Medicine and Health Sciences | Open Access Articles

Use Of Hospitals, Physician Visits, And Hospice Care During Last Six Months Of Life Among Cohorts Loyal To Highly Respected Hospitals In The United States, J. E. Wennberg, Elliot S. Fisher, Therese A. Stukel, Jonathan S. Skinner

Dartmouth Scholarship

Objective: To evaluate the use of healthcare resources during the last six months of life among patients of US hospitals with strong reputations for high quality care in managing chronic illness.

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The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley

Dartmouth Scholarship

AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its …

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Hearing Loss And Retarded Cochlear Development In Mice Lacking Type 2 Iodothyronine Deiodinase, Lily Ng, Richard J. Goodyear, Chad A. Woods, Mark J. Schneider

Dartmouth Scholarship

The later stages of cochlear differentiation and the developmental onset of hearing require thyroid hormone. Although thyroid hormone receptors (TRs) are a prerequisite for this process, it is likely that other factors modify TR activity during cochlear development. The mouse cochlea expresses type 2 deiodinase (D2), an enzyme that converts thyroxine, the main form of thyroid hormone in the circulation, into 3,5,3'-triiodothyronine (T3) the major ligand for TRs. Here, we show that D2-deficient mice have circulating thyroid hormone levels that would normally be adequate to allow hearing to develop but they exhibit an auditory phenotype similar to that caused by …

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Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper

Dartmouth Scholarship

Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD₅₀) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD₅₀ of CBA/J mice) died post infection, whereas CBA/J mice that received 15 …

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Impacts Of Sara And Agr In Staphylococcus Aureus Strain Newman On Fibronectin-Binding Protein A Gene Expression And Fibronectin Adherence Capacity In Vitro And In Experimental Infective Endocarditis, Yan-Qiong Xiong, Arnold S. Bayer, Michael R. Yeaman, Willem Van Wamel, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

We investigated the impacts of sarA and agr on fnbA expression and fibronectin-binding capacity in Staphylococcus aureus in vitro and in experimental endocarditis. Although sarA up-regulated and agr down-regulated both fnbA expression and fibronectin binding in vitro and in vivo, fnbA expression was positively regulated in the absence of both global regulators. Thus, additional regulatory loci contribute to fnbA regulation and fibronectin-binding capacities in S. aureus.

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Fibroblast Growth Factor 2 Endocytosis In Endothelial Cells Proceed Via Syndecan-4-Dependent Activation Of Rac1 And A Cdc42-Dependent Macropinocytic Pathway, Eugene Tkachenko, Esther Lutgens, Radu-Virgil Stan, Michael Simons

Dartmouth Scholarship

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex …

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Trans-Snare Interactions Elicit Ca2+ Efflux From The Yeast Vacuole Lumen, Alexey J. Merz, William T. Wickner

Dartmouth Scholarship

Ca2+ transients trigger many SNARE-dependent membrane fusion events. The homotypic fusion of yeast vacuoles occurs after a release of lumenal Ca2+. Here, we show that trans-SNARE interactions promote the release of Ca2+ from the vacuole lumen. Ypt7p-GTP, the Sec1p/Munc18-protein Vps33p, and Rho GTPases, all of which function during docking, are required for Ca2+ release. Inhibitors of SNARE function prevent Ca2+ release. Recombinant Vam7p, a soluble Q-SNARE, stimulates Ca2+ release. Vacuoles lacking either of two complementary SNAREs, Vam3p or Nyv1p, fail to release Ca2+ upon tethering. Mixing these two vacuole populations together allows Vam3p and Nyv1p to interact in trans and …

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Effect Of Escherichia Coli And Lactobacillus Rhamnosus On Macrophage Inflammatory Protein 3Α, Tumor Necrosis Factor Alpha, And Transforming Growth Factor Β Release By Polarized Rat Uterine Epithelial Cells In Culture, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Entry of bacteria from the vagina into the uterus raises the question of uterine epithelial cell (UEC) signaling in response to the presence of bacteria. Our model system helps to define microbially elicited UEC basolateral cytokine release, important in regulating underlying stromal immune cell protection. UECs from adult rats were grown in cell culture inserts to establish a confluent polarized monolayer as was determined by transepithelial resistance (TER). Polarized epithelial cell cultures were treated apically with live or heat-killed Escherichia coli or Lactobacillus rhamnosus prior to collection of basolateral media after 24 h of incubation. Coculture of polarized UECs with …

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Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Dartmouth Scholarship

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by inter- leukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this 􏰀-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in …

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The Nuclear Pore Complex And The Dead Box Protein Rat8p/Dbp5p Have Nonessential Features Which Appear To Facilitate Mrna Export Following Heat Shock, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole

Dartmouth Scholarship

Nuclear pore complexes (NPCs) play an essential role in RNA export. Nucleoporins required for mRNA export in Saccharomyces cerevisiae are found in the Nup84p and Nup82p subcomplexes of the NPC. The Nup82p subcomplex contains Nup82p, Rat7p/Nup159p, Nsp1p, Gle1p/Rss1p, and Rip1p/Nup42p and is found only on the cytoplasmic face of NPCs. Both Rat7p and Gle1p contain binding sites for Rat8p/Dbp5p, an essential DEAD box protein and putative RNA helicase. Rip1p interacts directly with Gle1p and is the only protein known to be essential for mRNA export after heat shock but not under normal growth conditions. We report that in cells lacking …

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Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green

Dartmouth Scholarship

LP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy, hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not mediate disease by upregulation of CD80 or CD86. We report here that there is nonetheless a necessity for CD40 signaling competence, specifically an intact tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.

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Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham

Dartmouth Scholarship

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that phagocyte-derived oxidants target these autoinducers for inactivation as an innate defense mechanism of the host. In a skin infection model, expression of phagocyte NADPH oxidase, myeloperoxidase, or inducible nitric oxide synthase was critical for defense against a quorum-sensing pathogen, Staphylococcus aureus, but not for defense against a quorum sensing-deficient mutant. A virulence-inducing peptide of S. aureus was inactivated in vitro and in vivo by reactive oxygen and nitrogen intermediates, including HOCl and ONOO(-). …

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Slbp Is Associated With Histone Mrna On Polyribosomes As A Component Of The Histone Mrnp, Michael L. Whitfield, Handan Kaygun, Judith A. Erkmann, W. H. Davin Townley-Tilson, Zbig Dominski, William F. Marzluff

Dartmouth Scholarship

The stem–loop binding protein (SLBP) binds the 3′ end of histone mRNA and is present both in nucleus, and in the cytoplasm on the polyribosomes. SLBP participates in the processing of the histone pre-mRNA and in translation of the mature message. Histone mRNAs are rapidly degraded when cells are treated with inhibitors of DNA replication and are stabilized by inhibitors of translation, resulting in an increase in histone mRNA levels. Here, we show that SLBP is a component of the histone messenger ribonucleoprotein particle (mRNP). Histone mRNA from polyribosomes is immunoprecipitated with anti-SLBP. Most of the SLBP in cycloheximide-treated cells …

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Interleukin-10 And Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

To understand the role of interleukin-10 (IL-10) in ocular toxoplasmosis, we compared C57BL/6 (B6) and BALB/c background mice lacking a functional IL-10 gene (IL-10(-/-)) and B6 transgenic mice expressing IL-10 under the control of the IL-2 promoter. Increased cellular infiltration and necrosis were observed in the eye tissue of IL-10(-/-) mice of both the B6 and BALB/c backgrounds with associated changes in the levels of cytokines in serum. In contrast, there was no evidence of necrosis in the eye tissue from IL-10 transgenic mice following parasite exposure. Our results demonstrate that IL-10 is important in the regulation of inflammation during …

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Interpreting Hemoglobin And Water Concentration, Oxygen Saturation, And Scattering Measured In Vivo By Near-Infrared Breast Tomography, Subhadra Srinivasan, Brian W. Pogue, Shudong Jiang, Hamid Dehghani, Christine Kogel, Sandra Soho, Jennifer J. Gibson, Tor D. Tosteson, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic …

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Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus is a gram-positive pathogen that is capable of expressing a variety of virulence proteins in response to environmental signals. Virulence protein expression in S. aureus is controlled by a network of regulatory loci including sarA and agr. The sarA/agr network is associated with the expression of cell wall-associated adhesins during exponential growth and the expression of secreted enzymes and toxins in the transition to post-exponential growth. A number of sarA homologs, including sarT and sarS, have been identified in the S. aureus genome. Previous studies have shown that sarA influences expression of both sarT and sarS in the …

