VLT/X-shooter spectroscopy of the afterglow of the Swift GRB 130606A: Chemical abundances and reionisation at z∼6z\sim6

The reionisation of the Universe is thought to have ended around z~6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise. We present the high S/N VLT/X-shooter spectrum of GRB130606A at z=5.913. We aim to measure the degree of ionisation of the IGM between 5.02<z<5.84 and to study the chemical abundance pattern and dust content of its host galaxy. We measured the flux decrement due to absorption at Ly$\alpha$, $\beta$ and $\gamma$ wavelength regions. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. Our measurements of the Ly$\alpha$-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction $x_{HI}<0.05$ (3$\sigma$). We obtain column density measurements of several elements. The ionisation corrections due to the GRB is estimated to be negligible (<0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z>5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, alpha-element enhancement, or a combination of both. The very high value of [Al/Fe]=2.40+/-0.78 might connected to the stellar population history. We estimate the host metallicity to be -1.7<[M/H]<-0.9 (2%-13% of solar). (trunc.)Comment: 15 pages, 12 figure

An analysis of the physical demands of international female soccer match-play and the physical characteristics of elite players

The purpose of the thesis was to provide a detailed analysis of the physical demands of competitive international female soccer match-play and the physical characteristics of elite players. To date, the majority of research has focussed on sub-elite players with a lack of information available on international level competitors. The aim of the first study (Chapter 4) was to analyse match physical performance using a computerised tracking system (Prozone Sports Ltd., Leeds, England). A total of 167 individual match observations from 122 players competing in competitive international matches during the 2011-2012 and 2012-2013 seasons were completed. Total distance and total high-speed running distances (>14.4 km.h-1) were influenced by outfield playing position, with central midfielders completing the highest (10985 ± 706 m and 2882 ± 500 m) and central defenders (9489 ± 562 m and 1901 ± 268 m) the lowest distances, respectively. Greater total very high-speed running distances (>19.8 km.h-1) were completed when a team was without (399 ± 143 m) compared to with (313 ± 210 m) possession of the ball. The majority of sprints (>25.1 km.h-1) were over short distances with 95 % being less than 10 m. This study provides novel findings regarding the physical demands of different playing positions in competitive international female match-play and important insights for physical coaches preparing elite female players for competition. The aim of the second study (Chapter 5) was to determine the incidence and nature of repeated sprint and high-speed activity in match-play. Repeated sprint activity (a minimum of two efforts (>25.1 km.h-1) with 20 s or less recovery between efforts) was found to be rare during international female match-play with 1.1 ± 1.1 bouts per match. Repeated high-speed activity (a minimum of two efforts (>19.8 km.h-1) was influenced by playing position; with attacking-based players completing more bouts (37-40 bouts per match) than defensive players (22-33 bouts per match). Repeated sprint and high-speed bouts frequently comprised two efforts per bout, with a maximum of three and six efforts respectively. Collectively, this study provides physical coaches with useful data for replicating the demands of repeated high-speed activity and an understanding of the positional demands in order to aid the specificity of training. The aim of the third study (Chapter 6) was to attempt to apply a suitable approach for determining speed zones and to evaluate the application of specific zones to influence data outcome. Maximum match-play running speed in elite females was measured using Global Positioning System technology (STATSports, Viper, Ireland) in 230 individual match observations of 67 outfield players, during 19 international matches from 2011-2015. Female-specific speed zones and activity classifications were scaled appropriately to maximum match-play running speed. The resultant female-specific speed zones were on average 12.5 % lower than the standardised male zones, which if applied to the data in Chapter 4 would result in a small increases in total high-speed running (25 % to 28 %) and total very high-speed running (8 % to 9 %) relative to total distance. The calculated female-specific sprinting threshold (>22.0 km.h-1) corresponds to 82 % of the average maximum female match-play running speed presently observed and consequently might be more representative than the standardised male sprinting threshold (>25.1 km.h-1). However, as it was not possible to validate activity classifications in the current study it is suggested that the standardised thresholds should continue to be used to permit between playing position and gender comparisons, however, the activity classifications (e.g. walking, jogging, sprinting etc.) should be removed and replaced with the actual velocities. The aim of the fourth study (Chapter 7) was to examine the reliability of both anthropometric and performance measures in elite female soccer players. The data suggest that both junior and senior elite female players are able to adequately reproduce a variety of anthropometric (coefficient of variation = 0.1-1.3 %) and performance (coefficient of variation = 0.6-7.7 %) related tests and that reliable measures can be obtained using the present protocols and one familiarisation session. The sample size estimations (n<20) provided important insights for the participant recruitment in Chapter 8 and also suggest that the anthropometric and performance assessments are suitable for the longitudinal tracking of the fitness status of elite female players. The aim of the fifth study (Chapter 8) was to examine the physical characteristics of elite players, which were assessed in 471 national team players from 2011-2015. Anthropometric and performance variables improved with age; with large differences observed between U15s and seniors for body mass (53.9 ± 7.8 v 62.5 ± 5.8 kg), 30 m linear speed (4.78 ± 0.22 v 4.52 ± 0.17 s), countermovement jump (28.3 ± 4.0 cm v 33.4 ± 4.0 cm) and Yo Yo Intermittent Recovery Test Level 1 (1101 ± 369 m v 1583 ± 416 m). Similarities were observed for anthropometric and performance variables between the younger (U15 and U17) and older (U19 and senior) age groups. Goalkeepers generally exhibited inferior anthropometric and performance capabilities to outfield players. Faster linear speed times over short distances observed were in attackers (1.047 s v 1.061-1.077 s), greater repeated speed performance in wide midfielders and attackers (4.89-4.91 s v 4.92-4.99 s) and improved intermittent endurance performance in wide defenders (1483 m v 1260-1336 m) compared to other outfield playing positions. The normative physical characteristics presented, provide unique data for professionals involved in player recruitment and talent identification, whilst the positional differences in performance characteristics, coupled with an in-depth understanding of the demands of match-play can be applied to ensure training specificity. Collectively, the present data provides the most in-depth description of the physical demands and physical characteristics of elite female soccer players to date. The data describing the demands of match-play provides valuable insights for physical coaches preparing elite female players for competition, whilst the normative physical characteristic data provides important information to professionals involved in player recruitment and talent identification and those responsible for physical development

