Inferring selection in the Anopheles gambiae species complex: an example from immune-related serine protease inhibitors

<p>Abstract</p> <p>Background</p> <p>Mosquitoes of the <it>Anopheles gambiae </it>species complex are the primary vectors of human malaria in sub-Saharan Africa. Many host genes have been shown to affect <it>Plasmodium </it>development in the mosquito, and so are expected to engage in an evolutionary arms race with the pathogen. However, there is little conclusive evidence that any of these mosquito genes evolve rapidly, or show other signatures of adaptive evolution.</p> <p>Methods</p> <p>Three serine protease inhibitors have previously been identified as candidate immune system genes mediating mosquito-Plasmodium interaction, and serine protease inhibitors have been identified as hot-spots of adaptive evolution in other taxa. Population-genetic tests for selection, including a recent multi-gene extension of the McDonald-Kreitman test, were applied to 16 serine protease inhibitors and 16 other genes sampled from the <it>An. gambiae </it>species complex in both East and West Africa.</p> <p>Results</p> <p>Serine protease inhibitors were found to show a marginally significant trend towards higher levels of amino acid diversity than other genes, and display extensive genetic structuring associated with the 2La chromosomal inversion. However, although serpins are candidate targets for strong parasite-mediated selection, no evidence was found for rapid adaptive evolution in these genes.</p> <p>Conclusion</p> <p>It is well known that phylogenetic and population history in the <it>An. gambiae </it>complex can present special problems for the application of standard population-genetic tests for selection, and this may explain the failure of this study to detect selection acting on serine protease inhibitors. The pitfalls of uncritically applying these tests in this species complex are highlighted, and the future prospects for detecting selection acting on the <it>An. gambiae </it>genome are discussed.</p

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

Free edges in epithelia as cues for motility

One of the primary functions of any epithelium is to act as a barrier. To maintain integrity, epithelia migrate rapidly to cover wounds and there is intense interest in understanding how wounds are detected. Numerous soluble factors are present in the wound environment and epithelia can sense the presence of adjacent denuded extracellular matrix. However, the presence of such cues is expected to be highly variable, and here we focus on the presence of edges in the epithelial sheets as a stimulus, since they are universally and continuously present in wounds. Using a novel tissue culture model, free edges in the absence of any other identifiable cues were found to trigger activation of the epidermal growth factor receptor and increase cell motility. Edges bordered by inert physical barriers do not activate the receptor, indicating that activation is related to mechanical factors rather than to specific cell-cell interactions

What do Attending Physicians Contribute in a House Officer-Based Ambulatory Continuity Clinic?

OBJECTIVE: To study the educational contributions of attending physicians in an internal medicine house staff ambulatory clinic. DESIGN: Cross-sectional, self-administered survey. SETTING: University-affiliated general internal medicine practice. PATIENTS/PARTICIPANTS: Internal medicine residents and attendings. MEASUREMENTS AND MAIN RESULTS: Attending and resident perceptions of whether attendings made contributions to teaching points, diagnosis (DX), therapy (RX), and health care maintenance (HCM) were assessed in 428 patient encounters. Resident assessments significantly exceeded attending self-assessments of contributions to teaching points (82% vs 74%, P = .001), DX (44% vs 34%, P = .001), RX (61% vs 55%, P = .02), and HCM (19% vs 15%, P = .04). Both residents and attendings perceived that contributions declined progressively with increasing resident year (P<.05). Primary care and categorical residents assessed attending contributions comparably. However, attendings perceived contributing more to RX and HCM for categorical residents than primary care (P<.05). Male and female residents assessed attending contributions comparably. However, attendings perceived contributing generally more to DX in male residents than female (P = .003). In 8% of encounters, either residents or attendings felt that patient evaluation by the attending was needed. In these encounters with personal patient evaluation by attendings, both residents and attendings felt that attendings made more contributions to DX (P = .001) and teaching points than in other encounters. CONCLUSIONS: Attending physicians consistently underestimate their perceived contributions to house officer ambulatory teaching. Their personal patient evaluation increases assistance with DX and teaching points. Given perceived declining contributions by training year, attendings may need to identify other teaching strategies for interactions with senior residents

Elongated Nanostructured Solar Cells with a Plasmonic Core

In this chapter the effects of the plasmonic response in an elongated nano-scale solar cell with a silver nanoneedle core are explored by measuring photocurrents. The silver nanoneedles formed the support of a conformally grown hydrogenated amorphous silicon (a-Si:H) n-i-p junction around it. A spherical morphology of the solar cell functions as a nano-lens, focusing incoming light directly on the plasmonic silver nanoneedle. We found that plasmonics, geometric optics, and Fresnel reflections affect the nanostructured solar cell performance, depending strongly on light incidence angle and polarization. Besides the plasmonic effects, nano-focusing, and orthogonalization of carrier and photon pathways are simultaneously present at illumination of this structure. In this chapter the photovoltaics characterization techniques and simulations are explained and discussed as well. This work provides valuable insight in solar cell processes in which novel concepts such as plasmonics, elongated nanostructures, and nanolenses are used