Next-generation sequencing (NGS) has revolutionized how research is carried out in many areas of biology and medicine. However, the analysis of NGS data remains a major obstacle to the efficient ...utilization of the technology, as it requires complex multi-step processing of big data demanding considerable computational expertise from users. While substantial effort has been invested on the development of software dedicated to the individual analysis steps of NGS experiments, insufficient resources are currently available for integrating the individual software components within the widely used R/Bioconductor environment into automated workflows capable of running the analysis of most types of NGS applications from start-to-finish in a time-efficient and reproducible manner.
To address this need, we have developed the R/Bioconductor package systemPipeR. It is an extensible environment for both building and running end-to-end analysis workflows with automated report generation for a wide range of NGS applications. Its unique features include a uniform workflow interface across different NGS applications, automated report generation, and support for running both R and command-line software on local computers and computer clusters. A flexible sample annotation infrastructure efficiently handles complex sample sets and experimental designs. To simplify the analysis of widely used NGS applications, the package provides pre-configured workflows and reporting templates for RNA-Seq, ChIP-Seq, VAR-Seq and Ribo-Seq. Additional workflow templates will be provided in the future.
systemPipeR accelerates the extraction of reproducible analysis results from NGS experiments. By combining the capabilities of many R/Bioconductor and command-line tools, it makes efficient use of existing software resources without limiting the user to a set of predefined methods or environments. systemPipeR is freely available for all common operating systems from Bioconductor ( http://bioconductor.org/packages/devel/systemPipeR ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We replicated and extended Shoda, Mischel, and Peake’s (1990) famous marshmallow study, which showed strong bivariate correlations between a child’s ability to delay gratification just before ...entering school and both adolescent achievement and socioemotional behaviors. Concentrating on children whose mothers had not completed college, we found that an additional minute waited at age 4 predicted a gain of approximately one tenth of a standard deviation in achievement at age 15. But this bivariate correlation was only half the size of those reported in the original studies and was reduced by two thirds in the presence of controls for family background, early cognitive ability, and the home environment. Most of the variation in adolescent achievement came from being able to wait at least 20 s. Associations between delay time and measures of behavioral outcomes at age 15 were much smaller and rarely statistically significant.
ChemMine Tools is an online service for small molecule data analysis. It provides a web interface to a set of cheminformatics and data mining tools that are useful for various analysis routines ...performed in chemical genomics and drug discovery. The service also offers programmable access options via the R library ChemmineR. The primary functionalities of ChemMine Tools fall into five major application areas: data visualization, structure comparisons, similarity searching, compound clustering and prediction of chemical properties. First, users can upload compound data sets to the online Compound Workbench. Numerous utilities are provided for compound viewing, structure drawing and format interconversion. Second, pairwise structural similarities among compounds can be quantified. Third, interfaces to ultra-fast structure similarity search algorithms are available to efficiently mine the chemical space in the public domain. These include fingerprint and embedding indexing algorithms. Fourth, the service includes a Clustering Toolbox that integrates cheminformatic algorithms with data mining utilities to enable systematic structure and activity based analyses of custom compound sets. Fifth, physicochemical property descriptors of custom compound sets can be calculated. These descriptors are important for assessing the bioactivity profile of compounds in silico and quantitative structure-activity relationship (QSAR) analyses. ChemMine Tools is available at: http://chemmine.ucr.edu.
We introduce an electro-optic hardware platform for nonlinear activation functions in optical neural networks. The optical-to-optical nonlinearity operates by converting a small portion of the input ...optical signal into an analog electric signal, which is used to intensity -modulate the original optical signal with no reduction in processing speed. Our scheme allows for complete nonlinear on-off contrast in transmission at relatively low optical power thresholds and eliminates the requirement of having additional optical sources between each of the layers of the network Moreover, the activation function is reconfigurable via electrical bias, allowing it to be programmed or trained to synthesize a variety of nonlinear responses. Using numerical simulations, we demonstrate that this activation function significantly improves the expressiveness of optical neural networks, allowing them to perform well on two benchmark machine learning tasks: learning a multi-input exclusive-OR (XOR) logic function and classification of images of handwritten numbers from the MNIST dataset. The addition of the nonlinear activation function improves test accuracy on the MNIST task from 85% to 94%.
Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization.The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly ...understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins. Quantitative mass spectrometry not only recapitulated known inhibitory postsynaptic proteins but also revealed a large network of new proteins, many of which are either implicated in neurodevelopmental disorders or are of unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion of one of these previously uncharacterized proteins, InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of miniature inhibitory currents, and increased excitability in the hippocampus. Our findings uncover a rich and functionally diverse assemblage of previously unknown proteins that regulate postsynaptic inhibition and might contribute to developmental brain disorders.