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The Virulence Activator Apha Links Quorum Sensing To Pathogenesis And Physiology In Vibrio Cholerae By Repressing The Expression Of A Penicillin Amidase Gene On The Small Chromosome, Gabriela Kovacikova, Wei Lin, Karen Skorupski

Dartmouth Scholarship

Activation of the tcpPH promoter on the Vibrio pathogenicity island by AphA and AphB initiates the Vibrio cholerae virulence cascade and is regulated by quorum sensing through the repressive action of HapR on aphA expression. To further understand how the chromosomally encoded AphA protein activates tcpPH expression, site-directed mutagenesis was used to identify the base pairs critical for AphA binding and transcriptional activation. This analysis revealed a region of partial dyad symmetry, TATGCA-N6-TNCNNA, that is important for both of these activities. Searching the V. cholerae genome for this binding site permitted the identification of a second one upstream of a …

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Ccr5 Mediates Specific Migration Of Toxoplasma Gondii—Primed Cd8+ Lymphocytes To Inflammatory Intestinal Epithelial Cells, Souphalone Luangsay, Lloyd H. Kasper, Nicolas Rachinel, Laurie A. Minns

Dartmouth Scholarship

Toxoplasma gondii, an obligate intracellular parasite, can invade intestinal epithelial cells and elicit a robust Th1 immune response. In this model of intestinal inflammation, CD8⁺ intraepithelial lymphocytes (IELs) secrete transforming growth factor (TGF)-β, which appears necessary for the maintenance of homeostasis in the intestine. However, the mechanism responsible for the IEL migration to the inflamed intestine is still unclear.An in vitro coculture cell system was used to quantify the IEL attraction by an infected intestinal epithelial cell line (m-IC_cl2). We used CCR5-deficient mice to determine which chemokine receptor—chemokine interaction could be responsible for the recruitment of …

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Salicylic Acid Attenuates Virulence In Endovascular Infections By Targeting Global Regulatory Pathways In Staphylococcus Aureus, Leon Iri Kupferwasser, Michael R. Yeaman, Cynthia C. Nast, Deborah Kupferwasser, Yan-Qiong Xiong, Marco Palma, Ambrose L. Cheung, Arnold S. Bayer

Dartmouth Scholarship

Aspirin has been previously shown to reduce the in vivo virulence of Staphylococcus aureus in experimental endocarditis, through antiplatelet and antimicrobial mechanisms. In the present study, salicylic acid, the major in vivo metabolite of aspirin, mitigated two important virulence phenotypes in both clinical and laboratory S. aureus strains: α-hemolysin secretion and fibronectin binding in vitro. In addition, salicylic acid reduced the expression of the α-hemolysin gene promoter, hla, and the fibronectin gene promoter, fnbA. Transcriptional analysis, fluorometry, and flow cytometry revealed evidence of salicylic acid–mediated activation of the stress-response gene sigB. Expression of the sigB-repressible global …

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Use Of In Vivo-Induced Antigen Technology (Iviat) To Identify Genes Uniquely Expressed During Human Infection With Vibrio Cholerae, Long Hang, Manohar John, Muhammad Asaduzzaman, Emily A. Bridges, Cecily Vanderspurt, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

In vivo-induced antigen technology is a method to identify proteins expressed by pathogenic bacteria during human infection. Sera from 10 patients convalescing from cholera infection in Bangladesh were pooled, adsorbed against in vitro-grown El Tor Vibrio cholerae O1, and used to probe a genomic expression library in Escherichia coli constructed from El Tor V. cholerae O1 strain N16961. We identified 38 positive clones in the screen, encoding pili (PilA and TcpA), cell membrane proteins (PilQ, MshO, MshP, and CapK), methyl-accepting chemotaxis proteins, chemotaxis and motility proteins (CheA and CheR), a quorum-sensing protein (LuxP), and four hypothetical proteins. Analysis of immune …

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The Triterpenoid Cddo Inhibits Expression Of Matrix Metalloproteinase-1, Matrix Metalloproteinase-13 And Bcl-3 In Primary Human Chondrocytes, Sarah Elliott, Ezra Hays, Michael Mayor, Michael Sporn, Matthew P. Vincenti

