Neutralization of chemokines RANTES and MIG increases virus antigen expression and spinal cord pathology during Theiler's virus infection.

The role of chemokines during some viral infections is unpredictable because the inflammatory response regulated by these molecules can have two, contrasting effects-viral immunity and immunopathologic injury to host tissues. Using Theiler's virus infection of SJL mice as a model of this type of disease, we have investigated the roles of two chemokines-regulated on activation, normal T cell-expressed and secreted (RANTES) chemokine and monokine induced by IFN-gamma (MIG)-by treating mice with antisera that block lymphocyte migration. Control, infected mice showed virus persistence, mild inflammation and a small degree of demyelination in the white matter of the spinal cord at 6 weeks post-infection. Treatment of mice with RANTES antiserum starting at 2 weeks post-infection increased both viral antigen expression and the severity of inflammatory demyelination at 6 weeks post-infection. MIG antiserum increased the spread of virus and the proportion of spinal cord white matter with demyelination. Overall, viral antigen levels correlated strongly with the extent of pathology. At the RNA level, high virus expression was associated with low IL-2 and high IL-10 levels, and RANTES antiserum decreased the IL-2/IL-10 ratio. Our results suggest that RANTES and MIG participate in an immune response that attempts to restrict viral expression while limiting immunopathology and that anti-chemokine treatment poses the risk of exacerbating both conditions in the long term

Rectified Gaussian Scale Mixtures and the Sparse Non-Negative Least Squares Problem

In this paper, we develop a Bayesian evidence maximization framework to solve the sparse non-negative least squares (S-NNLS) problem. We introduce a family of probability densities referred to as the Rectified Gaussian Scale Mixture (R- GSM) to model the sparsity enforcing prior distribution for the solution. The R-GSM prior encompasses a variety of heavy-tailed densities such as the rectified Laplacian and rectified Student- t distributions with a proper choice of the mixing density. We utilize the hierarchical representation induced by the R-GSM prior and develop an evidence maximization framework based on the Expectation-Maximization (EM) algorithm. Using the EM based method, we estimate the hyper-parameters and obtain a point estimate for the solution. We refer to the proposed method as rectified sparse Bayesian learning (R-SBL). We provide four R- SBL variants that offer a range of options for computational complexity and the quality of the E-step computation. These methods include the Markov chain Monte Carlo EM, linear minimum mean-square-error estimation, approximate message passing and a diagonal approximation. Using numerical experiments, we show that the proposed R-SBL method outperforms existing S-NNLS solvers in terms of both signal and support recovery performance, and is also very robust against the structure of the design matrix.Comment: Under Review by IEEE Transactions on Signal Processin

Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Quark condensate in one-flavor QCD

We compute the condensate in QCD with a single quark flavor using numerical simulations with the overlap formulation of lattice fermions. The condensate is extracted by fitting the distribution of low lying eigenvalues of the Dirac operator in sectors of fixed topological charge to the predictions of Random Matrix Theory. Our results are in excellent agreement with estimates from the orientifold large-N_c expansion.Comment: 12 pages, 4 figures, REVTeX4, v2: Small changes, extended introduction, published versio

Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI.

ObjectiveCerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI.Methods37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI.ResultsRegression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI.ConclusionsOur results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury