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 61 - 80 de 184,040
61.
Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens - Dalley, Jeffrey W.; Lääne, Kristjan; Theobald, David E. H.; Armstrong, Hannah C.; Corlett, Philip R.; Chudasama, Yogita; Robbins, Trevor W.
Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as d-amphetamine, were determined on Pavlovian...
62.
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase - Davis, Mindy I.; Bennett, Melanie J.; Thomas, Leonard M.; Bjorkman, Pamela J.
Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature and is a target for anticancer imaging and therapeutic agents. PSMA acts as a glutamate carboxypeptidase (GCPII) on small molecule substrates, including folate, the anticancer drug methotrexate, and the neuropeptide N-acetyl-l-aspartyl-l-glutamate. Here we present the 3.5-Å crystal structure of the PSMA ectodomain, which reveals a homodimer with structural similarity to transferrin receptor, a receptor for iron-loaded transferrin that lacks protease activity. Unlike transferrin receptor, the protease domain of PSMA contains a binuclear zinc site, catalytic residues, and a proposed substrate-binding arginine patch. Elucidation of...
63.
Massive nitrogen loss from the Benguela upwelling system through anaerobic ammonium oxidation - Kuypers, Marcel M. M.; Lavik, Gaute; Woebken, Dagmar; Schmid, Markus; Fuchs, Bernhard M.; Amann, Rudolf; Jørgensen, Bo Barker; Jetten, Mike S. M.
In many oceanic regions, growth of phytoplankton is nitrogen-limited because fixation of N2 cannot make up for the removal of fixed inorganic nitrogen (NH+4, NO-2, and NO-3) by anaerobic microbial processes. Globally, 30-50% of the total nitrogen loss occurs in oxygen-minimum zones (OMZs) and is commonly attributed to denitrification (reduction of nitrate to N2 by heterotrophic bacteria). Here, we show that instead, the anammox process (the anaerobic oxidation of ammonium by nitrite to yield N2) is mainly responsible for nitrogen loss in the OMZ waters of one of the most productive regions of the world ocean, the Benguela upwelling system....
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?-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases - Kanemori, Yoshinori; Uto, Katsuhiro; Sagata, Noriyuki
?-TrCP, the F-box protein of the SCF?-TrCP ubiquitin ligase (SCF, Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif (DpSG?XpS) in various SCF?-TrCP target proteins. The Cdc25A phosphatase, a key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin-dependent degradation in response to genotoxic stress. ?-TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk1 and other unknown kinases. However, Xenopus Cdc25A does not have a DSG motif at the corresponding site of human Cdc25A. Here, we report that both Xenopus Cdc25A and human Cdc25A have a previously undescribed nonphosphorylated DDG motif (DDG?XD) for recognition by...
65.
Capturing protein interactions in the secretory pathway of living cells - Nyfeler, Beat; Michnick, Stephen W.; Hauri, Hans-Peter
The secretory pathway is composed of membrane compartments specialized in protein folding, modification, transport, and sorting. Numerous transient protein-protein interactions guide the transport-competent proteins through the secretory pathway. Here we have adapted the yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA) to detect protein-protein interactions in the secretory pathway of living cells. Fragments of YFP were fused to the homooligomeric cargo-receptor lectin endoplasmic reticulum Golgi intermediate compartment (ERGIC)-53, to the ERGIC-53-interacting multicoagulation factor deficiency protein MCFD2, and to ERGIC-53's cargo glycoprotein cathepsin Z. YFP PCA analysis revealed the oligomerization of ERGIC-53 and its interaction with MCFD2, as well as...
66.
Neutrophil microtubules suppress polarity and enhance directional migration - Xu, Jingsong; Wang, Fei; Van Keymeulen, Alexandra; Rentel, Maike; Bourne, Henry R.
How do microtubules, which maintain and direct polarity of many eukaryotic cells, regulate polarity of blood neutrophils? In sharp contrast to most cells, disrupting a neutrophil's microtubule network with nocodazole causes it to polarize and migrate [Niggli, V. (2003) J. Cell Sci. 116, 813822]. Nocodazole induces the same responses in differentiated HL-60 cells, a model neutrophil cell line, and reduces their chemotactic prowess by causing them to pursue abnormally circuitous paths in migrating toward a stationary point source of an attractant, f-Met-Leu-Phe (fMLP). The chemotactic defect stems from dramatic nocodazole-induced imbalance between the divergent, opposed fMLP-induced backness and frontness signals...
