MAX PLANCK FLORIDA CORPORATION - Florida Company Profile

L8RJFGJXXS36

5YME4

2025-08-06

2024-08-08

2010-04-01

262117502

2023

128

5619729030

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2022

121

5619729030

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2015

117

5619729030

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2014

98

5619729030

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2013

85

5619729030

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2024-08-30

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Department of Health and Human Services

IDENTIFYING MITOCHONDRIAL MECHANISMS DRIVING LEARNING AND MEMORY - PROJECT SUMMARY THE OVERALL GOAL IS TO UNDERSTAND THE ENERGY SUPPLY MECHANISMS OF LEARNING AND MEMORY. THE HUMAN BRAIN IS A METABOLICALLY VULNERABLE ORGAN, WHERE EVEN AN ACUTE INTERRUPTION IN ENERGY SUPPLY LEADS TO IMMEDIATE COGNITIVE IMPAIRMENT. THIS ENERGY CONSUMPTION IS PRIMARILY AT NEURONAL SYNAPSES, WHICH REQUIRE ENERGY FOR DIVERSE PROCESSES SUCH AS MAINTAINING ION GRADIENTS, MAKING NEW PROTEINS, AND TRANSPORTING MOLECULES. BECAUSE MOST SYNAPSES ARE PLACED FAR FROM THEIR NEURONAL CELL BODY, MERE ATP DIFFUSION IS INSUFFICIENT TO COPE WITH THE IMMEDIATE (MINUTES) AND SUSTAINED (HOURS) ENERGY DEMANDS OF LOCAL BIOLOGICAL PROCESSES – A LOCAL ENERGY SOURCE IS NECESSARY. CONSISTENT WITH THIS NOTION, MY LAB RECENTLY SHOWED THAT MITOCHONDRIA ARE LOCALLY STABILIZED IN DENDRITES. LOCAL IMPAIRMENT OF STABLE MITOCHONDRIA AFFECTS THE ABILITY OF NEARBY SPINES TO UNDERGO SYNAPTIC PLASTICITY, THE CELLULAR BASIS OF LEARNING AND MEMORY (RANGARAJU ET AL., CELL 2019, BAPAT ET AL., BIORXIV 2023). THEREFORE, SPATIALLY STABLE MITOCHONDRIA ARE ESSENTIAL TO FULFILLING THE CONSTANT LOCAL ENERGY DEMANDS OF SYNAPTIC PLASTICITY FORMATION AND MAINTENANCE. IN LIGHT OF OUR RECENT UNPUBLISHED DATA, WE HYPOTHESIZE THAT MITOCHONDRIA SYNTHESIZE ATP ON-DEMAND DURING SYNAPTIC PLASTICITY, AND THE TEMPORAL AND SPATIAL COORDINATION OF MITOCHONDRIAL ENERGY PRODUCTION NEAR SYNAPSES DICTATES SYNAPTIC PLASTICITY IN TIME AND SPACE. SO FAR, THE KNOWN MECHANISMS OF MITOCHONDRIAL ENERGY PRODUCTION ARE PRIMARILY BASED ON INFORMATION AVERAGED ACROSS ALL SUBCELLULAR COMPARTMENTS, BUT HOW PLASTICITY STIMULI REGULATE SUBCELLULAR ENERGY SUPPLY NEAR SYNAPSES IS UNKNOWN. WE AT THE RANGARAJU LAB WILL DISCOVER NOVEL REGULATORS THAT DICTATE THE FLEXIBILITY OF LOCAL MITOCHONDRIAL ENERGY PRODUCTION IN TEMPORAL (MINUTES TO HOURS) AND SPATIAL (MS OF DENDRITE) SCALES RELEVANT FOR SYNAPTIC PLASTICITY FORMATION AND MAINTENANCE. TO TACKLE THIS CHALLENGE, WE COMBINE RECENT INNOVATIONS IN SUBCELLULAR PROTEOMICS AND CRISPR-BASED SCREENING IN PRIMARY NEURONAL CULTURES. IN ADDITION, WE HAVE DEVELOPED STATE-OF-THE-ART METHODS TO MEASURE ATP SYNTHESIS AND CALCIUM HANDLING IN INDIVIDUAL SPINES AND MITOCHONDRIA AT HIGH SPATIAL AND TEMPORAL RESOLUTION TO CHARACTERIZE SUBCELLULAR (DENDRITES, SPINES) REGULATION OF MITOCHONDRIAL ENERGY PRODUCTION AT DIFFERENT STAGES OF SYNAPTIC PLASTICITY. LASTLY, WE WILL CHARACTERIZE OUR NEWLY IDENTIFIED MECHANISMS IN VIVO IN BEHAVIORAL ASSAYS DURING VARIOUS FORMS OF LEARNING AND MEMORY (SPATIAL, MOTOR, SHORT- AND LONG-TERM). OVERALL, WE WILL SYSTEMATICALLY INVESTIGATE THE SYNAPTIC ENERGY LOGISTICS THAT ALLOW THE BRAIN TO PROCESS AND STORE INFORMATION. AS MITOCHONDRIAL DYSFUNCTION IS OFTEN LINKED TO MEMORY AND COGNITIVE IMPAIRMENT, FILLING THE KNOWLEDGE GAP BETWEEN MITOCHONDRIAL MECHANISMS AND COGNITIVE BEHAVIORS WILL PROVIDE NEW SOLUTIONS TO LEARNING AND MEMORY DISORDERS.

1737000.00

0.00

0.00

2024-06-24

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Department of Health and Human Services

OPTIMIZATION OF GENETICALLY ENCODED VOLTAGE AND NEUROTRANSMITTER INDICATORS FOR MULTIWAVELENGTH IN VIVO ANALYSIS OF BRAIN CIRCUITS - THE BRAIN IS REMARKABLY DYNAMIC, ADAPTIVE, AND FLEXIBLE IN RESPONSE TO ENVIRONMENTAL CHANGES. THESE CAPACITIES ARE ENABLED BY DIVERSE CELL TYPES WHICH COMMUNICATE WITH AN ARRAY OF CHEMICAL NEUROTRANSMITTERS (NTS) OR NEUROMODULATORS (NMS) AND RECEPTORS. NEUROCHEMICAL INPUTS HAVE A WIDE-RANGING AND DRAMATIC INFLUENCE ON NEURONAL ACTIVITY AND CIRCUIT DYNAMICS. TO UNDERSTAND THE LOGIC BY WHICH MULTIPLE CONVERGENT INPUTS SHAPE NEURONAL ACTIVITY, IT IS ESSENTIAL TO RECORD THE TIMING AND LOCATION OF NT AND NM RELEASE AND THE DYNAMIC CHANGES IN MEMBRANE VOLTAGE THAT RESULT. OUR TEAM HAS DEVELOPED GENETICALLY ENCODED INDICATORS, AS WELL AS HIGH-SPEED AND RESOLUTION MICROSCOPY, TO ALLOW SIMULTANEOUS OPTICAL MEASUREMENT OF VARIOUS NT/NM RELEASE AND DIFFUSION AND POST-SYNAPTIC ACTIVITY IN VIVO WITH CELL-TYPE AND CIRCUIT SPECIFICITY. BROAD APPLICATIONS OF THESE TECHNOLOGIES HAVE STARTED TO REVEAL HOW NEUROMODULATORS COLLECTIVELY MANIPULATE BRAIN-WIDE STATES. DESPITE THESE SUCCESSES, SIGNIFICANT HEADROOM EXISTS TO OPTIMIZE THESE INDICATORS TO ENABLE SENSITIVE IMAGING IN SMALL STRUCTURES, HIGHER THROUGHPUT, AND MEASUREMENTS IN SPARSELY-INNERVATED BRAIN AREAS. MOREOVER, EXISTING NT AND VOLTAGE INDICATORS ARE NEARLY ALL GREEN IN COLOR, AND OPTIMIZATION OF OTHER COLORS IS NEEDED TO ENABLE MULTIPLEXING, ALONG WITH HARDWARE TO PERFORM SUCH RECORDINGS AND ALGORITHMS TO PROCESS THEM. FINALLY, THESE NEW TOOLS MUST BE RIGOROUSLY AND SYSTEMATICALLY BENCHMARKED IN VIVO TO ALLOW THE LARGE COMMUNITY OF USERS TO BETTER DESIGN AND INTERPRET MEASUREMENTS IN BEHAVIORAL EXPERIMENTS. WITH AVAILABLE TECHNOLOGY, WE HAVE YET TO ADDRESS THE DIVERSITY OF CHEMICAL NEUROTRANSMISSION AT SCALES CRUCIAL TO UNDERSTANDING BRAIN CIRCUIT FUNCTION. THEREFORE THE OVERARCHING GOAL OF THIS UM1 PROPOSAL IS TO ESTABLISH A MULTIDISCIPLINARY, MULTI-INVESTIGATOR, AND MULTI-INSTITUTION PROGRAM FOCUSING ON DEVELOPING TOOLS FOR MEASURING MOLECULAR INPUTS TO NEURONS AND RESULTING ACTIVITY, INCLUDING: ENGINEERING OPTIMIZED AND MULTI-COLOR FP-BASED INDICATORS FOR NT/NM AND VOLTAGE (AIM 1); DETAILED CHARACTERIZATION AND BENCHMARKING OF INDICATORS IN VIVO (AIM 2); DISSEMINATING VETTED, BEST-OF-CLASS REAGENTS AND RELATED TESTING DATA (AIM 3). OUR EFFORT WILL PROVIDE THE FOUNDATION FOR UNRAVELING THE LOGIC OF INPUT-OUTPUT TRANSFORMATION IN DEFINED CELL TYPES IN VIVO, WHICH UNDERLIE INFORMATION PROCESSING, BRAIN STATES, CIRCUIT PLASTICITY, AND (ULTIMATELY) BEHAVIOR.

4316756.00

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0.00

2024-05-20

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Department of Health and Human Services

EXPERIENCE-DRIVEN DEVELOPMENT OF RELIABLE STIMULUS REPRESENTATIONS IN DYNAMIC CORTICAL NETWORKS - PROJECT SUMMARY/ABSTRACT THE ONSET OF SENSORY EXPERIENCE TRANSFORMS IMMATURE CORTICAL NETWORKS INTO MATURE REPRESENTATIONS THAT SUPPORT RELIABLE DISCRIMINATION OF BEHAVIORALLY RELEVANT STIMULI. CORTICAL RESPONSES ENCODE STIMULI BY THE PROFILE OF ACTIVITY ACROSS A POPULATION OF NEURONS (POPULATION RESPONSE). TO PROVIDE STIMULUS INFORMATION, POPULATION RESPONSES MUST BE DIFFERENT ACROSS STIMULI AND ALSO RELIABLE ACROSS PRESENTATIONS OF THE SAME STIMULUS. NOVEL TECHNIQUES THAT MEASURE ACTIVITY CHRONICALLY ACROSS LARGE NEURONAL POPULATIONS WITH SINGLE-TRIAL RESOLUTION IN DEVELOPING ANIMALS WILL NOW HELP US DEFINE HOW RELIABLE POPULATION RESPONSES MATURE WITH EXPERIENCE. THIS QUESTION IS FUNDAMENTAL AS A RELIABLE TRANSMISSION OF INFORMATION IS CRITICAL FOR PERCEPTION AND COGNITION. THE CANDIDATE’S PREVIOUS WORK SHOWS THAT A DEVELOPMENTAL ALIGNMENT BETWEEN THE STRUCTURE OF FEEDFORWARD INPUTS AND RECURRENT CONNECTIVITY IN SUPERFICIAL LAYERS 2/3 OF THE FERRET PRIMARY VISUAL CORTEX (V1) CONTRIBUTES TO THE EMERGENCE OF A RELIABLE REPRESENTATION OF EDGE ORIENTATION FOLLOWING THE ONSET OF VISUAL EXPERIENCE. DURING THE K99 PERIOD, THE CANDIDATE WILL EXPAND ON THESE INITIAL FINDINGS ADDRESSING TWO KEY QUESTIONS. FIRST, THE CANDIDATE WILL USE NOVEL METHODS HE HAS DESIGNED FOR 3-DIMENSIONAL ELECTRODE ARRAY RECORDINGS IN DEVELOPING FERRETS TO RESOLVE THE SEQUENCE OF CHANGES IN RESPONSE PROPERTIES AND CONNECTIVITY ACROSS LAYERS 2/3 AND LAYER 4, THE MAIN SOURCE OF FEEDFORWARD INPUTS TO LAYERS 2/3, THAT RESULT IN FEEDFORWARD-RECURRENT ALIGNMENT AFTER EXPERIENCE. SECOND, THE CANDIDATE WILL USE CHRONIC TWO-PHOTON IMAGING TO RESOLVE IF THE MATURATION OF INHIBITORY RESPONSES IN LAYERS 2/3 CONTRIBUTES TO INCREASE POPULATION RESPONSE RELIABILITY IN THIS LAYER. TO ACHIEVE THESE GOALS, THE CANDIDATE WILL BE MENTORED BY DR. DAVID FITZPATRICK, A WORLD-RENOWNED AUTHORITY ON VISION DEVELOPMENT AND AN EXPERT IN IMAGING TECHNIQUES. THROUGH COLLABORATIONS WITH DR. TING AT THE ALLEN INSTITUTE AND DR. YASUDA AT THE MAX PLANCK FLORIDA INSTITUTE FOR NEUROSCIENCE (MPFI), THE CANDIDATE WILL DEVELOP NOVEL GENETIC CONSTRUCTS TO DISRUPT ACTIVITY- DEPENDENT PLASTICITY IN SPECIFIC CORTICAL LAYERS OR NEURONAL TYPES IN FERRET V1. AS AN INDEPENDENT INVESTIGATOR, THE CANDIDATE WILL USE THESE TOOLS TO INVESTIGATE HOW SENSORY EXPERIENCE REFINES CORTICAL CIRCUITS TO PRODUCE A MATURE REPRESENTATION AT THE NEURONAL POPULATION LEVEL. AS A FIRST STEP TOWARDS THIS NOVEL SCIENTIFIC DIRECTION, THE CANDIDATE WILL CONSULT WITH DR. INAGAKI AT MPFI TO RESOLVE WHETHER EXPERIENCE-DRIVEN SYNAPTIC PLASTICITY IN LAYER 4 IS NECESSARY FOR THE EMERGENCE OF RELIABLE POPULATION RESPONSES IN LAYERS 2/3. THIS METHODOLOGICAL APPROACH DIFFERENTIATES THE CANDIDATE’S RESEARCH FROM DR. FITZPATRICK’S, WHICH FOCUSES ON SINGLE-CELL SYNAPTIC ARCHITECTURE AND RESPONSE PROPERTIES. TO ACQUIRE THE PROFESSIONAL SKILLS ESSENTIAL FOR A SUCCESSFUL TRANSITION TO INDEPENDENCE, THE CANDIDATE WILL CONSULT WITH DR. NAMBOODIRI, WHO WILL GUIDE THE CANDIDATE’S PLAN FOR TRAINING IN PROFESSIONAL DEVELOPMENT, FOSTERING HIS SUCCESS AS A YOUNG INVESTIGATOR. THROUGHOUT THE PROJECT PERIOD, THE MENTOR, COLLABORATORS, AND CONSULTANTS WILL WORK TOGETHER AS AN ADVISORY COMMITTEE TO GUIDE THE CANDIDATE AS HE IMPROVES HIS RESEARCH, SECURES AN INDEPENDENT RESEARCH POSITION, AND ESTABLISHES A SUCCESSFUL LAB AT HIS NEW INSTITUTION.

111759.00

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0.00

2023-10-26

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Department of Health and Human Services

IMAGING DYNAMICS IN ANXIOGENIC SEROTONIN CIRCUITRY - CONTACT PD/PI: WRIGHT, EMILY CLARISSA PROJECT SUMMARY ANXIETY DISORDERS ARE THE MOST COMMONLY DIAGNOSED MENTAL ILLNESSES; NATIONAL PREVALENCE DATA INDICATE THAT ABOUT 20% OF ADULTS IN THE US WILL BE DIAGNOSED. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) ARE ONE OF THE MOST WIDELY USED TREATMENTS, YET 40% OF PATIENTS DO NOT RESPOND. DESPITE DECADES OF TARGETING SEROTONIN, A CONSENSUS ON SEROTONIN FUNCTION AND RELEASE DYNAMICS IS LACKING. CONSEQUENTLY, HOW SSRI ADMINISTRATION MODULATES FINE TEMPORAL DYNAMICS OF SEROTONIN IN RELATION TO ANXIETY IS LARGELY UNKNOWN. PHARMACOLOGICAL APPROACHES, MICRODIALYSIS, AND CHEMOGENETIC MANIPULATIONS HAVE PRODUCED KEY INSIGHTS, BUT NONE PROVIDE MILLISECOND RESOLUTION FOR SEROTONIN RELEASE AND CORRELATES OF SPECIFIC REACTIONS AND BEHAVIORS UNTIL RECENTLY, DUE TO THE DEVELOPMENT OF TWO SENSITIVE GENETICALLY ENCODED SEROTONIN SENSORS (SLIGHT AND ISEROSNFR). I WILL THESE SENSORS COMBINED WITH FIBER-PHOTOMETRY TO OPTICALLY MEASURE BEHAVIORALLY DRIVEN SEROTONIN RELEASE IN AN ANXIOGENIC SEROTONIN CIRCUIT WITH HIGH TEMPORAL AND SPATIAL RESOLUTION. THE SERIES OF EXPERIMENTS OUTLINED IN THIS PROPOSAL ARE SIGNIFICANT BECAUSE THEY WILL: AIM 1) RIGOROUSLY DEMONSTRATE THE IN VIVO UTILITY OF SEROTONIN SENSORS IN DISSECTING ANXIETY CIRCUIT, PROVIDING END USERS IMPORTANT PROTOCOLS AND GUIDELINES FOR FAST TECHNOLOGICAL IMPLEMENTATION; AIM2) MAP DYNAMICS OF SEROTONIN RELEASE IN ANXIOGENIC CIRCUITS TO ANXIETY BEHAVIOR, AND DISCOVER HOW ACTIVITY IN THIS CIRCUIT IS IMPACTED IN ANXIOUS ANIMALS AND DETERMINE THE MECHANISTIC IMPACTS OF ACUTE VS. CHRONIC SSRI ADMINISTRATION ON ANXIOGENIC SEROTONIN SIGNALING; AIM 3) DETERMINE HOW TESTOSTERONE IMPACTS THE EFFICACY OF SSRI TREATMENT. PROJECT SUMMARY/ABSTRACT PAGE 6

224964.00

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0.00

2023-09-18

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Department of Health and Human Services

IDENTIFYING NEURONS FOR INTEROCEPTION USING SIMULTANEOUS PROFILING OF ACTIVITY- AND PROJECTION- SPECIFIC POPULATIONS - PROJECT SUMMARY INTEROCEPTION, THE PROCESS BY WHICH THE BODY SENSES ITS OWN INTERNAL STATE, IS CRITICAL TO MAINTAINING HOMEOSTASIS THROUGH THE DETECTION OF PHYSIOLOGICAL CHANGES THAT ENABLE THE BODY TO ADJUST TO CHANGING DEMANDS. DYSFUNCTION IN INTEROCEPTION MAY LEAD TO ERRONEOUS PREDICTION ERRORS CONCERNING THESE BODILY NEEDS AND IS INCREASINGLY CONSIDERED TO UNDERLIE A NUMBER OF MALADAPTIVE BEHAVIORS AND PSYCHIATRIC DISORDERS, INCLUDING ADDICTION AND EATING DISORDERS. DESPITE THIS, LITTLE PROGRESS HAS BEEN MADE IN IDENTIFYING THE UNDERLYING NEURAL CIRCUIT MECHANISMS OF INTEROCEPTION BECAUSE NON-VERBAL SUBJECTS (E.G. ANIMAL MODELS) CANNOT SELF-REPORT INTERNAL STATES. HERE, WE PROPOSE A NOVEL CONCEPTUAL BEHAVIORAL FRAMEWORK FOR STUDYING INTEROCEPTION IN ANIMAL MODELS IN ORDER TO IDENTIFY NEURONAL ENSEMBLES THAT ENCODE INTEROCEPTION. MOREOVER, HUMAN IMAGING STUDIES HAVE INFORMED US THAT INTEROCEPTION RELIES CRITICALLY ON AN UNDERSTUDIED AREA OF THE BRAIN, THE INSULAR CORTEX, BUT THE FUNCTIONS AND CORRESPONDING PROJECTIONS FROM THE INSULAR CORTEX SUBREGIONS (ANTERIOR TO POSTERIOR) HAVE NOT BEEN WELL-STUDIED. METHODS THAT CAN SIMULTANEOUSLY DELIVER PRECISE INFORMATION CONCERNING BEHAVIOR AND PROJECTIONS IN A HIGH-THROUGHPUT WAY ARE THEREFORE REQUIRED. MOLECULAR PROFILING TECHNIQUES HAVE BEEN INCREASINGLY USEFUL FOR IDENTIFYING CELL TYPES THAT MIGHT SERVES AS THE LINK BETWEEN GENES TO CIRCUITS, BUT CURRENT TECHNIQUES HAVE LIMITATIONS, NAMELY THE MODALITY BY WHICH THE PROFILING OCCURS. WE THEREFORE ALSO PROPOSE A NEW TRANSCRIPTOMIC MOLECULAR PROFILING TECHNIQUE, CALLED SNAP-TRAP (SIMULTANEOUS NEURONAL ACTIVITY AND PROJECTION – TRANSLATING RIBOSOME AFFINITY PURIFICATION), THAT ENABLES COINCIDENT PROFILING OF BOTH ACTIVITY-DEPENDENT AND PROJECTION-SPECIFIC NEURONAL MARKERS. WE WILL VALIDATE THIS TECHNIQUE USING A WELL-DEFINED NEURAL CIRCUIT WITH KNOWN MOLECULAR MARKERS AND BEHAVIORAL CONSEQUENCES. WE WILL THEN APPLY THE METHODOLOGY TO THE INSULAR CORTEX AND ITS ROLE IN INTEROCEPTION. THIS TECHNIQUE WILL ALSO ENABLE US TO MAKE COMPARISONS OF NEXT-GENERATION RNA-SEQUENCING TO SINGLE- CELL RNA SEQUENCING FOR THE PURPOSE OF IDENTIFYING USEFUL MARKERS FOR BEHAVIORAL VALIDATION. LASTLY, WE WILL MAP OUR FINDINGS BACK ONTO TISSUE SECTIONS TO ACHIEVE SPATIAL TRANSCRIPTOMIC INFORMATION. THROUGH THESE EXPERIMENTS WE HOPE TO ACHIEVE A COMPREHENSIVE TRANSCRIPTOMIC MAP OF THE INSULAR CORTEX THAT CAN BE PRECISELY DELINEATED ACCORDING TO PARTICULAR BEHAVIORS AND PROJECTIONS, AND CAN BE USED AS A BASIS FOR UNDERSTANDING HOW DYSFUNCTION IN INTEROCEPTION LEADS TO MALADAPTIVE BEHAVIORS. THE SNAP- TRAP TECHNIQUE MAY THEN BE USED BY THE BROADER NEUROSCIENCE COMMUNITY IN OTHER BRAIN REGIONS AND BEHAVIORAL TASKS TO GAIN INSIGHTS INTO THE NEURAL UNDERPINNINGS OF COMPLEX BEHAVIORS AND THEIR ASSOCIATED PSYCHIATRIC DISORDERS.

1699800.00

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26-2117502

% PETER GRUSS

Educational Organization, Local Association of Employees, Horticultural Organization, Business League, Voluntary Employees' Beneficiary Association (Govt. Emps.), Mutual Ditch or Irrigation Co., Cemetery Company, Other Mutual Corp. or Assoc.

2009-04

Medical Research: Research Institutes and/or Public Policy Analysis

Type of organization and use of contribution: A public charity. Deductibility Limitation: 50% (60% for cash contributions)

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