Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation

A critical step in X-chromosome inactivation (XCI), which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s) are strongly downregulated, while the levels of unspliced form(s) of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process

The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

Spontaneous compartment syndrome in a patient with diabetes and statin administration: a case report

Compartment syndrome is a condition characterized by pressure increasing in the inextensible muscular compartments that leads to a decrease of capillary perfusion with consequent ischemic lesions of the logia elements. The authors report a case of an unusual compartment syndrome with spontaneous onset in a patient with type II diabetes and chronic therapy with statins (Atorvastatin). The condition was successfully treated by a fasciotomy and medical support. The importance of a correct anamnesis and a high level of suspicion is emphasized

Status of Intraductal Therapy for Ductal Carcinoma in Situ

The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS

Assessing weight perception accuracy to promote weight loss among U.S. female adolescents: A secondary analysis

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity have become a global epidemic. The prevalence of overweight and obesity among U.S. adolescents has almost tripled in the last 30 years. Results from recent systematic reviews demonstrate that no single, particular intervention or strategy successfully assists overweight or obese adolescents in losing weight. An understanding of factors that influence healthy weight-loss behaviors among overweight and obese female adolescents promotes effective, multi-component weight-loss interventions. There is limited evidence demonstrating associations between demographic variables, body-mass index, and weight perception among female adolescents trying to lose weight. There is also a lack of previous studies examining the association of the accuracy of female adolescents' weight perception with their efforts to lose weight. This study, therefore, examined the associations of body-mass index, weight perception, and weight-perception accuracy with trying to lose weight and engaging in exercise as a weight-loss method among a representative sample of U.S. female adolescents.</p> <p>Methods</p> <p>A nonexperimental, descriptive, comparative secondary analysis design was conducted using data from Wave II (1996) of the National Longitudinal Study of Adolescent Health (Add Health). Data representative of U.S. female adolescents (N = 2216) were analyzed using STATA statistical software. Descriptive statistics and survey weight logistic regression were performed to determine if demographic and independent (body-mass index, weight perception, and weight perception accuracy) variables were associated with trying to lose weight and engaging in exercise as a weight-loss method.</p> <p>Results</p> <p>Age, Black or African American race, body-mass index, weight perception, and weight perceptions accuracy were consistently associated with the likeliness of trying to lose weight among U.S. female adolescents. Age, body-mass index, weight perception, and weight-perception accuracy were positively associated (<it>p </it>< 0.05) with trying to lose weight. Black/African American subjects were significantly less likely than their White counterparts to be trying to lose weight. There was no association between demographic or independent variables and engaging in exercise as a weight-loss method.</p> <p>Conclusions</p> <p>Findings suggest that factors influencing weight-loss efforts, including age, race, body-mass index, weight perception, and weight-perception accuracy, should be incorporated into existing or new multi-component weight-loss interventions for U.S. adolescent females in order to help reduce the national epidemic of overweight and obesity among U.S. female adolescents.</p

Predicting the development of stress urinary incontinence 3 years after hysterectomy

We aimed to develop a prediction rule to predict the individual risk to develop stress urinary incontinence (SUI) after hysterectomy. Prospective observational study with 3-year follow-up among women who underwent abdominal or vaginal hysterectomy for benign conditions, excluding vaginal prolapse, and who did not report SUI before surgery (n = 183). The presence of SUI was assessed using a validated questionnaire. Significant prognostic factors for de novo SUI were BMI (OR 1.1 per kg/m(2), 95% CI 1.0-1.2), younger age at time of hysterectomy (OR 0.9 per year, 95% CI 0.8-1.0) and vaginal hysterectomy (OR 2.3, 95% CI 1.0-5.2). Using these variables, we developed the following rule to predict the risk of developing SUI: 32 + BMI-age + (7.5 × route of surgery). We defined a prediction rule that can be used to counsel patients about their individual risk on developing SUI following hysterectom

The Eat Smart Study: A randomised controlled trial of a reduced carbohydrate versus a low fat diet for weight loss in obese adolescents

Background Despite the recognition of obesity in young people as a key health issue, there is limited evidence to inform health professionals regarding the most appropriate treatment options. The Eat Smart study aims to contribute to the knowledge base of effective dietary strategies for the clinical management of the obese adolescent and examine the cardiometablic effects of a reduced carbohydrate diet versus a low fat diet. Methods and design Eat Smart is a randomised controlled trial and aims to recruit 100 adolescents over a 2½ year period. Families will be invited to participate following referral by their health professional who has recommended weight management. Participants will be overweight as defined by a body mass index (BMI) greater than the 90th percentile, using CDC 2000 growth charts. An accredited 6-week psychological life skills program ‘FRIENDS for Life’, which is designed to provide behaviour change and coping skills will be undertaken prior to volunteers being randomised to group. The intervention arms include a structured reduced carbohydrate or a structured low fat dietary program based on an individualised energy prescription. The intervention will involve a series of dietetic appointments over 24 weeks. The control group will commence the dietary program of their choice after a 12 week period. Outcome measures will be assessed at baseline, week 12 and week 24. The primary outcome measure will be change in BMI z-score. A range of secondary outcome measures including body composition, lipid fractions, inflammatory markers, social and psychological measures will be measured. Discussion The chronic and difficult nature of treating the obese adolescent is increasingly recognised by clinicians and has highlighted the need for research aimed at providing effective intervention strategies, particularly for use in the tertiary setting. A structured reduced carbohydrate approach may provide a dietary pattern that some families will find more sustainable and effective than the conventional low fat dietary approach currently advocated. This study aims to investigate the acceptability and effectiveness of a structured reduced dietary carbohydrate intervention and will compare the outcomes of this approach with a structured low fat eating plan. Trial Registration: The protocol for this study is registered with the International Clinical Trials Registry (ISRCTN49438757)