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  • Polymer and Materials Science  (2,371)
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  • 1
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effect of surface roughness on osteoblast proliferation, differentiation, and protein synthesis was examined. Human osteoblast-like cells (MG63) were cultured on titanium (Ti) disks that had been prepared by one of five different treatment regimens. All disks were pretreated with hydrofluoric acid-nitric acid and washed (PT). PT disks were also: washed, and then electropolished (EP); fine sandblasted, etched with HCl and H2SO4, and washed (FA); coarse sandblasted, etched with HCl and H2SO4, and washed (CA); or Ti plasma-sprayed (TPS). Standard tissue culture plastic was used as a control. Surface topography and profile were evaluated by brightfield and darkfield microscopy, cold field emission scanning electron microscopy, and laser confocal microscopy, while chemical composition was mapped using energy dispersion X-ray analysis and elemental distribution determined using Auger electron spectroscopy. The effect of surface roughness on the cells was evaluated by measuring cell number, [3H]thymidine incorporation into DNA, alkaline phosphatase specific activity, [3H]uridine incorporation into RNA, [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagenase-digestible protein (NCP), and [35S]sulfate incorporation into proteoglycan.Based on surface analysis, the five different Ti surfaces were ranked in order of smoothest to roughest: EP, PT, FA, CA, and TPS. A TiO2 layer was found on all surfaces that ranged in thickness from 100 Å in the smoothest group to 300 Å in the roughest. When compared to confluent cultures of cells on plastic, the number of cells was reduced on the TPS surfaces and increased on the EP surfaces, while the number of cells on the other surfaces was equivalent to plastic. [3H]Thymidine incorporation was inversely related to surface roughness. Alkaline phosphatase specific activity in isolated cells was found to decrease with increasing surface roughness, except for those cells cultured on CA. In contrast, enzyme activity in the cell layer was only decreased in cultures grown on FA- and TPS-treated surfaces. A direct correlation between surface roughness and RNA and CDP production was found. Surface roughness had no apparent effect on NCP production. Proteoglycan synthesis by the cells was inhibited on all the surfaces studied, with the largest inhibition observed in the CA and EP groups. These results demonstrate that surface roughness alters osteoblast proliferation, differentiation, and matrix production in vitro. The results also suggest that implant surface roughness may play a role in determining phenotypic expression of cells in vivo.
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  • 2
    Publication Date: 2007-10-13
    Description: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Laura D -- Parsons, D Williams -- Jones, Sian -- Lin, Jimmy -- Sjoblom, Tobias -- Leary, Rebecca J -- Shen, Dong -- Boca, Simina M -- Barber, Thomas -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Dezso, Zoltan -- Ustyanksky, Vadim -- Nikolskaya, Tatiana -- Nikolsky, Yuri -- Karchin, Rachel -- Wilson, Paul A -- Kaminker, Joshua S -- Zhang, Zemin -- Croshaw, Randal -- Willis, Joseph -- Dawson, Dawn -- Shipitsin, Michail -- Willson, James K V -- Sukumar, Saraswati -- Polyak, Kornelia -- Park, Ben Ho -- Pethiyagoda, Charit L -- Pant, P V Krishna -- Ballinger, Dennis G -- Sparks, Andrew B -- Hartigan, James -- Smith, Douglas R -- Suh, Erick -- Papadopoulos, Nickolas -- Buckhaults, Phillip -- Markowitz, Sanford D -- Parmigiani, Giovanni -- Kinzler, Kenneth W -- Velculescu, Victor E -- Vogelstein, Bert -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- CA112828/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- GM070219/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1108-13. Epub 2007 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/metabolism ; Cell Line ; Chromosome Mapping ; Colorectal Neoplasms/*genetics/metabolism ; Computational Biology ; DNA, Neoplasm ; Databases, Genetic ; Genes, Neoplasm ; Genome, Human ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neoplasm Proteins/genetics/metabolism ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Titanium (Ti) surface roughness affects proliferation, differentiation, and matrix production of MG-63 osteoblast-like cells. Cytokines and growth factors produced in the milieu surrounding an implant may also be influenced by its surface, thereby modulating the healing process. This study examined the effect of surface roughness on the production of two factors known to have potent effects on bone, prostaglandin E2 (PGE2) and transforming growth factor β1 (TGF-β1). MG-63 cells were cultured on Ti disks of varying roughness. The surfaces were ranked from smoothest to roughest: electropolished (EP), pretreated with hydrofluoric acid-nitric acid (PT), fine sand-blasted, etched with HCl and H2SO4, and washed (EA), coarse sand-blasted, etched with HCl and H2SO4, and washed (CA), and Ti plasma-sprayed (TPS). Cells were cultured in 24-well polystyrene (plastic) dishes as controls and to determine when confluence was achieved. Media were collected and cell number determined 24 h postconfluence. PGE2 and TGF-β1 levels in the conditioned media were determined using commercial radioimmunoassay and enzyme-linked immunosorbent assay kits, respectively. There was an inverse relationship between cell number and Ti surface roughness. Total PGE2 content in the media of