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 121 - 140 de 184,040
121.
Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions - Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.
Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the...
122.
Use of DNA barcodes to identify flowering plants - Kress, W. John; Wurdack, Kenneth J.; Zimmer, Elizabeth A.; Weigt, Lee A.; Janzen, Daniel H.
Methods for identifying species by using short orthologous DNA sequences, known as DNA barcodes, have been proposed and initiated to facilitate biodiversity studies, identify juveniles, associate sexes, and enhance forensic analyses. The cytochrome c oxidase 1 sequence, which has been found to be widely applicable in animal barcoding, is not appropriate for most species of plants because of a much slower rate of cytochrome c oxidase 1 gene evolution in higher plants than in animals. We therefore propose the nuclear internal transcribed spacer region and the plastid trnH-psbA intergenic spacer as potentially usable DNA regions for applying barcoding to flowering...
123.
Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages - Rengarajan, Jyothi; Bloom, Barry R.; Rubin, Eric J.
Macrophages are central to host defense against microbes, but intracellular pathogens have evolved to evade their antimicrobial functions. Mycobacterium tuberculosis (MTB) has successfully exploited macrophages as its primary niche in vivo, but the bacterial genome-wide requirements that promote its intracellular survival remain undefined. Here we comprehensively identify the MTB genes required for survival by screening for transposon mutants that fail to grow within primary macrophages. We identify mutants showing decreased growth in macrophage environments that model stages of the host immune response. By systematically analyzing several biologically relevant data sets, we have been able to identify putative pathways that could...
124.
Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus - Chan, Kenneth S.; Verardi, Paulo H.; Legrand, Fatema A.; Yilma, Tilahun D.
The nef gene of human and simian immunodeficiency viruses (HIV and SIV) is important for pathogenicity and maintenance of high virus loads. We previously reported that recombinant vaccinia viruses (rVVs) expressing nef from attenuated SIVmac1A11 (vNef1A11) produced typical plaques on thymidine kinase-deficient 143B cells, whereas rVVs expressing nef derived from the pathogenic SIVmac239 (vNef157) formed plaques with altered morphology. Here, we show that vNef157 is attenuated in normal and nude mice, whereas the pathogenicity of vNef1A11 is similar to that of a control virus. Thus, Nef157 is an attenuating factor in the vaccinia virus (VV) system, contrasting sharply with its...
125.
A quantum mechanical polarizable force field for biomolecular interactions - Donchev, A. G.; Ozrin, V. D.; Subbotin, M. V.; Tarasov, O. V.; Tarasov, V. I.
We introduce a quantum mechanical polarizable force field (QMPFF) fitted solely to QM data at the MP2/aTZ(-hp) level. Atomic charge density is modeled by point-charge nuclei and floating exponentially shaped electron clouds. The functional form of interaction energy parallels quantum mechanics by including electrostatic, exchange, induction, and dispersion terms. Separate fitting of each term to the counterpart calculated from high-quality QM data ensures high transferability of QMPFF parameters to different molecular environments, as well as accurate fit to a broad range of experimental data in both gas and liquid phases. QMPFF, which is much more efficient than ab initio QM,...
126.
Identification of genes required for cellulose synthesis by regression analysis of public microarray data sets - Persson, Staffan; Wei, Hairong; Milne, Jennifer; Page, Grier P.; Somerville, Christopher R.
Coexpression patterns of gene expression across many microarray data sets may reveal networks of genes involved in linked processes. To identify factors involved in cellulose biosynthesis, we used a regression method to analyze 408 publicly available Affymetrix Arabidopsis microarrays. Expression of genes previously implicated in cellulose synthesis, as well as several uncharacterized genes, was highly coregulated with expression of cellulose synthase (CESA) genes. Four candidate genes, which were coexpressed with CESA genes implicated in secondary cell wall synthesis, were investigated by mutant analysis. Two mutants exhibited irregular xylem phenotypes similar to those observed in mutants with defects in secondary cellulose...
127.
Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle - Brunelli, Giorgio; Spano, PierFranco; Barlati, Sergio; Guarneri, Bruno; Barbon, Alessandro; Bresciani, Roberto; Pizzi, Marina
Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers....
128.
The NF1 tumor suppressor critically regulates TSC2 and mTOR - Johannessen, Cory M.; Reczek, Elizabeth E.; James, Marianne F.; Brems, Hilde; Legius, Eric; Cichowski, Karen
Loss-of-function mutations in the NF1 tumor suppressor gene underlie the familial cancer syndrome neurofibromatosis type I (NF1). The NF1-encoded protein, neurofibromin, functions as a Ras-GTPase activating protein (RasGAP). Accordingly, deregulation of Ras is thought to contribute to NF1 development. However, the critical effector pathways involved in disease pathogenesis are still unknown. We show here that the mTOR pathway is tightly regulated by neurofibromin. mTOR is constitutively activated in both NF1-deficient primary cells and human tumors in the absence of growth factors. This aberrant activation depends on Ras and PI3 kinase, and is mediated by the phosphorylation and inactivation of the...
129.
Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior - Yao, Lina; McFarland, Krista; Fan, Peidong; Jiang, Zhan; Inoue, Yuichiro; Diamond, Ivan
The nucleus accumbens (NAc) is central to heroin addiction. Activation of opiate receptors in the NAc dissociates Gi/o into ? and ?? subunits. G?i inhibits cAMP production, but ?? regulates several molecular pathways, including protein kinase A (PKA). We show in NAc/striatal neurons that opiates paradoxically activate PKA signaling by means of ?? dimers. Activation requires G?i3 and an activator of G protein signaling 3 (AGS3). AGS3 competes with ?? for binding to G?i3-GDP and enhances the action of unbound ??. AGS3 and G?i3 knockdown prevents opiate activation of PKA signaling. In rats self-administering heroin, AGS3 antisense in the NAc...
130.
Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues - Mijalski, T.; Harder, A.; Halder, T.; Kersten, M.; Horsch, M.; Strom, T. M.; Liebscher, H. V.; Lottspeich, F.; de Angelis, M. Hrab?; Beckers, J.
A major advantage of the mouse model lies in the increasing information on its genome, transcriptome, and proteome, as well as in the availability of a fast growing number of targeted and induced mutant alleles. However, data from comparative transcriptome and proteome analyses in this model organism are very limited. We use DNA chip-based RNA expression profiling and 2D gel electrophoresis, combined with peptide mass fingerprinting of liver and kidney, to explore the feasibility of such comprehensive gene expression analyses. Although protein analyses mostly identify known metabolic enzymes and structural proteins, transcriptome analyses reveal the differential expression of functionally diverse...
131.
Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia - Callicott, Joseph H.; Straub, Richard E.; Pezawas, Lukas; Egan, Michael F.; Mattay, Venkata S.; Hariri, Ahmad R.; Verchinski, Beth A.; Meyer-Lindenberg, Andreas; Balkissoon, Rishi; Kolachana, Bhaskar; Goldberg, Terry E.; Weinberger, Daniel R.
Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with schizophrenia in a family-based sample (P = 0.002). A common nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated with schizophrenia (P = 0.004). Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes. In addition to...
132.
Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors - Okumoto, Sakiko; Looger, Loren L.; Micheva, Kristina D.; Reimer, Richard J.; Smith, Stephen J; Frommer, Wolf B.
Glutamate is the predominant excitatory neurotransmitter in the mammalian brain. Once released, its rapid removal from the synaptic cleft is critical for preventing excitotoxicity and spillover to neighboring synapses. Despite consensus on the role of glutamate in normal and disease physiology, technical issues limit our understanding of its metabolism in intact cells. To monitor glutamate levels inside and at the surface of living cells, genetically encoded nanosensors were developed. The fluorescent indicator protein for glutamate (FLIPE) consists of the glutamate/aspartate binding protein ybeJ from Escherichia coli fused to two variants of the green fluorescent protein. Three sensors with lower affinities...
133.
A general method for greatly improving the affinity of antibodies by using combinatorial libraries - Rajpal, Arvind; Beyaz, Nurten; Haber, Lauric; Cappuccilli, Guido; Yee, Helena; Bhatt, Ramesh R.; Takeuchi, Toshihiko; Lerner, Richard A.; Crea, Roberto
Look-through mutagenesis (LTM) is a multidimensional mutagenesis method that simultaneously assesses and optimizes combinatorial mutations of selected amino acids. The process focuses on a precise distribution within one or more complementarity determining region (CDR) domains and explores the synergistic contribution of amino acid side-chain chemistry. LTM was applied to an anti-TNF-? antibody, D2E7, which is a challenging test case, because D2E7 was highly optimized (Kd = 1 nM) by others. We selected and incorporated nine amino acids, representative of the major chemical functionalities, individually at every position in each CDR and across all six CDRs (57 aa). Synthetic oligonucleotides, each...
134.
