The Governors Of The University Of Calgary

HYPERHYDRATION TO IMPROVE KIDNEY OUTCOMES IN CHILDREN WITH SHIGA TOXIN-PRODUCING E. COLI INFECTION (HIKO STEC): A MULTINATIONAL, EMBEDDED, CLUSTER, CROSSOVER, RANDOMIZED TRIAL - PROJECT SUMMARY THE HEMOLYTIC UREMIC SYNDROME (HUS) IS THE MOST SERIOUS COMPLICATION OF HIGH-RISK SHIGA TOXIN-PRODUCING ESCHERICHIA COLI (STEC) INFECTION AND THE MOST COMMON CAUSE OF ACQUIRED ACUTE KIDNEY INJURY IN OTHERWISE HEALTHY CHILDREN. HUS DEVELOPS IN UP TO 20% OF CHILDREN FOLLOWING STEC INFECTION, 60% OF WHOM REQUIRE TEMPORARY RENAL REPLACEMENT THERAPY (RRT); AN ADDITIONAL 50% DEVELOP SERIOUS EXTRARENAL COMPLICATIONS. ALTHOUGH MORTALITY FROM ACUTE HUS IS LOW (1-3%), IT HAS REMAINED CONSTANT FOR THREE DECADES AND APPROXIMATELY 30% OF HUS SURVIVORS EXPERIENCE LONG-TERM SEQUELAE, CHIEFLY CHRONIC KIDNEY DISEASE, HYPERTENSION, AND DIABETES. THERE HAVE BEEN ONLY THREE RELATIVELY SMALL, RANDOMIZED TRIALS TO PREVENT PROGRESSION TO HUS AND/OR TO REDUCE KIDNEY INJURY ONCE HUS IS ESTABLISHED; NONE HAVE DEMONSTRATED BENEFITS, AND NONE HAVE BEEN PERFORMED SINCE 1999. RECENT COHORT STUDIES SUGGEST THAT EARLY INTRAVASCULAR VOLUME EXPANSION (HYPERHYDRATION) IN STEC INFECTED CHILDREN COULD BE NEPHROPROTECTIVE IF AND WHEN HUS OCCURS. HOWEVER, MORE EVIDENCE IS NEEDED BEFORE HYPERHYDRATION SUPPLANTS TRADITIONAL ‘WAIT AND SEE’ (I.E., CONSERVATIVE FLUID MANAGEMENT) REACTIVE CARE APPROACHES WHICH FOCUS ON OUTPATIENT CARE AND MINIMIZING INTRAVENOUS FLUID ADMINISTRATION TO AVOID FLUID OVERLOAD IN CHILDREN WHO DO DEVELOP HUS. HERE, WE WILL CONFIRM OR REFUTE THE HYPOTHESIS THAT AGGRESSIVE VOLUME EXPANSION, ADMINISTERED EARLY IN STEC INFECTED CHILDREN, IS ASSOCIATED WITH BETTER RENAL OUTCOMES AND FEWER ADVERSE EVENTS THAN CONSERVATIVE MANAGEMENT BY ACCOMPLISHING THREE SPECIFIC AIMS: (1) DETERMINE THE EFFECTIVENESS OF HYPERHYDRATION IN DECREASING THE PREVALENCE OF MAJOR ADVERSE KIDNEY EVENTS BY 30 DAYS (DEFINED AS DEATH, RRT, OR SUSTAINED LOSS OF KIDNEY FUNCTION AT 30 DAYS) IN STEC-INFECTED CHILDREN VERSUS CONSERVATIVE FLUID MANAGEMENT; (2) DETERMINE THE EFFECTIVENESS AND SAFETY OF HYPERHYDRATION IN DECREASING HUS AND LIFE-THREATENING, EXTRARENAL COMPLICATIONS IN STEC-INFECTED CHILDREN VERSUS CONSERVATIVE FLUID MANAGEMENT; (3) CREATE A BIOREPOSITORY THAT WILL BE LINKED TO OUR CLINICAL DATA TO IDENTIFY PROGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS IN STEC-INFECTED CHILDREN. TO ACCOMPLISH THESE AIMS, WE WILL CONDUCT AN EMBEDDED, OPEN-LABEL, CLUSTER-RANDOMIZED CROSSOVER SUPERIORITY TRIAL IN 26 EMERGENCY DEPARTMENTS. PARTICIPATING SITES, LOCATED IN THE UNITED STATES AND CANADA, WILL BE RANDOMLY ALLOCATED TO THE ORDER OF PROTOCOL IMPLEMENTATION (HYPERHYDRATION OR CONSERVATIVE FLUID MANAGEMENT) IN THIS TWO-INTERVAL, TWO-INTERVENTION TRIAL, DEVELOPED WITH THE SUPPORT OF AN NIAID R34 GRANT. THE DESIGN, FACILITATED BY RAPID MOLECULAR ENTERIC DIAGNOSTICS, OVERCOMES MANY BARRIERS TO STUDYING THIS CHALLENGING DISEASE AND MAXIMIZES THE POTENTIAL THERAPEUTIC BENEFITS BY EMBEDDING THE INTERVENTION INTO ROUTINE CLINICAL CARE. IF WE CONFIRM OUR HYPOTHESIS, THIS PROJECT WILL PROVIDE THE FIRST CAUSAL EVIDENCE OF AN EFFECTIVE, IMPLEMENTATION-READY INTERVENTION FOR CHILDREN INFECTED WITH HIGH-RISK STEC.

PRODUCTION OF A GONOCOCCAL VACCINE FOR COUNTERING ANTIMICROBIAL RESISTANCE

7/8 PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

PREVENTION OF POST-TRAUMATIC CONTRACTURES WITH KETOTIFEN II (PERK II)

TRANSPLANTATION OF TESTIS STEM CELLS IN LARGE ANIMALS

1/3 COGNITIVE BEHAVIORAL SOCIAL SKILLS TRAINING FOR YOUTH AT RISK OF PSYCHOSIS

REDEFINING THE ZOONOTIC POTENTIAL OF CHRONIC WASTING DISEASE - THE RAPID EXPANSION OF CHRONIC WASTING DISEASE (CWD), A PRION DISEASE OF FREE-RANGING AND FARMED DEER, ELK AND MOOSE, IS A MAJOR AND ONGOING THREAT IN NORTH AMERICA. APPROXIMATELY 1 IN 36 AMERICANS HUNT DEER AND ELK AND EAT VENISON, AND IT IS ESTIMATED THAT 7,000 – 15,000 CWD-INFECTED CERVIDS ARE CONSUMED ANNUALLY. THIS FUELS GROWING CONCERNS ABOUT THE HUMAN HEALTH RISKS IMPOSED BY CWD. THERE ARE NO DOCUMENTED CASES OF CWD TRANSMISSION TO HUMANS, EVEN THOUGH WITH THE LONG INCUBATION PERIODS OF ALL PRION DISEASES AND THE UNKNOWN PRESENTATION OF CWD IN HUMANS DEFINITE CONCLUSIONS ARE NOT POSSIBLE. THE ZOONOTIC POTENTIAL OF PRION DISEASES HAS BEEN EXEMPLIFIED BY BOVINE SPONGIFORM ENCEPHALOPATHY (BSE, MAD COW DISEASE) WHICH RESULTED IN A NEW FORM OF HUMAN PRION DISEASE (VCJD). BSE WAS TRANSMISSIBLE TO CYNOMOLGUS MACAQUES AND TRANSGENIC MICE EXPRESSING THE HUMAN PRION PROTEIN. INITIAL RESULTS OF CWD TRANSMISSION STUDIES TO THE SAME NON-HUMAN PRIMATE AND MOUSE MODELS OF HUMAN PRION DISEASE WERE NOT SUCCESSFUL, CORROBORATING THE CONCLUSION THAT THE ZOONOTIC POTENTIAL OF CWD IS LOW, IF NOT ABSENT. OUR GROUPS WERE PART OF A CONSORTIUM THAT INOCULATED CYNOMOLGUS MACAQUES VIA DIFFERENT ROUTES WITH CWD. SOME ANIMALS EXHIBITED SUBTLE CLINICAL SIGNS REMINISCENT OF PRION DISEASE, AND UPON EUTHANASIA, WEAK SIGNS OF VACUOLATION, PRPSC DEPOSITION AND ASTROCYTOSIS IN THE BRAIN WERE FOUND, WHILE NO PROTEINASE K (PK) RESISTANT PRION PROTEIN (PRP) WAS DETECTABLE. WE HAVE NOW DEMONSTRATED FOR THE FIRST TIME THAT CWD FROM MACAQUES CAN TRANSMIT CLINICAL PRION DISEASE TO TRANSGENIC MOUSE MODELS OF CWD AND HUMAN PRION DISEASE, ALBEIT IN THE ABSENCE OF DETECTABLE PK-RESISTANT PRP. BONA FIDE PRPSC WAS ONLY DETECTED UPON 3RD PASSAGE FROM MOUSE TO BANK VOLE MODELS. ALTOGETHER, THIS IS THE FIRST EVIDENCE THAT CWD VERY LIKELY HAS ZOONOTIC POTENTIAL. THE GOAL OF THE CURRENT PROPOSAL IS TO REDEFINE THE ZOONOTIC POTENTIAL OF CWD BY CHARACTERIZING THE BIOLOGICAL PROPERTIES OF CWD PRIONS EMERGING UPON EXPERIMENTAL TRANSMISSION INTO MACAQUES, FOR OBTAINING IMPORTANT INFORMATION ON HOW CWD COULD MANIFEST IN HUMANS. IN AIM 1, WE WILL STUDY WHETHER CWD FROM MACAQUE (CWDMAC) IN BANK VOLES REPRESENTS A NEW PRION STRAIN, BY COMPARING BIOCHEMICAL AND BIOLOGICAL PROPERTIES TO AN ARRAY OF KNOWN PRION STRAINS FROM DIFFERENT SPECIES. AIM 2 ADDRESSES THE QUESTION WHETHER CWDMAC REPRESENTS AN INTERMEDIATE PRION STRAIN, ADAPTABLE TO CERVIDS OR HUMANS UPON PASSAGE, AND POSSESSING AN EXPANDED HOST RANGE. WE WILL ADDRESS THIS BY IN VIVO PASSAGE IN CERVIDIZED OR HUMANIZED MOUSE MODELS. IN VITRO, WE WILL UTILIZE SERIAL PMCA AND A NEWLY GENERATED PRP0/0 CELL CULTURE MODEL FOR INFECTION, UPON RECONSTITUTION WITH PRP FROM DIFFERENT SPECIES. IN AIM 3, WE WILL SHED LIGHT ON THE OBSERVED DISSOCIATION BETWEEN INFECTIVITY AND THE PRESENCE OF BONA FIDE PRPSC. WE PROPOSE TO IDENTIFY ATYPICAL PRP FRAGMENTS ASSOCIATED WITH CWDMAC, AND WE WILL ELUCIDATE BRAIN CELL RESPONSES TO CWDMAC EXPOSURE BY INNOVATIVE SINGLE CELL RNA SEQUENCING. IN SUMMARY, OUR STUDIES WILL UNCOVER THE POSSIBLE MANIFESTATION OF CWD IN HUMANS, WHICH IS OF CRITICAL IMPORTANCE FOR DRAWING DEFINITE CONCLUSIONS ABOUT THE ZOONOTIC POTENTIAL OF CWD.

MULTIPLE SCLEROSIS AS A CYTODEGENERATIVE PROTEOPATHY - PROJECT SUMMARY/ABSTRACT MS IS TRADITIONALLY CONSIDERED TO BE AN AUTOIMMUNE DEMYELINATING DISORDER OF THE CNS. HOWEVER THERE ARE A NUMBER OF INCONSISTENCIES WITH THIS “OUTSIDE-IN” HYPOTHESIS OF MS PATHOGENESIS WHICH LEAD US TO PROPOSE INSTEAD THAT MS IS PRIMARILY AN “INSIDE-OUT” DISEASE, WHERE A PRIMARY DEGENERATION MAINLY TARGETING THE MYELIN- OLIGODENDROCYTE, SECONDARILY ENTRAINS AN AUTO-IMMUNE REACTION IN THE PREDISPOSED HOST. HYPOTHESIS: MS IS A PRIMARY PROTEIN MISFOLDING DISORDER TARGETING THE MYELINATING UNIT, DRIVEN BY ACCUMULATION OF TRANSMISSIBLE PROTEIN AGGREGATES. SPECIFICALLY, THIS PROTEOPATHY IS UNDERPINNED BY A PATHOLOGICAL PRION (IN THE GENERIC SENSE) WHICH PROMOTES CHRONIC TOXICITY OF MYELIN AND OLIGODENDROCYTES, RESULTING IN DISRUPTION OF MYELIN INTEGRITY, LEADING TO SECONDARY AUTOIMMUNITY, THUS PROGRAMMING THE BROAD SPECTRUM OF INFLAMMATORY AND PROGRESSIVE MS PHENOTYPES. AIM 1: INTRACEREBRAL TRANSMISSION OF MS-LIKE PATHOLOGY. THIS AIM WILL CONDUCT A DETAILED EXAMINATION OF OUR ABILITY TO TRANSMIT AN MS-LIKE PATHOLOGY FROM HUMAN BRAIN HOMOGENATE (FROM DECEASED CONTROLS AND PROGRESSIVE MS SUBJECTS) TO WILD-TYPE AND HUMANIZED TRANSGENIC MICE, VIA DIRECT I.C. INOCULATION. THIS AIM WILL TEST THE HYPOTHESIS THAT HUMAN MS BRAIN CONTAINS TOXIC MISFOLDED PROTEIN AGGREGATES THAT CAN TRANSMIT PATHOLOGY AND PROPAGATE IN THE RECIPIENT HOSTS. HIGH- FIELD MRI, (IMMUNO)HISTOLOGY AND BEHAVIOR WILL BE USED TO MONITOR DEVELOPING PATHOLOGY. WE EXPECT TO FIND PATHOLOGY SIMILAR TO “NORMAL APPEARING WHITE MATTER” ABNORMALITIES IN HUMAN MS BRAIN (SUBTLE MYELINOPATHY, AXONAL DAMAGE, MICRO- AND ASTROGLIOSIS), AND NOTABLY, WE DO EXPECT A SIGNIFICANT LYMPHOCYTIC RESPONSE INDICATIVE OF ADAPTIVE IMMUNITY. NEGATIVE CONTROLS (NON-MS HUMAN BRAIN HOMOGENATE) WILL BE PERFORMED TO DEMONSTRATE MS SPECIFICITY. PASSAGING (IE TAKING INFECTED TRANSGENIC MOUSE BRAIN HOMOGENATE AND RE-INOCULATING INTO NAÏVE MICE) WILL SHOW THAT THE OFFENDING AGENT CONTINUES TO TRANSMIT. PRION PROTEIN IS THE ETIOLOGICAL AGENT ORIGINALLY HYPOTHESIZED, THEREFORE EXPERIMENTS WILL BE TAILORED ACCORDINGLY USING PRP TRANSGENICS, RECOGNIZING THAT PRP AND/OR ONE OF ITS INTERACTING PROTEINS COULD ALSO BE PLAYING A KEY ROLE. AIM 2: INTRAPERITONEAL TRANSMISSION OF MS-LIKE PATHOLOGY. WHILE DIRECT I.C. INOCULATION IS THE MOST ROBUST METHOD OF TRANSMITTING PRION-LIKE MISFOLDED PROTEINS, IT CARRIES THE RISK OF INDUCING NON-SPECIFIC PATHOLOGY, ESPECIALLY IN STRAINS THAT ARE MORE SUSCEPTIBLE TO VARIOUS INSULTS. THIS AIM WILL ATTEMPT TO TRANSMIT PATHOLOGY VIA A LESS INVASIVE ROUTE USING I.P. INJECTIONS. SIMILAR SOURCE MATERIAL WILL BE USED. ADVANTAGES INCLUDE POTENTIALLY EARLIER AND MORE SENSITIVE BEHAVIOURAL READOUTS (LOCOMOTOR DEFICITS, SENSORY ABNORMALITIES) IF THE EXPECTED MYELOPATHY IS INDUCED. MOREOVER, LARGER VOLUMES OF INOCULA AND MORE FREQUENT INJECTIONS ARE POSSIBLE WITH I.P. COMPARED TO I.C. INJECTION, POTENTIALLY INCREASING THE CHANCES OF TRANSMISSION. TERMINALLY, SIMILAR (IMMUNO)HISTOLOGY WILL BE PERFORMED. WE WILL ALSO EXAMINE THE SPLEEN FOR EVIDENCE OF MISFOLDED PROTEIN DEPOSITION AS A CLUE TO WHETHER THIS ORGAN PARTICIPATES IN PROCESSING AND AMPLIFICATION OF TRANSMISSIBLE SEEDS. AIM 3: BIOCHEMICAL ANALYSIS OF HUMAN MS BRAIN AND PASSAGED MOUSE CNS. A KEY OBSERVATION MADE DURING OUR PRELIMINARY BIOCHEMICAL STUDIES SHOWED A STRIKING ALTERATION IN THE INTERACTION BETWEEN PRION PROTEIN AND MYELIN BASIC PROTEIN, ONE OF THE MAJOR MYELIN PROTEINS. THIS AIM WILL EXPLORE IN GREATER DETAIL THIS POTENTIALLY VERY IMPORTANT INTERACTION THAT COULD BE KEY FOR MAINTENANCE OF MYELIN INTEGRITY. IMMUNOPRECIPITATION, WESTERNS, LC-MS AND BIOCHEMICAL ANALYSIS WILL BE PERFORMED TO PROBE DISRUPTIONS IN THIS INTERACTION. FOCUS WILL BE ON CITRULLINATION OF BOTH PROTEINS AS THIS POST- TRANSLATIONAL MODIFICATION ALTERS NET CHARGE, AND THEREFORE THE INTERACTION EFFICIENCY, EXERTING A POTENTIALLY IMPORTANT ADVERSE INFLUENCE ON PHYSIOLOGICAL PROTEI

EARLY DETECTION BLOOD TEST FOR UNIVERSAL BREAST CANCER SCREENING TO IMPROVE EARLY DIAGNOSIS FOR WOMEN OF ALL SOCIAL AND ETHNIC BACKGROUNDS

3/3-BRAIN CHEMISTRY AND GENETICS IN PEDIATRIC OCD

A SYSTEM FOR CULTURING MAMMALIAN SPERMATOGONIAL CELLS

DEFINING AND OVERCOMING A NOVEL EXTRACELLULAR MATRIX INHIBITOR OF REMYELINATION IN MS: FIBULIN-2

DEFINING A ROLE FOR MONOCYTE LICENSING IN THE REGULATION OF LEISHMANIA-SPECIFIC T CELL IMMUNITY FOLLOWING SHORT- AND LONG-TERM PRE-EXPOSURE TO SAND FLY BLOOD FEEDING - PROJECT SUMMARY EXPOSURE TO THE BITES OF BLOOD FEEDING ARTHROPODS ELICITS BOTH INNATE AND ADAPTIVE IMMUNE RESPONSES IN THE VERTEBRATE HOST. THESE RESPONSES HAVE LARGELY BEEN ATTRIBUTED TO INOCULATION OF ARTHROPOD-DERIVED SALIVARY PROTEINS INTO THE SKIN. IN TURN, IMMUNITY ELICITED BY SALIVARY PROTEINS SIGNIFICANTLY INFLUENCES THE OUTCOME OF INFECTION UPON SUBSEQUENT EXPOSURE TO ARTHROPOD TRANSMITTED PATHOGENS. HOWEVER, THE IMMUNOLOGICAL EVENTS THAT OCCUR FOLLOWING BLOOD FEEDING, AND MORE IMPORTANTLY, HOW THESE EVENTS CHANGE IN THE PHYSIOLOGICAL SETTING OF REPEATED EXPOSURE, ARE NOT WELL DEFINED. IN ADDITION, IF AND HOW THE ADAPTIVE IMMUNE RESPONSE TO SALIVARY PROTEINS DIRECTLY INFLUENCES THE ACTIVATION OF PATHOGEN-SPECIFIC CELLS IS NOT KNOWN. WITHOUT A CLEARER UNDERSTANDING OF THE INTERACTIONS BETWEEN SALIVARY- AND PATHOGEN-SPECIFIC IMMUNITY OUR ABILITY TO HARNESS THE POWER OF THE IMMUNE SYSTEM TO PREVENT OR TREAT VECTOR-TRANSMITTED DISEASES IS LIKELY TO REMAIN INADEQUATE. IN PRELIMINARY EXPERIMENTS, WE HAVE FOUND THAT THE MURINE ADAPTIVE AND INNATE IMMUNE RESPONSES TO THE BITES OF UNINFECTED LUTZOMIA LONGIPALPUS SAND FLIES, A BLOOD FEEDING ARTHROPOD AND VECTOR OF LEISHMANIASIS CAUSED BY THE PROTOZOAN PARASITIC PATHOGEN LEISHMANIA, CHANGES WITH REPEATED EXPOSURE TO UNINFECTED BITES. DURING REPEATED EXPOSURE TO BLOOD FEEDING AN INITIAL HOMOGENOUS PHASE OF SALIVARY PROTEIN-SPECIFIC T HELPER (TH) 1 IMMUNITY GIVES WAY TO A HETEROGENOUS RESPONSE AT THE POPULATION LEVEL AND ALTERS THE MONOCYTE RESPONSE. BOTH THE IMPACT OF THE DIVERSE AND LIKELY CROSS-REGULATORY RESPONSES ELICITED BY LONG-TERM PRE-EXPOSURE TO UNINFECTED BITES ON LEISHMANIA-SPECIFIC IMMUNITY AND THE MECHANISM BY WHICH SALIVARY-SPECIFIC IMMUNITY INFLUENCES LEISHMANIA-SPECIFIC IMMUNITY ARE UNKNOWN. IN LIGHT OF THESE OBSERVATIONS, WE HYPOTHESIZE THAT, FOLLOWING AN INITIAL TH1 DOMINATED RESPONSE TO BLOOD FEEDING, THE IMMUNE SYSTEM UNDERGOES A DIVERSIFICATION WITH ONGOING CHRONIC EXPOSURE RESULTING IN A HETEROGENOUS RESPONSE INVOLVING MULTIPLE CD4 T CELL SUBSETS. GIVEN THE INTIMATE CO-LOCALIZATION OF SAND FLY- AND PARASITE-DERIVED ANTIGENS, INCLUDING THE MICROBIOTA, AT A LEISHMANIA-INFECTED SAND FLY BITE SITE IN THE SKIN, SALIVA- OR BACTERIA- SPECIFIC T CELLS WILL SUBSEQUENTLY IMPACT LEISHMANIA-SPECIFIC IMMUNITY VIA CCR2+ INFLAMMATORY MONOCYTE LICENSING. THESE HYPOTHESES WILL BE TESTED EXPERIMENTALLY WITHIN THE FOLLOWING TWO AIMS: AIM 1: DETERMINE HOW INNATE AND ADAPTIVE IMMUNITY TO SAND FLY BITES AND SAND FLY DERIVED ANTIGENS CHANGES WITH REPEATED EXPOSURE.; AND AIM 2: DETERMINE THE IMPACT OF CHRONIC EXPOSURE TO SAND FLY BITES ON DE NOVO GENERATION OF LEISHMANIA-SPECIFIC T CELLS AND DEFINE A ROLE FOR CCR2+ MONOCYTES AS THE CENTRAL ANTIGEN PRESENTING CELL IN THIS PROCESS. CONDUCTING THESE STUDIES WILL PROVIDE A CRITICAL PRE-CLINICAL UNDERSTANDING OF HOW THE ‘HOST-VECTOR- PATHOGEN’ RELATIONSHIP MAY IMPACT THE SUCCESS OF PROPHYLACTIC AND THERAPEUTIC INTERVENTION STRATEGIES TO TREAT ARTHROPOD TRANSMITTED DISEASES.

EFFICIENT ANALYSIS OF OCEAN-ACOUSTIC BIG DATA FROM 3D SEABED SURVEYS WITH BAYESIAN MACHINE LEARNING AND

ANGIOGENESIS-HYPOXIA BIOMARKERS AND DISEASE IMPROVEMENT IN PROGRESSIVE MS

VOLUME EXPANSION IN CHILDREN WITH SHIGA TOXIN-PRODUCING E. COLI INFECTION TO PREVENT OR MITIGATE HEMOLYTIC UREMIC SYNDROME: PLANNING A MULTINATIONAL RANDOMIZED CLINICAL TRIAL

HARNESSING ENDOGENOUS REPAIR IN MULTIPLE SCLEROSIS

THIS PROPOSAL REPRESENTS A COLLABORATIVE EFFORT BETWEEN THE UNIVERSITY OF CALGARY, THE SITKA SOUND SCIENCE CENTER, AND THE US FISH AND WILDLIFE SERVICE. THIS PROPOSED RESEARCH AIMS TO ADDRESS CURRENT CHALLENGES IN DIFFERENTIATING STOCKS OF COASTAL WESTERN ALASKAN CHUM SALMON (ONCORHYNCHUS KETA) AND TO IMPROVE MANAGEMENT AND REDUCE BYCATCH. RECENT RUN FAILURES IN PORTIONS OF THIS GENETIC AGGREGATE HAVE LED TO WIDESPREAD CLOSURES OF SUBSISTENCE FISHERIES AND PROMPTED NUMEROUS CALLS TO ISOLATE ESTIMATED BYCATCH AND INTERCEPT HARVEST OF THE CHUM SALMON STOCKS BY FRESHWATER DRAINAGE. HOWEVER, THERE EXIST CHALLENGES CURRENTLY IN DIFFERENTIATING STOCKS BASED ON GENETIC MARKERS. THEREFORE, FURTHER DIFFERENTIATION OF GENETIC AGGREGATES WOULD REPRESENT A SIGNIFICANT IMPROVEMENT IN THE ABILITY TO QUANTIFY MARINE HARVEST PRESSURE ON COLLAPSED STOCKS. THIS WORK WILL FOCUS ON THE COASTAL WESTERN ALASKA CHUM SALMON GENETIC AGGREGATE FOR DEVELOPMENT OF A NOVEL TOOL IN DIFFERENTIATING COASTAL WESTERN ALASKAN SALMON STOCKS THROUGH GEOGRAPHICAL PROFILING OF TRACE ELEMENTS. THROUGH SAMPLE COLLECTION FROM THE YUKON RIVER, KUSKOKWIM RIVER, AND NORTON SOUND WATERSHEDS, WE WILL OBTAIN FISH TISSUES, WATER, AND SEDIMENT SAMPLES TOWARDS THE GOAL OF EXPLORING GEOGRAPHICAL DIFFERENCES IN CHUM SALMON TRACE ELEMENTS. THROUGH SAMPLING AT TERMINAL MIGRATION LOCATIONS WHERE FISH ARE SPAWNING, WE AIM TO SAMPLE FISH RETURNING TO NATAL WATERSHEDS. THESE DATA WILL BE CONSIDERED ALONGSIDE EXISTING GENETIC ANALYSES TO EXAMINE VARIATION AMONG MANAGEMENT STOCKS. WHERE POSSIBLE, WE WILL ALSO TEST OUT-MIGRATING JUVENILES. WE HYPOTHESIZE THAT A PROPORTION OF TESTED TRACE ELEMENTS WILL VARY SIGNIFICANTLY AMONG SAMPLED WATERSHEDS, MEANING THESE TRACE ELEMENTS WILL REPRESENT A NOVEL METHOD FOR STOCK DIFFERENTIATION OF ANADROMOUS FISH POPULATIONS IN THE BERING SEA THAT CURRENT GENETIC TECHNIQUES HAVE FAILED TO ISOLATE.

BAROPROSTHESIS TO REDUCE SECONDARY DAMAGE OF THE TRAUMATIC SPINAL CORD INJURY

AN ANIMAL MODEL FOR IDENTIFYING REGULATORY SEQUENCES OF THE HUMAN SHOX GENE

SUPPORT THE ESTABLISHMENT OF THE CDN ELECTRICITY POLICY FORUM TO ORGANIZE A NETWORK, CREATE DIALOGUE AND BUILD WORKING RELATIONSHIPS BETWEEN RESEARCHERS, PRACTITIONERS, AND POLICYMAKERS.

TO SUPPORT BLACK EXCELLENCE IN STEMM ACROSS THE CANADA/US BORDER VIRTUAL WORKSHOPS, A YEAR-LONG SERIES OF VIRTUAL WORKSHOPS AND CORRESPONDING WORKING GROUPS.