Life Sciences Commons^™

Il-23 Produced By Cns-Resident Cells Controls T Cell Encephalitogenicity During The Effector Phase Of Experimental Autoimmune Encephalomyelitis, Burkhard Becher, Brigit G. Durell, Randolph J. Noelle

Dartmouth Scholarship

CNS-resident cells, in particular microglia and macrophages, are a source of inflammatory cytokines during inflammation within the CNS. Expression of IL-23, a recently discovered cytokine, has been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE) in mice. Expression of the p40 subunit of IL-12 and IL-23 by microglia has been shown in situ and in vitro, but direct evidence for a functional significance of p40 expression by CNS cells during an immune response in vivo is still lacking. Here we report that p40 plays a critical role in maintaining encephalitogenicity during the disease course. By using …

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 …

Is Hp1 An Rna Detector That Functions Both In Repression And Activation?, Rebecca Kellum

Biology Faculty Publications

Heterochromatin is defined as regions of compact chromatin that persist throughout the cell cycle (Heitz, 1928). The earliest cytological observations of heterochromatin were followed by ribonucleotide labeling experiments that showed it to be transcriptionally inert relative to the more typical euchromatic regions that decondense during interphase. Genetic studies of rearrangements that place euchromatic genes next to blocks of heterochromatin also pointed out the repressive nature of heterochromatin (Grigliatti, 1991; and references therein). The discovery of the heterochromatin-enriched protein heterochromatin protein 1 (HP1) by Elgin and co-workers in the mid-1980s suggested that the distinct cytological features of this chromatin may be …

Minus-End Capture Of Preformed Kinetochore Fibers Contributes To Spindle Morphogenesis, Alexey Khodjakov, Lily Copenagle, Michael B. Gordon, Duane A. Compton, Tarun M. Kapoor

Dartmouth Scholarship

Near-simultaneous three-dimensional fluorescence/differential interference contrast microscopy was used to follow the behavior of microtubules and chromosomes in living alpha-tubulin/GFP-expressing cells after inhibition of the mitotic kinesin Eg5 with monastrol. Kinetochore fibers (K-fibers) were frequently observed forming in association with chromosomes both during monastrol treatment and after monastrol removal. Surprisingly, these K-fibers were oriented away from, and not directly connected to, centrosomes and incorporated into the spindle by the sliding of their distal ends toward centrosomes via a NuMA-dependent mechanism. Similar preformed K-fibers were also observed during spindle formation in untreated cells. In addition, upon monastrol removal, centrosomes established a transient …

Asymmetry Of The Central Apparatus Defines The Location Of Active Microtubule Sliding In Chlamydomonas Flagella, Matthew J. Wargo, Elizabeth F. Smith

Dartmouth Scholarship

Regulation of ciliary and flagellar motility requires spatial control of dynein-driven microtubule sliding. However, the mechanism for regulating the location and symmetry of dynein activity is not understood. One hypothesis is that the asymmetrically organized central apparatus, through interactions with the radial spokes, transmits a signal to regulate dynein-driven microtubule sliding between subsets of doublet microtubules. Based on this model, we hypothesized that the orientation of the central apparatus defines positions of active microtubule sliding required to control bending in the axoneme. To test this, we induced microtubule sliding in axonemes isolated from wild-type and mutant Chlamydomonas cells, and then …

G03-1514 Use Of Feed Contaminated With Fungal (Mold) Toxins (Mycotoxins), Michael P. Carlson, Steve M. Ensley

University of Nebraska-Lincoln Extension: Historical Materials

Mycotoxins are chemicals produced by fungi (molds) under certain conditions. They are not essential for fungal growth or reproduction, and they are toxic to animals or humans. They are naturally occurring chemicals found in grains, food and feed consumed by humans and animals and cannot be completely avoided. Accordingly, we try to control the amount of such chemicals ingested by humans and animals.

The purpose of this NebGuide is to provide guidelines on use of mycotoxin-contaminated feeds.

G03-1515 Sampling And Analyzing Feed For Fungal (Mold) Toxins (Mycotoxins), Michael P. Carlson, Steven M. Ensley

University of Nebraska-Lincoln Extension: Historical Materials

Mycotoxins are chemicals produced by fungi (molds) under certain conditions. They are not essential for fungal growth or reproduction, and are toxic to animals or humans. They are naturally present in feed and cannot always be avoided.

