Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

International audienceA combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase

Transplantation of Human Melanocytes

Recent advances in the culturing of pigment cells from human beings have made it possible to begin the transplantation of autologous melanocytes into areas of skin that are hypopigmented. In a patient with piebaldism we were able to take pigment cells from a shave biopsy of the normally pigmented skin of the back, expand the cells in culture, and return them to an area devoid of pigment cells and get a perfect take. To grow the cells in culture we used 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as well as cholera toxin and isobutylmethyl xanthine. At this time, one can substitute basic fibroblast growth factor for TPA. The procedure of using autologous pigment cell cultures opens the door for further advances in the treatment of patients who do not have melanocytes in certain areas of the skin, as seen in patients with vitiligo or piebaldism, or as a consequence of severe mechanical or thermal trauma

Bulk rock elastic moduli at high pressures, derived from the mineral textures and from extrapolated laboratory data

The elastic anisotropy of bulk rock depends on the mineral textures, the crack fabric and external parameters like, e.g., confining pressure. The texture-related contribution to elastic anisotropy can be predicted from the mineral textures, the largely sample-dependent contribution of the other parameters must be determined experimentally. Laboratory measurements of the elastic wave velocities are mostly limited to pressures of the intermediate crust. We describe a method, how the elastic wave velocity trends and, by this means, the elastic constants can be extrapolated to the pressure conditions of the lower crust. The extrapolated elastic constants are compared to the texture-derived ones. Pronounced elastic anisotropy is evident for phyllosilicate minerals, hence, the approach is demonstrated for two phyllosilicate-rich gneisses with approximately identical volume fractions of the phyllosilicates but different texture types

Workshop Organisation und Ordnung der Japanischen Wirtschaft II - Themenschwerpunkt: Einfluß von IT-Technologien auf Strukturen und Prozesse in Unternehmen

Der hier dokumentierte Workshop, der am 14. Dezember 2001 im Japanisch-Deutschen Zentrum Berlin stattfand, setzt die im Vorjahr begonnene Auseinandersetzung um die Auswirkungen der 'New Economy' fort. Das Thema behandelt in theoretischer und landesspezifischer, auch vergleichender, Perspektive die Frage, wie sich IT -Technologien auf Strukturen und Prozesse in Unternehmen auswirken. Dabei werden die folgenden Fragenkreise behandelt: 'Der Einfluss von Informationstechnologien auf Strukturen und Prozesse in Unternehmen - eine Übersicht zur Einführung' (Ruth); ''Culture matters'; EDI-Systementwicklung in der koreanischen Automobilindustrie' (Manske, Moon); 'Katalysator und Protagonist: Die Rolle der Informationstechnik im Paradigmenwandel von Untemehmensstrategien und -struktur' (Winand); 'Auswirkungen von IT-Technologien auf die Unternehmens- und Industrieorganisation in Japan' (Hemmert). -- The workshop documented here took place on December 14, 2001, at the Japanisch-Deutsches Zentrum Berlin (Japanese-Gennan Centre Berlin) and continued the discussion begun a year earJier on the 'New Economy' and its consequences. The theme looks, in a comparative manner, on the effects of IT technology on the structures and strategies of firms, both from a theoretical and country-specific point of view. The following questions are dealt with: 'The infIuence of information technology on the structures and strategies in firms - an introductory survey' (Ruth); ''Culture matters'; EDI system development in the Korean automobile industry' (Manske, Moon); 'Catalyst and Protagonist: The role of information technology in relation to the paradigmatic change of strategies and structures in firms' (Winand); 'Effects of IT technologies on the organisation offirms and industries in Japan' (Hemmert).Technologie,Informationstechnologie,Telekommunikation,Unternehmen,Japan,Korea

Genome-wide association analysis and functional annotation of positional candidate genes for feed conversion efficiency and growth rate in pigs

