Regents Of The University Of California At Riverside

CARES ACT: INSTITUTION ALLOCATION OF HEER FUNDS

HIGHER EDUCATION EMERGENCY FUNDS TO STUDENTS

HEALTH DISPARITIES RESEARCH AT UCR

NC4: CENTER FOR NETWORKED CONFIGURABLE COMMAND, CONTROL AND COMMUNICATIONS FOR RAPID SITUATIONAL AWARENESS

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF BTO IN THE AMOUNT OF 389,469 ON CONTRACT HR0011-17-2-0047.

SPINS AND HEAT IN NANOSCALE ELECTRONIC SYSTEMS (SHINES)

MARINE ECOSYSTEM SENSING, OBSERVATION AND MODELING LABORATORY

NEW AWARD - HIGH ENERGY PHYSICS

THE RESEARCH OBJECTIVE OF THIS PROPOSAL IS TO INVESTIGATE THE ROOT COLLAPSE ASSOCIATED WITH HUANGLONGBING (HLB)-IMPACTED TREES AND WAYS TO MITIGATE IT BY PROMOTING ROOT HEALTH. OUR PREVIOUS WORK DEMONSTRATES THAT AS HLB SEVERITY INCREASES, THE ROOT MICROBIOME BECOMES ENRICHED IN SOIL-BORNE PATHOGENS. WE WILL CONDUCT EXPERIMENTS TO EMPIRICALLY DETERMINE IF THESE PATHOGENS EXACERBATE THE HLB-ASSOCIATED ROOT AND CANOPY DECLINE. WE WILL INTEGRATE FIELD STUDIES THAT TEST HLB RESISTANT/TOLERANT ROOTSTOCKS AND USE OF SOIL AMENDMENTS THAT PROMOTE ROOT HEALTH TO DETERMINE IF THEY SUPPRESS PATHOGENS IN THE ROOTS AND PROLONG TREE LONGEVITY/PRODUCTIVITY UNDER HLB PRESSURE. THESE FIELD STUDIES WILL INCLUDE NEWLY ESTABLISHED GROVES AND MATURE GROVES. TO SUPPORT OUR FIELD TRIALS AND DECIPHER THE GENES/GENE PATHWAYS THAT DICTATE HOW PLANTS RESPOND TO HLB, WE WILL DETERMINE HOW ROOTSTOCKS AND SCIONS RESPOND TOCANDIDATUSLIBERIBACTER ASIATICUS USING CITRUS VARIETIES THAT ARE EITHER HIGHLY HLB-SUSCEPTIBLE OR HLB-RESISTANT USING A COMBINATION OF DISEASE PHENOTYPING AND GENE EXPRESSION ANALYSES. WE WILL INTEGRATE THIS RESEARCH WITH A ROBUST EXTENSION AND OUTREACH PROGRAM IN COMBINATION WITH AN ECONOMIC COST-BENEFIT ANALYSIS STRUCTURED AROUND ADOPTION OF TREATMENTS THAT ENHANCE ROOT HEALTH INTO COMMERCIAL CITRICULTURE.

**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** VITAL TO LOCAL RURAL COMMUNITIES AND THE NATIONAL ECONOMY, AGRICULTURE IN THE WESTERN U.S. FACES CHALLENGES INCLUDING DEGRADATION OF NATURAL RESOURCES, CLIMATE VARIABILITY, AND PEST OUTBREAKS. ARTIFICIAL INTELLIGENCE (AI) AND DIGITAL AGRICULTURE (DA), THE TRANSDISCIPLINARY APPLICATION OF HIGH-PERFORMANCE COMPUTING AND HYPERDIMENSIONAL DATA, CAN IMPROVE FARMING RESILIENCE. SHORT- AND MEDIUM-TERM, THIS PROJECT APPLIES DA TO OPTIMIZE CURRENT PRACTICES, MAXIMIZING EFFICIENCY, AND MINIMIZING WASTE. LONG-TERM, THE PROJECT DEVELOPS A FOUNDATION OF TOOLS AND KNOWLEDGE FOR A SHIFT TO HIGHLY-AUTOMATED MECHANIZED SYSTEMS FOR IRRIGATION, NUTRIENT, SALINITY, AND PEST MANAGEMENT. APPLIED RESEARCH SUPPORTING OBJECTIVES (SO) ARE SO1 -- A DECISION-SUPPORT TOOL FOR AGRICULTURAL INPUT MANAGEMENT WITH AI (AIM-AI) -- AND SO2 -- A TOOL FOR EARLY PEST DETECTION WITH AI (EPD-AI). TOOLS INTEGRATE PHYSICAL AND STATISTICAL MODELS, BIG-GEODATA (E.G., DAILY REMOTE SENSING), AND AI. SO1 WILL MERGE RECOMMENDATIONSFOR EVAPOTRANSPIRATION-BASED SOIL-WATER BALANCE IRRIGATION SCHEDULING, SALINITY LEACHING, AND FERTILIZATION INTO A SINGLE FRAMEWORK. IN SO2, AN AI CLASSIFIER WILL ESTIMATE PEST EMERGENCE IN ORGANIC AND CONVENTIONAL CROPS FOR TIMELY RESPONSE. AIM-AI AND EPD-AI WILL BE EVALUATED USING EXTENSIVE FIELD DATA. COOPERATIVE EXTENSION SOS WILL INFORM STAKEHOLDERS OF CURRENT RESEARCH-BASED TOOLS, KNOWLEDGE, AND ON-FARM PRACTICES (SO3), AND DISSEMINATE KNOWLEDGE FROM RESEARCH SOS (SO4) THROUGH TRAINING (FACE-TO-FACE AND ELECTRONIC), FIELD DAYS, PUBLICATIONS, AND SMARTPHONE AND WEB APPS. SO5 INCLUDES AN UNDERGRADUATE DA FELLOWSHIP TO EDUCATE FUTURE FARMERS, AND DA PROFESSIONALS AND ACADEMICS VIA STUDENT RESEARCH, MENTORSHIP, AND INDUSTRY EXTERNSHIPS. PROJECT SUCCESS IN FOSTERING RURAL PROSPERITY AND ENVIRONMENTAL SUSTAINABILITY WILL BE EVALUATED BY STAKEHOLDERS, SCIENTISTS, AND PROFESSIONAL EVALUATORS.

TEACHER QUALITY ENHANCEMENT GRANTS FOR STATE AND PARTNERSHIPS - PARTNERSHIP GRANTS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

HIGH ENERGY PHYSICS- ENERGY, INTENSITY, THEORETICAL FRONTIER

TAS::57 3600::TAS "(MURI - 2014)CONVERGENT EVOLUTION TO ENGINEERING: MULTISCALE STRUCTURES AND MECHANICS IN DAMAGE TOLERANT DATED 13 DEC 2013);

IRISS INTERKINGDOM SOIL SAFETY SENSORS - CERES DARPA BTO

MULTIPLE YEAR AWARD&INCREMENTAL FUNDING FOR YEARS ONE OF FIVE. THIS PROPOSAL IS ENTITLED, "ALTERNATIVE EARTHS: EXPLAINING PERSISTENT INHABITATION ON

COOPERATIVE AGREEMENT TO DEVELOP NANO MATERIALS & NANO DEVICES (CNN IV)

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** . ?

COOPERATIVE AGREEMENT 3D ELECTRONICS PHASE II

UC RIVERSIDE MARC U* STAR UNDERGRADUATE RESEARCH PROGRAM

MOLECULAR BASIS OF ECDYSTEROID ACTION IN THE MOSQUITO

CHEMICAL BIOLOGY OF DNA AND RNA ALKYLATION

INFLATION REDUCTION ACT (IRA) – HIGH-EFFICIENCY, DURABLE LOW-TEMPERATURE CATALYTIC METHANE OXIDATION SYSTEM FOR ON-SITE NATURAL GAS GENERATORS POWERING LIQUID NATURAL GAS COMPRESSORS THE PROJECT GOAL IS TO PROPOSE A COMMERCIALLY SCALABLE PROJECT PLAN TO DRAMATICALLY IMPROVE THE CATALYTIC ACTIVITY AND STABILITY OF PALLADIUM-BASED CATALYSTS IN A CATALYTIC OXIDATION SYSTEM FOR ACHIEVING “NEAR ZERO EMISSIONS” OF METHANE FROM NATURAL GAS GENERATORS AT GAS WELLS. THE OBJECTIVE IS TO DRAMATICALLY IMPROVE THE CATALYTIC ACTIVITY AND STABILITY OF PALLADIUM-BASED CATALYSTS FOR METHANE OXIDATION BY ENGINEERING PALLADIUM SITES AND SUPPORT MATERIALS SYNERGISTICALLY WITH ATOMIC PRECISION USING HIGH-TEMPERATURE SHOCK TECHNIQUE.

MOLECULAR INTERACTIONS DURING NEURAL CREST FORMATION

GENETIC CHARACTERIZATION OF PHYTOCHROME NUCLEAR BODIES IN PLANT LIGHT SIGNALING

BY YOUTH, FOR YOUTH: DIGITAL SUPPORTED PEER NAVIGATION FOR ADDRESSING CHILD MENTAL HEALTH INEQUITIES - PROJECT SUMMARY DESPITE SIGNIFICANT PROGRESS IN RESEARCH, PRACTICE, AND POLICY OVER THE PAST FEW DECADES, MANY CHILDREN AND YOUTH CONTINUE TO EXPERIENCE POOR MENTAL HEALTH OUTCOMES BASED ON THEIR SOCIOECONOMIC DISADVANTAGE, ETHNIC OR RACIAL MINORITY STATUS, OR IMMIGRANT STATUS. AFRICAN AMERICAN AND LATINO YOUTH HAVE 1.5–3 TIMES GREATER ODDS OF EXPERIENCING AN UNMET MENTAL HEALTH NEED THAN DO THEIR WHITE COUNTERPARTS AND ARE MORE LIKELY TO BE NEGATIVELY IMPACTED BY SOCIAL DETERMINANTS OF MENTAL HEALTH RELATED TO POVERTY. WITH THEIR UNRIVALED ABILITY TO REACH YOUTH, SCHOOL-BASED AND PEDIATRIC PRIMARY CARE SERVICES ARE IDEAL HUBS TO PROVIDE MENTAL HEALTH, HEALTHCARE, SOCIAL SERVICES, AND PREVENTION TO STUDENTS AND FAMILIES WHO OTHERWISE FACE BARRIERS TO CARE. USING PARTICIPATORY DESIGN AND COMMUNITY PARTNERED PARTICIPATORY RESEARCH (CPPR), UCLA AND UCSF PSYCHIATRY RESEARCH CENTERS WITH LOS ANGELES TRUST FOR CHILDREN’S HEALTH AND SAN FRANCISCO HEALTH NETWORK PROPOSE TO: (1) FULLY CO-DESIGN (WITH YOUTH, CAREGIVERS, CLINICIANS AND OTHER STAKEHOLDERS) AN INNOVATIVE MENTAL HEALTH DIGITAL TOOL, CALLED 4YOUTH, TO IMPLEMENT ALGORITHMICALLY SUPPORTED MENTAL HEALTH AND SOCIAL DETERMINANTS SCREENING AND TRIAGE, RESILIENCY APPS AND NAVIGATION ACTIVITIES AND HELP SUPPORT THE PRIMARY CARE-CLINICAL WORKFORCE WITHIN SCHOOL CENTERS AND PEDIATRIC SERVICES; (2) STUDY THE IMPLEMENTATION OF TWO MENTAL HEALTH NAVIGATION MODELS SEPARATELY (FAMILY NAVIGATON+4YOUTH AND YOUTH NAVIGATION+4YOUTH), AND THEIR COMBINED EFFECTIVENESS FOR IMPROVING CONNECTING AND MATCHING YOUTH TO THE RIGHT LEVEL OF CARE AND SUPPORTS. THIS PROJECT WILL BE INITIATED WITH YOUTH 11-24 YEARS OLD AND FAMILY AND COMMUNITY MEMBERS ACROSS 10 LOS ANGELES UNIFIED SCHOOL DISTRICT (LAUSD) WELLNESS CENTERS AND 10 SAN FRANCISCO HEALTH NETWORK PEDIATRIC PRIMARY CARE CENTERS, WHICH SERVE MOSTLY BLACK, LATINO, AND ASIAN CHILDREN. MOBILE TECHNOLOGY APPROACHES ARE GAINING EMPIRICAL SUPPORT AND HOLD GREAT POTENTIAL FOR ENHANCING MENTAL HEALTH NAVIGATOR MODELS. INCORPORATING SCALABLE DIGITAL HEALTH TOOLS, AND STATISTICALLY EVALUATED ALGORITHMS TO AID THE NAVIGATION PROCESS, SUCH AS SCREENING, TRIAGE, TRACKING, CONNECTING TO CARE, AND MULTI-LEVEL COMMUNICATION, WILL HELP ENSURE YOUTH ARE RECEIVING OPTIMAL CARE THAT NAVIGATORS, PROVIDERS AND OTHER RELEVANT SYSTEMS CAN MEASURE. A SUCCESSFUL OUTCOME OF THE PROJECT IS A CPPR DEVELOPED OPEN-SOURCE INTERVENTION IMPLEMENTABLE IN SCHOOL-BASED AND PEDIATRIC PRIMARY CARE SERVICES, FOR IMPROVING MENTAL HEALTH SERVICES ACCESS FOR MINORITIZED YOUTH.

MOSQUITOCIDAL ACTION OF BACILLUS THURINGIENSIS TOXINS

A NOVEL ROLE FOR PTPN2 IN INTESTINAL EPITHELIAL BARRIER REGULATION

SPIN PHYSICS WITH PHENIX AT RHIC

ARP: AMERICAN RESCUE PLAN (HEERF III)- MINORITY SERVING INSTITUTIONS (MSIS)

NEUROPROTECTION BY IFN-BETA IN AIDS

OUR RESEARCH OBJECTIVES ARE TO DESIGN AND IDENTIFY BACTERICIDES THAT CAN CURE/SUPPRESS OR PROPHYLACTICALLY TREAT HUANGLONGBING (HLB), AND TO TARGET THESE BACTERICIDES TO THE PHLOEM WHERE THE ASSOCIATED BACTERIUM, CANDIDATUS LIBERIBACTER ASIATICUS (CLAS), RESIDES. WE WILL DEVELOP TWO CLASSES OF BACTERICIDES, THE FIRST BASED ON SILVER AND SULFUR NANOPARTICLES, THE SECOND ROOTED IN NATURAL PRODUCT DISCOVERY, MINING ANTI-CLAS COMPOUNDS PRODUCED BY MICROBES THAT INHABIT HLB SURVIVOR TREES IN FLORIDA. THE DIFFICULTY WITH ANY ANTI-HLB FORMULATION IS OPTIMIZING ITS DELIVERY TO THE PHLOEM. IN ALL CASES, DELIVERY OF THE BACTERICIDES TO, AND WITHIN, THE PHLOEM SIEVE TUBES TO KILL CLAS WILL BE OF PARAMOUNT IMPORTANCE. THUS, WE WILL PERFORM DETAILED ANALYSES OF THE PHLOEM TRANSIT ROUTES THAT A GIVEN BACTERICIDE TAKES WHEN INTRODUCED THROUGH COMMON APPLICATION METHODS (TRUNK INJECTION, FOLIAR APPLICATION OR ROOT APPLICATIONS). WE WILL ALSO CONTINUE TO DEVELOP A PROMISING, NEW PETIOLE/BRANCH DELIVERY SYSTEM FOR USE IN FIELD TREES. WE WILL EXPLORE THE CHEMISTRY OF BACTERICIDES TO OPTIMIZE UPTAKE BY THE SIEVE TUBES. BECAUSE SIGNIFICANT AMOUNTS OF PHLOEM PLUGGING OCCURS IN CLAS-INFECTED TREES, WE WILL EVALUATE BACTERICIDE TRANSIT PATHWAYS AT THE WHOLE-PLANT LEVEL AT VARYING STAGES OF INFECTION. THIS WORK ON HLB-PHLOEM TRANSIT ROUTES WILL PROVIDE IMPORTANT INFORMATION FOR US AND FOR OTHERS IN THE HLB RESEARCH COMMUNITY WHO ARE EVALUATING DELIVERY OF MATERIALS TO THE PHLOEM. WE WILL INTEGRATE THIS RESEARCH WITH A ROBUST EXTENSION AND OUTREACH PROGRAM THAT WILL BE COUPLED WITH AN ECONOMIC COST-BENEFIT ANALYSIS STRUCTURED AROUND ADOPTION OF THESE TREATMENTS INTO COMMERCIAL CITRICULTURE.

HUANGLONGBING (HLB) IS A CITRUS DISEASE THAT IS CURRENTLY CAUSING ANNUAL LOSSES OF OVER 1 BILLION DOLLARS AND 7,900 JOBS IN FLORIDA. AS HLB SPREADS ACROSS THE US, HUGE LOSSES ARE ALSO EXPECTED IN ALL OF THE OTHER CITRUS PRODUCING REGIONS. CURRENT HLB MANAGEMENT STRATEGIES ARE NOT EFFECTIVE, AND THEY OFTEN INVOLVE REGULAR APPLICATIONS OF INSECTICIDES, WHICH CAN HAVE DETRIMENTAL EFFECTS ON THE ENVIRONMENT AND HUMAN HEALTH. IT IS THEREFORE IMPERATIVE THAT EFFECTIVE AND SUSTAINABLE HLB MANAGEMENT STRATEGIES ARE DEVELOPED.THE GOAL OF THIS PROJECT IS TO CREATE HIGHLY EFFECTIVE HLB TREATMENTS THAT CAN BOTH PREVENT AND CURE THIS DISEASE. OUR APPROACH WILL USE A VIRUS (CTV) TO DELIVER ANTIMICROBIAL AGENTS TO THE HABITAT (PHLOEM) OF THE HLB-ASSOCIATED PATHOGEN (CLAS). TO SUBSTANTIALLY INCREASE THE EFFICACY OF THIS APPROACH, WE ARE BORROWING A METHOD THAT IS USED IN HUMAN INFECTIOUS DISEASE, WHICH ENGINEERS PEPTIDES TO SPECIFICALLY TARGET THE PATHOGEN. THIS APPROACH SHOULD INCREASE THE EFFICACIES OF OUR ANTI-CLAS AGENTS BY SEVERAL ORDERS OF MAGNITUDE, WHICH WE EXPECT WILL TRANSFORM AN HLB TREATMENT THAT IS MINIMALLY TO MODERATELY EFFECTIVE INTO ONE THAT IS HIGHLY EFFECTIVE. THIS PROJECT WILL ALSO CREATE A COMPUTATIONAL MODEL OF HLB, WHICH WILL ENABLE A DEEP UNDERSTANDING OF CLAS, CITRUS AND THE INSECT THAT TRANSMITS CLAS (ACP), ALONG WITH ALL OF THEIR INTERACTIONS. THIS MODEL WILL THEREFORE PROVIDE RESEARCHERS, ENGINEERS AND AGRIBUSINESSES WITH A POWERFUL SUITE OF TOOLS AND AN UNPRECEDENTED KNOWLEDGE BASE - WHICH WE EXPECT WILL ENABLE THEM TO CREATE (I) ANTI-CLAS MOLECULES, (II) HLB-TOLERANT/RESISTANT CITRUS (III) EARLY DETECTION METHODS AS WELL AS (IV) MEDIA TO CULTIVATE CLAS UNDER LABORATORY CONDITIONS. THIS PROJECT ADDRESSES 5 OF THE 7 PRIORITIES OF THE CITRUS DISEASE SUBCOMMITTEE, DESCRIBED IN THE REQUEST FOR APPLICATIONS FROM THE CITRUS DISEASE RESEARCH AND EXTENSION PROGRAM. OUR PROJECT WILL ALSO PERFORM ANALYSES TO DETERMINE IF OUR HLB MANAGEMENT SOLUTIONS WILL BE ECONOMICALLY FEASIBLE. IN ADDITION, WE WILL ALSO IMPLEMENT AN EXTENSION AND OUTREACH PROGRAM FOR THE CITRUS STAKEHOLDER COMMUNITY, THE GENERAL PUBLIC, AND THE SCIENTIFIC COMMUNITY. WE WILL DISSEMINATE INFORMATION IN THREE GENERAL CATEGORIES. THE FIRST CATEGORY WILL BE THE HLB MANAGEMENT SOLUTIONS GENERATED BY THIS PROJECT. THE SECOND CATEGORY WILL BE OUR RESEARCH FINDINGS. THE THIRD CATEGORY WILL BE GENERAL HLB INFORMATION. THE INFORMATION WILL BE DISSEMINATED BY SEVERAL MECHANISMS INCLUDING PRESENTATIONS, PUBLICATIONS, A WEBSITE AND VIDEOS.IN SUM, THE GOAL OF THIS PROJECT IS TO CREATE EFFECTIVE AND SUSTAINABLE STRATEGIES TO MANAGE HLB. WE EXPECT THAT SUCCESS IN THESE EFFORTS WILL (I) PREVENT ENORMOUS ECONOMIC AND JOB LOSSES AS WELL AS (II) PREVENT SUBSTANTIAL DAMAGE TO THE ENVIRONMENTAL AND HUMAN HEALTH.

FEED THE FUTURE INNOVATION LAB ON CLIMATE RESILIENT COWPEA

GENOME-WIDE IMPACT OF MPING TRANSPOSITION ON RICE PHENOTYPIC DIVERSITY

RESEARCH TRAINING IN ENVIRONMENTAL TOXICOLOGY

GEAR-UP

MEMORY CONSOLIDATION DURING SLEEP IN HUMANS, RODENTS AND COMPUTATIONAL MODELS

CITRUS HUANGLONGBING (HLB) HAS NEGATIVELY IMPACTED ALL THE MAJOR CITRUS GROWING AREAS OF THE WORLD. THE FINANCIAL LOSSES INCURRED DUE TO HLB HAVE BEEN ESTIMATED TO BE SEVERAL BILLIONS OF DOLLARS IN THE US ALONE. CITRUS IS AN IMPORTANT FOOD CROP AND CONSUMED WIDELY IN THE USA AND OTHER PARTS OF THE WORLD. THE FRUITS ARE CONSIDERED TO BE NUTRIENT-DENSE AND ARE RICH IN BENEFICIAL PHYTOCHEMICALS LIKE FLAVONOIDS, CAROTENOIDS, COUMARINS, TERPENES, AND LIMONOIDS. THE MEDICINAL PROPERTIES ASSOCIATED WITH CITRUS FRUITS PROTECT AGAINST SEVERAL CHRONIC DISEASES. CITRUS IS ALSO AN ESSENTIAL COMPONENT OF THE DIET FOR MOST PEOPLE. JUICE DERIVED FROM VARIOUS TYPES OF CITRUS IS CONSUMED WIDELY. CULTIVATING CITRUS PROVIDES REVENUE THAT SUPPORTS MULTI-BILLION DOLLAR INDUSTRIES IN THE USA.THE DEVASTATION CAUSED BY HLB HAS NOW THREATENED THE CITRUS INDUSTRY IN FLORIDA. TEXAS AND CALIFORNIA, THE OTHER TWO PROMINENT CITRUS-PRODUCING STATES, ARE LIKELY TO BE IN A SIMILAR SITUATION IF THE DISEASE IS NOT CONTROLLED. DESPITE RESEARCH CONDUCTED ON HLB FOR THE PAST FIFTEEN YEARS, TANGIBLE, PRACTICAL SOLUTIONS ARE NOT AVAILABLE TO THE GROWERS. HLB IS APTLY DESCRIBED AS THE GREATEST THREAT TO CITRUS CULTIVATION IN THE USA. THE DISEASE COMPLEX IS COMPLICATED BECAUSE OF THE UNCULTIVABLE NATURE OF THE PATHOGEN (LEADING TO LACK OF UNDERSTANDING OF THE DISEASE ORGANISM), LATE SYMPTOM EXPRESSION (RESULTING IN THE SPREAD OF THE PATHOGEN BEFORE AN INFECTED PLANT CAN BE IDENTIFIED), AND, UNEQUAL DISTRIBUTION OF THE PATHOGEN IN THE HOST PLANTS (RESULTING IN SAMPLING ISSUES AND FALSE NEGATIVES IN HLB SURVEYS). IN ADDITION, THE WIDESPREAD DISTRIBUTION OF THE RAPIDLY PROLIFERATING PSYLLID VECTOR AND DIFFICULTIES ASSOCIATED WITH CONTROLLING OF PSYLLID POPULATIONS CONTRIBUTE TO THE CHALLENGES RELATED TO DEVELOPING PRACTICAL SOLUTIONS. SHORT-TERM DISEASE MANAGEMENT CAN BE ACHIEVED BY CONTROLLING PSYLLIDS, PREVENTING SPREAD BY ADHERING TO PHYTOSANITARY PRACTICES, AND IMPLEMENTING STRICT REGULATIONS. ENVIRONMENTALLY FRIENDLY AND FINANCIALLY SUSTAINABLE SOLUTIONS WILL BE NEEDED TO CONTINUE CITRUS CULTIVATION IN THE PRESENCE OF THE HLB ASSOCIATED PATHOGEN AND THE PSYLLID VECTOR. HLB HAS NOW ESTABLISHED IN THE THREE MAJOR CITRUS GROWING STATES OF THE USA. HLB DISEASE MANAGEMENT PRACTICES THAT ARE IN VOGUE ARE USEFUL FOR A LIMITED TIME ONLY; LONG-TERM CONTROL OF HLB WILL REQUIRE GENETIC SOLUTIONS. THE MOST PROMISING SOLUTION IS TO DEVELOP DISEASE-RESISTANT CULTIVARS THAT PREVENT THE ESTABLISHMENT OF THE ASSOCIATED PATHOGEN. SINCE THERE IS NO APPRECIABLE HLB RESISTANCE IN THE GENUS CITRUS, UTILIZING GENETIC RESOURCES OF WILD RELATIVES IS A VIABLE OPTION TO INTROGRESS RESISTANCE TRAITS INTO CULTIVATED CITRUS. WE HAVE PREVIOUSLY CHARACTERIZED HLB SENSITIVITY ACROSS A BROAD SPECTRUM OF PHYLOGENETICALLY DIVERSE CITRUS AND RELATIVE GENERA UNDER FIELD CONDITIONS. WE HAVE REPORTED THAT AUSTRALIAN LIMES IN THE GROUPS MICROCITRUS AND EREMOCITRUS, THAT DIVERGED FROM THE MANDARIN LINEAGE APPROXIMATELY 6 MILLION YEARS AGO, HAVE HLB RESISTANCE TRAIT THAT IS SUPERIOR TO CITRUS. BUILDING ON THIS INSIGHT, WE CREATED CITRUS X MICROCITRUS HYBRIDS THAT POSSESS BOTH GOOD FRUIT QUALITY AND STRONG HLB RESISTANCE; THESE MATERIALS ARE THE BUILDING BLOCKS OF NEW HLB SOLUTIONS THAT WE EXPLOIT HERE TODEVELOP COMMERCIALLY ACCEPTABLE, NON-TRANSGENIC, HLB-RESISTANT CULTIVARS.OUR PROJECT BUILDS ON PREVIOUS WORK WHERE WE IDENTIFIED NATURAL SOURCES OF HLB RESISTANCE, BRED FOR NEW HLB RESISTANT VARIETIES, AND DEVELOPED THE GENOMIC RESOURCES REQUIRED FOR MARKER-ASSISTED SELECTION OF HLB RESISTANCE. HERE, WE PROPOSE TO EVALUATE THE COMMERCIAL POTENTIAL OF THESE BY CONDUCTING MULTI-SITE EVALUATIONS OF A LIMITED NUMBER OF HYBRIDS IN FLORIDA, TEXAS, AND CALIFORNIA. OUR PROJECT AIMS TO DEVELOP AN INTEGRATED PIPELINE THAT WILL ACCELERATE THE FARM-LEVEL IMPLEMENTATION OF OUR RESEARCH AND HASTEN THE TIME-LINES FOR TRANSITIONING THESE MATERIALS FROM THE LAB TO THE GROWER. OUR PIPELINE WILL ENABLE THE RAPID IDENTIFICATION OF VALUABLE HYBRIDS BY COMBINING MULTIPLE STRATEGIES INCLUDING THE USE OF PRECOCIOUS FRUITING TO ACCELERATE FRUIT EVALUATION, METABOLOMICS AND GENOMICS TO QUICKLY ELIMINATE UNDESIRABLE HYBRIDS, AND MULTI- LOCATION FIELD TRIALS TO ASSESS HLB RESISTANCE, HORTICULTURAL PERFORMANCE, AND CONSUMER ACCEPTANCE IN REAL-WORLD CONTEXTS. OUR APPROACH IS TO INCORPORATE RESISTANCE-ASSOCIATED GENOMIC SEGMENTS FROM AUSTRALIAN LIMES TO CULTIVATED CITRUS TYPES. THE PROCESS OF SELECTING PROMISING HYBRIDS FROM BREEDING POPULATIONS IS GENERALLY TIME CONSUMING AND INVOLVES GREENHOUSE EVALUATIONS, PRELIMINARY HORTICULTURAL DATA, FIELD PERFORMANCE EVALUATIONS OF SINGLE TREES AND FINALLY, BY MULTI-LOCATION FIELD TRIALS. WE ARE PROPOSING A FAST-TRACK APPROACH TO DELIVER NEW CULTIVARS WHERE MULTIPLE EVALUATIONS WILL BE CARRIED OUT IN PARALLEL TO HASTEN THE PROCESS OF VARIETY DEVELOPMENT. MOLECULAR DATA (GENOMIC AND METABOLOMIC) DEVELOPED IN A COMPLEMENTARY PROJECT AND PHYTOPATHOLOGICAL DATA PROPOSED IN THE CURRENT PROJECT WILL BE USED TO SELECT ADVANCED HYBRIDS THAT MAY HAVE COMMERCIAL POTENTIAL.THROUGH THIS PROJECT, WE WILL BE ABLE TO EVALUATE THE FIELD PERFORMANCE OF FOUR F1 HYBRIDS IN SIX LOCATIONS AND IDENTIFY ADVANCED HYBRIDS WITH RESISTANCE TRAITS INCORPORATED. THE RESEARCH CONDUCTED WILL BE BENEFICIAL TO ACCELERATE CITRUS BREEDING AND DEVELOP TOOLS FOR SELECTION OF USEFUL HYBRIDS WITH PUTATIVE COMMERCIAL VALUE.

MCL-1 IN APOPTOSIS AND SIGNAL TRANSDUCTION: A STRUCTURE/FUNCTION APPROACH

FESD TYPE I: EARTHQUAKE FAULT SYSTEM DYNAMICS

MECHANISTIC INSIGHTS INTO MAMMALIAN DNA METHYLATION

REGULATION OF APETALA2 IN FLOWER DEVELOPMENT IN ARABIDOPSIS

INTEGRATIVE ANALYSIS OF PLASTICITY IN CELL FATE DETERMINATION IN PLANTS

OUR PROPOSED RESEARCH IS DEFINED BY ONE FUNDAMENTAL QUESTION: HOW DO OCEAN CHEMISTRY AND SOLID PLANETARY PROCESSES LEAD TO SUSTAINED HABITABILITY AND THE MAINTENANCE OF DETECTABLE ATMOSPHERIC BIOSIGNATURES? OUR SEARCH FOR THE ANSWER WILL REQUIRE

**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AVOCADO (PERSEA AMERICANA) IS A MAJOR FRUIT TREE CROP PRODUCED THROUGHOUT THE WORLD. IN 2017, GLOBAL AVOCADO PRODUCTION REACHED 5.9 MILLION (M) METRIC TONS. IN THE LAST 30 YEARS, THE AVOCADO MARKET HAS INCREASED ~ 2.5-FOLD AND PER CAPITA CONSUMPTION HAS QUADRUPLED DUE TO INCREASED GLOBAL AWARENESS OF THE AVOCADO'S HIGH NUTRITIONAL BENEFITS. YET THE MARKET SHARE FOR US-PRODUCED AVOCADOS HAS DECREASED FROM ~57 TO ~27% IN THE LAST DECADE AS MORE COUNTRIES ENTER THE MARKET. CALIFORNIA (CA) IS THE NATION'S LEADING PRODUCER GENERATING REVENUE IN EXCESS OF $412M, FOLLOWED BY FLORIDA (FL, $100M), WHERE IT IS THE SECOND MAJOR FRUIT CROP AFTER CITRUS, AND HAWAII (HI). AVOCADO GROWERS FACE NUMEROUS PRODUCTION CHALLENGES INCLUDING DEVASTATING DISEASES SUCH AS PHYTOPHTHORA ROOT ROT (PRR), CAUSED BY PHYTOPHTHORA CINNAMOMI (PC), LAUREL WILT (LW), AND SALINITY WHICH IN COMBINATION CAUSE SEVERE REDUCTION IN FRUIT YIELD, QUALITY, AND CAN DESTROY COMPLETE AVOCADO ORCHARDS IF NOT MANAGED PROPERLY. GROWERS RELY ON AVAILABLE PRR RESISTANT ROOTSTOCKS AND PHOSPHONATE-BASED FUNGICIDES FOR PRR MANAGEMENT, HOWEVER PC ISOLATES PARTIALLY OVERCOMING BOTH PRACTICES, HAVE BEEN RECENTLY DETECTED IN CA. THUS, EFFORTS TO SELECT ROOTSTOCKS HARBORING RESISTANCE TO THE CURRENT PC POPULATION AND SUITED FOR DIFFERENT ENVIRONMENTAL AND MANAGEMENT CONDITIONS ARE NEEDED TO REGAIN THE AVOCADO PRODUCTION AND NATIONAL MARKET SHARE. LW, CAUSED BY THE FUNGUS RAFFAELEA LAURICOLA (RL), HAS RAPIDLY SPREAD ACROSS THE AMERICAN SOUTHEAST UP TO TEXAS (TX) THROUGH BEETLE TRANSMISSION, ROOT GRAFTING, AND HUMAN-MEDIATED TRANSPORT. LW KILLS TREES WITHIN WEEKS TO MONTHS AND HAS NO CURRENT EFFECTIVE CONTROL METHOD. IN FL, LW HAS CAUSED ECONOMICAL LOSSES OF $13.2M. THE WORLD MARKET IS DOMINATED BY 'HASS,' WHICH IS SUSCEPTIBLE TO LW AND SALINITY. CURRENTLY, NO AVOCADO VARIETIES OR ROOTCTOCK:SCION COMBINATIONS RESISTANT TO LW ARE COMMERCIALLY AVAILABLE. WE FEAR THAT THE ARRIVAL OF LW TO CA AND OTHER PRODUCTION AREAS IS IMMINENT AND POSES A MAJOR EMERGING THREAT TO GLOBAL AVOCADO PRODUCTION AND SUSTAINABILITY. THUS, EFFORTS TO SELECT DISEASE RESISTANT MATERIAL, APPROPRIATE ROOTSTOCKS: SCION RESISTANT COMBINATIONS, AND IMPROVED DISEASE MANAGEMENT PRACTICES ARE CRITICAL AND URGENT TO SECURE THE $500+ M/YEAR US AVOCADO INDUSTRY. THE OVERALL GOAL OF THIS PROPOSAL IS TO IMPROVE AVOCADO PRODUCTION, COMPETITIVENESS, AND SUSTAINABILITY NATIONWIDE BY DELIVERING SEVERAL SHORT-, MID-, AND LONG-TERM OUTCOMES TO REDUCE LOSSES DUE TO PRR AND LW DISEASES THROUGH AN INTEGRATED PATHOGEN MANAGEMENT (IPM) APPROACH BY COMBINING THE USE OF: I) RESISTANT ROOTSTOCKS, II) NEW FUNGICIDES, III) ACCURATE IN-FIELD DIAGNOSTIC TOOLS, AND IV) NEW DISEASE MANAGEMENT PRACTICES INCLUDING THE USE OF REMOTE SENSING TECHNOLOGY.THIS PROJECT WILL ENHANCE US AVOCADO PRODUCTION AND MARKET GROWTH BY COMBINING EFFORTS FOR ROOTSTOCK SELECTION, BREEDING, AND DISEASE MANAGEMENT IN FL, CA, HI, TX, AND PUERTO RICO (PR). TO RESTORE THE AVOCADO INDUSTRY AND REPOSITION THE US MARKET IN COMPETITION WITH IMPORTED 'HASS,' AVOCADO, A MULTIDISCIPLINARY TEAM OF SCIENTISTS WILL COLLABORATE WITH INDUSTRY, NURSERIES, AND GROWERS TO SELECT PRR AND LW RESISTANT CULTIVARS FROM GERMPLASM COLLECTIONS AND CONDUCT MULTISTATE FIELD TRIALS. THE NATION'S OVERALL AVOCADO PRODUCTION CAN BE STRENGTHENED BY TESTING THE RESISTANT ROOTSTOCKS WITH DIFFERENT SCIONS INCLUDING 'HASS' WITHIN AND BETWEEN STATES. SINCE OUR GROWER COOPERATORS WILL HAVE DIFFERENT CULTURAL PRACTICES, WE WILL ASSESS THE PERFORMANCE OF EACH ROOTSTOCK AND ROOTSTOCK/ SCION COMBINATION UNDER DIFFERENT ENVIRONMENTAL CONDITIONS AND CULTURAL PRACTICES ENSURING THE PERFORMANCE AND SUITABILITY OF OUR MATERIAL IN EACH STATE AND TO MEASURE EARLY INDICATIONS OF ADOPTION.RECOGNIZING THAT ROOTSTOCK SELECTION, TESTING, AND RELEASE ARE LONG-TERM PROCESSES, WE WILL DEVELOP AND IMPROVE TOOLS FOR PRR AND LW DIAGNOSIS AND MANAGEMENT TO INCREASE PRODUCTION AND REDUCE INPUTS. WITH THE DETECTION OF POTASSIUM PHOSPHITE (PP) INSENSITIVE CA PC ISOLATES, THE REGISTRATION OF NEW FUNGICIDES FOR PRR CONTROL IS NECESSARY TO PREVENT THE SELECTION OF RESISTANT PATHOGEN SUB-POPULATIONS AND DEVELOP USAGE STRATEGIES FOR OPTIMUM PERFORMANCE AND PRODUCT FIELD DURABILITY. SEVERAL DNA-BASED DIAGNOSTIC TOOLS HAVE BEEN DEVELOPED FOR THE PRR AND LW PATHOGENS, HOWEVER, THESE TOOLS HAVE NOT BEEN ADOPTED BY GROWERS BECAUSE THEY REQUIRE EXPERTISE AND EXPENSIVE INSTRUMENTATION. EARLY LW DETECTION IN AVOCADO TREES, NATURAL HOSTS, AND INSECT VECTORS IS CRITICAL TO SCOUT NEW INTRODUCTIONS IN STATES WHERE THE DISEASE IN NOT YET PRESENT. WE WILL DEPLOY RAPID DNA- AND PROTEIN-BASED IN FIELD DIAGNOSTIC TOOLS FOR EARLY PRR AND LW DETECTION. IF WE DO NOT DEVELOP BETTER EARLY DETECTION STRATEGIES FOR LW DISEASE, WE FEAR THAT THE AVOCADO INDUSTRY IN OTHER STATES WILL FOLLOW THE SAME DECLINE AS FL. WE WILL APPLY AND FIELD VALIDATE REMOTE SENSING TECHNOLOGIES FOR DISEASE DIAGNOSIS TO DIFFERENTIATE LW, PRR, AND SALINITY DAMAGE. WITH THIS SYSTEM, SENSOR DATA AND ANALYSIS RESULTS WILL BE AVAILABLE TO GROWERS IN REAL-TIME FOR TIMELY DECISION MAKING AND DISEASE SPREAD PREVENTION. THE GENERATION OF GENOMIC RESOURCES AND GENETIC KNOWLEDGE FROM THIS PROPOSAL WILL AID THE FUTURE IMPLEMENTATION OF AVOCADO GENOME-ASSISTED BREEDING PLATFORMS TO ACCELERATE THE SELECTION AND DEVELOPMENT OF AVOCADO CULTIVARS HARBORING AGRICULTURAL AND HORTICULTURAL KEY TRAITS TO MEET THE CURRENT AND THE FUTURE PRESSING NEEDS OF THE US STAKEHOLDERS. OUTREACH AND EXTENSION TO GROWERS AND STAKEHOLDERS WILL DELIVER TIMELY NOTIFICATION OF EMERGING RESEARCH, GROWER RESOURCES, AND TRANSLATION OF OUTCOMES INTO ACTIONABLE RECOMMENDATIONS. EXTENSIVE ECONOMIC IMPACT ANALYSIS WILL CALCULATE COST SAVINGS TO ACCELERATE GROWER ADOPTION AND DEPLOYMENT OF PROJECT OUTCOMES. THE PROJECT WILL TRAIN GRADUATE AND UNDERGRADUATE STUDENTS AS WELL AS POSTDOCS AT FIVE UNIVERSITIES.

GRADUATE RESEARCH FELLOWSHIP (GRFP)

COOPERATIVE AGREEMENT TO DEVELOP NANO MATERIALS & NANO DEVICES (CNN VI)

THE FELLOWSHIPS AND INTERNSHIPS IN EXTREMELY LARGE DATA SETS (FIELDS) MIRO PROPOSES TO DEVELOP RESEARCH, EDUCATION, TRAINING AND COLLABORATIVE OPPOTU

GENE SILENCING AS AN ANTIVIRAL DEFENSE IN ANIMAL CELLS

THE ROLE OF MOSQUITO MICRORNAS IN BLOOD DIGESTION.

GRANT

WALNUTS ARE AN IMPORTANT PART OF THE ECONOMY OF CALIFORNIA AND REPRESENT A 2 BILLION DOLLAR A YEAR INDUSTRY IN THE U.S.A. MULTIPLE SOIL-BORNE PESTS AND PATHOGENS ALONG WITH NUMEROUS ABIOTIC STRESSES IMPACT THIS CROP NEGATIVELY. SUSTAINABILITY-ENCUMBERING CULPRITS INCLUDE: BLACK LINE DISEASE, CROWN GALL, PHYTOPHTHORA ROOT AND CROWN ROT, AND PLANT-PARASITIC NEMATODES. WATER QUANTITY AND QUALITY STRESSES ARE ALSO ROBBING YIELD. IN CALIFORNIA, ENGLISH WALNUT TREES ARE TRADITIONALLY, GROWN ON ROOTSTOCKS WITH THE MOST COMMON BEING, TO HUMANS AND THE ENVIRONMENT. IN ADDITION, USE OF MANY OF THE REMAINING CHEMICAL FUMIGANTS IS BECOMING COST PROHIBITIVE. IN A PRIOR SCRI SUPPORTED PROJECT, PROGENY FROM CROSSES OF J. MICROCARPA MOTHERT TREES WITH J. REGIA RESISTANCE TO CROWN GALL, PHYTOPHTHORA ROOT ROTS, ROOT LESION NEMATODE AND ROOT-KNOT NEMATODE. BREEDING POPULATIONS (>300 OFFSPRING) FROM EACH OF TWO SELECTED MOTHER TREES WERE GENERATED, GENETICALLY CHARACTERIZED, AND THEN EXAMINED FOR THEIR RESISTANCE TO THE DISEASES MENTIONED ABOVE. BY COMBINING THE DISEASE RESISTANCE DATA WITH THE GENETIC CHARACTERIZATION MULTIPLE REGIONS ON CHROMOSOME 11 WERE IDENTIFIED THAT APPEAR TO BE ASSOCIATED WITH THE OBSERVED DISEASE RESISTANCE. GENETIC MARKES ARE BEING DEVLOPED WITHIN THESE GENETIC REGIONS AND WILL BE USED TO SCREEN YOUNG WALUT SEEDINGS. THIS PROCESS WILL ALLOW DISCARDING GENOTYPES THAT DO NOT CARRY THE MARKERS ASSOCIATED WITH DISEASE REISTANCE. IN THIS PROCESS, MULTIPLE MOLECULAR SIGNALS ASSOCIATED WITH RESISTANCE WILL BE TESTED IN A POPULATION OF >5,000 SEEDLINGS AND ONLY THOSE WITH THE GENETIC MARKERS, PUTATIVELY CARRYING (MULITPLE) REISTANCE WILL BE SELECTED. LESS THAN 10% OF THIS POPULATION IS EXPECTED TO EXHIBIT RESISTANCE TO MULTIPLE PATHOGENS. THESE INDIVIDUALS WILL BE TESTED TO CONFIRM DISEASE RESISTANCE. IN A PARALLEL SERIES OF EXPERIMENTS WE WILL EXAMINE THESE OFF-SPRING TO VALIDATE TESTING SYSTEMS DESIGNED TO EXAMINE WATER STRESS TOLERANCE AND TOLERANCE TO BLACK LINE DISEASE. ELITE ROOTSTOCK CANDIDATES IDENTIFIED BY THESE PROCEDURES WILL BE PLACED IN FIELD TRIALS IN DIFFERENT GROWING REGIONS OF CALIFORNIA WHERE THEY WILL CONCOMITANTLY SERVE AS OUTREACH TEACHING TOOLS. OTHER MEMBERS OF THESE BREEDING POPULATIONS WILL BE USED FOR REFINEMENT OF SPECTRAL ANALYSIS FOR DETECTION OF (A)BIOTIC STRESSES. COMPREHENSIVE ECONOMIC ANALYSIS WILL DETERMINE BENEFITS OF USING NEW ROOTSTOCKS IN WALNUT PRODUCTION. BUILT ON PREVIOUS SUCCESS WITH SCRI SUPPORT, THIS PROJECT WILL PROVIDE URGENTLY NEEDED DISEASE RESISTANT ROOTSTOCKS AND BREEDING TOOLS FOR FUTURE DEVELOPMENT OF ENHANCED WALNUT ROOTSTOCKS.

2/2 DRUG DEVELOPMENT AND CAPACITY BUILDING: A UCR/COH-CCC PARTNERSHIP - THE UNITED STATES (U.S.) HAS LED THE WORLD IN DRUG DISCOVERY FOR OVER 50 YEARS. WHILE THIS IS A SIGNIFICANT ACCOMPLISHMENT, U.S. DRUGS HAVE BEEN ALMOST EXCLUSIVELY OPTIMIZED AND TESTED IN NON-HISPANIC EUROPEAN- AMERICANS AND BEEN MINIMALLY EVALUATED IN MEN- OR WOMEN-OF-COLOR. AS A RESULT, DRUGS THAT WORK WELL IN NON- HISPANIC EUROPEAN-AMERICANS (ANGLOS), MAY HAVE UNEXPECTED TOXICITY OR DECREASED EFFICACY IN MOST OF THE WORLD’S POPULATION. DISPARITIES IN U.S. DRUG DEVELOPMENT OCCUR THROUGHOUT THE ENTIRE DRUG DISCOVERY PIPELINE. ONLY A SMALL NUMBER OF BASIC SCIENTISTS ARE LATINO/HISPANIC- OR AFRICAN-AMERICAN. INITIAL DRUG DEVELOPMENT AND OPTIMIZATION TAKES PLACE IN CELL LINES DERIVED FROM ANGLOS. LESS THAN 2% OF PHYSICIANS CONDUCTING CLINICAL TRIALS ARE LATINO/HISPANIC- OR AFRICAN-AMERICAN6. MOST CLINICAL TRIALS PARTICIPANTS ARE ANGLOS. YET, NEW DRUGS ARE FDA APPROVED FOR LATINOS/HISPANICS- AND AFRICAN-AMERICANS/AFRICANS WITHOUT SUFFICIENT TESTING. IT IS UNACCEPTABLE THAT DRUGS ARE DEVELOPED BY, AND OPTIMIZED FOR, ONLY A FRACTION OF OUR CITIZENS. IN THIS U54 PARTNERSHIP WE AIM TO DEVELOP THE RESOURCES, INFRASTRUCTURE, AND TRAINING TO MENTOR THE NEXT GENERATION OF RESEARCHERS THAT REFLECT THE DIVERSITY OF OUR CATCHMENT AREA. BUILDING ON OUR SUCCESSFUL P20 GRANT, HERE IN THIS U54 PARTNERSHIP, UCR AND COHCCC AIM TO DEVELOP THE COLLABORATIONS, RESOURCES, AND TRAINING PROGRAMS TO REDUCE DISPARITIES IN DRUG DEVELOPMENT THROUGHOUT THE ENTIRE DRUG DEVELOPMENT PIPELINE. OUR GOAL IS FOR THIS PROGRAM TO BECOME A FOCAL POINT FOR UCR AND COHCCC TO MENTOR AND TRAIN A DIVERSE FORCE OF CANCER BIOLOGISTS AND ADDRESS THE DISPARITIES IN CANCER THERAPEUTICS AND DRUG DEVELOPMENT. ALREADY, OUR P20 HAS FOSTERED JOINT R01 GRANTS, K01 GRANTS, AND PRE-/POST-DOCTORAL FELLOWSHIPS. BOTH INSTITUTIONS ARE HIGHLY COMMITTED - COHCCC CONTRIBUTED OVER $800K TO OUR P20 GRANT AND WILL CONTRIBUTE $250K/YEAR TO ENSURE THE SUCCESS OF THIS U54 PARTNERSHIP. AIM 1 WILL STRENGTHEN UCR’S CANCER RESEARCH CAPACITY AND DEVELOP THE RESOURCES TO INCREASE UCR/COHCCC’S ABILITY TO JOINTLY DEVELOP THERAPEUTIC AGENTS OPTIMIZED FOR THE DIVERSE POPULATIONS IN OUR CATCHMENT AREA. AIM 2 WILL INCREASE THE CAPACITY OF UCR AND COHCCC TO JOINTLY DEVELOP DRUGS THAT TARGET DISPARITIES IN SURVIVAL AFFECTING THE DIVERSE INDIVIDUALS LIVING IN OUR SOUTHERN CALIFORNIA COMMUNITIES. AIM 3 WILL PROVIDE THE TRAINING, OPPORTUNITY, AND MENTORSHIP TO ENSURE THAT THE NEXT GENERATION OF THERAPEUTIC SCIENTISTS AND CLINICAL TRIALISTS REFLECT THE DIVERSITY OF SOUTHERN CALIFORNIA.

COLLEGE COST REDUCTION ACT

THE CIVIC OPENNESS, REASONING, AND ENGAGEMENT (CORE) INCUBATOR

LOUIS STOKES STEM PATHWAYS AND RESEARCH ALLIANCE: CALIFORNIA LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION

THE MINORITY SERVING INSTITUTIONS PARTNERSHIP PROGRAM (MSIPP) IS A VITAL PROGRAM WITHIN THE DOE/NNSA MANAGEMENT AND BUDGET, LEARNING AND CAREER MANAGEMENT WHICH AWARDS GRANTS TO MINORITY SERVING INSTITUTIONS (MSI) TO PREPARE NNSA’S NEXT-GENERATION TECHNICAL WORKFORCE. MSIPP ALIGNS INVESTMENTS IN UNIVERSITY CAPACITY AND WORKFORCE DEVELOPMENT WITH DOE/NNSA MISSION AREAS TO DEVELOP THE NEEDED SKILLS AND TALENT FOR DOE/NNSA’S ENDURING TECHNICAL WORKFORCE AND TO ENHANCE RESEARCH AND EDUCATION AT MSIS. THE PROGRAM’S PRIMARY MISSION IS TO CREATE AND FOSTER A SUSTAINABLE STEM-PIPELINE THAT PREPARES A DIVERSE WORKFORCE OF WORLD CLASS TALENT THROUGH STRATEGIC PARTNERSHIPS BETWEEN MINORITY SERVING INSTITUTIONS AND THE DOE/NNSA ENTERPRISE. TO EXECUTE THIS MISSION, MSIPP BUILDS A NETWORK OF NSE READY STUDENTS THROUGH ENRICHMENT ACTIVITIES FROM K-20 TO POST-DOCTORAL LEVEL. THROUGH UNIVERSITY-LAB CONSORTIA PARTNERSHIPS STUDENTS ARE EXPOSED TO CUTTING-EDGE RESEARCH AND ACTIVITIES IN THEIR RELEVANT FIELDS. THE FOLLOWING MSIPP CRUCIAL SUCCESS FACTORS ARE TO: 1. STRENGTHEN AND EXPAND MSI STEM CAPACITY AND RESEARCH EXPERIENCE IN DOE/NNSA MISSION AREAS OF INTEREST. 2. TARGET COLLABORATIONS BETWEEN MSIS AND DOE/NNSA LABORATORIES AND PLANTS THAT INCREASE SCIENTIST-TO-SCIENTIST INTERACTIONS, VISIBLE PARTICIPATION OF MSI FACULTY IN DOE/NNSA TECHNICAL ENGAGEMENTS AND ACTIVITIES AND PROVIDE MSIS DIRECT ACCESS TO DOE/NNSA FACILITIES RELATIVE TO STEM. 3. GROW THE NUMBER OF MINORITY STUDENTS WHO GRADUATE WITH STEM DEGREES. 4. GROW THE NUMBER OF MINORITY GRADUATES AND POST-DOCTORAL STUDENTS HIRED IN TO DOE/NNSA'S STEM WORKFORCE.

THE CURRENT LACK OF METHODS TO EFFECTIVELY COMBAT HLB MAKES DISCOVERY OF INNOVATIVE STRATEGIES IMPERATIVE FOR THE SURVIVAL OF THE CITRUS INDUSTRY. THE ULTIMATE GOAL OF THIS PROJECT IS TO PROVIDE EFFECTIVE SOLUTIONS TO CONTROL HLB BY DEVELOPING ANTIMICROBIAL THERAPIES TO SUPPRESS AND KILL CLAS IN HLB-POSITIVE TREES AND ANTIMICROBIAL PROTECTANTS TO VACCINATE HEALTHY YOUNG CITRUS TREES AGAINST INFECTION.THE PROJECT ADDRESSES THE FIRST CDS-CDRE PRIORITY AREA: 1. THERAPIES TO PREVENT OR SUPPRESS CANDIDATUS LIBERIBACTER ASIATICUS (CLAS) BACTERIA WITHIN TREES. OUR PROJECT IS BASED ON THE HYPOTHESIS THAT THE HLB RESISTANCE/TOLERANCE TRAITS OBSERVED IN CITRUS HYBRIDS AND CLOSE RELATIVES ARE DETERMINED BY A SET OF MASTER DEFENSE REGULATORS. BY COMPARATIVE ANALYSIS BETWEEN HLB-SENSITIVE CULTIVARS AND HLB-RESISTANT/TOLERANT CITRUS HYBRIDS AND RELATIVES, SUCH AS EREMOCITRUS GLAUCA, MICROCITRUS AUSTRALIASICA, AND PONCIRUS TRIFOLIATA, WE IDENTIFIED AND CLONED A NOVEL CLASS OF ANTIMICROBIAL PEPTIDES(APS) THAT CAN EFFECTIVELY INHIBIT/KILL THREE DIFFERENT LIBERIBACTER SPECIES, 1) CLAS THAT INFECTS CITRUS, 2) CANDIDATUS LIBERIBACTER SOLANACEARUM THAT INFECTS ALL SOLANACEOUS PLANTS AND 3) LIBERIBACTER CRESCENS, A CULTURABLE BACTERIUM THAT INFECTS PAPAYA, WHICH WE ARE USING AS A SURROGATE FOR THE UNCULTURABLE CLAS. MOST IMPORTANTLY, THE APS HAVE UNIQUE CHARACTERISTICS THAT ARE DISTINCT FROM OTHER ANTIMICROBIAL PEPTIDES AND MAKE THEM THE IDEAL SOLUTIONS FOR CONTROLLING HLB. FIRST, THE APS CAN STIMULATE IMMUNE RESPONSES IN CITRUS PLANTS, WHICH MAKES IT POSSIBLE TO DEVELOP PROTECTANTS USING APS TO VACCINATE HEALTHY SEEDLINGS. SECOND, THE APS ARE SAFE FOR HUMANS AND ANIMALS BECAUSE THEY ARE DERIVED FROM CITRUS AND CITRUS RELATIVES AND ARE PRESENT IN FRUIT OF AUSTRALIAN FINGER LIME AND LEMON, WHICH PEOPLE HAVE BEEN CONSUMING FOR HUNDREDS OF YEARS. THIRD, THE APS ARE STABLE AND CAN WITHSTAND HIGH TEMPERATURES AND PROTEOLYSIS IN PLANTS. FOURTH, THE APS HAVE NO OBVIOUS PHYTOTOXICITY IN CITRUS. AND FIFTH, SYNTHESIS OF THE APS IS COST-EFFECTIVE. UNLIKE MOST OTHER ANTIMICROBIAL PEPTIDES THAT ARE CYSTINE-RICH AND REQUIRE DISULFIDE BOND FORMATION TO BE ACTIVE, OUR APS DO NOT CONTAIN MANY CYSTINE RESIDUES, WHICH ALLOWS IN VITRO SYNTHESIS OF ACTIVE MOLECULES EASILY AND AT LOW COST.WE PROPOSE TO DEVELOP THERAPIES AND PROTECTANTS USING AP SOLUTIONS AND PERFORM AN ECONOMIC ANALYSIS OF THE COST EFFICIENCY OF DIFFERENT APPLICATION METHODS FOR TREATING HLB-POSITIVE TREES AND PROPHYLACTICALLY PROTECTING HEALTHY YOUNG TREES AGAINST CLAS INFECTION. VARIOUS COCKTAILS OF APS WILL BE FORMULATED, AND DIFFERENT DELIVERY METHODS WILL BE TESTED IN THE GREENHOUSE (DRS. JIN AND GODFREY IN CA, DRS. MCCOLLUM AND FOLIMONOVA IN FL) AND FIELD (DRS. MCCOLLUM AND DEWDNEY IN FL). THE AP SOLUTIONS AND DELIVERY METHODS PROVEN MOST EFFECTIVE WILL BE INTRODUCED TO GROWERS FOR FIELD EVALUATION. WE WILL ALSO TEST THE DELIVERY OF APS VIA EXPRESSION FROM A MODIFIED CITRUS TRISTEZA VIRUS VECTOR, WHICH HAS ALREADYBEEN DEVELOPED (DR. FOLIMONOVA AND SOUTHERN GARDENS. INC). THE AGRICULTURAL ECONOMIST DR. BABCOCK FROM UCR WILL PERFORM ECONOMIC ANALYSIS TO EVALUATE THE IMPACT OF USING THE ANTI-MICROBIAL COCKTAILS.WE PROPOSE TO DEVELOP THERAPIES AND PROTECTANTS USING AP SOLUTIONS AND PERFORM AN ECONOMIC ANALYSIS OF THE COST EFFICIENCY OF DIFFERENT APPLICATION METHODS FOR TREATING HLB-POSITIVE TREES AND PROPHYLACTICALLY PROTECTING HEALTHY YOUNG TREES AGAINST CLAS INFECTION. VARIOUS COCKTAILS OF APS WILL BE FORMULATED, AND DIFFERENT DELIVERY METHODS WILL BE TESTED IN THE GREENHOUSE (DRS. JIN AND GODFREY IN CA, DRS. MCCOLLUM AND FOLIMONOVA IN FL) AND FIELD (DRS. MCCOLLUM AND DEWDNEY IN FL). THE AP SOLUTIONS AND DELIVERY METHODS PROVEN MOST EFFECTIVE WILL BE INTRODUCED TO GROWERS FOR FIELD EVALUATION. WE WILL ALSO TEST THE DELIVERY OF APS VIA EXPRESSION FROM A MODIFIED CITRUS TRISTEZA VIRUS VECTOR, WHICH HAS ALREADY BEEN DEVELOPED (DR. FOLIMONOVA AND SOUTHERN GARDENS. INC). THE AGRICULTURAL ECONOMIST DR. BABCOCK FROM UCR WILL PERFORM ECONOMIC ANALYSIS TO EVALUATE THE IMPACT OF USING THE ANTI-MICROBIAL COCKTAILS.DRS. VIDALAKIS, DEWDNEY, MAUCK, KAHN AND JIN WILL BE ACTIVELY INVOLVED IN DIVERSE OUTREACH ACTIVITIES IN CITRUS PRODUCTION AREAS. WE WILL INFORM CITRUS GROWERS IN CA, FL, TX ABOUT THE PROGRESS OF OUR RESEARCH AND DISTRIBUTE THE FINAL AP APPLICATION PROTOCOLS IN DIFFERENT WAYS. WE WILL PREPARE EDUCATIONAL MATERIALS THAT WILL BE DELIVERED TO STAKEHOLDERS VIA CITRUS INDUSTRY MEETINGS NATIONWIDE IN CA, TX AND FL (FL: CITRUS EXPO AND CITRUS SHOW; CA: CITRUS RESEARCH BOARD'S MEETINGS, CA CITRUS MUTUAL; CITRUS CLONAL PROTECTION PROGRAM ANNUAL WALK THROUGH; FIELD DAYS AT UCR; AND TX: TEXAS CITRUS SHOWCASE). THESE EDUCATIONAL MATERIALS WILL INCLUDE 1) POWERPOINT PRESENTATIONS; AND 2) HARD COPY PAMPHLETS DESCRIBING THE PROJECT, 3) A PROJECT WEBSITE, AND 4) A FRUITMENTORTM YOUTUBE VIDEO. HOMEOWNERS AND CITRUS HOBBYISTS (GENERAL PUBLIC) WILL ALSO BE TARGETED BY DISTRIBUTING INFORMATION ABOUT THE IMPORTANCE OF HLB AND ACP AND HOW THEY CAN BECOME PART OF THE HLB SOLUTION. ALL EXTENSION AND OUTREACH MATERIALS WILL ALSO BE PART OF THE PROJECT WEBSITE. EDUCATIONAL OUTREACH WILL ALSO BE PART OF THIS PROJECT THROUGH THE LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION, CALIFORNIA ALLIANCE FOR MINORITY PARTICIPATION (CAMP). GROWER STAKEHOLDERS AND INDUSTRY REPRESENTATIVES FROM CA, FL AND TX WILL ALSO BE INCLUDED ON OUR ADVISORY PANEL. THE PD, DR. JIN, HAS BEEN AND WILL CONTINUE TO BE ACTIVELY INVOLVED IN PUBLIC EDUCATION ON CITRUS HLB DISEASES AND TO WORK WITH CALIFORNIA CITRUS PEST & DISEASE PREVENTION PROGRAM THROUGH INTERVIEWS WITH TV REPORTERS AND NEWSPAPER JOURNALISTS AT MEDIA CONFERENCES AND ENGAGEMENT WITH LOCAL COMMUNITIES.

EFFECTOROMICS OF THE HUANGLONGBING (HLB)-ASSOCIATED PATHOGEN

CONTRIBUTION OF INNATE IMMUNE RECEPTORS TO NEUROLOGICAL DYSFUNCTION AFTER TRAUMATIC BRAIN INJURY: MECHANISMS AND THERAPEUTIC IMPLICATIONS

HEALTH CARE AND OTHER FACILITIES

NEW CULTIVARS OF CROP PLANTS ARE OFTEN NEEDED TO ADDRESS EMERGING CHALLENGES, TO MEET THE NEEDS OF FARMERS, TO DEVELOP SUSTAINABLE CROP CULTIVATION METHODS, AND TO PROTECT THE ENVIRONMENT. THE CITRUS INDUSTRY IN THE UNITED STATES OF AMERICA IS FACED WITH A DEADLY DISEASE, HUANGLONGBING (HLB) OR CITRUS GREENING THAT HAS RAVAGED MANY CITRUS GROWING REGIONS IN THE COUNTRY AND HAS CAUSED SIGNIFICANT CONCERN IN OTHER AREAS WHERE THE DISEASE IS NOW SPREADING. THE SLOW DEVELOPMENT OF THE DISEASE, THE UN-CULTURABLE NATURE OF THE ASSOCIATED CAUSAL ORGANISM, AND THE COMPLEXITY OF THE PATHOSYSTEM MAKE CONTROLLING THIS DISEASE EXTREMELY DIFFICULT. A REVIEW PUBLISHED BY THE NATIONAL ACADEMY OF SCIENCE IN 2018 SUMMARIZED THE RESULTS OF ABOUT 12 YEARS OF RESEARCH CONDUCTED ON FINDING SOLUTIONS TO THE CITRUS HLB PROBLEM AND DECLARED THAT HLB MAY BE THE GREATEST CHALLENGE FACED BY THE CITRUS INDUSTRIES IN THE WESTERN WORLD. SINCE CITRUS IS ECONOMICALLY AND CULTURALLY VERY IMPORTANT FOR BOTH FLORIDA AND CALIFORNIA, WE NEED TO DEVELOP SOLUTIONS FOR LONG TERM CULTIVATION OF THIS IMPORTANT FRUIT CROP. THE DISEASE IS ASSOCIATED WITH CANDIDATUS LIBERIBACTER ASIATICUS, AN UNCULTURABLE ALPHA-PROTEOBACTERIUM AND IS SPREAD BY THE ASIAN CITRUS PSYLLID. EFFICIENT DISEASE MITIGATION WILL BE FEASIBLE WITH ADEQUATE VECTOR CONTROL. IMPLEMENTING MANAGEMENT TECHNIQUES FOR DISEASE MITIGATION WILL ALSO RESULT IN INCREASED COSTS FOR CULTIVATING CITRUS AND SOME OF THE APPROACHES PRACTICED NOW MAY RESULT IN DAMAGE TO THE ENVIRONMENT. ACCORDING TO SOME ESTIMATES, IN FLORIDA WHERE THE DISEASE HAS ESTABLISHED FOR ABOUT TWELVE YEARS, THE COST FOR CARING OF AN ACRE OF CITRUS HAS INCREASED FROM AN AVERAGE OF $769 IN THE YEAR 2000 TO ABOUT $2376 IN 2017. ENVIRONMENTALLY AND ECONOMICALLY SUSTAINABLE SOLUTIONS FOR CITRUS CULTIVATION IN PRESENCE OF HLB WILL REQUIRE DEVELOPMENT OF DISEASE RESISTANCE. AVAILABILITY OF COMMERCIAL VARIETIES THAT ARE RESISTANT WILL PROVIDE LONG-TERM, ECO-FRIENDLY, AND COST EFFECTIVE SOLUTIONS FOR THIS DEVASTATING DISEASE. THERE IS NO REPORT OF RESISTANCE TO HLB IN CITRUS. BECAUSE OF LONG CULTIVATION AND VEGETATIVE PROPAGATION METHODS USED ROUTINELY, NEW GENETIC MATERIAL IS OFTEN NOT INTRODUCED INTO CULTIVATED CITRUS AND THE CURRENTLY GROWN VARIETIES HAVE A NARROW GENETIC BASE. HOWEVER, CERTAIN RELATED GENERA IN THE CITRUS FAMILY ARE HLB RESISTANT OR HIGHLY TOLERANT. WE HAVE EXPLORED THE GENETIC DIVERSITY IN CLOSE RELATIVES OF CITRUS AND IDENTIFIED SOURCES OF HLB RESISTANCE IN AUSTRALIAN LIMES. USING THESE SEXUALLY COMPATIBLE DISEASE RESISTANT TAXA, WE HAVE GENERATED HYBRIDS OF CITRUS BY BREEDING WITH HLB RESISTANT CITRUS RELATIVES. MANY OF THE HYBRID PLANTS THAT WE HAVE DEVELOPED ARE VERY PROMISING SINCE THEY DO NOT HARBOR THE HLB PATHOGEN FOR EXTENDED PERIODS (MORE THAN TWO YEARS). OUR HYBRIDS ARE NOW UNDERGOING FIELD EVALUATIONS. ONE CAVEAT IS THAT THE HYBRID PLANTS INHERIT UNDESIRABLE FRUIT CHARACTERS ALONG WITH RESISTANCE TRAITS FROM THE CITRUS RELATIVE PARENT.TRADITIONAL BREEDING TO ELIMINATE UNWANTED FRUIT CHARACTERS WHILE MAINTAINING RESISTANCE WILL BE FEASIBLE BUT TIME CONSUMING. CITRUS HAS A GENERATION TIME OF 4-7 YEARS (DEPENDING ON CULTIVARS). USING A BREEDING POPULATION OF HYBRID PLANTS THAT ARE EITHER RESISTANT OR SUSCEPTIBLE, WE PROPOSE TO UTILIZE MODERN GENETICS METHODS TO GENERATE MOLECULAR TOOLS THAT WILL BE USEFUL IN DEVELOPING COMMERCIAL CITRUS CULTIVARS RESISTANT TO HLB. NOVEL INNOVATIVE METHODS OF CROP IMPROVEMENT ARE NOW POSSIBLE WITH ADVANCED AND AFFORDABLE SEQUENCING TECHNOLOGIES, GENE EDITING PROCEDURES AND ABILITY TO PYRAMID USEFUL GENES IN TRANSFORMED PLANTS. IDENTIFICATION OF TARGET GENES AND AVAILABILITY OF RESISTANCE-ASSOCIATED GENES WILL BE NECESSARY TO UTILIZE THESE TECHNOLOGIES TO OUR ADVANTAGE. ADVANCES IN GENETICS AND GENOMICS MAKE IT POSSIBLE TO DEVELOP AN UNDERSTANDING OF THE BASIS OF RESISTANCE AND IDENTIFY GENES THAT CAN THEN BE INTRODUCED INTO SPECIFIC CULTIVARS SO THAT HLB RESISTANCE CAN BE DEVELOPED IN COMMERCIAL CULTIVARS WITHOUT ALTERING THE DESIRABLE HORTICULTURAL TRAITS. IN THIS PROJECT, WE PROPOSE TO UTILIZE HYBRID POPULATIONS OF CITRUS (DERIVED FROM CROSSING CITRUS WITH DISEASE RESISTANT RELATIVE GENERA) TO GENERATE SEQUENCE INFORMATION THAT WILL LEAD TO THE IDENTIFICATION OF GENOMIC REGIONS ASSOCIATED WITH HLB RESISTANCE. USING A COMBINATION OF SEVERAL GENOMIC APPROACHES (WHOLE GENOME SEQUENCING, LOW DEPTH SKIM SEQUENCING OF HLB RESISTANT AND SUSCEPTIBLE F1 POPULATIONS, POOLED GENOME APPROACH, TRANSCRIPTOME PROFILING, QPCR ANALYSIS FOR DETERMINING GENE EXPRESSION PROFILES, AND BIOINFORMATIC ANALYSIS), WE PROPOSE TO IDENTIFY GENES THAT ARE ASSOCIATED WITH HLB RESISTANCE. FOR PROOF OF CONCEPT, WE WILL CLONE THE PUTATIVE RESISTANCE ASSOCIATED GENES INTO SUITABLE PLANT TRANSFORMATION VECTORS AND TRANSFORM A MODEL CITRUS PLANT, DUNCAN GRAPEFRUIT. THE TRANSFORMED PLANT WILL BE TESTED FOR PRESENCE OF TRANSGENE, EXPRESSION LEVELS, STABILITY, AND EVALUATED FOR HLB RESISTANCE. USEFUL CONSTRUCTS/GENES/INFORMATION ABOUT RESISTANT GENES WILL BE BENEFICIAL FOR GENERATING DISEASE RESISTANT CITRUS CULTIVARS USING MANY NOVEL TECHNOLOGIES. DEVELOPMENT OF GENOMICS-BASED TOOLS THAT CAN BE USED TO SELECT POTENTIALLY RESISTANT PROGENY WILL ALSO ACCELERATE TRADITIONAL BREEDING APPROACHES. GENES FOR HLB RESISTANCE, ONCE IDENTIFIED AND VALIDATED BY THE UNIVERSITY OF CALIFORNIA, RIVERSIDE, WILL BE MADE AVAILABLE THROUGH THE APPROPRIATE UNIVERSITY TECHNOLOGY TRANSFER MECHANISMS, INCLUDING PATENTING AND LICENSING OF INTELLECTUAL PROPERTY (IP), INTER-INSTITUTIONAL, MATERIAL TRANSFER, AND CONFIDENTIAL DISCLOSURE AGREEMENTS, SO THAT OTHERS CAN INCORPORATE THE HLB RESISTANT GENES INTO VARIOUS CITRUS CULTIVARS TO EXPEDITIOUSLY TRANSLATE THE RESEARCH RESULTS FOR COMMERCIAL APPLICATION TO SUPPORT THE CITRUS INDUSTRY. THE PROJECT HAS A MULTI-STATE ADVISORY PANEL CONSISTING OF A CITRUS SCIENTIST, A CITRUS NURSERYMAN, AN APPLE BREEDER AND A CITRUS PATHOLOGIST. THE ADVISORY BOARD WILL PROVIDE GUIDANCE ON GOALS, APPROACHES AND FUTURE DIRECTIONS.

TARGETING THE EPHA4 IN MOTOR NEURON DISEASE: A STRUCTURE-BASED APPROACH

ATOMIC LAYER DISPOSITION (ALD) OF METAL AND METAL OXIDE FILMS: A SURFACE SCIENCE STUDY

HISPANIC-SERVING INSTITUTIONS PROGRAM (STEM)

UC RIVERSIDE EARLY CHILDHOOD SERVICES CCAMPIS PROJECT

CHARACTERIZATION OF POTENTIAL HARM CAUSED BY ELECTRONIC CIGARETTE FLAVOR CHEMICALS AND THEIR REACTION PRODUCTS

COLLABORATIVE RESEARCH: NETWORK CLUSTER: GEOMICROBIOLOGY AND BIOGEOCHEMISTRY IN THE CRITICAL ZONE

NEW GRANT

METALS IN ELECTRONIC CIGARETTE AEROSOL

PIRE: SYNTHESIS OF OPTICAL MATERIALS FOR BIOAPPLICATIONS: RESEARCH, EDUCATION, RECRUITMENT AND OUTREACH (SOMBRERO)

DEFINING THE CELL AND MOLECULAR BASIS OF TOXOPLASMA RECRUDESCENCE - PROJECT SUMMARY REACTIVATION OF TOXOPLASMOSIS IS A SIGNIFICANT HEALTH THREAT TO PEOPLE CHRONICALLY INFECTED WITH THIS PARASITE AND IS LIFE-THREATENING TO INFECTED INDIVIDUALS THAT ARE OR BECOME IMMUNOCOMPROMISED. MILLIONS OF PEOPLE FACE THIS THREAT AS IT IS ESTIMATED ONE THIRD OF HUMAN POPULATIONS ARE INFECTED WITH THIS PATHOGEN. RECRUDESCENCE OF THE TOXOPLASMA BRADYZOITE TISSUE CYST IS THE CAUSE OF TOXOPLASMOSIS REACTIVATION, WHICH CAN NOT BE PREVENTED AS THERE IS NO CURRENT TREATMENT THAT ELIMINATES THE DORMANT TISSUE CYST IN CHRONICALLY INFECTED INDIVIDUALS. APPROACHES TO FIND THERAPEUTIC SOLUTIONS TO TREAT AND PREVENT CHRONIC TOXOPLASMOSIS HAVE SUFFERED FROM LIMITED ACCESSIBILITY TO THE RELEVANT TOXOPLASMA STAGES AND A LACK OF ACCURATE IN VITRO DEVELOPMENTAL MODELS. OUR GOAL IN THIS PROPOSAL IS TO BREAKTHROUGH THESE IMPASSES. WE HAVE DEVELOPED A NEW INNOVATIVE EX VIVO MODEL OF BRADYZOITE RECRUDESCENCE THAT WE WILL UTILIZE TO DEFINE THE HOST CELL SPECIFICITY (AIM 1A), WHOLE-CELL GENE EXPRESSION (AIM 1B) AND METABOLIC CHANGES (AIM 2) THAT UNFOLD WHEN A BRADYZOITE CONVERTS BACK TO THE TACHYZOITE AND ALSO IN A NEWLY DISCOVERED ALTERNATE PATHWAY WHERE BRADYZOITES DIRECTLY REPLICATE TO REFORM THE TISSUE CYST. THIS INFORMATION IS CRITICALLY NEEDED IN ORDER TO UNDERSTAND HOW WE MIGHT PREVENT TOXOPLASMOSIS REACTIVATION. THE LOSS OF DEVELOPMENTAL COMPETENCY IN VITRO THAT IS EXACERBATED IN CURRENT PROTOCOLS PRODUCING TRANSGENIC STRAINS IS ALSO A MAJOR IMPEDIMENT TO UNDERSTANDING THE MOLECULAR BASIS OF TISSUE CYST REACTIVATION. IN THIS PROPOSAL, WE WILL IMPLEMENT AND OPTIMIZE AN INNOVATIVE APPROACH TO GENERATE DEVELOPMENTALLY COMPETENT TRANSGENIC STRAINS (AIM 3A), AND USE THIS NEW PROTOCOL TO DEFINE CYCLIN AND OTHER PROTEIN MECHANISMS (AIM 3B) THAT HAVE CRITICAL ROLES IN REGULATING BRADYZOITE RECRUDESCENCE AND TISSUE CYST RE-FORMATION

RELMALPHA-EXPRESSING MACROPHAGES MEDIATE HOST DISEASE TOLERANCE IN MUCOSAL INFECTION

MULTISCALE MODELING AND EMPIRICAL STUDY OF A MECHANISM LIMITING BLOOD CLOT GROWTH

CHROMATIN STRUCTURE AND CONTROL OF GENE EXPRESSION IN THE HUMAN MALARIA PARASITE

REGULATION OF P53 BY TAF1

ROLE OF PXR IN EDC-INDUCED CARDIOVASCULAR DISEASE - PROJECT SUMMARY ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (CVD) IS THE LEADING CAUSE OF MORTALITY AND MORBIDITY WORLDWIDE AND RECENT LARGE-SCALE HUMAN STUDIES HAVE IMPLICATED A LINK BETWEEN EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS (EDCS) AND CVD. HOWEVER, HOW EXPOSURE TO EDCS AND OTHER ENVIRONMENTAL CHEMICALS INFLUENCES CVD RISK IS STILL POORLY UNDERSTOOD, AND CONTINUES TO HAMPER ASSESSMENT OF THE HEALTH RISKS OF EDC EXPOSURE. WITH THE NIEHS FUNDING SUPPORT, WE HAVE IDENTIFIED MANY EDCS AS POTENT AGONISTS OF THE XENOBIOTIC SENSOR PREGNANE X RECEPTOR (PXR). THE IDENTIFICATION OF EDCS AS PXR LIGANDS HAS PROVIDED AN IMPORTANT TOOL FOR THE STUDY OF NEW MECHANISMS THROUGH WHICH EDC EXPOSURE IMPACTS DISEASE. OUR LABORATORY WAS THE FIRST TO REVEAL THE NOVEL FUNCTION OF PXR IN THE REGULATION OF ATHEROSCLEROSIS DEVELOPMENT, AND HAS ALSO DEMONSTRATED THAT WIDELY-USED EDCS INCLUDING BISPHENOL A, DICYCLOHEXYL PHTHALATE, AND TRIBUTYL CITRATE INCREASE ATHEROSCLEROSIS AND DYSLIPIDEMIA THROUGH PXR SIGNALING IN VARIOUS MOUSE MODELS. INFLUENCES OF THE CHEMICAL ENVIRONMENT ON HUMAN HEALTH HAVE BECOME THE SUBJECT OF INTENSE INTEREST BUT VERY FEW STUDIES IN THE EDC RESEARCH FIELD HAVE FOCUSED ON ATHEROSCLEROSIS DEVELOPMENT. MY DIVERSE SCIENTIFIC TRAINING IN MOLECULAR BIOLOGY, TOXICOLOGY, PHARMACOLOGY, AND CARDIOVASCULAR RESEARCH HAS PUT ME IN A UNIQUE POSITION TO INVESTIGATE HOW “GENE-EDC INTERACTIONS” AFFECT ATHEROSCLEROSIS DEVELOPMENT AND LIPID HOMEOSTASIS. THIS EDC-INDUCED CVD REVOLUTIONIZING INNOVATIVE, VISIONARY ENVIRONMENTAL HEALTH RESEARCH PROGRAM (EICVD-RIVER) WILL ALLOW ME TO INVESTIGATE THE BROAD SCIENTIFIC THEME OF THE IMPACT OF EDC EXPOSURE ON LIPID HOMEOSTASIS AND ATHEROSCLEROSIS IN ADULTS AND THEIR OFFSPRING. EICVD-RIVER WILL ADDRESS THE FOLLOWING SPECIFIC SCIENTIFIC QUESTIONS: 1) HOW MANY COMMON CHEMICALS IN PLASTIC AND OTHER CONSUMER PRODUCTS ACT AS EDCS TO MODULATE PXR ACTIVITIES? CAN DIFFERENT EDC MIXTURES SYNERGISTICALLY ACTIVATE PXR? 2) THROUGH WHICH CELL-SPECIFIC MECHANISMS DO EDCS INDUCE DYSLIPIDEMIA AND ATHEROSCLEROSIS? 3) HOW DOES PXR REGULATE CERAMIDE HOMEOSTASIS TO AFFECT EDC- INDUCED ATHEROSCLEROSIS? 4) DO MICROPLASTICS HAVE A TROJAN HORSE EFFECT ON EDC-INDUCED ATHEROSCLEROSIS? CAN THEY BRING EDCS INTRACELLULARLY TO HAVE SYNERGISTIC OR ADDITIVE IMPACT ON PXR-MEDIATED ATHEROSCLEROSIS? 5) DOES PATERNAL EXPOSURE TO PXR AGONISTIC EDCS AFFECT THE ATHEROSCLEROSIS DEVELOPMENT OF THE OFFSPRING? HOW DOES PXR SIGNALING ALTER THE SPERM RNA CODE TO INCREASE CVD RISK OF THE OFFSPRING? THE PROPOSED STUDIES WILL CONTRIBUTE TO OUR UNDERSTANDING OF GENE-EDC INTERACTIONS IN PREDISPOSING INDIVIDUALS AND THEIR OFFSPRING TO CVD, AND MY EXPERTISE AND EXPERIENCE ARE AN IDEAL FIT FOR THE RIVER MECHANISM THAT SUPPORTS A MULTI- DIMENSIONAL LONG-TERM STUDY OF THE PROPOSED RESEARCH.

PERISOMATIC INHIBITORY NETWORK DYSFUNCTION IN NEUROLOGICAL DISEASE

IMPROVING OUTCOMES IN ENDOVASCULAR TREATMENT OF INTRACRANIAL ANEURYSMS: COMBINING ADDITIVE MANUFACTURING, IN-SILICO MODELING, AND SHAPE MEMORY POLYMERS - PROJECT SUMMARY/ABSTRACT SUBARACHNOID HEMORRHAGE (SAH) IS A DEVASTING ACUTE NEUROLOGICAL DISEASE THAT REMAINS A MAJOR CAUSE OF PREMATURE MORTALITY. SAH IS MOST CAUSED BY INCIDENTAL RUPTURE OF AN INTRACRANIAL ANEURYSM (ICA). THE MORTALITY RATE OF ANEURYSM RUPTURE CAN REACH AS HIGH AS 40% WITHIN THE FIRST WEEK OF INCIDENCE. EVEN IF THE ANEURYSM IS TREATED IN A TIMELY MANNER, THE CHANCE OF MODERATE TO SEVERE BRAIN DAMAGE IS 20-35%. ENDOVASCULAR COIL EMBOLIZATION IS THE CURRENT GOLD-STANDARD, MINIMALLY INVASIVE THERAPY OF ICAS; HOWEVER, EMERGING CLINICAL CHALLENGES OF COIL EMBOLIZATION ARE UNSATISFACTORY ANEURYSM RECURRENCE RATES: ~44% BY 5-6 YEARS AFTER THE INITIAL COIL THERAPY (OF WHICH MORE THAN 50% REQUIRING RE-TREATMENT), AND SUBOPTIMAL COMPLETE OCCLUSION, ESPECIALLY FOR TREATING WIDE-NECKED ICAS AND/OR ANEURYSMS WITH A COMPLEX 3D GEOMETRY. THUS, THERE IS A NEED FOR A DURABLE DEVICE TO TREAT UNRUPTURED ICAS THAT TARGETS PATIENT-SPECIFIC ANEURYSMS AND INTRA-ANEURYSMAL CIRCULATION AND PROVIDES LONG-LASTING COMPLETE OCCLUSION. OUR RESEARCH OBJECTIVES OF THIS PROJECT ARE TO: 1) DESIGN AND FABRICATE PERSONALIZED EMBOLIC DEVICES FOR TREATING SACCULAR, BIFURCATED IACS USING ADDITIVE MANUFACTURING AND A COMBINED EXPERIMENTAL/BIOMECHANICAL APPROACH, AND 2) PROVIDE A HOLISTIC BIOMECHANICAL AND HEMODYNAMIC COMPARISON BETWEEN OUR DEVICE AND OTHER SELECTED ENDOVASCULAR EMBOLIC TECHNIQUES. THIS PROPOSAL BUILDS UPON THE ASSEMBLED PRELIMINARY DATA, AND LEVERAGES DR. LEE’S EXPERIENCE WITH TISSUE BIOMECHANICS AND IN-SILICO MODELING, IN COLLABORATION WITH POLYMER SCIENCE AND ADDITIVE MANUFACTURING RESEARCHERS AT THE UNIVERSITY OF OKLAHOMA, CLINICAL AND NEUROSURGICAL EXPERTISE OF CLINICIANS AT INDIANA UNIVERSITY – MEDICINE, AND MICRO-DEVICE AND CATHETER EXPERT AT PURDUE. SPECIFICALLY, WE PROPOSE TO DESIGN, DEVELOP, AND EVALUATE PATIENT-SPECIFIC SMP EMBOLIC DEVICES USING 3D PRINTING-BASED POLYMER FABRICATION. OUR EMBOLIC DEVICES ARE DESIGNATED TO TARGET PERSONALIZED ANEURYSM FILLING AND MAXIMIZE THE RATE OF LONG-LASTING COMPLETE OCCLUSION. NEXT, THROUGH IN-VITRO FLOW LOOP TESTBED AND IN-VIVO SMALL ANIMAL STUDIES, THE EFFICACY AND ANEURYSM OCCLUSION OF OUR PERSONALIZED EMBOLIC DEVICES WILL BE SYSTEMATICALLY EVALUATED IN COMPARISON TO THE CLINICAL GOLD STANDARD AS WELL AS THREE OTHER CONTEMPORARY EMBOLIC METHODS. THE ENDPOINT OF THIS PROJECT WILL BE A CUTTING-EDGE SOLUTION FOR ICA EMBOLIZATION, THAT USES FUNDAMENTAL INFORMATION ON ANEURYSMS BASED ON HOLISTIC BIOMECHANICAL AND HEMODYNAMIC ANALYSES – ALLOWING INDIVIDUAL-OPTIMIZED ANEURYSM FILLING TO ACHIEVE IMMEDIATE & LONG-TERM COMPLETE OCCLUSION AND REDUCE ANEURYSM RECURRENCE. COLLECTIVELY, OUR DEVELOPMENTS WILL SERVE AS A LOGICAL FIRST STEP TOWARD ATTAINING OUR LONG- TERM GOAL TO ADVANCE THE STATE OF THE ART IN TRANSLATIONAL MEDICINE BY FACILITATING PERSONALIZED, PREVENTIVE MANAGEMENT OF UNRUPTURED ICAS AND REDUCE ANEURYSM RUPTURE-INDUCED HEMORRHAGIC STROKES.

ERYTHROCYTE-DERIVED PARTICLES FOR NEAR INFRARED PHOTOTHERAPY OF PORT WINE STAINS

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CITRUS HUANGLONGBING (HLB) IS CONSIDERED ONE OF THE MOST DIFFICULT CHALLENGES FOR SEVERAL CITRUS INDUSTRIES WORLDWIDE. THE FINANCIAL IMPACTS OF HLB ARE STAGGERING AND MAY RESULT IN CITRUS BEING REPLACED BY OTHER FRUIT TREES AND ALTERNATIVE CROPS. IN FLORIDA, WHERE THE DISEASE HAS BEEN WELL ESTABLISHED FOR OVER TEN YEARS, THE YIELD OF CITRUS TREES HAS BEEN REDUCED TO YIELDS REFLECTING THE FLORIDA INDUSTRY 70-100 YEARS AGO. THE REDUCED YIELD IS REFLECTED IN THE HIGH PRICE OF ORANGE JUICE FOR THE MORNING BREAKFAST. THE DISEASE THREATENS THE CITRUS CROP IN OTHER CITRUS-GROWING STATES LIKE CALIFORNIA, TEXAS, AND ARIZONA. FINDING LONG-TERM, SUSTAINABLE SOLUTIONS IS IMPERATIVE FOR CONTINUED CITRICULTURE.CITRUS HLB IS A COMPLEX DISEASE ASSOCIATED WITH A NON-CULTIVABLE BACTERIAL PATHOGEN, SPREAD BY A PSYLLID INSECT VECTOR THAT IS DIFFICULT TO CONTROL, AND THE DISEASE HAS NO KNOWN CURE; INFECTED TREES DECLINE, PRODUCE UNMARKETABLE FRUIT, AND DIE IN A FEW YEARS. MANAGEMENT OF THE DISEASE BY PREVENTING SPREAD, CONTROL OF THE INSECT VECTOR, AND APPLICATION OF ANTI-MICROBIAL SUBSTANCES ARE GOOD PRACTICES - BUT OF LIMITED VALUE FOR A TREE CROP THAT CAN LIVE FOR SEVERAL DECADES. DESPITE INTENSIVE RESEARCH FOR THE PAST FIFTEEN YEARS, TANGIBLE SOLUTIONS TO CONTROL HLB ARE NOT YET AVAILABLE. NOVEL APPROACHES ARE NEEDED TO FIND PRACTICAL METHODS TO MANAGE HLB IN THE CITRUS-GROWING STATES OF THE USA. CURRENT METHODS OF DISEASE MANAGEMENT ARE NOT FINANCIALLY AFFORDABLE. EXCESSIVE USE OF PESTICIDES TO CONTROL THE PSYLLID POPULATIONS IS ENVIRONMENTALLY UNSAFE; PESTICIDES WILL LOSE EFFECTIVENESS AFTER PROLONGED USE. ECOLOGICALLY FRIENDLY BIOLOGICAL CONTROL MECHANISMS THAT REDUCE THE PSYLLID POPULATION WILL NOT BE ADEQUATE TO MANAGE HLB SINCE A SINGLE INSECT VECTOR CARRYING THE PATHOGEN CAN SPREAD THE DISEASE IN A CITRUS GROVE. WHEN THE CITRUS PROCESSING PLANTS AND JUICE FACTORIES ARE CLOSED BECAUSE OF LOW YIELD AND DISEASED FRUIT, IT WILL BE VERY DIFFICULT TO REVIVE THIS INDUSTRY INFRASTRUCTURE. LONG-TERM STRATEGIES FOR DISEASE MANAGEMENT ARE URGENTLY NEEDED TO CONTINUE CITRUS CULTIVATION IN AREAS WHERE THE INSECT VECTOR AND THE PATHOGEN HAVE BEEN ESTABLISHED.CITRUS IS PROPAGATED MAINLY THROUGH GRAFTING. THE VEGETATIVE MODE OF PROPAGATION OF A LIMITED NUMBER OF CULTIVARS HAS RESULTED IN INNUMERABLE CULTIVATED TYPES, BUT THERE IS LITTLE GENETIC DIVERSITY IN CULTIVATED CITRUS. WHEN NEW PATHOGENS ARRIVE, THIS GENETIC UNIFORMITY CAN RESULT IN DISEASE EPIDEMICS AND DIRE CONSEQUENCES FOR THE CROP. IN ADDITION, THERE IS NO DOCUMENTED RESISTANCE TO HLB IN CULTIVATED CITRUS. HOWEVER, OTHER CITRUS-RELATED WILD PLANTS MAY HAVE RESISTANCE TRAITS TO HLB. BASED ON OUR PREVIOUS WORK, WE DETERMINED THAT CERTAIN NON-CITRUS TAXA THAT ARE CLOSELY RELATED TO CITRUS HAVE DISEASE-RESISTANCE TRAITS AND THESE MAY BE UTILIZED TO IMPART THE MUCH-NEEDED HLB RESISTANCE TO CULTIVATED CITRUS TYPES. OUR APPROACH IS TO GENERATE NOVEL HYBRIDS OF CITRUS USING CONVENTIONAL BREEDING METHODS WITH SEXUALLY C,OMPATIBLE CITRUS RELATIVES HAVING GENETIC RESISTANCE TO THE HLB PATHOGEN. TOWARDS THIS GOAL, WE HAVE CONDUCTED A BREEDING PROGRAM SINCE 2013 BY CROSSING CITRUS ACCESSIONS WITH DISEASE-RESISTANT/TOLERANT AUSTRALIAN LIME SPECIES BELONGING TO THE GENUS MICROCITRUS. CROP RELATIVES ARE UTILIZED AS SOURCES OF BENEFICIAL TRAITS IN OTHER CULTIVATED PLANTS. CITRUS IS SEXUALLY COMPATIBLE WITH MANY CLOSELY RELATED GENERA; THIS BIOLOGICAL PECULIARITY OF CULTIVATED CITRUS TYPES WAS EXPLOITED IN OUR BREEDING PROGRAM TO GENERATE HUNDREDS OF INTERGENERIC HYBRIDS.CITRUS BREEDING IS CONSIDERED VERY DIFFICULT AND TIME-CONSUMING SINCE THE GENERATION TIME CAN BE 4 TO 5 YEARS. SINCE OUR BREEDING PROGRAM HAS BEEN IN PROGRESS FOR TEN YEARS NOW, WE HAVE GENERATED PROGENY FROM SEVERAL DIFFERENT TYPES OF CROSSES. EVALUATION OF THE NOVEL HYBRIDS IN THE FIELD AND IN THE GREENHOUSE DETERMINED THAT HLB RESISTANCE TRAITS CAN BE INHERITED BY A SMALL PROPORTION OF THE BREEDING PROGENY. HOWEVER, SINCE ONE PARENT OF THE CROSS BEARS FRUIT THAT IS BARELY EDIBLE, MANY HYBRIDS OF THE FIRST-GENERATION CROSSES HAVE FRUITS THAT MAY NOT BE ACCEPTABLE AS SUBSTITUTE VARIETIES, EVEN THOUGH THEY HAVE DISEASE-RESISTANCE TRAITS. WE HAVE NOW GENERATED HYBRIDS OF THE SECOND GENERATION BY CROSSING THE PROMISING HYBRIDS FROM THE FIRST GENERATION TO COMMERCIAL TYPES OF CITRUS. A SMALL PERCENTAGE OF THE ADVANCED HYBRIDS IS EXPECTED TO HAVE RETAINED THE HLB RESISTANCE TRAITS AND MAY HAVE FRUIT QUALITIES SIMILAR TO COMMERCIAL CITRUS TYPES. WE PROPOSE TO UTILIZE MOLECULAR APPROACHES TO DEVELOP MARKERS THAT WILL AID IN THE SELECTION OF THE BREEDING PROGENY FROM THE SECOND GENERATION OF HYBRIDS TO IDENTIFY INDIVIDUALS WITH PROMISING HLB RESISTANCE. IF SUCH HYBRIDS CAN RESIST HLB IN FIELD CONDITIONS AND IF THEY HAVE FRUIT TRAITS THAT ARE DEEMED ACCEPTABLE BY THE PUBLIC, WE WILL HAVE NOVEL HYBRIDS WITH DISEASE RESISTANCE AND ACCEPTABLE ORGANOLEPTIC ATTRIBUTES. CULTIVAR DEVELOPMENT OF PROMISING INDIVIDUALS WILL BE REQUIRED BEFORE LARGE-SCALE CULTIVATION CAN BE ADOPTED.IF NOVEL HYBRIDS WITH GENETIC RESISTANCE TO HLB ARE DEVELOPED, IT WILL BE POSSIBLE TO CULTIVATE CITRUS DESPITE HAVING THE PATHOGEN AND THE INSECT VECTOR IN THE AREA. MANAGEMENT OF THE GROVES THAT HAVE RESISTANT CULTIVARS WILL BE SIMILAR TO THE GROVE MANAGEMENT DONE BEFORE HLB ARRIVED. FINANCIALLY IT WILL BE FEASIBLE TO CULTIVATE CITRUS IF ELABORATE, EXPENSIVE MANAGEMENT PRACTICES ARE NOT NECESSARY. ANOTHER ADVANTAGE IS THAT THE NOVEL HYBRIDS MAY HAVE NEW FLAVORS THAT MAY ENHANCE THE KNOWN CITRUS FLAVORS THAT ARE GENERALLY ASSOCIATED WITH CITRUS FRUITS. WE WILL LOOK FOR THE METABOLOMICS PROFILE OF NOVEL HYBRIDS TO IDENTIFY THE FLAVOR-ENHANCING COMPOUNDS IN THE HYBRID FRUITS AND COMPARE THEM WITH STANDARD CITRUS. REPLACEMENT OF PRESENTLY CULTIVATED CITRUS VARIETIES WITH NOVEL HYBRIDS WILL BE BENEFICIAL TO MANAGE HLB. THE MOLECULAR MARKERS WE PROPOSE TO DEVELOP IN THE PROJECT CAN BE USED IN THE FUTURE TO MAKE PRE-SELECTIONS FROM OUR BREEDING PROGRA,M IN CALIFORNIA. WE ENVISAGE THE DEVELOPMENT OF MULTIPLE VARIETIES RESEMBLING MANDARINS, SWEET ORANGES, GRAPEFRUIT, AND LEMONS SOON. THE AVAILABILITY OF HLB-RESISTANT HYBRIDS WITH CITRUS-LIKE FLAVORS (AND SOME NOVEL FLAVORS) WILL BE EXTREMELY BENEFICIAL TO RESTORING THE CITRUS INDUSTRY IN THE UNITED STATES. CITRUS FRUITS PROVIDE VALUABLE NUTRIENTS AND CONSTITUTE AN ESSENTIAL PART OF A HEALTHY DIET. RESTORING THE CITRUS INDUSTRIES WITH USEFUL, DISEASE-RESISTANT HYBRIDS WILL RESULT IN JOB CREATION AND IMPROVEMENT OF ECONOMIC SITUATIONS IN CITRUS-GROWING REGIONS.

EPHB SIGNALING IN DENDRITIC SPINE DEVELOPMENT

PORE SPACE ENGINEERING AND FUNTIONALIZATION IN POROUS METAL-ORGANIC FRAMEWORK MATERIALS

FY17 EVALUATING THE EXTENT OF ATTACK, DE

STRUCTURE, FUNCTION AND REACTIVITY OF CO DEHYDROGENASE FROM OLIGOTROPHA CARBOXIDOVORANS

READING ENHANCEMENTS FOR STUDENTS WITH AUTISM SPECTRUM DISORDERS (PROJECT READ): A READING COMPREHENSION INTERVENTION

AGING AND PERCEPTUAL LEARNING: BEHAVIORAL AND FMRI STUDIES

EXPLORING HEAVY ION COLLISIONS IN SIMPLE SYSTEMS: PARTON STRUCTURE IN HEAVY NUCLEI AND THE INITIAL CONDITION FOR THE STRONGLY INTERACTING QUARK GLUON

METHAMPHETAMINE EFFECT ON HIV PERSISTENCE

DESCRIPTION:THIS AGREEMENT PROVIDES FUNDING UNDER THE INFLATION REDUCTION ACT (IRA) TO THE UNIVERSITY OF CALIFORNIA, RIVERSIDE FOR HYDROFLUOROCARBON (HFC) RECLAIM AND INNOVATIVE DESTRUCTION. THE RECIPIENT WILL ADDRESS A CRITICAL ENVIRONMENTAL CONCERN TIED TO THE EMISSIONS OF HFCS, POTENT GREENHOUSE GASES WIDELY USED IN REFRIGERATION AND AIR CONDITIONING. THE CORE OBJECTIVE IS TO REDUCE HFC EMISSIONS THROUGH THE USE OF A COST-EFFECTIVE METAL OXIDE CATALYST. THIS CATALYST FACILITATES THE HYDROLYSIS OF HFC MOLECULES (USING HFC-134A AS AN EXAMPLE), AND THE RESULTING FLUORINE-CONTAINING COMPOUNDS CAN BE FULLY REMOVED BY SUBSEQUENT LIQUID ABSORPTION AND DESTRUCTIVE TREATMENT USING CHEMICAL AND BIOLOGICAL MODULES. THE CHEMICAL AND BIOLOGICAL TRANSFORMATIONS WILL CONVERT HFCS INTO ENVIRONMENTALLY BENIGN PRODUCTS, THEREBY MITIGATING THEIR IMPACT ON THE CLIMATE AND THE OVERALL ENVIRONMENTAL QUALITY AND PUBLIC HEALTH.ACTIVITIES:THE ACTIVITIES INCLUDES INITIATING LABORATORY-SCALE EXPERIMENTS AND CHEMICAL/BIOLOGICAL TREATMENT VALIDATION IN THE SHORT TERM, FOLLOWED BY THE SCALING UP OF TECHNOLOGY FOR PILOT DEMONSTRATIONS IN THE INTERMEDIATE TERM. THE IMPLEMENTATION OF THE TECHNOLOGIES AT THE SELECTED VALIDATION SITE (UC RIVERSIDE CAMPUS) AND THEIR EVALUATION FOR ENVIRONMENTAL AND PUBLIC HEALTH IMPACTS WILL BE INTERMEDIATE-TERM ACTIVITIES. THE LONG-TERM ACTIVITIES INCLUDE ESTABLISHING THE TECHNOLOGIES AS A PROVEN SOLUTION, PROMOTING WIDESPREAD ADOPTION, CONTRIBUTING TO INDUSTRY STANDARDS AND REGULATIONS, AND EVALUATING LONG-TERM ENVIRONMENTAL, ECONOMIC, AND SOCIAL IMPACTS. BY UNDERTAKING THESE COMPREHENSIVE ACTIVITIES AND ACHIEVING THE OUTLINED OUTCOMES, THE CATALYTIC HYDROLYSIS AND ASSISTING TECHNOLOGY PROJECT AIMS TO POSITION ITSELF AS A VALIDATED, SUSTAINABLE, AND READY-TO-DEPLOY SOLUTION FOR REDUCING HFC EMISSIONS BEYOND LABORATORY SETTINGS IN DISADVANTAGED COMMUNITIES.SUBRECIPIENT:NO SUBAWARDS ARE INCLUDED IN THIS ASSISTANCE AGREEMENT.OUTCOMES:THE ANTICIPATED DELIVERABLES INCLUDE: MORE EFFICIENT CATALYSTS FOR HFC HYDROLYSIS AND CO OXIDATION IN LAB SCALE AND APPLICATION SCALE, ANALYTICAL METHOD DEVELOPMENT AND VALIDATION, DETAILED COMPOSITION IN THE OFF-GAS OF THE GAS-PHASE CATALYTIC HFC HYDROLYSIS TREATMENT, NEAR-COMPLETE CONVERSION AND MINERALIZATION WITH OFF-GAS COLLECTION AND TREATMENT IN LIQUID PHASE USING CHEMICAL AND/OR BIOLOGICAL METHODS, DEVELOP PILOT SCALE OFF-GAS TREATMENT REACTORS, INSTALL ASSISTING LOW TEMPERATURE CO OXIDATION REACTOR, IMPLEMENT CONTINUOUS MONITORING OF EMISSIONS AND CONVERSION EFFICIENCY, ASSESS THE TRANSFERABILITY OF THE TECHNOLOGY TO DIVERSE APPLICATIONS, PREPARE A TECHNOLOGY TRANSFERABILITY REPORT, ASSESS THE TECHNOLOGY'S POSITIVE IMPACT ON CLIMATE CHANGE MITIGATION, IMPROVEMENTS IN AIR QUALITY, REGULATORY COMPLIANCE WITH ENVIRONMENTAL STANDARDS, ASSESS THE OVERALL SUSTAINABILITY OF THE CATALYTIC HYDROLYSIS AND ASSISTING TECHNOLOGY FOR HFC DESTRUCTION, SECURE NECESSARY PERMITS AND APPROVALS FOR EXPANDED DEPLOYMENT, AND IMPLEMENT FULL-SCALE DEPLOYMENT AT SELECTED SITES MONITOR TECHNOLOGY PERFORMANCE IN REAL-WORLD SETTINGS. THE EXPECTED OUTCOMES INCLUDE: QUANTITATIVELY, THE PROJECT AIMS TO DEMONSTRATE A MEASURABLE (GT; 90%) REDUCTION IN HFC EMISSIONS WITHIN THE STUDIED COMMUNITY, WITH SPECIFIC METRICS IN METRIC TONS OF CO2 EQUIVALENT. FURTHERMORE, THE OVERALL HFC CONVERSION EFFICIENCY (~100%) OF THE CATALYTIC PROCESS AND CHEMICAL-BIOLOGICAL POST-TREATMENT MODULES WILL BE A KEY QUANTITATIVE OUTCOME, MEASURED AS A PERCENTAGE OF SUCCESSFUL CONVERSION. THE PROJECT PLANS TO IDENTIFY AND ESTABLISH A SPECIFIC SITE (E.G., THE HVAC SYSTEM AT THE UC RIVERSIDE CAMPUS) FOR THE VALIDATION AND DEMONSTRATION PHASE, SHOWCASING THE REAL-WORLD APPLICABILITY OF THE PROPOSED TECHNOLOGIES. QUALITATIVELY, THE PROJECT WILL ASSESS ITS IMPACT ON CLIMATE CHANGE MITIGATION, EMPHASIZING THE POSITIVE CONTRIBUTION TO GREENHOUSE GAS REDUCTION GOALS. AIR QUALITY IMPROVEMENT, A CRITICAL QUALITATIVE OUTCOME, WILL BE EVALUATED FOR

TAS::89 0222::TAS; NEW; FTIR STUDIES OF PHOTOSYNTHETIC OXYGEN PRODUCTION; PI: RICHARD J. DEBUS

RESEARCH-PGR - ADAPTING CROPS TO A HARSH ENVIRONMENT: INTERPLAY BETWEEN ARBUSCULAR MYCORRHIZAL FUNGI, DROUGHT STRESS AND PLASTICITY OF PLANT ARCHITECTURE

MODELING THE ROLE OF AGE AT TRAUMATIC BRAIN INJURY IN THE DEVELOPMENT OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS - PROJECT SUMMARY GROWING CLINICAL EVIDENCE SUGGESTS THAT TRAUMATIC BRAIN INJURY (TBI) IS A MAJOR RISK-FACTOR OVER AN INDIVIDUAL’S LIFETIME, AND RESULTS IN SYMPTOMS AND PATHOPHYSIOLOGY CONSISTENT WITH ALZHEIMER’S DISEASE (AD) AND RELATED DEMENTIAS (ADRD). RODENT MODELS RECAPITULATE EARLY PATHOLOGICAL CLINICAL FEATURES OF TBI, BUT IT IS UNKNOWN IF THESE MODELS MANIFEST LONG-TERM ADRD FEATURES SUCH AS COGNITIVE DECLINE, NEURODEGENERATIVE BRAIN ATROPHY, CHRONIC INFLAMMATION, VASCULAR DISTURBANCES, AND ACCUMULATION OF AMYLOID-Β (AΒ) AND ALTERED FLUID BIOMARKER LEVELS. WELL-KNOWN RISK FACTORS FOR TBI-INDUCED ADRD (I.E. APOE, SEX ETC.) INFLUENCE SUSCEPTIBILITY FOR LIFESPAN PROGRESSION, BUT THE ROLE OF TBI PATHOPHYSIOLOGY HAS NOT BEEN WELL CHARACTERIZED. THIS PROPOSAL WILL FILL THESE KNOWLEDGE GAPS USING A CLOSED HEAD INJURY (CHI) TBI MODEL OVER THE ANIMAL’S LIFESPAN THAT EXHIBITS ADRD-LIKE FEATURES. USING THE CHI TBI MODEL, WE WILL EXAMINE HOW AD RISK ALLELES (I.E. HUMANIZED AMYLOID-Β (HAΒ), APOEΕ4, AND HAΒ.APOEΕ4) ACCELERATE ADRD PROGRESSION. IMPORTANTLY, COGNITIVE BEHAVIORAL OUTCOMES, CLINICALLY RELEVANT NEUROIMAGING (PET, MRI) USING ESTABLISHED PROTOCOLS (ADNI3) COMBINED WITH FLUID BIOMARKERS WILL BE USED TO ASSESS DISEASE ADVANCEMENT. CONSTRUCT AND FACE VALIDITY MEASURES (WITHIN AND BETWEEN PERFORMANCE SITES WILL BE DEMONSTRATED USING MULTI-MODAL DATA MODELING TO CONFIRM REPLICABILITY AND TO DIFFERENTIATE BETWEEN TBI+ADRD FROM TBI OR ADRD TRAJECTORIES ALONE. USING OUR CHI TBI MOUSE MODEL, WHICH REPLICATES HUMAN MILD/MODERATE TBI, AND EXHIBITS ALTERED BLOOD BRAIN BARRIER (BBB), PROGRESSIVE COGNITIVE DECLINE, LATE AΒ DEPOSITION, CHRONIC NEUROINFLAMMATION, AND PROGRESSIVE VASCULAR PERTURBATIONS, WE WILL ESTABLISH IN SEX AND AGE-SPECIFIC MANNER THE CONDITIONS FOR TBI EVOLUTION TO ADRD. WE ALSO WILL LEVERAGE NIA-FUNDED MODEL-AD PLATFORM MICE EXPRESSING HAΒ AND APOEΕ4 ON A C57BL/6J (B6) BACKGROUND, AS SIGNIFICANT RISK FACTORS FOR ADRD PROGRESSION. USING THESE MODELS EXPOSED TO TBI, WE WILL INVESTIGATE HOW INJURY EXPOSURE AT 3 EPOCHS (JUVENILE 17D; MIDDLE 8M, OLD 12M) ACROSS LIFESPAN (24M OF AGE) INFLUENCES PROGRESSION TO ADRD (AIM 1). A REPEATED CHI TBI WILL BE IDENTICALLY TESTED TO DEMONSTRATE A FURTHER INCREASED VULNERABILITY TO ADRD (AIM 2). FINALLY, WE WILL LEVERAGE THESE MULTI-MODAL DATA IN AN UNBIASED MANNER TO ESTABLISH INTERNAL/EXTERNAL CONSISTENCY AND REPRODUCIBILITY (CONSTRUCT VALIDITY) AS WELL AS MODELING HOW THIS MAPS TO HUMAN PROGRESSIVE TRAJECTORIES TO DISSOCIATE TBI+ADRD FROM TBI OR ADRD ALONE (AIM 3). THESE AIMS WILL DEMONSTRATE, VALIDATE, AND REPLICATE OUR HYPOTHESIS THAT TBI THROUGHOUT THE LIFESPAN CONTINUUM LEADS TO AGE-SPECIFIC TRAJECTORIES TOWARDS ADRD SYMPTOMOLOGY. THE PROPOSED RESEARCH WILL RESULT IN A DEEPLY PHENOTYPED TBI MODEL AS IT PROGRESSES TO ADRD, AND THE ROLE OF SEX AND AGE OF INJURY. THE DERIVED DATA WILL SERVE AS A SIGNIFICANT RESOURCE TO ACCELERATE FUTURE RESEARCH INTO THE MECHANISMS OF TBI ADRD.

PREDICTING POST-FIRE N CYCLING THROUGH TRAITS AND CROSS-KINGDOM INTERACTIONS

CHEMICAL AND MOLECULAR MECHANISMS OF MITOCHONDRIAL DNA DEGRADATION

DISSECTING INTERACTIONS ACROSS GENE REGULATORY LAYERS IN SINGLE CELLS

REGULATION OF LIVER-SPECIFIC GENE EXPRESSION

SUPPLEMENTAL ASSISTANCE TO INSTITUTIONS OF HIGHER EDUCATION (SAIHE) FUNDING FOR UC RIVERSIDE

SCIENCE TO POLICY EDUCATION: ACTIVATING KNOWLEDGE FOR SUSTAINABLE TRANSPORTATION (SPEAKS) -AS SOCIETY LOOKS INCREASINGLY TO SCIENTIFIC ADVANCES FOR SOLUTIONS TO MAJOR CHALLENGES, RESEARCHERS MUST ENGAGE WITH THE PUBLIC AND POLICYMAKERS TO DEVELOP AND IMPLEMENT NEW TECHNOLOGIES BASED ON THOSE ADVANCES TO BENEFIT SOCIETY. FOR EXAMPLE, SUCH ENGAGEMENT IS ESSENTIAL TO ADDRESS CLIMATE CHANGE, AS PEOPLE AND INDUSTRIES MUST QUICKLY AND EQUITABLY EMBRACE RENEWABLE ENERGY SOURCES AND SUSTAINABLY POWERED VEHICLES AND TECHNOLOGIES. THIS NSF RESEARCH TRAINEESHIP (NRT) PROJECT WILL TRAIN STEM GRADUATE STUDENTS TO INTEGRATE ENGINEERING, SOCIAL AND ENVIRONMENTAL SCIENCE, AND PUBLIC POLICY TO CONDUCT RESEARCH FOCUSED ON ACCELERATING THE INTEGRATION OF RENEWABLE ENERGY INTO THE ELECTRIC GRID, TAKING ADVANTAGE OF RENEWABLE HYDROGEN AND DIFFERENT ENERGY STORAGE CAPABILITIES. SUCH INTEGRATION WILL ULTIMATELY HELP ACCELERATE THE DECARBONIZATION OF TRANSPORTATION AND OTHER SECTORS. THIS PROJECT WILL USE A NOVEL SCIENCE-TO-POLICY (S2P) TRAINING PROGRAM TO TEACH STUDENTS TO ENGAGE STAKEHOLDER GROUPS AND UNDERSTAND AND INCORPORATE THEIR NEEDS INTO RESEARCH PROGRAMS WHILE COMMUNICATING THE SCIENCE, AND PRIORITIZING ATTENTION TO DIVERSITY, EQUITY, INCLUSION, AND ETHICS. THIS PROJECT ANTICIPATES TRAINING EIGHTY (80) PH.D. STUDENTS, INCLUDING THIRTY (30) FUNDED TRAINEES, FROM DIFFERENT ENGINEERING PROGRAMS, ENVIRONMENTAL SCIENCES, SOCIOLOGY, AND POLITICAL SCIENCE. FUNDED TRAINEES WILL INTERN IN LEGISLATIVE OFFICES, GOVERNMENT AGENCIES, NON-PROFITS, AND INDUSTRY FOR HANDS-ON CAREER PREPARATION WITH A TANGIBLE PRODUCT, SUCH AS A POLICY RECOMMENDATION OR REPORT. THIS PROJECT WILL CONVENE EXPERT PRACTITIONERS FROM THESE AREAS TO TEACH STUDENTS AND PARTICIPATE IN RESEARCH PROJECTS. PROJECT FACULTY AND RESEARCHERS FROM ENGINEERING, POLICY, SCIENCES, AND HUMANITIES WILL IMPLEMENT AN INTERDISCIPLINARY TRAINING PROGRAM PROVIDING PH.D. STUDENTS SKILLS AND EXPERIENCE NECESSARY TO ADDRESS KEY SCIENTIFIC CHALLENGES TO TRANSPORTATION DECARBONIZATION AND TO IMPLEMENT THEIR FINDINGS IN PUBLIC POLICY. FACULTY WILL ALSO WORK WITH CAMPUS LEADERSHIP TO INTEGRATE ELEMENTS OF THE S2P TRAINING PROGRAM IN CAMPUS-WIDE INTRODUCTORY GRADUATE COURSES AND COLLABORATE WITH THE NATIONAL SCIENCE POLICY NETWORK TO SHARE THIS TRAINING PROGRAM NATIONALLY. THIS TRAINING PROGRAM IS THE FIRST STEP IN TRANSFORMING STEM GRADUATE EDUCATION TO BETTER PREPARE STUDENTS FOR ANY CAREER AND TO TRANSLATE SOCIETALLY BENEFICIAL RESEARCH INTO PUBLIC POLICY. ACCELERATING DECARBONIZATION OF THE TRANSPORTATION SECTOR WHILE CONTINUING TO INTEGRATE RENEWABLES INTO THE ELECTRIC GRID IS CRITICAL TO ADDRESS CLIMATE CHANGE. TOWARDS THIS GOAL NRT TRAINEES WILL PURSUE THREE KEY ACTIVITIES. FIRST IS TO CONDUCT CUTTING-EDGE RESEARCH IN INTEGRATING THE HIGH RENEWABLES ELECTRIC GRID WITH TRANSPORTATION INFRASTRUCTURE, INVESTIGATING RENEWABLE HYDROGEN AS A FUEL AND ENERGY STORAGE MEDIUM. SECOND IS TO UNDERSTAND POLICIES AROUND SUSTAINABILITY, AIR POLLUTION, AND RENEWABLE ENERGY, LEARN TO COMMUNICATE SCIENCE TO ALL AUDIENCES, AND APPRECIATE THE NEEDS OF VARIOUS STAKEHOLDERS TO CREATE EQUITABLE SOLUTIONS FOR ENVIRONMENTAL JUSTICE. THIRD IS TO DEVELOP BEST PRACTICES FOR HUMAN INTERACTION WITH RENEWABLE ENERGY TECHNOLOGY BY DESIGNING SOLUTIONS BASED ON INDIVIDUAL, SOCIETAL, AND POLITICAL NEEDS. ENGAGING KEY STAKEHOLDER GROUPS DURING RESEARCH AND DEVELOPMENT WILL ACCELERATE THE DEPLOYMENT OF RENEWABLE TECHNOLOGIES AND FOSTER EFFECTIVE COMMUNICATION AND DECISION-MAKING ON SCIENTIFIC TOPICS. THIS PROJECT WILL PREPARE TRAINEES TO DEVELOP AND DEPLOY A MODEL FOR SCIENTIFIC RESEARCH THAT IS CLOSELY CONNECTED WITH SOCIETAL CHALLENGES THROUGH MEANINGFUL COMMUNITY ENGAGEMENT AND RESPONSIVE PROGRAMS. THE NSF RESEARCH TRAINEESHIP (NRT) PROGRAM IS DESIGNED TO ENCOURAGE THE DEVELOPMENT AND IMPLEMENTATION OF BOLD, NEW POTENTIALLY TRANSFORMATIVE MODELS FOR STEM GRADUATE EDUCATION TRAINING. THE PROGRAM IS DEDICATED TO EFFECTIVE TRAINING OF STEM GRADUATE STUDENTS IN HIGH PRIORITY INTERDISCIPLINARY OR CONVERGENT RESEARCH AREAS THROUGH COMPREHENSIVE TRAINEESHIP MODELS THAT ARE INNOVATIVE, EVIDENCE-BASED, AND ALIGNED WITH CHANGING WORKFORCE AND RESEARCH NEEDS. 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.

NRT: PLANTS-3D (DISCOVER, DESIGN AND DEPLOY): TRAINING DIVERSE GRADUATE STUDENT COHORTS IN PLANT SYNTHETIC BIOLOGY

IGERT: VIDEO BIOINFORMATICS

IGERT: WATER SENSE - WATER SOCIAL, ENGINEERING, AND NATURAL SCIENCES ENGAGEMENT

CHEMISTRY AND BIOLOGY OF DNA CARBOXYALKYLATION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. 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.

NEW; SISGR - DESIGN AND CHARACTERIZATION OF NOVEL PHOTOCATALYSTS WITH CORE-SHELL NANOSTRUCTURES; PI: FRANCISCO ZAERA

"CENTRAL COLLISIONS OF HEAVY ION PHYSICS

THE RULE OF 3 PROJECT AVANZANDO

CHEMICALLY-RICH STRUCTURE AND DYNAMICS IN THE ACTIVE SITE OF TRYPTOPHAN SYNTHASE

ROLE OF PXR IN DRUG-ELICITED CARDIOVASCULAR DISEASE - PROJECT SUMMARY ANTIPSYCHOTIC THERAPY IS WIDELY USED IN THE TREATMENT OF PSYCHIATRIC CONDITIONS INCLUDING BIPOLAR DISORDER, SCHIZOPHRENIA, AND MAJOR DEPRESSIVE DISORDER. THESE CONDITIONS, WHICH TOGETHER AFFECT MORE THAN 20% OF THE POPULATION, USUALLY REQUIRE LIFELONG MEDICATION. ATYPICAL ANTIPSYCHOTICS HAVE SUPERIOR THERAPEUTIC ACTION AND REDUCED ADVERSE EFFECTS AS COMPARED WITH TYPICAL ANTIPSYCHOTICS, BUT THE USE OF ATYPICAL ANTIPSYCHOTICS IS ALSO ASSOCIATED WITH DYSLIPIDEMIA AND AN INCREASED RISK OF CARDIOVASCULAR DISEASE (CVD) IN PATIENTS. THE UNDERLYING MECHANISMS RESPONSIBLE FOR THESE ADVERSE EFFECTS REMAIN LARGELY UNKNOWN, WHICH POSES SERIOUS HEALTH CHALLENGES TO PATIENTS UNDERGOING LONG-TERM ANTIPSYCHOTIC TREATMENT. TO THIS END, WE RECENTLY IDENTIFIED SEVERAL ATYPICAL ANTIPSYCHOTICS INCLUDING QUETIAPINE THAT PROMOTE DYSLIPIDEMIA, AS POTENT AGONISTS FOR THE NUCLEAR RECEPTOR PREGNANE X RECEPTOR (PXR). OUR PREVIOUS WORK REVEALED NOVEL AND UNSUSPECTED ROLES OF PXR IN LIPID HOMEOSTASIS AND ATHEROGENESIS, AND SHOWED THAT PXR LIGANDS INCREASE DYSLIPIDEMIA AND ATHEROSCLEROSIS IN ATHEROGENIC MOUSE MODELS INCLUDING PXR-HUMANIZED MICE. GIVEN INTESTINE AND LYMPHATIC SYSTEMS ARE ESSENTIAL FOR DIETARY LIPID ABSORPTION AND TRANSPORT, OUR LATEST PRELIMINARY STUDY USING NOVEL TISSUE-SPECIFIC PXR KNOCKOUT MOUSE MODELS DEMONSTRATED THAT EXPOSURE TO QUETIAPINE FAILS TO CAUSE HYPERLIPIDEMIA IN INTESTINE- SPECIFIC PXR KNOCKOUT MICE. HOW PXR SIGNALING IN ENTEROCYTES REGULATES THE INTESTINAL LIPID METABOLISM IS AN OPEN AND HIGHLY CLINICALLY RELEVANT QUESTION. FURTHERMORE, OUR PILOT STUDY REVEALED THAT ABLATION OF PXR BLUNTS VEGF RECEPTOR 3 SIGNALING IN LYMPHATIC ENDOTHELIAL CELLS AND REDUCES LYMPHATIC BUTTON JUNCTION FORMATION IN LACTEALS OF PXR-DEFICIENT MICE. IT IS COMPLETELY UNKNOW HOW LYMPHATIC PXR REGULATES LIPID ABSORPTION AND TRANSPORT BY GUT LYMPHATIC VESSELS. TO UNVEIL THE AFOREMENTIONED CENTRAL MYSTERY AND TO STUDY THE ACTION MODE OF PXR IN MEDIATING ANTIPSYCHOTIC-ELICITED ADVERSE EFFECTS ON LIPID HOMEOSTASIS AND ATHEROSCLEROSIS, WE PROPOSE THE FOLLOWING SPECIFIC AIMS TO DETERMINE THE MOLECULAR MECHANISMS OF THE ATHEROGENIC EFFECTS OF ATYPICAL ANTIPSYCHOTICS: 1) DEFINE THE ENTEROCYTE SIGNALING THROUGH WHICH PXR-ACTIVATING ANTIPSYCHOTICS REGULATE LIPID HOMEOSTASIS AND ATHEROSCLEROSIS; 2) DETERMINE THE MOLECULAR MECHANISMS UNDERLYING PXR- REGULATED LYMPHATIC LIPID ABSORPTION AND TRANSPORT IN ATHEROSCLEROSIS; AND 3) INVESTIGATE THE THERAPEUTIC POTENTIAL OF A NATURALLY OCCURRING PXR ANTAGONIST IN PREVENTING ANTIPSYCHOTIC-INDUCED DYSLIPIDEMIA AND ATHEROSCLEROSIS. SUCCESSFUL COMPLETION OF THE PROPOSED WORK WILL FILL IN THE VOID IN UNCOVERING NOVEL MOLECULAR MECHANISMS UNDERLYING ANTIPSYCHOTIC THERAPY-ASSOCIATED CVD RISK. OUR FINDINGS MAY ALSO INAUGURATE NEW CLASS OF THERAPEUTIC STRATEGIES TO TREAT DYSLIPIDEMIA IN PATIENTS UNDERGOING LONG-TERM ANTIPSYCHOTIC THERAPY.

RAPS-MEDIATED POST-TRANSCRIPTIONAL CONTROL IN APICOMPLEXAN PARASITES

CONNECTING LONG-LIVED PROTEIN ISOMERIZATION TO LYSOSOMAL FAILURE IN ALZHEIMER?S DISEASE

NEXT-GENERATION GPU COMPUTING RESOURCE FOR SIMULATING LIGAND-PROTEIN BINDING KINETICS/MECHANISM

ENDOCRINE DISRUPTOR MEDIATED ACTIVATION OF PXR CAUSES DYSLIPIDEMIA

LEAPFROG: LEARN AND PRUNE FEATURES IN BINARY PROGRAMS

NRT-DESE: NRT IN INTEGRATED COMPUTATIONAL ENTOMOLOGY (NICE)

THE ROLE OF NMD IN CORTICAL NEURAL PROGENITOR CELLS - PROJECT SUMMARY MUTATIONS IN KEY FACTORS OF NONSENSE-MEDIATED MRNA DECAY (NMD), INCLUDING UPF2, UPF3A, UPF3B, AND SMG6, ARE ENRICHED IN VARIOUS NEURODEVELOPMENTAL DISEASES. IN ADDITIONAL TO ENSURING TRANSCRIPT QUALITY BY DEGRADING ABERRANT TRANSCRIPTS WITH A PREMATURE STOP CODON, NMD MODULATES STABILITY OF SELECTIVE MRNAS TO FINE-TUNE TRANSCRIPT ABUNDANCE. WHETHER AND HOW NMD INFLUENCES BRAIN DEVELOPMENT REMAINS ELUSIVE. OUR LONG-TERM OBJECTIVE IS TO UNDERSTAND THE FUNCTIONAL ROLE OF NMD REGULATION FOR THE COMPLICATED AND DYNAMIC PROCESS OF NEUROGENESIS AND HOW ITS MIS-REGULATION LEADS TO NEURODEVELOPMENTAL DISORDERS. WE DETERMINE THE REQUIREMENT OF NMD FOR NEURAL DEVELOPMENT THROUGH SELECTIVE GENETIC ABLATION OF UPF2 AND IN VIVO MANIPULATION OF OTHER NMD FACTORS. OUR PRELIMINARY DATA SHOW THAT DELETION OF UPF2 IN NEURAL STEM AND PROGENITORS RESULTS IN MICROCEPHALY. UPF2 LOSS SPECIFICALLY AFFECTS THE CELL CYCLE AND LINEAGE PROGRESSION OF RADIAL GLIA CELLS (RGCS), THE MAJOR NEURAL PROGENITOR CELLS IN THE DEVELOPING NEOCORTEX. WE WILL COMBINE CUTTING EDGE MOLECULAR CELLULAR RIBOGENOMICS APPROACHES, MOUSE GENETICS, AND DEVELOPMENTAL NEUROBIOLOGY TO DISSECT THE MECHANISMS OF NMD REGULATING NEUROGENESIS. WE PROPOSE THREE INDEPENDENT AND INTERRELATED AIMS TO INVESTIGATE POSSIBLE VARIABLES UNDERLYING THE MICROCEPHALY PHENOTYPE. IN AIM 1, WE WILL DETERMINE THE CELL CYCLE BEHAVIORS OF RGCS IN NMD KNOCKOUT MICE QUALITATIVELY AND QUANTITATIVELY AND UNVEIL THE UNDERLYING REGULATORY MECHANISMS. IN AIM 2, WE WILL DETERMINE THE LINEAGE PROGRESSION OF RGCS AND THE RESULTING NEURONAL OUTPUTS PER TIME UNIT IN NMD KNOCKOUT MICE. BY CHARACTERIZING THESE MOLECULAR CELLULAR DEFECTS, WE ALSO AIM TO PROVIDE MECHANISTIC INSIGHTS TO TRANSCRIPTOMIC REGULATION OF RGC’S LINEAGE TRANSITIONS. NMD MAY REGULATE CELL FATES EITHER INDEPENDENT OF CELL CYCLE CONTROLS OR AS THE CONSEQUENCE OF AFFECTING THE CELL CYCLE. IN AIM 3, WE WILL TEST THESE TWO HYPOTHESES AND LEVERAGE OUR RESULTS TO REEXAMINE THE RELATIONSHIP BETWEEN CELL CYCLE AND CELL FATE. SUCCESSFUL COMPLETION OF THESE STUDIES WILL PROVIDE FUNDAMENTAL INSIGHTS INTO HOW SELECTIVE MRNA STABILITY UNDERLIES THE HIGHLY REGULATED CORTICAL NEUROGENESIS PROCESS IN THE MAMMALIAN BRAIN. THE PROPOSED STUDIES WILL ALSO SHED LIGHT ON SOME FUNDAMENTAL QUESTIONS ABOUT THE CONTROL OF CELL CYCLE, CELL FATE, AND THEIR RELATIONSHIP DURING NEURAL DEVELOPMENT.

THE ROLE OF HOST ENDOGENOUS SMALL RNAS IN INNATE IMMUNITY

INTEGRATION OF A DER MANAGEMENT SYSTEM IN RIVERSIDE

GRADUATE RESEARCH FELLOWSHIP PROGRAM

TYROSINE PHOSPHATASE REGULATION OF MUCOSAL MACROPHAGE-EPITHELIAL CELL CROSS-TALK

EQUIPMENT PURCHASE

DEFINING THE RETROGRADE PLASTID-TO-NUCLEUS STRESS SIGNALING PATHWAY

PROJECT ADELANTE MOVING FORWARD

MOLECULAR IMPROVEMENT OF BACTERIAL MOSQUITO LARVICIDES

GENE EXPRESSION IN PEYER'S PATCH FAE DEVELOPMENT

TAS::89 0227::TAS RECOVERY ACT-HIGH ENERGY PHYSICS

STUDY OF MATERIALS AND INTERFACE PROPERTIES FOR HIGH-EFFICIENCY SPIN INJECTION

COMBINATION TREATMENT OF ISCHEMIC STROKE WITH PERLECAN DV AND NEURAL STEM CELLS

RNA REGULATION OF INTRINSICALLY-DETERMINED NEURONAL PROPERTIES

IMPACT OF IMMUNE SENESCENCE ON HERPES ZOSTER IN A NONHUMAN PRIMATE MODEL

FUNCTION AND MECHANISM OF THE MAMMALIAN RNA INTERFERENCE RESPONSE TO VIRUS INFECTION

RESEARCH-PGR: IMPACT OF TRANSPOSABLE ELEMENT BURSTS ON THE RICE GENOME AND EPIGENOME -MECHANISMS THAT DIVERSIFY GENOMES, AT BOTH THE SEQUENCE AND EPIGENETIC LEVELS, UNDERLIE PHENOTYPIC VARIATION. WITH ACCELERATED CLIMATE CHANGE, IT IS ESSENTIAL THAT MECHANISMS DIVERSIFYING CROP GENOMES BE UNDERSTOOD AND APPLIED TO FEED FUTURE GENERATIONS. MOST PLANT AND ANIMAL GENOMES ARE DERIVED FROM TRANSPOSABLE ELEMENTS (TES), MOBILE FRAGMENTS OF DNA THAT OFTEN INCREASE IN COPY NUMBER AS THEY TRANSPOSE FROM ONE GENOMIC LOCUS TO ANOTHER. THE ABILITY OF TES TO INSERT NEAR GENES AND ALTER THEIR REGULATION AND TO PROMOTE GENOMIC REARRANGEMENTS AND EPIGENETIC CHANGES HAS RECENTLY BEEN RECOGNIZED AS A SIGNIFICANT CONTRIBUTOR TO ADAPTIVE EVOLUTION. STATED SIMPLY, TES CAN SHAKE UP OTHERWISE (STRUCTURALLY) CONSERVATIVE GENOMES. THIS PROJECT EXPLOITS LONG READ DNA SEQUENCING TECHNOLOGY AND SINGLE CELL EPIGENETIC ANALYSES TO REVEAL HOW THE RAPIDLY AMPLIFYING TE CALLED MPING ALTERS, IN REAL TIME, THE RICE GENOME, WHILE AVOIDING HOST (EPIGENETIC) SILENCING AND MUTAGENIC INSERTIONS. WITH RESPECT TO BROADER IMPACTS, THIS PROJECT ALSO ADDRESSES A CRISIS IN THE AGRICULTURAL WORKFORCE, WHICH IS THE OLDEST AND LEAST DIVERSE AMONG THE SCIENCES, BY INTRODUCING UNDERGRADUATES AT A HISPANIC SERVING INSTITUTION TO THE EXCITEMENT OF PLANT GENOMICS THROUGH AUTHENTIC RESEARCH EXPERIENCES FOR UP TO 2000 INCOMING STUDENTS/YEAR. THE RESEARCH GOALS OF THIS PROJECT ARE TWO-FOLD. THE FIRST IS TO UNDERSTAND THE TOTALITY OF STRUCTURAL GENOMIC VARIATION GENERATED IN THREE RECOMBINANT INBRED (RI) POPULATIONS BY THE MASSIVE AMPLIFICATION OF THE RICE TE FAMILY PING/MPING. BASED ON PRIOR RESULTS, IT IS ANTICIPATED THAT AT LEAST 50,000 ADDITIONAL MPING INSERTION SITES [WITH ~15% IN ACCESSIBLE CHROMATIN REGIONS (ACRS)] AND NUMEROUS STRUCTURAL VARIANTS (SVS) INCLUDING COPY NUMBER AND PRESENCE ABSENCE VARIANTS AND INVERSIONS WILL BE IDENTIFIED. THE SECOND GOAL IS TO DETERMINE THE CONSEQUENCES OF A SUBSET OF THESE LESIONS ON EPIGENETIC REGULATION AND REPRODUCTIVE ISOLATION BY GENERATING A RICE SINGLE CELL CIS-REGULATORY ATLAS AND ASSESSING THE IMPACT OF MPING INSERTS IN TARGETED RI LINES. WHILE THE VAST MAJORITY OF THE ~50,000 DE NOVO MPING INSERTIONS MAY BE NEUTRAL OR ELIMINATED BY SELECTION OVER EVOLUTIONARY TIME, IN THE SHORT TERM THEY WILL PROVIDE AN INVALUABLE TOOL TO EVALUATE THE FUNCTION OF ACRS MORE QUICKLY AND FOR FAR LESS COST THAN ANY OTHER METHOD CURRENTLY AVAILABLE. RESULTS OF THIS PROJECT WILL REVEAL THE POTENTIAL OF RAPID TE AMPLIFICATION TO RESHAPE THE EPIGENOME, LEAD TO REPRODUCTIVE ISOLATION, AND, FOR SVS, TO RAPIDLY GENERATE THE GENOMIC VARIATION THAT UNDERLIES PANGENOMES. ALL DATA GENERATED BY THIS PROJECT WILL BE MADE AVAILABLE THROUGH DEPOSITION AT ESTABLISHED LONG-TERM SEQUENCE REPOSITORIES SUCH AS THE NCBI SHORT READ ARCHIVE (SRA) AND GENE EXPRESSION OMNIBUS (GEO). 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.

MECHANISM OF NUCLEUS-TO-PLASTID LIGHT SIGNALING IN CONTROLLING PLASTID TRANSCRIPTION

MEMBRANE STEROID HORMONE TRANSPORTERS IN DEVELOPMENT AND REPRODUCTION

MOLECULAR MAYHEM: IMMUNE MODULATION AND EICOSANOID SIGNALING DURING INFECTION

SIGNALING TO CELL INTERCALATION IN ARABIDOPSIS

LIPOCALIN-2 IN HIV-ASSOCIATED NEURONAL INJURY

NORADRENERGIC MODULATION OF SENSORY PERCEPTION

COOPERATIVE AGREEMENT TO DEVELOP NANO MATERIALS & NANO DEVICES (CNN V)

BIOLOGICAL CONSEQUENCES AND REPAIR OF ALKYLATED THYMIDINE LESIONS

WEARABLE NANOSENSOR ARRAY FOR REAL-TIME MONITORING OF DIESEL AND GASOLINE EXHAUST

CAVEOLIN-1 CONTRIBUTES TO THE LONG-TERM FUNCTION AND STRUCTURE OF THE NEUROVASCULAR UNIT AFTER JUVENILE CONCUSSION - SUMMARY PROJECT THE MAJORITY OF TRAUMATIC BRAIN INJURY (TBI) IS MILD IN NATURE BUT IS KNOWN TO ELICIT LONG-TERM CONSEQUENCES, INCLUDING EMERGENCE OF DEMENTIA AND ACCELERATED AGE-RELATED DECLINES. THE HIGHEST-AT-RISK GROUP ARE CHILDREN WHOSE BRAINS ARE STILL UNDERGOING DEVELOPMENT. THIS PROPOSAL WILL INVESTIGATE THE SHORT- AND LONG-TERM, CELLULAR AND MOLECULAR CHANGES IN THE BRAIN FOLLOWING JUVENILE MTBI (JMTBI) WITH THE GOAL TO INTELLIGENTLY DEVELOP NEW THERAPEUTIC OPTIONS. CAVEOLIN-1 (CAV-1) IS AN ABUNDANT STRUCTURAL PROTEIN INVOLVED IN CAVEOLAE FORMATION AND CELL SIGNALING WHICH IS EXPRESSED IN CEREBRAL ENDOTHELIAL CELLS AND IN ASTROCYTES, KEY COMPONENTS OF THE NEUROVASCULAR UNIT (NVU). RECENT DEVELOPMENT OF A COMPOUND TO TARGET THE CAVEOLIN SCAFFOLDING DOMAIN (CSD), A COMPLEX THAT COMPARTMENTALIZES STRUCTURAL PROTEINS (E.G. CLAUDIN-5) AND SIGNALING MOLECULES (E.G. ENOS), HAS PROVIDED TOOLS TO EXPLORE THE ROLE OF CAV-1 IN ACQUIRED NEUROLOGICAL DISEASE. AFTER STROKE, WE FOUND INCREASED CAV-1 EXPRESSION AND CAV-AP TREATMENT WAS BENEFICIAL FOR POST-INJURY RECOVERY. HOWEVER, CONSENSUS IS LACKING WHETHER CAV-1 EXHIBITS BENEFICIAL OR DELETERIOUS ACTIONS IN OTHER ACQUIRED BRAIN DISORDERS, SUCH AS JMTBI. OUR MODEL OF JMTBI EXHIBITS ACCELERATED LOSS OF COGNITION ASSOCIATED WITH DECREASED VASCULAR FUNCTION OVER THEIR LIFESPAN. WE THEREFORE WILL TEST THE HYPOTHESIS THAT DYSFUNCTION IN NEUROVASCULAR COUPLING AFTER JMTBI CAN BE PREVENTED BY MODULATION OF CAV-1 SIGNALING, BLUNTING ACCELERATED HIPPOCAMPAL AND CORTICAL AGING. AIM 1 WILL DEMONSTRATE THAT CAV-1 IS CRITICAL FOR MAINTAINING NVU FUNCTIONALITY. WE EXAMINE THE ROLE OF VASCULAR CAV-1 IN MALE & FEMALE JMTBI MICE IN NORMAL (WT), VASCULAR CAV-1 DEFICIENT MICE (CAV-1-/-) AND IN CAV-AP TREATED MICE. WE BELIEVE THAT JMTBI MICE TREATED WITH CAV-AP WILL EXHIBIT VASCULAR RECOVERY, WHEREAS THE LOSS OF CAV-1 WILL WORSEN NVU OUTCOMES. IN AIM 2 WE WILL EXAMINE HOW CAV- 1 IN REACTIVE ASTROCYTE PROCESSES INFLUENCES PROGRESSION OF JMTBI. WE WILL MODULATE CAV-1 EXPRESSION DIRECTLY IN ASTROCYTES BY INJECTING AAV-GFAP-CAV-1-SHRNA AND AAV-GFAP-SYNCAV-1 IN CONTROL AND INJURED MICE AND QUANTIFY VASCULAR RECOVERY AND BEHAVIORAL OUTCOMES. INCREASED ASTROCYTIC CAV-1 WILL BE ASSOCIATED WITH IMPROVED NVU PROPERTIES AND COGNITIVE OUTCOMES. IN AIM 3 WE WILL EXAMINE MALE & FEMALE MICE OVER THEIR LIFESPAN AND EXAMINING IF INCREASED CAV-1 BLUNTS ACCELERATED BRAIN AGING THAT WE HAVE OBSERVED AFTER JMTBI. WE WILL ASSESS BEHAVIORAL, NEUROIMAGING AND HISTOLOGICAL OUTCOMES. JMTBI MICE TREATED WITH CAV-AP WILL EXHIBIT IMPROVED OUTCOMES RELATED TO ENHANCED NVU FUNCTION AND INTEGRITY. IN SUM, THE PROPOSED RESEARCH IS A CRITICAL FIRST STEP IN EXAMINING THE ROLE OF CAV-1 IN JMTBI AND IF THERAPEUTIC INTERVENTION CAN LEAD TO ENHANCED NVU STABILITY AND FUNCTION AND THEREBY MODERATE ACCELERATED AGING.

CROSS-KINGDOM RNA COMMUNICATIONS BETWEEN PLANT AND FUNGAL PATHOGENS

THE REGULATION AND FUNCTION OF NEURON-SPECIFIC ALTERNATIVE SPLICING

MARC AT UNIVERSITY OF CALIFORNIA RIVERSIDE - PROJECT SUMMARY THE UNIVERSITY OF CALIFORNIA RIVERSIDE (UCR) IS ONE OF THE MOST DIVERSE CAMPUSES IN THE NATION AND IS IN ONE OF THE MOST RAPIDLY GROWING AND DIVERSE REGIONS OF THE U.S. MOST UNDERGRADUATE STUDENTS AT UCR COME FROM THIS REGION AND ARE FROM UNDERREPRESENTED GROUPS IN THE SCIENCES. THUS, THERE IS A BROAD BASE OF UNDERREPRESENTED (UR) STUDENTS FROM WHICH TO SELECT AND PROMOTE INTEREST IN A RESEARCH CAREER IN BIOMEDICAL OR BEHAVIORAL SCIENCES. THE MAIN GOAL OF THE MARC PROGRAM AT UCR IS TO INCREASE THE NUMBER OF UR STUDENTS PURSUING PHD DEGREES AND RESEARCH CAREERS IN THE BIOMEDICALLY-RELATED SCIENCES. THIS TRAINING GRANT PROVIDES A SUMMER PRE-MARC DEVELOPMENT PROGRAM (9-10 STUDENTS/YEAR) TO INCREASE THE ELIGIBLE POOL OF STUDENTS FOR THE RESEARCH TRAINEE PROGRAM (16 POSITIONS/YEAR; 2-3 YEARS OF TRAINING). THE OBJECTIVES OF THE PROGRAM ARE: (1) INCREASE THE NUMBER OF UCR MINORITY STUDENTS MAJORING IN THE SCIENCES WHO ARE QUALIFIED TO BECOME MARC TRAINEES THROUGH OUTREACH TO LOCAL HIGH SCHOOLS AND COMMUNITY COLLEGES. (2) INCREASE THE NUMBER OF QUALIFIED STUDENTS WHO APPLY TO THE MARC PROGRAM BY USING FRESHMAN COURSES AND DISCOVERY SEMINARS, BY SYNERGIZING WITH HONORS AND EXISTING MINORITY PROGRAMS ON CAMPUS, AND BY ENGAGING STUDENTS IN PRE-MARC UNDERGRADUATE RESEARCH BEFORE THEIR SOPHOMORE YEAR AND STIMULATING THEIR INTEREST IN A BIOMEDICAL RESEARCH CAREER. (3) THE CORE OF THE PROGRAM IS PREPARING THE MARC TRAINEES FOR GRADUATE STUDIES IN HIGHLY COMPETITIVE RESEARCH INSTITUTIONS. WE WILL ACHIEVE THIS BY IMMERSING MARC TRAINEES IN INTENSIVE CUTTING-EDGE RESEARCH IN LABORATORIES OF FACULTY MENTORS ON CAMPUS DURING THE ACADEMIC YEAR AND IN ONE OTHER OFF-CAMPUS LABORATORY AT A HIGH-CALIBER RESEARCH INSTITUTION DURING ONE SUMMER; WE WILL ALSO PROVIDE SPECIFIC CLASSES THAT WILL PREPARE THE TRAINEES TO THINK CRITICALLY, TO DESIGN AND IMPLEMENT RIGOROUS AND ETHICAL EXPERIMENTS, TO LEARN MODERN RESEARCH METHODS, TO WRITE SCIENTIFIC REPORTS/PAPERS AND FELLOWSHIPS, AND TO BE EFFICIENT COMMUNICATORS IN FRONT OF EXPERT AND LAY AUDIENCES. GUIDANCE IN APPLYING TO GRADUATE PROGRAMS WILL BE PROVIDED. THIS WILL GIVE SELF-CONFIDENCE AND PREPARE THE TRAINEES TO ENTER AND SUCCEED IN THE MOST COMPETITIVE GRADUATE PROGRAMS IN THE U.S. THIS PROGRAM IS FOR 5 YEARS AND PROPOSES TO TRAIN ABOUT 48 MARC STUDENTS WITH THE GOAL THAT ABOUT 80% OF THEM WILL SUCCEED IN ENTERING HIGH QUALITY PHD OR MD/PHD PROGRAMS IN THE BIOMEDICAL SCIENCES. RELEVANCE: THIS MARC TRAINING GRANT WILL NOT ONLY CONTRIBUTE TO INCREASE THE NUMBER OF UR BIOMEDICAL SCIENTISTS BUT SHOULD ALSO HAVE BROADER IMPACTS. MARC SCHOLARS WILL BE ROLE MODELS THAT INSPIRE NEW GENERATIONS AND HELP BREAK DOWN DISCRIMINATORY BARRIERS.

INHIBITORY NETWORK PLASTICITY IN NEUROLOGICAL DISEASE - PROJECT SUMMARY: TEMPORAL LOBE EPILEPSY (TLE) DEVELOPS IN A THIRD OF OVER 300,000 PATIENTS AND LEAD TO LONG TERM MEMORY AND COGNITIVE DISORDERS WHICH IMPACT QUALITY OF LIFE. THE DENTATE GYRUS, A CIRCUIT SEVERELY IMPACTED IN HIPPOCAMPAL SCLEROSIS IN TLE, SERVES AS THE FIRST NODE IN THE FLOW OF CORTICAL INFORMATION TO THE HIPPOCAMPUS. THE DENTATE GYRUS IS A CRITICAL FOR EPISODIC MEMORY FUNCTION AND IS PROPOSED TO DISCRIMINATE HIGHLY SIMILAR INPUTS THROUGH A PROCESS KNOWN AS PATTERN SEPARATION, THE UNDERLYING MECHANISMS OF WHICH ARE NOT FULLY UNDERSTOOD. THE DENTATE RECEIVES HIGHLY STRUCTURED INPUTS WITH LATERAL ENTORHINAL CORTICAL PROJECTIONS WITH CONTENT OR OBJECT RELATED INFORMATION TARGETING THE DISTAL DENDRITES OF THE GRANULE CELLS THROUGH THE LATERAL PERFORANT PATH AND SPATIAL AND CONTEXTUAL INFORMATION FROM THE MEDIAL ENTORHINAL CORTEX REACHING THE MIDDLE DENDRITES THROUGH THE MEDIAL PERFORANT PATH. HOWEVER, THE CIRCUIT MECHANISMS UNDERLYING HOW THESE INPUTS STREAMS ARE PROCESSED TO DISCRIMINATE SUBTLE DIFFERENCES IN EACH MODALITY, HOW THEY ARE ASSOCIATED TO FORM EPISODIC MEMORY REPRESENTATIONS AND THEIR CONTRIBUTION TO DENTATE ELECTRICAL ACTIVITY PATTERNS ASSOCIATED MEMORY CONSOLIDATION AND RECALL ARE NOT KNOWN. WE PROPOSE THAT INPUT SPECIFIC RECRUITMENT OF INHIBITORY NEURONS AND THEIR LAYER SPECIFIC INHIBITION OF GRANULE CELL DENDRITES IS CRITICAL FOR THE ABILITY OF THE DENTATE TO DECORRELATE DISTINCT INPUT STREAMS. SINCE DENDRITE TARGETING DENTATE INTERNEURON SUBTYPES UNDERGO EXTENSIVE STRUCTURAL AND FUNCTIONAL PLASTICITY IN EPILEPSY, WE FURTHER PROPOSE THAT SEIZURE INDUCED CHANGES IN DENDRITIC INHIBITION COMPROMISE INPUT SPECIFIC RECRUITMENT OF INHIBITION AND UNDERMINE INPUT OUTPUT TRANSFORMATIONS. COMBINING ELECTRO- AND OPTOPHYSIOLOGY IN EX VIVO SLICES FROM TRANSGENIC MICE SUBJECT TO EXPERIMENTAL EPILEPSY AND BEHAVIORAL AND MULTISITE RECORDINGS WITH OPTOGENETIC INTERROGATION WILL ALLOW US TO ADDRESS THESE QUESTIONS. AIM 1 WILL DEVELOP A FUNDAMENTAL UNDERSTANDING OF INPUT SPECIFIC AND RECRUITMENT, AND FREQUENCY DEPENDENT DYNAMICS OF DENTATE INTERNEURON SUBTYPES AND HOW IT IS ALTERED IN EPILEPSY. AIM 2 WILL DETERMINE THE ROLE OF SOMATIC AND DENDRITIC INHIBITION IN DENTATE DECORRELATION OF LAYER SPECIFIC INPUTS AND THEIR TRANSFORMATIONS IN EPILEPSY AT THE CIRCUIT LEVEL. FINALLY, AIM 3 WILL EXAMINE DETERMINE THE ROLE OF INHIBITORY NEURON SUBTYPES TO BEHAVIORAL SPATIAL AND OBJECT DISCRIMINATION AND ELECTRICAL CORRELATES OF DENTATE MEMORY PROCESSING IN CONTROL AND EPILEPTIC MICE. IN LINE WITH THE PROPRIETIES ESTABLISHED IN THE 2021 AES/NINDS EPILEPSY RESEARCH BENCHMARKS, THESE STUDIES WILL ADDRESS MECHANISMS UNDERLYING NEUROPSYCHIATRIC COMORBIDITIES IN EPILEPSY AND IS OF BROADER RELEVANCE TO UNDERSTANDING MEMORY PROCESSING AND DECLINE IN AGEING AND ALZHEIMER’S DISEASE.

ORIGIN OF THE INNATE IMMUNITY SUPPRESSION CAUSED BY NAIROVIRUS' PROTEASE ACTIVITY

REGULATION OF VITELLOGENIC GENES IN THE MOSQUITO

SMALL MOLECULE SIGNALING IN REGULATION OF GUT MICROBIOTA STRUCTURE AND COLONIZATION RESISTANCE - PROJECT SUMMARY THE COMMUNITY OF COMMENSAL MICROBES IN THE GUT, THE GUT MICROBIOTA, PARTICIPATES IN NUMEROUS PROCESSES KEY FOR HUMAN HEALTH, INCLUDING PROTECTION AGAINST FOREIGN MICROORGANISMS. A GREATER MECHANISTIC UNDERSTANDING OF HOW THE GUT MICROBIOTA RESISTS THE INVASION OF FOREIGN BACTERIA, FROM PATHOGENS TO NEW COMMENSAL MICROORGANISMS, IS ESSENTIAL BOTH FOR THE CONTROL OF INFECTION AND IN TARGETED APPROACHES FOR MICROBIOTA MANIPULATION. OUR WORK HAS SHOWN THAT INTERPERSONAL DIFFERENCES IN THE GUT MICROBIOTA ARE AN IMPORTANT DRIVER OF OUTCOME OF INFECTION BY VIBRIO CHOLERAE, THE ETIOLOGIC AGENT OF CHOLERA, A DEVASTATING DIARRHEA AFFECTING MILLIONS OF PEOPLE EACH YEAR WORLDWIDE. AS A GENETICALLY TRACTABLE MODEL ORGANISM FOR EXAMINING INVASION OF THE GUT MICROBIAL COMMUNITY, STUDIES WITH V. CHOLERAE ALLOW FOR MECHANISTIC EXAMINATION OF MICROBIAL COLONIZATION AND INTER-BACTERIAL INTERACTION AND COMPETITION IN THE GASTROINTESTINAL TRACT. WE HAVE SHOWN THAT SMALL MOLECULE SIGNALING FACTORS, INCLUDING BACTERIAL QUORUM SENSING AUTOINDUCERS, AND MICROBIAL BILE AND DIET METABOLITES, MODULATES MICROBIOTA STRUCTURE AND IN TURN MULTIPLE PATHWAYS OF COLONIZATION RESISTANCE AGAINST V. CHOLERAE. THIS PROPOSAL AIMS TO DEFINE MOLECULAR MECHANISMS UNDERPINNING THE ABILITY OF DIVERSE HUMAN GUT COMMUNITIES TO DRIVE THE BIOCHEMICAL MILIEU OF THE GUT INTO COLONIZATION-RESISTANT OR SUSCEPTIBLE STATES, THUS SHAPING RESISTANCE AGAINST COLONIZATION OF BOTH PATHOGENS SUCH AS V. CHOLERAE AND NEW COMMENSALS. THE PROPOSED STUDIES AIM TO PROVIDE MECHANISTIC UNDERSTANDING FOR THE PROCESSES DRIVING ASSEMBLY OF GUT MICROBIAL COMMUNITIES AND IDENTIFY NEW TARGETS FOR PROPHYLACTIC AND THERAPEUTIC MANIPULATIONS OF THE GUT MICROBIOTA TO COMBAT INVADING MICROORGANISMS.

HOW LC INTEGRITY IN OLDER ADULTS MEDIATES PERCEPTUAL AND MEMORY PROCESSES - PROJECT SUMMARY THE OVERARCHING GOAL OF THE PRESENT PROPOSAL IS TO UNDERSTAND HOW INDIVIDUAL DIFFERENCES IN THE STRUCTURE AND FUNCTION OF LOCUS COERULEUS (LC) MODERATE PERCEPTION AND MEMORY IN AN OLDER ADULT POPULATION. THERE IS SUBSTANTIAL EVIDENCE THAT THE LC CIRCUIT PLAYS A CENTRAL ROLE IN COGNITIVE PROCESSES AND NEURONAL LOSS IN LC IS KNOWN TO OCCUR IN NEURODEGENERATIVE DISORDERS SUCH AS ADRD AND PD. INTEGRITY OF LC NEURONS IS HYPOTHESIZED TO MEDIATE THE PRESERVATION OF COGNITIVE ABILITIES DURING NORMAL AGING AS WELL. TO DATE, HOWEVER, THERE EXISTS A DEARTH OF RESEARCH THAT EITHER CHARACTERIZES DIFFERENTIAL EFFECTS OF LC INTEGRITY OR DETAILS RELATIONSHIPS BETWEEN LC INTEGRITY AND COGNITIVE FUNCTION IN OLDER ADULT HUMANS. MORE GENERALLY, THE LINK BETWEEN LC ACTIVITY AND COGNITIVE PROCESSES HAS NOT BEEN WELL CHARACTERIZED IN HUMANS. HISTORICAL REASONS FOR THIS IS THAT THE LC HAS BEEN DIFFICULT TO IMAGE DUE TO ITS SMALL SIZE AND THUS MOST HUMAN RESEARCH MAKES INFERENCES ABOUT LC FUNCTION BY USING PUPIL DILATION AS A SURROGATE MEASURE. TO OVERCOME EXISTING LIMITATIONS IN THE FIELD, WE PROPOSE A SERIES OF DETAILED PSYCHOPHYSICAL AND MRI-BASED STUDIES IN OLDER ADULTS AIMED TO CHARACTERIZE HOW LC STRUCTURE AND FUNCTION MODERATES BEHAVIOR AND IN TURN HOW THIS IS MEDIATED BY ACTIVITY IN INTERMEDIATE BRAIN REGIONS KNOWN TO BE INVOLVED IN PERCEPTUAL AND MEMORY PROCESSES. WE FURTHER PROPOSE COMPUTATIONAL APPROACHES TO CHARACTERIZE INDIVIDUAL DIFFERENCES IN HOW LC CIRCUIT INTEGRITY RELATES TO DIFFERENT PATTERNS OF COGNITIVE PERFORMANCE ACROSS TASKS, AND ADVANCED NEUROIMAGING METHODS TO LOCALIZE AND IMAGE THE LC, WHICH HAVE BEEN PIONEERED BY OUR GROUP. USING MRI-BASED METHODS, WE WILL EXAMINE LC INTEGRITY USING HIGH-RESOLUTION NEUROMELANIN-SENSITIVE STRUCTURAL IMAGING, TRACTOGRAPHY AND FUNCTIONAL CONNECTIVITY. THIS APPROACH WILL ALLOW US TO IDENTIFY CANDIDATE BIOMARKERS OF LC CIRCUIT INTEGRITY. WE WILL USE A SERIES OF WITHIN-SUBJECT DESIGNS WHERE WE MANIPULATE LC ACTIVITY AND EXAMINE WHETHER RELATIONSHIPS BETWEEN LC AND BEHAVIOR AND BRAIN REGIONS THOUGHT TO MEDIATE THOSE BEHAVIORS ARE CONSISTENT OR NOT BETWEEN DIFFERENT PERCEPTUAL MODALITIES AND MEMORY TASKS. OVERALL THIS STUDY WILL PROVIDE AN IMPORTANT AND MUCH NEEDED UNDERSTANDING OF HOW LC INTEGRITY UNDERLIES COGNITIVE DECLINES IN OLDER ADULTS. BY COMBINING ADVANCED NEUROIMAGING, WELL-CONTROLLED BEHAVIORAL ASSESSMENT, AND COMPUTATIONAL ANALYSIS, WE EXPECT TO UNCOVER PREVIOUSLY INACCESSIBLE IN VIVO MECHANISMS OF LC MODULATION AND GENERATE A UNIQUE DATASET TO ADDRESS FUNDAMENTAL MECHANISTIC QUESTIONS OF HOW THE LC INTEGRITY MODERATES COGNITION, HOW THIS VARIES ACROSS OLDER ADULTS AND THE EXTENT TO WHICH RELATIONSHIPS BETWEEN LC AND COGNITION ARE GENERALIZED OR INDIVIDUALIZED TO PARTICULAR DOMAINS. THE RESULTING UNDERSTANDING OF LC CIRCUIT CAN HELP EXPLAIN HOW DYSFUNCTIONAL MODULATORY CIRCUITS MAY GENERATE COGNITIVE DECLINES OR BE IMPLICATED IN NORMAL AGING AND AGE- RELATED DISORDERS SUCH AS ALZHEIMER'S AND ALZHEIMER'S RELATED DISORDERS. THIS, IN TURN, HAS POTENTIAL TO SUPPORT NON-INVASIVE METHODS FOR DIAGNOSING PATHOLOGIES ASSOCIATED WITH LC DECLINE AND DEVELOPING NEW TREATMENTS.

SOLID STATE ELECTRONIC STRUCTURE AND PROPERTIES OF NEUTRAL CARBON-BASED RADICALS

UNDERSTAND AND DETECT SEPSIS: PATHOGEN ISOLATION, BIOCHEMISTRY ASSAY, AND OPTOFLUIDIC SENSING - PROJECT SUMMARY BACKGROUND: SEPSIS IS A LIFE-THREATENING EMERGENCY, NORMALLY CAUSED BY THE BODY’S RESPONSE TO A BACTERIAL INFECTION. WITHOUT EARLY TREATMENT, SEPSIS CAN LEAD TO SEPTIC SHOCK WITH APPROXIMATELY 50% MORTALITY RATE. RAPID AND ACCURATE DIAGNOSIS OF SEPSIS IS THE KEY TO DECREASE THE MORTALITY RATE. HOWEVER, THERE IS NO GLOBAL STANDARD FOR SEPSIS TESTING DUE TO THE INADEQUATE SENSITIVITY AND SPECIFICITY OF THE CURRENT TECHNOLOGIES. THE PI HAS THE AMBITION TO ADDRESS THE CRITICAL AND FAR-REACHING BOTTLENECKS SPECIFICALLY OF CONCERN IN SEPSIS TESTING: 1) A RAPID AND SIMPLE METHOD TO ISOLATE AND CONCENTRATE BACTERIA FROM WHOLE BLOOD SAMPLE, 2) A SENSITIVE AND ONE-STEP CRISPR MICROFLUIDIC CHIP TO DETECT THE NUCLEIC ACID BIOMARKERS OF THE PATHOGENS, AND 3) A MULTIPLEXING AND MINIATURIZED OPTOFLUIDIC WAVEGUIDE PLATFORM TO ENHANCE THE FLUORESCENCE BASED DETECTION. OVERVIEW OF THE LABORATORY: THE PI ESTABLISHED HIS OWN LAB AT RIT IN 2018. WITH THE OVERWHELM START-UP SUPPORT BY THE HOME DEPARTMENT, THE PI IS LEADING AN ACTIVE AND INTERDISCIPLINARY RESEARCH GROUP WITH 1 POSTDOC RESEARCHER, 4 PH.D. STUDENTS, 2 MASTER STUDENTS, AND A COUPLE OF UNDERGRADUATE STUDENTS. WITHIN 2 YEARS, THE LAB HAS PUBLISHED ~10 JOURNAL ARTICLES IN THE FIELDS OF BACTERIA/VIRUS ISOLATION, CRISPR BIOCHEMISTRY ASSAY, AND OPTOFLUIDIC SENSING. EXPLOITING INTERDISCIPLINARY APPROACH, THE LAB IS WORKING ON TECHNOLOGIES TO QUICKLY IDENTIFY ANTIMICROBIAL RESISTANT BACTERIA IN WHOLE BLOOD SAMPLE. AS MORE STRAINS BECOME RESISTANT TO AVAILABLE THERAPIES, THE RISK FOR PEOPLE DEVELOPING LIFE-THREATENING SEPSIS IS INCREASING. THE RESEARCH TOPIC WE ARE WORKING ON WILL BE THE KEY FOR CLINICIANS TO PROVIDE QUICK CLINICAL DECISIONS AND INCREASE THE CHANCES OF SURVIVALS. IN ADDITION, THE TECHNOLOGIES DEVELOPED IN OUR LAB WILL ALSO LAY THE FOUNDATION FOR THE DIAGNOSIS AND TREATMENT OF MANY DIFFERENT KINDS OF DISEASES SUCH AS CANCER, VIRAL INFECTION, AND NEUROLOGICAL DISEASES. GOALS FOR THE NEXT 5 YEARS: OUR FIRST GOAL IS TO DEVELOP A FULLY AUTOMATED NANODEVICE THAT CAN COLLECT AND CONCENTRATE BACTERIA FROM WHOLE BLOOD WITH A RETRIEVAL EFFICIENCY OF 99% AND A CONCENTRATION FACTOR OF 10,000. WE WILL BEGIN WITH SPIKED SAMPLE AND THEN PROCEED TO CLINICAL SAMPLE. LEVERAGING THE UNIQUE PROPERTIES OF NANOMATERIALS AND NANOSTRUCTURES, THE SECOND GOAL IS TO DEVELOP A ONE-STEP AND ISOTHERMAL CRISPR CHIP FOR LOW CONCENTRATION (1 CFU/ML) BACTERIA DETECTION WITHOUT FRONT END TARGET AMPLIFICATION. TOWARDS THE END OF THE FIFTH YEAR, WE WILL INTEGRATE THE SAMPLE PREPARATION CHIP AND THE CRISPR DETECTION CHIP AS A SINGLE AND COMPACT UNIT FOR THE TESTING OF CLINICAL SAMPLES. THE THIRD GOAL IS TO DEVELOP A LIQUID-CORE, SUPERHYDROPHOBIC NANOSTRUCTURE CLADDING WAVEGUIDE PLATFORM FOR MULTIPLEXING BACTERIA DETECTION. THE HIGH FLUORESCENCE COLLECTION EFFICIENCY WILL ENABLE SENSITIVE SEPSIS DETECTION WITH MICROLITER LEVEL SAMPLE CONSUMPTION. OVERALL VISION OF THE RESEARCH PROGRAM: THE TECHNOLOGIES WE ARE DEVELOPING WILL HAVE A BROAD IMPACT TO THE BIOMEDICAL RESEARCH COMMUNITIES TO UNDERSTAND AND ENGINEERING SMALL MOLECULES, CELLS, AND TISSUES. THE PROPOSED WORK WILL ALSO ADVANCE DISEASE DIAGNOSIS, PREVENTION, AND TREATMENT.

RELM-ALPHA REGULATION OF HOOKWORM-INDUCED LUNG INFLAMMATION

BALANCE BETWEEN HNF4A ISOFORMS IN THE CARBOHYDRATE-LIPID METABOLIC SWITCH - ABSTRACT HEPATOCYTE NUCLEAR FACTOR 4A (HNF4A), A MASTER REGULATOR OF LIVER-SPECIFIC GENE EXPRESSION, IS REGULATED BY TWO PROMOTERS (P1 AND P2) WHICH DRIVE EXPRESSION OF TWO GROUPS OF HNF4A ISOFORMS REFERRED TO AS HNF4A1 AND HNF4A7. HNF4A IS A KNOWN REGULATOR OF GLUCONEOGENESIS AND MUTATED IN MATURITY ONSET DIABETES OF THE YOUNG ONE (MODY1). CONVENTIONALLY, IT WAS THOUGHT THAT HNF4A1, BUT NOT HNF4A7, IS EXPRESSED IN THE NORMAL ADULT LIVER, WHILE HNF4A1 IS DOWNREGULATED AND HNF4A7 IS UPREGULATED IN LIVER CANCER. NOW, RESEARCH IN OUR LAB REVEALS A PREVIOUSLY UNDESCRIBED ROLE FOR HNF4A7 IN THE NORMAL ADULT MOUSE LIVER – ONE INVOLVED IN THE DIURNAL VARIATIONS OF LIPID AND CARBOHYDRATE METABOLISM. MORE SPECIFICALLY, HNF4A1 APPEARS TO BE A MAJOR DRIVER OF GLUCONEOGENESIS WHILE HNF4A7 IS A DRIVER OF KETOGENESIS: WE PROPOSE THAT ALTERATIONS IN THE LEVELS OF THE HNF4A ISOFORMS DURING THE DAY FLIP THE MOLECULAR SWITCH BETWEEN THE TWO. OUR PRELIMINARY DATA ALSO SHOW THAT HNF4A7 IS REQUIRED FOR INCREASED LEVELS OF CIRCULATING KETONE BODIES IN FEMALE MICE. AMP-ACTIVATED PROTEIN KINASE (AMPK), AN ENERGY-SENSING ENZYME, HAS BEEN SHOWN TO PHOSPHORYLATE HNF4A1 IN VITRO, BUT EFFECTS IN VIVO AND ON HNF4A7 ARE NOT KNOWN. SIRT1 IS A DEACETYLASE THAT WORKS WITH AMPK TO REGULATE GLUCOSE AND LIPID METABOLISM. HNF4A1 IS KNOWN TO BE ACETYLATED AND OUR PRELIMINARY DATA SUGGEST THAT HNF4A7 BUT NOT HNF4A1 INTERACTS WITH SIRT1. HERE, WE PROPOSE TO USE HNF4A1-EXPRESSING (A1HMZ) AND HNF4A7-EXPRESSING EXON SWAP MICE (A7HMZ) TO DETERMINE THE PHYSIOLOGICAL FUNCTION OF THE HNF4A ISOFORMS IN THE SWITCH BETWEEN GLUCONEOGENESIS AND KETOGENESIS, AND TO CHARACTERIZE THE IMPACT OF SEX ON THOSE FUNCTIONS. IN AIM 1, WE WILL DETERMINE WHETHER INTERMITTENT FASTING AND A KETOGENIC DIET INCREASE THE LEVELS OF HNF4A7 IN THE LIVER, AND WHETHER THE INCREASE OCCURS IN ALL HEPATOCYTES, OR JUST A SUBSET. WE WILL DETERMINE THE CONSEQUENCES OF HNF4A7 ON GENE EXPRESSION. KIDNEY AND INTESTINES WILL ALSO BE EXPLORED. IN AIM 2, WE WILL DETERMINE WHETHER THE AMPK PATHWAY ACTS IN A DIFFERENTIAL FASHION ON THE HNF4A ISOFORMS TO HELP FLIP THE METABOLIC SWITCH. PHOSPHORYLATION BY AMPK AND DEACETYLATION BY SIRT1 WILL BE EXPLORED. FINALLY, IN AIM 3, WE WILL DETERMINE WHETHER THE ESTROGEN PATHWAY IMPACTS THE HNF4A ISOFORMS IN FEMALE MICE AND DETERMINE THE CONSEQUENCES FOR THE METABOLIC SWITCH. OUR COMPELLING PRELIMINARY DATA THAT THE HNF4A ISOFORMS ARE INVOLVED IN THE SWITCH BETWEEN GLUCONEOGENESIS AND KETOGENESIS SHED NEW LIGHT ON THIS BASIC METABOLIC PROCESS THAT OCCURS ON A DAILY BASIS AND UNDER CONDITIONS OF FEEDING AND FASTING. THE RESULTS FROM THIS PROPOSAL WILL ILLUMINATE NOT ONLY THE MOLECULAR MECHANISM UNDERLYING THE SWITCH BUT ALSO HOW THAT MECHANISM IS IMPACTED BY SEX. THE PROPOSED STUDIES HAVE THE POTENTIAL TO IMPACT OUR UNDERSTANDING OF NUMEROUS METABOLIC DISEASES, INCLUDING DIABETES, OBESITY, FATTY LIVER DISEASE AND CANCER. FINALLY, GIVEN THE FACT THAT KETONE BODIES SERVE AS A SOURCE OF FUEL FOR THE BRAIN, OUR RESULTS COULD HAVE A BROADER IMPACT, INCLUDING ON NEUROLOGICAL DISEASES, SUCH AS DEMENTIA.

CONNECTING CLASSROOMS TO CONGRESS: FOSTERING INFORMED CIVIC ENGAGEMENT VIA ONLINE DELIBERATIVE TOWN HALLS

THIS EDA INVESTMENT FUNDS THE OASIS ACCELERATOR: INLAND EMPIRE ENTREPRENEURSHIP ECOSYSTEM DEVELOPMENT PROJECT, TO HELP SCALE AND GROW SUSTAINABILITY-FOCUSED TECHNOLOGY START-UPS IN THE COASTAL SOUTHERN CALIFORNIA REGION. THE OASIS ACCELERATOR, BASED AT THE UNIVERSITY OF CALIFORNIA RIVERSIDE, WILL CREATE AN INTERCONNECTED NETWORK OF TEST BEDS AND DOMAIN EXPERTS TO ADMINISTER RESEARCH AND DEMONSTRATION PROJECTS, AS WELL AS INVEST IN STARTUP ADVOCATES TO SERVE AS BUSINESS AND TECHNICAL EXPERTS TO START-UP COMPANIES. THE OASIS ACCELERATOR WILL ALSO CONVENE A "GREEN TEAM" FOCUSED ON CONNECTING CLEAN/SMART START-UPS WITH BUSINESS ATTRACTION PACKAGES AND PLANS TO BUILD A DIVERSE SKILLED TALENT POOL IN THE TECHNOLOGY-ENABLED SUSTAINABILITY SECTOR. ONCE IMPLEMENTED, NEW RESEARCH PROJECTS AND BUSINESS ACTIVITY ADMINISTERED BY THE OASIS ACCELERATOR WILL ACCELERATE THE ESTABLISH OF A SUSTAINABILITY-FOCUSED INNOVATION ECOSYSTEM IN THE COASTAL SOUTHERN CALIFORNIA REGION.

DECODE: DATA-DRIVEN EXASCALE CONTROL OF OPTICALLY DRIVEN EXCITATIONS IN CHEMICAL AND MATERIAL SYSTEMS

THE OVERARCHING GOAL IS TO CREATE A CRITICAL MINERALS ANALYTICAL FACILITY AT UC RIVERSIDE (UCR) AND THE PALM DESERT CAMPUS OF UCR (UCR PD) TO MEET THE NEEDS OF THE EMERGING LITHIUM (LI) INDUSTRY IN THE SALTON SEA REGION OF THE IMPERIAL VALLEY, INCLUDING TRAINING OF A WORKFORCE.

SCALE-UP DEMONSTRATION OF HYBRID CATALYTIC BIOREFINING OF BIOMASS TO SUSTAINABLE AVIATION AND MARINE FUELS

THE COMPUTING SCHOLARS EXPERIENCE LAB PROGRAM -THIS PROJECT WILL CONTRIBUTE TO THE NATIONAL NEED FOR WELL-EDUCATED COMPUTING PROFESSIONALS BY SUPPORTING THE RETENTION AND GRADUATION OF HIGH-ACHIEVING, LOW-INCOME STUDENTS WITH DEMONSTRATED FINANCIAL NEED. OVER A SIX-YEAR DURATION, 55 SCHOLARS IN FOUR COHORTS WILL RECEIVE SUPPORT FOR FOUR YEARS, PLUS AN OPTIONAL FIFTH YEAR TO PURSUE AN M.S. DEGREE. STUDENTS FROM ALL COMPUTING PROGRAMS AT UCR WILL BE CONSIDERED: COMPUTER SCIENCE, COMPUTER ENGINEERING, DATA SCIENCE, COMPUTER SCIENCE WITH BUSINESS APPLICATIONS, AND ROBOTICS. A KEY INNOVATION IS THE CREATION OF THE SCHOLAR EXPERIENCE LAB (SCHOLAR XL) THROUGH WHICH STUDENTS WILL BE CONNECTED WITH INDUSTRY AND COMMUNITY PARTNERS TO WORK ON REAL AND MEANINGFUL PROJECTS, AND PARTICIPATE IN SKILLS DEVELOPMENT WORKSHOPS, WORK IN COLLABORATIVE LEARNING SPACES, AND GAIN OPPORTUNITIES TO PAIR WITH FACULTY ON RESEARCH PROJECTS. SPECIFIC OBJECTIVES OF THE PROJECT INCLUDE: (1) IMPROVING SOCIAL MOBILITY FOR SCHOLARS BY INCREASING THEIR RETENTION, SUCCESS AND COMPLETION RATES, AND (2) PROVIDING INDIVIDUAL FACULTY MENTORSHIP AND ACADEMIC COACHING THAT LEAD STUDENTS TOWARD INTERNSHIP OR RESEARCH OPPORTUNITIES AND POST-GRADUATION SUCCESS. THE PROJECT WILL LEVERAGE MANY EXISTING OPPORTUNITIES AND SUPPORT SERVICES SUCH AS SUMMER INTERNSHIP PROGRAMS, UNDERGRADUATE LEARNING ASSISTANTS, AND COMMUNITY OUTREACH PROGRAMS TO CREATE BONDING EXPERIENCES FOR EACH COHORT. THIS PROJECT IS FUNDED BY NSF?S SCHOLARSHIPS IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS PROGRAM, WHICH SEEKS TO INCREASE THE NUMBER OF LOW-INCOME ACADEMICALLY TALENTED STUDENTS WITH DEMONSTRATED FINANCIAL NEED WHO EARN DEGREES IN STEM FIELDS. IT ALSO AIMS TO IMPROVE THE EDUCATION OF FUTURE STEM WORKERS, AND TO GENERATE KNOWLEDGE ABOUT ACADEMIC SUCCESS, RETENTION, TRANSFER, GRADUATION, AND ACADEMIC/CAREER PATHWAYS OF LOW-INCOME STUDENTS. 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.

LEAP-HI: MANUFACTURING OF SILICON-BASED HYBRID ORGANIC-INORGANIC QUANTUM BUILDING BLOCKS

SL-CARE: STUDENT LEARNING COMMUNITIES AND RESEARCH ENGAGEMENT

600 MHZ NMR SPECTROMETER AND CPMAS CRYOPROBE - PROJECT SUMMARY: WE PROPOSE THE ACQUISITION OF THE FIRST CPMAS CRYOPROBE FOR SOLID-STATE NMR TO BE HOUSED IN THE UNITED STATES, ALONG WITH A DEDICATED 600 MHZ NMR SPECTROMETER TO SUPPORT BIOMOLECULAR RESEARCH AT UC RIVERSIDE AND THE SURROUNDING SOUTHERN CALIFORNIA REGION. THE INCREASED SENSITIVITY OF THIS INSTRUMENT WILL ENABLE TRANSFORMATIVE RESEARCH PROJECTS SUPPORTED BY NIH FUNDING THAT INCLUDE: HETEROCHROMATIN FORMATION AND GENE SILENCING, STRUCTURAL TRANSFORMATIONS OF NEURODEGENERATIVE DISEASE RELATED PROTEINS (AMYLOIDS), MEMBRANE PROTEIN EFFECTORS OF PATHOGEN INTERACTIONS WITH THE HOST, MECHANISTIC ENZYMOLOGY AND CHEMICAL STRUCTURE/DYNAMICS OF PYRIDOXAL-5'-PHOSPHATE-DEPENDENT ENZYMES, INHIBITION OF SS-LACTAMASES, AND THE MECHANICS OF BIOPOLYMERS. THESE PROBLEMS ALL SHARE A COMMON NEED FOR MOLECULAR CHARACTERIZATION AT THE LIMITS OF EXPERIMENTAL SENSITIVITY. ALTHOUGH WELL- EQUIPPED FOR SOLID-STATE NMR WITH CONVENTIONAL AND DYNAMIC NUCLEAR POLARIZATION (DNP) ENABLED DETECTION, THERE ARE CURRENTLY NO FACILITIES WITHIN SOUTHERN CALIFORNIA OR NORTH AMERICA WITH THE SENSITIVITY OF THE REQUESTED INSTRUMENTATION FOR SAMPLES THAT MUST BE MAINTAINED AT OR NEAR ROOM TEMPERATURE. AS SUCH, THIS EQUIPMENT WILL FILL A NOTICEABLE VOID IN THE TYPES OF NMR CHARACTERIZATION THAT CAN BE PERFORMED BOTH REGIONALLY AND NATIONALLY. THE PROPOSED CRYOPROBE AND SPECTROMETER WILL BECOME PART OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE’S ANALYTICAL CHEMISTRY INSTRUMENTATION FACILITY, WHICH SERVES THE CAMPUS, LOCAL COMMUNITY, AND EXTERNAL USERS FROM ACROSS THE COUNTRY.

UNIVERSITY OF CALIFORNIA- RIVERSIDE: NEW AWARD. CONTROL NUMBER: 1564-1587 TITLE: ''AN INNOVATIVE VEHICLE-POWERTRAIN ECO-OPERATION SYSTEM FOR EFFICIENT PLUG-IN HYBRID ELECTRIC BUSES''

QUANTITATIVE AND MECHANISTIC ANALYSES OF BOND SELECTIVE CHEMISTRY VIA NON-THERMAL EXCITATION OF METAL NANOSTRUCTURES

ACQUISITION AND CONSOLIDATION OF CONTEXTUAL FEAR MEMORY IN ENGRAM CELL PATHWAYS

MICRORNA TUNING OF NEURAL CREST OSTEOGENESIS

PREVENTING ALCOHOL USE DISORDERS AND ALCOHOL-RELATED HARMS IN PACIFIC ISLANDER YOUNG ADULTS - ABSTRACT NATIVE HAWAIIANS/PACIFIC ISLANDERS (NPI) IN THE U.S. ARE A RAPIDLY GROWING RACIAL GROUP THAT SUFFERS SEVERE ALCOHOL-RELATED DISPARITIES. IN NPI COMMUNITIES, YOUNG ADULTS (18-30 YEARS) ENDURE THE GREATEST BURDEN OF ALCOHOL USE DISORDERS (AUD) AND ALCOHOL-RELATED HARMS WITH OUR EARLIER NIAAA R21 STUDY REVEALING THAT ALMOST 50% OF COMMUNITY-DWELLING NPI YOUNG ADULTS ARE AT HEAVY RISK FOR, OR HAVE, AUDS WITH 40% EXPERIENCING ALCOHOL-RELATED HARMS (E.G., HEALTH, SOCIAL, WORK). DESPITE THIS, NPI YOUNG ADULTS HAVE RECEIVED MINIMAL ALCOHOL RESEARCH ATTENTION, LEADING TO A LACK OF EFFECTIVE INTERVENTIONS TO PREVENT OR REDUCE THEIR EXTREME AUD RISK. GUIDED BY THE FINDINGS OF OUR NIAAA R21, THIS RESUBMITTED R01 STUDY WILL RESPOND TO THIS PUBLIC HEALTH GAP BY REFINING AND EFFICACY TESTING SPEAR (STRATEGIES FOR PACIFIC EMPOWERMENT AND ALCOHOL REDUCTION): A NOVEL CULTURALLY GROUNDED AUD PREVENTION INTERVENTION FOR NPI YOUNG ADULTS. BUILDING ON OUR R21-DEVELOPED MODEL OF SPEAR INTERVENTION COMPONENTS FOR NPI YOUNG ADULTS (PREVIOUSLY CHOSEN AND SHAPED IN OUR R21 BY NPIS FROM EXISTING AUD PREVENTION INTERVENTIONS), IN AIM 1, WE WILL ASSEMBLE OUR TREATMENT MANUAL FROM OUR NPI-SHAPED R21 AUD PREVENTION COMPONENTS. TO ASSEMBLE THE MANUAL, WE WILL USE OUR CULTURALLY CONGRUENT INTERVENTION DESIGN METHODOLOGY FOR NPIS INVOLVING AN ADVISORY COUNCIL OF COMMUNITY EXPERTS AND CITIZENS’ PANELS—AN INNOVATIVE RESEARCH APPROACH THAT MIRRORS NPI COLLECTIVE DECISION-MAKING PRACTICES—TO OBTAIN CRITICAL FEEDBACK FOR REFINING SPEAR CONTENT/COMPONENTS FROM NPI YOUNG ADULTS WITH HIGH AUD RISK AND INFORMAL NPI PROVIDERS. IN AIM 2, WE WILL REVIEW AND REFINE OUR TREATMENT COMPONENTS AND MANUAL THROUGH EXPERT REVIEW BY 3 LEADING ALCOHOL RESEARCH EXPERTS AND FEASIBILITY PILOT TEST THE MANUAL WITH 36 NPI YOUNG ADULTS WITH HIGH AUD RISK FOR FEASIBILITY, ACCEPTABILITY, AND IMPACT, USING OUR FINDINGS TO FINALIZE SPEAR FOR OUR RANDOMIZED CONTROLLED TRIAL. IN AIM 3, WE WILL TEST THE EFFICACY OF SPEAR BY CONDUCTING A FULL-SCALE RANDOMIZED CONTROLLED TRIAL WITH 240 NPI YOUNG ADULTS WITH HIGH AUD RISK IN TWO LARGE NPI COMMUNITIES IN LOS ANGELES COUNTY AND NORTHWEST ARKANSAS FOR GENERALIZABILITY. ALIGNING WITH COMMUNITY RESEARCH PRINCIPLES, WE WILL SHARE STUDY FINDINGS WITH THE NPI COMMUNITY THROUGH PUBLIC REPORTS AND PRESENTATIONS, AND TO THE SCIENTIFIC COMMUNITY THROUGH ACADEMIC PRESENTATIONS AND MANUSCRIPTS.

MECHANISTIC INSIGHTS INTO FLAVIVIRUS NS5-MEDIATED STAT2 SUPPRESSION - THE FAMILY OF FLAVIVIRUS CONSISTS OF OVER 90 VECTOR-BORNE, SINGLE-STRANDED RNA-CONTAINING VIRUSES, INCLUDING DENGUE VIRUS (DENV) AND ZIKA VIRUS (ZIKV), WHICH CAUSE MAJOR EPIDEMICS AMONG HUMANS AND POSE A SERIOUS THREAT TO GLOBAL PUBLIC HEALTH. NO VACCINES OR ANTIVIRALS EXIST TO PREVENT OR TREAT INFECTIONS CAUSED BY DENV, ZIKV, AND SOME OTHER FLAVIVIRUSES. TO ESTABLISH INFECTION, FLAVIVIRUSES NEED TO OVERCOME THE ANTIVIRAL STATE INDUCED BY TYPE 1 INTERFERON (IFN-1), THE FIRST LINE OF HOST DEFENSE. IN THIS REGARD, FLAVIVIRUSES HAVE ENCODED SEVERAL ANTAGONISTS TO SUPPRESS IFN RESPONSES. FOR EXAMPLE, THE NONSTRUCTURAL NS5 PROTEINS OF DENV, ZIKV, AND SOME OTHER FLAVIVIRUSES HAVE BEEN SHOWN TO BE POTENT SUPPRESSOR OF IFN SIGNALING, TARGETING DIFFERENT STEPS OF THE IFN SIGNALING PATHWAY. LIKE DENV, ZIKV NS5 PROTEIN BIND HUMAN SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 2 (HSTAT2) PROTEIN AND TRIGGER ITS PROTEASOMAL DEGRADATION, ALBEIT USING DIFFERENT DOWNSTREAM MECHANISMS. TO ELUCIDATE THE MECHANISTIC BASIS OF FLAVIVIRUS NS5-MEDIATED HSTAT2 SUPPRESSION, WE PROPOSE TO PROVIDE STRUCTURAL INSIGHT INTO THE ZIKV NS5-HSTAT2 AND DENV NS5-HSTAT2 COMPLEXES, WHICH, IN TURN, WILL GUIDE INTERROGATION OF THE CONSEQUENCE(S) OF THE FLAVIVIRUS NS5-HSTAT2 INTERACTIONS IN PROTEASOME-MEDIATED DEGRADATION OF HSTAT2 AND SUPPRESSION OF IFN SIGNALING. TOWARD THIS GOAL, WE WILL USE STRUCTURAL, BIOCHEMICAL, MOLECULAR, CELLULAR AND VIROLOGY APPROACHES TO INVESTIGATE THE STRUCTURAL BASIS OF THE ZIKV NS5-HSTAT2 AND DENV NS5-HSTAT2 INTERACTIONS AND THEIR FUNCTIONAL CONSEQUENCE. IN AIM 1, WE WILL ESTABLISH THE STRUCTURAL BASIS OF THE ZIKV-HSTAT2 INTERACTION BY USING X-RAY CRYSTALLOGRAPHY AND CRYO-ELECTRON MICROSCOPY AND VALIDATE OUR OBSERVATIONS WITH MUTATIONAL AND IN VITRO PULL-DOWN ANALYSES. IN AIM 2, WE WILL EXAMINE THE ZIKV NS5-HSTAT2 INTERACTION AT A CELLULAR LEVEL AND INVESTIGATE THE FUNCTIONAL CONSEQUENCE OF THE ZIKV NS5-HSTAT2 INTERACTION THROUGH EVALUATION OF THE MUTATIONAL EFFECTS OF ZIKV NS5 ON HSTAT2 DEGRADATION, IFN RESPONSE AND VIRAL INFECTION. THE RESULTS OF THESE STUDIES WILL PROVIDE CRITICAL STRUCTURAL AND FUNCTIONAL INSIGHTS INTO THE VIRUS- AND SPECIES-SPECIFIC ZIKV NS5-HSTAT2 INTERACTION, THEREBY ESTABLISHING A MECHANISTIC LINK BETWEEN FLAVIVIRUS NS5 PROTEINS, HSTAT2 DEGRADATION, SUPPRESSION OF THE IFN RESPONSE AND VIRAL INFECTION. RESULTS FROM THE PROPOSED STUDIES WILL ULTIMATELY BENEFIT DEVELOPMENT OF NOVEL ANTIVIRALS AND LIVE VACCINES AGAINST FLAVIVIRUSES INFECTION.

