An investigation of elite athletes' and coaches' perceptions of mental ill-health in elite athletes

Research suggests elite athletes have an equal, possibly higher, probability of developing mental ill-health as the general population. However understanding of these issues amongst athletes and coaches remains largely unknown. The perceptions of 20 elite athletes and 16 elite coaches of mental ill-health amongst elite athletes were explored. Two concurrent, three round Delphi methods, using descriptive statistics and thematic analysis, were used to compare groups’ responses. Athletes and coaches expressed different opinions and experiences of mental ill-health amongst elite athletes. However, both felt the pressure athletes place upon themselves is a significant contributing factor and that obsessive compulsive disorder (OCD) and anxiety may be particularly prevalent. Whilst associated stigma was thought to be a barrier to support seeking, both groups felt sport and clinical psychologists would provide the most appropriate support, with coaches playing an important role. Implications for coaches, clinical and sport psychologists are explored and suggestions for future research are presented

An investigation of athletes’ and coaches’ perceptions of mental ill-health in elite athletes

Research suggests elite athletes have an equal, or in some circumstances possibly higher, probability of developing mental ill health as the general population, however understanding of these issues amongst athletes and coaches remains largely unknown. The perceptions of mental health problems amongst 19 elite athletes and 16 coaches were explored using two concurrent, three round Delphi surveys and the responses compared. Athletes and coaches expressed different opinions and experiences of mental ill health amongst elite athletes. However, both felt the pressure athletes place upon themselves is a significant contributing factor and that obsessional compulsive tendencies and anxiety may be particularly prevalent. Whilst associated stigma was thought to be a barrier to support seeking, both groups felt sport and clinical psychologists would provide the most appropriate support, with coaches playing an important signposting role. Implications for athletes, coaches, clinical and sport psychologists are explored and suggestions for future research are presented

Chloride Ions in the Pore of Glycine and GABA Channels Shape the Time Course and Voltage Dependence of Agonist Currents

In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK-293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mM). Our main finding is that glycine and GABA receptors "sense" chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation selective or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane

Paleoproterozoic Geomagnetic Field Strength From the Avanavero Mafic Sills, Amazonian Craton, Brazil

A recent hypothesis has suggested that Earth's inner core nucleated during the Mesoproterozoic, as evidenced by a rapid increase in the paleointensity (ancient geomagnetic field intensity) record; however, paleointensity data during the Paleoproterozoic and Mesoproterozoic period are limited. To address this problem, we have determined paleointensity from samples from three Paleoproterozoic Avanavero mafic sills (Amazonian Craton, Brazil): Cotingo, 1782 Ma, Puiuà 1788, and Pedra Preta, 1795 Ma. We adopted a multi-protocol approach for paleointensity estimates combining Thellier-type IZZI and LTD-IZZI methods, and the non-heating Preisach protocol. We obtained an average VDM value of 1.3 ± 0.7 × 1022Am2 (Cotingo) of 2.0 ± 0.4 × 1022Am2 (Puiuà) and 6 ± 4 × 1022Am2 (Pedra Preta); it is argued that the Cotingo estimate is the most robust. Our results are the first data from the upper Paleoproterozoic for South America and are comparable to data available from other regions and similar periods. The new data do not invalidate the hypothesis of that Earth's inner core nucleated during the Mesoproterozoic

Role of the Cys loop and transmembrane domain in the allosteric modulation of α4β2 nicotinic acetylcholine receptors

​Allosteric modulators of pentameric ligand gated ion channels (pLGICs) are thought to act on elements of the pathways that couple agonist binding to channel gating. Using α4β2 nicotinic acetylcholine receptors (nAChRs) and the α4β2-selective positive modulators 17β-estradiol (βEST) and desformylflustrabromine (dFBr), we have identified pathways that link the binding sites for these modulators to the Cys loop, a region that is critical for channel gating in all pLGICs. Previous studies have shown that the binding site for potentiating βEST is in the C-terminal (post-M4 region) of the α4 subunit. Here, using homology modelling in combination with mutagenesis and electrophysiology, we identified the binding site for potentiating dFBr on the top-half of a cavity between the third (M3) and fourth transmembrane (M4) α-helices of the α4 subunit. We found that the binding sites for βEST and dFBr communicate with the Cys loop, through interactions between the last residue of post-M4 and F170 of the conserved FPF sequence of the Cys loop, and that these interactions affect potentiating efficacy. In addition, interactions between a residue in M3 (Y309) and F167, a residue adjacent to the Cys loop FPF motif, also affect dFBr potentiating efficacy. Thus, the Cys loop acts as a key control element in the allosteric transduction pathway for potentiating βEST and dFBr. Overall, we propose that positive allosteric modulators that bind the M3-M4 cavity or post-M4 region increase the efficacy of channel gating through interactions with the Cys loop

Visually Relating Gene Expression and in vivo DNA Binding Data

Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative

Cooperative Transition between Open and Closed Conformations in Potassium Channels

Potassium (K+) ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed) towards the closed (open) conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel

Extreme geomagnetic field variability indicated by Eastern Mediterranean full-vector archaeomagnetic records

The magnetic field of the Earth can exhibit considerable variations at short time scales, even as short as decades. The archaeomagnetic studies of Middle Eastern artefacts (mainly from Israel and Jordan) show evidence for an exceptionally high intensity period from 1050-700 BC which displays two distinct spikes over the Levant, the Levantine Iron Age Anomaly (LIAA). Its exact duration and geographical extent are still poorly known. Despite the wealth of ancient settlements, the extensive cultural heritage and a long history of trade and immigration, the archaeomagnetism of Turkey and Cyprus remains largely unexplored. This study presents a large data set of ancient directions and intensities from seven archaeological sites in the Eastern Mediterranean covering a time span of ∼2000 yrs. The recorded directions from thirteen sets of samples are coherent with our earlier findings, yet show significantly larger swings than existing field models. In particular, we confirm the very large swing in inclination we found earlier, from 1910-1850 BC, that is also captured by the Greek PSV curve, and shallower by more than 10° than predicted by existing field models. Consequently, these models require substantial revision in this region. We were able to determine the archaeointensity from five sets of mud-bricks, from the thirteen attempted, allowing us to provide the full field vector. Furthermore, we present thirty-one new archaeointensity results from potsherds and mud-bricks that considerably enhance existing data, especially when a set of strict selection criteria is applied. Fourteen sets of potsherds from a single site (Tell Atchana) provide the longest sequence recorded so far in Turkey, from 2100 to 1350 BC. We find exceptionally high intensities of 145 and 175 ZAm2 around 700 BC, in well-dated mud-bricks and potsherds from two different locations (Tell Tayinat and Kilise Tepe), supporting extreme geomagnetic field variability in the region. Moreover, these two high intensities confirm the younger spike of the LIAA in Turkey

Rare and Frequent Promoter Methylation, Respectively, of TSHZ2 and 3 Genes That Are Both Downregulated in Expression in Breast and Prostate Cancers

Neoplastic cells harbor both hypomethylated and hypermethylated regions of DNA. Whereas hypomethylation is found mainly in repeat sequences, regional hypermethylation has been linked to the transcriptional silencing of certain tumor suppressor genes. We attempted to search for candidate genes involved in breast/prostate carcinogenesis, using the criteria that they should be expressed in primary cultures of normal breast/prostate epithelial cells but are frequently downregulated in breast/prostate cancer cell lines and that their promoters are hypermethylated.We identified several dozens of candidates among 194 homeobox and related genes using Systematic Multiplex RT-PCR and among 23,000 known genes and 23,000 other expressed sequences in the human genome by DNA microarray hybridization. An additional examination, by real-time qRT-PCR of clinical specimens of breast cancer, further narrowed the list of the candidates. Among them, the most frequently downregulated genes in tumors were NP_775756 and ZNF537, from the homeobox gene search and the genome-wide search, respectively. To our surprise, we later discovered that these genes belong to the same gene family, the 3-member Teashirt family, bearing the new names of TSHZ2 and TSHZ3. We subsequently determined the methylation status of their gene promoters. The TSHZ3 gene promoter was found to be methylated in all the breast/prostate cancer cell lines and some of the breast cancer clinical specimens analyzed. The TSHZ2 gene promoter, on the other hand, was unmethylated except for the MDA-MB-231 breast cancer cell line. The TSHZ1 gene was always expressed, and its promoter was unmethylated in all cases.TSHZ2 and TSHZ3 genes turned out to be the most interesting candidates for novel tumor suppressor genes. Expression of both genes is downregulated. However, differential promoter methylation suggests the existence of distinctive mechanisms of transcriptional inactivation for these genes

Nonparametric identification of regulatory interactions from spatial and temporal gene expression data

<p>Abstract</p> <p>Background</p> <p>The correlation between the expression levels of transcription factors and their target genes can be used to infer interactions within animal regulatory networks, but current methods are limited in their ability to make correct predictions.</p> <p>Results</p> <p>Here we describe a novel approach which uses nonparametric statistics to generate ordinary differential equation (ODE) models from expression data. Compared to other dynamical methods, our approach requires minimal information about the mathematical structure of the ODE; it does not use qualitative descriptions of interactions within the network; and it employs new statistics to protect against over-fitting. It generates spatio-temporal maps of factor activity, highlighting the times and spatial locations at which different regulators might affect target gene expression levels. We identify an ODE model for <it>eve </it>mRNA pattern formation in the <it>Drosophila melanogaster </it>blastoderm and show that this reproduces the experimental patterns well. Compared to a non-dynamic, spatial-correlation model, our ODE gives 59% better agreement to the experimentally measured pattern. Our model suggests that protein factors frequently have the potential to behave as both an activator and inhibitor for the same <it>cis</it>-regulatory module depending on the factors' concentration, and implies different modes of activation and repression.</p> <p>Conclusions</p> <p>Our method provides an objective quantification of the regulatory potential of transcription factors in a network, is suitable for both low- and moderate-dimensional gene expression datasets, and includes improvements over existing dynamic and static models.</p