Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure

BACKGROUND: In acute renal failure, a pronounced net protein catabolism occurs that has long been associated with corticoid action. By competitively blocking the glucocorticoid receptor with the potent antiglucocorticoid RU 38486, the present study addressed the question to what extent does corticoid action specific to uremia cause the observed muscle degradation, and does inhibition of glucocorticoid action reduce the protein wasting? METHODS: RU 38486 was administered in a dose of 50 mg/kg/24 h for 48 h after operation to fasted bilaterally nephrectomized (BNX) male adult Wistar rats and sham operated (SHAM) controls. Protein turnover was evaluated by high performance liquid chromatography (HPLC) of amino acid efflux in sera from isolated perfused hindquarters of animals treated with RU 38486 versus untreated controls. RESULTS: Administration of RU 38486 reduces the total amino acid efflux (TAAE) by 18.6% in SHAM and 15.6% in BNX and efflux of the indicator of net protein turnover, phenylalanine (Phe) by 33.3% in SHAM and 13% in BNX animals as compared to the equally operated, but untreated animals. However, the significantly higher protein degradation observed in BNX (0.6 ± 0.2 nmol/min/g muscle) versus SHAM (0.2 ± 0.1 nmol/min/g muscle) rats, as demonstrated by the marker of myofribrillar proteolytic rate, 3-Methylhistidine (3 MH) remains unaffected by administration of RU 38486 (0.5 ± 0.1 v. 0.2 ± 0.1 nmol/min/g muscle in BNX v. SHAM). CONCLUSION: RU 38486 does not act on changes of muscular protein turnover specific to uremia but reduces the effect of stress- stimulated elevated corticosterone secretion arising from surgery and fasting. A potentially beneficial effect against stress- induced catabolism in severe illness can be postulated that merits further study

Visual ecology of aphids – a critical review on the role of colours in host finding

We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

Size-Dependent Materials Properties Toward a Universal Equation

Due to the lack of experimental values concerning some material properties at the nanoscale, it is interesting to evaluate this theoretically. Through a “top–down” approach, a universal equation is developed here which is particularly helpful when experiments are difficult to lead on a specific material property. It only requires the knowledge of the surface area to volume ratio of the nanomaterial, its size as well as the statistic (Fermi–Dirac or Bose–Einstein) followed by the particles involved in the considered material property. Comparison between different existing theoretical models and the proposed equation is done

A dated phylogeny and collection records reveal repeated biome shifts in the African genus Coccinia (Cucurbitaceae)

Background: Conservatism in climatic tolerance may limit geographic range expansion and should enhance the effects of habitat fragmentation on population subdivision. Here we study the effects of historical climate change, and the associated habitat fragmentation, on diversification in the mostly sub-Saharan cucurbit genus Coccinia, which has 27 species in a broad range of biota from semi-arid habitats to mist forests. Species limits were inferred from morphology, and nuclear and plastid DNA sequence data, using multiple individuals for the widespread species. Climatic tolerances were assessed from the occurrences of 1189 geo-referenced collections and WorldClim variables. Results: Nuclear and plastid gene trees included 35 or 65 accessions, representing up to 25 species. The data revealed four species groups, one in southern Africa, one in Central and West African rain forest, one widespread but absent from Central and West African rain forest, and one that occurs from East Africa to southern Africa. A few individuals are differently placed in the plastid and nuclear (LFY) trees or contain two ITS sequence types, indicating hybridization. A molecular clock suggests that the diversification of Coccinia began about 6.9 Ma ago, with most of the extant species diversity dating to the Pliocene. Ancestral biome reconstruction reveals six switches between semi-arid habitats, woodland, and forest, and members of several species pairs differ significantly in their tolerance of different precipitation regimes. Conclusions: The most surprising findings of this study are the frequent biome shifts (in a relatively small clade) over just 6 - 7 million years and the limited diversification during and since the Pleistocene. Pleistocene climate oscillations may have been too rapid or too shallow for full reproductive barriers to develop among fragmented populations of Coccinia, which would explain the apparently still ongoing hybridization between certain species. Steeper ecological gradients in East Africa and South Africa appear to have resulted in more advanced allopatric speciation there

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

The ethical desirability of moral bioenhancement: A review of reasons

Background: The debate on the ethical aspects of moral bioenhancement focuses on the desirability of using biomedical as opposed to traditional means to achieve moral betterment. The aim of this paper is to systematically review the ethical reasons presented in the literature for and against moral bioenhancement. Discussion: A review was performed and resulted in the inclusion of 85 articles. We classified the arguments used in those articles in the following six clusters: (1) why we (don't) need moral bioenhancement, (2) it will (not) be possible to reach consensus on what moral bioenhancement should involve, (3) the feasibility of moral bioenhancement and the status of current scientific research, (4) means and processes of arriving at moral improvement matter ethically, (5) arguments related to the freedom, identity and autonomy of the individual, and (6) arguments related to social/group effects and dynamics. We discuss each argument separately, and assess the debate as a whole. First, there is little discussion on what distinguishes moral bioenhancement from treatment of pathological deficiencies in morality. Furthermore, remarkably little attention has been paid so far to the safety, risks and side-effects of moral enhancement, including the risk of identity changes. Finally, many authors overestimate the scientific as well as the practical feasibility of the interventions they discuss, rendering the debate too speculative. Summary: Based on our discussion of the arguments used in the debate on moral enhancement, and our assessment of this debate, we advocate a shift in focus. Instead of speculating about non-realistic hypothetical scenarios such as the genetic engineering of morality, or morally enhancing 'the whole of humanity', we call for a more focused debate on realistic options of biomedical treatment of moral pathologies and the concrete moral questions these treatments raise

