Digital Commons Network^™

Rab-10 Is Required For Endocytic Recycling In The Caenorhabditis Elegans Intestine, Carlos Chih-Hsiung Chen, Peter J. Schweinsberg, Shilpa Vashist, Darren P. Mareiniss, Eric J. Lambie, Barth D. Grant

Dartmouth Scholarship

The endocytic pathway of eukaryotes is essential for the internalization and trafficking of macromolecules, fluid, membranes, and membrane proteins. One of the most enigmatic aspects of this process is endocytic recycling, the return of macromolecules (often receptors) and fluid from endosomes to the plasma membrane. We have previously shown that the EH-domain protein RME-1 is a critical regulator of endocytic recycling in worms and mammals. Here we identify the RAB-10 protein as a key regulator of endocytic recycling upstream of RME-1 in polarized epithelial cells of the Caenorhabditis elegans intestine. rab-10 null mutant intestinal cells accumulate abnormally abundant RAB-5-positive early …

Interdependency Of Pharmacokinetic Parameters: A Chicken-And-Egg Problem? Not!, Reza Mehvar

Pharmacy Faculty Articles and Research

Pharmacokinetic (PK) software packages are widely used by scientists in different disciplines to estimate PK parameters. However, their use without a clear understanding of physiological parameters affecting the PK parameters and how different PK parameters are related to each other may result in erroneous interpretation of data. Often, mathematical relationships used for the estimation of PK parameters obscure the true physiological relationships among these parameters, prompting a discussion of which parameter came first and giving the appearance of the-chicken-and-the-egg dilemma. In this article, the author attempts to show how different PK parameters are related to physiological parameters and each other …

Laboratory Diagnosis Of Tuberculosis In Primary Care, David Brett-Major, Thomas E. Walsh

Journal Articles: Epidemiology

No abstract provided.

Collections To Pests: How Insects And Humans Share Responsibility For Object Destruction In Museums, Diana Massar

Seton Hall University Dissertations and Theses (ETDs)

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Mutant Neurogenin-3 In Congenital Malabsorptive Diarrhea, Jiafang Wang, Galen Cortina, S. Vincent Wu, Robert Tran, Jang-Hyeon Cho, Ming-Jer Tsai, Travis J. Bailey, Milan Jamrich, Marvin E. Ament, William R. Treem, Ivor D. Hill, Jorge H. Vargas, George Gershman, Douglas G. Farmer, Laurie Reyen, Martin G. Martín

Biology

Background: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells. Methods: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays. Results: The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had …

Innate Antiviral Response Targets Hiv-1 Release By The Induction Of Ubiquitin-Like Protein Isg15, Atsushi Okumura, Gengshi Lu, Ian Pitha-Rowe, Paula M. Pitha

Dartmouth Scholarship

The goal of this study was to elucidate the molecular mechanism by which type I IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits release of HIV-1 virions without having any effect on the synthesis of HIV-1 proteins in the cells. ISG15 expression specifically inhibited ubiquitination of Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag-Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells. Elimination …

Embryonic Stem Cell-Derived Hematopoietic Stem Cells, Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, George Q. Daley

Dartmouth Scholarship

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4 , we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites …

Visibility, Visual Awareness, And Visual Masking Of Simple Unattended Targets Are Confined To Areas In The Occipital Cortex Beyond Human V1/V2, Peter U. Tse, Susanna Martinez-Conde, Alexander A. Schlegel, Stephen L. Macknik

Dartmouth Scholarship

In visual masking, visible targets are rendered invisible by modifying the context in which they are presented, but not by modifying the targets themselves. Here, we localize the neuronal correlates of visual awareness in the human brain by using visual masking illusions. We compare monoptic visual masking activation, which we find within all retinotopic visual areas, with dichoptic masking activation, which we find only in those retinotopic areas downstream of V2. Because monoptic and dichoptic masking are equivalent in magnitude perceptually, the present results establish a lower bound for maintenance of visual awareness of simple unattended targets. Moreover, we find …

Experts Recommend Strategies For Strengthening The Use Of Advanced Practice Nurses In Nursing Homes., Mathy Mezey, Sarah Greene Burger, Harrison G Bloom, Alice Bonner, Mary Bourbonniere, Barbara Bowers, Jeffrey B Burl, Elizabeth Capezuti, Diane Carter, Jacob Dimant, Sarah A Jerro, Susan C Reinhard, Marilyn Ter Maat

College of Nursing Faculty Papers & Presentations

In 2003, The John A. Hartford Foundation Institute for Geriatric Nursing, New York University Division of Nursing, convened an expert panel to explore the potential for developing recommendations for the caseloads of advanced practice nurses (APNs) in nursing homes and to provide substantive and detailed strategies to strengthen the use of APNs in nursing homes. The panel, consisting of nationally recognized experts in geriatric practice, education, research, public policy, and long-term care, developed six recommendations related to caseloads for APNs in nursing homes. The recommendations address educational preparation of APNs; average reimbursable APN visits per day; factors affecting APNs caseload …

Taxol-Stabilized Microtubules Can Position The Cytokinetic Furrow In Mammalian Cells, Katie Shannon, Julie C. Canman, C. Ben Moree, Jennifer S. Tirnauer, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

How microtubules act to position the plane of cell division during cytokinesis is a topic of much debate. Recently, we showed that a subpopulation of stable microtubules extends past chromosomes and interacts with the cell cortex at the site of furrowing, suggesting that these stabilized microtubules may stimulate contractility. To test the hypothesis that stable microtubules can position furrows, we used taxol to rapidly suppress microtubule dynamics during various stages of mitosis in PtK1 cells. Cells with stabilized prometaphase or metaphase microtubule arrays were able to initiate furrowing when induced into anaphase by inhibition of the spindle checkpoint. In these …

The Chemical Species Of Aluminum Influences Its Paracellular Flux Across And Uptake Into Caco-2 Cells, A Model Of Gastrointestinal Absorption, Yuzhao Zhou, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in 35-mm-diameter plastic cell culture dishes. When 8 mM ²⁷Al was introduced as the ion, citrate, maltolate, fluoride, or hydroxide, the apical to basolateral apparent permeability (P_app) of Al correlated highly with the P_app of lucifer yellow …

Ergonomics: Implications On Computer End-Users, Maheen Ghauri, Dr. Arshad Siddiqi

International Conference on Information and Communication Technologies

Ergonomics is the application of scientific information related to humans to the design of objects, systems and environment for human use. The objective is to apply human characteristics to the design of computer-based work environments to reduce problems of people at work. Lack of ergonomics has serious repercussions on end-users, including physical and mental illnesses. Using ergonomics to design computer-intensive environments would maximize efficiency, productivity and job satisfaction of employees. Unfortunately, in the Government Sector in Pakistan, there is no application of ergonomics in computer-based environments, and this leads to inefficiencies, errors, and safety and health issues. The purpose of …

The Human Paf Complex Coordinates Transcription With Events Downstream Of Rna Synthesis., Bing Zhu, Subhrangsu S. Mandal, Anh-Dung Pham, Yong Zheng, Hediye Erdjument-Bromage, Surinder K. Batra, Paul Tempst, Danny Reinberg

Journal Articles: Biochemistry & Molecular Biology

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates …

Avoiding Versus Seeking: The Relationship Of Information Seeking To Avoidance, Blunting, Coping, Dissonance, And Related Concepts, Donald O. Case, James E. Andrews, J. David Johnson, Suzanne L. Allard

Information Science Faculty Publications

QUESTION: How have theorists and empirical researchers treated the human tendency to avoid discomforting information?

DATA SOURCES: A historical review (1890-2004) of theory literature in communication and information studies, coupled with searches of recent studies on uptake of genetic testing and on coping strategies of cancer patients, was performed.

STUDY SELECTION: The authors' review of the recent literature included searches of the MEDLINE, PsychInfo, and CINAHL databases between 1992 and summer of 2004 and selective, manual searches of earlier literature. Search strategies included the following subject headings and key words: MeSH headings: Genetic Screening/psychology, Decision Making, Neoplasms/diagnosis/genetics/psychology; CINAHL headings: Genetic …

A Model Program For Youth Suicide Prevention, Hatim A. Omar

Pediatrics Faculty Publications

Youth suicide continues to be one of the leading causes of death in the United States. Nation wide it is the third leading cause of death in the 10-24 year old age group. The rate of suicide varies somewhat from state to state. In the state of Kentucky, youth suicide is the second leading cause of death. This article describes a grass root, community-based program for youth suicide prevention and its impact on the community. The Stop Youth Suicide Campaign was launched in October 2000 and included more than 30 local agencies. This program worked. through public education, education of …

Avoiding Versus Seeking: The Relationship Of Information Seeking To Avoidance, Blunting, Coping, Dissonance, And Related Concepts, Donald O. Case, James E. Andrews, J. David Johnson, Suzanne L. Allard

School of Information Faculty Publications

QUESTION: How have theorists and empirical researchers treated the human tendency to avoid discomforting information?

