Medical Sciences Commons^™

Endothelial Nitric Oxide Synthase Is Critical For Ischemic Remodeling, Mural Cell Recruitment, And Blood Flow Reserve, Jun Yu, Ebu D. Demuinck, Zhenwu Zhuang, Mary Drinane

Dartmouth Scholarship

The genetic loss of endothelial-derived nitric oxide synthase (eNOS) in mice impairs vascular endothelial growth factor (VEGF) and ischemia-initiated blood flow recovery resulting in critical limb ischemia. This result may occur through impaired arteriogenesis, angiogenesis, or mobilization of stem and progenitor cells. Here, we show that after ischemic challenge, eNOS knockout mice [eNOS (-/-)] have defects in arteriogenesis and functional blood flow reserve after muscle stimulation and pericyte recruitment, but no impairment in endothelial progenitor cell recruitment. More importantly, the defects in blood flow recovery, clinical manifestations of ischemia, ischemic reserve capacity, and pericyte recruitment into the growing neovasculature can …

Flow Reversal Events Increase The Abundance Of Nontroglobitic Fish In The Subterranean Rivers Of Mammoth Cave National Park, Kentucky, Michael Ruhl

Masters Theses & Specialist Projects

Mammoth Cave National Park (MCNP) is home to the longest cave system in the World and is dissected by the Green River, one of the most speciose watersheds on the continent. Cave springs create a direct aquatic link between subterranean waterways and the Green River. The history of these subterranean river systems is filled with eyewitness reports of various species of surface water (nontroglobitic) fishes, including introduced rainbow trout. This study documents the occurrence of Green River fish species in the cave system of MCNP. Four sites were sampled over a two year period using a variety of gears. In …

Resting Potential–Dependent Regulation Of The Voltage Sensitivity Of Sodium Channel Gating In Rat Skeletal Muscle In Vivo, Gregory N. Filatov, Martin J. Pinter, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Normal muscle has a resting potential of −85 mV, but in a number of situations there is depolarization of the resting potential that alters excitability. To better understand the effect of resting potential on muscle excitability we attempted to accurately simulate excitability at both normal and depolarized resting potentials. To accurately simulate excitability we found that it was necessary to include a resting potential–dependent shift in the voltage dependence of sodium channel activation and fast inactivation. We recorded sodium currents from muscle fibers in vivo and found that prolonged changes in holding potential cause shifts in the voltage dependence of …

Factors Affecting Distribution And Abundance Of Aquatic Macroinvertebrates In Autumnal Wetlands In Mammoth Cave National Park, Kentucky, Usa, Jered Studinski

Masters Theses & Specialist Projects

Despite a recent surge of interest in temporary lentic systems, a strong theory linking the biota to its environment has not emerged. Data were collected from ten autumnal wetlands at Mammoth Cave National Park, Kentucky, U.S.A., in an effort to elucidate the environmental variables (EV's) that affected both between- and within-pond macroinvertebrate distribution and abundance. Canonical correspondence analyses performed with between-pond data failed to find strong relationships between the macroinvertebrates and EV's. Additionally, the theory that hydroperiod would effect richness did not apply to these ponds. Within-pond canonical correspondence analyses, however, yielded strong relationships. Further testing using regression analysis and …

The Neural Mechanisms Of Speech Comprehension: Fmri Studies Of Semantic Ambiguity, Jennifer M Rodd, Matthew H Davis, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

A number of regions of the temporal and frontal lobes are known to be important for spoken language comprehension, yet we do not have a clear understanding of their functional role(s). In particular, there is considerable disagreement about which brain regions are involved in the semantic aspects of comprehension. Two functional magnetic resonance studies use the phenomenon of semantic ambiguity to identify regions within the fronto-temporal language network that subserve the semantic aspects of spoken language comprehension. Volunteers heard sentences containing ambiguous words (e.g. 'the shell was fired towards the tank') and well-matched low-ambiguity sentences (e.g. 'her secrets were written …

The Effects Of An Analgesic (Biofreeze®) On The Motoneuron Pool Excitability Of The Soleus Muscle, Desiree R. Barth

All-Inclusive List of Electronic Theses and Dissertations

Objective: The purpose of this study was to determine the effects on the Hoffman reflex and motor response with an analgesic (Biofreeze®). Design: The study was a 2X6 design. The independent variables in this study were treatment and time. The dependent variables were the H-reflex (volts) and the M response (volts). Treatment was randomly assigned to control for the effects of order. Setting: This study took place in the Exercise Physiology Laboratory located in the Health and Human Performance Building at Indiana State University. Subjects: 14 volunteers who were physically active and had no known neurological problems. Measurements: Skin and …

Implications Of Spatial Autocorrelation And Dispersal For The Modeling Of Species Distributions, Volker Bahn

Biological Sciences Faculty Publications

Modeling the geographical distributions of wildlife species is important for ecology and conservation biology. Spatial autocorrelation in species distributions poses a problem for distribution modeling because it invalidates the assumption of independence among sample locations. I explored the prevalence and causes of spatial autocorrelation in data from the Breeding Bird Survey, covering the conterminous United States, using Regression Trees, Conditional Autoregressive Regressions (CAR), and the partitioning of variance. I also constructed a simulation model to investigate dispersal as a process contributing to spatial autocorrelation, and attempted to verify the connection between dispersal and spatial autocorrelation in species’ distributions in empirical …

Experimental Ocular Toxoplasmosis In Genetically Susceptible And Resistant Mice, Fangli Lu, Shiguang Huang, Mark S. Hu, Lloyd H. Kasper

Dartmouth Scholarship

Genetic factors determining the pathogenesis and course of ocular toxoplasmosis are poorly understood. In this study, we explored the development of experimental ocular pathogenesis in genetically dissimilar mice infected with either the RH strain, the PLK strain, or the immunodominant surface antigen 1 (SAG1 [P30])-deficient mutant of the RH strain of Toxoplasma gondii. At 11 days postinfection, ocular infection of C57BL/6 mice with all of the strains of parasites resulted in severe inflammatory lesions and high numbers of parasites in eye tissue; less severe ocular lesions at earlier histopathology and prolonged survival were observed in this mouse strain infected …

Tcpf Is A Soluble Colonization Factor And Protective Antigen Secreted By El Tor And Classical O1 And O139 Vibrio Cholerae Serogroups, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was …

Heparin Stimulates Staphylococcus Aureus Biofilm Formation, Robert M. Q. Shanks, Niles P. Donegan, Martha L. Graber, Sarah E. Buckingham, Michael Zegans, Ambrose Cheung, George A. O'Toole

Dartmouth Scholarship

Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA …

Sara Positively Controls Bap-Dependent Biofilm Formation In Staphylococcus Aureus, María P. Trotonda, Adhar C. Manna, Ambrose L. Cheung, Iñigo Lasa, José R. Penadés

Dartmouth Scholarship

The biofilm-associated protein Bap is a staphylococcal surface protein involved in biofilm formation. We investigated the influence of the global regulatory locus sarA on bap expression and Bap-dependent biofilm formation in three unrelated Staphylococcus aureus strains. The results showed that Bap-dependent biofilm formation was diminished in the sarA mutants by an agr-independent mechanism. Complementation studies using a sarA clone confirmed that the defect in biofilm formation was due to the sarA mutation. As expected, the diminished capacity to form biofilms in the sarA mutants correlated with the decreased presence of Bap in the bacterial surface. Using transcriptional fusion and …

A Role For Mitogen-Activated Protein Kinase (Erk1/2) Activation And Non-Selective Pore Formation In P2x7 Receptor-Mediated Thymocyte Death, Rodolphe Auger, Iris Motta, Karim Benihoud, David M. Ojcius, Jean M. Kanellopoulos

All Dugoni School of Dentistry Faculty Articles

Extracellular ATP (ATPe) binds to P2X7 receptors (P2X7R) expressed on the surface of cells of hematopoietic lineage, including murine thymocytes. Activation of P2X7R by ATPe results in the opening of cation-specific channels, and prolonged ATPe exposure leads to the formation of non-selective pores enabling transmembrane passage of solutes up to 900 Da. In the presence of ATPe, P2X7R-mediated thymocyte death is due primarily to necrosis/lysis and not apoptosis, as measured by the release of lactate dehydrogenase indicative of a loss of plasma membrane integrity. The present study is focused on the identification of P2X7R signaling mediators in ATP-induced thymocyte necrosis/lysis. …

Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams

Biochemistry and Microbiology

Background

The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …

A Critical Role For The Programmed Death Ligand 1 In Fetomaternal Tolerance, Indira Guleria, Arezou Khosroshahi, Mohammed Javeed Ansari, Antje Habicht, Miyuki Azuma, Hideo Yagita, Randolph J. Noelle

Dartmouth Scholarship

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell

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 …

Animal Models Of Head Trauma, Ibolja Cernak

Biomedicine and Animal Models in Research Collection

Animal models of traumatic brain injury (TBI) are used to elucidate primary and secondary sequelae underlying human head injury in an effort to identify potential neuroprotective therapies for developing and adult brains. The choice of experimental model depends upon both the research goal and underlying objectives. The intrinsic ability to study injuryinduced changes in behavior, physiology, metabolism, the blood/tissue interface, the blood brain barrier, and/or inflammatory- and immune-mediated responses, makes in vivo TBI models essential for neurotrauma research. Whereas human TBI is a highly complex multifactorial disorder, animal trauma models tend to replicate only single factors involved in the pathobiology …

Anticuerpos Contra El Virus De La Estomatitis Vesicularen Sajinos (Tayassu Tajacu) De Zoocriaderos De Iquitos Y Pucallpa, Aldo D. Wilson, Mariluz Araínga, Hugo Galvez C., Alberto Manchego S., Hermelinda G. Rivera

Journal Articles: Pharmacology & Experimental Neuroscience

The objetive of this study was to detect antibodies against vesicular stomatitis virus (VSV) collared peccaries in (Tayassu tajacu) from farms of Iquitos and Pucallpa, Peru. Blood samples were collected in animals olders than 6 months of age (pregnant females were not included) from a farm in Iquitos (n = 21) and from four farms in Pucallpa (n = 47), for detection of antibodies against Indiana 1 and New Jersey serotype of VSV by viral neutralization test. No specific antibodies against both serotypes of VSV were detected, indicating that the peccaries were not exposed to VSV, and suggesting absence of …

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 …

Functionally Active T1-T1 Interfaces Revealed By The Accessibility Of Intracellular Thiolate Groups In Kv4 Channels., Guangyu Wang, Mohammad Shahidullah, Carmen A Rocha, Candace Strang, Paul J Pfaffinger, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gating of voltage-dependent K(+) channels involves movements of membrane-spanning regions that control the opening of the pore. Much less is known, however, about the contributions of large intracellular channel domains to the conformational changes that underlie gating. Here, we investigated the functional role of intracellular regions in Kv4 channels by probing relevant cysteines with thiol-specific reagents. We find that reagent application to the intracellular side of inside-out patches results in time-dependent irreversible inhibition of Kv4.1 and Kv4.3 currents. In the absence or presence of Kv4-specific auxiliary subunits, mutational and electrophysiological analyses showed that none of the 14 intracellular cysteines is …

Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna

Dartmouth Scholarship

The global regulatory locus sarA comprises a 375-bp open reading frame that is driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We mutated the weaker P3 and P2 promoters to ascertain the effect of the change on SarA protein and target gene expression. Our results indicated that the solely active P1 promoter led to a lower SarA protein level, which has an effect on agr transcription and subsequently had corresponding effects on hla, sspA, and spa transcription, probably in both agr-independent and agr-dependent manners.

Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira

Dartmouth Scholarship

We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3alpha secretion due to …

A Human T-Cell Lymphotropic Virus Type 1 Enhancer Of Myc Transforming Potential Stabilizes Myc-Tip60 Transcriptional Interactions, Soumya Awasthi, Anima Sharma, Kasuen Wong, Junyu Zhang, Elizabeth F. Matlock, Lowery Rogers, Pamela Motloch, Shigeki Takemoto, Hirokuni Taguchi, Michael D. Cole

Dartmouth Scholarship

The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30II is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the …

Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung

Dartmouth Scholarship

Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by Staphylococcus aureus. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants (SCVs), often in combination with isogenic normal S. aureus phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G.

