PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 81 - 100 de 184,040
81.
Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella - Schmidt, Eric W.; Nelson, James T.; Rasko, David A.; Sudek, Sebastian; Eisen, Jonathan A.; Haygood, Margo G.; Ravel, Jacques
Prochloron spp. are obligate cyanobacterial symbionts of many didemnid family ascidians. It has been proposed that the cyclic peptides of the patellamide class found in didemnid extracts are synthesized by Prochloron spp., but studies in which host and symbiont cells are separated and chemically analyzed to identify the biosynthetic source have yielded inconclusive results. As part of the Prochloron didemni sequencing project, we identified patellamide biosynthetic genes and confirmed their function by heterologous expression of the whole pathway in Escherichia coli. The primary sequence of patellamides A and C is encoded on a single ORF that resembles a precursor peptide....
82.
Utility of siRNA against Keap1 as a strategy to stimulate a cancer chemopreventive phenotype - Devling, Tim W. P.; Lindsay, Christopher D.; McLellan, Lesley I.; McMahon, Michael; Hayes, John D.
A duplex 21 nucleotide small interfering RNA (siRNA) against human Keap1 is described that represents a unique class of cancer chemopreventive agent. This siRNA can knockdown Keap1 mRNA and thereby relieve negative regulation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-mediated gene expression. The siRNA lowered endogenous Keap1 mRNA to <30% of control levels between 24 and 72 h after transfection in human HaCaT keratinocyte cells and was capable of blocking ectopic expression of FLAG-tagged human Keap1 protein but not that of ectopic V5-tagged mouse Keap1 protein. Transfection of human HaCaT cells with Keap1 siRNA markedly enhanced endogenous levels...
83.
Clathrin heavy and light chain isoforms originated by independent mechanisms of gene duplication during chordate evolution - Wakeham, Diane E.; Abi-Rached, Laurent; Towler, Mhairi C.; Wilbur, Jeremy D.; Parham, Peter; Brodsky, Frances M.
In humans, there are two isoforms each of clathrin heavy chain (CHC17 and CHC22) and light chain (LCa and LCb) subunits, all encoded by separate genes. CHC17 forms the ubiquitous clathrin-coated vesicles that mediate membrane traffic. CHC22 is implicated in specialized membrane organization in skeletal muscle. CHC17 is bound and regulated by LCa and LCb, whereas CHC22 does not functionally interact with either light chain. The imbalanced interactions between clathrin subunit isoforms suggest a distinct evolutionary history for each isoform pair. Phylogenetic and sequence analysis placed both heavy and light chain gene duplications during chordate evolution, 510-600 million years ago....
84.
The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells - Schisler, Jonathan C.; Jensen, Per Bo; Taylor, David G.; Becker, Thomas C.; Knop, Filip Krag; Takekawa, Shiro; German, Michael; Weir, Gordon C.; Lu, Danhong; Mirmira, Raghavendra G.; Newgard, Christopher B.
We have previously described rat insulinoma INS-1-derived cell lines with robust or poor glucose-stimulated insulin secretion (GSIS). In the current study, we have further resolved these lines into three classes: class 1, glucose-unresponsive/glucagon-expressing; class 2, glucose-unresponsive/glucagon-negative; and class 3, glucose-responsive/glucagon-negative. The transcription factor Nkx2.2 was expressed with relative abundance of 3.3, 1.0, and 1.0 in class 1, class 2, and class 3 cells, respectively, whereas Nkx6.1 expression had the opposite trend: 1.0, 2.6, and 6.4 in class 1, class 2, and class 3 cells, respectively. In class 1 cells, overexpressed Nkx6.1 suppressed glucagon expression but did not affect the levels...
85.
Conservation and evolvability in regulatory networks: The evolution of ribosomal regulation in yeast - Tanay, Amos; Regev, Aviv; Shamir, Ron
Transcriptional modules of coregulated genes play a key role in regulatory networks. Comparative studies show that modules of coexpressed genes are conserved across taxa. However, little is known about the mechanisms underlying the evolution of module regulation. Here, we explore the evolution of cis-regulatory programs associated with conserved modules by integrating expression profiles for two yeast species and sequence data for a total of 17 fungal genomes. We show that although the cis-elements accompanying certain conserved modules are strictly conserved, those of other conserved modules are remarkably diverged. In particular, we infer the evolutionary history of the regulatory program governing...
86.
Late-emigrating neural crest cells in the roof plate are restricted to a sensory fate by GDF7 - Lo, Liching; Dormand, Emma L.; Anderson, David J.
Lineage-tracing experiments have shown that some premigratory neural crest cells generate both sensory (S) and autonomic (A) derivatives, whereas others generate only S derivatives. Whether this lineage heterogeneity reflects random variation in a homogeneous population or an early sensory specification of some premigratory crest cells has not been clear. Using Cre recombinase-based fate mapping, we show that GDF7, which is exclusively expressed in the roof plate, marks neural crest cells with a 10-fold higher bias to the sensory lineage than those marked (at the same stage of development) by an inducible Wnt1-Cre, which is expressed more broadly in the dorsal...
87.
Coevolution of TCR-MHC interactions: Conserved MHC tertiary structure is not sufficient for interactions with the TCR - Kim, Hye-Jung; Guo, Donglin; Sant'Angelo, Derek B.
The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like...
88.
Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord - Mentis, George Z.; Alvarez, Francisco J.; Bonnot, Agnes; Richards, Dannette S.; Gonzalez-Forero, David; Zerda, Ricardo; O'Donovan, Michael J.
Mammalian spinal motoneurons are considered to be output elements of the spinal cord that generate exclusively cholinergic actions on Renshaw cells, their intraspinal synaptic targets. Here, we show that antidromic stimulation of motor axons evokes depolarizing monosynaptic potentials in Renshaw cells that are depressed, but not abolished, by cholinergic antagonists. This residual potential was abolished by 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of cholinergic antagonists, motor axon stimulation triggered locomotor-like activity that was blocked by 2-amino-5-phosphonovaleric acid. Some cholinergic motoneuronal terminals on both Renshaw cells and motoneurons were enriched in glutamate, but none expressed vesicular glutamate transporters. Our results...
89.
Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception - Zelcer, Noam; van de Wetering, Koen; Hillebrand, Michel; Sarton, Elise; Kuil, Annemieke; Wielinga, Peter R.; Tephly, Thomas; Dahan, Albert; Beijnen, Jos H.; Borst, Piet
Glucuronidation is a major detoxification pathway for endogenous and exogenous compounds in mammals that results in the intracellular formation of polar metabolites, requiring specialized transporters to cross biological membranes. By using morphine as a model aglycone, we demonstrate that multidrug resistance protein 3 (MRP3/ABCC3), a protein present in the basolateral membrane of polarized cells, transports morphine-3-glucuronide (M3G) and morphine-6-glucuronide in vitro. Mrp3(-/-) mice are unable to excrete M3G from the liver into the bloodstream, the major hepatic elimination route for this drug. This results in increased levels of M3G in liver and bile, a 50-fold reduction in the plasma levels...
90.
The Poggendorff illusion explained by natural scene geometry - Howe, Catherine Q.; Yang, Zhiyong; Purves, Dale
One of the most intriguing of the many discrepancies between perceived spatial relationships and the physical structure of visual stimuli is the Poggendorff illusion, when an obliquely oriented line that is interrupted no longer appears collinear. Although many different theories have been proposed to explain this effect, there has been no consensus about its cause. Here, we use a database of range images (i.e., images that include the distance from the image plane of every pixel in the scene) to show that the probability distribution of the possible locations of line segments across an interval in natural environments can fully...
91.
Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis - Arita, Makoto; Yoshida, Masaru; Hong, Song; Tjonahen, Eric; Glickman, Jonathan N.; Petasis, Nicos A.; Blumberg, Richard S.; Serhan, Charles N.
Resolvin E1 (RvE1; 5S,12R,18R-trihydroxyeicosapentaenoic acid) is an antiinflammatory lipid mediator derived from omega-3 fatty acid eicosapentaenoic acid (EPA). At the local site of inflammation, aspirin treatment enhances EPA conversion to 18R-oxygenated products, including RvE1, which carry potent antiinflammatory signals. Here, we obtained evidence for reduced leukocyte infiltration in a mouse peritonitis model, where the administration of EPA and aspirin initiated the generation of RvE1 in the exudates. Similar results were obtained with the administration of synthetic RvE1, which blocked leukocyte infiltration. RvE1 also protected against the development of 2,4,6-trinitrobenzene sulfonic acid-induced colitis. The beneficial effect was reflected by increased survival...
92.
The frequencies of calcium oscillations are optimized for efficient calcium-mediated activation of Ras and the ERK/MAPK cascade - Kupzig, Sabine; Walker, Simon A.; Cullen, Peter J.
Ras proteins are binary switches that, by cycling through inactive GDP- and active GTP-bound conformations, regulate multiple cellular signaling pathways, including those that control growth and differentiation. For some time, it has been known that receptor-mediated increases in the concentration of intracellular free calcium ([Ca2+]i) can modulate Ras activation. Increases in [Ca2+]i often occur as repetitive Ca2+ spikes or oscillations. Induced by electrical or receptor stimuli, these repetitive Ca2+ oscillations increase in frequency with the amplitude of receptor stimuli, a phenomenon critical for the induction of selective cellular functions. Here, we show that Ca2+ oscillations are optimized for Ca2+-mediated activation...
93.
The importance of weak absorption features in promoting tropospheric radical production - Matthews, Jamie; Sinha, Amitabha; Francisco, Joseph S.
Atmospheric field measurement and modeling studies have long noted discrepancies between observation and predictions of OH and HO2 concentrations in the atmosphere. Novel photochemical mechanisms have been proposed to explain these differences. Although inclusion of these additional sources improves agreement, they are unable to fully account for the observations. We report and demonstrate the importance of weak electronic absorption features, normally ignored or not measured, in contributing to significant OH radical production. Experiments on methyl hydroperoxide, a prototypical organic peroxide in large abundance in the troposphere, highlights how photochemistry in the neglected electronic absorption tail makes an important addition to...
94.
CD147 is a regulatory subunit of the ?-secretase complex in Alzheimer's disease amyloid ?-peptide production - Zhou, Shuxia; Zhou, Hua; Walian, Peter J.; Jap, Bing K.
?-Secretase is a membrane protein complex that cleaves the ?-amyloid precursor protein (APP) within the transmembrane region, after prior processing by ?-secretase, producing amyloid ?-peptides A?40 and A?42. Errant production of A?-peptides that substantially increases A?42 production has been associated with the formation of amyloid plaques in Alzheimer's disease patients. Biophysical and genetic studies indicate that presenilin-1, which contains the proteolytic active site, and three other membrane proteins [nicastrin, anterior pharynx defective-1 (APH-1), and presenilin enhancer-2 (PEN-2)] are required to form the core of the active ?-secretase complex. Here, we report the purification of the native ?-secretase complexes from HeLa...
95.
Using fingerprint image quality to improve the identification performance of the U.S. Visitor and Immigrant Status Indicator Technology Program - Wein, Lawrence M.; Baveja, Manas
Motivated by the difficulty of biometric systems to correctly match fingerprints with poor image quality, we formulate and solve a game-theoretic formulation of the identification problem in two settings: U.S. visa applicants are checked against a list of visa holders to detect visa fraud, and visitors entering the U.S. are checked against a watchlist of criminals and suspected terrorists. For three types of biometric strategies, we solve the game in which the U.S. Government chooses the strategy's optimal parameter values to maximize the detection probability subject to a constraint on the mean biometric processing time per legal visitor, and then...
96.
Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog - Premkumar, Lakshmanane; Greenblatt, Harry M.; Bageshwar, Umesh K.; Savchenko, Tatyana; Gokhman, Irena; Sussman, Joel L.; Zamir, Ada
Protein molecular adaptation to drastically shifting salinities was studied in dCA II, an ?-type carbonic anhydrase (EC 4.2.1.1) from the exceptionally salt-tolerant unicellular green alga Dunaliella salina. The salt-inducible, extracellular dCA II is highly salt-tolerant and thus differs from its mesophilic homologs. The crystal structure of dCA II, determined at 1.86-Å resolution, is globally similar to other ?-type carbonic anhydrases except for two extended ?-helices and an added Na-binding loop. Its unusual electrostatic properties include a uniformly negative surface electrostatic potential of lower magnitude than that observed in the highly acidic halophilic proteins and an exceptionally low positive potential at...
97.
Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib - Kwak, Eunice L.; Sordella, Raffaella; Bell, Daphne W.; Godin-Heymann, Nadia; Okimoto, Ross A.; Brannigan, Brian W.; Harris, Patricia L.; Driscoll, David R.; Fidias, Panos; Lynch, Thomas J.; Rabindran, Sridhar K.; McGinnis, John P.; Wissner, Allan; Sharma, Sreenath V.; Isselbacher, Kurt J.; Settleman, Jeffrey; Haber, Daniel A.
Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to...
98.
VEGFintegrin interplay controls tumor growth and vascularization - De, Sarmishtha; Razorenova, Olga; McCabe, Noel Patrick; O'Toole, Timothy; Qin, Jun; Byzova, Tatiana V.
Cross-talk between the major angiogenic growth factor, VEGF, and integrin cell adhesion receptors has emerged recently as a critical factor in the regulation of angiogenesis and tumor development. However, the molecular mechanisms and consequences of this intercommunication remain unclear. Here, we define a mechanism whereby integrin ?v?3, through activation, clustering, and signaling by means of p66 Shc (Src homology 2 domain containing), regulates the production of VEGF in tumor cells expressing this integrin. Tumors with activatable but not inactive ?3 integrin secrete high levels of VEGF, which in turn promotes extensive neovascularization and augments tumor growth in vivo. This stimulation...
99.
Sumoylation induced by the Arf tumor suppressor: A p53-independent function - Tago, Kenji; Chiocca, Susanna; Sherr, Charles J.
The mouse p19Arf protein has both p53-dependent and p53-independent tumor-suppressive activities. Arf triggers sumoylation of many cellular proteins, including Mdm2 and nucleophosmin (NPM/B23), with which p19Arf physically interacts in vivo, and this occurs equally well in cells expressing or lacking functional p53. In an Arf-null NIH 3T3 cell derivative (MT-Arf cells) engineered to reexpress an Arf transgene driven by a zinc-inducible metallothionein promoter, sumoylation of endogenous Mdm2 and NPM proteins was initiated as p19Arf was induced and was observed before p53-dependent cell cycle arrest. Predominately nucleoplasmic molecules visualized by immunofluorescence with antibodies to small ubiquitin-like modifier (SUMO) 1 localized to...
100.
Targeting quantum dots to surface proteins in living cells with biotin ligase - Howarth, Mark; Takao, Keizo; Hayashi, Yasunori; Ting, Alice Y.
Escherichia coli biotin ligase site-specifically biotinylates a lysine side chain within a 15-amino acid acceptor peptide (AP) sequence. We show that mammalian cell surface proteins tagged with AP can be biotinylated by biotin ligase added to the medium, while endogenous proteins remain unmodified. The biotin group then serves as a handle for targeting streptavidin-conjugated quantum dots (QDs). This labeling method helps to address the two major deficiencies of antibody-based labeling, which is currently the most common method for targeting QDs to cells: the size of the QD conjugate after antibody attachment and the instability of many antibodyantigen interactions. To demonstrate...
81.
