t(16;21)(q24;q22) in therapy-related acute myelogenous leukemia arising from myelodysplastic syndrome

Case report of a translocation : t(16;21)(q24;q22) in therapy-related acute myelogenous leukemia arising from myelodysplastic syndrome

Genome-wide association study identifies common variants associated with circulating vitamin E levels

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P= 1.7 × 10−8) and rs11057830 on 12q24.31 (P= 2.0 × 10−8) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P= 2.7 × 10−10). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P= 7.8 × 10−12 (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 × 10−10 (rs2108622 on 19pter-p13.11 near CYP4F2) and P= 8.2 × 10−9 (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n= 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P< 1 × 10−4 identified

Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily

The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases

Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans

The study of Drosophila neurodegenerative mutants combined with genetic and biochemical analyses lead to the identification of multiple complex mutations in 60 patients with a novel form of ataxia/leukoencephalopathy

Autosomal recessive cerebellar ataxias

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia

Kunskapsöverföring i projektbaserade organisationer- En strävan efter att slippa uppfinna hjulet igen

A big part of assets in companies today consists of their employees knowledge and skills. In today’s society knowledge insensitive companies are increasing. The survival of these companies lie in the knowledge of their employees, which make it of great importance that knowledge transfer is managed properly. Knowledge transfer is important since it makes it possible for co-workers to apply old solutions to new problems that arise, using knowledge that already existing within the organization. From a knowledge transfer point of view, using project as an overall structure has both advantages and disadvantages. Since work comprehended in a project is limited in time knowledge and experiences made from a project may not come to use in a future project. Members of a temporary organization do not have a department to return to and there fore no natural way to transfer the knowledge they gained. Purpose of this paper is to describe knowledge transfer in project-based organization and barriers for doing so between projects. The study is conducted at two Swedish companies, SABO AB and Struktur Svenska Kontor AB in the service sector using interviews, studies of documents and observations. Our paper contribute to research by describing problems with knowledge transfer in two small project-based service organization using new concepts and cast shed on problems depending by the organisation, members and the character of project within in the organization. Key words: .En stor del av tillgångarna hos många av dagens organisationer utgörs av deras medarbetares kunskap och skicklighet. Vi lever i ett samhälle där kunskapsintensiva företag kommer att bli allt fler. I och med att dessa organisationer fortsätter att existera på grund av medarbetarnas kunskap är det av stor vikt att kunskapsöverföring fungerar väl. Kunskapsöverföring är viktig eftersom den möjliggör för medarbetare att använda sig av gamla lösningar på nya problem. Många av dagens företag organiserar sig i projektform, en företeelse som har blivit allt vanligare på senare tid. Att organisera sin verksamhet i projektform kan medföra både för och nackdelar när det gäller kunskapsöverföring. Detta beroende på att de konstellationer som byggs upp under ett projekt upphör när projektet är avslutat. Projektmedlemmar har heller ingen avdelning att återvända till, vilket gör att kunskap och erfarenheter från ett projekt blir svårare att sprida vidare. Syftet med uppsatsen är att beskriva kunskapsöverföring i projektbaserade organisationer samt vilka problem de har när det gäller kunskapsöverföringen mellan projekt. Undersökningen grundar sig på intervjuer, dokumentstudier och observationer som har genomförts på SABO AB och Struktur Svenska Kontor AB. Dessa företag är tjänsteproducerade och organiserar sin verksamhet i projektfrom. Vår uppsats bidrar till tidigare forskning genom att beskriva hinder för kunskapsöverföring i två små projektbaserade tjänsteföretag genom att använda nya koncept och belysa problem beroende av organisationen, individen och projektens karaktär inom organisationen

Les intoxications par les nouveaux antidépresseurs (évaluation de la toxicité de l'Effexor au travers des cas du centre antipoison d'Angers de 1997 à 2005)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF