Digital Commons Network^™

Experimental Autoimmune Encephalitis And Inflammation In The Absence Of Interleukin-12, Burkhard Becher, Brigit G. Durell, Randolph J. Noelle

Dartmouth Scholarship

IL-12 is considered a critical proinflammatory cytokine for autoimmune diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-12 is a heterodimer composed of a p35 subunit and a common p40 subunit shared by other cytokines. Both IL-12 p40^–/– and p35^–/– mice fail to produce IL-12 p70 heterodimer. However, in contrast to p40^–/– mice, p35^–/– mice are highly susceptible to the induction of EAE, establishing that IL-12 p70 is not essential for the development of EAE. When compared with wild-type mice, both p40^–/– and p35^–/– mice show deficiencies in primary …

Optimisation Of Bile Production During Normothermic Preservation Of Porcine Livers., Charles J. Imber, Shawn D. St Peter, Inigo Lopez De Cenarruzabeitia, Hugh Lemonde, Mike Rees, Andrew Butler, Peter T. Clayton, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Machine perfusion of livers may provide a mechanism for extended preservation of marginal donor organs before transplantation, as well as a method for viability assessment. It has proved possible in a series of experimental porcine liver perfusions to maintain liver viability for up to 72 h. However, a reduction in bile production with associated histological evidence of cholestasis was seen after 10 h of perfusion, damaging the biliary canaliculi during the preservation period and leaving these organs in an unacceptable condition for transplantation. It was proposed that reduction in bile production was the result of a relentless depletion of available …

Regulation Of Flagellar Dynein By Calcium And A Role For An Axonemal Calmodulin And Calmodulin-Dependent Kinase, Elizabeth F. Smith

Dartmouth Scholarship

Ciliary and flagellar motility is regulated by changes in intraflagellar calcium. However, the molecular mechanism by which calcium controls motility is unknown. We tested the hypothesis that calcium regulates motility by controlling dynein-driven microtubule sliding and that the central pair and radial spokes are involved in this regulation. We isolated axonemes from Chlamydomonasmutants and measured microtubule sliding velocity in buffers containing 1 mM ATP and various concentrations of calcium. In buffers with pCa > 8, microtubule sliding velocity in axonemes lacking the central apparatus (pf18 and pf15) was reduced compared with that of wild-type axonemes. In contrast, at …

Identification Of The Vibrio Cholerae Enterobactin Receptors Vcta And Irga: Irga Is Not Required For Virulence, Alexandra R. Mey, Elizabeth E. Wyckoff, Amanda G. Oglesby, Eva Rab, Ronald K. Taylor, Shelley M. Payne

Dartmouth Scholarship

The gram-negative enteric pathogen Vibrio cholerae requires iron for growth. V. cholerae has multiple iron acquisition systems, including utilization of heme and hemoglobin, synthesis and transport of the catechol siderophore vibriobactin, and transport of several siderophores that it does not itself make. One siderophore that V. cholerae transports, but does not make, is enterobactin. Enterobactin transport requires TonB and is independent of the vibriobactin receptor ViuA. In this study, two candidate enterobactin receptor genes, irgA (VC0475) and vctA (VCA0232), were identified by analysis of the V. cholerae genomic sequence. A single mutation in either of these genes did not significantly …

Treatment With Soluble Interleukin-15ralpha Exacerbates Intracellular Parasitic Infection By Blocking The Development Of Memory Cd8+ T Cell Response, Imtiaz A. Khan, Magali Moretto, Xiao-Qing Wei, Martha Williams, Joseph D. Schwartzman, F Y. Liew

Dartmouth Scholarship

Interferon (IFN)-γ–producing CD8⁺ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8⁺ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8⁺ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor α (sIL-15Rα) to block the host endogenous IL-15. The treatment markedly reduced the ability …

Stretch-Induced Calcium Release In Smooth Muscle., Guangju Ji, Robert J Barsotti, Morris E Feldman, Michael I Kotlikoff

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor-mediated Ca(2+) release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to approximately 120% of slack length (DeltaL = 20) evoked Ca(2+) release from intracellular stores in the form of single Ca(2+) sparks and propagated Ca(2+) waves. Ca(2+) …

Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …

Searching For The Middle Ground: Mechanisms Of Chromosome Alignment During Mitosis, Tarun M. Kapoor, Duane A. Compton

Dartmouth Scholarship

The contributions of key molecules predicted to align chromosomes at the center of the mitotic spindle have been recently examined. New results dictate that models for how chromosomes align during the early stages of mitosis must be revised to integrate properties of microtubule-based motor proteins as well as microtubule dynamics.

