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Full-Text Articles in Medicine and Health Sciences
Combined Effects Of Aldehyde Dehydrogenase Variants And Maternal Mitochondrial Genes On Alcohol Consumption, Yedy Israel, Maria E. Quintanilla, Amalia Sapag, Lutske Tampier
Combined Effects Of Aldehyde Dehydrogenase Variants And Maternal Mitochondrial Genes On Alcohol Consumption, Yedy Israel, Maria E. Quintanilla, Amalia Sapag, Lutske Tampier
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Two lines of rats bred to differ in their voluntary alcohol consumption — the alcohol-abstaining UChA rats and the alcohol-drinking UChB rats — differ in how effectively toxic acetaldehyde is removed during alcohol metabolism. UChB animals carry efficient variants of the aldehyde dehydrogenase 2 (ALDH2) genes and have active mitochondria, resulting in fast removal of acetaldehyde. UChA animals, in contrast, carry less efficient ALDH2 variants and less active mitochondria, which result in transient elevations of acetaldehyde levels after alcohol ingestion. Cross-breeding studies have demonstrated that the presence of active mitochondria inherited from UChB females can fully abolish the reduction of …
Nucleolin Is Required For Rna Polymerase I Transcription In Vivo, Brendan Rickards, S. Flint, Michael D. Cole, Gary Leroy
Nucleolin Is Required For Rna Polymerase I Transcription In Vivo, Brendan Rickards, S. Flint, Michael D. Cole, Gary Leroy
Dartmouth Scholarship
Eukaryotic genomes are packaged with histones and accessory proteins in the form of chromatin. RNA polymerases and their accessory proteins are sufficient for transcription of naked DNA, but not of chromatin, templates in vitro. In this study, we purified and identified nucleolin as a protein that allows RNA polymerase II to transcribe nucleosomal templates in vitro. As immunofluorescence confirmed that nucleolin localizes primarily to nucleoli with RNA polymerase I, we demonstrated that nucleolin allows RNA polymerase I transcription of chromatin templates in vitro. The results of chromatin immunoprecipitation experiments established that nucleolin is associated with chromatin containing rRNA genes transcribed …
Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst
Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst
Dartmouth Scholarship
HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …
Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood
Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood
Dartmouth Scholarship
The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86−/− mice. In the …
Binding Of Internalized Receptors To The Pdz Domain Of Gipc/Synectin Recruits Myosin Vi To Endocytic Vesicles, Samia N. Naccache, Tama Hasson, Arie Horowitz
Binding Of Internalized Receptors To The Pdz Domain Of Gipc/Synectin Recruits Myosin Vi To Endocytic Vesicles, Samia N. Naccache, Tama Hasson, Arie Horowitz
Dartmouth Scholarship
Myosin VI (myo6) is the only actin-based molecular motor that translocates along actin filaments toward the minus end. Myo6 participates in two steps of endocytic trafficking; it is recruited to both clathrin-coated pits and to ensuing uncoated endocytic vesicles (UCV). Although there is evidence suggesting that the PDZ adaptor protein GIPC/synectin is involved in the association of myo6 with UCV, the recruitment mechanism is unknown. We show that GIPC/synectin is required for both internalization of cell surface receptors and for coupling of myo6 to UCV. This coupling occurs via a mechanism wherein engagement of the GIPC/synectin PDZ domain by C …
Circadian Rhythmicity By Autocatalysis, Arun Mehra, Christian I. Hong, Mi Shi, Jennifer J. Loros, Jay C. Dunlap, Peter Ruoff
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.
Mixed Germ Cell Sex Cord-Stromal Tumors Of The Testis And Ovary. Morphological, Immunohistochemical, And Molecular Genetic Study Of Seven Cases, Michal Michal, Tomas Vanacek, Radek Sima, Petr Mukensnabl, Ondrej Hes, Dmitry V. Kazakov, Jozef Matoska, Anna Zuntova, Vladimir Dvorak, Alexander Talerman
Mixed Germ Cell Sex Cord-Stromal Tumors Of The Testis And Ovary. Morphological, Immunohistochemical, And Molecular Genetic Study Of Seven Cases, Michal Michal, Tomas Vanacek, Radek Sima, Petr Mukensnabl, Ondrej Hes, Dmitry V. Kazakov, Jozef Matoska, Anna Zuntova, Vladimir Dvorak, Alexander Talerman
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to …
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
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 …
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
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 …