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Shiga toxin-producing Escherichia coli (STEC) is a major cause of serious human gastrointestinal illness and has the potential to cause life-threatening complications, such as hemolytic uremic syndrome (HUS) (1). An [...]

Motivation and cohesion have both been found to have an effect on persistence and learning (Martens & Webber, 2002), as well as overall performance (Turman, 2003), signifying their imperative nature to any successful team. However, these two factors have yet to be examined in relation to one another when exploring gender as a contributing variable. The purpose of this study was to determine if gender and motivation type were related to athletes' perceptions of team cohesion. In order to address this concept, 253 male and female collegiate athletes completed a demographics questionnaire, the Sport Motivation Scale (SMS; Pelletier et al., 1995), and the Group Environment Questionnaire (GEQ; Carron et al., 1985). Results revealed significant positive correlations between perceptions of task and social cohesion with each of the three intrinsic motivation types and two extrinsic motivation types (i.e. integrated regulation and identified regulation). Negative relationships were found between a motivation and task and social cohesion. However, gender was not a significant predictor of perceived cohesion when moderated with motivation type; only self-determination score was a significant predictor of both task and social cohesion. These outcomes indicate that fostering intrinsic motivation, despite gender, in sport teams may contribute to more positive social and task cohesion among the group., A considerable amount of research has been conducted to understand why individuals choose to participate in sport (Kipp & Amorose, 2008). Two of the most common answers relate to athletes' [...]

Pre-performance routines and specifically putting routines are individualized tasks, which raises the question of whether the temporal consistency correlates with the behavioral consistency of routines (Penick & Shrake, 1992). The purpose of this study was to investigate the duration of pre-putt routines of highly skilled golfers and the accuracy of made putts. Participants consisted of collegiate golfers from 30 Division I Universities during two separate 54-hole collegiate golf tournaments. Putts of 3 feet (.91 meters) to 10 feet (3.04 meters) in length were recorded and divided into two categories of .91 meters to 1.82 meters and 1.82 meters to 3.04 meters. Two separate between-subjects and one within-subjects logistic regression models were conducted. The between-subjects model revealed duration of putting routines was a significant predictor of the likelihood of making the putt for only one tournament. The within-subjects model revealed significant findings in that players deviating less in routine duration were more likely to make the putt. Findings suggest a potential link between temporal consistencies and putting outcomes in relation for avenues of future research., The sport of golf presents researchers with various opportunities to examine athletes' behaviors in specific situations. Golf also provides an arena to test assumptions concerning motor control and performance, due [...]

Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC) locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC. [ABSTRACT FROM AUTHOR]

Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP--seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)--a general mechanism which may confer tissue-specific gene expression in multiple lineages. [ABSTRACT FROM AUTHOR]

Technical advances in lipidomic analysis have generated tremendous amounts of quantitative lipid molecular species data, whose value has not been fully explored. We describe a novel computational method to infer mechanisms of de novo lipid synthesis and remodeling from lipidomic data. We focus on the mitochondrial-specific lipid cardiolipin (CL), a polyglycerol phospholipid with four acyl chains. The lengths and degree of unsaturation of these acyl chains vary across CL molecules, and regulation of these differences is important for mitochondrial energy metabolism. We developed a novel mathematical approach to determine mechanisms controlling the steady-state distribution of acyl chain combinations in CL . We analyzed mitochondrial lipids from 18 types of steady-state samples, each with at least 3 replicates, from mouse brain, heart, lung, liver, tumor cells, and tumors grown in vitro. Using a mathematical model for the CL remodeling mechanisms and a maximum likelihood approach to infer parameters, we found that for most samples the four chain positions have an independent and identical distribution, indicating they are remodeled by the same processes. Furthermore, for most brain samples and liver, the distribution of acyl chains is well-fit by a simple linear combination of the pools of acyl chains in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG). This suggests that headgroup chemistry is the key determinant of acyl donation into CL, with chain length/saturation less important. This canonical remodeling behavior appears damaged in some tumor samples, which display a consistent excess of CL molecules having particular masses. For heart and lung, the "proportional incorporation" assumption is not adequate to explain the CL distribution, suggesting additional acyl CoA-dependent remodeling that is chain-type specific. Our findings indicate that CL remodeling processes can be described by a small set of quantitative relationships, and that bioinformatic approaches can help determine these processes from high-throughput lipidomic data. [ABSTRACT FROM AUTHOR]

Athletes participating in all levels of sport experience extraordinarily high levels of stress, expectations, and physical challenges. The throws event athlete in track and field should strive to achieve an optimal state of arousal and concentration during specific competitions. A strong body of research evaluating the qualities of the flow state in athletics and psychological skills training is present in sport psychology. A practical guide for coaches to apply psychological skills training in a periodized training plan is missing. The purpose of this article is to: 1) describe a periodized annual plan for mental skills training and 2) suggest a method to interject those skills into the competition day routine to achieve flow for the track and field thrower. [ABSTRACT FROM AUTHOR]

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mutations in the isocitrate dehydrogenase gene IDH1 are common in low-grade glioma, where they result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation, and gliomagenesis. IDH1 mutations also cosegregate with mutations in the ATRX gene and the TERT promoter, suggesting that IDH mutation may drive the creation or selection of telomere-stabilizing events as part of immortalization/transformation process. To determine whether and how this may occur, we investigated the phenotype of pRb-/p53-deficient human astrocytes engineered with IDH1 wild-type (WT) or R132H-mutant (IDH1 mut ) genes as they progressed through their lifespan. IDH1 mut expression promoted 2HG production and altered histone methylation within 20 population doublings (PD) but had no effect on telomerase expression or telomere length. Accordingly, cells expressing either IDH1 WT or IDH1 mut entered a telomere-induced crisis at PD 70. In contrast, only IDH1 mut cells emerged from crisis, grew indefinitely in culture, and formed colonies in soft agar and tumors in vivo Clonal populations of postcrisis IDH1 mut cells displayed shared genetic alterations, but no mutations in ATRX or the TERT promoter were detected. Instead, these cells reactivated telomerase and stabilized their telomeres in association with increased histone lysine methylation (H3K4me3) and c-Myc/Max binding at the TERT promoter. Overall, these results show that although IDH1 mut does not create or select for ATRX or TERT promoter mutations, it can indirectly reactivate TERT, and in doing so contribute to astrocytic immortalization and transformation. Cancer Res; 76(22); 6680-9. ©2016 AACR., Competing Interests: There are no relationships that could be construed as resulting in an actual, potential, or perceived conflict of interest with regard to this manuscript., (©2016 American Association for Cancer Research.)

Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients., (©2016 American Association for Cancer Research.)

The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution., (Copyright © 2015 Elsevier Inc. All rights reserved.)