DATA SOURCES: A historical review (1890-2004) of theory literature in communication and information studies, coupled with searches of recent studies on uptake of genetic testing and on coping strategies of cancer patients, was performed.

STUDY SELECTION: The authors' review of the recent literature included searches of the MEDLINE, PsychInfo, and CINAHL databases between 1992 and summer of 2004 and selective, manual searches of earlier literature. Search strategies included the following subject headings and key words: MeSH headings: Genetic Screening/psychology, Decision Making, Neoplasms/diagnosis/genetics/psychology; CINAHL headings: Genetic …

Erythroid Cell-Specific Α-Globin Gene Regulation By The Cp2 Transcription Factor Family, Ho C. Kang, Jui Hyung Chae, Yeon H. Lee, Mi-Ae Park, June Ho Shin, Sung-Hyun Kim, Sang-Kyu Ye, Yoon Shin Cho, Steven Fiering, Chul Geun Kim

Dartmouth Scholarship

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of …

Gonadal Steroids Differentially Modulate Neurotoxicity Of Hiv And Cocaine: Testosterone And Ici 182,780 Sensitive Mechanism, Sherie L. Kendall, Caroline F. Anderson, Avindra Nath, Jadwiga Turchan-Cholewo, Cantey L. Land, Charles F. Mactutus, Rosemarie M. Booze

Behavioral Science Faculty Publications

BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, …

Information-Seeking Behaviors Of Practitioners In A Primary Care Practice-Based Research Network (Pbrn), James E. Andrews, Kevin A. Pearce, Carol Ireson, Margaret M. Love

School of Information Faculty Publications

OBJECTIVE: The aim of this study was to examine the information-seeking behaviors (e.g., information resource usage patterns, access to types of sources and to medical libraries, and use of particular information technologies) of members in a primary care practice-based research network (PBRN) to inform future efforts supporting primary care practitioners in their daily care of patients.

METHODS: Every primary care practitioner who was a member of the Kentucky Ambulatory Network-including family practitioners, general practitioners, nurse practitioners, and physician assistants-was surveyed. The cross-sectional survey included twenty-six questions to investigate the information-seeking behavior of primary care practitioners.

RESULTS: The response rate was …

Clinical Characteristics Of Individuals Using An Online Alcohol Evaluation Program., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Access to treatment for substance abuse disorders is limited, and practical strategies are needed to expand opportunities for individuals to receive effective interventions. Automated or semi-automated treatments have shown promise in other disorders. Identifying the characteristics of patients who will be able to benefit from this unconventional approach will increase the likelihood of success. The current study examined 1,297 individuals using an online alcohol evaluation program. Subjects had high scores on the Alcohol Use Disorders Identification Test (AUDIT) and a substantial amount of ambivalence about the possible harm that their drinking caused, but they also had very low levels of …

Developing And Deploying A New Member Of The Dental Team: A Pediatric Oral Health Therapist, David A. Nash

Oral Health Science Faculty Publications

There are inadequate numbers of dentists able and willing to treat America's children, specifically children from low income and minority populations. This has led to the well-publicized disparities in oral health among children. In the early part of the 20^th century New Zealand faced a significant problem with oral disease among its children and introduced a School Dental Service, staffed by allied dental professionals with two years' training in caring for the teeth of children, "school dental nurses." A significant number of countries have adopted the model. This article reviews the history of attempts to develop such an approach …

The Meaning Of Computers To A Group Of Men Who Are Homeless., Kathleen Swenson Miller, Stacey Bunch-Harrison, Brett Brumbaugh, Rekha Sankaran Kutty, Kathleen Fitzgerald

Department of Occupational Therapy Faculty Papers

The purpose of this pilot study was to explore the experience with computers and the meaning of computers to a group of homeless men living in a long-term shelter. This descriptive exploratory study used semistructured interviews with seven men who had been given access to computers and had participated in individually tailored occupation based interventions through a Work Readiness Program. Three themes emerged from analyzing the interviews: access to computers, computers as a bridge to life-skill development, and changed self-perceptions as a result of connecting to technology. Because they lacked computer knowledge and feared failure, the majority of study participants …

Persuasive Email Messages For Patient Communication, Muhammad Walji, Kathy Johnson-Throop, Todd Johnson, Elmer Bernstam, Jiajie Zhang

Faculty, Staff and Student Publications

To improve health and reduce costs, we need to encourage patients to make better health care decisions. Since email is widely available, it may be useful for patient-directed interventions. However, we know little about how the contents of an email message can influence a health-related decision. We propose a model to understand how patients may process persuasive email messages.

Prophylactic Defibrillator Implantation—Toward An Evidence-Based Approach, Alan H. Kadish

Office of the President Publications and Research

The author discusses research on using implantable cardioverter-defibrillators for the primary prevention of sudden death.

The Kidney-Specific Wnk1 Isoform Is Induced By Aldosterone And Stimulates Epithelial Sodium Channel-Mediated Na+ Transport, Anikó Naray-Fejes-Toth, Peter M. Snyder, Géza Fejes-Toth

Dartmouth Scholarship

WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in the control of blood pressure. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. How overexpression of WNK1 leads to Na⁺ retention and hypertension is not entirely clear. Similarly, there is no information on the hormonal regulation of expression of WNK kinases. There are two main WNK1 transcripts expressed in the kidney: the originally described “long” WNK1 and a shorter transcript that is specifically expressed in the kidney (KS-WNK1). The goal …

Factors Influencing Appraisal Of Upset In Black Caregivers Of Persons With Alzheimer Disease And Related Dementias, Susan Toth-Cohen

Department of Occupational Therapy Faculty Papers

Black caregivers of persons with Alzheimer disease and related dementias (ADRD) have demonstrated significantly lower levels of stress and burden than white caregivers, as measured by instruments that assess caregiving burden and stressfulness of specific problem behaviors. However, the reasons for reported differences are unclear and cannot be attributed solely to race. This descriptive study used content analysis to compare black caregivers’ descriptions and interpretations of responses to memory and behavioral issues of relatives with ADRD to 11 explanations for lower levels of upset proposed in the caregiving literature. Findings confirmed only two explanations from the literature, social support and …

Control Of Mitochondrial Motility And Distribution By The Calcium Signal: A Homeostatic Circuit., Muqing Yi, David Weaver, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria are dynamic organelles in cells. The control of mitochondrial motility by signaling mechanisms and the significance of rapid changes in motility remains elusive. In cardiac myoblasts, mitochondria were observed close to the microtubular array and displayed both short- and long-range movements along microtubules. By clamping cytoplasmic [Ca2+] ([Ca2+]c) at various levels, mitochondrial motility was found to be regulated by Ca2+ in the physiological range. Maximal movement was obtained at resting [Ca2+]c with complete arrest at 1-2 microM. Movement was fully recovered by returning to resting [Ca2+]c, and inhibition could be repeated with no apparent desensitization. The inositol 1,4,5-trisphosphate- or …

Felix Platter: A Sixteenth-Century Medical Student, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Binding Between The Niemann–Pick C1 Protein And A Photoactivatable Cholesterol Analog Requires A Functional Sterol-Sensing Domain, Nobutaka Ohgami, Dennis C. Ko, Matthew Thomas, Matthew P. Scott, Catherine C. Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Niemann-Pick type C (NPC) 1 protein plays important roles in moving cholesterol and other lipids out of late endosomes by means of vesicular trafficking, but it is not known whether NPC1 directly interacts with cholesterol. We performed photoaffinity labeling of intact cells expressing fluorescent protein (FP)-tagged NPC1 by using [(3)H]7,7-azocholestanol ([(3)H]AC). After immunoprecipitation, (3)H-labeled NPC1-GFP appeared as a single band. Including excess unlabeled sterol to the labeling reaction significantly diminished the labeling. Altering the NPC1 sterol-sensing domain (SSD) with loss-of-function mutations (P692S and Y635C) severely reduced the extent of labeling. To further demonstrate the specificity of labeling, we show that …

From Biomedicine To Natural History Research: Est Resources For Ambystomatid Aalamanders, Srikrishna Putta, Jeramiah J. Smith, John A. Walker, Mathieu Rondet, David W. Weisrock, James Monaghan, Amy K. Samuels, D. Kevin Kump, David C. King, Nicholas J. Maness, Bianca Habermann, Elly Tanaka, Susan V. Bryant, David M. Gardiner, David M. Parichy, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories.

RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the …