Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

Cultural information gathering by Australian students in France

Interviews with Australian university students returning from study in France indicate that problems in accessing crucial information are common experiences, and frequently lead to students reproducing stereotypes of French administrative inefficiency. Our paper argues that the issue is not one of information per se but of cultural differences in the dissemination of information. It analyses the ways in which students interpret their information-gathering difficulties, and the appropriateness of the strategies they devise for overcoming them. It then examines the pedagogical implications for preparing students for study abroad, suggesting means of both equipping students with alternative ways of understanding 'information skills' and intervening in the perpetuation of stereotypes. Cet article se base sur une quarantaine d'interviews avec des étudiants australiens ayant effectué des séjours d'études en France. La difficulté d'accéder aux renseignements jugés indispensables revient souvent au cours des entretiens, source de frustrations qui amène les Australiens à reproduire un stéréotype de l'inefficacité française. Nous posons qu'il s'agit moins d'un manque d'informations que d'une différence culturelle dans la diffusion des renseignements. Notre analyse porte sur les façons dont les étudiants interprètent leurs difficultés, ainsi que sur l'utilité de leurs stratégies pour réunir les données souhaitées. Ce travail a des conséquences pédagogiques pour la préparation de tels séjours : nous suggérons des moyens de conduire les étudiants à concevoir autrement la recherche de l'information et leurs expériences, intervenant ainsi dans la transmission des stéréotypes.

Assessing cost-effectiveness in mental health: vocational rehabilitation for schizophrenia and related conditions

Objective: Existing evidence suggests that vocational rehabilitation services, in particular individual placement and support (IPS), are effective in assisting people with schizophrenia and related conditions gain open employment. Despite this, such services are not available to all unemployed people with schizophrenia who wish to work. Existing evidence suggests that while IPS confers no clinical advantages over routine care, it does improve the proportion of people returning to employment. The objective of the current study is to investigate the net benefit of introducing IPS services into current mental health services in Australia. Method: The net benefit of IPS is assessed from a health sector perspective using cost-benefit analysis. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis of the net benefit, defined as the benefits of IPS (comprising transfer payments averted, income tax accrued and individual income earned) minus the costs. The second stage involves application of 'second-filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using the multivariate probabilistic sensitivity analysis. Results: The costs of IPS are $A10.3M (95% uncertainty interval $A7.4M-$A13.6M), the benefits are $A4.7M ($A3.1M-$A6.5M), resulting in a negative net benefit of $A5.6M ($A8.4M-$A3.4M). Conclusions: The current analysis suggests that IPS costs are greater than the monetary benefits. However, the evidence-base of the current analysis is weak. Structural conditions surrounding welfare payments in Australia create disincentives to full-time employment for people with disabilities.

Downregulation of IgE antibody and allergic responses in the lung by epidermal biolistic microparticle delivery

Background: Biolistic injections provide a needle-free delivery of antigen-laden microparticles to the epithelium. The precision of the injection preferentially targets the Langerhans cell network, which, although ideal for vaccination, might not be suitable for the downregulation of immune responses in immunotherapy. Objective: We sought to determine the ability of biolistic injection of antigen into the epithelium of sensitized mice to inhibit IgE antibody and lung inflammatory responses produced by further exposure to antigen. Methods: Mice were sensitized by means of a needle injection of ovalbumin (OVA) in alum and given a series of biolistic injections of OVA or vehicle control, followed by a boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after the boost. The mice were then challenged intranasally, and the infiltration of inflammatory cells was measured by means of bronchoalveolar lavage. Airway reactivity of the challenged mice was measured by examining responses to methacholine with forced oscillatory techniques. Results: Biolistic injection of OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1 antibody responses induced by boosting. IgG2a antibody responses were reduced rather than stimulated. The eosinophilic inflammation in the bronchoalveolar lavage fluid induced by intranasal challenge was also markedly inhibited. Lung hyperreactivity showed an initial increase and then a decrease of responsiveness to methacholine, with elastance returning to the level of unsensitized mice. Biolistic injection into the buccal epithelium was also inhibitory. Conclusions: Biolistic injection of allergen inhibited the boosting of IgE antibody and eosinophilic lung inflammatory responses without inducing TO immunity.