UNDERSTANDING STRUCTURAL FLEXIBILITY AND EVOLUTIONARY DIVERGENCE OF PROTEINS

THE PURPOSE OF THIS FUNDING OPPORTUNITY IS TO PROVIDE FEDERA FINANCIAL ASSISTANCE FOR THE CALIFORNIA CITRUS CLEAN PLANTNETWORK.

UC RIVERSIDE/OFFICE OF TRIO PROGRAMS, UB CLASSIC (UBC)

SOLID STATE ELECTRONIC STRUCTURE AND PROPERTIES OF NEUTRAL CARBON-BASED RADICALS

MECHANISMS BEHIND RAPID TIP GROWTH

DEMYELINATION IS COUPLED TO NEURONAL HYPEREXCITABILITY LEADING TO SEIZURES

DEVELOPMENTAL TOXICITY OF ORGANOPHOSPHATE-BASED FLAME RETARDANTS

SHEAR STRESS, AMPK, AND ENDOTHELIAL FUNCTIONS

COMPUTATIONAL MODELING OF SPATIAL GENOME ORGANIZATION AND GENE REGULATION

MOLECULAR MARKERS OF CEREBROVASCULAR PATHOLOGIES IN ALZHEIMER'S DISEASE AND RELATED DEMENTIAS - SUMMARY PROJECT CLINICAL AND PRECLINICAL STUDIES HAVE DEMONSTRATED PERTURBATIONS TO THE CEREBROVASCULAR NETWORK IN ALZHEIMER’S DISEASE (AD) IN SEX-SPECIFIC MANNER. ALTERED BLOOD FLOW, CEREBROVASCULAR REACTIVITY, AND VESSEL TOPOLOGIES ARE ALL HALLMARKS OF PROGRESSING AD IN ANIMAL MODELS AND IN HUMAN SUBJECTS. BLOOD-BORNE PROTEIN BIOMARKERS HAVE REPORTED ALTERED PROFILES IN HUMANS AND MOUSE MODELS OF AD. AD RESEARCH HAS PREDOMINATELY FOCUSED ON NEURONAL, INFLAMMATORY AND GLIAL MARKERS OF DISEASE PROGRESSION. AT THE PRESENT TIME THERE ARE NO STUDIES THAT DIRECTLY RELATE AD-INDUCED CHANGES IN ANGIOARCHITECTURE TO BLOOD-BORNE PROTEIN BIOMARKERS OF ENDOTHELIAL STRESS AND VASCULAR DYSFUNCTION. SIMILARLY, THERE ARE NO STUDIES LINKING BLOOD BORNE PROTEIN BIOMARKERS TO VESSEL GENOMICS, SPECIFICALLY TARGETING ENDOTHELIAL CELL GENES. THIS IS A CRITICAL GAP WITH SIGNIFICANT CLINICAL VALUE BECAUSE SEVERAL STUDIES SUGGEST THAT VASCULAR ABNORMALITIES PRECEDE AD ONSET. THEREFORE, BLOOD-BORNE PROTEIN BIOMARKERS COULD BE USED TO PREDICT LIKELIHOOD OF VULNERABILITY TO AD, DISEASE ONSET AND PROGRESSION. THIS GAP IN KNOWLEDGE WILL BE ADDRESSED BY THIS PROPOSAL, WITH THE GOAL OF DESCRIBING THE TEMPORAL EVOLUTION AND RELATIONSHIPS BETWEEN DAMAGED VASCULAR NETWORKS AND BLOOD-BASED PROTEIN BIOMARKERS AND VASCULAR GENES. WE HAVE PREVIOUSLY REPORTED IN AD MOUSE MODELS THERE IS AN ALTERED VASCULAR DENSITY AND COMPLEXITY WITH INCREASING AGE. SEX DIFFERENCES HAVE ALSO BEEN POORLY STUDIED WITHIN THE CONTEXT OF VASCULAR BIOMARKERS, A GAP WE WILL ALSO DIRECTLY ADDRESS IN THIS PROPOSAL. FOUR INTERRELATED BUT NOT INTERDEPENDENT AIMS WILL ELUCIDATE THE RELATIONSHIP BETWEEN VESSEL GENOMICS, CEREBROVASCULAR STRUCTURE AND FUNCTION MODIFICATIONS AND BLOOD-BORNE PROTEIN BIOMARKERS OF ENDOTHELIAL AND VASCULAR FUNCTIONS. AIM 1 WILL EXAMINE IN FINE DETAIL THE TIMELINE OF VASCULAR FUNCTION STRUCTURAL CHANGES OVER THE LIFETIME (4, 12, >18MO) IN 5XFAD MICE OF BOTH SEXES. KNOWN RISK VARIANTS WILL BE ADDED TO CLARIFY THE EFFECTS OF AMYLOID SS SEEDING. THE BLOOD-BASED BIOMARKERS WILL FOCUS ON PROTEINS OF ENDOTHELIAL STRESS, VASCULAR DAMAGE AND RECOVERY (VEGF, VWF, CLAUDIN-5, ETC), GLIAL (GFAP), INFLAMMATION (IL-1B, TNFA, HMGB1, IL6, MMP9) AND NEURONAL DAMAGE AND NEURODEGENERATION (NF-L, TAU AND ITS VARIOUS PHOSPHORYLATED FORMS AND ABETA40 AND 42). WE BELIEVE THAT A PANEL OF BLOOD-BORNE BIOMARKERS WILL ACCURATELY REFLECT THE UNDERLYING CEREBROVASCULAR ABNORMALITIES WITH INCREASING AGE. AIM 2 WILL UTILIZE THE 3XTG AD MOUSE THAT HAS EARLY AMYLOID SS FOLLOWED BY TAU DEPOSITION AND 3XTG MICE WITH THE ADDITION OF RISK VARIANTS. AIMS 1-3 WILL UTILIZE THE IDENTICAL METHODS BIOMARKERS, GENOMES AND STRUCTURE/FUNCTION ASSESSMENTS. AIM 4 WILL MODEL ALL THE FINDINGS TO IDENTIFY A UNIQUE BIOMARKER SET THAT HAS PREDICTIVE CAPABILITIES FOR AD ONSET. THE PROPOSED PROJECT WILL PROVIDE TECHNICAL AND CONCEPTUAL INNOVATIONS THROUGH USING A UNIQUE COMBINATORY APPROACH TO ESTABLISH DIRECT RELATIONSHIPS BETWEEN BLOOD-BORNE BIOMARKERS AND VASCULAR FUNCTION AND TOPOLOGY, AS WELL AS GENOMIC MARKERS FROM THE SAME ANIMALS OF BOTH SEXES USING PWI MRI, 2-PHOTON MICROSCOPY, VESSEL PAINTING, STATE-OF-THE-ART SPATIAL TRANSCRIPTOMICS AND SINGLE-NUCLEUS RNA-SEQ AND BLOOD-BORNE PROTEIN BIOMARKERS. SUCH INNOVATIVE BIOMARKERS WOULD ENABLE EARLY IDENTIFICATION OF PATIENTS WITH ELEVATED RISK FOR AD, PREDICTION OF AD ONSET AND SEVERITY, AND OBJECTIVE MONITORING TREATMENT EFFICACY, OUR LONG-TERM RESEARCH OBJECTIVES.

DYNAMIC CEREBROVASCULAR MORPHOLOGY CHANGES IN ACUTE ISCHEMIC STROKE - SUMMARY THE GOAL OF THIS PROPOSAL IS TO INVESTIGATE THE DYNAMIC CHANGES IN CEREBROVASCULAR MORPHOLOGY AFTER ACUTE ISCHEMIC STROKE AND REPERFUSION THERAPY AND ALSO USE CEREBROVASCULAR MORPHOLOGICAL FEATURES TO IMPROVE STROKE OUTCOME PREDICTIONS. STROKE IS AMONG THE LEADING CAUSES OF DEATH AND DISABILITY WORLDWIDE. ACUTE ISCHEMIC STROKE (AIS) CONSTITUTES APPROXIMATELY 90% OF ALL STROKES AND IS CAUSED BY A BLOCKAGE OR SIGNIFICANT NARROWING OF THE BRAIN VESSELS. THE RESULTANT DISRUPTION IN THE BLOOD FLOW PATTERNS DOWNSTREAM OF THE OCCLUSION COULD PLACE THE UNDER-PERFUSED REGIONS OF THE BRAIN AT RISK. ACUTE REPERFUSION THERAPIES CAN RESTORE THE BLOOD FLOW BUT VESSEL RECANALIZATION AND IMPROVE OUTCOMES WHEN PERFORMED EARLY AFTER AIS. A WELL-CONNECTED COLLATERAL SUPPLY SYSTEM, A REDUNDANT NETWORK OF BYPASS VESSELS EXISTING IN THE BRAIN, IS CORRELATED WITH SMALLER FINAL INFARCT SIZE AND MORE FAVORABLE OUTCOMES. HOWEVER, A DETAILED EVALUATION OF THE COLLATERAL SUPPLY REMAINS CHALLENGING DUE TO THE SMALL VESSEL SIZE AND NETWORK COMPLEXITY. TIMELY DIAGNOSIS AND TREATMENT OF AIS, AS WELL AS AN ACCURATE PREDICTION OF RESPONSE TO REPERFUSION THERAPIES, RISK OF MAJOR COMPLICATIONS, AND LONG-TERM OUTCOMES, ARE PIVOTAL TO PATIENTS, FAMILIES, AND PROVIDERS TO GUIDE TREATMENT PATHWAYS. HOWEVER, ACCURATE PREDICTIVE MODELS ARE LACKING DESPITE EFFORTS TO USE A LARGE NUMBER OF CLINICAL AND IMAGING BIOMARKERS. BRAIN VASCULAR MORPHOLOGY AND GEOMETRICAL FEATURES HAVE BEEN SHOWN TO CORRELATE WITH THE DEVELOPMENT OF CEREBROVASCULAR DISORDERS. WE RECENTLY DEVELOPED AN AUTOMATIC ALGORITHM THAT CAN EXTRACT THE BRAIN’S VASCULAR MORPHOLOGIC AND GEOMETRIC FEATURES FROM THE COMMONLY USED MR AND CT ANGIOGRAMS IN HEALTHY SUBJECTS AND AIS PATIENTS. WE PROPOSE DEVELOPING FURTHER AND VALIDATING THIS ALGORITHM TO AUTOMATICALLY EXTRACT COMPLEX CEREBROVASCULAR MORPHOLOGY IN REAL-TIME. WE ALSO PROPOSE DEVELOPING PREDICTOR MODELS TO ACCURATELY USE THE CEREBROVASCULAR MORPHOLOGIC FEATURES, COLLATERAL INDEX, AND OTHER CLINICAL AND IMAGING INFORMATION COLLECTED AT ADMISSION TO PREDICT MAJOR COMPLICATIONS AND LONG-TERM OUTCOMES AFTER AIS.

GENETIC CONTROL MECHANISMS OF LONG-TERM NEURONAL SURVIVAL - PROJECT SUMMARY THE PROPOSED RESEARCH AIMS TO UNRAVEL FUNDAMENTAL MECHANISMS BEHIND NEURONAL SURVIVAL ACROSS AN ORGANISM'S LIFESPAN, SHEDDING LIGHT ON SPECIALIZED RNA REGULATION PIVOTAL FOR PROLONGED NEURONAL RESILIENCE. ESSENTIAL FOR LEARNING, MEMORY, AND ENVIRONMENTAL ADAPTATION, MATURE NEURONS MUST PERSIST THROUGHOUT AN ORGANISM'S LIFE, YET OUR UNDERSTANDING OF THE INTRICATE GENETIC REGULATIONS ENABLING THIS ENDURANCE REMAINS INCOMPLETE. PRIOR STUDIES PREDOMINANTLY EMPHASIZED COMPETITION FOR EXTERNAL CUES AND GROWTH FACTORS IN ESTABLISHING NEURAL CIRCUITS AND PREVENTING CELL DEATH. OUR RESEARCH UNCOVERS INTRINSIC GENETIC MECHANISMS FACILITATING CONTINUOUS NEURONAL SURVIVAL. NOTABLY, DURING DIFFERENTIATION, NEURONS ALTER THEIR APOPTOSIS REGULATION, BECOMING MORE RESISTANT TO CELL DEATH TRIGGERS. THIS TRANSFORMATION COINCIDES WITH GLOBAL REPROGRAMMING OF APOPTOSIS-RELATED GENES AT BOTH TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS, RESULTING IN THE GENERATION OF NEURAL-SPECIFIC ALTERNATIVE ISOFORMS. A SIGNIFICANT FOCUS LIES ON UNDERSTANDING THE ROLE OF SPECIFIC GENE ELEMENTS WHICH EXHIBIT CRUCIAL REGULATORY FUNCTIONS. WE HAVE DETERMINED A DOZEN OF THESE SPLICING CONTROLS WITH IMPLICATED FUNCTIONS IN CONTROLLING NEURONAL SURVIVAL AND CELL DEATH. OUR PRELIMINARY DATA SHOW THAT SPLICING ALTERNATION SIGNIFICANTLY IMPAIRS NEURONAL HEALTH. WE PROPOSE THREE INDEPENDENT AND INTERRELATED OVERARCHING AIMS FOR SYSTEMATIC EXPLORATION OF THESE ELEMENTS IN INFLUENCING NEURONAL APOPTOSIS. ADDITIONALLY, BY INVESTIGATING THE IMPACT OF EXON DELETIONS AND GENETIC MANIPULATIONS, WE SEEK TO DETERMINE THEIR CONTINUOUS NECESSITY FOR LONG-TERM NEURONAL SURVIVAL. OUR INTERDISCIPLINARY TEAM, ADEPT IN GENETICS, NEUROBIOLOGY, MOLECULAR CELLULAR BIOCHEMISTRY, AND COMPUTATIONAL BIOLOGY, UNIQUELY POSITIONS US TO TACKLE THESE CRITICAL QUESTIONS. THROUGH INNOVATIVE METHODOLOGIES AND RIGOROUS INVESTIGATIONS, WE ENDEAVOR TO UNVEIL NEURON- SPECIFIC REGULATORY MECHANISMS GOVERNING APOPTOSIS COMPETENCE. SUCH DISCOVERIES MAY NOT ONLY RESHAPE OUR COMPREHENSION OF INTRINSIC NEURONAL SURVIVAL STRATEGIES BUT ALSO PAVE THE WAY FOR NOVEL STRATEGIES TO ENHANCE NEURONAL RESILIENCE AND COMBAT NEUROLOGICAL DISORDERS AFFECTING BRAIN TISSUE EQUILIBRIUM AND CIRCUITRY FORMATION.

REDUCING LOSSES TO POTATO AND TOMATO LATE BLIGHT BY MONITORING PATHOGEN POPULATIONS, IMPROVED RESISTANT PLANTS, EDUCATION, AND EXTENSION

EFRI 2-DARE: NOVEL SWITCHING PHENOMENA IN ATOMIC HETEROSTRUCTURES FOR MULTIFUNCTIONAL APPLICATIONS

CHEMISTRY AND BIOLOGY OF ALKYL PHOSPHOTRIESTER LESIONS

OXIDATIVE CROSSLINK LESIONS AND CPG MUTAGENESIS

GUT MICROBIOME-MEDIATED SMALL-MOLECULE SIGNALING AND RESISTANCE TO INVADING MICROORGANISMS

DEVELOPMENTAL ACOUSTIC EXPOSURE AS A NOVEL APPROACH TO TREAT FRAGILE X SYNDROME

REDUCING LOSSES TO POTATO AND TOMATO LATE BLIGHT BY MONITORING PATHOGEN POPULATIONS, IMPROVED RESISTANT PLANTS, EDUCATION, AND EXTENSION

REDUCING LOSSES TO POTATO AND TOMATO LATE BLIGHT BY MONITORING PATHOGEN POPULATIONS, IMPROVED RESISTANT PLANTS, EDUCATION, AND EXTENSION

REDUCING LOSSES TO POTATO AND TOMATO LATE BLIGHT BY MONITORING PATHOGEN POPULATIONS, IMPROVED RESISTANT PLANTS, EDUCATION, AND EXTENSION

REDUCING LOSSES TO POTATO AND TOMATO LATE BLIGHT BY MONITORING PATHOGEN POPULATIONS, IMPROVED RESISTANT PLANTS, EDUCATION, AND EXTENSION

INTERROGATING THE ROLE OF REACTIVE ASTROCYTES DURING TOXOPLASMA-INDUCED BRAIN INFLAMMATION - PROJECT SUMMARY TOXOPLASMA GONDII IS A COMMON PROTOZOAN PARASITE THAT FORMS A LIFELONG INFECTION IN THE BRAIN. DESPITE CHRONIC INFECTION, TOXOPLASMA ONLY CAUSES CLINICAL PATHOLOGY IN THE IMMUNE COMPROMISED AND THEREFORE TRIGGERS AN EFFECTIVE AND WELL-BALANCED IMMUNE RESPONSE IN THE BRAIN. T. GONDII REPLICATION AND INNATE IMMUNITY ARE STRONGLY REGULATED BY CNS RESIDENT ASTROCYTES. ASTROCYTES ORDINARILY EXECUTE VITAL PROCESSES FOR PROPER BRAIN FUNCTION AND REPROGRAM INTO REACTIVE ASTROCYTES (RAS) DURING BRAIN INFLAMMATION. THE BENEFICIAL OR DETRIMENTAL ROLES OF RAS IN BRAIN INFLAMMATION AND NEUROTOXICITY HAS REMAINED DEBATED AND LARGELY UNKNOWN. DURING TOXOPLASMA INFECTION, ASTROCYTES LIMIT PARASITE PROLIFERATION IN A STAT1-DEPEND- ENT MANNER, PRODUCE MULTIPLE CYTOKINES AND CHEMOKINES TO ATTRACT IMMUNE CELLS TO THE BRAIN, AND MODIFY EXTRACELLULAR CONCENTRATIONS OF NEUROTRANSMITTERS TO REGULATE THE INFLAMMATORY ENVIRONMENT OF THE TISSUE LIKE MANY IMMUNE CELLS, ASTROCYTES ARE INCREASINGLY RECOGNIZED AS FALLING INTO DISTINCT FUNCTIONAL SUBSETS BUT UNLIKE IMMUNE CELLS OUR ABILITY TO MANIPULATE RAS OR STUDY THEIR FUNCTION IN A DISEASE- OR INFECTION- SPECIFIC MANNER HAS BEEN LIMITED. HERE WE PROPOSE TO CHARACTERIZE, TRACK AND SELECTIVELY MANIPULATE RAS TO DETERMINE THEIR DIVERSITY AND FUNCTIONAL ROLES IN THE IMMUNE RESPONSE DURING CHRONIC TOXOPLASMA IN- FECTION. WE HAVE GENERATED A NOVEL TAMOXIFEN-INDUCIBLE CRE KNOCK-IN MOUSE LINE DRIVEN BY THE LIPOCALIN 2 (LCN2) PROMOTER (LCN2CREERT2). BY CROSSING TO THE AI9 TDTOMATO REPORTER LINE, WE HAVE VISUALIZED RAS IN VARIOUS PATHOLOGICAL STATES INCLUDING SYSTEMIC INFLAMMATION AND T. GONDII INFECTION. TRADITIONAL ASTRO- CYTE PROMOTERS WILL BE USED IN COMBINATION WITH LCN2CREERT2 TO SELECTIVELY TARGET RAS FOR GENETIC MANIPU- LATION AT ANY POINT DURING PROGRESSION OF INFECTION, WHILE LEAVING HEALTHY ASTROCYTES, NEURONS, AND OTHER GLIAL CELL TYPES INTACT, TRANSFORMING OUR UNDERSTANDING OF ASTROCYTE FUNCTION AND UNDERLYING INFLAMMATORY MECHANISMS DURING TOXOPLASMA INFECTION. THREE AIMS ARE PROPOSED: IN AIM1 INFECTION-INDUCED ASTROCYTE SUBSETS WILL BE IDENTIFIED AND CHARACTERIZED OVER THE COURSE OF INFECTION USING FLOW CYTOMETRY AND SCRNASEQ ANALYSIS. IN AIM2 WE WILL TRACK THE RESOLUTION OF RAS IN THE CONTEXT OF HIGH AND LOW INFLAMMATORY ENVIRONMENTS FOLLOWING INFECTION AND IN AIM3 WE WILL MANIPULATE RA GENE EXPRESSION TO DETERMINE THE BENEFICIAL AND DETRIMENTAL ROLES OF RAS DURING CHRONIC TOXOPLASMA INFECTION. THE RATIONALE FOR THE PRO- POSED RESEARCH IS THAT DETERMINING THE DEVELOPMENT, FUNCTION AND RESPONSIVENESS OF ASTROCYTE SUBSETS DURING CHRONIC INFECTION WILL PROVIDE NEW KNOWLEDGE ON THE LONG-TERM CONSEQUENCES OF TOXOPLASMA IN- FECTION AND THE BASIS OF A WORKING INFLAMMATORY RESPONSE IN THE BRAIN.

DISRUPTION OF HOST-SEEKING BEHAVIOR IN AEDES AND CULEX MOSQUITOES USING ODORANTS

ACUTE NEURAL INJURY AND POSTTRAUMATIC EPILEPSY - PROJECT SUMMARY POSTTRAUMATIC EPILEPSY (PTE) REFERS TO CHRONIC UNPROVOKED SEIZURES FOLLOWING TRAUMATIC BRAIN INJURY (TBI), AND IS A MAJOR CLINICAL PROBLEM IN BOTH THE MILITARY AND CIVILIAN POPULATIONS. DESPITE THE IMPORTANCE OF PTE, THE LOCUS OF WHERE PTE DEVELOPS RELATIVE TO THE SITE OF HEAD INJURY AND THUS THE ANATOMY OF DEVELOPMENT OF PTE IN DISTRIBUTED BRAIN NETWORKS IS NOT WELL UNDERSTOOD. CONSEQUENTLY, THE PHYSIOLOGICAL CHANGES OCCURRING SPECIFICALLY IN THE PTE SEIZURE FOCUS UNDERLYING EPILEPSY HAVE NOT BEEN DETERMINED. OUR LONG-TERM GOAL IS TO IDENTIFY MECHANISMS OF PTE. THE OBJECTIVE HERE IS TO DETERMINE THE ANATOMIC LOCUS OF PTE IN THE CONTROLLED CORTICAL IMPACT (CCI) MODEL OF TBI AND TO DETERMINE UNDERLYING CELLULAR, MOLECULAR, AND PHYSIOLOGICAL ALTERATIONS ACCOMPANYING PTE. OUR CENTRAL HYPOTHESIS IS THAT FOLLOWING CCI, LOCALIZED MOLECULAR CHANGES THAT IMPAIR ASTROCYTIC FUNCTION AND DIVERGENT INJURY-INDUCED MICROCIRCUIT REORGANIZATION OF INTRATELENCEPALIC (IT) AND EXTRATELENCEPALIC (ET) LAYER 5 PYRAMIDAL CELLS (L5PCS) AND HIPPOCAMPAL CA1 PYRAMIDAL CELLS (HPCS) UNDERLIE EMERGENCE OF SEIZURE FOCI. BY USING MULTIELECTRODE ARRAY (MEA) ELECTROENCEPHALOGRAPHY (EEG) TO DEFINE THE SEIZURE FOCUS AT VARIOUS TIME POINTS AFTER CCI AND COMPARING THE MOLECULAR, CELLULAR AND CIRCUIT ALTERATIONS IN ELECTROGRAPHICALLY DEFINED SEIZURE FOCI IN PTE MICE WITH CORRESPONDING LOCI IN SEIZURE-FREE INJURED MICE, WE WILL IDENTIFY THE CELLULAR AND CIRCUIT CHANGES AND ELECTROGRAPHIC MARKERS THAT PREDICT TRANSITION TO PTE. FIRST, WE WILL DEFINE THE ANATOMIC LOCUS AND ELECTROGRAPHIC BIOMARKERS OF PTE ONSET IN THE ANIMAL MODEL OF CONTROLLED CORTICAL IMPACT (CCI) USING MULTIELECTRODE ARRAY (MEA) ELECTROENCEPHALOGRAPHY (EEG). SECOND, WE WILL DETERMINE WHICH CELLULAR AND MOLECULAR CHANGES IN THE SEIZURE FOCUS UNDERLIE THE ONSET OF PTE. THIRD, WE WILL IDENTIFY CELL-TYPE SPECIFIC CHANGES IN L5PC (IT AND ET) AND HPC PHYSIOLOGY AND COMPROMISES IN ASTROCYTIC TRANSPORTER FUNCTION THAT UNDERLIE EMERGENCE OF SEIZURE FOCI. THESE EXPERIMENTS ARE ANTICIPATED TO HAVE A POSITIVE IMPACT BY ELUCIDATING THE NECESSARY AND SUFFICIENT CHANGES IN THE BRAIN UNDERLYING PTE AND IDENTIFYING NEW CELLULAR AND MOLECULAR TARGETS FOR TREATMENT.

FUNCTIONAL ANALYSIS OF INSECT TASTE RECEPTORS

IGERT IN CHEMICAL GENOMICS: FORGING COMPLEMENTATION AT THE INTERFACE OF CHEMISTRY, ENGINEERING, COMPUTATIONAL SCIENCES AND CELL BIOLOGY

QUANTITATIVE ADDUCTOMICS APPROACHES FOR ASSESSING THE OCCURRENCE AND REPAIR OF DNA ADDUCTS

A NOVEL RNA POLYPHOSPHATASE PIR-1 PLAYS IMPORTANT ROLES IN SILENCING VIRUSES AND REGULATING GENES IN C. ELEGANS

INTEGRATING PERCEPTUAL LEARNING APPROACHES INTO EFFECTIVE THERAPIES FOR LOW VISIO