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A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance - Xing, Deyin; Orsulic, Sandra
Cell lines and tumors with defined genetic alterations provide ideal systems in which to test the molecular mechanisms of tumor sensitivity to pathway-targeted therapy. We have generated mouse ovarian epithelial tumor cell lines that contain various combinations of genetic alterations in the p53, c-myc, K-ras and Akt genes. Using both in vitro and in vivo approaches, we investigated the effect of rapamycin on cell proliferation, tumor growth, and the accumulation of peritoneal ascites. We demonstrated that rapamycin effectively inhibits the growth of tumors that rely on Akt signaling for proliferation, whereas tumors in which Akt signaling is not the driving...
68.
The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis - Xin, Li; Lawson, Devon A.; Witte, Owen N.
Sca-1 (stem cell antigen-1) enriches for murine prostate cells capable of regenerating tubular structures containing basal and luminal cell lineages in a dissociated cell prostate regeneration system. Sca-1+ fractions are enriched for cells at the G0 stage of the cell cycle, and Sca-1+ cells cluster in the proximal region of prostatic tubules where replication-quiescent cells have been localized. Castration-induced enrichment for androgen-independent cells results in a concomitant enrichment for Sca-1+ cells. Genetic perturbations of PTEN/AKT signaling in prostate-regenerating cells leads to the initiation of tumorigenesis, and cancer progression is associated with a dramatic increase in Sca-1+ cells. Sca-1-enriched prostate-regenerating cells...
69.
p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow - Vidal, Anxo; Zacharoulis, Stergios; Guo, Wenjun; Shaffer, David; Giancotti, Filippo; Bramley, Anna H.; de la Hoz, Carmen; Jensen, Kristian K.; Kato, Daniel; MacDonald, Daniel D.; Knowles, Joseph; Yeh, Nancy; Frohman, Lawrence A.; Rafii, Shahin; Lyden, David; Koff, Andrew
Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial progenitor cells as well as endothelial cells coopted from surrounding vessels. Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to establish the vasculature; however, which cell cycle regulators play a role in these processes is largely unknown. Here, we report that mice lacking the cell cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in xenografts and spontaneously arising tumors. This defect is associated with impaired mobilization of endothelial and myelomonocytic angiogenic progenitors from the bone marrow. This article documents the role of these molecules in...
70.
Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo - Noble, Wendy; Planel, Emmanuel; Zehr, Cindy; Olm, Vicki; Meyerson, Jordana; Suleman, Farhana; Gaynor, Kate; Wang, Lili; LaFrancois, John; Feinstein, Boris; Burns, Mark; Krishnamurthy, Pavan; Wen, Yi; Bhat, Ratan; Lewis, Jada; Dickson, Dennis; Duff, Karen
Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature of tauopathies, including Alzheimer's disease. Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it in vivo, transgenic mice overexpressing mutant human tau were treated with the glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in significant inhibition of GSK-3 activity. Lithium administration also resulted in significantly lower levels of phosphorylation at several epitopes of tau known to be hyperphosphorylated in Alzheimer's disease and significantly...
71.
Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra - Timms, Barry G.; Howdeshell, Kembra L.; Barton, Lesley; Bradley, Sarahann; Richter, Catherine A.; vom Saal, Frederick S.
Exposure of human fetuses to man-made estrogenic chemicals can occur through several sources. For example, fetal exposure to ethinylestradiol occurs because each year ?3% of women taking oral contraceptives become pregnant. Exposure to the estrogenic chemical bisphenol A occurs through food and beverages because of significant leaching from polycarbonate plastic products and the lining of cans. We fed pregnant CD-1 mice ethinylestradiol (0.1 ?g/kg per day) and bisphenol A (10 ?g/kg per day), which are doses below the range of exposure by pregnant women. In male mouse fetuses, both ethinylestradiol and bisphenol A produced an increase in the number and...
