Loss of Visually Driven Synaptic Responses in Layer 4 Regular-Spiking Neurons of Rat Visual Cortex in Absence of Competing Inputs

Monocular deprivation (MD) during development shifts the ocular preference of primary visual cortex (V1) neurons by depressing closed-eye responses and potentiating open-eye responses. As these 2 p ..

Parallel Magnetic Field Tuning of Valley Splitting in AlAs Two-Dimensional Electrons

We demonstrate that, in a quasi-two-dimensional electron system confined to an AlAs quantum well and occupying two conduction-band minima (valleys), a parallel magnetic field can couple to the electrons' orbital motion and tune the energies of the two valleys by different amounts. The measured density imbalance between the two valleys, which is a measure of the valley susceptibility with respect to parallel magnetic field, is enhanced compared to the predictions of non-interacting calculations, reflecting the role of electron-electron interaction.Comment: 4+ pages, 4 figures, accepted for publication in Phys. Rev.

Pseudoclavibacter-like subcutaneous infection: a case report

<p>Abstract</p> <p>Background</p> <p><it>Arthrobacter</it>-like organisms, including <it>Pseudoclavibacter </it>organisms, have rarely been documented as being responsible for infection in humans.</p> <p>Case presentation</p> <p>An 81-year-old French man developed a subcutaneous infection despite antibiotic treatment combining clindamycin and metronidazole for chronic wound infection. A skin biopsy showed numerous polymorphonuclear cells and no bacteria, but a subcutaneous swab yielded numerous polymorphonuclear cells, a few Gram-positive cocci, Gram-negative cocci, and Gram-positive rods. The Gram-positive rod sequence exhibited 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419350" ext-link-type="gen">EF419350</ext-link>] and 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419347" ext-link-type="gen">EF419347</ext-link>]. The genetic data and unique peptide profile of this <it>Pseudoclavibacter</it>-like isolate, determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry, underscored its uniqueness.</p> <p>Conclusions</p> <p><it>Pseudoclavibacter</it>-like organisms are identifiable in cutaneous and subcutaneous infections in humans.</p

Tau-Driven Neuronal and Neurotrophic Dysfunction in a Mouse Model of Early Tauopathy.

Tauopathies are neurodegenerative diseases characterized by intraneuronal inclusions of hyperphosphorylated tau protein and abnormal expression of brain-derived neurotrophic factor (BDNF), a key modulator of neuronal survival and function. The severity of both these pathological hallmarks correlate with the degree of cognitive impairment in patients. However, how tau pathology specifically modifies BDNF signaling and affects neuronal function during early prodromal stages of tauopathy remains unclear. Here, we report that the mild tauopathy developing in retinal ganglion cells (RGCs) of the P301S tau transgenic (P301S) mouse induces functional retinal changes by disrupting BDNF signaling via the TrkB receptor. In adult P301S mice, the physiological visual response of RGCs to pattern light stimuli and retinal acuity decline significantly. As a consequence, the activity-dependent secretion of BDNF in the vitreous is impaired in P301S mice. Further, in P301S retinas, TrkB receptors are selectively upregulated, but uncoupled from downstream extracellular signal-regulated kinase (ERK) 1/2 signaling. We also show that the impairment of TrkB signaling is triggered by tau pathology and mediates the tau-induced dysfunction of visual response. Overall our results identify a neurotrophin-mediated mechanism by which tau induces neuronal dysfunction during prodromal stages of tauopathy and define tau-driven pathophysiological changes of potential value to support early diagnosis and informed therapeutic decisions. SIGNIFICANCE STATEMENT: This work highlights the potential molecular mechanisms by which initial tauopathy induces neuronal dysfunction. Combining clinically used electrophysiological techniques (i.e., electroretinography) and molecular analyses, this work shows that in a relevant model of early tauopathy, the retina of the P301S mutant human tau transgenic mouse, mild tau pathology results in functional changes of neuronal activity, likely due to selective impairment of brain-derived neurotrophic factor signaling via its receptor, TrkB. These findings may have important translational implications for early diagnosis in a subset of Alzheimer's disease patients with early visual symptoms and emphasize the need to clarify the pathophysiological changes associated with distinct tauopathy stages to support informed therapeutic decisions and guide drug discovery.journal articleresearch support, non-u.s. gov't2016 Feb 17importe

Electrochemical integration of graphene with light absorbing copper-based thin films

We present an electrochemical route for the integration of graphene with light sensitive copper-based alloys used in optoelectronic applications. Graphene grown using chemical vapor deposition (CVD) transferred to glass is found to be a robust substrate on which photoconductive Cu_{x}S films of 1-2 um thickness can be deposited. The effect of growth parameters on the morphology and photoconductivity of Cu_{x}S films is presented. Current-voltage characterization and photoconductivity decay experiments are performed with graphene as one contact and silver epoxy as the other

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception

BPGA- an ultra-fast pan-genome analysis pipeline

Recent advances in ultra-high-throughput sequencing technology and metagenomics have led to a paradigm shift in microbial genomics from few genome comparisons to large-scale pan-genome studies at different scales of phylogenetic resolution. Pan-genome studies provide a framework for estimating the genomic diversity of the dataset, determining core (conserved), accessory (dispensable) and unique (strain-specific) gene pool of a species, tracing horizontal gene-flux across strains and providing insight into species evolution. The existing pan genome software tools suffer from various limitations like limited datasets, difficult installation/requirements, inadequate functional features etc. Here we present an ultra-fast computational pipeline BPGA (Bacterial Pan Genome Analysis tool) with seven functional modules. In addition to the routine pan genome analyses, BPGA introduces a number of novel features for downstream analyses like core/pan/MLST (Multi Locus Sequence Typing) phylogeny, exclusive presence/absence of genes in specific strains, subset analysis, atypical G + C content analysis and KEGG & COG mapping of core, accessory and unique genes. Other notable features include minimum running prerequisites, freedom to select the gene clustering method, ultra-fast execution, user friendly command line interface and high-quality graphics outputs. The performance of BPGA has been evaluated using a dataset of complete genome sequences of 28 Streptococcus pyogenes strains

Using Sequence Similarity Networks for Visualization of Relationships Across Diverse Protein Superfamilies

The dramatic increase in heterogeneous types of biological data—in particular, the abundance of new protein sequences—requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity—GPCRs and kinases from humans, and the crotonase superfamily of enzymes—we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships

Efficient oligonucleotide probe selection for pan-genomic tiling arrays

Background: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. Results: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pangenome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. Conclusion: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.https://doi.org/10.1186/1471-2105-10-29