1,033 research outputs found

    The Mr 28,000 gap junction proteins from rat heart and liver are different but related

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    The sequence of the amino-terminal 32 residues of the rat heart Mr 28,000 gap junction protein presented here allows, for the first time, a sequence comparison of gap junctional proteins from different tissues (heart and liver). Comparison of the rat heart gap junction protein sequence and that available from rat liver reveals 43% sequence identity and conservative changes at an additional 25% of the positions. Both proteins exhibit a hydrophobic domain which could represent a transmembrane span of the junction. This result unequivocally demonstrates the existence of at least two forms of the gap junction protein. As yet, no homology is evident between the gap junctional proteins of either heart or liver and main intrinsic protein from rat eye lens

    The weather report from IRC+10216: Evolving irregular clouds envelop carbon star

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    High angular resolution images of IRC+10216 are presented in several near-infrared wavelengths spanning more than 8 years. These maps have been reconstructed from interferometric observations obtained at both Keck and the VLT, and also from stellar occultations by the rings of Saturn observed with the Cassini spacecraft. The dynamic inner regions of the circumstellar environment are monitored over eight epochs ranging between 2000 January and 2008 July. The system is shown to experience substantial evolution within this period including the fading of many previously reported persistent features, some of which had been identified as the stellar photosphere. These changes are discussed in the context of existing models for the nature of the underlying star and the circumstellar environment. With access to these new images, we are able to report that none of the previously identified bright spots in fact contains the star, which is buried in its own dust and not directly visible in the near-infrared

    The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

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    New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

    (-)-Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells

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    Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100μM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25μM HA (11.19±0.39μm) or 25μM EPI (11.01±0.21μm) compared to the vehicle control (VC; 7.61±0.16μm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P = .024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/β II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health

    Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

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    Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. Methods and Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP (WASL) locus is associated with carotid-femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. Conclusions: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness

    100 million years of turtle paleoniche dynamics enable the prediction of latitudinal range shifts in a warming world

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    Past responses to environmental change provide vital baseline data for estimating the potential resilience of extant taxa to future change. Here, we investigate the latitudinal range contraction that terrestrial and freshwater turtles (Testudinata) experienced from the Late Cretaceous to the Paleogene (100.5-23.03 mya) in response to major climatic changes. We apply ecological niche modeling (ENM) to reconstruct turtle niches, using ancient and modern distribution data, paleogeographic reconstructions, and the HadCM3L climate model to quantify their range shifts in the Cretaceous and late Eocene. We then use the insights provided by these models to infer their probable ecological responses to future climate scenarios at different representative concentration pathways (RCPs 4.5 and 8.5 for 2100), which project globally increased temperatures and spreading arid biomes at lower to mid-latitudes. We show that turtle ranges are predicted to expand poleward in the Northern Hemisphere, with decreased habitat suitability at lower latitudes, inverting a trend of latitudinal range contraction that has been prevalent since the Eocene. Trionychids and freshwater turtles can more easily track their niches than Testudinidae and other terrestrial groups. However, habitat destruction and fragmentation at higher latitudes will probably reduce the capability of turtles and tortoises to cope with future climate changes

    Climate change impacts on Yangtze River discharge at the Three Gorges Dam

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    The Yangtze River basin is home to more than 400 million people and contributes to nearly half of China's food production. Therefore, planning for climate change impacts on water resource discharges is essential. We used a physically based distributed hydrological model, Shetran, to simulate discharge in the Yangtze River just below the Three Gorges Dam at Yichang (1007200km2), obtaining an excellent match between simulated and measured daily discharge, with Nash–Sutcliffe efficiencies of 0.95 for the calibration period (1996–2000) and 0.92 for the validation period (2001–2005). We then used a simple monthly delta change approach for 78 climate model projections (35 different general circulation models – GCMs) from the Coupled Model Intercomparison Project Phase 5 (CMIP5) to examine the effect of climate change on river discharge for 2041–2070 for Representative Concentration Pathway 8.5. Projected changes to the basin's annual precipitation varied between −3.6 and +14.8% but increases in temperature and consequently evapotranspiration (calculated using the Thornthwaite equation) were projected by all CMIP5 models, resulting in projected changes in the basin's annual discharge from −29.8 to +16.0%. These large differences were mainly due to the predicted expansion of the summer monsoon north and west into the Yangtze Basin in some CMIP5 models, e.g. CanESM2, but not in others, e.g. CSIRO-Mk3-6-0. This was despite both models being able to simulate current climate well. Until projections of the strength and location of the monsoon under a future climate improve, large uncertainties in the direction and magnitude of future change in discharge for the Yangtze will remain
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