This project has received funding from the European Union‘s Seventh Framework Programme for research, technological development and demonstration as part of the ECO-FCE project under grant agreement No. 311794.peer-reviewedFeed conversion efficiency is a measure of how well an animal converts feed into live weight and it is typically expressed as feed conversion ratio (FCR). FCR and related traits like growth rate (e.g. days to 110 kg—D110) are of high interest for animal breeders, farmers and society due to implications on animal performance, feeding costs and environmental sustainability. The objective of this study was to identify genomic regions associated with FCR and D110 in pigs. A total of 952 terminal line boars, showing an individual variation in FCR, were genotyped using 60K SNP-Chips. Markers were tested for associations with estimated breeding values (EBV) for FCR and D110. For FCR, the largest number of associated SNPs was located on chromosomes 4 (30 SNPs), 1 (25 SNPs), X (15 SNPs) and 6 (12 SNPs). The most prominent genomic regions for D110 were identified on chromosomes 15 (10 SNPs), 1 and 4 (both 9 SNPs). The most significantly associated SNPs for FCR and D110 mapped 129.8 Kb from METTL11B (chromosome 4) and 32Kb from MBD5 (chromosome 15), respectively. A list of positional genes, closest to significantly associated SNPs, was used to identify enriched pathways and biological functions related to the QTL for both traits. A number of candidate genes were significantly overrepresented in pathways of immune cell trafficking, lymphoid tissue structure, organ morphology, endocrine system function, lipid metabolism, and energy production. After resequencing the coding region of selected positional and functional candidate genes, six SNPs were genotyped in a subset of boars. SNPs in PRKDC, SELL, NR2E1 and AKRIC3 showed significant associations with EBVs for FCR/D110. The study revealed a number of chromosomal regions and candidate genes affecting FCR/D110 and pointed to corresponding biological pathways related to lipid metabolism, olfactory reception, and also immunological status.This project has received funding from the European Union‘s Seventh Framework Programme for research, technological development and demonstration as part of the ECO-FCE project under grant agreement No. 311794

The axon-myelin unit in development and degenerative disease

Axons are electrically excitable, cable-like neuronal processes that relay information between neurons within the nervous system and between neurons and peripheral target tissues. In the central and peripheral nervous systems, most axons over a critical diameter are enwrapped by myelin, which reduces internodal membrane capacitance and facilitates rapid conduction of electrical impulses. The spirally wrapped myelin sheath, which is an evolutionary specialisation of vertebrates, is produced by oligodendrocytes and Schwann cells; in most mammals myelination occurs during postnatal development and after axons have established connection with their targets. Myelin covers the vast majority of the axonal surface, influencing the axon's physical shape, the localisation of molecules on its membrane and the composition of the extracellular fluid (in the periaxonal space) that immerses it. Moreover, myelinating cells play a fundamental role in axonal support, at least in part by providing metabolic substrates to the underlying axon to fuel its energy requirements. The unique architecture of the myelinated axon, which is crucial to its function as a conduit over long distances, renders it particularly susceptible to injury and confers specific survival and maintenance requirements. In this review we will describe the normal morphology, ultrastructure and function of myelinated axons, and discuss how these change following disease, injury or experimental perturbation, with a particular focus on the role the myelinating cell plays in shaping and supporting the axon

Beyond Money and Grantmaking: The Emerging Role of Community Foundations

Content pending

Crystallographic preferred orientations of exhumed subduction channel rocks from the Eclogite Zone of the Tauern Window (Eastern Alps, Austria), and implications on rock elastic anisotropies at great depths

Highlights • Analysis of crystallographic preferred orientations of high-pressure polymineralic rocks by time-of-flight neutron diffraction • Elastic properties of a complete set of subduction channel rocks calculated from their crystallographic preferred orientation • Vp/Vs ratio and P-wave anisotropy of eclogites and metasediments • Influence of eclogite retrogression during exhumation on their elastic properties • Evaluation of the seismic signature of both clastic and carbonate sediments in subduction channels Abstract Crystallographic preferred orientations (CPO) of rocks from an exhumed subduction channel of the Alpine orogen were determined using time-of-flight neutron diffraction. This method allows the investigation of large polymineralic samples and, more importantly, the application of full pattern fit methods to constrain CPOs of mineralogically complex rocks. Samples studied include intensely deformed fresh and retrogressed eclogites, as well as metasediments, which are interleaved with the eclogites in the subduction channel. From the CPO, seismic properties of the samples were calculated. P- wave anisotropies of the eclogite samples are fairly low, with an average of about 1.5%, and mainly constrained by pronounced omphacite CPO. Growth and deformation of retrograde amphibole in the eclogites also led to a pronounced CPO, which has a large impact on seismic anisotropies by raising them to up to 3.7% and changing the orientations of velocity maxima. Elastic anisotropies of the subducted metasediments are higher (up to 7.4%) and constrained by quartz and mica CPO in clastics and by calcite CPO in marble. VP/VS ratios may help to distinguish fresh eclogites from retrogressed ones, and both rock types from mantle peridotites of downgoing lithospheric slabs in seismic imaging. Our data also indicate that subducted terrigenous sediments are not only strongly anisotropic, but also have low VP/VS ratios. This way there may be potential to image them by seismic tomography at depth in active subduction channels