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Seventeen Amino Acid Peptide (Peptide P) For Treating Ischemia And Reperfusion Injury, Peter R. Oeltgen, Mark S. Kindy

Molecular and Cellular Biochemistry Faculty Patents

Peptide P, having the amino acid sequence Tyr-D-Ala-Phe-Ala-Asp-Val-Ala-Ser-Thr-Ile-Gly-Asp-Phe-His-Ser-Ile-NH2-SEQ ID NO:1, is useful to treat ischemia.

Mammalian Micrornas: A Small World For Fine-Tuning Gene Expression, Cinzia Sevignani, George A. Calin, Linda D. Siracusa, Carlo M. Croce

Department of Microbiology and Immunology Faculty Papers

The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA and RNA-protein and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by non-coding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5’ and 3’-untranslated regions, transposable elements and intergenic regions, but also a large rapidly emerging family, named microRNAs. MicroRNAs are short 20-22 nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce …

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …

Assessment Of Executive Function In Preschool-Aged Children, Peter K. Isquith, Jennifer S. Crawford, Kimberly A. Espy, Gerard G. Gioia

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Assessment of the overarching self-regulatory mechanisms, or executive functions, in any age group is challenging, in part due to the complexity of this domain, in part due to their dynamic essence, and in part due to the inextricable links between these central processes and the associated domain-specific processes, such as language, motor function, and attention, over which they preside. While much progress has been made in clinical assessment approaches for measuring executive functions in adults and to some extent in adolescents and school-aged children, the toolkit for the preschool evaluator remains sparse. The past decade, however, has seen a substantial …

Inhibitory Processes In Young Children And Individual Variation In Short-Term Memory, Kimberly A. Espy, Rebecca Bull

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

A precise definition of executive control remains elusive, related in part to the variations among executive tasks in the nature of the task demands, which complicate the identification of test-specific versus construct-specific performance. In this study, tasks were chosen that varied in the nature of the stimulus (verbal, nonverbal), response (naming, somatic motor), conflict type (proactive interference, distraction), and inhibitory process (attention control, response suppression) required. Then performance differences were examined in 184 young children (age range = 3 years 6 months to 6 years 1 month), comparing those with high (5 or more digits) and low (3 or fewer …

Charge Screening By Internal Ph And Polyvalent Cations As A Mechanism For Activation, Inhibition, And Rundown Of Trpm7/Mic Channels, J. Ashot Kozak, Masayuki Matsushita, Angus C. Nairn, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

The Mg²⁺-inhibited cation (MIC) current, believed to represent activity of TRPM7 channels, is found in lymphocytes and mast cells, cardiac and smooth muscle, and several other eukaryotic cell types. MIC current is activated during whole-cell dialysis with divalent-free internal solutions. Millimolar concentrations of intracellular Mg²⁺ (or other divalent metal cations) inhibit the channels in a voltage-independent manner. The nature of divalent inhibition and the mechanism of channel activation in an intact cell remain unknown. We show that the polyamines (spermine, spermidine, and putrescine) inhibit the MIC current, also in a voltage-independent manner, with a potency that parallels …

Rhamnolipids Modulate Swarming Motility Patterns Of Pseudomonas Aeruginosa, Nicky C. Caiazza, Robert M. Q. Shanks, G. A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is capable of twitching, swimming, and swarming motility. The latter form of translocation occurs on semisolid surfaces, requires functional flagella and biosurfactant production, and results in complex motility patterns. From the point of inoculation, bacteria migrate as defined groups, referred to as tendrils, moving in a coordinated manner capable of sensing and responding to other groups of cells. We were able to show that P. aeruginosa produces extracellular factors capable of modulating tendril movement, and genetic analysis revealed that modulation of these movements was dependent on rhamnolipid biosynthesis. An rhlB mutant (deficient in mono- and dirhamnolipid production) and …