The purposes of this NebGuide are to provide information about sampling feeds to detect the presence of mycotoxins in them and about how feeds may be analyzed for mycotoxins.

G03-1527 Annual Forages For The Nebraska Panhandle, Burt A. Weichenthal, David D. Baltensperger, K. P. Vogel, S. D. Masterson, J.M. Blumenthal, J.M. Krall

University of Nebraska-Lincoln Extension: Historical Materials

Annual forages have value as pasture, green chop, silage, and hay. With adequate soil moisture, these forages grow very rapidly during their appropriate growing seasons. Advantages and disadvantages of various annual forages, results of dryland and irrigated forage trials, tips for achieving quality forage, and issues related to animal health and feeding forages are discussed in this NebGuide.

G03-1513 Understanding Fungal (Mold) Toxins (Mycotoxins), Michael P. Carlson, Steveb M. Ensley

University of Nebraska-Lincoln Extension: Historical Materials

Mycotoxins are chemicals produced by fungi (molds) under certain conditions. They are not essential for fungal growth or reproduction, and are toxic to animals or humans.

This NebGuide briefly discusses mycotoxins commonly encountered in grains and feeds used in Nebraska and the mycotoxicoses they cause. Mycotoxin sources and clinical signs, lesions, diagnostic aids and treatment for each mycotoxicosis are listed.

Nf03-571 Aspergillus Flavus And Aflatoxins In Corn, Jim Stack, Michael Carlson

University of Nebraska-Lincoln Extension: Historical Materials

The severe weather conditions of the 2002 growing season resulted in an increase in the incidence and severity of aflatoxin contamination of both food grade and feed grade corn in Nebraska.

The mycotoxin called aflatoxin is produced by the grain mold Aspergillus flavus. Not all isolates of A. flavus produced aflatoxin and isolates that are capable of producing aflatoxin do not always synthesize the toxin. Many factors including environmental conditions and host suscepbitility, determine the incidence and severity of grain mold and subsequent mycotoxin contamination.

This NebFact discusses the cause and occurrence of aflatoxin in corn; the effects it has …

Nf03-570 Fumonisins In Corn, Jim Stack, Michael Carlson

University of Nebraska-Lincoln Extension: Historical Materials

During the past two years, millers have rejected some Nebraska food grade corn because it was contaminated with the mycotoxin fumonisin. Most of the contaminated samples and the highest levels of contamination were detected in corn from counties in the eastern half of Nebraska.

Fumonisins are mycotoxins produced by the grain molds Fusarium verticillioides and Fusarium proliferatum. These fungi are commonly found in corn throughout the United States.

This NebFact discusses the cause and occurrence of fumonisin in corn; the effects it has on plants, animals and humans; and management options to minimize fumonisin contamination.

G03-1501 Prudent Use Of Antibiotics In Companion Animals, Katherine Irwin, David R. Smith, Grasso M. Ebako, Steve Ensley, Dicky D. Griffin, Arden Wohlers

University of Nebraska-Lincoln Extension: Historical Materials

This NebGuide explains why antibiotics must be used with care and how to prudently use antibiotics to treat companion animals.

Antibiotics are used to improve animal health and performance. You, as the animal owner or caregiver, make important decisions about how antibiotics are finally used in companion animals. Antibiotics should be used prudently to ensure they are effective and will continue to benefit man and animals in the future. Are you prepared to make the best decisions about using antibiotics in animals?

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …

Ccr4-Bearing T Cells Participate In Autoimmune Diabetes., Soon H. Kim, Mary M. Cleary, Howard S. Fox, Icos Coporation, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore, …

The Cd154/Cd40 Interaction Required For Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated By Upregulation Of The Cd80/Cd86 Costimulatory Molecules, Kathy A. Green, W. James Cook, Arlene H. Sharpe, William R. Green

Dartmouth Scholarship

C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40^−/− and CD154^−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4⁺ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86^−/− B6 mice develop MAIDS after LP-BM5 infection.

Gag Proteins Of The Two Drosophila Telomeric Retrotransposons Are Targeted To Chromosome Ends, Svetlana Rashkova, Sarah E. Karam, Rebecca Kellum, Mary-Lou Pardue

Biology Faculty Publications

Drosophila telomeres are formed by two non-LTR retrotransposons, HeT-A and TART, which transpose only to chromosome ends. Successive transpositions of these telomeric elements yield arrays that are functionally equivalent to the arrays generated by telomerase in other organisms. In contrast, other Drosophila non-LTR retrotransposons transpose widely through gene-rich regions, but not to ends. The two telomeric elements encode very similar Gag proteins, suggesting that Gag may be involved in their unique targeting to chromosome ends. To test the intrinsic potential of these Gag proteins for targeting, we tagged the coding sequences with sequence of GFP and expressed the constructs …

Mad2 And Bubr1 Function In A Single Checkpoint Pathway That Responds To A Loss Of Tension, Katie Shannon, Julie C. Canman, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

The spindle checkpoint monitors microtubule attachment and tension at kinetochores to ensure proper chromosome segregation. Previously, PtK1 cells in hypothermic conditions (23°C) were shown to have a pronounced mitotic delay, despite having normal numbers of kinetochore microtubules. At 23°C, we found that PtK1 cells remained in metaphase for an average of 101 min, compared with 21 min for cells at 37°C. The metaphase delay at 23°C was abrogated by injection of Mad2 inhibitors, showing that Mad2 and the spindle checkpoint were responsible for the prolonged metaphase. Live cell imaging showed that kinetochore Mad2 became undetectable soon after chromosome congression. Measurements …

Meiotic Cohesion Requires Accumulation Of Ord On Chromosomes Before Condensation, Eric M. Balicky, Matthew W. Endres, Cary Lai, Sharon E. Bickel

Dartmouth Scholarship

Cohesion between sister chromatids is a prerequisite for accurate chromosome segregation during mitosis and meiosis. To allow chromosome condensation during prophase, the connections that hold sister chromatids together must be maintained but still permit extensive chromatin compaction. In Drosophila, null mutations in the orientation disruptor (ord) gene lead to meiotic nondisjunction in males and females because cohesion is absent by the time that sister kinetochores make stable microtubule attachments. We provide evidence that ORD is concentrated within the extrachromosomal domains of the nuclei ofDrosophila primary spermatocytes during early G2, but accumulates on the meiotic chromosomes by …

Defective Cd19-Dependent Signaling In B-1a And B-1b B Lymphocyte Subpopulations., Goutam Sen, Hsin-Jung Wu, Gabriel Bikah, Chandrasekar Venkataraman, Darrell A Robertson, E Charles Snow, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Peritoneal and pleural cavities in mice and humans contain a unique population of B-lymphocytes called B-1 cells that are defective in B cell antigen receptor (BCR) signaling but have an increased propensity to produce autoantibodies. Several molecules such as Btk, Vav, and CD19 known to be important for BCR signaling have been shown to be critical for the development of B-1 cells from undefined precursors. Here we demonstrate that B-1 cell unresponsiveness to BCR cross-linking is in part due to defective signaling through CD19, a molecule known to modulate signaling thresholds in B cells. The defective CD19 signaling is manifested …

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 …

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.

Analyses Of Diet And Geographic Variation In Leaf-Nosed Snakes, Phyllorhynchus, Stephanie A. Gardner

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This study revealed that P. decurtatus primarily eat squamate eggs, and that the diet of P. browni appears to consist entirely of squamate eggs; gecko tails constitute a very small proportion of the diet of P. decurtatus. Feeding in both species occurred throughout their active seasons and both species increased prey consumption in August. The sexes of P. browni, but not P. decurtatus showed different monthly feeding patterns. Desert-of-collection did not affect P. decurtatus monthly feeding patterns. Phyllorhynchus decurtatus collected from the Sonoran Desert and P. browni, which is found only in the Sonoran Desert, showed similar …

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 …

A Middle Pleistocene Age And Biogeography For The Extinct Rodent Megalomys Curazensis From Curaçao, Netherlands Antilles, Donald A. Mcfarlane, Joyce Lundberg

WM Keck Science Faculty Papers

The extinct oryzomyine rodent Megalomys curazensis has been known from abundant but fragmentary remains on the island of Curaçao since 1959. Here we demonstrate an age of 130 000 to 400 000 years before present based on geomorphological context, and propose a biogeographical model for the genus.

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.

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 …

Presented Antigen From Damaged Pancreatic Beta Cells Activates Autoreactive T Cells In Virus-Mediated Autoimmune Diabetes., Marc S. Horwitz, Alex Ilic, Cody Fine, Enrique Rodriguez, Nora Sarvetnick

Journal Articles: Regenerative Medicine

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged beta cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice …