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 101 - 120 de 184,040
101.
A vital role of tubulin-tyrosine-ligase for neuronal organization - Erck, Christian; Peris, Leticia; Andrieux, Annie; Meissirel, Claire; Gruber, Achim D.; Vernet, Muriel; Schweitzer, Annie; Saoudi, Yasmina; Pointu, Hervé; Bosc, Christophe; Salin, Paul A.; Job, Didier; Wehland, Juergen
Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of ?-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL). This tyrosination cycle is conserved in evolution, yet its physiological importance is unknown. Here, we find that TTL suppression in mice causes perinatal death. A minor pool of tyrosinated (Tyr-)tubulin persists in TTL null tissues, being present mainly in dividing TTL null cells where it originates from tubulin synthesis, but it is lacking in postmitotic TTL null cells such as neurons, which is apparently deleterious because early death in TTL null mice...
102.
Human-modified temperatures induce species changes: Joint attribution - Root, Terry L.; MacMynowski, Dena P; Mastrandrea, Michael D.; Schneider, Stephen H.
Average global surface-air temperature is increasing. Contention exists over relative contributions by natural and anthropogenic forcings. Ecological studies attribute plant and animal changes to observed warming. Until now, temperaturespecies connections have not been statistically attributed directly to anthropogenic climatic change. Using modeled climatic variables and observed species data, which are independent of thermometer records and paleoclimatic proxies, we demonstrate statistically significant joint attribution, a two-step linkage: human activities contribute significantly to temperature changes and human-changed temperatures are associated with discernible changes in plant and animal traits. Additionally, our analyses provide independent testing of grid-box-scale temperature projections from a general circulation...
103.
Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells - Herzog, Jeremy; Maekawa, Yoichi; Cirrito, Thomas P.; Illian, Beverly S.; Unanue, Emil R.
CD4 T cells recognized posttranslationally modified peptides of the protein hen egg-white lysozyme (HEL), consisting of nitration of tyrosines and modifications of tryptophans in the T cell contact residues of the peptides. T cells were directed against modifications of a chemically dominant HEL peptide as well as a minor HEL peptide, bound to the class II histocompatibility molecule I-Ak. The modified peptides were generated in vivo after immunization with native HEL molecules or were generated ex vivo by peroxynitrite treatment of HEL. Moreover, antigen-presenting cells (APC), either macrophages or dendritic cells activated in culture or in vivo, generated the modified...
104.
Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans - Song, Kaimei; Rabin, Ronald L.; Hill, Brenna J.; De Rosa, Stephen C.; Perfetto, Stephen P.; Zhang, Hongwei H.; Foley, John F.; Reiner, Jeffrey S.; Liu, Jie; Mattapallil, Joseph J.; Douek, Daniel C.; Roederer, Mario; Farber, Joshua M.
The pathways for differentiation of human CD4+ T cells into functionally distinct subsets of memory cells in vivo are unknown. The identification of these subsets and pathways has clear implications for the design of vaccines and immune-targeted therapies. Here, we show that populations of apparently naïve CD4+ T cells express the chemokine receptors CXCR3 or CCR4 and demonstrate patterns of gene expression and functional responses characteristic of memory cells. The proliferation history and T cell receptor repertoire of these chemokine-receptor+ cells suggest that they are very early memory CD4+ T cells that have rested down before acquiring the phenotypes described...
105.
Rapid identification and strain-typing of respiratory pathogens for epidemic surveillance - Ecker, David J.; Sampath, Rangarajan; Blyn, Lawrence B.; Eshoo, Mark W.; Ivy, Cristina; Ecker, Joseph A.; Libby, Brian; Samant, Vivek; Sannes-Lowery, Kristin A.; Melton, Rachael E.; Russell, Kevin; Freed, Nikki; Barrozo, Chris; Wu, Jianguo; Rudnick, Karl; Desai, Anjali; Moradi, Emily; Knize, Duane J.; Robbins, David W.; Hannis, James C.; Harrell, Patina M.; Massire, Christian; Hall, Thomas A.; Jiang, Yun; Ranken, Raymond; Drader, Jared J.; White, Neill; McNeil, John A.; Crooke, Stanley T.; Hofstadler, Steven A.
Epidemic respiratory infections are responsible for extensive morbidity and mortality within both military and civilian populations. We describe a high-throughput method to simultaneously identify and genotype species of bacteria from complex mixtures in respiratory samples. The process uses electrospray ionization mass spectrometry and base composition analysis of PCR amplification products from highly conserved genomic regions to identify and determine the relative quantity of pathogenic bacteria present in the sample. High-resolution genotyping of specific species is achieved by using additional primers targeted to highly variable regions of specific bacterial genomes. This method was used to examine samples taken from military recruits...
106.
Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase - Ro, Dae-Kyun; Arimura, Gen-Ichiro; Lau, Stephen Y. W.; Piers, Edward; Bohlmann, Jörg
Cytochrome P450 monooxygenases (P450s) are important enzymes for generating some of the enormous structural diversity of plant terpenoid secondary metabolites. In conifers, P450s are involved in the formation of a suite of diterpene resin acids (DRAs). Despite their important role in constitutive and induced oleoresin defense, a P450 gene of DRA formation has not yet been identified. By using phylogenetic cluster analysis of P450-like ESTs from loblolly pine (Pinus taeda), functional cDNA screening in yeast (Saccharomyces cerevisiae), and in vitro enzyme characterization, we cloned and identified a multifunctional and multisubstrate cytochrome P450 enzyme, CYP720B1 [abietadienol/abietadienal oxidase (PtAO)]. PtAO catalyzes an...
107.
Epigenetic programming in the preimplantation rat embryo is disrupted by chronic paternal cyclophosphamide exposure - Barton, Tara S.; Robaire, Bernard; Hales, Barbara F.
Preconceptional paternal exposure to cyclophosphamide, a widely used anticancer agent, leads to increases in embryo loss, malformations, and behavioral deficits in offspring; these abnormalities are transmissible to subsequent generations [Auroux, M., Dulioust, E., Selva, J. & Rince, P. (1990) Mutat. Res. 229, 189200]. Little information exists on the mechanisms underlying this male-mediated developmental toxicity. We assessed the impact of paternal cyclophosphamide exposure on the dynamic regulation of histone H4 acetylation at lysine 5 and DNA methylation in preimplantation rat embryos. Zygotes sired by drug-treated males displayed advanced developmental progression, increased pronuclear areas, and disruption of the epigenetic programming of both...
108.
Anthrax lethal factor inhibition - Shoop, W. L.; Xiong, Y.; Wiltsie, J.; Woods, A.; Guo, J.; Pivnichny, J. V.; Felcetto, T.; Michael, B. F.; Bansal, A.; Cummings, R. T.; Cunningham, B. R.; Friedlander, A. M.; Douglas, C. M.; Patel, S. B.; Wisniewski, D.; Scapin, G.; Salowe, S. P.; Zaller, D. M.; Chapman, K. T.; Scolnick, E. M.; Schmatz, D. M.; Bartizal, K.; MacCoss, M.; Hermes, J. D.
The primary virulence factor of Bacillus anthracis is a secreted zinc-dependent metalloprotease toxin known as lethal factor (LF) that is lethal to the host through disruption of signaling pathways, cell destruction, and circulatory shock. Inhibition of this proteolytic-based LF toxemia could be expected to provide therapeutic value in combination with an antibiotic during and immediately after an active anthrax infection. Herein is shown the crystal structure of an intimate complex between a hydroxamate, (2R)-2-[(4-fluoro-3-methylphenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, and LF at the LF-active site. Most importantly, this molecular interaction between the hydroxamate and the LF active site resulted in (i) inhibited LF protease activity...
109.
Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments - McCormick, Peter J.; Martina, José A.; Bonifacino, Juan S.
Major histocompatibility complex class II (MHC-II) molecules are composed of two polymorphic chains, ? and ?, which assemble with an invariant chain, Ii, in the endoplasmic reticulum. The assembled MHC-II complexes are transported to the Golgi complex and then to late endosomes/lysosomes, where Ii is degraded and ?? dimers bind peptides derived from exogenous antigens. Targeting of MHC-II molecules to these compartments is mediated by two dileucine-based signals in the cytoplasmic domain of Ii. These signals bind in vitro to two adaptor protein (AP) complexes, AP-1 and AP-2, which are components of clathrin coats involved in vesicle formation and cargo...
110.
MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes - Erion, Mark D.; van Poelje, Paul D.; Dang, Qun; Kasibhatla, Srinivas Rao; Potter, Scott C.; Reddy, M. Rami; Reddy, K. Raja; Jiang, Tao; Lipscomb, William N.
In type 2 diabetes, the liver produces excessive amounts of glucose through the gluconeogenesis (GNG) pathway and consequently is partly responsible for the elevated glucose levels characteristic of the disease. In an effort to find safe and efficacious GNG inhibitors, we targeted the AMP binding site of fructose 1,6-bisphosphatase (FBPase). The hydrophilic nature of AMP binding sites and their widespread use for allosteric regulation of enzymes in metabolic pathways has historically made discovery of AMP mimetics suitable for drug development difficult. By using a structure-based drug design strategy, we discovered a series of compounds that mimic AMP but bear little...
111.
Odor maps in the olfactory cortex - Zou, Zhihua; Li, Fusheng; Buck, Linda B.
In the olfactory system, environmental chemicals are deconstructed into neural signals and then reconstructed to form odor perceptions. Much has been learned about odor coding in the olfactory epithelium and bulb, but little is known about how odors are subsequently encoded in the cortex to yield diverse perceptions. Here, we report that the representation of odors by fixed glomeruli in the olfactory bulb is transformed in the cortex into highly distributed and multiplexed odor maps. In the mouse olfactory cortex, individual odorants are represented by subsets of sparsely distributed neurons. Different odorants elicit distinct, but partially overlapping, patterns that are...
112.
Holliday junction dynamics and branch migration: Single-molecule analysis - Karymov, Mikhail; Daniel, Douglas; Sankey, Otto F.; Lyubchenko, Yuri L.
The Holliday junction (HJ) is a central intermediate in various genetic processes including homologous and site-specific recombination and DNA replication. Branch migration allows the exchange between homologous DNA regions, but the detailed mechanism for this key step of DNA recombination is unidentified. Here, we report direct real-time detection of branch migration in individual molecules. Using appropriately designed HJ constructs we were able to follow junction branch migration at the single-molecule level. Branch migration is detected as a stepwise random process with the overall kinetics dependent on Mg2+ concentration. We developed a theoretical approach to analyze the mechanism of HJ branch...
113.
Sensitive detection of human papillomavirus in cervical, head/neck, and schistosomiasis-associated bladder malignancies - Yang, H.; Yang, K.; Khafagi, A.; Tang, Y.; Carey, T. E.; Opipari, A. W.; Lieberman, R.; Oeth, P. A.; Lancaster, W.; Klinger, H. P.; Kaseb, A. O.; Metwally, A.; Khaled, H.; Kurnit, D. M.
We assayed for the presence of human papilloma virus (HPV) DNA in serum and/or peripheral blood fraction (PBF) of individuals with cervical, head/neck, or bladder cancer due to schistosomiasis. Using mass spectroscopy coupled with competitive PCR, HPV DNA was detected at the individual molecule level by using MassARRAY assays. The resultant sensitivity was superior to real-time fluorescent PCR-based assays, while specificity was maintained. Our principal findings were: (i) Virtually all tested cervical cancers and schistosomiasis-associated bladder cancers, and a plurality of head/neck cancers, are associated with HPV DNA in the tumor. (ii) All 27 bladder cancers due to schistosomiasis were...
114.
