HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed in individually microdissected Globus pallidus neurons (Preliminary analysis)

We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved

A phylomedicine approach to understanding the evolution of auditory sensory perception and disease in mammals

Hereditary deafness affects 0.1% of individuals globally and is considered as one of the most debilitating diseases of man. Despite recent advances, the molecular basis of normal auditory function is not fully understood and little is known about the contribution of single-nucleotide variations to the disease. Using cross-species comparisons of 11 'deafness' genes (Myo15, Ush1g, Strc, Tecta, Tectb, Otog, Col11a2, Gjb2, Cldn14, Kcnq4, Pou3f4) across 69 evolutionary and ecologically divergent mammals, we elucidated whether there was evidence for: (i) adaptive evolution acting on these genes across mammals with similar hearing capabilities; and, (ii) regions of long-term evolutionary conservation within which we predict disease-associated mutations should occur. We find evidence of adaptive evolution acting on the eutherian mammals in Myo15, Otog and Tecta. Examination of selection pressures in Tecta and Pou3f4 across a taxonomic sample that included a wide representation of auditory specialists, the bats, did not uncover any evidence for a role in echolocation. We generated ‘conservation indices' based on selection estimates at nucleotide sites and found that known disease mutations fall within sites of high evolutionary conservation. We suggest that methods such as this, derived from estimates of evolutionary conservation using phylogenetically divergent taxa, will help to differentiate between deleterious and benign mutations

Electroweak Baryogenesis: Concrete in a SUSY Model with a Gauge Singlet

SUSY models with a gauge singlet easily allow for a strong first order electroweak phase transition (EWPT) if the vevs of the singlet and Higgs fields are of comparable size. We discuss the profile of the stationary expanding bubble wall and CP-violation in the effective potential, in particular transitional CP-violation inside the bubble wall during the EWPT. The dispersion relations for charginos contain CP-violating terms in the WKB approximation. These enter as source terms in the Boltzmann equations for the (particle--antiparticle) chemical potentials and fuel the creation of a baryon asymmetry through the weak sphaleron in the hot phase. This is worked out for concrete parameters.Comment: 46 pages, LaTeX, 11 figures, discussion of source terms and transport equations modified, version to appear in Nucl. Phys.

Lepton Electric Dipole Moments in Non-Degenerate Supersymmetric Seesaw Models

In the context of supersymmetric seesaw models of neutrino masses with non-degenerate heavy neutrinos, we show that Dirac Yukawa interactions N^c_i (Y_nu)_{ij} L_j H_2 induce large threshold corrections to the slepton soft masses via renormalization. While still yielding rates for lepton-flavour-violating processes below the experimental bounds, these contributions may increase the muon and electron electric dipole moments d_mu and d_e by several orders of magnitude. In the leading logarithmic approximation, this is due to three additional physical phases in Y_nu, one of which also contributes to leptogenesis. The naive relation d_mu/d_e\approx -m_mu/m_e is violated strongly in the case of successful phenomenological textures for Y_nu, and the values of d_mu and/or d_e may be within the range of interest for the future experiments.Comment: 16page. Some references are adde

CP Violation, Higgs Couplings, and Supersymmetry

Supersymmetric extensions of the standard model generically contain additional sources of CP violation. We discuss how at one loop a potentially large CP violating coupling of the lightest Higgs, h^0, to leptons is induced in the minimal supersymmetric standard model (MSSM). The CP violating couplings of h^0 in extensions of the MSSM, such as the next-to-minimal supersymmetric standard model (NMSSM) are also considered. We indicate how this CP violation might be observed; in particular a polarization-dependent production asymmetry, in the context of a muon collider, provides a means to access this coupling cleanly. In the MSSM, existing limits on the electric dipole moment (EDM) of the electron, coupled with standard universality assumptions, severly constrains any such signal. Nevertheless, extensions of the MSSM, such as the NMSSM, allow CP-violating signals as large as 100%.Comment: 13 pages LaTeX, 4 figures (some typos fixed, discussion clarified

The Buffer Gas Beam: An Intense, Cold, and Slow Source for Atoms and Molecules

Beams of atoms and molecules are stalwart tools for spectroscopy and studies of collisional processes. The supersonic expansion technique can create cold beams of many species of atoms and molecules. However, the resulting beam is typically moving at a speed of 300-600 m/s in the lab frame, and for a large class of species has insufficient flux (i.e. brightness) for important applications. In contrast, buffer gas beams can be a superior method in many cases, producing cold and relatively slow molecules in the lab frame with high brightness and great versatility. There are basic differences between supersonic and buffer gas cooled beams regarding particular technological advantages and constraints. At present, it is clear that not all of the possible variations on the buffer gas method have been studied. In this review, we will present a survey of the current state of the art in buffer gas beams, and explore some of the possible future directions that these new methods might take

Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection

Inverse Current Source Density Method in Two Dimensions: Inferring Neural Activation from Multielectrode Recordings

The recent development of large multielectrode recording arrays has made it affordable for an increasing number of laboratories to record from multiple brain regions simultaneously. The development of analytical tools for array data, however, lags behind these technological advances in hardware. In this paper, we present a method based on forward modeling for estimating current source density from electrophysiological signals recorded on a two-dimensional grid using multi-electrode rectangular arrays. This new method, which we call two-dimensional inverse Current Source Density (iCSD 2D), is based upon and extends our previous one- and three-dimensional techniques. We test several variants of our method, both on surrogate data generated from a collection of Gaussian sources, and on model data from a population of layer 5 neocortical pyramidal neurons. We also apply the method to experimental data from the rat subiculum. The main advantages of the proposed method are the explicit specification of its assumptions, the possibility to include system-specific information as it becomes available, the ability to estimate CSD at the grid boundaries, and lower reconstruction errors when compared to the traditional approach. These features make iCSD 2D a substantial improvement over the approaches used so far and a powerful new tool for the analysis of multielectrode array data. We also provide a free GUI-based MATLAB toolbox to analyze and visualize our test data as well as user datasets

Robotic neurorehabilitation: a computational motor learning perspective

Conventional neurorehabilitation appears to have little impact on impairment over and above that of spontaneous biological recovery. Robotic neurorehabilitation has the potential for a greater impact on impairment due to easy deployment, its applicability across of a wide range of motor impairment, its high measurement reliability, and the capacity to deliver high dosage and high intensity training protocols