28 research outputs found

    Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

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    Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies

    Moult cycle specific differential gene expression profiling of the crab Portunus pelagicus

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    Background: Crustacean moulting is a complex process involving many regulatory pathways. A holistic approach to examine differential gene expression profiles of transcripts relevant to the moulting process, across all moult cycle stages, was used in this study. Custom cDNA microarrays were constructed for Portunus pelagicus. The printed arrays contained 5000 transcripts derived from both the whole organism, and from individual organs such as the brain, eyestalk, mandibular organ and Y-organ from all moult cycle stages.Results: A total of 556 clones were sequenced from the cDNA libraries used to construct the arrays. These cDNAs represented 175 singletons and 62 contigs, resulting in 237 unique putative genes. The gene sequences were classified into the following biological functions: cuticular proteins associated with arthropod exoskeletons, farnesoic acid O-methyltransferase (FaMeT), proteins belonging to the hemocyanin gene family, lectins, proteins relevant to lipid metabolism, mitochondrial proteins, muscle related proteins, phenoloxidase activators and ribosomal proteins. Moult cycle-related differential expression patterns were observed for many transcripts. Of particular interest were those relating to the formation and hardening of the exoskeleton, and genes associated with cell respiration and energy metabolism.Conclusions: The expression data presented here provide a chronological depiction of the molecular events associated with the biological changes that occur during the crustacean moult cycle. Tracing the temporal expression patterns of a large variety of transcripts involved in the moult cycle of P. pelagicus can provide a greater understanding of gene function, interaction, and regulation of both known and new genes with respect to the moulting process

    Dynamically Integrating Knowledge in Teams: Transforming Resources into Performance

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    In knowledge-based environments, teams must develop a systematic approach to integrating knowledge resources throughout the course of projects in order to perform effectively. Yet, many teams fail to do so. Drawing on the resource-based view of the firm, we examine how teams can develop a knowledge-integration capability to dynamically integrate members‘ resources into higher performance. We distinguish among three sets of resources: relational, experiential, and structural, and propose that they differentially influence a team‘s knowledge-integration capability. We test our theoretical framework using data on knowledge workers in professional services, and discuss implications for research and practice

    Nd and Sr isotopes in the Aleutians: multicomponent parenthood of island-arc magmas

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    Young volcanic rocks from different sections of the Aleutian Islands-Alaska Peninsula Arc have been measured for ^(87)Sr/^(86)Sr, ^(143)Nd/^(144)Nd and some trace elements. We found the ^(143)Nd/^(144)Nd to be highly restricted in range (ɛ_(Nd)=6 to 7) and low as compared to midocean ridge basalts (MORB). This indicates that the source of the Aleutian Arc magmas is different from MORB and remarkably isotopically homogeneous with respect to Nd. The range reported here for arc rocks is substantially smaller than found by other workers. However, the Sr isotope ratios vary considerably (ɛ_(Sr)=−24 to −14). Those samples from small volcanic centers north of the main arc (second arc) are characterized by low ɛ_(Sr). Our data in combination with previous studies suggest that there are slight geochemical differences between discrete sections of the arc. The general uniformity of Nd isotope ratios are thought to be the surface expression of an efficient mixing or homogenization process beneath the arc plate, but which still causes a wide dispersion in Sr isotopic composition. To relate the arc rocks to the broader tectonic setting and to identify possible sources of arc magmas, measurements were done on volcanic and sedimentary rocks from the North Pacific/Bering Sea area. Alkali basalts from the back-arc islands St. George, Nunivak and St. Lawrence and alkali-rich tholeiites from the fore-arc have ɛ_(Nd)=+4 to +9 and are correlated on the ɛ_(Sr)-ɛ_(Nd)diagram parallel to the mantle array but shifted to lower ɛ_(Sr). These samples are thought to be isotopically representative of the mantle transported to that region. A tholeiitic basalt from the Kamchatka Basin ocean floor (back-arc), however, yielded typical MORB values (ɛ_(Nd)=10, ɛ_(Sr)=−24). Composite sediment samples were made from DSDP cores in the Aleutian Abyssal Plain, Gulf of Alaska and the Alka Basin which represent mixtures of continentally and arc-derived materials. These composites have intermediate Nd isotopic (ɛ_(Nd)= −2 and +2) and high Sr isotopic values (ɛ_(Sr)=+9 and +37). These data show that possible source materials of the Aleutian Arc volcanics are isotopically different from and much more heterogeneous than the arc rocks themselves. On the basis of this study and of literature data, we developed a set of alternative models for volcanic arc magma generation, based on the restricted range in ɛ_(Nd) and the wider range in ɛ_(Sr) for arc rocks. Different isotopic and trace element characteristics found in different arcs or arc sections are explained by varying mixing proportions or concentrations in source materials. The basic observations require rather strict mixing ratios to obtain constant ɛ_(Nd). The preferred model is one where the melting of subducted oceanic crust is controlled by the amount of trapped sediment with the melting restricted to the upper part of the altered basaltic layer. Homogenization within the upper part of the oceanic crust is brought about by hydrothermal circulation attending dewatering of the slab during subduction and possibly some oxygen exchange of the magmas on ascent

    Einsatz von Flachs in Reibbelaegen. Teilprojekt 1: Entwicklung und Erprobung von Verfahren zur chemischen und thermischen Vorbebandlung von Flachsfasern fuer den Einsatz in Brems- und Kupplungsbelaegen Abschlussbericht

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    Several methods for chemical and thermal treatment of flax fibres are developed: dry, wet, thermal, and oxidation process. The appropriate techniques are established. Scaling up to production size is possible, and is being realized in 2 cases. The aim was to produce technical fibres of constant quality and to modify yarns starting from flax raw material. Application is planned as reinforcement and process fibres in pressed disk and drum brake linings as well as in pressed and coiled clutch facings for cars, trucks, rail vehicles, and industrial devices. During the project pilot plants were designed and built for the a.m. processes. These were used to produce series of differently modified flax short fibres and yarns which were delivered to the project partners. Based on the requirements and the feed-back of the manufacturers and on accompanying laboratory research pilot plants and techniques have been optimized. Several fibre types from the SETRALIT "t"r"a"d"e"m"a"r"k FT, FNT, and FG series are technically, ecologically, and economically advantageous when used in friction linings as a substitute for asbestos and synthetic fibres. Mixtures of SETRALIT with aramides may be used, too. Use of standard friction linings containing flax fibres in the automative and other industries can be expected in the medium term. The SETRALIT procedures can be applied on all plant fibres like hemp, sisal etc., and are suitable for manufacturing technical short fibres used in other industrial sectors (e.g. construction materials, plastics, gaskets). (orig.)Available from TIB Hannover: F95B373 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

    Umweltfreundliche Aufbereitung von Altpapier durch Schalleinsatz Abschlussbericht

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    SIGLEAvailable from TIB Hannover: F02B561 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman
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