IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway.

Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients.

Development and validation of the Eating Pathology Symptoms Inventory (EPSI).

Many current measures of eating disorder (ED) symptoms have 1 or more serious limitations, such as inconsistent factor structures or poor discriminant validity. The goal of this study was to overcome these limitations through the development of a comprehensive multidimensional measure of eating pathology. An initial pool of 160 items was developed to assess 20 dimensions of eating pathology. The initial item pool was administered to a student sample (N = 433) and community sample (N = 407) to determine the preliminary structure of the measure using exploratory and confirmatory factor analyses. The revised measure was administered to independent samples of patients recruited from specialty ED treatment centers (N = 158), outpatient psychiatric clinics (N = 303), and students (N = 227). Analyses revealed an 8-factor structure characterized by Body Dissatisfaction, Binge Eating, Cognitive Restraint, Excessive Exercise, Restricting, Purging, Muscle Building, and Negative Attitudes Toward Obesity. Scale scores showed excellent convergent and discriminant validity; other analyses demonstrated that the majority of scales were invariant across sex and weight categories. Eating Pathology Symptoms Inventory scale scores had excellent internal consistency (median coefficient alphas ranged from .84-.89) and reliability over a 2- to 4-week period (mean retest r = .73). The current study represents one of the most comprehensive scale development projects ever conducted in the field of EDs and will enhance future basic and treatment research focused on EDs.

Gauging visibility: how female clerical workers manage work-related distress.

Our aim was to explain how female clerical workers manage work-related distress, using a feminist grounded theory method. Thirty-seven interviews were conducted with 24 female clerical workers. They engage in the process of gauging visibility to manage a recognition-vulnerability paradox. To gauge visibility, they take the lay of the land by attending to threats, resources, and supports within withering or flourishing work conditions. When distressing events occur, they select tactics of taking it in, taking it on, or letting it go, which are influenced by the quality of their work conditions. Their efforts to manage distress affect their workplace visibility, potentially enhancing their recognition or exacerbating their vulnerability. Gauging visibility can either diminish or enhance employees' health and well-being. Our findings emphasize social processes and structural conditions, shift attention to organization-wide efforts to alter workplace conditions, and suggest initiatives that enhance employees' opportunities for recognition, safety, and collective actions.

Binding cooperativity in phage lambda is not sufficient to produce an effective switch.

In the wild-type phage lambda, binding of CI to O(R)2 helps polymerase bound to P(RM) transition from a closed to open complex. Activators on other promoters increase the polymerase-DNA binding energy, or affect both the binding energy and the closed-open transition probability. Using a validated mathematical model, we show that these two modes of upregulation have very different effects on the promoter function. We predict that if CI(2) bound to O(R)2 produced equal increase in RNAP-DNA binding constant (compared to wild-type increase in the closed-open transition probability), the lysogen would be significantly less stable.

Qualitative teamwork issues and strategies: coordination through mutual adjustment.

Multidisciplinary research teams that include faculty, students, and volunteers can be challenging and enriching for all participants. Although such teams are becoming commonplace, minimal guidance is available about strategies to enhance team effectiveness. In this article, the authors highlight strategies to guide qualitative teamwork through coordination of team members and tasks based on mutual adjustment. Using a grounded theory exemplar, they focus on issues of (a) building the team, (b) developing reflexivity and theoretical sensitivity, (c) tackling analytic and methodological procedures, and (d) developing dissemination guidelines. Sharing information, articulating project goals and elements, acknowledging variation in individual goals, and engaging in reciprocity and respectful collaboration are key elements of mutual adjustment. The authors summarize conclusions about the costs and benefits of the process.

The etiology of white pox, a lethal disease of the Caribbean elkhorn coral, Acropora palmata.

Populations of the shallow-water Caribbean elkhorn coral, Acropora palmata, are being decimated by white pox disease, with losses of living cover in the Florida Keys typically in excess of 70%. The rate of tissue loss is rapid, averaging 2.5 cm2 x day(-1), and is greatest during periods of seasonally elevated temperature. In Florida, the spread of white pox fits the contagion model, with nearest neighbors most susceptible to infection. In this report, we identify a common fecal enterobacterium, Serratia marcescens, as the causal agent of white pox. This is the first time, to our knowledge, that a bacterial species associated with the human gut has been shown to be a marine invertebrate pathogen.