Des Moines University Osteopathic Medical Center

TELEHEALTH EQUIPMENT

BASIC/CORE AREA HEALTH EDUCATION CENTERS

DES MOINES UNIVERSITY- CARES ACT HEERF FUNDS- STUDENT PORTION

DES MOINES UNIVERSITY- CARES ACT HEERF FUNDS- STUDENT PORTION

MIRNAS, WHOLE DIET, AND CORONARY HEART DISEASE

IN CASES OF CRIMINAL DISMEMBERMENT, FORENSIC ANTHROPOLOGISTS ARE TASKED WITH PROVIDING MEDICOLEGAL AGENCIES WITH ACCURATE INFORMATION ABOUT THE DISMEMBERMENT METHODS AND TOOL(S) UTILIZED. RESIDUAL KERF VARIABLES ARE USED TO PREDICT TOOL CLASS CHARACTERISTICS, SUCH AS POWER SOURCE, TOOTH SET, TOOTH SHAPE AND TOOTH SIZE. THIS INFORMATION CAN ASSIST IN THE SEARCH FOR SUSPECTS AND WEAPONS AND AS EVIDENCE DURING LEGAL PROCEEDINGS. CURRENT METHODS, HOWEVER, RELY MOSTLY ON ANECDOTAL RELATIONSHIPS BETWEEN CUT CHARACTERISTICS AND TOOL PARAMETERS, WITH FORENSIC BODIES CALLING FOR MORE OBJECTIVE AND STATISTICALLY RIGOROUS METHODS. SOME STUDIES HAVE TRIED TO ADDRESS THESE CONCERNS, BUT USE ANIMAL MODELS, DE-FLESHED REMAINS, AND/OR BONES RESTRAINED IN DEVICES, WHICH DOES NOT ACCURATELY REFLECT FORENSIC HUMAN DISMEMBERMENT EVENTS. MANY STUDIES ALSO HAVE LIMITED SAMPLE SIZES OR TEST FOR A SINGLE PARAMETER AND TEND TO FOCUS ON INCOMPLETE CUTS. THE PROPOSED PROJECT WILL PROVIDE AN OVERDUE EMPIRICAL ASSESSMENT OF THE RELIABILITY OF KERF VARIABLES TO PREDICT SAW CLASS CHARACTERISTICS, PROVIDE REQUIRED ERROR RATE DOCUMENTATION, AND FACILITATE STANDARDIZATION IN FORENSIC ANTHROPOLOGICAL SAW MARK ANALYSIS FOR APPLICATION IN CRIMINAL DISMEMBERMENT CASES. IN THE PROPOSED PROJECT, TWENTY MANUALLY- AND MECHANICALLY-POWERED RECIPROCATING SAWS WILL BE USED TO CREATE EXPERIMENTAL SAW CUTS (COMPLETE AND INCOMPLETE) IN A CADAVERIC (FLESHED) HUMAN SAMPLE, MIMICKING TRUE DISMEMBERMENT SCENARIOS. A SECOND SAMPLE OF DISSECTED DONORS (UNFLESHED) WILL BE USED TO ASSESS THE EFFECT OF SOFT TISSUE ON RESIDUAL CUT CHARACTERISTICS. TWO PREVIOUSLY PROCURED SAW CUT SAMPLES (BONES AND/OR NEGATIVE MOLDS) ARE AVAILABLE FOR ANALYSIS. SAW MARK DATA WILL BE COLLECTED FROM THESE SAMPLES AS WELL, RESULTING IN A COMBINED SAMPLE OF 908 SAW CUTS FROM 44 SAWS. A SUBSAMPLE OF 70 CUT SURFACES WILL BE UTILIZED FOR BLINDED INTER- AND INTRA-OBSERVER ERROR ANALYSES. RANDOM FOREST MODELS/DECISION TREE ANALYSES WILL BE PERFORMED ON RELIABLE FEATURES TO ASSESS UTILITY AND ACCURACY IN PREDICTING TOOL CLASS CHARACTERISTICS. EXPECTED OUTCOMES INCLUDE DEVELOPMENT OF STATISTICALLY RIGOROUS METHODS TO ESTIMATE SAW CLASS CHARACTERISTICS; DOCUMENTATION OF ERROR RATES; CREATION OF AN ATLAS WITH EXPANDED FEATURE DEFINITIONS AND NUMEROUS PHOTOGRAPHIC EXAMPLES TO ASSIST OTHERS IN FORENSIC RESEARCH AND CASE COMPARISONS; AND A LARGE COLLECTION OF SAW MARK DATA AND MOLDS THAT WILL BE MADE AVAILABLE TO OTHERS. THIS RESEARCH WILL ADVANCE THE FIELD OF FORENSIC ANTHROPOLOGY, BUT WILL ALSO BENEFIT MEDICOLEGAL AGENCIES, CRIMINAL JUSTICE SYSTEMS, AND THE GENERAL PUBLIC, AS ANY ERRONEOUS CONCLUSIONS DRAWN FROM UNRELIABLE SAW MARK ANALYSES CAN HAVE MAJOR LEGAL IMPLICATIONS ON INVESTIGATIONS AND CONVICTIONS. CA/NCF