The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae)

[Abstract] The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at −25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinan

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD

High-intensity endurance capacity assessment as a tool for talent identification in elite youth female soccer.

Talent identification and development programmes have received broad attention in the last decades, yet evidence regarding the predictive utility of physical performance in female soccer players is limited. Using a retrospective design, we appraised the predictive value of performance-related measures in a sample of 228 youth female soccer players previously involved in residential Elite Performance Camps (age range: 12.7-15.3 years). With 10-m sprinting, 30-m sprinting, counter-movement jump height, and Yo-Yo Intermittent Recovery Test Level 1 (IR1) distance as primary predictor variables, the Akaike Information Criterion (AIC) assessed the relative quality of four penalised logistic regression models for determining future competitive international squads U17-U20 level selection. The model including Yo-Yo IR1 was the best for predicting career outcome. Predicted probabilities of future selection to the international squad increased with higher Yo-Yo IR1 distances, from 4.5% (95% confidence interval, 0.8 to 8.2%) for a distance lower than 440 m to 64.7% (95% confidence interval, 47.3 to 82.1%) for a score of 2040 m. The present study highlights the predictive utility of high-intensity endurance capacity for informing career progression in elite youth female soccer and provides reference values for staff involved in the talent development of elite youth female soccer players

Oxygen uptake kinetics in trained adolescent females

Little evidence exists with regard to the effect that exercise training has upon oxygen uptake kinetics in adolescent females. PURPOSE: The aim of the study was to compare [Formula: see text] and muscle deoxygenation kinetics in a group of trained (Tr) and untrained (Utr) female adolescents. METHOD: Twelve trained (6.4 ± 0.9 years training, 10.3 ± 1.4 months per year training, 5.2 ± 2.0 h per week) adolescent female soccer players (age 14.6 ± 0.7 years) were compared to a group (n = 8) of recreationally active adolescent girls (age 15.1 ± 0.6 years) of similar maturity status. Subjects underwent two, 6-min exercise transitions at a workload equivalent to 80 % of lactate threshold from a 3-min baseline of 10 W. All subjects had a passive rest period of 1 h between each square-wave transition. Breath-by-breath oxygen uptake and muscle deoxygenation were measured throughout and were modelled via a mono-exponential decay with a delay relative to the start of exercise. RESULT: Peak [Formula: see text] was significantly (p < 0.05) greater in the Tr compared to the Utr (Tr: 43.2 ± 3.2 mL kg(-1 )min(-1) vs. Utr: 34.6 ± 4.0 mL kg(-1 )min(-1)). The [Formula: see text] time constant was significantly (p < 0.05) faster in the Tr compared to the Utr (Tr: 26.3 ± 6.9 s vs. Utr: 35.1 ± 11.5 s). There was no inter-group difference in the time constant for muscle deoxygenation kinetics (Tr: 8.5 ± 3.0 s vs. Utr: 12.4 ± 8.3 s); a large effect size, however, was demonstrated (-0.804). CONCLUSION: Exercise training and/or genetic self-selection results in faster kinetics in trained adolescent females. The faster [Formula: see text] kinetics seen in the trained group may result from enhanced muscle oxygen utilisation

Reference values for performance test outcomes relevant to English female soccer players

The purpose of this study was to present reference standards for physical performance test outcomes relevant to elite female soccer players. We analysed mixed-longitudinal data (n = 1715 observations) from a sample of 479 elite youth and senior players as part of the English Football Association’s national development programme (age range: 12.7 to 36.0 years). Semi-parametric generalized additive models for location, scale and shape (GAMLSS) estimated age-related reference centiles for 5-m sprinting, 30-m sprinting, countermovement jump (CMJ) height, and Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IR1) performance. The estimated reference centiles indicated that the median of the distribution of physical performance test scores varied non-linearly with advancing chronological age, improving until around 25 years for each performance variable. These are the first reference ranges for performance test outcomes in elite English female soccer players. These data can assist practitioners when interpreting physical test performance outcomes to track an individual’s progress over time and support decision making regarding player recruitment and development

Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus

Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.Patricia Patricio, Antonio Mateus-Pinheiro, Monica Morais, and Nuno Dinis Alves received fellowships from the Portuguese Foundation for Science and Technology (FCT). Michal Korostynski and Marcin Piechota were funded by the POIG De-Me-Ter 3.1 and NCN 2011/03/D/NZ3/01686 grants. This study was co-funded by the Life and Health Sciences Research Institute (ICVS) and ON. 2-O NOVO NORTE-North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/ 2013, through the European Regional Development Fund (ERDF) and by the SwitchBox Consortium (Contract FP7-Health-F2-2010-259772 from the European Union). The authors declare no conflict of interest

Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene

Abstract Glucocorticoids act in part via glucocortocoid receptor binding to hormone response elements (HREs), but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE distance less than 200 bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE information from known target genes. This criterion predicts a substantial number of novel responsive genes, when applied to genomic regions 10 kb upstream of genes. Multiple-tissue in situ hybridization showed that mRNA expression of 6 out of 10 selected genes was induced in a tissue-specific manner in mice treated with a single dose of corticosterone, with the spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowed for discovery of novel tissue specific glucocorticoid target genes, which may exemplify responses underlying the permissive actions of glucocorticoids