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Full-Text Articles in Medicine and Health Sciences

Analysis Of Mitotic Microtubule-Associated Proteins Using Mass Spectrometry Identifies Astrin, A Spindle-Associated Protein, Gary J. Mack, Duane A. Compton Dec 2001

Analysis Of Mitotic Microtubule-Associated Proteins Using Mass Spectrometry Identifies Astrin, A Spindle-Associated Protein, Gary J. Mack, Duane A. Compton

Dartmouth Scholarship

We purified microtubules from a mammalian mitotic extract and obtained an amino acid sequence from each microtubule-associated protein by using mass spectrometry. Most of these proteins are known spindle-associated components with essential functional roles in spindle organization. We generated antibodies against a protein identified in this collection and refer to it as astrin because of its association with astral microtubule arrays assembled in vitro. Astrin is approximately 134 kDa, and except for a large predicted coiled-coil domain in its C-terminal region it lacks any known functional motifs. Astrin associates with spindle microtubules as early as prophase where it concentrates at …


Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade Dec 2001

Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class …


Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma Dec 2001

Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma

Dartmouth Scholarship

An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible PBAD promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfpuvr fusion carried on a shuttle …


Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor Dec 2001

Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor

Dartmouth Scholarship

Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In …


Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade Dec 2001

Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Cholera is an enteric disease caused by Vibrio cholerae. Toxin-coregulated pilus (TCP), a type 4 pilus expressed by V. cholerae, is a cholera virulence factor that is required for host colonization. The TCP polymer is composed of subunits of TcpA pilin. Antibodies directed against TcpA are protective in animal models of cholera. While natural or recombinant forms of TcpA are difficult to purify to homogeneity, it is anticipated that synthesized TcpA peptides might serve as immunogens in a subunit vaccine. We wanted to assess the potential for effects of the immune response (Ir) gene that could complicate a peptide-based …


The Type 2 Iodothyronine Deiodinase Is Essential For Adaptive Thermogenesis In Brown Adipose Tissue, Lucia A. De Jesus, Suzy D. Carvalho, Mirian O. Ribeiro, Mark Schneider, Sung-Woo Kim, John W. Harney, P. Reed Larsen, Antonio C. Bianco Nov 2001

The Type 2 Iodothyronine Deiodinase Is Essential For Adaptive Thermogenesis In Brown Adipose Tissue, Lucia A. De Jesus, Suzy D. Carvalho, Mirian O. Ribeiro, Mark Schneider, Sung-Woo Kim, John W. Harney, P. Reed Larsen, Antonio C. Bianco

Dartmouth Scholarship

Type 2 iodothyronine deiodinase (D2) is a selenoenzyme, the product of the recently cloned cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue (BAT). Here we report that despite a normal plasma 3,5,3′-triiodothyronine (T3) concentration, cold-exposed mice with targeted disruption of the Dio2 gene (Dio2–/–) become hypothermic due to impaired BAT thermogenesis and survive by compensatory shivering with consequent acute weight loss. This occurs despite normal basal mitochondrial uncoupling protein 1 (UCP1) concentration. In Dio2–/– brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and …


Distinct Retrieval And Retention Mechanisms Are Required For The Quality Control Of Endoplasmic Reticulum Protein Folding, Shilpa Vashist, Woong Kim, William J. Belden, Eric D. Spear, Charles Barlowe, Davis T.W. Ng Oct 2001

Distinct Retrieval And Retention Mechanisms Are Required For The Quality Control Of Endoplasmic Reticulum Protein Folding, Shilpa Vashist, Woong Kim, William J. Belden, Eric D. Spear, Charles Barlowe, Davis T.W. Ng

Dartmouth Scholarship

Proteins destined for the secretory pathway must first fold and assemble in the lumen of endoplasmic reticulum (ER). The pathway maintains a quality control mechanism to assure that aberrantly processed proteins are not delivered to their sites of function. As part of this mechanism, misfolded proteins are returned to the cytosol via the ER protein translocation pore where they are ubiquitinated and degraded by the 26S proteasome. Previously, little was known regarding the recognition and targeting of proteins before degradation. By tracking the fate of several mutant proteins subject to quality control, we demonstrate the existence of two distinct sorting …


Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung Aug 2001

Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung

Dartmouth Scholarship

In searching the Staphylococcus aureus genome, we found several homologs to SarA. One of these genes, sarT, codes for a basic protein with 118 residues and a predicted molecular size of 16,096 Da. Northern blot analysis revealed that the expression of sarT was repressed by sarA and agr. An insertion sarT mutant generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on the expression of sarR and sarA. The RNAIII level was notably increased in the sarT mutant, particularly in postexponential-phase cells, while the augmentative effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as determined …


Marek's Disease Virus (Mdv) Encodes An Interleukin-8 Homolog (Vil-8): Characterization Of The Vil-8 Protein And A Vil-8 Deletion Mutant Mdv, Mark S. Parcells, Su-Fang Lin, Robert L. Dienglewicz, Vladimir Majerciak, Dan R. Robinson, Hua-Chien Chen, Zining Wu, George R. Dubyak, Peter Brunovskis, Henry D. Hunt Jun 2001

Marek's Disease Virus (Mdv) Encodes An Interleukin-8 Homolog (Vil-8): Characterization Of The Vil-8 Protein And A Vil-8 Deletion Mutant Mdv, Mark S. Parcells, Su-Fang Lin, Robert L. Dienglewicz, Vladimir Majerciak, Dan R. Robinson, Hua-Chien Chen, Zining Wu, George R. Dubyak, Peter Brunovskis, Henry D. Hunt

Dartmouth Scholarship

Chemokines induce chemotaxis, cell migration, and inflammatory responses. We report the identification of an interleukin-8 (IL-8) homolog, termed vIL-8, encoded within the genome of Marek's disease virus (MDV). The 134-amino-acid vIL-8 shares closest homology to mammalian and avian IL-8, molecules representing the prototype CXC chemokine. The gene for vIL-8 consists of three exons which map to the BamHI-L fragment within the repeats flanking the unique long region of the MDV genome. A 0.7-kb transcript encoding vIL-8 was detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor phosphonoacetate, indicating …


Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green Apr 2001

Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green

Dartmouth Scholarship

Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or …


Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel Jan 2001

Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel

Dartmouth Scholarship

No abstract provided.


Central Chemosensitivity, Sleep, And Wakefulness, E. E. Nattie, A Li Jan 2001

Central Chemosensitivity, Sleep, And Wakefulness, E. E. Nattie, A Li

Dartmouth Scholarship

No abstract provided.