Signal peptidechaperone interactions on the twin-arginine protein transport pathway - Hatzixanthis, Kostas; Clarke, Thomas A.; Oubrie, Arthur; Richardson, David J.; Turner, Raymond J.; Sargent, Frank
The twin-arginine transport (Tat) system is a protein-targeting pathway of prokaryotes and chloroplasts. Most Escherichia coli Tat substrates are complex metalloenzymes that must be correctly folded and assembled before transport, and a preexport chaperone-mediated proofreading process is therefore in operation. The paradigm proofreading chaperone is TorD, which coordinates maturation and export of the key respiratory enzyme trimethylamine N-oxide reductase (TorA). It is demonstrated here that purified TorD binds tightly and with exquisite specificity to the TorA twin-arginine signal peptide in vitro. It is also reported that the TorD family constitutes a hitherto unexpected class of nucleotide-binding proteins. The affinity of...
135.
Dissociated phenotypes in presenilin transgenic mice define functionally distinct ?-secretases - Mastrangelo, Peter; Mathews, Paul M.; Chishti, M. Azhar; Schmidt, Stephen D.; Gu, Yongjun; Yang, Jing; Mazzella, Matthew J.; Coomaraswamy, Janaky; Horne, Patrick; Strome, Bob; Pelly, Heather; Levesque, Georges; Ebeling, Chris; Jiang, Ying; Nixon, Ralph A.; Rozmahel, Richard; Fraser, Paul E.; George-Hyslop, Peter St; Carlson, George A.; Westaway, David
?-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex. This endoproteolytic activity cleaves within transmembrane domains of amyloid-? precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-? (A?) 40 peptide to greater production of A?42. Although studies in PS1/PS2-deficient embryonic cells define overlapping activities for these proteins, in vivo complementation of PS1-deficient animals described here reveals an unexpected spectrum of activities dictated by PS1 and PS2 alleles. Unlike PS1 transgenes, wild-type PS2 transgenes expressed in the mouse CNS support little...
136.
DNA shuffling as a tool for protein crystallization - Keenan, Robert J.; Siehl, Daniel L.; Gorton, Rebecca; Castle, Linda A.
The success of structural studies performed on an individual target in small scale or on many targets in the systemwide scale of structural genomics depends critically on three parameters: (i) obtaining an expression system capable of producing large quantities of the macromolecule(s) of interest, (ii) purifying this material in soluble form, and (iii) obtaining diffraction-quality crystals suitable for x-ray analysis. The attrition rate caused by these constraints is often quite high. Here, we present a strategy that addresses each of these three parameters simultaneously. Using DNA shuffling to introduce functional sequence variability into a protein of interest, we screened crude...
137.
Effects of threshold choice on biological conclusions reached during analysis of gene expression by DNA microarrays - Pan, Kuang-Hung; Lih, Chih-Jian; Cohen, Stanley N.
Global analysis of gene expression by using DNA microarrays is employed increasingly to search for differences in biological properties between normal and diseased tissue. In such studies, expression that deviates from defined thresholds commonly is used for creating genetic signatures that characterize disease vs. normality. Although it is axiomatic that the threshold parameters applied to microarray analysis will alter the contents of such genetic signatures, the extent to which threshold choice can affect the fundamental conclusions made from microarray-based studies has not been elucidated. We used gabriel (Genetic Analysis By Rules Incorporating Expert Logic), a platform of knowledge-based algorithms for...
138.
A quasi-Monte Carlo Metropolis algorithm - Owen, Art B.; Tribble, Seth D.
This work presents a version of the MetropolisHastings algorithm using quasi-Monte Carlo inputs. We prove that the method yields consistent estimates in some problems with finite state spaces and completely uniformly distributed inputs. In some numerical examples, the proposed method is much more accurate than ordinary MetropolisHastings sampling.
139.
Arranging matter by magnetic nanoparticle assemblers - Yellen, Benjamin B.; Hovorka, Ondrej; Friedman, Gary
We introduce a method for transporting colloidal particles, large molecules, cells, and other materials across surfaces and for assembling them into highly regular patterns. In this method, nonmagnetic materials are manipulated by a fluid dispersion of magnetic nanoparticles. Manipulation of materials is guided by a program of magnetic information stored in a substrate. Dynamic control over the motion of nonmagnetic particles can be achieved by reprogramming the substrate magnetization on the fly. The unexpectedly large degree of control over particle motion can be used to manipulate large ensembles of particles in parallel, potentially with local control over particle trajectory.
140.
In vivo formation and repair of DNA double-strand breaks after computed tomography examinations - Löbrich, Markus; Rief, Nicole; Kühne, Martin; Heckmann, Martina; Fleckenstein, Jochen; Rübe, Christian; Uder, Michael
Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA double-strand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcinogenesis. We have enumerated ?-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and/or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the doselength product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis...
121.