Fibroblast Growth Factor–Specific Modulation Of Cellular Response By Syndecan-4, Arie Horowitz, Eugene Tkachenko, Michael Simons

Dartmouth Scholarship

Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKC alpha, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP(2) (PIP(2)(-)) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ(-)) produced a FGF2-specific dominant negative phenotype in …

Extended Preservation Of Non-Heart-Beating Donor Livers With Normothermic Machine Perfusion., Shawn D. St Peter, C J. Imber, I Lopez, D Hughes, P J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-heart-beating donor (NHBD) livers represent an important organ pool, but are seldom utilized clinically and require rapid retrieval and implantation. Experimental work with oxygenated perfusion during preservation has shown promising results by recovering function in these livers. This study compared sanguinous perfusion with cold storage for extended preservation of the NHBD liver in a porcine model.

METHODS: Porcine livers were subjected to 60 min of in vivo total warm ischaemia before flushing, after which they were preserved by one of two methods: group 1 (n = 4), University of Wisconsin (UW) solution by standard cold storage for 24 h; …

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …

Short-Lived And Long-Lived Bone Marrow Plasma Cells Are Derived From A Novel Precursor Population, Brian P. O'Connor, Marilia Cascalho, Randolph J. Noelle

Dartmouth Scholarship

The contribution that long-lived bone marrow (BM) plasma cells (PCs) provide to enduring humoral immunity has been underscored by a number of recent studies. However, little is known about the immediate precursors that give rise to long-lived PCs in the BM of immune individuals. We have identified subsets of antigen-experienced B cells within the immune BM that are precursors to PCs. These PC precursors arise in the BM 14 days after immunization and persist for greater than 9 months. Phenotypically distinct subsets of PC precursors give rise to short-lived or long-lived PCs. The differentiation of PC precursors to PCs occurs …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …

Cd8+-T-Cell Immunity Against Toxoplasma Gondii Can Be Induced But Not Maintained In Mice Lacking Conventional Cd4+ T Cells, Lori Casciotti, Kenneth H. Ely, Martha E. Williams, Imtiaz A. Khan

Dartmouth Scholarship

T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8⁺ T cells are considered the major effector cells against this parasite. It is believed that CD4⁺ T cells may be crucial for induction of the CD8⁺-T-cell response against T. gondii. In the present study, CD4^−/− mice were used to evaluate the role of conventional CD4⁺ T cells in the immune response against T. gondii infection. CD4^−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their …

Valuing Man's And Woman's Best Friend: The Moral And Legal Status Of Companion Animals, Rebecca J. Huss

Law Faculty Publications

This article first provides an overview of the philosophicla basis of the allocation (or non-allocation) of moral status to nonhuman animals considering historical and modern views of animals. Second, it analyzes the legal status of animals under the current system and discusses the idea of extending legal personhood to such animals. Next it considers the common law and statutory basis for the current valuation of companion animals. Finally, this article supports and promotes the idea that there is a rational basis for changing the way that companion animals should be valued by the legal system and recommends the adoption of …

G02-1445 Understanding Vaccines, Dicky D. Griffin, Steve Ensley, David R. Smith, Grant Dewell

University of Nebraska-Lincoln Extension: Historical Materials

This NebGuide explains the basics of vaccine value, the differences between types of vaccines used in animals, and discusses vaccine selection and vaccination program development.

Vaccines are an important part of disease prevention and control. Like insurance, vaccines come at a cost, including the price of the vaccine, labor to administer the vaccine, localized tissue damage from vaccine injections, and increased metabolic demand of the animal causing potential performance loss during the time the animal is developing a proper immune response. The increased metabolic demand can cause the animal to look depressed and therefore may be confused with illness. This …

Nf02-505 Drinking Water: Chloramines Waters Disinfection In Omaha Metropolitan Utilities District, Sharon Skipton, Bruce I. Dvorak

University of Nebraska-Lincoln Extension: Historical Materials

Bacteria and other disease-causing organisms in drinking water can cause intestinal infections, dysentery, and a variety of other illnesses. Water disinfection reduces disease-causing organisms and prevents the transmission of disease. This publication discusses the disinfection process used by Metropolitan Utilities District and how it will change in 2002.

G02-1464 West Nile Virus - Getting Prepared, Grasso M. Ebako, Sheila Scheideler, Wayne Kramer, Ron J. Johnson, David R. Smith, Del Wilmot, David J. Steffen

University of Nebraska-Lincoln Extension: Historical Materials

This NebGuide provides background information and answers to commonly asked questions about this disease. West Nile Virus is spread by mosquitoes and affects birds (mostly Corvidae such as crows, blue jays and magpies), horses, and people. As West Nile Virus appears in neighboring states, the threat of diagnosing a case in Nebraska becomes more likely.

Inhibition Of The Splicing Of Glucose-6-Phosphate Dehydrogenase Precursor Mrna By Polyunsaturated Fatty Acids, Huimin Tao, Wioletta Szeszel-Fedorowicz, Batoul Amir-Ahmady, Matthew A. Gibson, Laura P. Stabile, Lisa M. Salati

Faculty & Staff Scholarship

No abstract provided.