Tissue-Specific Target Analysis of Disease-Associated MicroRNAs in Human Signaling Pathways

MicroRNAs are a large class of post-transcriptional regulators that bind to the 3′ untranslated region of messenger RNAs. They play a critical role in many cellular processes and have been linked to the control of signal transduction pathways. Recent studies indicate that microRNAs can function as tumor suppressors or even as oncogenes when aberrantly expressed. For more general insights of disease-associated microRNAs, we analyzed their impact on human signaling pathways from two perspectives. On a global scale, we found a core set of signaling pathways with enriched tissue-specific microRNA targets across diseases. The function of these pathways reflects the affinity of microRNAs to regulate cellular processes associated with apoptosis, proliferation or development. Comparing cancer and non-cancer related microRNAs, we found no significant differences between both groups. To unveil the interaction and regulation of microRNAs on signaling pathways locally, we analyzed the cellular location and process type of disease-associated microRNA targets and proteins. While disease-associated proteins are highly enriched in extracellular components of the pathway, microRNA targets are preferentially located in the nucleus. Moreover, targets of disease-associated microRNAs preferentially exhibit an inhibitory effect within the pathways in contrast to disease proteins. Our analysis provides systematic insights into the interaction of disease-associated microRNAs and signaling pathways and uncovers differences in cellular locations and process types of microRNA targets and disease-associated proteins

Microstructural evolution and trace element mobility in Witwatersrand pyrite

Microstructural analysis of pyrite from a single sample of Witwatersrand conglomerate indicates a complex deformation history involving components of both plastic and brittle deformation. Internal deformation associated with dislocation creep is heterogeneously developed within grains, shows no systematic relationship to bulk rock strain or the location of grain boundaries and is interpreted to represent an episode of pyrite deformation that predates the incorporation of detrital pyrite grains into the Central Rand conglomerates. In contrast, brittle deformation, manifest by grain fragmentation that transects dislocation-related microstructures, is spatially related to grain contacts and is interpreted to represent post-depositional deformation of the Central Rand conglomerates. Analysis of the low-angle boundaries associated with the early dislocation creep phase of deformation indicates the operation of {100} slip systems. However, some orientation boundaries have geometrical characteristics that are not consistent with simple {100} deformation.These boundaries may represent the combination of multiple slip systems or the operation of the previously unrecognized {120} slip system. These boundaries are associated with order of magnitude enrichments in As, Ni and Co that indicate a deformation control on the remobilization of trace elements within pyrite and a potential slip system control on the effectiveness of fast-diffusion pathways. The results confirm the importance of grain-scale elemental remobilization within pyrite prior to their incorporation into the Witwatersrand gold-bearing conglomerates. Since the relationship between gold and pyrite is intimately related to the trace element geochemistry of pyrite, the results have implications for the application of minor element geochemistry to ore deposit formation, suggest a reason for heterogeneous conductivity and localized gold precipitation in natural pyrite and provide a framework for improving mineral processing

Aerobic exercise in adolescents with obesity: preliminary evaluation of a modular training program and the modified shuttle test

BACKGROUND: Increasing activity levels in adolescents with obesity requires the development of exercise programs that are both attractive to adolescents and easily reproducible. The aim of this study was to develop a modular aerobic training program for adolescents with severe obesity, with a focus on variety, individual targets and acquiring physical skills. We report here the effects on aerobic fitness from a pilot study. Furthermore, we examined the feasibility of the modified shuttle test (MST) as an outcome parameter for aerobic fitness in adolescents with severe obesity. METHODS: Fifteen adolescents from an inpatient body weight management program participated in the aerobic training study (age 14.7 ± 2.1 yrs, body mass index 37.4 ± 3.5). The subjects trained three days per week for 12 weeks, with each session lasting 30–60 minutes. The modular training program consisted of indoor, outdoor and swimming activities. Feasibility of the MST was studied by assessing construct validity, test-retest reliability and sensitivity to change. RESULTS: Comparing pretraining and end of training period showed large clinically relevant and significant improvements for all aerobic indices: e.g. VO(2 peak )17.5%, effect size (ES) 2.4; W(max )8%, ES 0.8. In addition, a significant improvement was found for the efficiency of the cardiovascular system as assessed by the oxygen pulse (15.8%, ES 1.6). Construct validity, test-retest reliability and sensitivity to change of the MST were very good. MST was significantly correlated with VO(2 peak )(r = 0.79) and W(max )(r = 0.84) but not with anthropometric measures. The MST walking distance improved significantly by 32.5%, ES 2.5. The attendance rate at the exercise sessions was excellent. CONCLUSION: This modular, varied aerobic training program has clinically relevant effects on aerobic performance in adolescents with severe obesity. The added value of our aerobic training program for body weight management programs for adolescents with severe obesity should be studied with a randomized trial. This study further demonstrated that the MST is a reliable, sensitive and easy to administer outcome measure for aerobic fitness in adolescent body weight management trials