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Search Results: 1 - 10 of 119965 matches for " Harry T Orr "
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Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis
Juan Crespo-Barreto,John D. Fryer,Chad A. Shaw,Harry T. Orr,Huda Y. Zoghbi
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001021
Abstract: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1?/? mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1?/? and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1?/? mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases.
Lithium Therapy Improves Neurological Function and Hippocampal Dendritic Arborization in a Spinocerebellar Ataxia Type 1 Mouse Model
Kei Watase,Jennifer R Gatchel,Yaling Sun,Effat Emamian,Richard Atkinson,Ronald Richman,Hidehiro Mizusawa,Harry T Orr,Chad Shaw,Huda Y Zoghbi
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040182
Abstract: Background Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by progressive motor and cognitive dysfunction. Caused by an expanded polyglutamine tract in ataxin 1 (ATXN1), SCA1 pathogenesis involves a multifactorial process that likely begins with misfolding of ATXN1, which has functional consequences on its interactions, leading to transcriptional dysregulation. Because lithium has been shown to exert neuroprotective effects in a variety of conditions, possibly by affecting gene expression, we tested the efficacy of lithium treatment in a knock-in mouse model of SCA1 (Sca1154Q/2Q mice) that replicates many features of the human disease. Methods and Findings Sca1154Q/2Q mice and their wild-type littermates were fed either regular chow or chow that contained 0.2% lithium carbonate. Dietary lithium carbonate supplementation resulted in improvement of motor coordination, learning, and memory in Sca1154Q/2Q mice. Importantly, motor improvement was seen when treatment was initiated both presymptomatically and after symptom onset. Neuropathologically, lithium treatment attenuated the reduction of dendritic branching in mutant hippocampal pyramidal neurons. We also report that lithium treatment restored the levels of isoprenylcysteine carboxyl methyltransferase (Icmt; alternatively, Pccmt), down-regulation of which is an early marker of mutant ATXN1 toxicity. Conclusions The effect of lithium on a marker altered early in the course of SCA1 pathogenesis, coupled with its positive effect on multiple behavioral measures and hippocampal neuropathology in an authentic disease model, make it an excellent candidate treatment for human SCA1 patients.
Gluon Radiation in Top Mass Reconstruction: Effect of Hadronic W Decays
L. H. Orr,T. Andre,T. Stelzer
Physics , 1998,
Abstract: Top quark events in hadron collisions often contain additional hadronic jets from gluon bremsstrahlung off the quarks and gluons in the hard subprocesses. Such extra jets must be taken into account in attempts to reconstruct the momentum of the top quark from those of its decay products. We have performed a complete calculation of gluon radiation in top production and decay at the Fermilab Tevatron including hadronically decaying W bosons. In this talk we discuss the effect of gluon radiation on the reconstructed mass of the top quark, using various top mass reconstruction scenarios. Implications for the LHC are briefly discussed.
Gnostic Dilemmas in Western Psychologies of Spirituality
Harry T. Hunt
International Journal of Transpersonal Studies , 2003,
Abstract: Early Gnosticism is identified as a form of Weber’s inner-worldly mysticism that, following the critique of Plotinus, entailed spiritual metapathologies of inflated grandiosity, despair, and/orsocial withdrawal. These vulnerabilities re-emerge in the naturalistic psychologies of spirituality begun by Emerson, Nietzsche, Jung, and Maslow and more implicitly within contemporary personality and neuropsychological research on numinous/transpersonal experience. An updated version of Gnostic dilemma and its conflicted dualism may be endemic to any would-be science of the spiritual and to much current transpersonal psychology as well.
Consciousness and Society: Societal Aspects and Implications of Transpersonal Psychology
Harry T. Hunt
International Journal of Transpersonal Studies , 2010,
Abstract: Although transpersonal psychologies of self realization emphasize individual development, earlier shamanic traditions also showed a central societal aspect and group based consciousness. Indeed, many have understood the transpersonal movement as developing towards an abstract globalized neo-shamanism. That altered states of consciousness, whether as integrative realizations of the numinous or as dissociative “hypnoid” states, could be felt and shared collectively was a familiar concept to the first generation of sociologists, who saw all consciousness as social and dialogic in form. Durkheim, in particular, foresaw a globalized spirituality of the future, his “cult of man,” in which modern individuation would progress to the point where all we would have in common for the collective representations of spiritual awareness would be our shared sense of human beingness. This view foreshadowed De Chardin, and is presented explicitly or implicitly in Jung, Gurdjieff, Heidegger, Maslow, and Almaas. The implications of a societal, collective face of transpersonalism for a future planetary spirituality are pursued in terms of both a global ecological consciousness and the potential transpersonal significance of SETI (Search for Extra-Terrestrial Intelligence).
Theoretical Studies on the Effect of Confinement on Quantum Dots Using the Brus Equation  [PDF]
Ephrem O. Chukwuocha, Michael C. Onyeaju, Taylor S. T. Harry
World Journal of Condensed Matter Physics (WJCMP) , 2012, DOI: 10.4236/wjcmp.2012.22017
Abstract: Quantum confinement effect in semiconductor quantum dots (QD's) of CdSe, ZnS and GaAs has been studied using the Brus Equation. It is found that the simple models obtained for the three different semiconductor nanocrystals exhibit the size dependence predicted by the particle-in-a-box model. The result shows that ground state confinement energy is inversely proportional to the size (radius). Thus, as one increases the radius (size), the confinement energy decreases, but never reaches zero. i.e., the lowest possible energy for the quantum dot sample is not zero.
A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci
Eimear E. Kenny,Itsik Pe'er,Amir Karban,Laurie Ozelius,Adele A. Mitchell,Sok Meng Ng,Monica Erazo,Harry Ostrer,Clara Abraham,Maria T. Abreu,Gil Atzmon,Nir Barzilai,Steven R. Brant,Susan Bressman,Edward R. Burns,Yehuda Chowers,Lorraine N. Clark,Ariel Darvasi,Dana Doheny,Richard H. Duerr,Rami Eliakim,Nir Giladi,Peter K. Gregersen,Hakon Hakonarson,Michelle R. Jones,Karen Marder,Dermot P. B. McGovern,Jennifer Mulle,Avi Orr-Urtreger,Deborah D. Proctor,Ann Pulver,Jerome I. Rotter,Mark S. Silverberg,Thomas Ullman,Stephen T. Warren,Matti Waterman,Wei Zhang,Aviv Bergman,Lloyd Mayer,Seymour Katz,Robert J. Desnick,Judy H. Cho ,Inga Peter
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002559
Abstract: Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10?6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10?8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10?9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10?8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10?8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10?9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.
Inhibition of MHC class I is a virulence factor in herpes simplex virus infection of mice.
Orr Mark T,Edelmann Kurt H,Vieira Jeffrey,Corey Lawrence
PLOS Pathogens , 2005,
Abstract: Herpes simplex virus (HSV) has a number of genes devoted to immune evasion. One such gene, ICP47, binds to the transporter associated with antigen presentation (TAP) 1/2 thereby preventing transport of viral peptides into the endoplasmic reticulum, loading of peptides onto nascent major histocompatibility complex (MHC) class I molecules, and presentation of peptides to CD8 T cells. However, ICP47 binds poorly to murine TAP1/2 and so inhibits antigen presentation by MHC class I in mice much less efficiently than in humans, limiting the utility of murine models to address the importance of MHC class I inhibition in HSV immunopathogenesis. To address this limitation, we generated recombinant HSVs that efficiently inhibit antigen presentation by murine MHC class I. These recombinant viruses prevented cytotoxic T lymphocyte killing of infected cells in vitro, replicated to higher titers in the central nervous system, and induced paralysis more frequently than control HSV. This increase in virulence was due to inhibition of antigen presentation to CD8 T cells, since these differences were not evident in MHC class I-deficient mice or in mice in which CD8 T cells were depleted. Inhibition of MHC class I by the recombinant viruses did not impair the induction of the HSV-specific CD8 T-cell response, indicating that cross-presentation is the principal mechanism by which HSV-specific CD8 T cells are induced. This inhibition in turn facilitates greater viral entry, replication, and/or survival in the central nervous system, leading to an increased incidence of paralysis.
The polarization of Pc5 ULF waves around dawn: A possible ionospheric conductivity gradient effect
G. Chisham,D. Orr,T. K. Yeoman,D. K. Milling
Annales Geophysicae (ANGEO) , 2003,
Abstract: In this study over 100 Pc5 events observed on the SAMNET magnetometer array have been catalogued. The ground horizontal polarization of these waves has been investigated and it has been shown that there are large differences between the polarization azimuth distributions on either side of noon. In the morning the azimuth distributions are spread evenly across all possible orientations whereas in the afternoon they are predominantly in a North-South orientation. The difference appears to be the result of a specific polarization pattern that occurred across the SAMNET array for 31 of the Pc5 events. These 31 Pc5 events all occurred in the morning sector, close to the dawn terminator. It is suggested that this special polarization pattern is a consequence of ionospheric conductivity gradients that occur at around dawn. This theory is reinforced by the comparison of the local times of these polarization variations with the local time of sunrise. By employing ionospheric conductivity data from the EISCAT radar for two of these Pc5 events, this connection has been studied in more detail.
Gluon Radiation in t\bar{t} Production at the Tevatron p\bar{p} Collider
Lynne H. Orr,T. Stelzer,W. J. Stirling
Physics , 1994, DOI: 10.1103/PhysRevD.52.124
Abstract: We present a complete calculation of the matrix elements for the processes $q \bar q, gg \to b W^+ \bar b W^- g$ and $qg \to b W^+ \bar b W^- q$ which are relevant for the study of events with an additional jet in $t \bar t$ production at the Tevatron $p \bar p $ collider. Our calculation includes (i) the contributions from gluons emitted during the top production and decay stages and the interference between these, and (ii) the complete set of Feynman diagrams corresponding to both resonant and non-resonant top production. We study the distribution in phase space of the additional parton jet and make comparisons with previous studies based on the soft-gluon approximation and with results from parton-shower Monte Carlo simulations. The implications for top mass measurements are briefly discussed.
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