HYDROXYMETHYLATION, INCIDENT TYPE 2 DIABETES AND INCIDENT OBESITY - HYDROXYMETHYLATED CYTOSINE (5HMC) IN DNA IS AN EPIGENETIC MODIFICATION THAT REGULATES GENE TRANSCRIPTION. TYPE 2 DIABETES (T2D) AND OBESITY (OB) ARE DISEASES THAT ARE SERIOUS GLOBAL PUBLIC HEALTH CHALLENGES. LITTLE IS KNOWN ABOUT THE ROLE OF 5HMC IN THE DEVELOPMENT OF T2D AND OB. IN OUR EXPLORATORY STUDY TO INVESTIGATE HYDROXYMETHYLATION USING A CO-TWIN CONTROL DESIGN, WE INCLUDED THREE MONOZYGOTIC TWIN PAIRS (MZ) DISCORDANT FOR INCIDENT T2D (IT2D) AND FIVE SEPARATE MZ PAIRS DISCORDANT FOR PREVALENT OB FROM OUR PREVIOUS R21 (1R21HL127368-01) STUDY OF CARDIOVASCULAR DISEASE. USING CIRCULATING 5HMC AS AN AGGREGATE SURROGATE FOR CUMULATIVE SYSTEMIC HYDROXYMETHYLATION, INTRIGUINGLY, WE FOUND STATISTICALLY SIGNIFICANT, WHOLE-GENOME DIFFERENTIALLY HYDROXYMETHYLATED REGIONS (DHMRS) RELATED TO IT2D AND PREVALENT OB, RESPECTIVELY, AFTER CONTROLLING FOR GENETIC VARIATION IN GERMLINE CONSISTING OF 3.2 BILLION BASE PAIRS, AGE-PERIOD-COHORT EFFECTS, AND MULTIPLE-TESTING. DUE TO THE VERY LIMITED SAMPLE SIZE AND LACK OF TWIN PAIRS DISCORDANT FOR INCIDENT OB (IOB) IN OUR PRIOR EXPLORATORY STUDY, IT IS IMPERATIVE TO PERFORM THE PROSPECTIVE RESEARCH IN A RELATIVELY LARGE SAMPLE TO GENERATE STRONG EVIDENCE. THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) TWIN STUDY IS A WELL- CHARACTERIZED, 46-YEAR FOLLOW-UP STUDY INITIATED IN 1969. LEVERAGING EXISTING RICH RESOURCES IN THE NHLBI TWIN STUDY AND OUR ESTABLISHED, MULTI-MECHANISM STUDENTS' RESEARCH ENGAGEMENT PLAN, WE PROPOSE THIS R15 STUDY. OUR OVERALL OBJECTIVES ARE TO