72.
Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds - Ihee, Hyotcherl; Rajagopal, Sudarshan; rajer, Vukica; Pahl, Reinhard; Anderson, Spencer; Schmidt, Marius; Schotte, Friedrich; Anfinrud, Philip A.; Wulff, Michael; Moffat, Keith
Determining 3D intermediate structures during the biological action of proteins in real time under ambient conditions is essential for understanding how proteins function. Here we use time-resolved Laue crystallography to extract short-lived intermediate structures and thereby unveil signal transduction in the blue light photoreceptor photoactive yellow protein (PYP) from Halorhodospira halophila. By analyzing a comprehensive set of Laue data during the PYP photocycle (forty-seven time points from one nanosecond to one second), we track all atoms in PYP during its photocycle and directly observe how absorption of a blue light photon by its p-coumaric acid chromophore triggers a reversible photocycle....
73.
A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration - Hageman, Gregory S.; Anderson, Don H.; Johnson, Lincoln V.; Hancox, Lisa S.; Taiber, Andrew J.; Hardisty, Lisa I.; Hageman, Jill L.; Stockman, Heather A.; Borchardt, James D.; Gehrs, Karen M.; Smith, Richard J. H.; Silvestri, Giuliana; Russell, Stephen R.; Klaver, Caroline C. W.; Barbazetto, Irene; Chang, Stanley; Yannuzzi, Lawrence A.; Barile, Gaetano R.; Merriam, John C.; Smith, R. Theodore; Olsh, Adam K.; Bergeron, Julie; Zernant, Jana; Merriam, Joanna E.; Gold, Bert; Dean, Michael; Allikmets, Rando
Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of ?900 AMD cases and 400 matched controls. We...
74.
Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons - Lopez-Coviella, Ignacio; Follettie, Maximillian T.; Mellott, Tiffany J.; Kovacheva, Vesela P.; Slack, Barbara E.; Diesl, Veronica; Berse, Brygida; Thies, R. Scott; Blusztajn, Jan Krzysztof
Basal forebrain cholinergic neurons (BFCN) participate in processes of learning, memory, and attention. Little is known about the genes expressed by BFCN and the extracellular signals that control their expression. Previous studies showed that bone morphogenetic protein (BMP) 9 induces and maintains the cholinergic phenotype of embryonic BFCN. We measured gene expression patterns in septal cultures of embryonic day 14 mice and rats grown in the presence or absence of BMP9 by using species-specific microarrays and validated the RNA expression data of selected genes by immunoblot and immunocytochemistry analysis of their protein products. BMP9 enhanced the expression of multiple genes...
75.
Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity - Lerner-Marmarosh, Nicole; Shen, Jenny; Torno, Michael D.; Kravets, Anatoliy; Hu, Zhenbo; Maines, Mahin D.
We describe here the tyrosine kinase activity of human biliverdin reductase (BVR) and its potential role in the insulin-signaling pathway. BVR is both a substrate for insulin receptor (IR) tyrosine kinase (IRK) activity and a kinase for serine phosphorylation of IR substrate 1 (IRS-1). Our previous studies have revealed serine/threonine kinase activity of BVR. Y198, in the YMKM motif found in the C-terminal domain of BVR, is shown to be a substrate for insulin-activated IRK. This motif in IRS proteins provides a docking site for proteins that contain a Src homology 2 domain. Additionally, Y228 in the YLSF sequence and...
76.
HIV-1-specific IFN-?/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells - Zimmerli, Simone C.; Harari, Alexandre; Cellerai, Cristina; Vallelian, Florence; Bart, Pierre-Alexandre; Pantaleo, Giuseppe
Functional and phenotypic characterization of virus-specific CD8 T cells against cytomegalovirus, Epstein-Barr virus, influenza (flu), and HIV-1 were performed on the basis of the ability of CD8 T cells to secrete IFN-? and IL-2, to proliferate, and to express CD45RA and CCR7. Two functional distinct populations of CD8 T cells were identified: (i) dual IFN-?/IL-2-secreting cells and (ii) single IFN-?-secreting cells. Virus-specific IFN-?/IL-2-secreting CD8 T cells were CD45RA-CCR7-, whereas single IFN-? CD8 T cells were either CD45RA-CCR7- or CD45RA+CCR7-. The proportion of virus-specific IFN-?/IL-2-secreting CD8 T cells correlated with that of proliferating CD8 T cells, and the loss of HIV-1-specific...
