Time-of-day variation on performance measures in repeated-sprint tests: A systematic review.

The lack of standardization of methods and procedures have hindered agreement in the literature related to time-of-day effects on repeated sprint performance and needs clarification. Therefore, the aim of the present study was to investigate and systematically review the evidence relating to time-of-day based on performance measures in repeated-sprints. The entire content of PubMed (MEDLINE), Scopus, SPORTDiscus® (via EBSCOhost) and Web of Science was searched. Only experimental research studies conducted in male adult participants aged ≥18yrs, published in English before June 2019 were included. Studies assessing repeated-sprints between a minimum of two time-points during the day (morning versus evening) were deemed eligible. The primary search revealed that a total of 10 out of 112 articles were considered eligible and subsequently included. Seven articles were deemed strong and three moderate quality. Eight studies found repeated-sprint performance across the first, first few, or all sprints, to increase in favor of the evening. The magnitude of difference is dependent on the modality and the exercise protocol used. The non-motorized treadmill established an average 3.5–8.5% difference in distance covered, average and peak velocity, and average power, across all sprints in three studies and in peak power in two studies. In cycling, power output differed across all sprints by 6.0% in one study and 8.0% for the first sprint only in five studies. All four studies measuring power decrement values (i.e. rate of fatigue) established differences up to 4.0% and two out of five studies established total work to be significantly higher by 8.0%. Repeated-sprint performance is affected by time-of-day with greater performance in the late/early afternoon. The magnitude is dependent on the variable assessed and the mode of exercise. There is a clear demand for more rigorous investigations which control factors that specifically relate to investigations of time-of-day and are specific to the sport of individuals

Football-induced fatigue in hypoxia impairs repeated sprint ability and perceptual-cognitive skills

The present study investigated the effects of football-induced fatigue during hypoxia on RS and perceptual-cognitive skills. Ten male semi-professional football players underwent four sessions; a control session (0-m) to quantify RS in a non-fatigued state; and three further sessions at hypoxia (0-m;1500-m;3000-m) examining RS and perceptual-cognitive skill responses for a given physical workload. Anticipation and decision-making accuracy were obtained at the 30-min mark of each half. The mean number of trials (%) in which the player made the correct response was used for analysis. HR, TC, RPE and % saturation of O2 were measured during the warm-up, football-induced fatigue and RS test. It was found that HR, RPE and % saturation of O2 were different between conditions (P<0.05; ES=0.44-6.13). Further, RS were affected by football-induced fatigue for DC (4.8%; P=0.019; ES=0.68) and AV (5.5%; P=0.006; ES=0.79). In hypoxia, it was observed that football-induced fatigue decreased by 6.5% in DC, 6.3% in AV and 3.1% in PV at 1500-m compared to 0-m (P<0.05). Further significant changes were found at 3000-m compared to 0-m decreasing 12.8% in DC, 12.8% in AV and 6.2% in PV (P<0.0005). More pronounced declines in perceptual-cognitive skills were found as altitude increased (5.0-12.5 %; P<0.05; ES=1.17-2.41) and between both halves (5.3-6.7 %; P<0.05). The data demonstrates that the RS test was highly sensitive to fatigue and hypoxia for a given physical load. Simulated matches in hypoxia revealed larger decreases, when compared to normoxia in RS and perceptual-cognitive skills, highlighting the need for optimal acclimatisation strategies, including physical and technical preparation, prior to playing a

TraR, a Homolog of a RNAP Secondary Channel Interactor, Modulates Transcription

Recent structural and biochemical studies have identified a novel control mechanism of gene expression mediated through the secondary channel of RNA Polymerase (RNAP) during transcription initiation. Specifically, the small nucleotide ppGpp, along with DksA, a RNAP secondary channel interacting factor, modifies the kinetics of transcription initiation, resulting in, among other events, down-regulation of ribosomal RNA synthesis and up-regulation of several amino acid biosynthetic and transport genes during nutritional stress. Until now, this mode of regulation of RNAP was primarily associated with ppGpp. Here, we identify TraR, a DksA homolog that mimics ppGpp/DksA effects on RNAP. First, expression of TraR compensates for dksA transcriptional repression and activation activities in vivo. Second, mutagenesis of a conserved amino acid of TraR known to be critical for DksA function abolishes its activity, implying both structural and functional similarity to DksA. Third, unlike DksA, TraR does not require ppGpp for repression of the rrnB P1 promoter in vivo and in vitro or activation of amino acid biosynthesis/transport genes in vivo. Implications for DksA/ppGpp mechanism and roles of TraR in horizontal gene transfer and virulence are discussed

Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

EEG Correlates of Attentional Load during Multiple Object Tracking

While human subjects tracked a subset of ten identical, randomly-moving objects, event-related potentials (ERPs) were evoked at parieto-occipital sites by task-irrelevant flashes that were superimposed on either tracked (Target) or non-tracked (Distractor) objects. With ERPs as markers of attention, we investigated how allocation of attention varied with tracking load, that is, with the number of objects that were tracked. Flashes on Target discs elicited stronger ERPs than did flashes on Distractor discs; ERP amplitude (0–250 ms) decreased monotonically as load increased from two to three to four (of ten) discs. Amplitude decreased more rapidly for Target discs than Distractor discs. As a result, with increasing tracking loads, the difference between ERPs to Targets and Distractors diminished. This change in ERP amplitudes with load accords well with behavioral performance, suggesting that successful tracking depends upon the relationship between the neural signals associated with attended and non-attended objects

A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain

Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought

Goals and principles for programmatic river restoration monitoring and evaluation: collaborative learning across multiple projects

River restoration is a relatively recent undertaking, with high levels of complexity and uncertainty involved. Many restoration projects have been monitored over the past three decades, however, results have rarely been compared across projects thereby limiting our ability to identify factors that influence restoration outcomes. Programmatic monitoring and evaluation (ProME) that builds on standardized surveys and systematic cross‐project comparison allows for collaborative learning, transfer of results across restoration projects and for adaptive management and monitoring. We present a conceptual framework for ProME consisting of four goals and nine principles. First, ProME accounts for complexity, uncertainty, and change in order to contribute to sustainable river management over the long term. Second, ProME promotes collaborative learning and adaptation by standardizing the sampling design for the field surveys at multiple projects and by disseminating findings across stakeholders. Third, ProME verifies to what extent restoration has been achieved, i.e., it must quantify the size and direction of change. Fourth, ProME identifies why the observed effects were present, thereby improving our mechanistic understanding of river functioning. We conclude with potential extensions of the framework (e.g., evaluating cumulative effects of projects within a catchment). Our conceptual framework presents a structured approach toward a more systematic learning and evidence‐based action in river restoration, while taking into account the wider picture of environmental change within which river restoration projects will inevitably operate

Equity in healthcare for coronary heart disease, Wales (UK) 2004–2010: A population-based electronic cohort study

Despite substantial falls in coronary heart disease (CHD) mortality in the United Kingdom (UK), marked socioeconomic inequalities in CHD risk factors and CHD mortality persist. We investigated whether inequity in CHD healthcare in Wales (UK) could contribute to the observed social gradient in CHD mortality. Linking data from primary and secondary care we constructed an electronic cohort of individuals (n = 1199342) with six year follow-up, 2004–2010. We identified indications for recommended CHD interventions, measured time to their delivery, and estimated risk of receiving the interventions for each of five ordered deprivation groups using a time-to-event approach with Cox regression frailty models. Interventions in primary and secondary prevention included risk-factor measurement, smoking management, statins and antihypertensive therapy, and in established CHD included medication and revascularization. For primary prevention, five of the 11 models favoured the more deprived and one favoured the less deprived. For medication in secondary prevention and established CHD, one of the 15 models favoured the more deprived and one the less deprived. In relation to revascularization, six of the 12 models favoured the less deprived and none favoured the more deprived–this evidence of inequity exemplified by a hazard ratio for revascularization in stable angina of 0.79 (95% confidence interval 0.68, 0.92). The main study limitation is the possibility of under-ascertainment or misclassification of clinical indications and treatment from variability in coding. Primary care components of CHD healthcare were equitably delivered. Evidence of inequity was found for revascularization procedures, although this inequity is likely to have only a modest effect on social gradients in CHD mortality. Policymakers should focus on reducing inequalities in CHD risk factors, particularly smoking, as these, rather than inequity in healthcare, are likely to be key drivers of inequalities in CHD mortality

A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

<p>Abstract</p> <p>Background</p> <p>NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.</p> <p>Methods</p> <p>An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance.</p> <p>Results</p> <p>GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells.</p> <p>Conclusions</p> <p>NET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.</p