259 research outputs found

    GEIRA: gene-environment and gene–gene interaction research application

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    The GEIRA (Gene-Environment and Gene–Gene Interaction Research Application) algorithm and subsequent program is dedicated to genome-wide gene-environment and gene–gene interaction analysis. It implements concepts of both additive and multiplicative interaction as well as calculations based on dominant, recessive and co-dominant genetic models, respectively. Estimates of interactions are incorporated in a single table to make the output easily read. The algorithm is coded in both SAS and R. GEIRA is freely available to non-commercial users at http://www.epinet.se. Additional information, including user’s manual and example datasets is available online at http://www.epinet.se

    Polynomial super-gl(n) algebras

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    We introduce a class of finite dimensional nonlinear superalgebras L=L0ˉ+L1ˉL = L_{\bar{0}} + L_{\bar{1}} providing gradings of L0ˉ=gl(n)sl(n)+gl(1)L_{\bar{0}} = gl(n) \simeq sl(n) + gl(1). Odd generators close by anticommutation on polynomials (of degree >1>1) in the gl(n)gl(n) generators. Specifically, we investigate `type I' super-gl(n)gl(n) algebras, having odd generators transforming in a single irreducible representation of gl(n)gl(n) together with its contragredient. Admissible structure constants are discussed in terms of available gl(n)gl(n) couplings, and various special cases and candidate superalgebras are identified and exemplified via concrete oscillator constructions. For the case of the nn-dimensional defining representation, with odd generators Qa,QˉbQ_{a}, \bar{Q}{}^{b}, and even generators Eab{E^{a}}_{b}, a,b=1,...,na,b = 1,...,n, a three parameter family of quadratic super-gl(n)gl(n) algebras (deformations of sl(n/1)sl(n/1)) is defined. In general, additional covariant Serre-type conditions are imposed, in order that the Jacobi identities be fulfilled. For these quadratic super-gl(n)gl(n) algebras, the construction of Kac modules, and conditions for atypicality, are briefly considered. Applications in quantum field theory, including Hamiltonian lattice QCD and space-time supersymmetry, are discussed.Comment: 31 pages, LaTeX, including minor corrections to equation (3) and reference [60

    Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination

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    Basic helix-loop-helix transcription factors Olig1 and Olig2 critically regulate oligodendrocyte development. Initially identified as a downstream effector of Olig1, an oligodendrocyte-specific zinc finger transcription repressor, Zfp488, cooperates with Olig2 function. Although Zfp488 is required for oligodendrocyte precursor formation and differentiation during embryonic development, its role in oligodendrogenesis of adult neural progenitor cells is not known. In this study, we tested whether Zfp488 could promote an oligodendrogenic fate in adult subventricular zone (SVZ) neural stem/progenitor cells (NSPCs). Using a cuprizone-induced demyelination model in mice, we examined the effect of retrovirus-mediated Zfp488 overexpression in SVZ NSPCs. Our results showed that Zfp488 efficiently promoted the differentiation of the SVZ NSPCs into mature oligodendrocytes in vivo. After cuprizone-induced demyelination injury, Zfp488-transduced mice also showed significant restoration of motor function to levels comparable to control mice. Together, these findings identify a previously unreported role for Zfp488 in adult oligodendrogenesis and functional remyelination after injury

    Viruses in extreme environments

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    The original publication is available at www.springerlink.comInternational audienceThe tolerance limits of extremophiles in term of temperature, pH, salinity, desiccation, hydrostatic pressure, radiation, anaerobiosis far exceed what can support non-extremophilic organisms. Like all other organisms, extremophiles serve as hosts for viral replication. Many lines of evidence suggest that viruses could no more be regarded as simple infectious ‘‘fragments of life'' but on the contrary as one of the major components of the biosphere. The exploration of niches with seemingly harsh life conditions as hypersaline and soda lakes, Sahara desert, polar environments or hot acid springs and deep sea hydrothermal vents, permitted to track successfully the presence of viruses. Substantial populations of double-stranded DNA virus that can reach 109 particles per milliliter were recorded. All these viral communities, with genome size ranging from 14 kb to 80 kb, seem to be genetically distinct, suggesting specific niche adaptation. Nevertheless, at this stage of the knowledge, very little is known of their origin, activity, or importance to the in situ microbial dynamics. The continuous attempts to isolate and to study viruses that thrive in extreme environments will be needed to address such questions. However, this topic appears to open a new window on an unexplored part of the viral world

