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Full-Text Articles in Medicine and Health Sciences
Structural Basis Of Bilayer Deformation By Membrane-Associated Scaffolds, Adam Frost
Structural Basis Of Bilayer Deformation By Membrane-Associated Scaffolds, Adam Frost
Yale Medicine Thesis Digital Library
The assembly of amphipathic lipids into fluid bilayers that are impermeable to macromolecules is fundamental to the existence of viruses, organelles, and cells. Conversely, membrane compartmentalization poses problems, since essential processes like cell division, cell migration, endo-, exo-, and transcytosis all require cells to remodel and even break their membranes without opening lethal leaks. Evolutionary forces have consequently generated proteins that can reversibly mold membranes into planes, spheres, cylinders, and saddle-shaped surfaces. Principally, the BAR (Bin, Amphiphysin, RVS) domain superfamily of proteins are recruited from the cytoplasm to induce or stabilize states of high membrane curvature, while the Dynamin superfamily …
Mechanistic And Structure-Function Analysis Of Thymidylate Synthase-Dihydrofolate Reductase From Protozoal Parasites: Implications For The Development Of Non-Active Site Inhibitors, Chloé E. Atreya
Yale Medicine Thesis Digital Library
A major advance in the field of bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) is the recent crystallization of two apicomplexan TS-DHFR enzymes, from Cryptosporidium hominis and Plasmodium falciparum, which demonstrate significant structural differences from the well-known kinetoplastid TS-DHFR structure (Leishmania major ). A principal finding of this dissertation research is that the significant structural differences between the apicomplexa and kinetoplastid bifunctional TS-DHFR enzymes translate as significant mechanistic differences between parasite classes and among parasites within the same class.An in depth mechanistic analysis of C. hominis TS-DHFR and a preliminary analysis of the P. falciparum enzyme were completed. Results with C. hominis …
The Splicing Of U12-Type Introns Is A Rate-Limiting Step In Gene Expression, Abhijit A. Patel
The Splicing Of U12-Type Introns Is A Rate-Limiting Step In Gene Expression, Abhijit A. Patel
Yale Medicine Thesis Digital Library
Metazoan genes have recently been found to contain a novel class of introns that display non-canonical consensus sequences and are excised by a distinct splicing machinery. These introns occur very rarely, and have been called U12-type introns because recognition of their branch point sequences requires the U12 snRNP, which performs an analogous function to the U2 snRNP in splicing major-class introns. The persistence of two spliceosomes throughout virtually all of metazoan evolution suggests that the two spliceosomes play distinct and probably indispensable cellular roles. One enticing possibility is that the U12-type spliceosome functions in post-transcriptional regulation, serving as the rate-determining …
Genetic And Biochemical Characterization Of Drosophila Singed, A Homolog Of The Actin Bundling Protein Fascin, Kelly Cant
Yale Medicine Thesis Digital Library
Drosophila singed mutants were named for their gnarled bristle phenotype, however, severe alleles are also female sterile due to a defect in nurse cell cytoplasm transport. Recently, singed protein was shown to have 35% peptide identity with the actin bundling protein fascin. I present evidence that singed is a homolog of fascin. In vivo, singed is required for actin filament bundle formation in the cytoplasm of nurse cells during oogenesis and in the cellular extension that forms a bristle. In vitro, purified bacterially-expressed singed bundles actin filaments with the same 12 nm periodicity and stoichiometry reported for sea urchin fascin.While …
Calcium/Diacylglycerol-Dependent Protein Phosphorylation In The Nervous System, Katherine Ann Albert
Calcium/Diacylglycerol-Dependent Protein Phosphorylation In The Nervous System, Katherine Ann Albert
Yale Medicine Thesis Digital Library
Calcium/diacylglycerol-dependent protein kinase, most often referred to as protein kinase C, is of interest to research groups across many scientific disciplines for two major reasons. First, protein kinase C is of general importance in signal transduction because its second messenger activator, diacylglycerol, is generated by phosphoinositide metabolism in response to a host of biologically active molecules. Second, protein kinase C has been identified as the cellular receptor for tumor-promoting phorbol esters. Protein kinase C is of particular interest to neuroscientists because its highest activity is in the nervous system. The studies described in this dissertation were undertaken to analyze the …
Identification, Characterization, And Purification Of A 65,000 Dalton Protein In Rat Brain That Is Photolabeled By Nitro-Containing Benzodiazepines, Allen Clarke Bowling
Identification, Characterization, And Purification Of A 65,000 Dalton Protein In Rat Brain That Is Photolabeled By Nitro-Containing Benzodiazepines, Allen Clarke Bowling
Yale Medicine Thesis Digital Library
Benzodiazepines bind to two well-characterized classes of nanomolar-affinity binding sites, the central and the peripheral types. Although these sites appear to mediate many of the effects of these compounds, they cannot account for all of the biochemical and physiologic effects of the benzodiazepines. In this investigation, a protein that is photolabeled by NO2-containing benzodiazepines was identified and characterized in rat brain by performing photaffinity labeling experiments with [3H] -clonazepam and [3H] -flunitrazepam. These experiments demonstrate that this photolabeled protein has a molecular weight of 65,000 daltons. Photolabeling of the protein was saturable, inhibited in a stereoselective manner by benzodiazepine enantiomers, …
Interferon Action: A. Studies Of The Effect Of Interferons On Sv40 Replication. B. Studies Of The 2'-5' A System, Mariano Agustín García-Blanco
Interferon Action: A. Studies Of The Effect Of Interferons On Sv40 Replication. B. Studies Of The 2'-5' A System, Mariano Agustín García-Blanco
Yale Medicine Thesis Digital Library
This thesis is divided into two parts: the first deals with studies that focus on the effect of interferons on the expression of foreign genetic material. The second part deals with the interferon-regulated (2'5')oligoadenylate system. This system is most probably an effector arm of the anti-viral anti-mitogenic actions of interferons.I show here that interferons inhibit the expression of both early SV40 RNA and SV40 Tag, and SV40 DNA replication in SV40 infected cells. Interferons selectively inhibit the expression of the Tag encoded by superinfecting SV40 virions in SV40-transformed cells superinfected with SV40. The effect of interferon was seen when cells …
Purification, Characterization And Distribution Of A Calmodulin-Dependent Protein Kinase From Rat Brain Cytosol, James Richard Goldenring
Purification, Characterization And Distribution Of A Calmodulin-Dependent Protein Kinase From Rat Brain Cytosol, James Richard Goldenring
Yale Medicine Thesis Digital Library
Tubulin is a major endogenous substrate for Ca('2+)- calmodulin-dependent kinase activity in rat brain cytosol. This dissertation details the purification and characterization of a calmodulin-dependent tubulin kinase from rat brain cytosol. The kinase, purified from chelated brain cytosol by sequential chromatography on phosphocellulose, calmodulin-affinity resin, and Fractogel TSK-55F, contains two calmodulin-binding, autophosphorylating subunits of 52,000 and 63,000 daltons, designated rho and sigma, respectively. The kinase holoenzyme complex has a native molecular weight of 600,000 daltons. Both kinase subunits demonstrate isoelectric points near neutrality. The kinase phosphorylated microtubule-associated protein 2, alpha tubulin and beta tubulin as major substrates. Calmodulin-dependent phosphorylation of …
Membrane Protein Phosphorylation And Hormone-Responsive Cation Cotransport In The Turkey Erythrocyte, Seth Leo Alper
Membrane Protein Phosphorylation And Hormone-Responsive Cation Cotransport In The Turkey Erythrocyte, Seth Leo Alper
Yale Medicine Thesis Digital Library
No abstract provided.
Functional Residues And Mechanism Of Binding Of Dna "Melting" Proteins, Richard Arthur Anderson
Functional Residues And Mechanism Of Binding Of Dna "Melting" Proteins, Richard Arthur Anderson
Yale Medicine Thesis Digital Library
No abstract provided.