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38,696 grants matching “als”
Poly(ADP-ribose)-dependent TDP-43 pathology in oxidative stress (R21)
$408,375Shaida A. Andrabi · University Of Alabama At Birmingham · R21 · FY2023 · AG
THE DEVELOPMENTAL ORGINS OF SUICIDE MORTALITY
$408,345Stephen Gilman · Eunice Kennedy Shriver National Institute Of Child Health & Human Development · Y01 · FY2017 · HD
Oxidative pentose phosphate pathway regulates AMPK homeostasis by balancing opposing LKB1 and PP2A
$408,334Jing Chen · University Of Chicago · R01 · FY2021 · CA
Astrocyte-Neuron Signaling
$408,212Philip G Haydon · Tufts University Boston · R01 · FY2012 · NS
Astrocyte-Neuron Signaling
$408,212Philip G Haydon · Tufts University Boston · R01 · FY2010 · NS
Astrocyte-Neuron Signaling
$408,212Philip G Haydon · Tufts University Boston · R01 · FY2011 · NS
Dissecting the DNA Damage Response with Functional Proteomics
$408,179Minkyu Kim · University Of Texas Hlth Science Center · R35 · FY2025 · GM
Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles
$408,166Roger Keith Reeves · Duke University · R01 · FY2023 · AI
Alzheimer's Brain-Seeded Abeta Fibrils
$408,143Stephen C. Meredith · University Of Chicago · R01 · FY2019 · AG
Molecular Basis of Reovirus Pathogenesis
$408,130Terence S. Dermody · Vanderbilt University · R37 · FY2012 · AI
Electrophysiology
$408,081Paul J. Abbas · University Of Iowa · P50 · FY2008 · DC
Visual Summary-Statistic Processing in Infancy
$408,066Benjamin Balas · North Dakota State University · R15 · FY2014 · EY
Acquisition Of A Fluorescence-Activated Cell Sorter To Support Research And Research Training at Chicago State University, A Minority Serving, Undergraduate Institution
$408,042Walid M Al-Ghoul · Chicago State University · · FY2005 · BIO
Genetic influences on alcoholism vulnerability in American Indians
$408,010David Goldman · National Institute On Alcohol Abuse And Alcoholism · ZIA · FY2011 · AA
Tunnel Junction Based AlGaN Ultraviolet Lasers
$407,999Shamsul Arafin · Ohio State University, The · · FY2020 · ENG
Osteoprotegerin Regulation of the Atherosclerotic Lesion Expansion
$407,951Marta Scatena · University Of Washington · R01 · FY2010 · HL
Optimizing the Combination of Electric and Acoustic Hearing
$407,914Christopher W Turner · University Of Iowa · RC1 · FY2010 · DC
CBT for Adherence and Depression in Diabetes
$407,856Steven A Safren · Massachusetts General Hospital · R01 · FY2009 · MH
PHOSPHORYLATION ON WATER WORLDS AS A CONSEQUENCE OF PHOSPHITE OXIDATION THE ELEMENT PHOSPHORUS IS CRITICAL TO MODERN BIOCHEMISTRY AND PRESUMABLY WOULD HAVE BEEN IMPORTANT IN THE EARLY EVOLUTION OF LIFE. HOWEVER PHOSPHORUS AS PHOSPHATE (PO43-) IS POORLY REACTIVE AND MINIMALLY SOLUBLE AND HENCE ITS PREBIOTIC CHEMISTRY HAS BEEN ARGUED TO BE RATHER LIMITED IN SCOPE. SEVERAL PREBIOTIC STUDIES HAVE ATTEMPTED TO REPLACE PHOSPHATE WITH OTHER IONS OR LINKERS IN NUCLEIC ACIDS SUGGESTING THAT THE ROLE OF PHOSPHATE IS A POST-ORIGIN BIOCHEMICAL ADDITION TO LIFE. THIS WORK PROPOSES A NEW HYPOTHESIS: THAT THE INCORPORATION OF PHOSPHATE WITHIN BIOMOLECULES WAS A NATURAL CONSEQUENCE OF THE EARLY GEOCHEMISTRY OF THE EARLY EARTH. MORE SPECIFICALLY ORGANOPHOSPHATES WERE FORMED BY REACTION OF ABUNDANT CONDENSED PHOSPHATES FORMED FROM OXIDATION OF INTRINSIC REDUCED OXIDATION STATE PHOSPHORUS. THIS HYPOTHESIS IS BASED ON SEVERAL RECENT FINDINGS COMING FROM OUR LAB. FIRST IS A DEMONSTRATION OF PHOSPHORYLATION USING THE MINERAL SCHREIBERSITE (FE NI)3P THAT PRODUCED NUCLEOTIDES FROM NUCLEOSIDES BY A "JUST ADD WATER" EXPERIMENT (GULL ET AL. SCIENTIFIC REPORTS 2015). THIS PHOSPHORYLATION DEMONSTRATED THAT PHOSPHORYLATED PRODUCTS CAN COME ABOUT SPONTANEOUS FROM MINERAL-WATER-ORGANIC INTERACTIONS. THE REACTION PATHWAY LEADING TO NUCLEOTIDES HAS NOT YET BEEN DETERMINED BUT MAY INVOLVE A POLYPHOSPHATE AS A PHOSPHORYLATING AGENT. WE PROPOSE TO ELUCIDATE THE PATHWAYS OF PHOSPHORYLATION FROM REACTIVE P COMPOUNDS UNDER PLAUSIBLE CONDITIONS BUILDING ON OUR PRIOR WORK USING NMR RAMAN AND XRD ANALYSES. THE ORIGIN OF THE PHOSPHORYLATING AGENT IN THE ABOVE REACTIONS IS PROBABLY LINKED TO THE REDOX CHEMISTRY OF SCHREIBERSITE. OUR GROUP HAS STUDIED THIS EXTENSIVELY AND IF POLYPHOSPHATES ARE THE ROUTE OF THIS PHOSPHORYLATION PASEK ET AL. (ANG. CHEM. 2008) PROVIDES A LIKELY SOURCE FROM REDUCED OXIDATION STATE PHOSPHORUS COMPOUNDS. THIS REACTION IS BETWEEN REDUCED P COMPOUNDS SUCH AS PHOSPHITE (HPO32-) AND HYDROGEN PEROXIDE MEDIATED BY AN IRON CATALYST. WE PROPOSE TO INVESTIGATE HOW REDUCED OXIDATION STATE P COMPOUNDS GENERATE PLAUSIBLE PHOSPHORYLATING AGENTS DURING OXIDATION. THE ORIGIN OF THE REDUCED OXIDATION STATE PHOSPHORUS COMPOUNDS IS LIKELY THE MOST NOVEL PART OF THIS PROPOSED WORK. WE HAVE RECENTLY DEMONSTRATED (PASEK ET AL. PNAS 2013) THAT REDUCE P COMPOUNDS WERE PRESENT IN A 3.52 BILLION YEAR OLD CARBONATE ROCK. THE ORIGIN OF THIS PHOSPHITE WAS AT THE TIME ATTRIBUTED TO METEORITIC MATERIALS. WE NOW BELIEVE THAT THE PHOSPHITE ORIGINATES FROM NATURAL GEOCHEMICAL REACTIONS OCCURRING ON THE EARTH'S SURFACE AKIN TO: 2FEO + HPO42- = FE2O3 + HPO32- THIS REACTION YIELDS ABOUT 0.1% PHOSPHITE AT EQUILIBRIUM AND 200OC (HERSCHY ET AL. IN REVIEW). IF THIS REACTION WAS ACTIVE ON A LARGE SCALE THROUGH LOW-TEMPERATURE DIAGENESIS AND BURIAL OF SEDIMENT THEN PHOSPHITE COULD HAVE BEEN A SIGNIFICANT FRACTION OF THE CHEMISTRY OF THE EARLY OCEANS. WE HAVE INITIAL DATA THAT DEMONSTRATE REDUCED P WAS WIDESPREAD IN THE ARCHEAN IN SEDIMENTARY ROCKS LIKELY FROM THIS PATHWAY AND WILL INVESTIGATE OTHER SOURCES AS PART OF THIS GRANT. WE WILL EXPLORE THESE PROCESSES USING NMR HPLC RAMAN ICP-MS XRD AND TGA ANALYSES COUPLED TO MODELING. THIS WORK IS DIRECTLY RELEVANT TO EXOBIOLOGY SPECIFICALLY "RESEARCH IN THE AREA OF PREBIOTIC EVOLUTION SEEKS TO UNDERSTAND THE PLANETARY AND MOLECULAR PROCESSES THAT SET THE PHYSICAL AND CHEMICAL CONDITIONS WITHIN WHICH LIVING SYSTEMS MAY HAVE ARISEN". THIS WORK WILL SUPPLEMENT OUR EMERGING WORLDS RESEARCH (FOCUSED ON HIGH-TEMPERATURE REACTIONS) AND WILL FOCUS ON HOW REDUCED P COMPOUNDS ARE FORMED HOW THEY OXIDIZE AND WHAT THE OXIDATION PRODUCTS CAN DO.
$407,838University Of South Florida · · FY2020 · National Aeronautics and Space Administration
Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone Loss
$407,765Mone Zaidi · Icahn School Of Medicine At Mount Sinai · R01 · FY2020 · DK
Axonal TDP-43 Dysregulation in ALS and Dementia
$407,758Christopher James Donnelly · University Of Pittsburgh At Pittsburgh · R21 · FY2023 · NS
A comparison of cognitive and dynamic therapy for MDD in community settings
$407,713Mary Beth Gibbons · University Of Pennsylvania · R01 · FY2013 · HS
RESEARCH CORE
$407,636Martha I Arrieta · University Of South Alabama · P20 · FY2014 · MD
Novel Cre-Dependent AAVs with Minimal Off-Target Expression to Study Neural Circuits
$407,589Edward Perez-Reyes · University Of Virginia · R01 · FY2024 · MH
Longitudinal Imaging of Frontal Cortex Afferents in a Mouse Model of Anxiety
$407,581Linda E. Wilbrecht · Ernest Gallo Clinic And Research Center · R01 · FY2009 · MH