Athlete Self-Report Measure Use and Associated Psychological Alterations

The experience of athletes and practitioners has led to the suggestion that use of an athlete self-report measure (ASRM) may increase an athlete’s self-awareness, satisfaction, motivation, and confidence. This study sought to provide empirical evidence for this assertion by evaluating psychological alterations associated with ASRM use across a diverse athlete population. Athletes (n = 335) had access to an ASRM for 16 weeks and completed an online survey at baseline, and weeks 4, 8, and 16. Generalized estimating equations were used to evaluate the associations between ASRM compliance and outcome measures. Compared to baseline, confidence and extrinsic motivation were most likely increased at weeks 4, 8, and 16. Satisfaction and intrinsic motivation were most likely decreased at week 4, but no different to baseline values at weeks 8 and 16. Novice athletes and those who were instructed to use an ASRM (rather than using one autonomously) were less responsive to ASRM use. This study provides preliminary evidence for ASRM to prompt initial dissatisfaction and decreased intrinsic motivation which, along with increased confidence and extrinsic motivation, may provide the necessary stimulus to improve performance-related behaviors. Novice and less autonomous athletes may benefit from support to develop motivation, knowledge, and skills to use the information gleaned from an ASRM effectivel

Reduction of T-Helper Cell Responses to Recall Antigen Medicated by Codelivery with Peptidoglycan via the Intestinal Nanomineral-Antigen Pathway

Naturally occurring intestinal nanomineral particles constituently form in the mammalian gut and trap luminal protein and microbial components. These cargo loaded nanominerals are actively scavenged by M cells of intestinal immune follicles, such as Peyer’s patches and are passed to antigen-presenting cells. Using peripheral blood mononuclear cell populations as an in vitro model of nanomineral uptake and antigen presentation, we show that monocytes avidly phagocytose nanomineral particles bearing antigen and peptidoglycan (PGN), and that the presence of PGN within particles downregulates their cell surface MHC class II and upregulates programmed death receptor ligand 1. Nanomineral delivery of antigen suppresses antigen-specific CD4+ T cell responses, an effect that is enhanced in the presence of PGN. Blocking the interleukin-10 receptor restores CD4+ T cell responses to antigen codelivered with PGN in nanomineral form. Using human intestinal specimens, we have shown that the in vivo nanomineral pathway operates in an interleukin-10 rich environment. Consequently, the delivery of a dual antigen–PGN cargo by endogenous nanomineral in vivo is likely to be important in the establishment of intestinal tolerance, while their synthetic mimetics present a potential delivery system for therapeutic applications targeting the modulation of Peyer’s patch T cell responses

Oestrogen receptor-α variant mRNA expression in primary human breast tumours and matched lymph node metastases

We have shown previously that the relative expression of a truncated oestrogen receptor-α variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-α variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-α variant mRNAs appeared conserved between any primary and its matched secondary tumour. © 1999 Cancer Research Campaig

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Anorectal motility in patients with achalasia of the esophagus: recognition of an esophago-rectal syndrome

BACKGROUND: During my study of constipation, I encountered patients who had achalasia of the esophagus (AE) as well. The possibility of an existing relationship between the 2 conditions was studied. METHOD: Investigations to study the anorectal motility in 9 AE patients included: the intestinal transit time, anorectal manometry, rectoanal inhibitory reflex, defecography and electromyography (EMG) of external anal sphincter and levator ani muscle. Anorectal biopsy was done. The study comprised 8 healthy volunteers as controls. RESULTS: 6/9 AE patients had constipation presenting as strainodynia (excessive prolonged straining at stool). Rectocele was present in 4 of them. The 6 constipated patients showed significantly high rectal neck pressure (p < 0.05), absent rectoanal inhibitory reflex and aganglionosis in the anorectal biopsy. The EMG revealed diminished activity in 4 of the 6 constipated patients. The remaining 3 patients with AE had normal anorectal function. Heller's myotomy with Nissen's fundoplication improved the dysphagia, but not the constipation which was, however, relieved after performance of anorectal myectomy. CONCLUSION: The high incidence of constipation with AE postulates a relationship between the 2 conditions. Both have the same pathologic lesion which is aganglionosis. This study is preliminary and requires further studies on a larger number of patients

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Sex-differential impact of human cytomegalovirus infection on in vitro reactivity to toll-like receptor 2, 4 and 7/8 stimulation in Gambian infants

Human cytomegalovirus (HCMV) infection rates approach 100% by the first year of lifein low-income countries. It is not known if this drives changes to innate immunity in early life andthereby altered immune reactivity to infections and vaccines. Given the panoply of sex differences inimmunity, it is feasible that any immunological effects of HCMV would differ in males and females.We analysed ex vivo innate cytokine responses to a panel of toll-like receptor (TLR) ligands in 108nine-month-old Gambian males and females participating in a vaccine trial. We found evidencethat HCMV suppressed reactivity to TLR2 and TLR7/8 stimulation in females but not males. Thisis likely to contribute to sex differences in responses to infections and vaccines in early life and hasimplications for the development of TLR ligands as vaccine adjuvants. Development of an effectiveHCMV vaccine would be able to circumvent some of these potentially negative effects of HCMVinfection in childhood

Soy versus whey protein bars: Effects on exercise training impact on lean body mass and antioxidant status

BACKGROUND: Although soy protein may have many health benefits derived from its associated antioxidants, many male exercisers avoid soy protein. This is due partly to a popular, but untested notion that in males, soy is inferior to whey in promoting muscle weight gain. This study provided a direct comparison between a soy product and a whey product. METHODS: Lean body mass gain was examined in males from a university weight training class given daily servings of micronutrient-fortified protein bars containing soy or whey protein (33 g protein/day, 9 weeks, n = 9 for each protein treatment group). Training used workouts with fairly low repetition numbers per set. A control group from the class (N = 9) did the training, but did not consume either type protein bar. RESULTS: Both the soy and whey treatment groups showed a gain in lean body mass, but the training-only group did not. The whey and training only groups, but not the soy group, showed a potentially deleterious post-training effect on two antioxidant-related related parameters. CONCLUSIONS: Soy and whey protein bar products both promoted exercise training-induced lean body mass gain, but the soy had the added benefit of preserving two aspects of antioxidant function

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter