479 research outputs found

    Critical test of multi-{\it j} supersymmetries from magnetic moment measurements

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    Magnetic moment measurements in odd nuclei directly probe the distribution of fermion states and hence provide one of the most critical tests for multi-jj supersymmetries in collective nuclei. Due to complexity of calculations and lack of data, such tests have not been performed in the past. Using the Mathematica software, we derive analytic expressions for magnetic moments in the SO(BF)(6)×SU(F)(2)SO^{(BF)}(6) \times SU^{(F)}(2) limit of the U(6/12)U(6/12) supersymmetry and compare the results with recent measurements in 195^{195}Pt.Comment: 10 pages with 1 figur

    Caspase-1 Dependent IL-1β Secretion Is Critical for Host Defense in a Mouse Model of Chlamydia pneumoniae Lung Infection

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    Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1β rescues CP infected Caspase-1−/− mice from mortality, indicating that IL-1β secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1β secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation

    Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

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    Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

    Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

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    The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

    ReCROP: bioinocula and CROPping systems: an integrated biotechnological approach for improving crop yield, biodiversity and REsilience of Mediterranean agro-ecosystems

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    The Mediterranean economy is highly dependent on agriculture. However, agricultural sustainability and productivity in this region is under serious threat due to climate change and the depletion of water resources. This is worsened by poor management practices, such as the overuse of chemical fertilizers, pesticides, overgrazing and monoculture farming. Recent climate change models indicate that European and Northern African regions will undergo extreme climatic events throughout the year, this will negatively impact crop yield and productivity. Summer droughts and heat waves periods will increase for most parts of Europe, as well as short intense rain events. Preserving and improving productive agricultural land in this region is vital, especially through the application of sustainable soil and crop management practices that promote soil fertility and water conservation; this will improve resilience to degradation and to extreme climatic events. ReCROP is a European project that aims to identify sustainable and resilient agricultural production systems in the Mediterranean region through the combined use of biotechnological tools, such as bioinoculants, and environmentally friendly agronomic practices. ReCROP will assess different agroecosystems with key local crops (i.e vineyards, maize and aromatic/medicinal plants) of the Mediterranean region under field conditions to help improve crop resilience, yield, water conservation and soil health under the current scenario of climate change. Soil organisms play a key role in ecosystem processes, leading to essential soil functions and are used as bioindicators of soil quality. Their monitoring is crucial to assess the impact of beneficial agricultural practices on soil functioning. One of the goals of ReCROP will be to evaluate the beneficial impact of different agricultural practices on the structural and functional soil diversity at different levels of the soil food web. The macrofauna and mesofauna (i.e springtails and mites) as well as microbial biomass, activity and biodiversity of soil microbial communities (bacteria, archaea, fungi) will be monitored with a special effort to produce a multitaxa index of soil biological quality. This work will contribute to identify which practices are beneficial for the biodiversity of Mediterranean agricultural soils, thus providing resistance and resilience, in terms of soil functioning and against soil disturbances.info:eu-repo/semantics/publishedVersio

    Insulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77

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    OBJECTIVE: Nur77 is an orphan nuclear receptor with pleotropic functions. Previous studies have identified Nur77 as a transcriptional regulator of glucose utilization genes in skeletal muscle and gluconeogenesis in liver. However, the net functional impact of these pathways is unknown. To examine the consequence of Nur77 signaling for glucose metabolism in vivo, we challenged Nur77 null mice with high-fat feeding. RESEARCH DESIGN AND METHODS: Wild-type and Nur77 null mice were fed a high-fat diet (60% calories from fat) for 3 months. We determined glucose tolerance, tissue-specific insulin sensitivity, oxygen consumption, muscle and liver lipid content, muscle insulin signaling, and expression of glucose and lipid metabolism genes. RESULTS: Mice with genetic deletion of Nur77 exhibited increased susceptibility to diet-induced obesity and insulin resistance. Hyperinsulinemic-euglycemic clamp studies revealed greater high-fat diet–induced insulin resistance in both skeletal muscle and liver of Nur77 null mice compared with controls. Loss of Nur77 expression in skeletal muscle impaired insulin signaling and markedly reduced GLUT4 protein expression. Muscles lacking Nur77 also exhibited increased triglyceride content and accumulation of multiple even-chained acylcarnitine species. In the liver, Nur77 deletion led to hepatic steatosis and enhanced expression of lipogenic genes, likely reflecting the lipogenic effect of hyperinsulinemia. CONCLUSIONS: Collectively, these data demonstrate that loss of Nur77 influences systemic glucose metabolism and highlight the physiological contribution of muscle Nur77 to this regulatory pathway.National Institutes of Health (HD-00850, DK-081683-01, DK-30425, HL030568); American Diabetes Associatio

    A novel approach to measure mitochondrial respiration in frozen biological samples.

