436 research outputs found

    Examining a Hypothyroid Model of Depressive Symptoms in Mice: Tests of Behavioral Measures

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    There is abundant evidence suggesting that Major Depressive Disorder (MDD) is closely related to thyroid hormone (TH) function, but the exact nature of this relationship is poorly defined in the literature. The present study examined whether hypothyroidism could viably model symptoms of MDD in mice using established behavioral paradigms. It was expected that hypothyroidism would produce anhedonia-like behavior in the saccharin preference test, anxiety-like behavior in the elevated plus maze, and spatial memory impairment in the object placement task. C57BL/6J mice were randomly assigned to one of three groups, which received either a control diet, diet infused with 6-propyl-2-thiouracil (hypothyroid group), or a combination of 6-propyl-2-tiouracil and thyroxine (hyperthyroid group). Each group had ad libitum access to food and water for 4 weeks prior to behavioral assessment. Contrary to our hypothesis, hypothyroid mice did not exhibit more anhedonia or greater spatial memory impairment than controls. However, they did spend a significantly lower percentage of time in the open arms of the elevated plus-maze compared to both the control and hyperthyroid groups. Additionally, hyperthyroidism was associated with increased preference for sweetened water over tap water in the saccharin preference test. These findings raise interesting questions about how TH could regulate specific components of the depressive phenotype, which will be discussed at length. This project also lays the groundwork for a larger investigation of glutamate neurotransmission in hypothyroidism-induced depression. As a future extension of this research, AMPA receptor binding will be examined in the obtained cortical and hippocampal tissue so that relationships between depressive behaviors, thyroid status, and glutamatergic activity can be explored in a truly integrated fashion

    Evidence for a Finite Temperature Insulator

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    In superconductors the zero-resistance current-flow is protected from dissipation at finite temperatures (T) by virtue of the short-circuit condition maintained by the electrons that remain in the condensed state. The recently suggested finite-T insulator and the "superinsulating" phase are different because any residual mechanism of conduction will eventually become dominant as the finite-T insulator sets-in. If the residual conduction is small it may be possible to observe the transition to these intriguing states. We show that the conductivity of the high magnetic-field insulator terminating superconductivity in amorphous indium-oxide exhibits an abrupt drop, and seem to approach a zero conductance at T<0.04 K. We discuss our results in the light of theories that lead to a finite-T insulator

    Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

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    Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a "proof of concept clinical trial" further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18:3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-alpha, IL-1 beta) was increased and anti-inflammatory TGF-beta markedly decreased with loss of membrane n-6 fatty acids linoleic (18:2n-6) and arachidonic acids (20:4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-beta, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS

    The impact of ischemic stroke on connectivity gradients

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    The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke

    The role of science in physical natural hazard assessment : report to the UK Government by the Natural Hazard Working Group

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    Following the tragic Asian tsunami on 26 December 2004, the Prime Minister asked the Government’s Chief Scientific Adviser, Sir David King, to convene a group of experts (the Natural Hazard Working Group) to advise on the mechanisms that could and should be established for the detection and early warning of global physical natural hazards. 2. The Group was asked to examine physical hazards which have high global or regional impact and for which an appropriate early warning system could be put in place. It was also asked to consider the global natural hazard frameworks currently in place and under development and their effectiveness in using scientific evidence; to consider whether there is an existing appropriate international body to pull together the international science community to advise governments on the systems that need to be put in place, and to advise on research needed to fill current gaps in knowledge. The Group was asked to make recommendations on whether a new body was needed, or whether other arrangements would be more effective

    Service-Oriented Multigranular Optical Network Architecture for Clouds

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    This paper presents a novel service-oriented network architecture to bridge the informational gap between user applications and optical networks providing technology-agnostic multigranular optical network services for clouds. A mediation layer (service plane) between user applications and network control is proposed to facilitate a mapping process between user application requests and the network services. At the network level, a multigranular optical network (MGON) is proposed and implemented to support dynamic wavelength and subwavelength granularities with different transport formats [optical burst switched (OBS), optical burst transport (OBT)], reservation protocols (one-way, two-way), and different quality-of-service (QoS) levels per service type. The service-oriented multigranular optical network has been designed, implemented, and demonstrated on an experimental testbed. The testbed consists of service and network resource provisioning, service abstraction, and network resource virtualization. The service-to-network interoperation is provided by means of a gateway that maps service requests to technology-specific parameters and a common signaling channel for both service and network resource provisioning

    Connectivity Concordance Mapping: A New Tool for Model-Free Analysis of fMRI Data of the Human Brain

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    Functional magnetic resonance data acquired in a task-absent condition (“resting state”) require new data analysis techniques that do not depend on an activation model. Here, we propose a new analysis method called Connectivity Concordance Mapping (CCM). The main idea is to assign a label to each voxel based on the reproducibility of its whole-brain pattern of connectivity. Specifically, we compute the correlations of time courses of each voxel with every other voxel for each measurement. Voxels whose correlation pattern is consistent across measurements receive high values. The result of a CCM analysis is thus a voxel-wise map of concordance values. Regions of high inter-subject concordance can be assumed to be functionally consistent, and may thus be of specific interest for further analysis. Here we present two fMRI studies to demonstrate the possible applications of the algorithm. The first is a eyes-open/eyes-closed paradigm designed to highlight the potential of the method in a relatively simple domain. The second study is a longitudinal repeated measurement of a patient following stroke. Longitudinal clinical studies such as this may represent the most interesting domain of applications for this algorithm
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