Effects Of Gramicidin-A On The Adsorption Of Phospholipids To The Air–Water Interface, Samares C. Biswas, Shankar B. Rananavare, Stephen B. Hall

Chemistry Faculty Publications and Presentations

Prior studies suggest that the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of the lipids in pulmonary surfactant to an air–water interface by stabilizing a negatively curved rate-limiting structure that is intermediate between bilayer vesicles and the surface film. This model predicts that other peptides capable of stabilizing negative curvature should also promote lipid adsorption. Previous reports have shown that under appropriate conditions, gramicidin-A (GrA) induces dioleoyl phosphatidylcholine (DOPC), but not dimyristoyl phosphatidylcholine (DMPC), to form the negatively curved hexagonal-II (HII) phase. The studies reported here determined if GrA would produce the same effects on adsorption of DMPC and …

Studies On The Basis For The Properties Of Fibrin Produced From Fibrinogen-Containing Γ′ Chains, Kevin R. Siebenlist, Michael W. Mosesson, Irene Hernandez, Leslie A. Bush, Enrico Di Cera, John R. Shainoff, James P. Diorio, Laurie Stajanovic

Biomedical Sciences Faculty Research and Publications

Human fibrinogen 1 is homodimeric with respect to its γ chains (`γ_A-γ_A'), whereas fibrinogen 2 molecules each contain one γ_A (γ_A1-411V) and one γ' chain, which differ by containing a unique C-terminal sequence from γ'408 to 427L that binds thrombin and factor XIII. We investigated the structural and functional features of these fibrins and made several observations. First, thrombin-treated fibrinogen 2 produced finer, more branched clot networks than did fibrin 1. These known differences in network structure were attributable to delayed release of fibrinopeptide (FP) A from fibrinogen 2 by thrombin, which in …

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Animal tests yield misleading results.

Do Inhalation General Anesthetic Drugs Induce The Neuronal Release Of Endogenous Opioid Peptides?, Raymond M. Quock, Linda K. Vaughn

Biomedical Sciences Faculty Research and Publications

The antagonism of some effects of inhalation general anesthetic agents by naloxone suggests that there may be an opioid component to anesthetic action. There is evidence that this opioid action component is due to neuronal release of endogenous opioid peptides. The strongest evidence is provided by studies that monitor changes in the concentration of opioid peptides in the perfused brain following inhalation of the anesthetic. Indirect or circumstantial evidence also comes from studies of anesthetic effects on regional brain levels of opioid peptides, antagonism of selected anesthetic effects by antisera to opioid peptides and anesthetic-induced changes radioligand binding to opioid …

Murine Monoclonal Anti-Idiotype Antibody 11d10 And Methods Of Use Thereof, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention provides a monoclonal anti-idiotype antibody 11D10 that elicits an immune response against a specific epitope of a high molecular weight mucin of human milk fat globule (HMFG) and a hybridoma that produces 11D10. The hybridoma that produces 11D10 was selected by specific procedures. 11D10 induces an immunological response to HMFG in nice, rabbits, monkeys and patients with advanced HMFG-associated tumors. This invention provides compositions derived from polynucleotide sequences encoding the variable light and/or variable heavy regions of monoclonal anti-idiotype antibody 11D10, as well as polypeptides encoded thereby. The invention also provides compositions which can be used in …

Selective Role For Superoxide In Insp3 Receptor-Mediated Mitochondrial Dysfunction And Endothelial Apoptosis., Muniswamy Madesh, Brian J Hawkins, Tatyana Milovanova, Cunnigaiper D Bhanumathy, Suresh K Joseph, Satish P Ramachandrarao, Kumar Sharma, Tomohiro Kurosaki, Aron B Fisher

