake. We hypothesize lower energy intake is due to a prolonged overnight fast and a decrease in the time available for eating.