378 research outputs found

    Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

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    The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

    WIMP-nucleus scattering in chiral effective theory

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    We discuss long-distance QCD corrections to the WIMP-nucleon(s) interactions in the framework of chiral effective theory. For scalar-mediated WIMP-quark interactions, we calculate all the next-to-leading-order corrections to the WIMP-nucleus elastic cross-section, including two-nucleon amplitudes and recoil-energy dependent shifts to the single-nucleon scalar form factors. As a consequence, the scalar-mediated WIMP-nucleus cross-section cannot be parameterized in terms of just two quantities, namely the neutron and proton scalar form factors at zero momentum transfer, but additional parameters appear, depending on the short-distance WIMP-quark interaction. Moreover, multiplicative factorization of the cross-section into particle, nuclear and astro-particle parts is violated. In practice, while the new effects are of the natural size expected by chiral power counting, they become very important in those regions of parameter space where the leading order WIMP-nucleus amplitude is suppressed, including the so-called "isospin-violating dark matter" regime. In these regions of parameter space we find order-of-magnitude corrections to the total scattering rates and qualitative changes to the shape of recoil spectra.Comment: 23 pages, 6 figures, 1 tabl

    Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

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    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions

    Zeros of the W_L Z_L -> W_L Z_L amplitude: where vector resonances stand

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    A Higgsless electroweak theory may be populated by spin-1 resonances around E ~ 1TeV as a consequence of a new strong interacting sector, frequently proposed as a tool to smear the high-energy behaviour of scattering amplitudes, for instance, elastic gauge boson scattering. Information on those resonances, if they exist, must be contained in the low-energy couplings of the electroweak chiral effective theory. Using the facts that: i) the scattering of longitudinal gauge bosons, W_L, Z_L, can be well described in the high-energy region E >> M_W by the scattering of the corresponding Goldstone bosons (equivalence theorem) and ii) the zeros of the scattering amplitude carry the information on the heavier spectrum that has been integrated out; we employ the O(p^4) electroweak chiral Lagrangian to identify the parameter space region of the low-energy couplings where vector resonances may arise. An estimate of their masses is also provided by our method.Comment: 10 pages, 4 figure

    Measuring every particle's size from three-dimensional imaging experiments

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    Often experimentalists study colloidal suspensions that are nominally monodisperse. In reality these samples have a polydispersity of 4-10%. At the level of an individual particle, the consequences of this polydispersity are unknown as it is difficult to measure an individual particle size from microscopy. We propose a general method to estimate individual particle radii within a moderately concentrated colloidal suspension observed with confocal microscopy. We confirm the validity of our method by numerical simulations of four major systems: random close packing, colloidal gels, nominally monodisperse dense samples, and nominally binary dense samples. We then apply our method to experimental data, and demonstrate the utility of this method with results from four case studies. In the first, we demonstrate that we can recover the full particle size distribution {\it in situ}. In the second, we show that accounting for particle size leads to more accurate structural information in a random close packed sample. In the third, we show that crystal nucleation occurs in locally monodisperse regions. In the fourth, we show that particle mobility in a dense sample is correlated to the local volume fraction.Comment: 7 pages, 5 figure

    Random Matrix Theory for the Hermitian Wilson Dirac Operator and the chGUE-GUE Transition

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    We introduce a random two-matrix model interpolating between a chiral Hermitian (2n+nu)x(2n+nu) matrix and a second Hermitian matrix without symmetries. These are taken from the chiral Gaussian Unitary Ensemble (chGUE) and Gaussian Unitary Ensemble (GUE), respectively. In the microscopic large-n limit in the vicinity of the chGUE (which we denote by weakly non-chiral limit) this theory is in one to one correspondence to the partition function of Wilson chiral perturbation theory in the epsilon regime, such as the related two matrix-model previously introduced in refs. [20,21]. For a generic number of flavours and rectangular block matrices in the chGUE part we derive an eigenvalue representation for the partition function displaying a Pfaffian structure. In the quenched case with nu=0,1 we derive all spectral correlations functions in our model for finite-n, given in terms of skew-orthogonal polynomials. The latter are expressed as Gaussian integrals over standard Laguerre polynomials. In the weakly non-chiral microscopic limit this yields all corresponding quenched eigenvalue correlation functions of the Hermitian Wilson operator.Comment: 27 pages, 4 figures; v2 typos corrected, published versio

    Acute febrile illness is associated with Rickettsia spp infection in dogs

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    BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR
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