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 181 - 200 de 184,040
181.
DNA lesions induced by UV A1 and B radiation in human cells: Comparative analyses in the overall genome and in the p53 tumor suppressor gene - Besaratinia, Ahmad; Synold, Timothy W.; Chen, Hsiu-Hua; Chang, Cheng; Xi, Bixin; Riggs, Arthur D.; Pfeifer, Gerd P.
The UV components of sunlight (UVA and UVB) are implicated in the etiology of human skin cancer. The underlying mechanism of action for UVB carcinogenicity is well defined; however, the mechanistic involvement of UVA in carcinogenesis is not fully delineated. We investigated the genotoxicity of UVA1 versus UVB in the overall genome and in the p53 tumor suppressor gene in normal human skin fibroblasts. Immuno-dot blot analysis identified the cis-syn cyclobutane pyrimidine-dimer (CPD) as a distinctive UVB-induced lesion and confirmed its formation in the genomic DNA of UVA1-irradiated cells dependent on radiation dose. HPLC/tandem MS analysis showed an induction of...
182.
A reversible molecular valve - Nguyen, Thoi D.; Tseng, Hsian-Rong; Celestre, Paul C.; Flood, Amar H.; Liu, Yi; Stoddart, J. Fraser; Zink, Jeffrey I.
In everyday life, a macroscopic valve is a device with a movable control element that regulates the flow of gases or liquids by blocking and opening passageways. Construction of such a device on the nanoscale level requires (i) suitably proportioned movable control elements, (ii) a method for operating them on demand, and (iii) appropriately sized passageways. These three conditions can be fulfilled by attaching organic, mechanically interlocked, linear motor molecules that can be operated under chemical, electrical, or optical stimuli to stable inorganic porous frameworks (i.e., by self-assembling organic machinery on top of an inorganic chassis). In this article, we...
183.
Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase - Luo, Ji; Sobkiw, Cassandra L.; Logsdon, Nicole M.; Watt, John M.; Signoretti, Sabina; O'Connell, Fionnuala; Shin, Eyoung; Shim, Youngju; Pao, Lily; Neel, Benjamin G.; DePinho, Ronald A.; Loda, Massimo; Cantley, Lewis C.
Mice with heterozygous deletion of the PTEN tumor suppressor gene develop a range of epithelial neoplasia as well as lymphoid hyperplasia. Previous studies suggest that PTEN suppresses tumor formation by acting as a phosphoinositide phosphatase to limit signaling by phosphoinositide 3-kinase (PI3K). Here, we examined the effect of deleting various regulatory subunits of PI3K (p85? and p85?) on epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice. Interestingly, we found the loss of one p85? allele with or without the loss of p85? led to increased incidence of intestinal polyps. Signaling downstream of PI3K was enhanced in the PTEN+/-p85?+/-p85?-/- polyps, as...
184.
Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition - Chang, Chung-I; Ihara, Kentaro; Chelliah, Yogarany; Mengin-Lecreulx, Dominique; Wakatsuki, Soichi; Deisenhofer, Johann
The peptidoglycan-recognition protein LCa (PGRP-LCa) is a transmembrane receptor required for activation of the Drosophila immune deficiency pathway by monomeric Gram-negative peptidoglycan. We have determined the crystal structure of the ectodomain of PGRP-LCa at 2.5-Å resolution and found two unique helical insertions in the LCa ectodomain that disrupt an otherwise L-shaped peptidoglycan-docking groove present in all other known PGRP structures. The deficient binding of PGRP-LCa to monomeric peptidoglycan was confirmed by biochemical pull-down assays. Recognition of monomeric peptidoglycan involves both PGRP-LCa and -LCx. We showed that association of the LCa and LCx ectodomains in vitro depends on monomeric peptidoglycan. The...
185.
One-dimensional hole gas in germanium/silicon nanowire heterostructures - Lu, Wei; Xiang, Jie; Timko, Brian P.; Wu, Yue; Lieber, Charles M.
