A two-component regulatory system modulates twitching motility in Dichelobacter nodosus

© 2015 Elsevier B.V. All rights reserved. Dichelobacter nodosus is the essential causative agent of footrot in sheep and type IV fimbriae-mediated twitching motility has been shownto be essential for virulence.Wehave identified a two-component signal transduction system (TwmSR) that shows similarity to chemosensory systems from other bacteria. Insertional inactivation of the gene encoding the response regulator, TwmR, led to a twitching motility defect, with the mutant having a reduced rate of twitching motility when compared to the wild-type and a mutant complemented with the wild-type twmR gene. The reduced rate of twitching motility was not a consequence of a reduced growth rate or decreased production of surface located fimbriae, but video microscopy indicated that it appeared to result from an overall loss of twitching directionality. These results suggest that a chemotactic response to environmental factors may play an important role in the D. nodosus-mediated disease process

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Microtopographic drivers of vegetation patterning in blanket peatlands recovering from erosion

Blanket peatlands are globally rare, and many have been severely eroded. Natural recovery and revegetation (‘self-restoration’) of bare peat surfaces are often observed but are poorly understood, thus hampering the ability to reliably predict how these ecosystems may respond to climatic change. We hypothesised that morphometric/topographic-related microclimatic variables may be key controls on successional pathways and vegetation patterning in self-restoring blanket peatlands. We predicted the occurrence probability of four common peatland plant species (Calluna vulgaris, Eriophorum vaginatum, Eriophorum angustifolium, and Sphagnum spp.) using a digital surface model (DSM) generated from drone imagery at a pixel size of 20 cm, a suite of variables derived from the DSM, and an ensemble learning method (random forests). All four species models provided accurate fine-scale predictions of habitat suitability (accuracy > 90%, area under curve (AUC) > 0.9, recall and precision > 0.8). Mean elevation (within a 1 m radius) was often the most influential variable. Topographic position, wind exposure, and the heterogeneity or ruggedness of the surrounding surface were also important for all models, whilst light-related variables and a wetness index were important in the Sphagnum model. Our approach can be used to improve prediction of future responses and sensitivities of peatland recovery to climatic changes and as a tool to identify areas of blanket peatlands that may self-restore successfully without management intervention

Le formalisme du contrat d'assurance: analyse des règles en vigueur à l'aune des progrès techniques et de certaines pratiques contractuelles

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Microchamber Cultures of Bladder Cancer: A Platform for Characterizing Drug Responsiveness and Resistance in PDX and Primary Cancer Cells

Abstract Precision cancer medicine seeks to target the underlying genetic alterations of cancer; however, it has been challenging to use genetic profiles of individual patients in identifying the most appropriate anti-cancer drugs. This spurred the development of patient avatars; for example, patient-derived xenografts (PDXs) established in mice and used for drug exposure studies. However, PDXs are associated with high cost, long development time and low efficiency of engraftment. Herein we explored the use of microfluidic devices or microchambers as simple and low-cost means of maintaining bladder cancer cells over extended periods of times in order to study patterns of drug responsiveness and resistance. When placed into 75 µm tall microfluidic chambers, cancer cells grew as ellipsoids reaching millimeter-scale dimeters over the course of 30 days in culture. We cultured three PDX and three clinical patient specimens with 100% success rate. The turn-around time for a typical efficacy study using microchambers was less than 10 days. Importantly, PDX-derived ellipsoids in microchambers retained patterns of drug responsiveness and resistance observed in PDX mice and also exhibited in vivo-like heterogeneity of tumor responses. Overall, this study establishes microfluidic cultures of difficult-to-maintain primary cancer cells as a useful tool for precision cancer medicine