Dartmouth Scholarship

A synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), has been reported to have anti-inflammatory properties and to decrease the interleukin-1 (IL-1)-induced expression of matrix metalloproteinase-1 (MMP-1) and MMP-13. We have shown previously that IL-1 induces expression of the inhibitor of NF-κB (IκB) family member Bcl-3, and that this contributes to MMP-1 expression. To quantify the effects of CDDO on IL-1-induced MMP-1, MMP-13 and Bcl-3 expression, we stimulated the chondrosarcoma cell line SW-1353 and human primary chondrocytes with IL-1, in the presence or absence of CDDO. Harvested RNA was subjected to quantitative real-time reverse-transcriptase polymerase chain reaction. In SW-1353 cells, 300 nM CDDO …

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Crystal Structure Of The Sars Protein From Staphylococcus Aureus, Ronggui Li, Adhar C. Manna, Shaodong Dai, Ambrose L. Cheung, Gongyi Zhang

Dartmouth Scholarship

The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). One of these determinants, protein A (spa), is activated by sarS, which encodes a 250-residue DNA-binding protein. Genetic analysis indicated that the agr locus likely mediates spa repression by suppressing the transcription of sarS. Contrary to SarA and SarR, which require homodimer formation for proper function, SarS is unusual within the SarA protein family in that it contains two homologous halves, with each half sharing sequence similarity to SarA and SarR. Here we report the 2.2 Å …

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Alginate Is Not A Significant Component Of The Extracellular Polysaccharide Matrix Of Pa14 And Pao1 Pseudomonas Aeruginosa Biofilms, Daniel J. Wozniak, Timna J. O. Wyckoff, Melissa Starkey, Rebecca Keyser, Parastoo Azadi, George A. O'Toole, Matthew R. Parsek

Dartmouth Scholarship

The bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis (CF) patients. Such infections are extremely difficult to control because the bacteria exhibit a biofilm-mode of growth, rendering P. aeruginosa resistant to antibiotics and phagocytic cells. During the course of infection, P. aeruginosa usually undergoes a phenotypic switch to a mucoid colony, which is characterized by the overproduction of the exopolysaccharide alginate. Alginate overproduction has been implicated in protecting P. aeruginosa from the harsh environment present in the CF lung, as well as facilitating its persistence as a biofilm by providing an extracellular matrix that promotes adherence. Because of …

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A Functional Relationship Between Numa And Kid Is Involved In Both Spindle Organization And Chromosome Alignment In Vertebrate Cells, Aime A. Levesque, Louisa Howard, Michael B. Gordon, Duane A. Compton

Dartmouth Scholarship

We examined spindle morphology and chromosome alignment in vertebrate cells after simultaneous perturbation of the chromokinesin Kid and either NuMA, CENP-E, or HSET. Spindle morphology and chromosome alignment after simultaneous perturbation of Kid and either HSET or CENP-E were no different from when either HSET or CENP-E was perturbed alone. However, short bipolar spindles with organized poles formed after perturbation of both Kid and NuMA in stark contrast to splayed spindle poles observed after perturbation of NuMA alone. Spindles were disorganized if Kid, NuMA, and HSET were perturbed, indicating that HSET is sufficient for spindle organization in the absence of …

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Probucol Prevents Early Coronary Heart Disease And Death In The High-Density Lipoprotein Receptor Sr-Bi/Apolipoprotein E Double Knockout Mouse, Anne Braun, Songwen Zhang, Helena E. Miettinen, Shamsah Ebrahim, Teresa M. Holm, Eliza Vasile, Mark J. Post

Dartmouth Scholarship

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment …

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Copper Chelation Represses The Vascular Response To Injury, Lazar Mandinov, Anna Mandinova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev, Ivan Kehayov, Vihren Kolev, Raffaella Soldi, Cinzia Bagala, Ebo D. De Muinck, Volkhard Lindner, Mark J. Post, Michael Simons

Dartmouth Scholarship

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of …

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Vam10p Defines A Sec18p-Independent Step Of Priming That Allows Yeast Vacuole Tethering, Masashi Kato, William Wickner

Dartmouth Scholarship

YOR068c, termed VAM10 (altered vacuole morphology), lies within the VPS5 gene on the opposite DNA strand. VAM10 deletion causes vacuole fragmentation in vivo. The in vitro fusion of purified yeast vacuoles is stimulated by recombinant Vam10p and blocked by antibody to Vam10p. Vam10p acts early in the priming stage of fusion, independent of Sec18p. After priming, recombinant Vam10p will not stimulate fusion and anti-Vam10p antibodies will not inhibit; Vam10p provides a functional marker for this Sec18p-independent priming step. Pure Vam10p restores normal, Ypt7p-dependent tethering to vacuoles from a vam10Δ strain.