Two-dimensional electron and hole gas systems, enabled through band structure design and epitaxial growth on planar substrates, have served as key platforms for fundamental condensed matter research and high-performance devices. The analogous development of one-dimensional (1D) electron or hole gas systems through controlled growth on 1D nanostructure substrates, which could open up opportunities beyond existing carbon nanotube and nanowire systems, has not been realized. Here, we report the synthesis and transport studies of a 1D hole gas system based on a free-standing germanium/silicon (Ge/Si) core/shell nanowire heterostructure. Room temperature electrical transport measurements clearly show hole accumulation in undoped Ge/Si nanowire...
186.
Ratcheting of the substrate from the zymogen to proteinase conformations directs the sequential cleavage of prothrombin by prothrombinase - Bianchini, Elsa P.; Orcutt, Steven J.; Panizzi, Peter; Bock, Paul E.; Krishnaswamy, Sriram
Prothrombinase catalyzes thrombin formation by the ordered cleavage of two peptide bonds in prothrombin. Although these bonds are likely ?36 Å apart, sequential cleavage of prothrombin at Arg-320 to produce meizothrombin, followed by its cleavage at Arg-271, are both accomplished by equivalent exosite interactions that tether each substrate to the enzyme and facilitate presentation of the scissile bond to the active site of the catalyst. We show that impairing the conformational transition from zymogen to active proteinase that accompanies the formation of meizothrombin has no effect on initial cleavage at Arg-320 but inhibits subsequent cleavage at Arg-271. Full thermodynamic rescue...
187.
The structure of the 80S ribosome from Trypanosoma cruzi reveals unique rRNA components - Gao, Haixiao; Ayub, Maximiliano Juri; Levin, Mariano J.; Frank, Joachim
We present analysis, by cryo-electron microscopy and single-particle reconstruction, of the structure of the 80S ribosome from Trypanosoma cruzi, the kinetoplastid protozoan pathogen that causes Chagas disease. The density map of the T. cruzi 80S ribosome shows the phylogenetically conserved eukaryotic rRNA core structure, together with distinctive structural features in both the small and large subunits. Remarkably, a previously undescribed helical structure appears in the small subunit in the vicinity of the mRNA exit channel. We propose that this rRNA structure likely participates in the recruitment of ribosome onto the 5? end of mRNA, in facilitating and modulating the initiation...
188.
Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted HutchinsonGilford progeria syndrome mutation - Yang, Shao H.; Bergo, Martin O.; Toth, Julia I.; Qiao, Xin; Hu, Yan; Sandoval, Salemiz; Meta, Margarita; Bendale, Pravin; Gelb, Michael H.; Young, Stephen G.; Fong, Loren G.
HutchinsonGilford progeria syndrome (HGPS), a progeroid syndrome in children, is caused by mutations in LMNA (the gene for prelamin A and lamin C) that result in the deletion of 50 aa within prelamin A. In normal cells, prelamin A is a CAAX protein that is farnesylated and then processed further to generate mature lamin A, which is a structural protein of the nuclear lamina. The mutant prelamin A in HGPS, which is commonly called progerin, retains the CAAX motif that triggers farnesylation, but the 50-aa deletion prevents the subsequent processing to mature lamin A. The presence of progerin adversely affects...
189.
Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesis - Rodriguez, Jorge A.; Shaw, Bryan Francis; Durazo, Armando; Sohn, Se Hui; Doucette, Peter A.; Nersissian, Aram M.; Faull, Kym F.; Eggers, Daryl K.; Tiwari, Ashutosh; Hayward, Lawrence J.; Valentine, Joan Selverstone
The relative stabilities and structural properties of a representative set of 20 ALS-mutant Cu,Zn-superoxide dismutase apoproteins were examined by using differential scanning calorimetry and hydrogen-deuterium (H/D) exchange followed by MS. Contrary to recent reports from other laboratories, we found that ALS-mutant apoproteins are not universally destabilized by the disease-causing mutations. For example, several of the apoproteins with substitutions at or near the metal binding region (MBR) (MBR mutants) exhibited melting temperatures (Tm) in the range 51.6°C to 56.2°C, i.e., similar to or higher than that of the WT apoprotein (Tm = 52.5°C). The apoproteins with substitutions remote from the MBR...
190.
Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth - Benson, M. Douglas; Romero, Mario I.; Lush, Mark E.; Lu, Q. Richard; Henkemeyer, Mark; Parada, Luis F.
The inability of CNS axons to regenerate after traumatic spinal cord injury is due, in part, to the inhibitory effects of myelin. The three major previously identified constituents of this activity (Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein) were isolated based on their potent inhibition of axon outgrowth in vitro. All three myelin components transduce their inhibitory signals through the same Nogo receptor/p75 neurotrophin receptor/LINGO-1 (NgR1/p75/LINGO-1) complex. In this study, we considered that molecules known to act as repellants in vertebrate embryonic axonal pathfinding may also inhibit regeneration. In mice, ephrin-B3 functions during development as a midline repellant for axons...
191.
Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus - McIntyre, Christa K.; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D.; Steward, Oswald; Guzowski, John F.; McGaugh, James L.
Activation of ?-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the ?-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of...
192.
An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus - Wiedenheft, Blake; Mosolf, Jesse; Willits, Deborah; Yeager, Mark; Dryden, Kelly A.; Young, Mark; Douglas, Trevor
Evolution of an oxygenic atmosphere required primordial life to accommodate the toxicity associated with reactive oxygen species. We have characterized an archaeal antioxidant from the hyperthermophilic acidophile Sulfolobus solfataricus. The amino acid sequence of this ?22-kDa protein shares little sequence similarity with proteins with known function. However, the protein shares high sequence similarity with hypothetical proteins in other archaeal and bacterial genomes. Nine of these hypothetical proteins form a monophyletic cluster within the broad superfamily of ferritin-like diiron-carboxylate proteins. Higher order structural predictions and image reconstructions indicate that the S. solfataricus protein is structurally related to a class of DNA-binding...
193.
Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms - Morishita, Tsuyoshi; Tsutsui, Masato; Shimokawa, Hiroaki; Sabanai, Ken; Tasaki, Hiromi; Suda, Osamu; Nakata, Sei; Tanimoto, Akihide; Wang, Ke-Yong; Ueta, Yoichi; Sasaguri, Yasuyuki; Nakashima, Yasuhide; Yanagihara, Nobuyuki
Nitric oxide (NO) is produced in almost all tissues and organs, exerting a variety of biological actions under physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS), including neuronal, inducible, and endothelial NOSs. Because there are substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. Here, we have successfully developed mice in which all three NOS genes are completely deleted by crossbreeding singly NOS-/- mice. NOS expression and activities were totally absent in the triply NOS-/- mice before and after treatment...
194.
Ethylene-mediated cross-talk between calcium-dependent protein kinase and MAPK signaling controls stress responses in plants - Ludwig, Andrea A.; Saitoh, Hiromasa; Felix, Georg; Freymark, Gerald; Miersch, Otto; Wasternack, Claus; Boller, Thomas; Jones, Jonathan D. G.; Romeis, Tina
Plants are constantly exposed to environmental changes and need to integrate multiple external stress cues. Calcium-dependent protein kinases (CDPKs) are implicated as major primary Ca2+ sensors in plants. CDPK activation, like activation of mitogen-activated protein kinases (MAPKs), is triggered by biotic and abiotic stresses, although distinct stimulus-specific stress responses are induced. To investigate whether CDPKs are part of an underlying mechanism to guarantee response specificity, we identified CDPK-controlled signaling pathways. A truncated form of Nicotiana tabacum CDPK2 lacking its regulatory autoinhibitor and calcium-binding domains was ectopically expressed in Nicotiana benthamiana. Infiltrated leaves responded to an abiotic stress stimulus with the...
195.
Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein - Arai, Hirofumi; Berlett, Barbara S.; Chock, P. Boon; Stadtman, Earl R.
Oxidation of low-density lipoprotein (LDL) may play an important role in atherosclerosis. We studied the effects of bicarbonate/CO2 and phosphate buffer systems on metal ion-catalyzed oxidation of LDL to malondialdehyde (MDA) and to protein carbonyl and MetO derivatives. Our results revealed that LDL oxidation in mixtures containing free iron or heme derivatives was much greater in bicarbonate/CO2 compared with phosphate buffer. However, when copper was substituted for iron in these mixtures, the rate of LDL oxidation in both buffers was similar. Iron-catalyzed oxidation of LDL was highly sensitive to inhibition by phosphate. Presence of 0.3-0.5 mM phosphate, characteristic of human...