CHARACTERIZE CIRCULATING 5HMC IN RELATION TO IT2D AND IOB AND TO OFFER AN EXCELLENT OPPORTUNITY FOR STUDENTS TO BE ENGAGED IN PUBLIC HEALTH EPIGENOME RESEARCH. THESE OBJECTIVES WILL BE ACHIEVED BY PURSUING THREE SPECIFIC AIMS: 1) MEASURE WHOLE GENOME HYDROXYMETHYLATION (5HMC) IN BLOOD DNA SAMPLES; 2) TEST IF DNA REGIONS ARE DIFFERENTIALLY HYDROXYMETHYLATED IN RELATION TO IT2D (AIM 2-1) AND IOB (AIM 2-2) INDEPENDENT OF GERMLINE AND COMMON ENVIRONMENT; WHICH, IN TURN, WILL IDENTIFY NOVEL DIFFERENTIALLY HYDROXYMETHYLATED REGIONS; AND 3) CHARACTERIZE SOCIOBEHAVIORAL AND OTHER ENVIRONMENTAL CORRELATES OF HYDROXYMETHYLATION IN LITERATURE-BASED CANDIDATE AND NOVEL DNA REGIONS INDEPENDENT OF GERMLINE AND COMMON ENVIRONMENT. WE WILL INCLUDE ALL AVAILABLE TWIN PAIRS DISCORDANT FOR IT2D [17 MZ AND 20 DIZYGOTIC TWIN PAIRS (DZ)] AND SEPARATE TWIN PAIRS DISCORDANT FOR IOB (11 MZ PAIRS AND 15 DZ PAIRS) FROM NHLBI TWIN STUDY. THE NHLBI TWIN STUDY TWINS WERE BORN BETWEEN 1917 AND 1927, A PERIOD WHEN 2 MALE MZ PAIRS AND 4 MALE DZ PAIRS OF TWINS WERE BORN PER 1,000 LIVE BIRTHS. AN ILLUSTRATIVE EXAMPLE IS THAT INCLUSION OF OUR DMZ TWIN SAMPLE SIZE IS EQUIVALENT TO THAT OF AT LEAST 126,746 SINGLETONS. THE SIGNIFICANCE OF OUR STUDY IS TO PROVIDE INNOVATIVE EVIDENCE ABOUT IT2D AND IOB-DISCRIMINATING HYDROXYMETHYLATION INDUCED ENVIRONMENTALLY, WHICH COULD IMPACT DISEASE PREVENTION AND TREATMENT THROUGH THE IMPROVEMENT OF MODIFIABLE ENVIRONMENTAL FACTORS. OUR STUDY WILL OFFER A UNIQUE OPPORTUNITY FOR ENGAGING MEDICAL AND GRADUATE STUDENTS AT THE APPLICANT'S INSTITUTE IN THE PUBLIC HEALTH EPIGENOME RESEARCH.

