Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor

Tumor suppressor in lung cancer-1 (TSLC1) loss is common in many human cancers, including meningioma. In this study, we demonstrate that TSLC1 protein and RNA expression is lost in 60% to 65% of high-grade gliomas, and that TSLC1 reintroduction into glioma cells results in growth suppression. Moreover, Tslc1 loss in mice results in increased astrocyte proliferation in vivo and in vitro. These data indicate that TSLC1 functions as a glioma tumor suppressor. ©2006AAN Enterprises, Inc.Fil: Houshmandi, S.S.. Washington University in St. Louis; Estados UnidosFil: Surace, Ezequiel Ignacio. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Zhang, H.B.. Washington University in St. Louis; Estados UnidosFil: Fuller, G.N.. University of Texas; Estados UnidosFil: Gutmann, D.H.. Washington University in St. Louis; Estados Unido

Experience in implementing harvest strategies in Australia's south-eastern fisheries

The Southern and Eastern Scalefish and Shark Fishery (SESSF) is a complex multi-species fishery, with 34 stock units under quota management, for which a harvest strategy framework was developed in 2005. The framework involves the application of a set of tier-based harvest control rules (HCR) designed to provide a precautionary approach to management. The harvest strategy framework has been applied from 2005 to 2007, resulting in substantial reductions in quotas across the fishery. The experience in implementing the framework, both positive and negative, is described, and general lessons are drawn. Key lessons include the importance of formally testing such strategies using management strategy evaluation, the impact of external management drivers on implementation of the approach, the need to define strategies for setting "bycatch quotas" in multi-species fisheries, and the need for flexibility and pragmatism in the early stages of implementing such an approach

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Using simulated consultations to develop communications skills for neurology trainees.

Item does not contain fulltextCommunication skills are essential for clinical medicine yet, unlike in general practice, trainees in specialist and general medicine are not formally trained in them. We have used videotaped recording of simulated consultations to evaluate their acceptability and usefulness for training neurology specialist registrars. Twelve specialist registrars in neurology participated; their perceptions of the method were assessed using quantified scales and focus groups. All but one of the 12 trainees found the exercise useful both for improving clinical skills and for the imparting of information. The median visual analogue scores (0=useless, 100=very useful) for history taking and for imparting information were 91 and 90%, respectively. The median scores [and interquartile range (IQR)] of perceived usefulness for communication skills increased before to after (for use of video) from 68 (58-78) to 88 (80-92)% (P < 0.02), and (for use of simulated patients) from 51 (40-71) to 86 (79-89)% (P < 0.02). The focus groups provided additional qualitative data supporting the technique. We conclude that videotaped consultations with simulated patients are valued by most neurology trainees, both for improving their history-taking skills and for imparting information. The technique could be used more widely in neurology training, and may have a role in assessment

Melanotic paraganglioma arising in the temporal horn following Langerhans cell histiocytosis

PubMed ID: 18196230Intracerebral paragangliomas are rare because of the lack of paraganglial cells in the cerebral tissue. We report a rare case of melanotic paraganglioma arising from the temporal horn of the lateral ventricle in a patient with prior Langerhans cell histiocytosis (LCH) treated with chemotherapy and radiation. © 2007 Springer-Verlag