Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.Bio-organic Synthesi

Plasma Diagnostics of the Interstellar Medium with Radio Astronomy

Contains fulltext : 119335.pdf (preprint version ) (Open Access

Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective

Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer’s disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents—and occasionally microbes—may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research

Coarse-grained deltas approaching shallow-water canyon heads:A case study from the Lower Pleistocene Messina Strait, Southern Italy

The tide-dominated Messina Strait (southern Italy) is a 3 km wide marine passageway, whose block-faulted borders form steep subaqueous zones incised by canyons and gullies. These erosional features retreat towards the shorelines and are often in direct connection with subaerial valley-bounded river deltas. High-energy density-flows generated by river floods periodically enter the canyon heads, attaining supercritical-flow regime and accreting large, upslope-migrating bedforms. Although these bedforms have been documented in recent studies, little attention has been paid to the definition of the type of delta entering canyon heads, the internal features of river-influenced deposits accumulated in the nearshore zone, and their interplay with tidal currents flowing axially to the strait. This study focuses on a Lower Pleistocene coarse-grained succession exposed along the north-eastern margin of the modern Messina Strait, investigated using conventional facies analysis and sedimentological logging, integrated with photogrammetric techniques and interpretation of drone-acquired imagery. Facies confinement between basement blocks suggests a subaqueous delta complex shed from the tectonically controlled margin of the ancient strait and entering shallowly submerged canyon heads. Basal breccias, conglomerates and pebbly sandstones exhibiting channel-form discontinuities and upslope dipping backsets are interpreted as cyclic-step and antidune deposits. Units composed of these facies are comprised between master erosional surfaces and tidal ravinement surfaces. The tidal ravinements suggest that canyon infill occurred during a major phase of sea-level rise, punctuated by minor falls and stillstands. These surfaces are overlain by mixed bioclastic–siliciclastic, arenitic, trough and planar cross-strata, representing dunes migrating roughly parallel to the palaeo-coastline and originated by tidal currents amplified by the narrowing of the ancient Messina Strait. Tidal-influenced sedimentation dominated over the fluvial-influenced processes during the late transgression, overfilling the canyon relief. The exceptionally good exposure of depositional architectures and facies characteristics is key to outline the general features of a specific type of delta system, fed by valley-bounded rivers and entering canyon heads in the nearshore of tectonically-controlled, tide-influenced steep strait margins. The pre-existing subaqueous incised topography forced the delta front to be split into lobe branches during the canyon infilling, hampering clinoform architectures and preserving large supercritical-flow sedimentary structures. This study suggests these as possible criteria for the recognition of similar systems in outcrop or subsurface