NATURAL TRAP CAVE REVISITED: ANCIENT DNA, CLIMATE AND THE MEGAFAUNAL EXTINCTION

DEVELOPMENT OF A NOVEL VASORELAXING PEPTIDE - PROJECT SUMMARY REDUCED NITRIC OXIDE (NO) AVAILABILITY IS A COMMON PATHOPHYSIOLOGICAL FEATURE OF MANY CARDIOVASCULAR DISEASES. WHILE NO DONORS ARE USED, SIGNIFICANT ISSUES LIMIT THEIR UTILITY, INCLUDING THE DEVELOPMENT OF NITRATE TOLERANCE AND ENDOTHELIAL DYSFUNCTION. ALTHOUGH INTERMITTENT NITRATE THERAPY IS COMMON PRACTICE, THIS STRATEGY HAS LIMITATIONS AND IS NOT CONSIDERED A SOLUTION TO NITRATE TOLERANCE ISSUES. EXTENSIVE INTRAVENOUS USE OF SODIUM NITROPRUSSIDE IS ASSOCIATED WITH A RISK FOR CYANIDE POISONING. THERE IS THUS A STRONG NEED TO IDENTIFY NEW APPROACHES TO PROMOTE ENDOGENOUS NO PRODUCTION. THE STROMAL INTERACTION MOLECULE 1 (STIM1), A CA2+-SENSING PROTEIN IN THE ENDOPLASMIC RETICULUM (ER), IS A CRITICAL DETERMINANT OF STORE-OPERATED CA2+ ENTRY, WHICH IN ENDOTHELIAL CELLS (ECS) IS REQUIRED FOR SUSTAINED ENDOGENOUS NO PRODUCTION. VASCULAR SMOOTH MUSCLE-SPECIFIC STIM1 DELETION BLUNTED HYPERTENSION AND CARDIAC HYPERTROPHY CAUSED BY ANGIOTENSIN II. IN CONTRAST, ENDOTHELIAL STIM1 IS PREDICTABLY IMPORTANT FOR VASORELAXATION, SUCH THAT EC-SPECIFIC STIM1 DELETION ATTENUATES ENDOTHELIUM- DEPENDENT VASODILATION AND INCREASES BLOOD PRESSURE. HOWEVER, NO STRATEGY CURRENTLY EXISTS TO DIRECTLY TARGET ENDOTHELIAL STIM1 FOR CLINICAL BENEFIT. IN THIS APPLICATION, WE PROPOSE TO DEVELOP A NOVEL VASORELAXING PEPTIDE (EFG2) THAT ACTS BY PROMOTING ENDOGENOUS NO PRODUCTION AND HAS SEVERAL UNIQUE PROPERTIES THAT ARE OF POTENTIAL CLINICAL BENEFIT. OUR PEPTIDE IS DERIVED FROM THE G PROTEIN-COUPLED ESTROGEN RECEPTOR, IS DESIGNED TO BE SPECIFIC FOR THE ENDOTHELIUM, AND DIRECTLY TARGETS STIM1 TO TRIGGER ENDOTHELIAL CA2+ ENTRY WITHOUT DEPLETING ER CA2+ STORE, THEREBY STIMULATING ENDOGENOUS NO PRODUCTION WHILE PROTECTING ER FUNCTION. OUR OBJECTIVES IN THIS PROPOSAL ARE TO DELINEATE THE MECHANISMS OF ACTION OF EFG2 IN ENDOTHELIAL CELLS, ASSESS ITS EFFECTS ON SEVERAL ASPECTS OF EC FUNCTION, BEGIN TESTING ITS POTENTIAL AS A VASORELAXING AGENT USING A MODEL OF HYPERTENSION, AND THROUGH THESE STUDIES, PROVIDE TRAINING FOR STUDENTS IN THE GRADUATE AND MEDICAL PROGRAMS AT DMU. THREE SPECIFIC AIMS ARE PROPOSED. AIM 1 WILL DELINEATE THE MECHANISMS OF ACTION OF EFG2 IN ENDOTHELIAL CELLS, BY TESTING ITS ABILITY TO ACTIVATE THE PROTOTYPICAL ICRAC CURRENT AND DOCUMENT ITS TARGET DOMAINS ON STIM1 THAT ARE RESPONSIBLE FOR ITS EFFECT TO TRIGGER ENDOTHELIAL CA2+ ENTRY. AIM 2 WILL ASSESS THE EFFECTS OF EFG2 ON SEVERAL ASPECTS OF EC FUNCTION, BY TESTING THE HYPOTHESES THAT EFG2 PROMOTES ENOS ACTIVITY, REDUCES INFLAMMATION-INDUCED EXPRESSION OF VASCULAR ADHESION MOLECULES AND SMOOTH MUSCLE PROLIFERATION, BUT DOES NOT CAUSE ER STRESS. AIM 3 WILL TEST THE HYPOTHESIS THAT EFG2 REDUCES BLOOD PRESSURE IN HYPERTENSIVE RATS IN A NO-DEPENDENT FASHION. COMPLETION OF THE STUDIES WILL INTRODUCE A MECHANISTICALLY NOVEL VASORELAXING PEPTIDE WITH SEVERAL UNIQUE FEATURES THAT ARE OF POTENTIAL CLINICAL BENEFIT, PROVIDE QUALITY STUDENT TRAINING, AND ENHANCE OVERALL RESEARCH OUTCOMES OF DES MOINES UNIVERSITY.

ELUCIDATING THE ROLE OF THE BRANCHED CHAIN AMINOTRANSFERASES (BCATC AND BCATM) AS NOVEL METABOLIC CHECKPOINTS OF ANTI-LYMPHOMA T CELL IMMUNITY - PROJECT SUMMARY NEW IMMUNOTHERAPIES TARGETING LYMPHOMAS DELIVERED PROMISING RESULTS DURING RECENT CLINICAL TRIALS. HOWEVER, THESE THERAPIES WERE ONLY EFFECTIVE IN A SMALL SUBSET OF PATIENTS WITH SHORT PERIODS OF REMISSION. THE RESULTS FROM THESE STUDIES SUGGESTED THE EXISTENCE OF IMMUNOSUPPRESSION IN THE TUMOR MICROENVIRONMENT. INDEED, THE LYMPHOMA MICROENVIRONMENT IS A VERY DYNAMIC NETWORK BETWEEN LYMPHOMA CELLS AND NON-MALIGNANT COMPONENTS THAT MAY PROMOTE TUMOR GROWTH AND CONSEQUENTLY DRUG RESISTANCE. PROGRESS IN T CELL METABOLISM HAS DEMONSTRATED THAT T CELLS EXPERIENCE A METABOLIC DISADVANTAGE IN THE TUMOR MICROENVIRONMENT, WHICH OFTEN MANIFESTS IN T CELL EXHAUSTION THAT JEOPARDIZES THEIR POTENTIAL TO DESTROY CANCER CELLS. THIS REVEALS A CRITICAL NEED TO EXPLORE NEW (METABOLIC) APPROACHES TO IMPROVE T CELL PERFORMANCE. OUR RESEARCH TEAM PROPOSES TO TARGET THE METABOLISM OF THE BRANCHED CHAIN AMINO ACIDS (BCAAS) AS A NOVEL METABOLIC CHECKPOINT OF T CELL ACTIVATION IN THE LYMPHOMA MICROENVIRONMENT. OUR RATIONALE STEMS FROM THE FINDINGS THAT THE BCAA, LEUCINE, IS INDISPENSABLE FOR T CELLS ACTIVATION, WHILE BCAA METABOLISM, INITIATED BY THE CYTOSOLIC (BCATC) AND MITOCHONDRIAL (BCATM) BRANCHED-CHAIN AMINOTRANSFERASES, IS A MEANS TO DIRECT LEUCINE TOWARD DEGRADATION. THE OBJECTIVE IN THIS APPLICATION IS TO DETERMINE WHETHER A LOSS OF EXPRESSION OF BCATC AND BCATM IS BENEFICIAL FOR THE DURABILITY AND FUNCTIONAL INTEGRITY OF T CELLS DURING LYMPHOMA ERADICATION IN UNIQUE PRE-CLINICAL MOUSE MODELS CREATED IN OUR LABORATORY. THE LONG-TERM GOAL OF THIS APPLICATION IS TO PROVIDE NEW MEANS TO IMPROVE THE T CELL-MEDIATED IMMUNE RESPONSE AND TO ADDRESS THE CHALLENGES WITH T CELL-DRIVEN ANTI-LYMPHOMA IMMUNOTHERAPY. THE CENTRAL HYPOTHESIS IS THAT BCATC, SUPPORTED BY BCATM, SERVES TO PROVIDE CHECKPOINT CONTROL ON T CELL FUNCTION BY BEING A PART OF A NEGATIVE FEEDBACK LOOP REGULATION OF T CELL ACTIVATION. DELETION OF THE BCAT GENES FROM T CELLS, INDIVIDUALLY OR IN COMBINATION, MAY PROVIDE A METABOLIC ADVANTAGE OF T CELLS ALLOWING THEM TO REMAIN ACTIVATED AND TO SUCCESSFULLY COMBAT LYMPHOMA GROWTH. TO TEST THE CENTRAL HYPOTHESIS, WE IDENTIFIED THREE SPECIFIC AIMS: (1) INVESTIGATE HOW THE EXPRESSION OF BCATC AND BCATM CHANGES UPON T CELL SUBSET DIFFERENTIATION AND WHETHER THE BCAT PROTEINS ARE ESSENTIAL FOR T CELL LINEAGE COMMITMENT AND FUNCTION, (2) DETERMINE WHETHER A BLOCKAGE IN THE TRANSAMINATION OF BCAAS ENHANCES THE T CELL RESPONSE TO LYMPHOMA TUMORS, AND (3) INVESTIGATE WHETHER A LOSS OF EXPRESSION OF BCATC IN MOUSE T CELLS CAN OVERCOME THE LYMPHOMA RESISTANCE TO ANTI-CTLA4 THERAPY. COMPLETION OF THIS PROJECT WILL NOT ONLY PROVIDE THE OPPORTUNITY TO IMPROVE THE CURRENT TREATMENT OPTIONS FOR LYMPHOMA PATIENTS BUT WILL ALSO ENGAGE STUDENTS IN PRE-CLINICAL CANCER STUDIES. THE STUDENTS WILL HIGHLY BENEFIT FROM ACQUIRING HANDS-ON RESEARCH EXPERIENCE IN CANCER, WHICH CAN BE TRANSLATED INTO ENHANCED RESEARCH SKILLS, SCIENTIFIC REASONING, AND BETTER UNDERSTANDING OF TREATMENT APPROACHES.

MACROPHAGE POLARIZATION BY C1Q AND RELATED MOLECULES

ANTIDEPRESSANT ACTIONS OF GLUTAMATERGIC AGENTS

IDENTIFICATION OF NOVEL ANTIDEPRESSANT MECHANISM OF KETAMINE BY KINOME PROFILING

CHARACTERIZATION OF A NOVEL C1Q-DEPENDENT ENGULFMENT PATHWAY IN AUTOIMMUNITY

REGULATION OF GPER-MEDIATED SIGNALING IN THE VASCULATURE BY CALMODULIN

POSITIVE IDENTIFICATION USING FRONTAL SINUS COMPARISONS: DEVELOPING EMPIRICALLY-BASED GUIDELINES

THE ROLE OF THE CAROTID BODY CHEMOREFLEX IN THE DEVELOPMENT OF RENAL DYSFUNCTION IN CHRONIC HEART FAILURE

EQUIPMENT: MRI: TRACK 1: ACQUISITION OF A 3-DIMENSIONAL MOTION CAPTURE SYSTEM FOR GRADUATE STEM RESEARCH AND EDUCATION -THIS PROJECT WILL ENHANCE STEM RESEARCH AND EDUCATION BY INTEGRATING A 3D MOTION ANALYSIS SYSTEM INTO THE RESEARCH AND CURRICULUM OF THREE COLLEGES AT DES MOINES UNIVERSITY. THE SYSTEM WILL ALLOW RESEARCHERS TO DISCOVER NEW WAYS TO HELP PERSONS WITH INJURIES OR DISABILITIES AND IMPROVE MOVEMENT PERFORMANCE OF ALL PEOPLE. IN ADDITION, THE MOTION CAPTURE SYSTEM WILL ENHANCE HIGH SCHOOL AND COLLEGE OUTREACH PROGRAMS. TRAINING WILL BE DEVELOPED TO PREPARE THE NEXT GENERATION OF SCIENTISTS TO ENGAGE WITH ADVANCED COMPUTER MODELS OF HUMAN MOTION AND FUNCTION. STUDENTS WILL HAVE THE OPPORTUNITY TO INTERACT WITH MOTION CAPTURE TOOLS SUPPORTED BY FACULTY WHO WILL ENGAGE STUDENTS IN MOTION ANALYSIS RESEARCH. THIS PROJECT WILL PROVIDE INTERACTIVE EXPERIENCES USING CUTTING-EDGE 3D MOTION CAPTURE AND ANALYSIS TECHNOLOGY TO IMPROVE THEIR UNDERSTANDING OF HOW THE BODY MOVES, INCLUDING THE EFFECTS OF ABNORMAL OR ALTERED MOVEMENT. THE OBJECTIVES OF THIS INTERDISCIPLINARY PROJECT ARE TO: 1. EXPAND MOVEMENT SCIENCE RESEARCH RELATED TO MOTION ANALYSIS, BIOMECHANICS, BIOMECHANICAL DATA ANALYSIS, AND MUSCULOSKELETAL MODELING; 2. TRAIN THE NEXT GENERATION OF HEALTH SCIENCE AND MEDICAL PROFESSIONALS IN APPLICATIONS OF STEM INCLUDING BIOMECHANICAL CONCEPTS AND TECHNOLOGY USED TO STUDY HUMAN MOVEMENT AND FUNCTION; AND 3. INTEGRATE HANDS-ON LEARNING EXPERIENCES INTO CURRICULA THAT ENRICHES STUDENT UNDERSTANDING OF BIOMECHANICAL PRINCIPLES, TECHNOLOGY, AND COMPUTER SCIENCE RELATED TO ANALYSIS AND STUDY OF HUMAN MOVEMENT AND FUNCTION. THE PROJECT TEAM WILL TRAIN A FUTURE WORKFORCE PREPARED BY EXPERIENCES WITH 3D MOTION CAPTURE TO ENHANCE THE STUDY OF HUMAN MOVEMENT. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