Neutrophil extracellular traps (NETs) comprise an ejected lattice of chromatin enmeshed with granular and nuclear proteins that are capable of capturing and killing microbial invaders. Although ...widely employed to combat infection, the antimicrobial mechanism of NETs remains enigmatic. Efforts to elucidate the bactericidal component of NETs have focused on the role of NET-bound proteins including histones, calprotectin and cathepsin G protease; however, exogenous and microbial derived deoxyribonuclease (DNase) remains the most potent inhibitor of NET function. DNA possesses a rapid bactericidal activity due to its ability to sequester surface bound cations, disrupt membrane integrity and lyse bacterial cells. Here we demonstrate that direct contact and the phosphodiester backbone are required for the cation chelating, antimicrobial property of DNA. By treating NETs with excess cations or phosphatase enzyme, the antimicrobial activity of NETs is neutralized, but NET structure, including the localization and function of NET-bound proteins, is maintained. Using intravital microscopy, we visualized NET-like structures in the skin of a mouse during infection with Pseudomonas aeruginosa. Relative to other bacteria, P. aeruginosa is a weak inducer of NETosis and is more resistant to NETs. During NET exposure, we demonstrate that P. aeruginosa responds by inducing the expression of surface modifications to defend against DNA-induced membrane destabilization and NET-mediated killing. Further, we show induction of this bacterial response to NETs is largely due to the bacterial detection of DNA. Therefore, we conclude that the DNA backbone contributes both to the antibacterial nature of NETs and as a signal perceived by microbes to elicit host-resistance strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous benefits have been attributed to alkaline-electrolyzed-reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured ...to be due to the intrinsic properties of ERW (e.g., negative oxidation-reduction potential (ORP), alkaline pH, H
gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, free electrons, active hydrogen, mineral hydrides). The associated pseudoscientific marketing has contributed to the reluctance of mainstream science to accept ERW as having biological effects. Finally, through many in vitro and in vivo studies, each one of these propositions was examined and refuted one-by-one until it was conclusively demonstrated that H
was the exclusive agent responsible for both the negative ORP and the observed therapeutic effects of ERW. This article briefly apprised the history of ERW and comprehensively reviewed the sequential research demonstrating the importance of H
. We illustrated that the effects of ERW could be readily explained by the known biological effects of H
and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H
concentration of ERW should be measured to ensure it is comparable to those used in clinical studies.
Microplastics (MP; 1 μm to 1 mm) of various shapes and compositions are ingested by numerous marine animals. Recently, proposals have been made to adopt bivalve molluscs as bioindicators of MP ...pollution. To serve as indicators of MP pollution, however, the proposed organisms should ingest, without bias, the majority of plastic particles to which they are exposed. To test this premise, eastern oysters, Crassostrea virginica, and blue mussels, Mytilus edulis, were offered variously sized polystyrene microspheres (diameters 19–1000 μm) and nylon microfibers (lengths 75–1075 × diameter 30 μm), and the proportion of each rejected in pseudofeces and egested in feces was determined. For both species, the proportion of microspheres rejected increased from ca. 10–30% for the smallest spheres to 98% for the largest spheres. A higher proportion of the largest microsphere was rejected compared with the longest microfiber, but similar proportions of microfibers were ingested regardless of length. Differential egestion of MP also occurred. As a result of particle selection, the number and types of MP found in the bivalve gut will depend upon the physical characteristics of the particles. Thus, bivalves will be poor bioindicators of MP pollution in the environment, and it is advised that other marine species be explored.
Virtually all examined plant species harbour fungal endophytes which asymptomatically infect or colonize living plant tissues, including leaves, branches, stems and roots. Endophyte-host interactions ...are complex and span the mutualist-pathogen continuum. Notably, mutualist endophytes can confer increased fitness to their host plants compared with uncolonized plants, which has attracted interest in their potential application in integrated plant health management strategies. In this review, we report on the many benefits that fungal endophytes provide to agricultural plants against common non-insect pests such as fungi, bacteria, nematodes, viruses, and mites. We report endophytic modes of action against the aforementioned pests and describe why this broad group of fungi is vitally important to current and future agricultural practices. We also list an extensive number of plant-friendly endophytes and detail where they are most commonly found or applied in different studies. This review acts as a general resource for understanding endophytes as they relate to potential large-scale agricultural applications.
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