Caveolin-1 Expression Enhances Endothelial Capillary Tubule Formation, Jun Liu, Xiao Bo Wang, David S. Park, Michael P. Lisanti

Faculty & Staff Scholarship

No abstract provided.

Positive And Negative Roles Of Cd72 In B Cell Function., Hsin-Jung Wu, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Regulation of B cell activation depends on integration of signals transmitted by the B cell receptor (BCR) and a variety of co-receptors. CD72 is a B cell co-receptor that is expressed in all stages of B cell development except plasma cells. Ligation of CD72 enhances B cell growth and differentiation. Recently, the class IV semaphoring, CD100, has been identified as the natural ligand for CD72. Cytoplasmic domain of CD72 has been shown to be associated with SHP-1 leading to the proposal that the positive effects of CD72 on B cell response may result from sequestration of negative signals from BCR. …

Algal Blooms Reduce The Uptake Of Toxic Methylmercury In Freshwater Food Webs, Paul C. Pickhardt, Carol L. Folt, Celia Y. Chen, Bjoern Klaue, Joel D. Blum

Dartmouth Scholarship

Mercury accumulation in fish is a global public health concern, because fish are the primary source of toxic methylmercury to humans. Fish from all lakes do not pose the same level of risk to consumers. One of the most intriguing patterns is that potentially dangerous mercury concentrations can be found in fish from clear, oligotrophic lakes whereas fish from greener, eutrophic lakes often carry less mercury. In this study, we experimentally tested the hypothesis that increasing algal biomass reduces mercury accumulation at higher trophic levels through the dilution of mercury in consumed algal cells. Under bloom dilution, as algal biomass …

Beta-Galactosidase As A Marker Of Ischemic Injury And A Mechanism For Viability Assessment In Porcine Liver Transplantation., Shawn D. St Peter, Charles J. Imber, Inigo Lopez De Cenarruzabeitia, James Mcguire, Tim James, Richard Taylor, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Glycohydrolases are a group of enzymes contained predominantly within lysosomes, which are released during Kupffer cell activation or death. One of these, beta-galactosidase, has been proposed as a marker of ischemia-reperfusion injury in the liver because Kupffer cell activation represents a primary event in the injurious reperfusion cascade. In this study, we compared B-galactosidase with more traditional indicators of liver injury and function in a porcine model of liver preservation. Porcine livers were allocated into two groups: group C (n = 5), preserved in University of Wisconsin solution by standard cold storage for 24 hours, and group W (n = …

Transcriptional Interference By Independently Regulated Genes Occurs In Any Relative Arrangement Of The Genes And Is Influenced By Chromosomal Integration Position, Susan K. Eszterhas, Eric E. Bouhassira, David I. K. Martin, Steven Fiering

Dartmouth Scholarship

Transcriptional interference is the influence, generally suppressive, of one active transcriptional unit on another unit linked in cis. Its wide occurrence in experimental systems suggests that it may also influence transcription in many loci, but little is known about its precise nature or underlying mechanisms. Here we report a study of the interaction of two nearly identical transcription units juxtaposed in various arrangements. Each reporter gene in the constructs has its own promoter and enhancer and a strong polyadenylation signal. We used recombinase-mediated cassette exchange (RMCE) to insert the constructs into previously tagged genomic sites in cultured cells. This …

Identification Of Structural Features In The G-Protein Regulatory Motif Required For Regulation Of Heterotrimeric G-Proteins, Yuri K. Peterson, Starr Hazard, Stephen G. Graber, Stephen M. Lanier

Faculty & Staff Scholarship

No abstract provided.

Man's Best Friend: Property Or Family Member - An Examination Of The Legal Classification Of Companion Animals And Its Impact On Damages Recoverable For Their Wrongful Death Or Injury, William C. Root

Villanova Law Review (1956 - )

No abstract provided.

Differential Synthesis Of Beta-Tubulin Isotypes In Gerbil Nasal Epithelia, Karen Woo, Heather Jensen Smith, Richard F. Ludueña, Richard Hallworth

Journal Articles: Eppley Institute

Compartmentalization of beta-tubulin isotypes within cells according to function was examined in gerbil olfactory and respiratory epithelia by using specific antibodies to four beta-tubulin isotypes (beta(I), beta(II), beta(III), and beta(IV)). Isotype synthesis was cell-type-specific, but the localization of the isotypes was not compartmentalized. All four isotypes were found in the cilia, dendrites, somata, and axons of olfactory neurons. Only two isotypes (beta(I) and beta(IV)) were present in the cilia of nasal respiratory epithelial cells. The beta(IV) isotype, thought to be an essential component of cilia, was present in olfactory neurons and respiratory epithelial cells, which are ciliated, but was not …

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 …

Regulation Of Type-Ii Collagen Gene Expression During Human Chondrocyte De-Differentiation And Recovery Of Chondrocyte-Specific Phenotype In Culture Involves Sry-Type High-Mobility-Group Box (Sox) Transcription Factors, David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of …