STOP knockout and NMDA NR1 hypomorphic mice exhibit deficits in sensorimotor gating.

International audienceSchizophrenia is a chronic and debilitating disease which is thought to arise from a neuro-developmental disorder. Both the stable tubule-only polypeptide (STOP) protein and the N-methyl-D-aspartate (NMDA) NR1 subunit are involved in neuronal development and physiology. It has therefore been postulated that transgenic mice lacking either the STOP or the NMDAR1 gene would show a 'schizophrenic-like' phenotype. Here, STOP knockout and NMDA NR1 hypomorphic mice were assessed in a behavioural measure that can be used to detect schizophrenic-like phenotypes: a change in sensorimotor gating, measured through prepulse inhibition (PPI). STOP knockout mice were further assessed in another measure of 'schizophrenic-like behaviour': hyperlocomotion. The PPI deficit exhibited by both the STOP knockout and NMDA knockdown mice could not be reversed by acute treatment with the atyptical antipsychotic, clozapine (1 mg/kg, i.p.) but the hyperlocomotion shown by the STOP knockout mice was reversed with the same acute dose of clozapine

Supporting academic publication: evaluation of a writing course combined with writers' support group

Publication rates are a vital measure of individual and institutional performance, yet many nurse academics publish rarely or not at all. Despite widespread acceptance of the need to increase academic publication rates and the pressure university faculty may experience to fulfil this obligation, little is known about the effectiveness of practical strategies to support academic writing. In this small cohort study (n=8) comprising nurses and other professionals involved in university education, a questionnaire survey was used to evaluate the effectiveness of a one-week "Writing for Publication" course combined with a monthly writers support group to increase publication rates. Two year pre and post submissions increased from 9 to 33 articles in peer-reviewed journals. Publications (in print) per person increased from a baseline of 0.5-1.2 per year. Participants reported increased writing confidence and greater satisfaction with the publishing process. Peer support and receiving recognition and encouragement from line managers were also cited as incentives to publish. Writing for publication is a skill that can be learned. The evaluated model of a formal writing course, followed by informal monthly group support meetings, can effectively increase publication rates

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons

The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons

Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan highlands.

Contains fulltext : 125827.pdf (publisher's version ) (Open Access

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage : The UK-REBOA Randomized Clinical Trial

Funding/Support: This research (project No. 14/199/09) was funded by the National Institute for Health and Care Research Health Technology Assessment Programme. The Health Services Research Unit and the Health Economics Research Unit are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPostprin

Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor

We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority

Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer.

Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene