Digital Commons Network^™

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 …

Hierarchical Processing In Spoken Language Comprehension., Matthew H Davis, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Understanding spoken language requires a complex series of processing stages to translate speech sounds into meaning. In this study, we use functional magnetic resonance imaging to explore the brain regions that are involved in spoken language comprehension, fractionating this system into sound-based and more abstract higher-level processes. We distorted English sentences in three acoustically different ways, applying each distortion to varying degrees to produce a range of intelligibility (quantified as the number of words that could be reported) and collected whole-brain echo-planar imaging data from 12 listeners using sparse imaging. The blood oxygenation level-dependent signal correlated with intelligibility along the …

Mammalian Erv46 Localizes To The Endoplasmic Reticulum–Golgi Intermediate Compartment And To Cis-Golgi Cisternae, Lelio Orci, Mariella Ravazzola, Gary J. Mack, Charles Barlowe, Stefan Otte

Dartmouth Scholarship

Yeast endoplasmic reticulum (ER) vesicle protein Erv46p is a novel membrane protein involved in transport through the early secretory pathway. Investigation of mammalian Erv46 (mErv46) reveals that it is broadly expressed in tissues and protein-secreting cells. By immunofluorescence microscopy, mErv46 displays a crescent-shaped perinuclear staining pattern that is characteristic of the Golgi complex. Quantitative immunoelectron microscopy indicates that mErv46 is restricted to the cis face of the Golgi apparatus and to vesicular tubular structures between the transitional ER and cis-Golgi. Minor amounts of mErv46 reside in ER membranes and later Golgi cisternae. On Brefeldin A treatment, mErv46 redistributes to punctate …

The Association Of Academic Health Sciences Libraries Annual Statistics: A Thematic History, James Shedlock, Gary D. Byrd

Library Press and Events

No abstract provided.

Cell-Cycle Regulatory Proteins In Podocyte Cell In Idiopathic Nephrotic Syndrome Of Childhood., Tarak Srivastava, Robert E. Garola, J M. Whiting, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The podocyte cell is believed to play an important role in idiopathic nephrotic syndrome (INS) of childhood. In adults with cellular and collapsing focal segmental glomerulosclerosis (FSGS), the expression of cell-cycle regulatory proteins such as p27, p57, and cyclin D is decreased and expression of cyclin A, Ki-67, and p21 is observed in podocyte cells suggestive of a dysregulated podocyte phenotype. We investigated for alterations in the expression of cyclin kinase inhibitors, p27, p57, p21, and cyclins D and A in the podocyte cell of children with INS.

METHODS: Forty-two kidney biopsies were investigated; 14 with minimal-change disease (MCD), …

Human Acyl-Coenzyme A:Cholesterol Acyltransferase Expressed In Chinese Hamster Ovary Cells: Membrane Topology And Active Site Location, Song Lin, Xiaohui Lu, Catherine C.Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2) have been identified. The expression of ACAT1 is ubiquitous, whereas that of ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain seven transmembrane domains (TMDs). To study ACAT2 topology, we inserted two different antigenic tags (hemagglutinin, monoclonal antibody Mab1) at various hydrophilic regions flanking each of its predicted TMDs, and expressed the recombinant proteins in mutant Chinese hamster ovary cells lacking endogenous ACAT. Each tagged ACAT2 was expressed in the endoplasmic reticulum as a single undegraded protein band …

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 …

An Automated Treatment For Jet Lag Delivered Through The Internet., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Seventy percent of persons who suffer from psychiatric illness do not receive treatment. Cost-effective, automated treatment can be delivered through the Internet but can be complicated by the lack of professional supervision. This open study piloted a fully automated, publicly available treatment for jet lag as a means of highlighting some of the issues involved in delivering treatment over the Internet. Twenty study participants rated the severity of their jet lag symptoms and their adherence to a light-exposure schedule calculated to accelerate adaptation to a new time zone. A significant negative correlation was observed between how closely participants followed the …

Glucuronidation Enzymes, Genes And Psychiatry, Jose De Leon

Psychiatry Faculty Publications

The phase I cytochrome P450 (CYP) isoenzymes have received substantial attention in the pharmacogenetic literature. Researchers are beginning to examine the role of the phase II UDP-glucuronosyltransferase (UGT) enzymes, which produce products that are more water-soluble, less toxic and more readily excreted than the parent compounds. Several reasons may have contributed to neglect of UGTs (compared to CYPs) including: (1) the overlapping activity of UGTs and lack of selective probes; (2) the complexity of the glucuronidation cycle; and (3) the difficulty in developing analytic methods to measure glucuronides. Current CYP knowledge is used as a model to predict advances in …

Transfection Of Il-10 Expression Vectors Into Endothelial Cultures Attenuates Alpha4beta7-Dependent Lymphocyte Adhesion Mediated By Madcam-1., Makoto Sasaki, Paul Jordan, Jeff Houghton, Xianmin Meng, Makoto Itoh, Takashi Joh, J Steven Alexander

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression …

Responsiveness Of Bovine Cumulus-Oocyte-Complexes (Coc) To Porcine And Recombinant Human Fsh, And The Effect Of Coc Quality On Gonadotropin Receptor And Cx43 Marker Gene Mrnas During Maturation In Vitro., Michele D Calder, Anita N Caveney, Lawrence C Smith, Andrew J Watson

Obstetrics & Gynaecology Publications

Substantially less development to the blastocyst stage occurs in vitro than in vivo and this may be due to deficiencies in oocyte competence. Although a large proportion of bovine oocytes undergo spontaneous nuclear maturation, less is known about requirements for proper cytoplasmic maturation. Commonly, supraphysiological concentrations of FSH and LH are added to maturation media to improve cumulus expansion, fertilization and embryonic development. Therefore, various concentrations of porcine FSH (pFSH) and recombinant human FSH (rhFSH) were investigated for their effect on bovine cumulus expansion in vitro. Expression of FSHr, LHr and Cx43 mRNAs was determined in cumulus-oocyte complexes to determine …

Promoters Of The Murine Embryonic Β-Like Globin Genes Ey And Βh1 Do Not Compete For Interaction With The Β-Globin Locus Control Region, Xiao Hu, Michael Bulger, Julia N. Roach, Susan K. Eszterhas, Emmanuel Olivier, Eric Bouhassira, Mark Groudine, Steven Fiering

Dartmouth Scholarship

Mammalian β-globin loci contain multiple β-like genes that are expressed at different times during development. The murine β-globin locus contains two genes expressed during the embryo stage, Ey and βh1, and two genes expressed at both the fetal and postnatal stages, β-major and β-minor. Studies of transgenic human β-like globin loci in mice have suggested that expression of one gene at the locus will suppress expression of other genes at the locus. To test this hypothesis we produced mouse lines with deletions of either the Ey or βh1 promoter in the endogenous murine β-globin locus. Promoter deletion eliminated expression of …

Effects Of Tacrolimus On Ischemia-Reperfusion Injury., Shawn D. St Peter, Adyr A. Moss, David C. Mulligan

Manuscripts, Articles, Book Chapters and Other Papers

In addition to efficacious immunosuppression for the benefit of organ transplantation, tacrolimus has diverse actions that result in amelioration of ischemia-reperfusion injury. Knowledge is accumulating rapidly on the mechanisms through which tacrolimus exerts these cytoprotective effects, including alterations in microcirculation, free radical metabolism, calcium-activated pathways, inflammatory cascades, mitochondrial stability, apoptosis, stress-response proteins, and tissue recovery. Within the nucleus, actions mediating the effects of tacrolimus appear to be dominantly influenced by interactions with the transcription factor, nuclear factor-kappaB. Because tacrolimus is a cornerstone agent in immunosuppression regimens throughout the world and knowledge of its cellular mechanisms is evolving, it is important …

Tacrolimus As A Liver Flush Solution To Ameliorate The Effects Of Ischemia/Reperfusion Injury Following Liver Transplantation., Shawn D. St Peter, David J. Post, Manuel I. Rodriguez-Davalos, David D. Douglas, Adyr A. Moss, David C. Mulligan

Manuscripts, Articles, Book Chapters and Other Papers

The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. …

Might A Psychosocial Approach Improve Our Understanding Of Itching And Scratching?, Herbert M. Adler

Department of Psychiatry and Human Behavior Faculty Papers

No abstract provided.

Regulation Of Human Col9a1 Gene Expression. Activation Of The Proximal Promoter Region By Sox9., Ping Zhang, Sergio A. Jimenez, David G Stokes

Department of Medicine Faculty Papers

The COL9A1 gene contains two promoter regions, one driving expression of a long alpha1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream). To determine how the chondrocyte-specific expression of the COL9A1 gene is regulated, we have begun to characterize the upstream chondrocyte-specific promoter region of the human COL9A1 gene. Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells. Inclusion of the first intron had no effect on promoter …

G03-1485 Guidelines For The Prudent Use Of Antibiotics In Food 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 food animals.

Antibiotics are used to improve animal health and productivity. You, the animal caregiver, make important decisions about how antibiotics are finally used in food producing animals. Antibiotics should be used prudently to ensure they are effective, do not leave residues in food, and will continue to benefit man and animals in the future. Are you prepared to make the best decisions about using antibiotics in animals?

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.

Relationships Between Human Auditory Cortical Structure And Function, Deborah A Hall, Heledd C Hart, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

The human auditory cortex comprises multiple areas, largely distributed across the supratemporal plane, but the precise number and configuration of auditory areas and their functional significance have not yet been clearly established. In this paper, we discuss recent research concerning architectonic and functional organisation within the human auditory cortex, as well as architectonic and neurophysiological studies in non-human species, which can provide a broad conceptual framework for interpreting functional specialisation in humans. We review the pattern in human auditory cortex of the functional responses to various acoustic cues, such as frequency, pitch, sound level, temporal variation, motion and spatial location, …

Educating Adolescents About Puberty: What Are We Missing?, Hatim A. Omar, Darby H. Mcelderry, Rana M. Zakharia

Pediatrics Faculty Publications

Adolescents undergo significant physical and cognitive changes during their pubertal development. These changes contribute to and impact their future development. Educating adolescents at an early age about their expected development decreases the possible anxiety associated with this period of life and also helps adolescents make better choices in regards to their sexuality. In order to assess the degree of education regarding pubertal development and sexuality, we conducted a survey of late adolescents (Median age 19 years) and parents of adolescents. A total of 409 adolescents (237 females, 172 males) and 124 parents completed the survey. 14.4% of teens (36.6% of …

Platelets Stimulate Fibroblast-Mediated Contraction Of Collagen Gels, Ulrika Zagai, Karin Fredriksson, Stephen I. Rennard, Joachim Lundahl, C. Magnus Sköld

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) contribute to this effect.

METHODS: Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing), were cast together with human lung fibroblasts in three-dimensional collagen gels. …

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.

Our Adolescents--Our Future, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

The Permeability Of The Endoplasmic Reticulum Is Dynamically Coupled To Protein Synthesis, Anirban Roy, William F. Wonderlin

Faculty & Staff Scholarship

No abstract provided.

Nucleotide Excision Repair- And Polymerase Eta-Mediated Error-Prone Removal Of Mitomycin C Interstrand Cross-Links, H. Zheng, X. Wang, A. J. Warren, R. J. Legerski, Rodney S. Nairn, Joshua W. Hamilton, Lei Li

Dartmouth Scholarship

Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which both strands of the double helix are covalently joined, precluding strand opening during replication and transcription. The repair of DNA ICLs has become a focus of study since ICLs are recognized as the main cytotoxic lesion inflicted by an array of alkylating compounds used in cancer treatment. As is the case for double-strand breaks, a damage-free homologous copy is essential for the removal of ICLs in an error-free manner. However, recombination-independent mechanisms may exist to remove ICLs in an error-prone fashion. We have developed an in vivo …

Sex Education In The Schools: What Role Does It Play?, Darby H. Mcelderry, Hatim A. Omar

Pediatrics Faculty Publications

Information regarding pubertal development, sex, pregnancy, and contraception should be provided to children and adolescents in an age-appropriate manner from parents, health care providers, and schools. This article reviews the medical literature on school sex education programs, adolescents' perception of these programs, and the role played by the media, parents, and health care professionals in sexual education of teens.

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.