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reactive oxygen species (ROS) play a divergent role in both cell survival and cell death during ischemia/reperfusion (I/R) injury and associated inflammation. In this study, ROS generation by activated macrophages evoked an intracellular Ca2+ ([Ca2+]i) transient in endothelial cells that was ablated by a combination of superoxide dismutase and an anion channel blocker. [Ca2+]i store depletion, but not extracellular Ca2+ chelation, prevented [Ca2+]i elevation in response to O2*- that was inositol 1,4,5-trisphosphate (InsP3) dependent, and cells lacking the three InsP3 receptor (InsP3R) isoforms failed to display the [Ca2+]i transient. Importantly, the O2*--triggered Ca2+ mobilization preceded a loss in mitochondrial membrane …

Cpg Oligodeoxynucleotides Stimulate Cord Blood Mononuclear Cells To Produce Immunoglobulins., Cheri D Landers, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

CpG oligodeoxynucleotides (ODNs) stimulate adult B cells leading to cellular proliferation and immunoglobulin production. It is unknown if CpG-ODNs similarly stimulate neonatal human B cells. Neonates have immature immune responses and are poorly responsive to thymus independent antigens such as polysaccharides. We determined umbilical cord cells' response to CpG-ODNs. Adult and umbilical cord B cells produced similar amounts of IgM (adult 1371 +/- 352 vs. cord 1873 +/- 1084 ng/ml) in response to CpG-ODN stimulation. Although CpG-ODN was able to stimulate adult IgG and IgA production, cord cells produced less IgG (153 +/- 58 vs. 10 +/- 2.5 ng/ml) and …

Role Of Zmpste24 In Prelamin A Maturation., Douglas Paul Corrigan

Electronic Theses and Dissertations

The nuclear lamins form a karyoskeleton providing structural rigidity to the nucleus. One member of the lamin family, lamin A, is first synthesized as a 74 kDa precursor, prelamin A. Following the endopeptidase and methylation reactions which occur after farnesylation of the CAAX-box cysteine, there is a second endoproteolysis that occurs 15 amino acids upstream from the C-terminal farnesylated cysteine residue. Studies with knockout mice have implicated the enzyme Zmpste24 as a candidate to carry out one or both of these proteolytic reactions. In this body of work, the CAAX endopeptidase activity of recombinant, membrane reconstituted, Zmpste24 is demonstrated using …

Angiogenesis And Myogenesis In A Chronic Ischemic Heart., Esha Ibrahim

Electronic Theses and Dissertations

Miniswine underwent procedures to evaluate treating chronic ischemia with the implantation of autologous satellite cells and laser transmyocardial revascularization (TMR). The objective was to combine two therapies to restore cardiac function. This experiment involved three surgical procedures: (1) placing a constrictor on the coronary artery; (2) producing channels and implanting cells; (3) obtaining samples. The swine were divided into groups: Group 1, Ischemia; Group 2, Ischemia + Laser TMR; Group 3, Ischemia + Laser TMR+ Cells; Group 4, Ischemia + Cells. Sonomicrometry and Millar pressure transducers were used to determine contractility, left ventricular pressure, and pressure-volume loops. There were no …

C-Jun N-Terminal Kinase (Jnk) Is Required For Survival And Proliferation Of B-Lymphoma Cells, Murali Gururajan, Roger Chui, Anbu K. Karuppannan, Jiyuan Ke, C. Darrell Jennings, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Several primary murine and human B lymphomas and cell lines were found to constitutively express high levels of the activated form of c-jun N-terminal kinase (JNK), a member of the mitogen-activated protein (MAP) kinase family. Proliferation of murine B lymphomas CH31, CH12.Lx, BKS-2, and WEHI-231 and the human B lymphomas BJAB, RAMOS, RAJI, OCI-Ly7, and OCI-Ly10 was strongly inhibited by SP600125, an anthrapyrazolone inhibitor of JNK, in a dose-dependent manner. The lymphoma cells underwent apoptosis and arrested at the G2/M phase of cell cycle. Furthermore, JNK-specific small interfering RNA (siRNA) inhibited the growth of both murine and human B lymphomas. …

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 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 …

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 …

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 …

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 …

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 …