Diets And Coexistence Of The Sea Urchins Lytechinus Variegatus And Arbacia Punctulata (Echinodermata) Along The Central Florida Gulf Coast, Janessa Cobb, John M. Lawrence

Integrative Biology Faculty and Staff Publications

The basis for coexistence of similar species is fundamental in community ecology. One mechanism for coexistence is differentiation of diets. Lytechinus variegatus and Arbacia punctulata coexist in different microhabitats along the Florida gulf coast. Their great difference in morphology might affect their choice of microhabitats and diet. We analyzed diets of both species at 1 offshore and 1 nearshore site where both occurred in relatively equal numbers, an offshore site dominated by A. punctulata and an offshore site dominated by L. variegatus. Gut contents were analyzed to determine the diet. A. punctulata prim. consumed sessile invertebrates except on dates …

Evaluating Forensic Dna Evidence, Dan E. Krane, William C. Thompson

Biological Sciences Faculty Publications

No abstract provided.

Genes Encoding Several Poly (Adp-Ribose) Glycohydrolase (Parg) Enzymes, The Proteins And Fragments Thereof, And Antibodies Immnoreactive Therewith, Myron Jacobson, Elaine L. Jacobson, Jean-Christoph Amé, Winston Lin

Graduate Center for Nutritional Sciences Faculty Patents

The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods …

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

Dynamic Matrix Composition In Engineered Cartilage With Stochastic Supplementation Of Growth Factors, Asit K. Saha, J. (Jagannath) Mazumdar, Sean S. Kohles

Mechanical and Materials Engineering Faculty Publications and Presentations

Dynamic extracellular matrix (ECM) synthesis is explored in a hypothesized engineered cartilage construct. Growth (α) and decay (β) rate parameters are developed from a previous engineered cartilage model. The presented mathematical model was constructed from the parameterized experimental data using a deterministic and stochastic examination of ECM synthesis based on a negative feedback control mechanism. A growth factor supplementation is incorporated in a probabilistic mathematical approach. The growth factor component modified an initial deterministic model through a Gaussian white noise fluctuation. As the primary constituents of ECM, the mathematical tool is intended to characterize the probable steady state distribution of …

Effects Of Feeding Regular Eggs, N-3 Fatty Acid Enriched Eggs, And Walnuts, On Blood Lipids, Membrane Incorporation Of Fatty Acids, And Serum Lutein, In Free-Living Lacto-Ovo Vegetarians, Bonny Burns-Whitmore

Loma Linda University Electronic Theses, Dissertations & Projects

Americans do not receive enough n-3 fatty acids (F. A.) in their diets. Walnuts are good source of α-linolenic acid (ALA), while n-3 F.A. enriched eggs provide a dietary source of DHA. Whether ALA and DHA have equivalent effects modifying cardiovascular risk factors is not known. This study compared the changes in blood and erythrocyte membrane lipids in twenty free-living lacto-ovo vegetarians following the consumption of regular eggs (6/wk), n-3 F.A. enriched eggs (6/wk), or walnuts (6 oz/wk) in a triple crossover design.

Results indicate significant differences between treatments for serum triacylglycerols (TAGs), total cholesterol (TC), apo B, apo B: …

The Effect Of Electrical Stimulation On Blood Flow In Chronic Wounds In Patients With And Without Diabetes, Daryl J. Lawson

Loma Linda University Electronic Theses, Dissertations & Projects

Background and Purpose. Only 3% of the U S population is afflicted by diabetes, yet one of the most common chronic wounds is the diabetic ulcer. Decrease in blood flow may be one reason why only 31% of neuropathic diabetic ulcers heal in 20-weeks. The purpose of this investigation was to compare healing rates and blood flow of chronic stage III and IV wounds in people with diabetes and those without diabetes over four weeks of treatment. Blood flow was measured before, during, and after stimulation using one of two different electrical stimulation waveforms in a 32°C room.

Subjects …