77.
Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway - Chen, Sifeng; Kapturczak, Matthias H.; Wasserfall, Clive; Glushakova, Olena Y.; Campbell-Thompson, Martha; Deshane, Jessy S.; Joseph, Reny; Cruz, Pedro E.; Hauswirth, William W.; Madsen, Kirsten M.; Croker, Byron P.; Berns, Kenneth I.; Atkinson, Mark A.; Flotte, Terence R.; Tisher, C. Craig; Agarwal, Anupam
Interleukin 10 (IL-10) is a pleiotropic cytokine with well known antiinflammatory, immunosuppressive, and immunostimulatory properties. Chronic allograft rejection, characterized by vascular neointimal proliferation, is a major cause of organ transplant loss, particularly in heart and kidney transplant recipients. In a Dark Agouti to Lewis rat model of aortic transplantation, we evaluated the effects of a single intramuscular injection of a recombinant adeno-associated viral vector (serotype 1) encoding IL-10 (rAAV1-IL-10) on neointimal proliferation and inflammation. rAAV1-IL-10 treatment resulted in a significant reduction of neointimal proliferation and graft infiltration with macrophages and T and B lymphocytes. The mechanism underlying the protective effects...
78.
Structural properties of A? protofibrils stabilized by a small molecule - Williams, Angela D.; Sega, Matt; Chen, Maolian; Kheterpal, Indu; Geva, Merav; Berthelier, Valerie; Kaleta, David T.; Cook, Kelsey D.; Wetzel, Ronald
Metastable oligomeric and protofibrillar forms of amyloidogenic proteins have been implicated as on-pathway assembly intermediates in amyloid formation and as the major toxic species in a number of amyloid diseases including Alzheimer's disease. We describe here a chemical biology approach to structural analysis of A? protofibrils. Library screening yielded several molecules that stimulate A? aggregation. One of these compounds, calmidazolium chloride (CLC), rapidly and efficiently converts A?(1-40) monomers into clusters of protofibrils. As monitored by electron microscopy, these protofibrils persist for days when incubated in PBS at 37°C, with a slow transition to fibrillar structures apparent only after several weeks....
79.
Dissecting human cytomegalovirus gene function and capsid maturation by ribozyme targeting and electron cryomicroscopy - Yu, Xuekui; Trang, Phong; Shah, Sanket; Atanasov, Ivo; Kim, Yong-Hwan; Bai, Yong; Zhou, Z. Hong; Liu, Fenyong
Human CMV (HCMV) is the leading viral cause of birth defects and causes one of the most common opportunistic infections among transplant recipients and AIDS patients. Cleavage of internal scaffolding proteins by the viral protease (Pr) occurs during HCMV capsid assembly. To gain insight into the mechanism of HCMV capsid maturation and the roles of the Pr in viral replication, an RNase P ribozyme was engineered to target the Pr mRNA and down-regulate its expression by >99%, generating premature Pr-minus capsids. Furthermore, scaffolding protein processing and DNA encapsidation were inhibited by 99%, and viral growth was reduced by 10,000-fold. 3D...
80.
Insights into TOR function and rapamycin response: Chemical genomic profiling by using a high-density cell array method - Xie, Michael W.; Jin, Fulai; Hwang, Heejun; Hwang, Seungmin; Anand, Vikram; Duncan, Mara C.; Huang, Jing
With the advent of complete genome sequences, large-scale functional analyses are generating new excitement in biology and medicine. To facilitate genomewide functional analyses, we developed a high-density cell array with quantitative and automated readout of cell fitness. Able to print at >×10 higher density on a standard microtiter plate area than currently possible, our cell array allows single-plate screening of the complete set of Saccharomyces cerevisiae gene-deletion library and significantly reduces the amount of small molecules and other materials needed for the study. We used this method to map the relation between genes and cell fitness in response to rapamycin,...
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