Development of a transgenic mouse model susceptible to human coronavirus 229E - Lassnig, Caroline; Sanchez, Carlos M.; Egerbacher, Monika; Walter, Ingrid; Majer, Susanne; Kolbe, Thomas; Pallares, Pilar; Enjuanes, Luis; Müller, Mathias
Human coronavirus (HCoV) 229E is a group 1 coronavirus and is specific to humans. So far, no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into signal transducers and activators of transcription (Stat) 1 null mice and by adaptation of HCoV-229E to grow in primary APN transgenic, Stat1 null fibroblasts. Double transgenic mice allow the study of human coronavirus group...
115.
Electrostatic mechanism of nucleosomal array folding revealed by computer simulation - Sun, Jian; Zhang, Qing; Schlick, Tamar
Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended beads-on-a-string conformation at low salt. Energy analyses indicate that the repulsion among linker...
116.
Climate change threats to plant diversity in Europe - Thuiller, Wilfried; Lavorel, Sandra; Araújo, Miguel B.; Sykes, Martin T.; Prentice, I. Colin
Climate change has already triggered species distribution shifts in many parts of the world. Increasing impacts are expected for the future, yet few studies have aimed for a general understanding of the regional basis for species vulnerability. We projected late 21st century distributions for 1,350 European plants species under seven climate change scenarios. Application of the International Union for Conservation of Nature and Natural Resources Red List criteria to our projections shows that many European plant species could become severely threatened. More than half of the species we studied could be vulnerable or threatened by 2080. Expected species loss and...
117.
Hamilton's indicators of the force of selection - Baudisch, Annette
To quantify the force of selection, Hamilton [Hamilton, W. D. (1966) J. Theor. Biol. 12, 1245] derived expressions for the change in fitness with respect to age-specific mutations. Hamilton's indicators are decreasing functions of age. He concluded that senescence is inevitable: survival and fertility decline with age. I show that alternative parameterizations of mutational effects lead to indicators that can increase with age. I then consider the case of deleterious mutations with age-specific effects. In this case, it is the balance between mutation and selection pressure that determines the equilibrium number of mutations in a population. In this balance, the...
118.
Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia - Gold, Philip W.; Wong, Ma-Li; Goldstein, David S.; Gold, Herman K.; Ronsaville, Donna S.; Esler, Murray; Alesci, Salvatore; Masood, Anwar; Licinio, Julio; Geracioti, Thomas D.; Perini, Giulia; DeBellis, Michael D.; Holmes, Courtney; Vgontzas, Alexandros N.; Charney, Dennis S.; Chrousos, George P.; McCann, Samuel M.; Kling, Mitchel A.
The mortality of chronic heart failure (CHF) doubles either when CHF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by ?40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed...
119.
Dynamic positioning of the fission yeast cell division plane - Daga, Rafael R.; Chang, Fred
A key question in cytokinesis is how the cell division plane is positioned. Whereas microtubules of the mitotic apparatus specify the division site in animal cells, we show here that the nucleus plays this role in the fission yeast Schizosaccharomyces pombe. By centrifuging cells to move the nucleus, we find that the nucleus (or a nuclear-associated structure) actively influences the position of contractile ring assembly during early mitosis. Displacement of the nucleus during this induction period can lead to formation of multiple rings. The nucleus signals its position in a microtubule-independent manner by emitting the protein mid1p. Furthermore, movement of...
120.
The coordinate regulation of the p53 and mTOR pathways in cells - Feng, Zhaohui; Zhang, Haiyan; Levine, Arnold J.; Jin, Shengkan
Cell growth and proliferation requires an intricate coordination between the stimulatory signals arising from nutrients and growth factors and the inhibitory signals arising from intracellular and extracellular stresses. Alteration of the coordination often causes cancer. In mammals, the mTOR (mammalian target of rapamycin) protein kinase is the central node in nutrient and growth factor signaling, and p53 plays a critical role in sensing genotoxic and other stresses. The results presented here demonstrate that activation of p53 inhibits mTOR activity and regulates its downstream targets, including autophagy, a tumor suppression process. Moreover, the mechanisms by which p53 regulates mTOR involves AMP...
101.
