Muscle fatigue: from observations in humans to underlying mechanisms studied in intact single muscle fibres

Prolonged dynamic exercise and sustained isometric contractions induce muscle fatigue, as manifested by decreased performance and a reduction in the maximum voluntary contraction force. Studies with non-invasive measurements in exercising humans show that mechanisms located beyond the sarcolemma are important in the fatigue process. In this review, we describe probable cellular mechanisms underlying fatigue-induced changes in excitation-contraction (E-C) coupling occurring in human muscle fibres during strenuous exercise. We use fatigue-induced changes observed in intact single muscle fibres, where force and cellular Ca2+ handling can be directly measured, to explain changes in E-C coupling observed in human muscle during exercis

Research on HIV cure: Mapping the ethics landscape

According to current estimates, 36.7 million people are infected with HIV worldwide. Despite large-scale and growing programs to prevent and treat HIV infection, possible approaches to achieve a cure for HIV infection are of strong interest. In the development of candidate approaches to achieve an HIV cure, issues of future translation to human study participants, evidence-based practice, clinical care, diverse populations, and populations in low- and middle-income countries should all be considered. An HIV cure should be effective, safe, simple, affordable, and scalable. Acceptability research is a critical adjunct to ongoing biomedical HIV cure research efforts. Anticipating some of the ethical and implementation challenges related to HIV cure strategies is necessary before the availability of effective interventions. Ongoing engagement of stakeholders is needed to resolve ethical, logistical, social, cultural, policy, regulatory, and implementation challenges at all stages of the HIV cure research development process

Transcriptional control by adenovirus E1A conserved region 3 via p300/CBP

The human adenovirus type 5 (HAdV-5) E1A 13S oncoprotein is a potent regulator of gene expression and is used extensively as a model for transcriptional activation. It possesses two independent transcriptional activation domains located in the N-terminus/conserved region (CR) 1 and CR3. The protein acetyltransferase p300 was previously identified by its association with the N-terminus/CR1 portion of E1A and this association is required for oncogenic transformation by E1A. We report here that transcriptional activation by 13S E1A is inhibited by co-expression of sub-stoichiometric amounts of the smaller 12S E1A isoform, which lacks CR3. Transcriptional inhibition by E1A 12S maps to the N-terminus and correlates with the ability to bind p300/CBP, suggesting that E1A 12S is sequestering this limiting factor from 13S E1A. This is supported by the observation that the repressive effect of E1A 12S is reversed by expression of exogenous p300 or CBP, but not by a CBP mutant lacking actyltransferase activity. Furthermore, we show that transcriptional activation by 13S E1A is greatly reduced by siRNA knockdown of p300 and that CR3 binds p300 independently of the well-characterized N-terminal/CR1-binding site. Importantly, CR3 is also required to recruit p300 to the adenovirus E4 promoter during infection. These results identify a new functionally significant interaction between E1A CR3 and the p300/CBP acetyltransferases, expanding our understanding of the mechanism by which this potent transcriptional activator functions

Research on HIV cure: Mapping the ethics landscape.

In an essay, Karine Dubé and coauthors discuss the ethics of preclinical and clinical studies relevant to achieving an HIV cure

Valorisation to biogas of macroalgal waste streams: a circular approach to bioproducts and bioenergy in Ireland

© 2016 The Author(s) Seaweeds (macroalgae) have been recently attracting more and more interest as a third generation feedstock for bioenergy and biofuels. However, several barriers impede the deployment of competitive seaweed-based energy. The high cost associated to seaweed farming and harvesting, as well as their seasonal availability and biochemical composition currently make macroalgae exploitation too expensive for energy production only. Recent studies have indicated a possible solution to aforementioned challenges may lay in seaweed integrated biorefinery, in which a bioenergy and/or biofuel production step ends an extractions cascade of high-value bioproducts. This results in the double benefit of producing renewable energy while adopting a zero waste approach, as fostered by recent EU societal challenges within the context of the Circular Economy development. This study investigates the biogas potential of residues from six indigenous Irish seaweed species while discussing related issues experienced during fermentation. It was found that Laminaria and Fucus spp. are the most promising seaweed species for biogas production following biorefinery extractions producing 187–195 mL CH4 gVS−1 and about 100 mL CH4 gVS−1 , respectively, exhibiting overall actual yields close to raw un-extracted seaweed