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Regulation And Localization Of Endogenous Human Tristetraprolin, Anna-Marie Fairhurst, John E. Connolly, Katharine A Hintz, Nicolas J Goulding

Dartmouth Scholarship

Tumor necrosis factor (TNF) has been implicated in the development and pathogenicity of infectious diseases and autoimmune disorders, such as septic shock and arthritis. The zinc-finger protein tristetraprolin (TTP) has been identified as a major regulator of TNF biosynthesis. To define its intracellular location and examine its regulation of TNF, a quantitive intracellular staining assay specific for TTP was developed. We establish for the first time that in peripheral blood leukocytes, express

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Rhythmic Binding Of A White Collar-Containing Complex To The Frequency Promoter Is Inhibited By Frequency, Allan C. Froehlich, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

The biological clock of Neurospora crassa includes interconnected transcriptional and translational feedback loops that cause both the transcript and protein encoded by the frequency gene (frq) to undergo the robust daily oscillations in abundance, which are essential for clock function. To understand better the mechanism generating rhythmic frq transcript, reporter constructs were used to show that the oscillation in frq message is transcriptionally regulated, and a single cis-acting element in the frq promoter, the Clock Box (C box), is both necessary and sufficient for this rhythmic transcription. Nuclear protein extracts used in binding assays revealed that a White Collar (WC)-1- …

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Genomic And Proteomic Profiling Of Responses To Toxic Metals In Human Lung Cells, Angeline S. Andrew, Amy J. Warren, Aaron Barchowsky, Kaili A. Temple, Linda Klei, Nicole V. Soucy, Kimberly A. O'Hara, Joshua W. Hamilton

Dartmouth Scholarship

Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3 M Cd(II) (as cadmium chloride), 10 M Cr(VI) (as sodium dichromate), 3 g/cm2 Ni(II) (as nickel subsulfide), 5 M or 50 M As(III) (as sodium arsenite), or …

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Full-Text Articles in Medicine and Health Sciences

Use Of Hospitals, Physician Visits, And Hospice Care During Last Six Months Of Life Among Cohorts Loyal To Highly Respected Hospitals In The United States, J. E. Wennberg, Elliot S. Fisher, Therese A. Stukel, Jonathan S. Skinner

Dartmouth Scholarship

The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley

Dartmouth Scholarship

Hearing Loss And Retarded Cochlear Development In Mice Lacking Type 2 Iodothyronine Deiodinase, Lily Ng, Richard J. Goodyear, Chad A. Woods, Mark J. Schneider

Dartmouth Scholarship

Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper

Dartmouth Scholarship

Dartmouth Scholarship

Fibroblast Growth Factor 2 Endocytosis In Endothelial Cells Proceed Via Syndecan-4-Dependent Activation Of Rac1 And A Cdc42-Dependent Macropinocytic Pathway, Eugene Tkachenko, Esther Lutgens, Radu-Virgil Stan, Michael Simons

Dartmouth Scholarship

Trans-Snare Interactions Elicit Ca2+ Efflux From The Yeast Vacuole Lumen, Alexey J. Merz, William T. Wickner

Dartmouth Scholarship

Effect Of Escherichia Coli And Lactobacillus Rhamnosus On Macrophage Inflammatory Protein 3Α, Tumor Necrosis Factor Alpha, And Transforming Growth Factor Β Release By Polarized Rat Uterine Epithelial Cells In Culture, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Dartmouth Scholarship

The Nuclear Pore Complex And The Dead Box Protein Rat8p/Dbp5p Have Nonessential Features Which Appear To Facilitate Mrna Export Following Heat Shock, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole

Dartmouth Scholarship

Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green

Dartmouth Scholarship

Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham

Dartmouth Scholarship

Slbp Is Associated With Histone Mrna On Polyribosomes As A Component Of The Histone Mrnp, Michael L. Whitfield, Handan Kaygun, Judith A. Erkmann, W. H. Davin Townley-Tilson, Zbig Dominski, William F. Marzluff

