332 research outputs found

    The effect of prior upper body exercise on subsequent wingate performance

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    It has been reported previously that the upper body musculature is continually active during high intensity cycle ergometry. The aim of this study was to examine the effects of prior upper body exercise on subsequent Wingate (WAnT) performance. Eleven recreationally active males (20.8 ± 2.2 yrs; 77.7 ± 12.0 kg;  1.79 ± 0.04 m) completed two trials in a randomised order. In one trial participants completed 2 × 30 s WAnT tests (WAnT1 and WAnT2) with a 6 min recovery period; in the other trial, this protocol was preceded with 4 sets of biceps curls to induce localised arm fatigue. Prior upper body exercise was found to have a statistically significant detrimental effect on peak power output (PPO) during WAnT1 (P < 0.05) but no effect was observed for mean power output (MPO) (P > 0.05). Handgrip (HG) strength was also found to be significantly lower following the upper body exercise. These results demonstrate that the upper body  is meaningfully involved in the generation of leg power during intense cycling

    Persistent Binding and Functional Antagonism by Xanomeline at the Muscarinic M 5

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    Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells

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    Introduction: Doxorubicin (DOX), a chemotherapeutic drug, induces senescence and increases the secretion of senescence-associated secretory phenotype (SASP) in endothelial cells (ECs), which contributes to DOX-induced inflammaging. Metformin, an anti-diabetic drug, demonstrates senomorphic effects on different models of senescence. However, the effects of metformin on DOX-induced endothelial senescence have not been reported before. Senescent ECs exhibit a hyper-inflammatory response to lipopolysachharide (LPS). Therefore, in our current work, we identified the effects of metformin on DOX-induced endothelial senescence and LPS-induced hyper-inflammation in senescent ECs.Methods: ECs were treated with DOX ± metformin for 24 h followed by 72 h incubation without DOX to establish senescence. Effects of metformin on senescence markers expression, SA-β-gal activity, and SASP secretion were assessed. To delineate the molecular mechanisms, the effects of metformin on major signaling pathways were determined. The effect of LPS ± metformin was determined by stimulating both senescent and non-senescent ECs with LPS for an additional 24 h.Results: Metformin corrected DOX-induced upregulation of senescence markers and decreased the secretion of SASP factors and adhesion molecules. These effects were associated with a significant inhibition of the JNK and NF-κB pathway. A significant hyper-inflammatory response to LPS was observed in DOX-induced senescent ECs compared to non-senescent ECs. Metformin blunted LPS-induced upregulation of pro-inflammatory SASP factors.Conclusion: Our study demonstrates that metformin mitigates DOX-induced endothelial senescence phenotype and ameliorates the hyper-inflammatory response to LPS. These findings suggest that metformin may protect against DOX-induced vascular aging and endothelial dysfunction and ameliorate infection-induced hyper-inflammation in DOX-treated cancer survivors

    Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration

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    SummaryThe accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer’s disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here we show that Aβ oligomers can be assigned to one of at least two classes (type 1 and type 2) based on their temporal, spatial, and structural relationships to amyloid fibrils. The type 2 oligomers are related to amyloid fibrils and represent the majority of oligomers generated in vivo, but they remain confined to the vicinity of amyloid plaques and do not impair cognition at levels relevant to AD. Type 1 oligomers are unrelated to amyloid fibrils and may have greater potential to cause global neural dysfunction in AD because they are dispersed. These results refine our understanding of the pathogenicity of Aβ oligomers in vivo

    Eddy sensors for small diameter stainless steel tubes.

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    The goal of this project was to develop non-destructive, minimally disruptive eddy sensors to inspect small diameter stainless steel metal tubes. Modifications to Sandia's Emphasis/EIGER code allowed for the modeling of eddy current bobbin sensors near or around 1/8-inch outer diameter stainless steel tubing. Modeling results indicated that an eddy sensor based on a single axial coil could effectively detect changes in the inner diameter of a stainless steel tubing. Based on the modeling results, sensor coils capable of detecting small changes in the inner diameter of a stainless steel tube were designed, built and tested. The observed sensor response agreed with the results of the modeling and with eddy sensor theory. A separate limited distribution SAND report is being issued demonstrating the application of this sensor

    The Democratic Biopolitics of PrEP

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    PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

    Abundance and species diversity hotspots of tracked marine predators across the North American Arctic

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    Aim: Climate change is altering marine ecosystems worldwide and is most pronounced in the Arctic. Economic development is increasing leading to more disturbances and pressures on Arctic wildlife. Identifying areas that support higher levels of predator abundance and biodiversity is important for the implementation of targeted conservation measures across the Arctic. Location: Primarily Canadian Arctic marine waters but also parts of the United States, Greenland and Russia. Methods: We compiled the largest data set of existing telemetry data for marine predators in the North American Arctic consisting of 1,283 individuals from 21 species. Data were arranged into four species groups: (a) cetaceans and pinnipeds, (b) polar bears Ursus maritimus (c) seabirds, and (d) fishes to address the following objectives: (a) to identify abundance hotspots for each species group in the summer–autumn and winter–spring; (b) to identify species diversity hotspots across all species groups and extent of overlap with exclusive economic zones; and (c) to perform a gap analysis that assesses amount of overlap between species diversity hotspots with existing protected areas. Results: Abundance and species diversity hotpots during summer–autumn and winter–spring were identified in Baffin Bay, Davis Strait, Hudson Bay, Hudson Strait, Amundsen Gulf, and the Beaufort, Chukchi and Bering seas both within and across species groups. Abundance and species diversity hotpots occurred within the continental slope in summer–autumn and offshore in areas of moving pack ice in winter–spring. Gap analysis revealed that the current level of conservation protection that overlaps species diversity hotspots is low covering only 5% (77,498 km 2 ) in summer–autumn and 7% (83,202 km 2 ) in winter–spring. Main conclusions: We identified several areas of potential importance for Arctic marine predators that could provide policymakers with a starting point for conservation measures given the multitude of threats facing the Arctic. These results are relevant to multilevel and multinational governance to protect this vulnerable ecosystem in our rapidly changing world
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