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  • 1
    Publication Date: 1999-10-16
    Description: Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta-defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta-defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin. Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, D -- Chertov, O -- Bykovskaia, S N -- Chen, Q -- Buffo, M J -- Shogan, J -- Anderson, M -- Schroder, J M -- Wang, J M -- Howard, O M -- Oppenheim, J J -- N01-CO-56000/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):525-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521347" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/immunology ; Binding, Competitive ; Cell Line ; Chemokine CCL20 ; Chemokines, CC/metabolism/pharmacology ; Chemotaxis ; Chemotaxis, Leukocyte ; Defensins ; Dendritic Cells/*immunology ; Humans ; *Immunity, Active ; *Immunity, Innate ; Immunologic Memory ; *Macrophage Inflammatory Proteins ; Pertussis Toxin ; Proteins/pharmacology/*physiology ; Receptors, CCR6 ; Receptors, Chemokine/genetics/*metabolism ; Recombinant Proteins/pharmacology ; T-Lymphocyte Subsets/*immunology ; Transfection ; Virulence Factors, Bordetella/pharmacology ; *beta-Defensins
    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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  • 2
    Publication Date: 1988-07-15
    Description: In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated. The exposed children were shorter and lighter than controls; they had abnormalities of gingiva, skin, nails, teeth, and lungs more frequently than did controls. The exposed children showed delay of developmental milestones, deficits on formal developmental testing, and abnormalities on behavioral assessment. These findings are most consistent with a generalized disorder of ectodermal tissue. This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rogan, W J -- Gladen, B C -- Hung, K L -- Koong, S L -- Shih, L Y -- Taylor, J S -- Wu, Y C -- Yang, D -- Ragan, N B -- Hsu, C C -- New York, N.Y. -- Science. 1988 Jul 15;241(4863):334-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3133768" target="_blank"〉PubMed〈/a〉
    Keywords: Conjunctivitis/chemically induced/congenital ; Female ; Growth Disorders/chemically induced ; Humans ; Lactation ; Maternal-Fetal Exchange ; Nails, Malformed ; Oils/*adverse effects ; Pigmentation Disorders/chemically induced/congenital ; Polychlorinated Biphenyls/*poisoning ; Pregnancy ; Taiwan
    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
    Publication Date: 2008-08-30
    Description: Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Young Duk -- Cho, Hawon -- Koo, Jae Yeon -- Tak, Min Ho -- Cho, Yeongyo -- Shim, Won-Sik -- Park, Seung Pyo -- Lee, Jesun -- Lee, Byeongjun -- Kim, Byung-Moon -- Raouf, Ramin -- Shin, Young Ki -- Oh, Uhtaek -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Oct 30;455(7217):1210-5. doi: 10.1038/nature07313. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724360" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism/pharmacology ; Chloride Channels/chemistry/deficiency/genetics/*metabolism ; Chlorides/*metabolism ; Electric Conductivity ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Intracellular Space/drug effects/metabolism ; Ion Transport/drug effects ; Mice ; Oocytes/metabolism ; Pilocarpine/pharmacology ; RNA, Small Interfering/genetics/metabolism ; Rats ; Receptors, G-Protein-Coupled/*metabolism ; Salivation/drug effects ; Xenopus
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-07-19
    Description: Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 A resolution, complemented by extensive site-specific mutagenesis, and a hybrid model of glucagon bound to GCGR to understand the molecular recognition of the receptor for its native ligand. Beyond the shared seven transmembrane fold, the GCGR transmembrane domain deviates from class A G-protein-coupled receptors with a large ligand-binding pocket and the first transmembrane helix having a 'stalk' region that extends three alpha-helical turns above the plane of the membrane. The stalk positions the extracellular domain (~12 kilodaltons) relative to the membrane to form the glucagon-binding site that captures the peptide and facilitates the insertion of glucagon's amino terminus into the seven transmembrane domain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820480/" 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/PMC3820480/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siu, Fai Yiu -- He, Min -- de Graaf, Chris -- Han, Gye Won -- Yang, Dehua -- Zhang, Zhiyun -- Zhou, Caihong -- Xu, Qingping -- Wacker, Daniel -- Joseph, Jeremiah S -- Liu, Wei -- Lau, Jesper -- Cherezov, Vadim -- Katritch, Vsevolod -- Wang, Ming-Wei -- Stevens, Raymond C -- F32 DK088392/DK/NIDDK NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50GM073197/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Jul 25;499(7459):444-9. doi: 10.1038/nature12393. Epub 2013 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23863937" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Glucagon/chemistry/metabolism ; Humans ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Binding ; Protein Structure, Tertiary ; Receptors, CXCR4/chemistry/classification ; Receptors, Glucagon/*chemistry/*classification/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-01-28