OSTEOID A NEW FORENSIC TOOL: DEVELOPING A PRACTICAL ONLINE RESOURCE FOR SPECIES IDENTIFICATION OF SKELETAL REMAINS

GLUD1 REGULATION OF STRUCTURAL PLASTICITY IN CHRONIC ETHANOL EXPOSURE AND PROTRACTED WITHDRAWAL - PROJECT SUMMARY LONG-LASTING VULNERABILITY TO RELAPSE IS A MAJOR HURDLE TO ACHIEVING SUCCESSFUL TREATMENT OUTCOMES IN PERSONS WITH A SUBSTANCE USE DISORDER. THE GLUTAMATE RECEPTOR SYSTEM IS HIGHLY IMPLICATED IN THE DEVELOPMENT AND MAINTENANCE OF FUNCTIONAL AND STRUCTURAL ALTERATIONS DRIVING A RETURN TO DRUG USE. INCREASING OUR UNDERSTANDING OF GLUTAMATERGIC REGULATION OF NEUROBIOLOGICAL ALTERATIONS DURING DRUG USE AND WITHDRAWAL, WE PROPOSE TO EXPLORE A NEW TARGET FOR THE DEVELOPMENT OF THERAPEUTIC AGENTS. DELTA-TYPE IONOTROPIC GLUTAMATE RECEPTORS (GLUD) HAVE BEEN IDENTIFIED AS REGULATORS IN THE FORMATION OF SYNAPTIC CONNECTIONS, AS THEY SERVE TO REGULATE THE ALIGNMENT AND DEVELOPMENT OF DENDRITIC SPINES. A RECENT STUDY HAS INDICATED THAT GLUD1 RECEPTOR FUNCTION/EXPRESSION PLAYS A ROLE IN STRUCTURAL PLASTICITY IN A MODEL OF PSYCHOSTIMULANT USE. IT IS CURRENTLY UNKNOWN WHAT ROLE GLUD1 PLAYS IN ALTERING STRUCTURAL PLASTICITY FOLLOWING CHRONIC ETHANOL EXPOSURE OR PROTRACTED WITHDRAWAL. USING AN ETHANOL EXPOSURE MODEL THIS APPLICATION SEEKS TO IDENTIFY THE ROLE GLUD1 HOLDS IN THE REGULATION OF DENDRITIC SPINE DENSITY AND MORPHOLOGY UNDER ETHANOL EXPOSURE AND AFTER PROTRACTED WITHDRAWAL. WE WILL FOCUS ON THE BASOLATERAL AMYGDALA (BLA), A KEY REGION FOR ETHANOL ACTION. WE HYPOTHESIZE THAT GLUD1 DYNAMICALLY CONTROLS CHRONIC ETHANOL- AND WITHDRAWAL-ASSOCIATED CHANGES IN SPINE MORPHOLOGY IN THE BLA. WE WILL TEST THIS HYPOTHESIS IN ONE SPECIFIC AIM, COMPRISED OF THREE INDEPENDENT EXPERIMENTS. ALL EXPERIMENTS WILL COMPARE MALE AND FEMALE RATS. FIRST, WE WILL CHARACTERIZE DENDRITIC SPINE MORPHOLOGY UNDER CONTROL CONDITIONS, ETHANOL EXPOSURE, AND ACROSS VARIOUS WITHDRAWAL TIME POINTS (DAY 1, 21, 42), USING IONTOPHORETIC DYE INJECTION AND CONFOCAL MICROSCOPY METHODS. WE WILL ALSO CHARACTERIZE GLUD1 EXPRESSION IN SURFACE MEMBRANE FRACTIONS USING A BIOTINYLATION PROCEDURE FOLLOWED BY WESTERN BLOT ANALYSIS AT EACH EXPERIMENTAL TIME POINT. FINALLY, WE WILL UTILIZE DYE INJECTIONS AND CONFOCAL MICROSCOPY PAIRED WITH INJECTION OF A SHRNA VIRAL CONSTRUCT TO KNOCK DOWN GLUD1 LEVELS IN THE BLA PRIOR TO ETHANOL EXPOSURE. THIS EXPERIMENT WILL IDENTIFY THE SPECIFIC ROLE GLUD1 PLAYS IN DENDRITIC SPINE EXPRESSION AND MORPHOLOGY ACROSS OUR TREATMENT GROUPS AND SEX. TOGETHER, THESE STUDIES WILL REVEAL THE ROLE OF GLUD1 IN REGULATION OF STRUCTURAL PLASTICITY DURING ETHANOL EXPOSURE AND WITHDRAWAL. AS SUCH, GLUD1 REGULATION OF STRUCTURAL PLASTICITY COULD CONTRIBUTE TO WELL CHARACTERIZED FUNCTIONAL ALTERATIONS OF THE GLUTAMATERGIC RECEPTOR SYSTEM DURING SHORT TERM WITHDRAWAL. THIS WOULD IMPLICATE GLUD1 AS A KEY HUB, CAPABLE OF REGULATING FUNCTIONAL AND STRUCTURAL PLASTICITY, MAKING IT A PROMISING TARGET FOR THERAPEUTIC DEVELOPMENT. LONG TERM OBJECTIVES ARE TO IDENTIFY THE OVERALL IMPACT OF GLUD1 REGULATION ON BOTH STRUCTURAL AND FUNCTIONAL PLASTICITY ACROSS ADDITIONAL BRAIN REGIONS IMPACTED BY DRUG TAKING AND WITHDRAWAL.

