Effect of bilberry juice on indices of muscle damage and inflammation in runners completing a half-marathon: a randomised, placebo-controlled trial.

Background: Emerging evidence indicates that fruits rich in polyphenols may attenuate exercise-induced muscle damage and associated markers of inflammation and soreness. This study was conducted to determine whether bilberry juice (BJ), which is particularly rich in polyphenols, reduces markers of muscle damage in runners completing a half marathon. Methods: A total of 21 recreationally trained runners (age 30.9 ± 10.4 y; mass 71.6 ± 11.0 kg; M=16; F=5) were recruited to a single blind, randomised, placebo-controlled, parallel study. Participants were block randomised to consume 2 x 200 ml of BJ or energy-matched control drink (PLA) for 5 d before the Sheffield Half Marathon, on race day, and for 2 days post-race. Measurements of delayed onset muscle soreness (DOMS), muscle damage (creatine kinase; CK) and inflammation (c-reactive protein ; CRP) were taken at baseline, pre-race, post-race, 24 h post-race and 48 h post-race. The effect of treatment on outcome measures was analysed using magnitude-based inferences based on data from 19 participants; 2 participants were excluded from the analyses because they did not provide samples for all time points. Results: The half marathon caused elevations in DOMS, CRP and CK. BJ had a possibly harmful effect on DOMS from pre-race to immediately post-race (11.6%, 90% CI ± 14.7%), a likely harmful effect on CRP from pre-race to 24 h post-race (mean difference ES 0.56, 90% CI ± 0.72) and a possibly harmful effect on CRP from pre-race to 48 h post-race (ES 0.12, 90% CI ± 0.69). At other time points, the differences between the BJ and PLA groups in DOMS and CRP were unclear, possibly trivial or likely trivial. Differences in the changes in CK between BJ and PLA were unclear at every time point other than from baseline to pre-race, where BJ had a possibly harmful effect on reducing muscle damage (ES 0.23, 90% CI ± 0.57). Conclusion: Despite being a rich source of antioxidant and anti-inflammatory phytochemicals, BJ evoked small to moderate increases in exercise-induced DOMS and CRP. Further larger studies are required to confirm these unexpected preliminary results

SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production

It has become increasing clear that alterations in cellular metabolism have a key role in the generation and maintenance of cancer. Some of the metabolic changes can be attributed to the activation of oncogenes or loss of tumor suppressors. Here, we show that the mitochondrial sirtuin, SirT3, acts as a tumor suppressor via its ability to suppress reactive oxygen species (ROS) and regulate hypoxia inducible factor 1α (HIF-1α). Primary mouse embryo fibroblasts (MEFs) or tumor cell lines expressing SirT3 short-hairpin RNA exhibit a greater potential to proliferate, and augmented HIF-1α protein stabilization and transcriptional activity in hypoxic conditions. SirT3 knockdown increases tumorigenesis in xenograft models, and this is abolished by giving mice the anti-oxidant N-acetyl cysteine. Moreover, overexpression of SirT3 inhibits stabilization of HIF-1α protein in hypoxia and attenuates increases in HIF-1α transcriptional activity. Critically, overexpression of SirT3 decreases tumorigenesis in xenografts, even when induction of the sirtuin occurs after tumor initiation. These data suggest that SirT3 acts to suppress the growth of tumors, at least in part through its ability to suppress ROS and HIF-1α

Group Living Enhances Individual Resources Discrimination: The Use of Public Information by Cockroaches to Assess Shelter Quality

In group-living organisms, consensual decision of site selection results from the interplay between individual responses to site characteristics and to group-members. Individuals independently gather personal information by exploring their environment. Through social interaction, the presence of others provides public information that could be used by individuals and modulates the individual probability of joining/leaving a site. The way that individual's information processing and the network of interactions influence the dynamics of public information (depending on population size) that in turn affect discrimination in site quality is a central question. Using binary choice between sheltering sites of different quality, we demonstrate that cockroaches in group dramatically outperform the problem-solving ability of single individual. Such use of public information allows animals to discriminate between alternatives whereas isolated individuals are ineffective (i.e. the personal discrimination efficiency is weak). Our theoretical results, obtained from a mathematical model based on behavioral rules derived from experiments, highlight that the collective discrimination emerges from competing amplification processes relying on the modulation of the individual sheltering time without shelters comparison and communication modulation. Finally, we well demonstrated here the adaptive value of such decision algorithm. Without any behavioral change, the system is able to shift to a more effective strategy when alternatives are present: the modification of the spatio-temporal distributions of individuals leading to the collective selection of the best resource. This collective discrimination implying such parsimonious and widespread mechanism must be shared by many group living-species

