Notes

[Flaviviridae along with mitochondria: Whatever you always aspired to find out about their own relationship however ended up scared in order to ask].
Classic concepts of genetic (gene) diversity (heterozygosity) such as Nei & Li's nucleotide diversity were defined within a population context. Although variations are often measured in population context, the basic carriers of variation are individuals. Hence, measuring variations such as SNP of an individual against a reference genome, which has been ignored previously, is certainly in its own right. Indeed, similar practice has been a tradition in community ecology, where the basic unit of diversity measure is individual community sample. We propose to use Renyi's-entropy-based Hill numbers to define individual-level genetic diversity and similarity and demonstrate the definitions with the SNP (single nucleotide polymorphism) datasets from the 1000-Genomes Project. Hill numbers, derived from Renyi's entropy (of which Shannon's entropy is a special case), have found widely applications including measuring the quantum information entanglement and ecological diversity. The demonstrated individual-level SNP diversity not only complements the existing population-level genetic diversity concepts, but also offers building blocks for comparative genetic analysis at higher levels. The concept of individual covers, but is not limited to, individual chromosome, region of chromosome, gene cluster(s), or whole genome. Similarly, the SNP can be replaced by other structural variants or mutation types such as indels.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Extracellular matrix in solid tumors has emerged as a specific, stable, and abundant target for affinity-guided delivery of anticancer drugs. Here we describe the homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues. TNC-C binding PL3 peptide (amino acid sequence AGRGRLVR) was identified by in vitro biopanning on recombinant TNC-C. Besides TNC-C, PL3 interacts via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). Functionalization of iron oxide nanoworms (NWs) and metallic silver nanoparticles (AgNPs) with PL3 peptide increased tropism of systemic nanoparticles towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice (eight and five-fold respectively). Treatment of glioma-bearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. PL3-coated nanoparticles were found to accumulate in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance. The systemic tumor-targeting properties and binding of PL3-NPs to the clinical tumor sections, suggest that the PL3 peptide may have applications as a targeting moiety for the selective delivery of imaging and therapeutic agents to solid tumors.Elevated intraocular pressure (IOP) narrows Schlemm's canal (SC), theoretically increasing luminal shear stress. Using engineered adenoviruses containing a functional fragment of the shear-responsive endothelial nitric oxide synthase (eNOS) promoter, we tested effects of shear stress and elevated flow rate on reporter expression in vitro and ex vivo. Cultured human umbilical vein endothelial cells (HUVECs) and SC cells were transduced with adenovirus containing eNOS promoter driving secreted alkaline phosphatase (SEAP) or green fluorescent protein (GFP) and subjected to shear stress. In parallel, human anterior segments were perfused under controlled flow. After delivering adenoviruses to the SC lumen by retroperfusion, the flow rate in one anterior segment of pair was increased to double pressure. In response to high shear stress, HUVECs and SC cells expressed more SEAP and GFP than control. Similarly, human anterior segments perfused at higher flow rates released significantly more nitrites and SEAP into perfusion effluent, and SC cells expressed increased GFP near collector channel ostia compared to control. These data establish that engineered adenoviruses have the capacity to quantify and localize shear stress experienced by endothelial cells. This is the first in situ demonstration of shear-mediated SC mechanobiology as a key IOP-sensing mechanism necessary for IOP homeostasis.Helminth parasites have been shown to have systemic effects in the host. Using shotgun metagenomic sequencing, we characterise the gut microbiome and resistome of 113 Zimbabwean preschool-aged children (1-5 years). We test the hypothesis that infection with the human helminth parasite, Schistosoma haematobium, is associated with changes in gut microbial and antimicrobial resistance gene abundance/diversity. Here, we show that bacteria phyla Bacteroidetes, Firmicutes, Proteobacteria, and fungi phyla Ascomycota, Microsporidia, Zoopagomycota dominate the microbiome. The abundance of Proteobacteria, Ascomycota, and Basidiomycota differ between schistosome-infected versus uninfected children. Specifically, infection is associated with increases in Pseudomonas, Stenotrophomonas, Derxia, Thalassospira, Aspergillus, Tricholoma, and Periglandula, with a decrease in Azospirillum. We find 262 AMR genes, from 12 functional drug classes, but no association with individual-specific data. To our knowledge, we describe a novel metagenomic dataset of Zimbabwean preschool-aged children, indicating an association between urogenital schistosome infection and changes in the gut microbiome.Gre, one of the conserved transcription factors in bacteria, modulates RNA polymerase (RNAP) activity to ensure processivity and fidelity of RNA synthesis. Gre factors regulate transcription by inducing the intrinsic-endonucleolytic activity of RNAP, allowing the enzyme to resume transcription from the paused and arrested sites. While Escherichia coli and a number of eubacteria harbor GreA and GreB, genus mycobacteria has a single Gre (GreA). TDXd To address the importance of the GreA in growth, physiology and gene expression of Mycobacterium smegmatis, we have constructed a conditional knock-down strain of GreA. The GreA depleted strain exhibited slow growth, drastic changes in cell surface phenotype, cell death, and increased susceptibility to front-line anti-tubercular drugs. Transcripts and 2D-gel electrophoresis (2D-PAGE) analysis of the GreA conditional knock-down strain showed altered expression of the genes involved in transcription regulation. Among the genes analysed, expression of RNAP subunits (β, β' and ω), carD, hupB, lsr2, and nusA were affected to a large extent.
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