Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis: Historical Advances, Current Knowledge, and Future Challenges.

We provide an overview of groundbreaking studies that laid the foundation for our current understanding of exercise-induced mitochondrial biogenesis and its contribution to human skeletal muscle fitness. We highlight the mechanisms by which skeletal muscle responds to the acute perturbations in cellular energy homeostasis evoked by a single bout of endurance-based exercise and the adaptations resulting from the repeated demands of exercise training that ultimately promote mitochondrial biogenesis through hormetic feedback loops. Despite intense research efforts to elucidate the cellular mechanisms underpinning mitochondrial biogenesis in skeletal muscle, translating this basic knowledge into improved metabolic health at the population level remains a future challenge

Transitions in coral reef accretion rates linked to intrinsic ecological shifts on turbid-zone nearshore reefs

This is the final version of the article. Available from the Geological Society of America via the DOI in this record.Nearshore coral communities within turbid settings are typically perceived to have limited reef-building capacity. However, several recent studies have reported reef growth over millennial time scales within such environments and have hypothesized that depth-variable community assemblages may act as equally important controls on reef growth as they do in clear-water settings. Here, we explicitly test this idea using a newly compiled chronostratigraphic record (31 cores, 142 radiometric dates) from seven proximal (but discrete) nearshore coral reefs located along the central Great Barrier Reef (Australia). Uniquely, these reefs span distinct stages of geomorphological maturity, as reflected in their elevations below sea level. Integrated age-depth and ecological data sets indicate that contemporary coral assemblage shifts, associated with changing light availability and wave exposure as reefs shallowed, coincided with transitions in accretion rates at equivalent core depths. Reef initiation followed a regional ∼1 m drop in sea level (1200–800 calibrated yr B.P.) which would have lowered the photic floor and exposed new substrate for coral recruitment by winnowing away fine seafloor sediments. We propose that a two-way feedback mechanism exists where past growth history influences current reef morphology and ecology, ultimately driving future reef accumulation and morphological change. These findings provide the first empirical evidence that nearshore reef growth trajectories are intrinsically driven by changes in coral community structure as reefs move toward sea level, a finding of direct significance for predicting the impacts of extrinsically driven ecological change (e.g., coral-algal phase shifts) on reef growth potential within the wider coastal zone on the Great Barrier Reef.This work was supported by Natural Environment Research Council (NERC) grant NE/J023329/1 to Perry and Smithers and NERC Radiocarbon Dating Allocations 1727.1013 and 1838.1014 to Morgan, Perry, and Gulliver

Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors.

Transforming growth factor beta-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/ p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year nonrelapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/ p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor beta-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor beta-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

A mechanism for extremely weak SpaP-expression in Streptococcus mutans strain Z1

Background: Streptococcus mutans surface-protein antigen (SpaP, PAc, or antigen I/II) has been well known to play an important role in initial attachment to tooth surfaces. However, strains with weak SpaP-expression were recently reported to be found in natural populations of S. mutans. The S. mutans gbpC-negative strain Z1, which we previously isolated from saliva and plaque samples, apparently expresses relatively low levels of SpaP protein compared to S. mutans strains MT8148 or UA159. Objective: To elucidate the mechanism for weak SpaP-expression in this strain, the spaP gene region in strain Z1 was amplified by polymerase chain reaction (PCR) and analyzed. Methods: Allelic exchange mutants between strains Z1 and UA159 involving the spaP gene region were constructed. The SpaP protein expressed in the mutants was detected with Coomasie Brilliant Blue (CBB)-staining and Western blot analysis following SDS-PAGE. Results: The 4689 bp spaP gene coding sequence for Z1 appeared to be intact. In contrast, a 20 bp nucleotide sequence appeared to be deleted from the region immediately upstream from the Z1 spaP gene when compared to the same region in UA159. The 216 bp and 237 bp intergenic fragments upstream from the spaP gene, respectively, from Z1 and UA159 were isolated, modified, and transformed into the other strain by allelic replacement. The resultant UA159-promoter region-mutant exhibited extremely weak SpaP-expression similar to that of strain Z1 and the Z1 complemented mutant expressed Spa protein levels like that of strain UA159. Conclusion: These results suggest that weak SpaP-expression in strain Z1 resulted from a 20 bp-deletion in the spaP gene promoter region

Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts

Breaking the generic mould? Grayson Perry, Channel 4 and the production of British arts television

© 2018, © The Author(s) 2018. This article examines Channel 4’s critically acclaimed series, Grayson Perry: Who Are You? (2014). Using interviews with those involved in making the series and textual analysis, we argue that the elements that contributed to the success of the series are inherently difficult to replicate due to the political economy of contemporary television production, thereby threatening the sustainability of the genre. However, while arts television rarely constitutes a commercial success in a traditional ratings sense, we outline the strategic value of the genre in contributing to Channel 4’s identity as Britain’s alternative public service broadcaster

Effect of formant frequency spacing on perceived gender in pre-pubertal children's voices

<div><p>Background</p><p>It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children's voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.</p><p>Methodology/Principal findings</p><p>In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.</p><p>Conclusions/Significance</p><p>These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children's voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.</p></div

Can sacrificial feeding areas protect aquatic plants from herbivore grazing? Using behavioural ecology to inform wildlife management

Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems