Structural bases of the functions of RNA-protein machines

Summary

Principal Investigator: THOMAS ARTHUR STEITZ
Abstract: DESCRIPTION (provided by applicant): The objective of this Program is to develop a fundamental physical and chemical understanding of the mechanisms by which RNA molecules and their complexes with proteins carry out their biological functions. During the next five years, several different systems that are involved in the processes of protein synthesis by ribosomes, catalysis by RNA enzymes, RNA helicases and ribo-switches will be studied. While the primary technique used will be single crystal X-ray diffraction, these structural studies will be integrated with genetic, biochemical, chemical and computational approaches. A major goal will be to capture these macromolecular machines at each step of the various processes they carry out, enabling the production of movies showing the molecular motions involved in these mechanisms. Of special interest are the motions that occur in the course of protein synthesis as the ribosome proceeds through its elongation cycle, the co-translational passage of secreted proteins through membranes, the remodeling of RNA by a DEAD box helicase, the mechanisms of riboswitches and other RNAs using allosteric mechanisms, the allosteric consequence of aminoacyl-tRNA synthetase recognition of the tRNA anticodon, and the mechanism of catalysis by a group I intron RNA. Also of interest will be the ways in which the structures and properties of RNA molecules can be utilized to carry out various biological functions often analogous to those performed by proteins.
Funding Period: 1997-04-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc Diamonds in the rough: a strong case for the inclusion of weak-intensity X-ray diffraction data
    Jimin Wang
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Acta Crystallogr D Biol Crystallogr 70:1491-7. 2014
  2. pmc The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs
    Carly A Shanahan
    Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA
    Org Biomol Chem 10:9113-29. 2012
  3. pmc Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1
    Jennifer B Nguyen
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    J Struct Biol 181:82-8. 2013
  4. pmc MDA5 assembles into a polar helical filament on dsRNA
    Ian C Berke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:18437-41. 2012
  5. pmc The hexameric helicase DnaB adopts a nonplanar conformation during translocation
    Ornchuma Itsathitphaisarn
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Cell 151:267-77. 2012
  6. pmc Expression, purification, crystallization and preliminary crystallographic studies of Rhagium inquisitor antifreeze protein
    Aaron Hakim
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 68:547-50. 2012
  7. pmc Identification of ligand analogues that control c-di-GMP riboswitches
    Kazuhiro Furukawa
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    ACS Chem Biol 7:1436-43. 2012
  8. pmc Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors
    Xuexin Duan
    Department of Electrical Engineering, Yale University, New Haven, Connecticut 06520, USA
    Nat Nanotechnol 7:401-7. 2012
  9. pmc How hibernation factors RMF, HPF, and YfiA turn off protein synthesis
    Yury S Polikanov
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    Science 336:915-8. 2012
  10. pmc Engineered allosteric ribozymes that sense the bacterial second messenger cyclic diguanosyl 5'-monophosphate
    Hongzhou Gu
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, United States
    Anal Chem 84:4935-41. 2012

Research Grants

  1. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
  2. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
  3. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013

Detail Information

Publications49

  1. pmc Diamonds in the rough: a strong case for the inclusion of weak-intensity X-ray diffraction data
    Jimin Wang
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Acta Crystallogr D Biol Crystallogr 70:1491-7. 2014
    ..Averaging starts with uniform density inside double-shelled spherical masks and NCS matrices that are derived from bound heavy-atom clusters at the vertices of cuboctahedrally symmetric protein particles...
  2. pmc The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs
    Carly A Shanahan
    Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA
    Org Biomol Chem 10:9113-29. 2012
    ..Efforts towards the synthesis of c-di-GMP and its analogs are discussed as well as studies aimed at targeting these macromolecular effectors with chemically synthesized cyclic dinucleotide analogs...
  3. pmc Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1
    Jennifer B Nguyen
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    J Struct Biol 181:82-8. 2013
    ..The structure of LRRFIP1-CC constitutes a valuable tool for probing the mechanism of LRRFIP1 signaling and for structural studies of larger LRRFIP1 constructs...
  4. pmc MDA5 assembles into a polar helical filament on dsRNA
    Ian C Berke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:18437-41. 2012
    ..We conclude that MDA5 is a polymerization-dependent signaling platform that uses the amyloid-like self-propagating properties of MAVS to amplify signaling...
  5. pmc The hexameric helicase DnaB adopts a nonplanar conformation during translocation
    Ornchuma Itsathitphaisarn
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Cell 151:267-77. 2012
    ..We propose a hand-over-hand mechanism in which sequential hydrolysis of NTP causes a sequential 5' to 3' movement of the subunits along the helical axis of the staircase, resulting in the unwinding of two nucleotides per subunit...
  6. pmc Expression, purification, crystallization and preliminary crystallographic studies of Rhagium inquisitor antifreeze protein
    Aaron Hakim
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 68:547-50. 2012
    ..X-ray diffraction data were collected to 1.3 Å resolution using a synchrotron-radiation source. The crystals belonged to the trigonal space group P3(1)21 (or P3(2)21), with unit-cell parameters a = b = 46.46, c = 193.21 Å...
  7. pmc Identification of ligand analogues that control c-di-GMP riboswitches
    Kazuhiro Furukawa
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    ACS Chem Biol 7:1436-43. 2012
    ..Moreover, we demonstrate the potential of an engineered allosteric ribozyme for the rapid screening of chemical libraries for compounds that bind c-di-GMP riboswitches...
  8. pmc Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors
    Xuexin Duan
    Department of Electrical Engineering, Yale University, New Haven, Connecticut 06520, USA
    Nat Nanotechnol 7:401-7. 2012
    ....
  9. pmc How hibernation factors RMF, HPF, and YfiA turn off protein synthesis
    Yury S Polikanov
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    Science 336:915-8. 2012
    ..The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation...
  10. pmc Engineered allosteric ribozymes that sense the bacterial second messenger cyclic diguanosyl 5'-monophosphate
    Hongzhou Gu
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, United States
    Anal Chem 84:4935-41. 2012
    ..Moreover, these ribozymes could be employed in high-throughput screens to identify compounds that trigger c-di-GMP riboswitch function...
  11. pmc Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome
    Matthieu G Gagnon
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    Science 335:1370-2. 2012
    ..This structure gives insights into the mechanism of YaeJ function and provides a basis for understanding how it rescues stalled ribosomes...
  12. ncbi Structural basis of innate immune recognition of viral RNA
    Ian C Berke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Cell Microbiol 15:386-94. 2013
    ..Many open questions remain including the role of proteolytic activation in RNA recognition by TLR3 and how unanchored ubiquitin chains contribute to RNA recognition by RIG-I and MDA5...
  13. pmc Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme
    Moshe Dessau
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America
    PLoS Genet 8:e1003102. 2012
    ....
  14. pmc Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses
    Jimin Wang
    Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA Electronic address
    Virology 454:93-101. 2014
    ..The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. ..
  15. pmc A widespread self-cleaving ribozyme class is revealed by bioinformatics
    Adam Roth
    1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA 2 Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA 3
    Nat Chem Biol 10:56-60. 2014
    ..The twister ribozyme motif provides another example of a natural RNA catalyst and calls attention to the potentially varied biological roles of this and other classes of widely distributed self-cleaving RNAs. ..
  16. pmc Riboswitches in eubacteria sense the second messenger c-di-AMP
    James W Nelson
    Department of Chemistry, Yale University, New Haven, Connecticut, USA
    Nat Chem Biol 9:834-9. 2013
    ..Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP. ..
  17. pmc Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses
    Adel M Nour
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America
    PLoS Pathog 9:e1003585. 2013
    ..Virus entry modulates intracellular calcium release and phosphatidylinositol-3-phosphate kinase signaling. Moreover, the broadly cross-reactive therapeutic antibody scFv11 binds to virus-like particles and inhibits fusion. ..
  18. pmc Peroxiredoxin-1 from the human hookworm Ancylostoma ceylanicum forms a stable oxidized decamer and is covalently inhibited by conoidin A
    Jennifer B Nguyen
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Chem Biol 20:991-1001. 2013
    ..This work demonstrates the promise of conoidin compounds as probes to evaluate peroxiredoxins as drug targets in human parasites. ..
  19. pmc The initiation of mammalian protein synthesis and mRNA scanning mechanism
    Ivan B Lomakin
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Nature 500:307-11. 2013
    ..Conformational changes associated with the captured functional states reveal the dynamics of the interactions in the P site of the ribosome. These results have functional implications for the mechanism of mRNA scanning. ..
  20. pmc Crystal structure of glycoprotein E2 from bovine viral diarrhea virus
    Yue Li
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 110:6805-10. 2013
    ..From the structure of E2, we propose alternative possible membrane fusion mechanisms. We expect the pestivirus fusion apparatus to be conserved in hepatitis C virus...
  21. pmc Crystal structure of an insect antifreeze protein and its implications for ice binding
    Aaron Hakim
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 288:12295-304. 2013
    ..By matching several planes of hexagonal ice, these waters may help freeze the AFP to the ice surface, thus providing the molecular basis of ice binding...
  22. pmc Crystal structure of glycoprotein C from Rift Valley fever virus
    Moshe Dessau
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 110:1696-701. 2013
    ..Unanticipated similarities between G(C) and flavivirus envelope proteins reveal an evolutionary link between the two virus families and provide insights into the organization of G(C) in the outer shell of RVFV...
  23. pmc Identification of c-di-GMP derivatives resistant to an EAL domain phosphodiesterase
    Carly A Shanahan
    Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA
    Biochemistry 52:365-77. 2013
    ..This suggests a general strategy for designing c-di-GMP derivatives with increased enzymatic stability that also possess desirable properties for development as chemical probes of c-di-GMP signaling...
  24. ncbi Mechanism and distribution of glmS ribozymes
    Phillip J McCown
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA
    Methods Mol Biol 848:113-29. 2012
    ..Representatives of glmS ribozymes also serve as excellent experimental models to elucidate how RNAs fold to recognize small molecule ligands and promote chemical transformations...
  25. pmc MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA
    Ian C Berke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA
    EMBO J 31:1714-26. 2012
    ..We propose a signalling model in which the CARDs on MDA5-RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry...
  26. pmc Structural and biochemical characterization of linear dinucleotide analogues bound to the c-di-GMP-I aptamer
    Kathryn D Smith
    Department of Chemistry, Yale University, New Haven, Connecticut 06520 8321, United States
    Biochemistry 51:425-32. 2012
    ..These data reveal principles that, along with published work, will contribute to the design of c-di-GMP analogues with properties desirable for use as chemical tools and potential therapeutics...
  27. pmc Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome
    Gregor Blaha
    Department of Molecular Biophysics, Yale University, New Haven, CT 06520, USA
    Science 325:966-70. 2009
    ..EF-P facilitates the proper positioning of the fMet-tRNA(i)(fMet) for the formation of the first peptide bond during translation initiation...
  28. pmc A structural view on the mechanism of the ribosome-catalyzed peptide bond formation
    Miljan Simonovic
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, MBRB 1170, 900 S Ashland Ave, Chicago, IL 60607, USA
    Biochim Biophys Acta 1789:612-23. 2009
    ..A current understanding of the mechanism of the ribosome-catalyzed peptide bond formation is the focus of this review. Implications on the mechanism of peptide release are discussed as well...
  29. pmc U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome
    Güliz Gürel
    Department of Chemistry, Yale University, New Haven, CT 06520, USA
    J Mol Biol 389:146-56. 2009
    ..In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms...
  30. pmc Structural and chemical basis for glucosamine 6-phosphate binding and activation of the glmS ribozyme
    Jesse C Cochrane
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    Biochemistry 48:3239-46. 2009
    ....
  31. pmc Mutations outside the anisomycin-binding site can make ribosomes drug-resistant
    Gregor Blaha
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    J Mol Biol 379:505-19. 2008
    ..The conformational effects of some mutations of the second kind propagate through the ribosome for considerable distances and are reversed when A-site substrates bind to the ribosome...
  32. pmc RNA catalysis: ribozymes, ribosomes, and riboswitches
    Scott A Strobel
    Yale University, Department of Molecular Biophysics and Biochemistry, New Haven, CT 06520 8114, USA
    Curr Opin Chem Biol 11:636-43. 2007
    ..This catalytic breadth raises intriguing evolutionary questions about how RNA lost its biological role in some cases, but not in others, and what catalytic roles RNA might still be playing in biology...
  33. pmc Negamycin binds to the wall of the nascent chain exit tunnel of the 50S ribosomal subunit
    Susan J Schroeder
    Department of Chemistry, Yale University, New Haven, Connecticut 06520 8107, USA
    Antimicrob Agents Chemother 51:4462-5. 2007
    ..The mechanism of antibiotic action and the function of this unexplored tunnel region remain intriguingly elusive...
  34. pmc Structural metals in the group I intron: a ribozyme with a multiple metal ion core
    Mary R Stahley
    Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Ave, New Haven, CT 06520 8114, USA
    J Mol Biol 372:89-102. 2007
    ..The structural data are correlated to the biochemical results to further understand the role of metal ions in group I intron structure and function...
  35. pmc The structures of antibiotics bound to the E site region of the 50 S ribosomal subunit of Haloarcula marismortui: 13-deoxytedanolide and girodazole
    Susan J Schroeder
    Department of Chemistry, Yale University, New Haven, CT 06520 8107, USA
    J Mol Biol 367:1471-9. 2007
    ..Girodazole is specific for eukarytes and archaea because it makes interactions with L15 that are not possible in eubacteria...
  36. pmc Structural investigation of the GlmS ribozyme bound to Its catalytic cofactor
    Jesse C Cochrane
    Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA
    Chem Biol 14:97-105. 2007
    ..This demonstrates that RNA, like protein enzymes, can employ the chemical diversity of small molecules to promote catalytic activity...
  37. pmc Structural basis of ligand binding by a c-di-GMP riboswitch
    Kathryn D Smith
    Department of Chemistry, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 16:1218-23. 2009
    ....
  38. pmc Plasticity of the RNA kink turn structural motif
    Alexandra H Antonioli
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    RNA 16:762-8. 2010
    ..Such plasticity suggests that the K-turn is not a primary element in RNA folding, but instead is shaped by other structural elements within the RNA or ribonucleoprotein assembly...
  39. pmc Prospects for riboswitch discovery and analysis
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Mol Cell 43:867-79. 2011
    ..Some of the greatest prospects for riboswitch research and some of the more interesting mysteries are discussed in this review...
  40. pmc Differential analogue binding by two classes of c-di-GMP riboswitches
    Carly A Shanahan
    Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States
    J Am Chem Soc 133:15578-92. 2011
    ..These data suggest an explanation for the predicted preferential use of the class I motif over the class II motif in the c-di-GMP signaling pathway...
  41. pmc Structural basis of cooperative ligand binding by the glycine riboswitch
    Ethan B Butler
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    Chem Biol 18:293-8. 2011
    ..These interactions provide a structural basis for how the glycine riboswitch cooperatively regulates gene expression...
  42. pmc Interactions of the c-di-GMP riboswitch with its second messenger ligand
    Kathryn D Smith
    Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA
    Biochem Soc Trans 39:647-51. 2011
    ..The binding kinetics reveal that this is a kinetically controlled riboswitch and mutations to the riboswitch lead to increases in the off-rate. This riboswitch is therefore flexible in sequence as well as kinetic properties...
  43. pmc An expanded collection and refined consensus model of glmS ribozymes
    Phillip J McCown
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 17:728-36. 2011
    ..These findings reveal that glmS ribozymes have a broader phylogenetic distribution than previously known and suggest that additional rare structural variants may remain to be discovered...
  44. pmc Association of OLE RNA with bacterial membranes via an RNA-protein interaction
    Kirsten F Block
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Mol Microbiol 79:21-34. 2011
    ..Therefore, the majority of the complex structure formed by OLE RNA may perform a biochemical function that requires membrane localization...
  45. ncbi An allosteric self-splicing ribozyme triggered by a bacterial second messenger
    Elaine R Lee
    Department of Molecular, Cellular, and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    Science 329:845-8. 2010
    ..Our findings indicate that some self-splicing ribozymes are not selfish elements but are harnessed by cells as metabolite sensors and genetic regulators...
  46. pmc Structural and biochemical determinants of ligand binding by the c-di-GMP riboswitch
    Kathryn D Smith
    Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA
    Biochemistry 49:7351-9. 2010
    ..Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation...
  47. pmc A eubacterial riboswitch class that senses the coenzyme tetrahydrofolate
    Tyler D Ames
    Department of Molecular, Cellular and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    Chem Biol 17:681-5. 2010
    ..These findings expand the number of coenzymes that are directly sensed by RNA and reveal possible riboswitch-controlled regulons that respond to changes in single-carbon metabolism...
  48. pmc The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome
    Robin E Stanley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 17:289-93. 2010
    ....
  49. pmc A fast and efficient procedure to produce scFvs specific for large macromolecular complexes
    Si Wu
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Immunol Methods 318:95-101. 2007
    ..We also describe a fast and easy method to overcome the abundance of amber stop codons in the positive phage clones. The resulting antibodies have been used in ELISA and Western blot analysis...

Research Grants30

  1. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
    ..The ultimate goal of all the proposed studies is to define the molecular events that feature in the formation of human prions in order to develop therapeutics that cure the human prion diseases. ..
  2. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
    ..ular tone, in the pathophysiology of hypertension and cardiovascular disease. ..
  3. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..