Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients

Introduction MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis. Methods Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR. Results Rheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals. In addition, two targets of miR-146a, namely tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK-1), were similarly expressed between rheumatoid arthritis patients and control individuals, despite increased expression of miR-146a in patients with rheumatoid arthritis. Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-α production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-α production. Conclusions Recent studies have shown that synovial tissue and synovial fibroblasts from patients with rheumatoid arthritis exhibit increased expression of certain microRNAs. Our data thus demonstrate that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts. The increased microRNA expression in rheumatoid arthritis patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy, but this will require confirmation using a large and well defined cohort. Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-α production in patients with rheumatoid arthritis

Supporting induction: relationships count

This article examines the structural changes to the induction of teachers in Scotland using the perceptions of a group of final year student teachers. This group would be the first probationer teachers to experience revised arrangements for new teacher induction in 37 years. Their preferences and concerns are highlighted, as the new procedures roll out in schools nationwide, in an attempt to stress the importance of relationships to the success of the induction scheme. The argument put forward in this article is based on the notion that personal intelligence is central to effective relationships and therefore crucially important in the context of this mentoring relationship. The views of our sample provide evidence to suggest that the quality of interactions between the mentor and the probationer teacher are paramount in providing a good induction experience. These views are substantiated by experiences in England and in induction literature elsewhere. A synthesis of this evidence is used to make recommendations for those involved in supporting induction in schools, local authorities or teacher education institutions

Sjögren’s syndrome-associated microRNAs in CD14+ monocytes unveils targeted TGFβ signaling

SjS-associated miRNA expression levels are positively associated in CD14+ monocytes. Linear regression analyses were used to define associations between miRNAs in HC (circle, n = 17), SLE (triangle, n = 17), and RA (diamond, n = 18) patient groups. Cutoff values established by ROC curve analyses are indicated by dotted lines. P < 0.05 was considered statistically significant. (PDF 125 kb

Catchment-wide interactive effects of anthropogenic structures and river levels on fish spawning migrations

Worldwide, rivers are extensively fragmented by anthropogenic structures, reducing longitudinal connectivity, inhibiting migration and leading to severe declines in many fish populations, especially for diadromous species. However, few studies have determined the effects of annual differences in hydrology on catchment penetration past barriers to spawning habitats. We investigated the upstream spawning migration of 120 (n = 61 & 59) acoustic tagged river lamprey (Lampetra fluviatilis) across two contrasting (dry and wet) years in the River Yorkshire Ouse, England. Overall, significantly more lamprey reached spawning habitat (76% vs 39%) and penetrated significantly further upstream (median [km] from release, 53.9 vs 16.8) in the wet year than the dry year. Passage at weirs was almost exclusively during elevated river levels, which directly and collectively influenced catchment-wide distribution, especially in the dry year. Indeed, higher proportions entered two upper tributaries in the wet year (9.8% vs 27.1% and 9.8% vs 30.5%), due to increased passage efficiencies at the two main river weirs (60.5–87.5% and 54.5–83.8%), and reached assumed spawning locations 66.5% and 10.9% quicker. By contrast, there was no difference in numbers of lamprey entering, or time taken to arrive at assumed spawning location, in the two lower river tributaries between years. Our study supports the landscape-scale paradigm for ecosystem restoration because of the observed catchment-level effects of hydrology and barrier distribution on fish migration. Connectivity restoration for migratory fish should be implemented at a catchment scale, with planning incorporating spatial information regarding accessibility to key habitats to reap the largest gains

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

<p>Abstract</p> <p>Background</p> <p>Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia.</p> <p>Methods</p> <p>Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2.</p> <p>Results</p> <p>Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia.</p> <p>Conclusion</p> <p>Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.</p