cultures grown on the three roughest surfaces (FA, CA, and TPS) was significantly increased 1.5-4.0 times over that found in media of cultures grown on plastic or smooth surfaces. When PGE2 production was expressed per cell number, CA and TPS cultures exhibited six- to eightfold increases compared to cultures on plastic and smooth surfaces. There was a direct relationship between TGF-β1 production and surface roughness, both in terms of total TGF-β1 per culture and when normalized for cell number. TGF-β1 production on rough surfaces (CA and TPS) was three to five times higher than on plastic. These studies indicate that substrate surface roughness affects cytokine and growth factor production by MG-63 cells, suggesting that surface roughness may modulate the activity of cells interacting with an implant, and thereby affect tissue healing and implant success. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 4
    ISSN: 0021-9304
    Keywords: implant ; titanium ; osteoblasts ; surface roughness ; 1α,25- (OH)2D3 ; differentiation ; local factor ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Surface roughness has been shown to affect differentiation and local factor production of MG63 osteoblast-like cells. This study examined whether surface roughness alters cellular response to circulating hormones such as 1α,25-(OH)2D3. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then were machined and acid-etched (MA). Ti disks also were sandblasted (SB), sandblasted and acid etched (CA), or plasma sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were: PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on standard tissue culture polystyrene (plastic) or the Ti surfaces and then treated for 24 h with either 10-8M or 10-7M 1α,25-(OH)2D3 or vehicle (control). Cellular response was measured by assaying cell number, cell layer alkaline phosphatase specific-activity, and the production of osteocalcin, latent (L) TGFβ, and PGE2. Alkaline phosphatase activity was affected by surface roughness; as the surface became rougher, the cells showed a significant increase in alkaline phosphatase activity. Addition of 1α,25-(OH)2D3 to the cultures caused a dose-dependent stimulation of alkaline phosphatase activity that was synergistic with the effect caused by surface roughness alone. 1α,25-(OH)2D3 also caused a synergistic increase in osteocalcin production as well as local factor (LTGFβ and PGE2) production on the rougher CA, SB, and PS surfaces, but it had no effect on the production on smooth surfaces. The inhibitory effect of surface roughness on cell number was not affected by 1α,25-(OH)2D3 except on the SB surface. 1α,25-(OH)2D3 decreased cell number, increased alkaline phosphatase activity and osteocalcin production, and had no effect on LTGFβ or PGE2 production by MG63 cells grown on tissue culture polystyrene. These data suggest that bone cell response to systemic hormones is modified by surface roughness and that surface roughness increases the responsiveness of MG63 cells to 1α,25-(OH)2D3. They also suggest that the endocrine system is actively involved in normal bone healing around implants. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 77-85, 1998.
    Additional Material: 6 Ill.
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  • 5
    ISSN: 0021-9304
    Keywords: implant ; titanium ; osteoblasts ; prostaglandin ; indomethacin ; surface roughness ; 1α,25-(OH)2D3 ; differentiation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Surface roughness affects proliferation, differentiation (alkaline phosphatase and osteocalcin), local factor production [transforming growth factor (TGFβ) and prostaglandin E2 (PGE2)], and response to 1,25-(OH)2D3 (1,25) of MG63 osteoblast-like cells. In this study, we examined whether the effect of surface roughness on MG63 cells is mediated by prostaglandins produced by the cells. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then machined and acid-etched (MA). Disks were also coarse grit-sandblasted (SB), coarse grit-sandblasted and acid-etched (CA), or plasma-sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on the Ti disks in the presence or absence of 10-7M indomethacin (Indo), a specific inhibitor of cyclooxygenase activity, resulting in decreased prostaglandin production. When the cells reached confluence, cell number, cell layer alkaline phosphatase specific activity (ALPase), and osteocalcin (OC) and latent TGFβ (LTGFβ) production were determined. In addition, confluent cultures which had been grown in the absence of Indo were exposed to 10-7M 1,25, 10-7M Indo, or a combination of the two for 24 h. On the rougher surfaces, cell number was decreased and ALPase, OC, and LTGFβ were increased. When indomethacin was present throughout the culture period, the effect of surface roughness on cell number, OC, and LTGFβ was abolished. ALPase was reduced, but surface roughness-dependent effects were still observed. Addition of indomethacin to confluent cultures for 24 h had no effect on any of the parameters examined, with one exception: Cells cultured on MA surfaces exhibited a more differentiated phenotype. 1,25 increased all parameters examined on SB, CA, and PS surfaces. When indomethacin was added with 1,25, the 1,25-dependent effects on cell number and OC and LTGFβ production were abolished; however, ALPase was unaffected. This indicates that bone cell response to systemic hormones may be modified by implant surface roughness. This effect may be mediated, at least in part, by prostaglandins produced by the same cells. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 489-496, 1998.