Dartmouth Scholarship

Interleukin-10 And Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

Dartmouth Scholarship

Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

The Virulence Activator Apha Links Quorum Sensing To Pathogenesis And Physiology In Vibrio Cholerae By Repressing The Expression Of A Penicillin Amidase Gene On The Small Chromosome, Gabriela Kovacikova, Wei Lin, Karen Skorupski

Dartmouth Scholarship

Ccr5 Mediates Specific Migration Of Toxoplasma Gondii—Primed Cd8+ Lymphocytes To Inflammatory Intestinal Epithelial Cells, Souphalone Luangsay, Lloyd H. Kasper, Nicolas Rachinel, Laurie A. Minns

Dartmouth Scholarship

Salicylic Acid Attenuates Virulence In Endovascular Infections By Targeting Global Regulatory Pathways In Staphylococcus Aureus, Leon Iri Kupferwasser, Michael R. Yeaman, Cynthia C. Nast, Deborah Kupferwasser, Yan-Qiong Xiong, Marco Palma, Ambrose L. Cheung, Arnold S. Bayer

Dartmouth Scholarship

Use Of In Vivo-Induced Antigen Technology (Iviat) To Identify Genes Uniquely Expressed During Human Infection With Vibrio Cholerae, Long Hang, Manohar John, Muhammad Asaduzzaman, Emily A. Bridges, Cecily Vanderspurt, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

The Triterpenoid Cddo Inhibits Expression Of Matrix Metalloproteinase-1, Matrix Metalloproteinase-13 And Bcl-3 In Primary Human Chondrocytes, Sarah Elliott, Ezra Hays, Michael Mayor, Michael Sporn, Matthew P. Vincenti

Dartmouth Scholarship

Crystal Structure Of The Sars Protein From Staphylococcus Aureus, Ronggui Li, Adhar C. Manna, Shaodong Dai, Ambrose L. Cheung, Gongyi Zhang

Dartmouth Scholarship

Alginate Is Not A Significant Component Of The Extracellular Polysaccharide Matrix Of Pa14 And Pao1 Pseudomonas Aeruginosa Biofilms, Daniel J. Wozniak, Timna J. O. Wyckoff, Melissa Starkey, Rebecca Keyser, Parastoo Azadi, George A. O'Toole, Matthew R. Parsek

Dartmouth Scholarship

A Functional Relationship Between Numa And Kid Is Involved In Both Spindle Organization And Chromosome Alignment In Vertebrate Cells, Aime A. Levesque, Louisa Howard, Michael B. Gordon, Duane A. Compton

Dartmouth Scholarship

Probucol Prevents Early Coronary Heart Disease And Death In The High-Density Lipoprotein Receptor Sr-Bi/Apolipoprotein E Double Knockout Mouse, Anne Braun, Songwen Zhang, Helena E. Miettinen, Shamsah Ebrahim, Teresa M. Holm, Eliza Vasile, Mark J. Post

Dartmouth Scholarship

Copper Chelation Represses The Vascular Response To Injury, Lazar Mandinov, Anna Mandinova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev, Ivan Kehayov, Vihren Kolev, Raffaella Soldi, Cinzia Bagala, Ebo D. De Muinck, Volkhard Lindner, Mark J. Post, Michael Simons

Dartmouth Scholarship

Vam10p Defines A Sec18p-Independent Step Of Priming That Allows Yeast Vacuole Tethering, Masashi Kato, William Wickner

Dartmouth Scholarship

Regulation And Localization Of Endogenous Human Tristetraprolin, Anna-Marie Fairhurst, John E. Connolly, Katharine A Hintz, Nicolas J Goulding

Dartmouth Scholarship

Rhythmic Binding Of A White Collar-Containing Complex To The Frequency Promoter Is Inhibited By Frequency, Allan C. Froehlich, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

Genomic And Proteomic Profiling Of Responses To Toxic Metals In Human Lung Cells, Angeline S. Andrew, Amy J. Warren, Aaron Barchowsky, Kaili A. Temple, Linda Klei, Nicole V. Soucy, Kimberly A. O'Hara, Joshua W. Hamilton

Dartmouth Scholarship