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    Respirometry is the gold standard measurement of mitochondrial oxidative function, as it reflects the activity of the electron transport chain complexes working together. However, the requirement for freshly isolated mitochondria hinders the feasibility of respirometry in multi-site clinical studies and retrospective studies. Here, we describe a novel respirometry approach suited for frozen samples by restoring electron transfer components lost during freeze/thaw and correcting for variable permeabilization of mitochondrial membranes. This approach preserves 90-95% of the maximal respiratory capacity in frozen samples and can be applied to isolated mitochondria, permeabilized cells, and tissue homogenates with high sensitivity. We find that primary changes in mitochondrial function, detected in fresh tissue, are preserved in frozen samples years after collection. This approach will enable analysis of the integrated function of mitochondrial Complexes I to IV in one measurement, collected at remote sites or retrospectively in samples residing in tissue biobanks

    Dynamic modeling of the reactive twin-screw co-rotating extrusion process: experimental validation by using inlet glass fibers injection response and application to polymers degassing

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    International audienceIn this paper is described an original dynamic model of a reactive co-rotating twinscrew extrusion (TSE) process operated by the Rhodia company for the Nylon-66 degassing finishing step. In order to validate the model, dynamic experiments have been performed on a small-scale pilot plant. These experiments consist in a temporary injection of glass fibers at the inlet of the extruder after it has reached a given operating point. The outlet glass fibers mass fraction time variation is then measured. This experiment does not lead to the RTD measurement. As a matter of fact, due to the high quantity of glass fibers that is introduced, the behavior of the flow through the extruder is perturbed so that the glass fibers cannot be considered as an inert tracer. The dynamic model that we have published elsewhere (Choulak et al., Ind. Eng. Chem. Res., 2004, 43(23), 7373-7382) is adapted to take into account this nonlinear behavior of the extruder with respect to the glass fibers injection and is favorably compared to experimental results. The description of the degassing operation is also included in the model. The model allows simulations of the complete dynamic behavior of the process. When the steady state is reached, the good position of the degassing vent with respect to the partially and fully filled zones positions can also be checked, thus illustrating the way the model can be used for design purposes

    ÉTUDE EXPÉRIMENTALE ET THÉORIQUE DES NOYAUX DE TRANSITION 68,70,72,74Ge

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    Les isotopes de 68,70,72,74Ge ont été étudiés avec une haute résolution en énergie au moyen de la réaction (p, t). Un grand nombre de nouveaux niveaux 0+, 2+ et 4+ à basse énergie ont été mis en évidence. Des calculs semi-microscopiques de surfaces d'énergie potentielle et de spectres ont été effectués et des conclusions sont données sur la structure des noyaux Ge

    Leaf yellowing of the wheat cultivar Mace in the absence of yellowspot disease

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    The wheat variety Mace is currently dominating the southern wheat growing regions of Australia. It is high yielding in most environments and resistant to many diseases including yellow spot (also known as tan spot). However, observations of foliar yellowing of Mace have recently been reported in the field. This has raised concerns over a possible breakdown of resistance to yellow spot, which is caused by the necrotrophic fungal pathogen Pyrenophora triticirepentis. West Australian field samples of yellowing Mace leaves were evaluated for P. triticirepentis infection, and this pathogen was determined to be absent. Instead, Alternaria spp. were isolated from the wheat leaves. Pathogenicity assays showed that the recovered Alternaria spp. were unable to cause disease symptoms on Mace. Furthermore, spontaneous foliar lesions were observed in Mace grown in the absence of pathogens. It is therefore likely that such yellowing is a physiological trait, which will not respond to fungicide application. A marginal impact on yield cannot be excluded
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