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  • 6
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Although it is well accepted that implant success is dependent on various surface properties, little is known about the effect of surface roughness on cell metabolism or differentiation, or whether the effects vary with the maturational state of the cells interacting with the implant. In the current study, we examined the effect of titanium (Ti) surface roughness on chondrocyte proliferation, differentiation, and matrix synthesis using cells derived from known stages of endochondral development. Chondrocytes derived from the resting zone (RCs) and growth zone (GCs) of rat costochondral cartilage were cultured on Ti disks that were prepared as follows: HF-HNO3-treated and washed (PT); PT-treated and electropolished (EP); fine sand-blasted, HCl-H2SO4-etched, and washed (FA); coarse sand-blasted, HCl-H2SO4-etched, and washed (CA); or Ti plasma-sprayed (TPS). Based on surface analysis, the Ti surfaces were ranked from smoothest to roughest: EP, PT, FA, CA, and TPS. Cell proliferation was assessed by cell number and [3H]-thymidine incorporation, and RNA synthesis was assessed by [3H]-uridine incorporation. Differentiation was determined by alkaline phosphatase specific activity (AL-Pase). Matrix production was measured by [3H]-proline incorporation into collagenase-digestible (CDP) and noncollagenase-digestible (NCP) protein and by [35S]-sulfate incorporation into proteoglycan. GCs required two trypsinizations for complete removal from the culture disks; the number of cells released by the first trypsinization was generally decreased with increasing surface roughness while that released by the second trypsinization was increased. In RC cultures, cell number was similarly decreased on the rougher surfaces; only minimal numbers of RCs were released by a second trypsinization. [3H]-thymidine incorporation by RCs decreased with increasing surface roughness while that by GCs was increased. [3H]-Uridine incorporation by both GCs and RCs was greater on rough surfaces. Conversely, ALPase in the cell layer and isolated cells of both cell types was significantly decreased. GC CDP and NCP production was significantly decreased on rough surfaces while CDP production by RC cells was significantly decreased on smooth surfaces. [35S]-sulfate incorporation by RCs and GCs was decreased on all surfaces compared to tissue culture plastic. The results of this study indicate that surface roughness affects chondrocyte proliferation, differentiation, and matrix synthesis, and that this regulation is cell maturation dependent. © 1996 John Wiley & Sons, Inc.