196.
Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation - Bordeleau, Marie-Eve; Matthews, James; Wojnar, Joanna M.; Lindqvist, Lisa; Novac, Olivia; Jankowsky, Eckhard; Sonenberg, Nahum; Northcote, Peter; Teesdale-Spittle, Paul; Pelletier, Jerry
RNA helicases are the largest group of enzymes in eukaryotic RNA metabolism. The DEXD/H-box putative RNA helicases form the helicase superfamily II, whose members are defined by seven highly conserved amino acid motifs, making specific targeting of selected members a challenging pharmacological problem. The translation initiation factor eIF4A is the prototypical DEAD-box RNA helicase that works in conjunction with eIF4B and eIF4H and as a subunit of eIF4F to prepare the mRNA template for ribosome binding, possibly by unwinding the secondary structure proximal to the 5? m7GpppN cap structure. We report the identification and characterization of a small molecule inhibitor...
197.
Mutually dependent secretion of proteins required for mycobacterial virulence - Fortune, S. M.; Jaeger, A.; Sarracino, D. A.; Chase, M. R.; Sassetti, C. M.; Sherman, D. R.; Bloom, B. R.; Rubin, E. J.
The ESX-1 locus is a region critical for full virulence in Mycobacterium tuberculosis, which encodes two secreted proteins as well as other genes involved in their secretion. The mechanism of secretion of the two proteins, ESAT-6 and CFP-10, and their function remain unknown. Using proteomic methods to search for additional proteins secreted by the ESX-1 locus, we discovered that a protein encoded by a chromosomally unlinked gene, espA, is also secreted by strains that contain the ESX-1 locus but not by strains with ESX-1 deletions. Mutations in individual ESX-1 genes, including those that encode ESAT-6 and CFP-10, were found to...
198.
Evolution of heterochromatic genes of Drosophila - Yasuhara, Jiro C.; DeCrease, Christine H.; Wakimoto, Barbara T.
Heterochromatin is generally associated with gene silencing, yet in Drosophila melanogaster, heterochromatin harbors hundreds of functional protein-encoding genes, some of which depend on heterochromatin for expression. Here we document a recent evolutionary transition of a gene cluster from euchromatin to heterochromatin, which occurred <20 million years ago in the drosophilid lineage. This finding reveals evolutionary fluidity between these two genomic compartments and provides a powerful approach to identifying differences between euchromatic and heterochromatic genes. Promoter mapping of orthologous gene pairs led to the discovery of the slippery promoter, characterized by multiple transcriptional start sites predominately at adenines, as a common...
199.
Obesity alters gut microbial ecology - Ley, Ruth E.; Bäckhed, Fredrik; Turnbaugh, Peter; Lozupone, Catherine A.; Knight, Robin D.; Gordon, Jeffrey I.
We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that,...
200.
Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells - Chintala, Sreenivasulu; Li, Wei; Lamoreux, M. Lynn; Ito, Shosuke; Wakamatsu, Kazumasa; Sviderskaya, Elena V.; Bennett, Dorothy C.; Park, Young-Mee; Gahl, William A.; Huizing, Marjan; Spritz, Richard A.; Ben, Songtao; Novak, Edward K.; Tan, Jian; Swank, Richard T.
In mammals, >100 genes regulate pigmentation by means of a wide variety of developmental, cellular, and enzymatic mechanisms. Nevertheless, genes that directly regulate pheomelanin production have not been described. Here, we demonstrate that the subtle gray (sut) mouse pigmentation mutant arose by means of a mutation in the Slc7a11 gene, encoding the plasma membrane cystine/glutamate exchanger xCT [Kanai, Y. & Endou, H. (2001) Curr. Drug Metab. 2, 339-354]. A resulting low rate of extracellular cystine transport into sut melanocytes reduces pheomelanin production. We show that Slc7a11 is a major genetic regulator of pheomelanin pigment in hair and melanocytes, with minimal...
181.