RURAL HEALTH OUTREACH SPECIAL INITIATIVE

AUTOCLAVE FOR DMU SHARED BIOMEDICAL RESEARCH FACILITY - ABSTRACT THE ANIMAL RESEARCH ENVIRONMENT AT DES MOINES UNIVERSITY INCLUDES A STRONG GROUP OF NIH FUNDED INVESTIGATORS WITH EXCELLENT EQUIPMENT AND STAFF SUPPORT HOUSED IN A MODERN ANIMAL CARE FACILITY. A SIGNIFICANT WEAKNESS OF THE CURRENT EXPERIMENTAL CAPABILITIES IS OUR 13-YEAR-OLD AUTOCLAVE THAT IS CONNECTED TO A STANDALONE BUT INTEGRATED 50-YR OLD BOILER (NO LONGER IN PRODUCTION) AND A WATER PURIFICATION SYSTEM. THIS INTEGRATED OLD EQUIPMENT FREQUENTLY BREAKS DOWN AND REQUIRES REPAIRS, CAUSING UNANTICIPATED EXPENDITURES AND DELAYS IN CONDUCTING ANIMAL USE RESEARCH. SUCH BREAKDOWNS OCCUR FREQUENTLY BECAUSE OF THE AGE AND CONDITION OF THE EXISTING AUTOCLAVE. AUTOCLAVING IS THE MOST EFFECTIVE AND RELIABLE MEANS OF STERILIZING LABORATORY MATERIALS. AUTOCLAVES ARE AN INDISPENSABLE WELL-ESTABLISHED MAINSTREAM TECHNOLOGY THAT IS USED UBIQUITOUSLY IN BIOMEDICAL FACILITIES TO STERILIZE EQUIPMENT/PRODUCTS BEFORE USE IN AN EXPERIMENT OR TO RENDER ITEMS NON-INFECTIOUS BEFORE DISPOSAL. DESPITE ITS IMPORTANCE TO NIH RESEARCH, OUR CURRENT AUTOCLAVE, WHILE WELL MAINTAINED AND HEAVILY USED, HAS LOST PACE WITH THE CURRENT STATE- OF-THE-ART IN SENSITIVITY, RELIABILITY AND TIMELINESS FOR OUR ANIMAL AND GENERAL BIOMEDICAL RESEARCH. WE THEREBY REQUEST FUNDS TO PURCHASE A NEW EFFICIENT INTEGRATED STEAM STERILIZER (AUTOCLAVE) - AN INTEGRATED SYSTEM THAT INCLUDES A MICROCOMPUTER-CONTROLLED STEAM STERILIZER, A STEAM BOILER, A WATER SAVING SYSTEM AND A CONTROL SYSTEM - TO ALLOW FOR RELIABLE STERILIZATION OF ANIMAL AND BIOMEDICAL RELATED RESEARCH TOOLS/MATERIALS TO SUPPORT OUR MAJOR AND MINOR USERS THAT HAVE A NEED FOR THIS TECHNOLOGY. A MODERN INTEGRATED AUTOCLAVE WILL SUPPORT US IN ENSURING EFFICIENT WORKFLOWS AS WELL AS A SAFE AND CONTAMINATION FREE VIVARIUM AND RESEARCH ENVIRONMENT. AN ESTABLISHED SUSTAINED TRACK RECORD OF HEAVY USE OVER THE LAST THIRTEEN YEARS, FREQUENT PUBLICATIONS FROM THE MANY NIH AND EXTERNALLY FUNDED BIOMEDICAL RESEARCHER COMMUNITY AND MENTORED STUDENT RESEARCH AND TRAINING ON DES MOINES UNIVERSITY’S CAMPUS WILL ENSURE THAT THE NEW INTEGRATED STEAM STERILIZER WILL PAY FOR ITSELF IN RESEARCH PRODUCTIVITY.

COLLABORATIVE RESEARCH: RUI: CHRONOLOGY AND ECOLOGY OF LATE PLEISTOCENE MEGAFAUNA AT RANCHO LA BREA