Informed consent for MRI and fMRI research: Analysis of a sample of Canadian consent documents

<p>Abstract</p> <p>Background</p> <p>Research ethics and the measures deployed to ensure ethical oversight of research (e.g., informed consent forms, ethics review) are vested with extremely important ethical and practical goals. Accordingly, these measures need to function effectively in real-world research and to follow high level standards.</p> <p>Methods</p> <p>We examined approved consent forms for Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) studies approved by Canadian research ethics boards (REBs).</p> <p>Results</p> <p>We found evidence of variability in consent forms in matters of physical and psychological risk reporting. Approaches used to tackle the emerging issue of incidental findings exposed extensive variability between and within research sites.</p> <p>Conclusion</p> <p>The causes of variability in approved consent forms and studies need to be better understood. However, mounting evidence of administrative and practical hurdles within current ethics governance systems combined with potential sub-optimal provision of information to and protection of research subjects support other calls for more scrutiny of research ethics practices and applicable revisions.</p

Comparative Analysis of Viral Gene Expression Programs during Poxvirus Infection: A Transcriptional Map of the Vaccinia and Monkeypox Genomes

Poxviruses engage in a complex and intricate dialogue with host cells as part of their strategy for replication. However, relatively little molecular detail is available with which to understand the mechanisms behind this dialogue.We designed a specialized microarray that contains probes specific to all predicted ORFs in the Monkeypox Zaire (MPXV) and Vaccinia Western Reserve (VACV) genomes, as well as >18,000 human genes, and used this tool to characterize MPXV and VACV gene expression responses in vitro during the course of primary infection of human monocytes, primary human fibroblasts and HeLa cells. The two viral transcriptomes show distinct features of temporal regulation and species-specific gene expression, and provide an early foundation for understanding global gene expression responses during poxvirus infection.The results provide a temporal map of the transcriptome of each virus during infection, enabling us to compare viral gene expression across species, and classify expression patterns of previously uncharacterized ORFs

Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer.

Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Convergent Evolution in Aquatic Tetrapods: Insights from an Exceptional Fossil Mosasaur

Mosasaurs (family Mosasauridae) are a diverse group of secondarily aquatic lizards that radiated into marine environments during the Late Cretaceous (98–65 million years ago). For the most part, they have been considered to be simple anguilliform swimmers – i.e., their propulsive force was generated by means of lateral undulations incorporating the greater part of the body – with unremarkable, dorsoventrally narrow tails and long, lizard-like bodies. Convergence with the specialized fusiform body shape and inferred carangiform locomotory style (in which only a portion of the posterior body participates in the thrust-producing flexure) of ichthyosaurs and metriorhynchid crocodyliform reptiles, along with cetaceans, has so far only been recognized in Plotosaurus, the most highly derived member of the Mosasauridae. Here we report on an exceptionally complete specimen (LACM 128319) of the moderately derived genus Platecarpus that preserves soft tissues and anatomical details (e.g., large portions of integument, a partial body outline, putative skin color markings, a downturned tail, branching bronchial tubes, and probable visceral traces) to an extent that has never been seen previously in any mosasaur. Our study demonstrates that a streamlined body plan and crescent-shaped caudal fin were already well established in Platecarpus, a taxon that preceded Plotosaurus by 20 million years. These new data expand our understanding of convergent evolution among marine reptiles, and provide insights into their evolution's tempo and mode

Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis.

Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition. Although the factors that trigger these deficits are diverse, there is increasing evidence that they converge on a common pathological hub that involves NMDA receptor hypofunction and oxidative stress. These factors have been separately linked to schizophrenia pathogenesis, but evidence now suggests that they are mechanistically interdependent and contribute to a common schizophrenia-associated pathology

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150