Digital Commons Network^™

Mechanistic Differences In Rna-Dependent Dna Polymerization And Fidelity Between Murine Leukemia Virus And Hiv-1 Reverse Transcriptases, Mark Skasko, Kellie K. Weiss, Holly M. Reynolds, Varuni Jamburuthugoda, Kwi Lee, Baek Kim

Biology

We compared the mechanistic and kinetic properties of murine leukemia virus (MuLV) and human immunodeficiency virus type 1 (HIV-1) reverse transcriptases (RTs) during RNA-dependent DNA polymerization and mutation synthesis using pre-steady-state kinetic analysis. First, MuLV RT showed 6.5-121.6-fold lower binding affinity (Kd) to deoxynucleotide triphosphate (dNTP) substrates than HIV-1 RT, although the two RTs have similar incorporation rates (kpol). Second, compared with HIV-1 RT, MuLV RT showed dramatic reduction during multiple dNTP incorporations at low dNTP concentrations. Presumably, due to its low dNTP binding affinity, the dNTP binding step becomes rate-limiting in the multiple rounds of the dNTP incorporation by …

Muscle Cramps And Weakness Secondary To Graft Versus Host Disease Fasciitis., Camille B. Carroll, D. A. Hilton, M. Hamon, J. P. Zajicek

Peninsula Medical School

No abstract provided.

Identifying Inaccuracies On Emergency Medicine Residency Applications., Eric D Katz, Lee Shockley, Lawrence Kass, David Howes, Janis P Tupesis, Christopher Weaver, Osman R Sayan, Victoria Hogan, Jason Begue, Diamond Vrocher, Jackie Frazer, Timothy Evans, Gene Hern, Ralph Riviello, Antonio Rivera, Keith Kinoshita, Edward Ferguson

Department of Emergency Medicine Faculty Papers

BACKGROUND: Previous trials have showed a 10-30% rate of inaccuracies on applications to individual residency programs. No studies have attempted to corroborate this on a national level. Attempts by residency programs to diminish the frequency of inaccuracies on applications have not been reported. We seek to clarify the national incidence of inaccuracies on applications to emergency medicine residency programs. METHODS: This is a multi-center, single-blinded, randomized, cohort study of all applicants from LCME accredited schools to involved EM residency programs. Applications were randomly selected to investigate claims of AOA election, advanced degrees and publications. Errors were reported to applicants' deans …

Identification Of Recql1 As A Holliday Junction Processing Enzyme In Human Cell Lines, Gary Leroy, Robert Carroll, Saw Kyin, Masayuki Seki, Michael D. Cole

Dartmouth Scholarship

Homologous recombination provides an effective way to repair DNA double-strand breaks (DSBs) and is required for genetic recombination. During the process of homologous recombination, a heteroduplex DNA structure, or a ‘Holliday junction’ (HJ), is formed. The movement, or branch migration, of this junction is necessary for recombination to proceed correctly. In prokaryotes, the RecQ protein or the RuvA/RuvB protein complex can promote ATP-dependent branch migration of Holliday junctions. Much less is known about the processing of Holliday junctions in eukaryotes. Here, we identify RecQL1 as a predominant ATP-dependent, HJ branch migrator present in human nuclear extracts. A reduction in the …

Arsenite Regulates Cystic Fibrosis Transmem­Brane Conductance Regulator And P-Glycoprotein: Evidence Of Pathway Independence, Rangan Maitra, Joshua Hamilton

Dartmouth Scholarship

In the past, people have argued for and against the theory of reciprocal regulation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and P-glycoprotein (Pgp). Data have indicated that this may occur in vitro during drug-induced selection of cells, and in vivo during development. Much of this debate has been caused by a severe lack of mechanistic details involved in such regulation. Our past data indicate that certain Pgp modulators can affect CFTR expression and function. The goal of this study was to investigate the effects of trivalent arsenic (arsenite), a known transcriptional activator of Pgp, on CFTR expression. In …

Analysis Of Oligonucleotide Array Experiments With Repeated Measures Using Mixed Models, Hao Li, Constance L. Wood, Thomas V. Getchell, Marilyn L. Getchell, Arnold J. Stromberg

Statistics Faculty Publications

BACKGROUND: Two or more factor mixed factorial experiments are becoming increasingly common in microarray data analysis. In this case study, the two factors are presence (Patients with Alzheimer's disease) or absence (Control) of the disease, and brain regions including olfactory bulb (OB) or cerebellum (CER). In the design considered in this manuscript, OB and CER are repeated measurements from the same subject and, hence, are correlated. It is critical to identify sources of variability in the analysis of oligonucleotide array experiments with repeated measures and correlations among data points have to be considered. In addition, multiple testing problems are more …

Influence Of Age, Gender, And Race On Depression In Heart Failure Patients., Ronald Freudenberger, Stacey C. Cahn, Christine Skotzko

PCOM Scholarly Works

No abstract provided.

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 …

Improved Quantification Of Small Objects In Near-Infrared Diffuse Optical Tomography, Subhadra Srinivasan, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Xiaomei Song, Keith D. Paulsen

Dartmouth Scholarship

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final …

Multiple Mechanisms Regulate Numa Dynamics At Spindle Poles, Olga Kisurina-Evgenieva, Gary Mack, Quansheng Du, Ian Macara, Alexey Khodjakov, Duane A. Compton

Dartmouth Scholarship

The large coiled-coil protein NuMA plays an essential role in organizing microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles. Using fluorescence recovery after photobleaching, we show that an exogenously expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange between soluble and spindle-associated pools in living cells. These dynamics require cellular energy and display an average half-time for fluorescence recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle poles is regulated, we exploited the association of NuMA with microtubule asters formed in …

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 …

The Kini Kinesin Kif2a Is Required For Bipolar Spindle Assembly Through A Functional Relationship With Mcak, Neil J. Ganem, Duane A. Compton

Dartmouth Scholarship

Although the microtubule-depolymerizing KinI motor Kif2a is abundantly expressed in neuronal cells, we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells. RNAi-induced knockdown of Kif2a expression inhibited cell cycle progression because cells assembled monopolar spindles. Bipolar spindle assembly was restored in cells lacking Kif2a by treatments that altered microtubule assembly (nocodazole), eliminated kinetochore–microtubule attachment (loss of Nuf2), or stabilized microtubule plus ends at kinetochores (loss of MCAK). Thus, two KinI motors, MCAK and Kif2a, play distinct roles in mitosis, and MCAK activity at kinetochores must be balanced by Kif2a activity at poles for spindle …

Melioration And The Behavioral Addiction Process: An Experimental Analysis, Jared Micah Dinehart

Theses and Dissertations

Melioration can be a factor contributing to behavioral addiction. In this study, 76 university undergraduates operated a "money machine" by selecting between choices that corresponded to maximization and melioration. Participants initially made choices consistent with a strategy of melioration and demonstrated significantly greater variability in choice behavior when visual cues were presented aimed at exposing the internality (or consequence) of the choice situation. Removal of the visual cues resulted in a return to lower responding. Visual cues may aid in interrupting the behavioral addiction pattern by limiting exclusive use of a melioration choice strategy. Methods of restructuring and experimentation with …

Comparison Of Transcranial Electric Motor And Somatosensory Evoked Potential Monitoring During Cervical Spine Surgery., Alan S Hilibrand, Daniel M Schwartz, Venkat Sethuraman, Alexander R Vaccaro, Todd J Albert

Rothman Institute Papers

BACKGROUND: There has been little enthusiasm for somatosensory evoked potential monitoring in cervical spine surgery as a result, in part, of the increased risk of motor tract injury at this level, to which somatosensory monitoring may be insensitive. Transcranial electric motor evoked potential monitoring allows assessment of the motor tracts; therefore, we compared transcranial electric motor evoked potential and somatosensory evoked potential monitoring during cervical spine surgery to determine the temporal relationship between the changes in the potentials demonstrated by each type of monitoring and neurological sequelae and to identify patient-related and surgical factors associated with intraoperative neurophysiological changes.

METHODS: …

Pv1 Is A Key Structural Component For The Formation Of The Stomatal And Fenestral Diaphragms, Radu V. Stan, Eugene Tkachenko, Ingrid R. Niesman

Dartmouth Scholarship

PV1 is an endothelial-specific integral membrane glycoprotein associated with the stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar organelles and the diaphragms of endothelial fenestrae. Multiple PV1 homodimers are found within each stomatal and fenestral diaphragm. We investigated the function of PV1 within these diaphragms and their regulation and found that treatment of endothelial cells in culture with phorbol myristate acetate (PMA) led to upregulation of PV1. This correlated with de novo formation of stomatal diaphragms of caveolae and transendothelial channels as well as fenestrae upon PMA treatment. The newly formed diaphragms could be labeled with anti-PV1 antibodies. The upregulation …

Differences In Peripheral Noradrenergic Function Among Actively Drinking And Abstinent Alcohol-Dependent Individuals., Ashwin A. Patkar, Charles A. Marsden, Prakash C. Naik, David A. Kendall, Raman Gopalakrishnan, Michael J. Vergare, Stephen P. Weinstein

Department of Psychiatry and Human Behavior Faculty Papers

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly …

Passing The Boards: Can Usmle And Orthopaedic In-Training Examination Scores Predict Passage Of The Abos Part-I Examination?, Gregg R Klein, Matthew S Austin, Susan Randolph, Peter F Sharkey, Alan S Hilibrand

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Revised Estimates Of Dimension And Exercise Variance Components In Assessment Center Postexercise Dimension Ratings, Charles E. Lance, Tracy A. Lambert, Amanda G. Gewin, Filip Lievens, James M. Conway

Research Collection Lee Kong Chian School Of Business

The authors reanalyzed assessment center (AC) multitrait-multimethod (MTMM) matrices containing correlations among postexercise dimension ratings (PEDRs) reported by F. Lievens and J. M. Conway (2001). Unlike F. Lievens and J. M. Conway, who used a correlated dimension-correlated uniqueness model, we used a different set of confirmatory-factor-analysis-based models (1-dimension-correlated Exercise and 1-dimension-correlated uniqueness models) to estimate dimension and exercise variance components in AC PEDRs. Results of reanalyses suggest that, consistent with previous narrative reviews, exercise variance components dominate over dimension variance components after all. Implications for AC construct validity and possible redirections of research on the validity of ACs are discussed.

Relationship Between Serotonin Transporter Gene Polymorphisms And Platelet Serotonin Transporter Sites Among African-American Cocaine-Dependent Individuals And Healthy Volunteers., Ashwin A. Patkar, Wade H. Berrettini, Paolo Mannelli, Raman Gopalakrishnan, Margret R. Hoehe, Louai Bilal, Stephen Weinstein, Michael J. Vergare

Department of Psychiatry and Human Behavior Faculty Papers

Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites …

Mitotic Rate And Younger Age Are Predictors Of Sentinel Lymph Node Positivity: Lessons Learned From The Generation Of A Probabilistic Model., Vernon K Sondak, Jeremy M G Taylor, Michael S Sabel, Yue Wang, Lori Lowe, Amelia C Grover, Alfred E Chang, Alan M. Yahanda Md, Facs, James Moon, Timothy M Johnson

PCI Publications and Projects

BACKGROUND: Sentinel lymph node (SLN) biopsy allows surgeons to identify patients with subclinical nodal involvement who may benefit from lymphadenectomy and, possibly, adjuvant therapy. Several factors have been variably, and sometimes discordantly, reported to have predictive value for SLN metastasis to best select which patients require SLN biopsy.

METHODS: We reviewed 419 patients who underwent SLN biopsy for melanoma from a prospectively collected melanoma database. To derive a probabilistic model for the occurrence of a positive SLN, a multivariate logistic model was fit by using a stepwise variable selection method. The accuracy of each model was evaluated by using receiver …

Muc4 Mucin Expression In Human Pancreatic Tumours Is Affected By Organ Environment: The Possible Role Of Tgfbeta2., A. Choudhury, N. Moniaux, A. B. Ulrich, B. M. Schmied, J. Standop, Parviz M. Pour, S. J. Gendler, Michael A. Hollingsworth, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P

The Health Belief Model And Factors Relating To Potential Use Of A Vaccine For Shigellosis In Kaeng Koi District, Saraburi Province, Thailand, Piyarat Butraporn, Alfred Pach, Robert P. Pack, Rungwit Masngarmmeung

Faculty & Staff Scholarship

Shigellosis is an important cause of morbidity and mortality throughout the world. Approximately, 1.1 million deaths occur a year due to this disease, making it the fourth leading cause of mortality worldwide. This paper explores local interest in and potential use of a vaccine for shigellosis in Thailand where Shigella poses an important public-health concern. Data for this study were collected during June- November 2002 from 522 subjects surveyed using a sociobehavioural questionnaire in Kaeng Koi district in central Thailand. The community demand and likely use of a vaccine were examined in relation to the Health Belief Model, which provides …

Surveillance For Waterborne-Disease Outbreaks Associated With Drinking Water--United States, 2001-2002, Brian G. Blackburn, Gunther F. Craun, Jonathan S. Yoder, Vincent Hill, Rebecca L. Calderon, Nora Chen, Sherline H. Lee, Deborah A. Levy, Michael J. Beach

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with drinking water that occurred during January 2001-December 2002 and on three previously unreported outbreaks that occurred during 2000.

DESCRIPTION OF SYSTEM: Public health departments in the states, …

Macrophage Tropism Of Hiv-1 Depends On Efficient Cellular Dntp Utilization By Reverse Transcriptase, Tracy L. Diamond, Mikhail Roshal, Varuni K. Jamburuthugoda, Holly M. Reynolds, Aaron R. Merriam, Kwi Y. Lee, Mini Balakrishnan, Robert A. Bambara, Vincente Planelles, Stephen Dewhurst, Baek Kim

Biology

Retroviruses utilize cellular dNTPs to perform proviral DNA synthesis in infected host cells. Unlike oncoretroviruses, which replicate in dividing cells, lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus, are capable of efficiently replicating in non-dividing cells (terminally differentiated macrophages) as well as dividing cells (i.e. activated CD4+ T cells). In general, non-dividing cells are likely to have low cellular dNTP content compared with dividing cells. Here, by employing a novel assay for cellular dNTP content, we determined the dNTP concentrations in two HIV-1 target cells, macrophages and activated CD4+ T cells. We found that human …

Provision Of 24 Hour Acute Neurology Care By Neurologists: Manpower Requirements In The Uk., C. Carroll, J. Zajicek

Peninsula Medical School

OBJECTIVES: The ABN has published standards of care for patients with acute neurological disease. Derriford Hospital provides a 24 hour neurology intake service to a population of 500,000 with the equivalent of four consultants, three specialist registrars (SpRs), and four senior house officers (SHOs) with a 37 bed ward. The authors undertook a prospective study of all neurology admissions to enable calculation of manpower necessary to meet the ABN guidelines. METHODS: All admissions to the neurology department were analysed prospectively for a three month period (March to May 2002). RESULTS: There were 629 admissions (equating to 2500 per year); data …

Stroke In Devon: Knowledge Was Good, But Action Was Poor., C. Carroll, J. Hobart, C. Fox, L. Teare, J. Gibson

Peninsula Medical School

BACKGROUND AND AIM: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. METHODS: Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. RESULTS: Forty per cent of stroke …

The Moral Authority Of Symbolic Appeals In Biomedical Ethics, Sharon Sytsma

Faculty Articles, Papers, and Other Scholarship

No abstract provided.

Depressive Deficits In Forgetting, Paula T. Hertel, M. Gerstle

Psychology Faculty Research

The aim of this study was to investigate whether difficulties in forgetting (like difficulties in remembering) are associated with depressive states. First, dysphoric and nondysphoric students learned 40 word pairs, each consisting of a positive or negative adjective and a neutral noun (target). Next, the students practiced responding with some targets and suppressing others, when given the adjective as cue, for a varied number of repetitions. On the final test, they were told to disregard the prior instruction to suppress and to recall the target associated with every cue. Compared with nondysphoric students, dysphoric students recalled similar percentages of targets …

Melanoma And Seborrheic Keratosis Differentiation Using Texture Features, Srinivas V. Deshabhoina, Scott E. Umbaugh, William V. Stoecker, Randy Hays Moss, Subhashini K. Srinivasan

Chemistry Faculty Research & Creative Works

Purpose: To explore texture features in two-dimensional images to differentiate seborrheic keratosis from melanoma.

Methods: A systematic approach to consistent classification of skin tumors is described. Texture features, based on the second-order histogram, were used to identify the features or a combination of features that could consistently differentiate a malignant skin tumor (melanoma) from a benign one (seborrheic keratosis). Two hundred and seventy-one skin tumor images were separated into training and test sets for accuracy and consistency. Automatic induction was applied to generate classification rules. Data analysis and modeling tools were used to gain further insight into the feature space. …