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Full-Text Articles in Medicine and Health Sciences

Gammaherpesvirus Persistence Alters Key Cd8 T-Cell Memory Characteristics And Enhances Antiviral Protection, Joshua J. Obar, Shinichiro Fuse, Erica K. Leung, Sarah C. Bellfy, Edward J. Usherwood Sep 2006

Gammaherpesvirus Persistence Alters Key Cd8 T-Cell Memory Characteristics And Enhances Antiviral Protection, Joshua J. Obar, Shinichiro Fuse, Erica K. Leung, Sarah C. Bellfy, Edward J. Usherwood

Dartmouth Scholarship

In herpesvirus infections, the virus persists for life but is contained through T-cell-mediated immune surveillance. How this immune surveillance operates is poorly understood. Recent studies of other persistent infections have indicated that virus persistence is associated with functional deficits in the CD8(+) T-cell response. To test whether this is the case in a herpesvirus infection, we used a mutant murine gammaherpesvirus that is defective in its ability to persist in the host. By comparing the immune response to this virus with a revertant virus that can persist, we were able to dissect the changes in the antiviral CD8(+) T-cell response …


Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell Aug 2006

Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.


Circadian Rhythmicity By Autocatalysis, Arun Mehra, Christian I. Hong, Mi Shi, Jennifer J. Loros, Jay C. Dunlap, Peter Ruoff Jul 2006

Circadian Rhythmicity By Autocatalysis, Arun Mehra, Christian I. Hong, Mi Shi, Jennifer J. Loros, Jay C. Dunlap, Peter Ruoff

Dartmouth Scholarship

The temperature compensated in vitro oscillation of cyanobacterial KaiC phosphorylation, the first example of a thermodynamically closed system showing circadian rhythmicity, only involves the three Kai proteins (KaiA, KaiB, and KaiC) and ATP. In this paper, we describe a model in which the KaiA- and KaiB-assisted autocatalytic phosphorylation and dephosphorylation of KaiC are the source for circadian rhythmicity. This model, based upon autocatalysis instead of transcription-translation negative feedback, shows temperature-compensated circadian limit-cycle oscillations with KaiC phosphorylation profiles and has period lengths and rate constant values that are consistent with experimental observations.


Cardiac-Specific Elevations In Thyroid Hormone Enhance Contractility And Prevent Pressure Overload-Induced Cardiac Dysfunction, Maria G. Trivieri, Gavin Y. Oudit, Rajan Sah, Benoit-Giles Kerfant, Hui Sun, Anthony O. Gramolini, Yan Pan, Alan D. Wickenden, Walburga Croteau Apr 2006

Cardiac-Specific Elevations In Thyroid Hormone Enhance Contractility And Prevent Pressure Overload-Induced Cardiac Dysfunction, Maria G. Trivieri, Gavin Y. Oudit, Rajan Sah, Benoit-Giles Kerfant, Hui Sun, Anthony O. Gramolini, Yan Pan, Alan D. Wickenden, Walburga Croteau

Dartmouth Scholarship

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and …


A Pdz-Binding Motif As A Critical Determinant Of Rho Guanine Exchange Factor Function And Cell Phenotype, Miaoliang Liu, Arie Horowitz Feb 2006

A Pdz-Binding Motif As A Critical Determinant Of Rho Guanine Exchange Factor Function And Cell Phenotype, Miaoliang Liu, Arie Horowitz

Dartmouth Scholarship

We identified a Rho guanine exchange factor (GEF) expressed as two splice variants, which differ only in either having or lacking a Postsynaptic density 95, Disk large, Zona occludens-1 (PDZ) motif. The PDZ adaptor protein synectin bound the longer splice variant, Syx1, which was targeted to the plasma membrane in a synectin-dependent manner. The shorter variant, Syx2, was diffusely distributed in the cytoplasm. Fluorescence resonance energy transfer (FRET) imaging revealed similar differences between the spatial patterns of active RhoA in Syx1 versus Syx2-expressing cells. Expression of Syx1 augmented endothelial cell (EC) migration and tube formation, whereas Syx2 expression did not. …


Thimerosal-Induced Neuritoxicity: Apoptosis Occurs Through A Mitochondrial-Mediated Pathway Via The Jnk Signaling Pathway, Michelle L. Herdman Jan 2006

Thimerosal-Induced Neuritoxicity: Apoptosis Occurs Through A Mitochondrial-Mediated Pathway Via The Jnk Signaling Pathway, Michelle L. Herdman

Theses, Dissertations and Capstones

Thimerosal is an organic mercurial containing an ethylmercury moiety attached to the sulfur atom of thiosalicylate. Since the 1930s, thimerosal has been used as an antiseptic and a preservative in a wide variety of products, including medicinal preparations administered to children and pregnant women. Past exposures to mercurials have indicated that mercury is a neurotoxin, and can also affect the kidney, skin, eyes, and immune system. Additionally, fetuses exposed to mercurials are more susceptible to toxicity because the nervous system is continuously developing. However, despite its widespread use, thimerosal was only studied on a limited basis until the end of …


Innate Antiviral Response Targets Hiv-1 Release By The Induction Of Ubiquitin-Like Protein Isg15, Atsushi Okumura, Gengshi Lu, Ian Pitha-Rowe, Paula M. Pitha Jan 2006

Innate Antiviral Response Targets Hiv-1 Release By The Induction Of Ubiquitin-Like Protein Isg15, Atsushi Okumura, Gengshi Lu, Ian Pitha-Rowe, Paula M. Pitha

Dartmouth Scholarship

The goal of this study was to elucidate the molecular mechanism by which type I IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits release of HIV-1 virions without having any effect on the synthesis of HIV-1 proteins in the cells. ISG15 expression specifically inhibited ubiquitination of Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag-Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells. Elimination …