    Seroepidemiology of Human Polyomaviruses

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    In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/− 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was ∼2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood

    Sox6 Is Necessary for Efficient Erythropoiesis in Adult Mice under Physiological and Anemia-Induced Stress Conditions

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    BACKGROUND: Definitive erythropoiesis is a vital process throughout life. Both its basal activity under physiological conditions and its increased activity under anemia-induced stress conditions are highly stimulated by the hormone erythropoietin. The transcription factor Sox6 was previously shown to enhance fetal erythropoiesis together and beyond erythropoietin signaling, but its importance in adulthood and mechanisms of action remain unknown. We used here Sox6 conditional null mice and molecular assays to address these questions. METHODOLOGY/PRINCIPAL FINDINGS: Sox6fl/flErGFPCre adult mice, which lacked Sox6 in erythroid cells, exhibited compensated anemia, erythroid cell developmental defects, and anisocytotic, short-lived red cells under physiological conditions, proving that Sox6 promotes basal erythropoiesis. Tamoxifen treatment of Sox6fl/flCaggCreER mice induced widespread inactivation of Sox6 in a timely controlled manner and resulted in erythroblast defects before reticulocytosis, demonstrating that impaired erythropoiesis is a primary cause rather than consequence of anemia in the absence of Sox6. Twenty five percent of Sox6fl/flErGFPCre mice died 4 or 5 days after induction of acute anemia with phenylhydrazine. The others recovered slowly. They promptly increased their erythropoietin level and amplified their erythroid progenitor pool, but then exhibited severe erythroblast and reticulocyte defects. Sox6 is thus essential in the maturation phase of stress erythropoiesis that follows the erythropoietin-dependent amplification phase. Sox6 inactivation resulted in upregulation of embryonic globin genes, but embryonic globin chains remained scarce and apparently inconsequential. Sox6 inactivation also resulted in downregulation of erythroid terminal markers, including the Bcl2l1 gene for the anti-apoptotic factor Bcl-xL, and in vitro assays indicated that Sox6 directly upregulates Bcl2l1 downstream of and beyond erythropoietin signaling. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that Sox6 is necessary for efficient erythropoiesis in adult mice under both basal and stress conditions. It is primarily involved in enhancing the survival rate and maturation process of erythroid cells and acts at least in part by upregulating Bcl2l1

    Observers and Locality in Everett Quantum Field Theory

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    A model for measurement in collapse-free nonrelativistic fermionic quantum field theory is presented. In addition to local propagation and effectively-local interactions, the model incorporates explicit representations of localized observers, thus extending an earlier model of entanglement generation in Everett quantum field theory [M. A. Rubin, Found. Phys. 32, 1495-1523 (2002)]. Transformations of the field operators from the Heisenberg picture to the Deutsch-Hayden picture, involving fictitious auxiliary fields, establish the locality of the model. The model is applied to manifestly-local calculations of the results of measurements, using a type of sudden approximation and in the limit of massive systems in narrow-wavepacket states. Detection of the presence of a spin-1/2 system in a given spin state by a freely-moving two-state observer illustrates the features of the model and the nonperturbative computational methodology. With the help of perturbation theory the model is applied to a calculation of the quintessential "nonlocal" quantum phenomenon, spin correlations in the Einstein-Podolsky-Rosen-Bohm experiment.Comment: Some changes to introduction and discussion sections, typos corrected, conclusions unchanged. To appear in Foundations of Physic
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