A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP

Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, BCoR-L1 associates with histone deacetylase (HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.

Electrospraying a reproducible method for production of polymeric microspheres for biomedical applications

The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 um. Particles were shown to be spherical with a homogenous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components.

Vibrational spectroscopic study of the antimonate mineral bindheimite Pb2Sb2O6(O,OH)

Raman spectroscopy complimented with infrared spectroscopy has been used to characterise the antimonate mineral bindheimite Pb2Sb2O6(O,OH). The mineral is characterised by an intense Raman band at 656 cm-1 assigned to SbO stretching vibrations. Other lower intensity bands at 664, 749 and 814 cm-1 are also assigned to stretching vibrations. This observation suggests the non-equivalence of SbO units in the structure. Low intensity Raman bands at 293, 312 and 328 cm-1 are assigned to the OSbO bending vibrations. Infrared bands at 979, 1008, 1037 and 1058 cm-1 may be assigned to δ OH deformation modes of SbOH units. Infrared bands at 1603 and 1640 cm-1 are assigned to water bending vibrations, suggesting that water is involved in the bindheimite structure. Broad infrared bands centred upon 3250 cm-1 supports this concept. Thus the true formula of bindheimite is questioned and probably should be written as Pb2Sb2O6(O,OH,H2O)

Structured Telephone Support or Telemonitoring Programs for Patients with Chronic Heart Failure

Background: Specialised disease management programmes for chronic heart failure (CHF) improve survival, quality of life and reduce healthcare utilisation. The overall efficacy of structured telephone support or telemonitoring as an individual component of a CHF disease management strategy remains inconclusive. Objectives: To review randomised controlled trials (RCTs) of structured telephone support or telemonitoring compared to standard practice for patients with CHF in order to quantify the effects of these interventions over and above usual care for these patients. Search strategy: Databases (the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database (HTA) on The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED and Science Citation Index Expanded and Conference Citation Index on ISI Web of Knowledge) and various search engines were searched from 2006 to November 2008 to update a previously published non-Cochrane review. Bibliographies of relevant studies and systematic reviews and abstract conference proceedings were handsearched. No language limits were applied. Selection criteria: Only peer reviewed, published RCTs comparing structured telephone support or telemonitoring to usual care of CHF patients were included. Unpublished abstract data was included in sensitivity analyses. The intervention or usual care could not include a home visit or more than the usual (four to six weeks) clinic follow-up. Data collection and analysis: Data were presented as risk ratio (RR) with 95% confidence intervals (CI). Primary outcomes included all-cause mortality, all-cause and CHF-related hospitalisations which were meta-analysed using fixed effects models. Other outcomes included length of stay, quality of life, acceptability and cost and these were described and tabulated. Main results: Twenty-five studies and five published abstracts were included. Of the 25 full peer-reviewed studies meta-analysed, 16 evaluated structured telephone support (5613 participants), 11 evaluated telemonitoring (2710 participants), and two tested both interventions (included in counts). Telemonitoring reduced all-cause mortality (RR 0.66, 95% CI 0.54 to 0.81, P < 0.0001) with structured telephone support demonstrating a non-significant positive effect (RR 0.88, 95% CI 0.76 to 1.01, P = 0.08). Both structured telephone support (RR 0.77, 95% CI 0.68 to 0.87, P < 0.0001) and telemonitoring (RR 0.79, 95% CI 0.67 to 0.94, P = 0.008) reduced CHF-related hospitalisations. For both interventions, several studies improved quality of life, reduced healthcare costs and were acceptable to patients. Improvements in prescribing, patient knowledge and self-care, and New York Heart Association (NYHA) functional class were observed. Authors' conclusions: Structured telephone support and telemonitoring are effective in reducing the risk of all-cause mortality and CHF-related hospitalisations in patients with CHF; they improve quality of life, reduce costs, and evidence-based prescribing.

Workplace mobbing : experiences in the public sector

This paper discusses the counterproductive behaviour of ‘workplace mobbing’ where gossip, rumour, innuendo, and malicious accusations are reported to unfairly target and discredit targeted workers. The discussion is based on an Australian study of reports from public sector employees who self identified as targets of workplace mobbing. The behaviours are typically covert and are sometimes instigated and perpetuated by management. In focusing on three themes that emerged from the interview study, the paper discusses the sometimes toxic nature of public sector culture, mobbing behaviours and workplace expulsion. It also discusses some recommended regulatory and organizational responses that could potentially reduce the occurrence of such behaviours.

Teachers' personal epistemologies and teacher education : emergent themes and future research

This chapter summarizes the responses to four questions in each of the chapters in this volume. The questions addressed the use of a conceptual framework that guides the chapter, issues of domain-generality, how personal epistemology relates to teaching, and how personal epistemologies change. We concluded that all of the chapters discussed the distinction between constructivist and transmission teaching practices, while suggesting that there are many inconsistencies in understanding the relationship between the nature of beliefs and teachers’ practices regardless of the relative sophistication of teachers’ personal epistemologies. We also summarized a multi-component instructional model for calibrating teaching practices based on suggestions in each of the chapters, and made four suggestions for future research, including the need for an integrated theory that accounts for the development and manifestations of personal pistemology in the classroom, the generalizability of fi ndings across different measurements, a set of guidelines to promote teacher epistemological change, and an explicit instructional model that explains the development and calibration of beliefs and practices. The goal of this volume was to examine the relationship between teachers’ personal epistemologies and teacher education. Sixteen different chapters addressed one or more aspects of this issue. Although each of the chapters addressed different aspects of teachers’ personal epistemologies, a number of common themes are apparent across the chapters. We believe it is useful to articulate these themes in greater detail to provide a better retrospective understanding of this volume, as well as a better prospective framework for future research and changes to teacher training programs. We divide this chapter into two main sections. The fi rst section addresses four key questions about the nature of teachers’ personal epistemologies that were discussed in the introductory chapter as part of a larger set of questions. These questions focus on how to conceptualize these beliefs as explicit models; whether beliefs are domain-specifi c or domain-general; how beliefs are related to teaching; and how beliefs change over time. We provide a summary of each chapter in terms of these four questions. The second section proposes four general suggestions for future research based on the studies reported within this volume.

Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract

Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.

Influence of preexercise muscle glycogen content on transcriptional activity of metabolic and myogenic genes in well-trained humans

To determine whether pre-exercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen content in both legs (P < 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt; P < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: ?14-fold, P < 0.01; RING (really interesting novel gene) finger: ?3-fold, P < 0.05] but decreased for atrogin in Norm following RT (P < 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.

Sponsorship-linked marketing: The role of articulation in memory

Corporate sponsorship of events contributes significantly to marketing aims, including brand awareness as measured by recall and recognition of sponsor‐event pairings. Unfortunately, resultant advantages accrue disproportionately to brands having a natural or congruent fit with the available sponsorship properties. In three cued‐recall experiments, the effect of articulation of sponsorship fit on memory for sponsor‐event pairings is examined. While congruent sponsors have a natural memory advantage, results demonstrate that memory improvements via articulation are possible for incongruent sponsor‐event pairings. These improvements are, however, affected by the presence of competitor brands and the way in which memory is accessed.