A new tool based on faecal stanols can distinguish specific mammalian species in modern and past environments

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The origins, evolution, and functional potential of alternative splicing in vertebrates.

Alternative splicing (AS) has the potential to greatly expand the functional repertoire of mammalian transcriptomes. However, few variant transcripts have been characterized functionally, making it difficult to assess the contribution of AS to the generation of phenotypic complexity and to study the evolution of splicing patterns. We have compared the AS of 309 protein-coding genes in the human ENCODE pilot regions against their mouse orthologs in unprecedented detail, utilizing traditional transcriptomic and RNAseq data. The conservation status of every transcript has been investigated, and each functionally categorized as coding (separated into coding sequence [CDS] or nonsense-mediated decay [NMD] linked) or noncoding. In total, 36.7% of human and 19.3% of mouse coding transcripts are species specific, and we observe a 3.6 times excess of human NMD transcripts compared with mouse; in contrast to previous studies, the majority of species-specific AS is unlinked to transposable elements. We observe one conserved CDS variant and one conserved NMD variant per 2.3 and 11.4 genes, respectively. Subsequently, we identify and characterize equivalent AS patterns for 22.9% of these CDS or NMD-linked events in nonmammalian vertebrate genomes, and our data indicate that functional NMD-linked AS is more widespread and ancient than previously thought. Furthermore, although we observe an association between conserved AS and elevated sequence conservation, as previously reported, we emphasize that 30% of conserved AS exons display sequence conservation below the average score for constitutive exons. In conclusion, we demonstrate the value of detailed comparative annotation in generating a comprehensive set of AS transcripts, increasing our understanding of AS evolution in vertebrates. Our data supports a model whereby the acquisition of functional AS has occurred throughout vertebrate evolution and is considered alongside amino acid change as a key mechanism in gene evolution

Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by β1 integrins

The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified β1 integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCγ nor Akt was necessary for this response. Furthermore, β1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that β1 integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism

Développement d'outils microbiologiques et chimiques permettant d'identifier l'origine des pollutions fécales dans les eaux de baignades

La pollution organique issue des effluents d'élevage et des stations d'épuration urbaines conduit à un problème essentiel de santé publique lié à la contamination des eaux de surface où s'exercent des activités sensibles telles que la baignade. S'il est possible de déterminer les pollutions localisées liées à un dysfonctionnement des systèmes de traitement, il est beaucoup plus difficile d'identifier les pollutions organiques diffuses qui participent pourtant majoritairement à la dégradation de la qualité des eaux de surface. La problématique des pollutions diffuses est d'autant plus importante que la nouvelle réglementation européenne concernant les eaux de baignade (Directive 2006/7/CE) demande de constituer des profils de baignade qui nécessitent une identification et une hiérarchisation des sources de pollutions fécales. Le dénombrement de Escherichia coli et des entérocoques intestinaux stipulé par les textes réglementaires européens, représente actuellement le seul outil analytique permettant la mise en évidence d'une contamination fécale du milieu aquatique, sans toutefois différencier l'origine humaine ou animale de cette contamination. Il est donc nécessaire de développer de nouvelles méthodes de détection de la pollution fécale qui puissent non seulement mettre en évidence une contamination mais aussi en indiquer l'origine. C'est d'ailleurs dans cet objectif que s'est développé depuis quelques années, le concept de "Microbial Source Tracking" ("Traceurs de Sources Microbiennes") qui consiste à identifier à l'aide de marqueurs microbiologiques ou chimiques les sources de pollutions fécales. Dans ce contexte, six laboratoires de recherche se sont associés pour développer des techniques de traçage des contaminations fécales afin de proposer un outil opérationnel utilisable pour différencier les sources de pollution, de leur point d'émission jusqu'au milieu récepteur final que constituent les eaux de surface. Les marqueurs qui ont fait l'objet de cette étude sont des molécules chimiques naturelles (stéroïdes, caféine), des molécules de synthèse retrouvées dans les effluents de stations d'épuration ou des rapports de fluorescence de la matière organique ainsi que des micro-organismes (bactériophages, bactéries). A la suite des développements méthodologiques, plusieurs marqueurs ont été sélectionnés : - bactéries appartenant aux groupes bactériens dominants du tractus intestinal humain (Bifidobacterium adolescentis) et porcin (Lactobacillus amylovorus) ; - Bacteroidales spécifiques des humains, porcins et bovins (HF183, Pig-2-Bac, Rum-2-Bac); - génogroupes humains des bactériophages F ARN spécifiques; - rapports de stéroïdes : coprostanol/(24ethylcoprostanol+coprostanol) (R1) et sitostanol/coprostanol (R2); - caféine, benzophénone et tri(2-chloroethyl)phosphate (TCEP)

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

Cryptogamic ground covers as analogues for early terrestrial biospheres: Initiation and evolution of biologically mediated proto-soils

Modern cryptogamic ground covers (CGCs), comprising assemblages of bryophytes (hornworts, liverworts, mosses), fungi, bacteria, lichens and algae, are thought to resemble early divergent terrestrial communities. However, limited in-situ plant and other fossils in the rock record, and a lack of CGC-like soils reported in the pre-Silurian sedimentological record, have hindered understanding of the structure, composition, and interactions within the earliest CGCs. A key question is how the earliest CGC-like organisms drove weathering on primordial terrestrial surfaces (regolith), leading to the early stages of soil development as proto-soils, and subsequently contributing to large-scale biogeochemical shifts in the Earth System. Here, we employed a novel qualitative, quantitative and multi-dimensional imaging approach through X-ray micro-computed tomography, scanning electron, and optical microscopy to investigate whether different combinations of modern CGC organisms from primordial-like settings in Iceland develop organism-specific soil-forming features at the macro- and micro-scales. Additionally, we analysed CGCs growing on hard rocky substrates to investigate the initiation of weathering processes non-destructively in 3D. We show that thalloid CGC organisms (liverworts, hornworts) develop thin organic layers at the surface (<1 cm) with limited subsurface structural development, whereas leafy mosses and communities of mixed-organisms form profiles that are thicker (up to ~7 cm), structurally more complex, and more organic-rich. We term these thin layers and profiles proto-soils. Component analyses from X-ray micro-computed tomography data show that thickness and structure of these proto-soils are determined by the type of colonising organism(s), suggesting that the evolution of more complex soils through the Palaeozoic may have been driven by a shift in body plan of CGC-like organisms from flattened and appressed to upright and leafy. Our results provide a framework for identifying CGC-like proto-soils in the rock record and a new proxy for understanding organism-soil interactions in ancient terrestrial biospheres and their contribution to the early stages of soil-formation

The impact of snow cover on nutrients dynamics in Western Siberia territories

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