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  • 7
    Publication Date: 2006-10-21
    Description: Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Papassotiropoulos, Andreas -- Stephan, Dietrich A -- Huentelman, Matthew J -- Hoerndli, Frederic J -- Craig, David W -- Pearson, John V -- Huynh, Kim-Dung -- Brunner, Fabienne -- Corneveaux, Jason -- Osborne, David -- Wollmer, M Axel -- Aerni, Amanda -- Coluccia, Daniel -- Hanggi, Jurgen -- Mondadori, Christian R A -- Buchmann, Andreas -- Reiman, Eric M -- Caselli, Richard J -- Henke, Katharina -- de Quervain, Dominique J-F -- P30AG19610/AG/NIA NIH HHS/ -- R01MH057899/MH/NIMH NIH HHS/ -- U01-HL086528-01/HL/NHLBI NIH HHS/ -- U24NS051872/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 20;314(5798):475-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Psychiatry Research, University of Zurich, Zurich 8057, Switzerland. papas@bli.unizh.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17053149" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Alleles ; Animals ; Attention ; Brain/*physiology ; Brain Chemistry ; Calcium-Binding Proteins/genetics ; Cohort Studies ; Female ; Gene Expression ; Genotype ; Haplotypes ; Hippocampus/chemistry/*physiology ; Humans ; Intracellular Signaling Peptides and Proteins ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics ; *Memory ; Mice ; Middle Aged ; Phosphoproteins ; *Polymorphism, Single Nucleotide ; Proteins/analysis/*genetics/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Switzerland ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 1998-12-18
    Description: The pathogenesis of asthma reflects, in part, the activity of T cell cytokines. Murine models support participation of interleukin-4 (IL-4) and the IL-4 receptor in asthma. Selective neutralization of IL-13, a cytokine related to IL-4 that also binds to the alpha chain of the IL-4 receptor, ameliorated the asthma phenotype, including airway hyperresponsiveness, eosinophil recruitment, and mucus overproduction. Administration of either IL-13 or IL-4 conferred an asthma-like phenotype to nonimmunized T cell-deficient mice by an IL-4 receptor alpha chain-dependent pathway. This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897229/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grunig, G -- Warnock, M -- Wakil, A E -- Venkayya, R -- Brombacher, F -- Rennick, D M -- Sheppard, D -- Mohrs, M -- Donaldson, D D -- Locksley, R M -- Corry, D B -- 03344/PHS HHS/ -- 47412/PHS HHS/ -- K08 HL003344/HL/NHLBI NIH HHS/ -- T32 HL07185/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2261-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856950" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Allergens/immunology ; Animals ; Asthma/genetics/*immunology/pathology/physiopathology ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid/cytology ; Chromosomes, Human, Pair 5 ; Goblet Cells/pathology ; Humans ; Immunoglobulin Fc Fragments ; Interleukin-13/antagonists & inhibitors/genetics/pharmacology/*physiology ; Interleukin-13 Receptor alpha1 Subunit ; Interleukin-4/genetics/pharmacology/*physiology ; Mice ; Mice, Inbred BALB C ; Ovalbumin/immunology ; Phenotype ; Receptors, Interleukin/genetics/immunology/physiology ; Receptors, Interleukin-13 ; Receptors, Interleukin-4/genetics/physiology ; Recombinant Fusion Proteins/pharmacology ; Th2 Cells/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2006-04-08
    Description: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482474/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482474/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Judge, Daniel P -- Holm, Tammy M -- Cohn, Ronald D -- Loeys, Bart L -- Cooper, Timothy K -- Myers, Loretha -- Klein, Erin C -- Liu, Guosheng -- Calvi, Carla -- Podowski, Megan -- Neptune, Enid R -- Halushka, Marc K -- Bedja, Djahida -- Gabrielson, Kathleen -- Rifkin, Daniel B -- Carta, Luca -- Ramirez, Francesco -- Huso, David L -- Dietz, Harry C -- K08 HL067056/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 7;312(5770):117-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16601194" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Antagonists/administration & dosage/therapeutic use ; Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use ; Animals ; Antibodies/immunology ; Aorta/pathology ; Aortic Aneurysm/etiology/*prevention & control ; *Disease Models, Animal ; Elastic Tissue/pathology ; Female ; Losartan/administration & dosage/*therapeutic use ; Lung/pathology ; Lung Diseases/drug therapy/pathology ; Marfan Syndrome/complications/*drug therapy/metabolism/pathology ; Mice ; Microfilament Proteins/genetics ; Mutation ; Neutralization Tests ; Pregnancy ; Pregnancy Complications/drug therapy ; Propranolol/administration & dosage/therapeutic use ; Pulmonary Alveoli/pathology ; Receptor, Angiotensin, Type 1/metabolism ; Signal Transduction ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-04-11
    Description: The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785900/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785900/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ashall, Louise -- Horton, Caroline A -- Nelson, David E -- Paszek, Pawel -- Harper, Claire V -- Sillitoe, Kate -- Ryan, Sheila -- Spiller, David G -- Unitt, John F -- Broomhead, David S -- Kell, Douglas B -- Rand, David A -- See, Violaine -- White, Michael R H -- BB/C007158/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C008219/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C520471/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/D010748/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E004210/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E012965/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F005938/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0071581/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC0082191/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBC5204711/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBD0107481/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBF0059381/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500346/Medical Research Council/United Kingdom -- G0500346(73596)/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):242-6. doi: 10.1126/science.1164860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359585" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Feedback, Physiological ; *Gene Expression ; Humans ; I-kappa B Proteins/metabolism ; Mice ; Models, Biological ; Models, Statistical ; NF-kappa B/*metabolism ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; Stochastic Processes ; Transcription Factor RelA/*metabolism ; *Transcription, Genetic ; Transfection ; Tumor Necrosis Factor-alpha/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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