345 research outputs found

    Brain serotonin critically contributes to the biological effects of electroconvulsive seizures

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    Compounds targeting serotonin (5-HT) are widely used as antidepressants. However, the role of 5-HT in mediating the effects of electroconvulsive seizure (ECS) therapy remains undefined. Using Tph2(-/-) mice depleted of brain 5-HT, we studied the effects of ECS on behavior and neurobiology. ECS significantly prolonged the start latency in the elevated O-Maze test, an effect that was abolished in Tph2(-/-) mice. Furthermore, in the absence of 5-HT, the ECS-induced increase in adult neurogenesis and in brain-derived neurotrophic factor signaling in the hippocampus were significantly reduced. Our results indicate that brain 5-HT critically contributes to the neurobiological responses to ECS

    Probing structural relaxation in complex fluids by critical fluctuations

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    Complex fluids, such as polymer solutions and blends, colloids and gels, are of growing interest in fundamental and applied soft-condensed-matter science. A common feature of all such systems is the presence of a mesoscopic structural length scale intermediate between atomic and macroscopic scales. This mesoscopic structure of complex fluids is often fragile and sensitive to external perturbations. Complex fluids are frequently viscoelastic (showing a combination of viscous and elastic behaviour) with their dynamic response depending on the time and length scales. Recently, non-invasive methods to infer the rheological response of complex fluids have gained popularity through the technique of microrheology, where the diffusion of probe spheres in a viscoelastic fluid is monitored with the aid of light scattering or microscopy. Here we propose an alternative to traditional microrheology that does not require doping of probe particles in the fluid (which can sometimes drastically alter the molecular environment). Instead, our proposed method makes use of the phenomenon of "avoided crossing" between modes associated with the structural relaxation and critical fluctuations that are spontaneously generated in the system.Comment: 4 pages, 4 figure

    Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions

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    Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression

    Finite-temperature correlations in the one-dimensional trapped and untrapped Bose gases

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    We calculate the dynamic single-particle and many-particle correlation functions at non-zero temperature in one-dimensional trapped repulsive Bose gases. The decay for increasing distance between the points of these correlation functions is governed by a scaling exponent that has a universal expression in terms of observed quantities. This expression is valid in the weak-interaction Gross-Pitaevskii as well as in the strong-interaction Girardeau-Tonks limit, but the observed quantities involved depend on the interaction strength. The confining trap introduces a weak center-of-mass dependence in the scaling exponent. We also conjecture results for the density-density correlation function.Comment: 18 pages, Latex, Revtex

    Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase

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    Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/- hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency

    Momentum distribution and correlation function of quasicondensates in elongated traps

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    We calculate the spatial correlation function and momentum distribution of a phase-fluctuating, elongated three-dimensional condensate, in a trap and in free expansion. We take the inhomogeneous density profile into account {\it{via}} a local density approximation. We find an almost Lorentzian momentum distribution, in stark contrast with a Heisenberg-limited Thomas-Fermi condensate.Comment: 5 pages, 2 figures; final version, references update

    TURBOMOLE: Modular program suite for ab initio quantum-chemical and condensed-matter simulations

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    TURBOMOLE is a collaborative, multi-national software development project aiming to provide highly efficient and stable computational tools for quantum chemical simulations of molecules, clusters, periodic systems, and solutions. The TURBOMOLE software suite is optimized for widely available, inexpensive, and resource-efficient hardware such as multi-core workstations and small computer clusters. TURBOMOLE specializes in electronic structure methods with outstanding accuracy–cost ratio, such as density functional theory including local hybrids and the random phase approximation (RPA), GW-Bethe–Salpeter methods, second-order Møller–Plesset theory, and explicitly correlated coupled-cluster methods. TURBOMOLE is based on Gaussian basis sets and has been pivotal for the development of many fast and low-scaling algorithms in the past three decades, such as integral-direct methods, fast multipole methods, the resolution-of-the-identity approximation, imaginary frequency integration, Laplace transform, and pair natural orbital methods. This review focuses on recent additions to TURBOMOLE’s functionality, including excited-state methods, RPA and Green’s function methods, relativistic approaches, high-order molecular properties, solvation effects, and periodic systems. A variety of illustrative applications along with accuracy and timing data are discussed. Moreover, available interfaces to users as well as other software are summarized. TURBOMOLE’s current licensing, distribution, and support model are discussed, and an overview of TURBOMOLE’s development workflow is provided. Challenges such as communication and outreach, software infrastructure, and funding are highlighted
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