    Description: Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1beta and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins), as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of NEK7, caspase-1 activation and IL-1beta release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasomes. NLRP3-activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high-molecular-mass NLRP3-NEK7 complex, which, along with ASC oligomerization and ASC speck formation, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed that NEK7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yuan -- Zeng, Melody Y -- Yang, Dahai -- Motro, Benny -- Nunez, Gabriel -- R01AI063331/AI/NIAID NIH HHS/ -- R01DK091191/DK/NIDDK NIH HHS/ -- T32 HL007517/HL/NHLBI NIH HHS/ -- T32DK094775/DK/NIDDK NIH HHS/ -- T32HL007517/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Feb 18;530(7590):354-7. doi: 10.1038/nature16959. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins/deficiency/genetics/metabolism ; Biocatalysis ; Carrier Proteins/chemistry/genetics/*metabolism ; Caspase 1/metabolism ; Catalytic Domain ; Cells, Cultured ; Cryopyrin-Associated Periodic Syndromes/genetics ; Enzyme Activation ; HEK293 Cells ; Humans ; Inflammasomes/*chemistry/*metabolism ; Interleukin-1beta/secretion ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Potassium/*metabolism ; Protein Binding ; Protein Multimerization ; Protein-Serine-Threonine Kinases/chemistry/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Electronic Resource
    Electronic Resource
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 27 (1989), S. 819-835 
    ISSN: 0887-6266
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The rheological behavior of the thermotropic liquid crystal copolyesters composed of p-hydroxybenzoic acid and 2-hydroxy-6-naphthoic acid (indicated as HBA/HNA) is investigated for three different compositions: 75:25, 58:42, 30:70 (in mol%). The inherent viscosities are 9.2, 5.1, and 7.8 dl/g, respectively. Yield stress is observed for all three samples. This indicates the existence of crystallites in the melt which may be related to the shear thinning viscosity at low shear stress. Melt fracture, and a die swell ratio which increases with shear rate, are also observed at higher temperatures and at low shear stress for the two copolyesters having compositions 75:25 and 30:70. We have also estimated for 30HBA/70HNA at 335°C the entrance pressure loss, Δpent, and ΔPent/δw, where δw is the shear stress at the capillary wall. The large value of ΔPent/δw suggest that HBA/HNA is a highly elastic polymeric material. It is found that both ΔPent and ΔPent/δw increase with shear rate. However, the high elasticity does not account for the disappearance of melt fracture and contraction of die swell at high shear stress. This abnormal phenomenon is ascribed to the formation of a network of crystallites caused by blocky regions in the copolymer.
    Additional Material: 18 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Surface and Interface Analysis 24 (1996), S. 803-810 
    ISSN: 0142-2421
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The mercaptoesters have been recognized as an effective coupling agent for bonding metals using acrylate and epoxy adhesives with enhanced bonding strength and improved durability. Here, we report the results of our investigation of the interaction of thioester coupling agents with a gold surface using a grazing angle FTIR (GA/FTIR) spectroscopic technique. We investigated the interaction of alkyl functional thioesters (octylthioglycolate, dodecyl-thioglycolate and stearylthioglycolate) coupling agents with the metal at the interface region. The formation of strong chemical bonding is proven to be the key feature of this application rather than wetting or hydrogen bonding for conventional adhesive applications. Based on our results we have concluded that the deposited layers exist as thioester bonded to the gold surface through the sulfur-metal bond and that the polarization results indicate that only those thioesters containing C12 and C18 hydrocarbon tail chains self-assemble readily and close pack on the surface. For dodecyl thioglycolate, the C12 alkyl chains are densely packed and oriented perpendicular to the substrate surface. For the stearyl thioglycolate, the C18 alkyl tail chains are also closely packed and oriented, but the chains appear to tilt from the normal surface. However, the carbonyl group of the C18 thioester appears to be parallel to the surface. For short-chain mercaptoesters, such as octyl thioglycolate, the alkyl chains do not self-assemble or orient on the gold surface. The molecular orientation of the coupling agent at the interface region has also been shown to play an important role in determining the interaction of the adhesive with the coupling agent layers. Results of the interfacial shear strength promotion on mild steel by the mercaptoester coupling agents are also reported.
    Additional Material: 10 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Surface and Interface Analysis 20 (1993), S. 407-415 
    ISSN: 0142-2421
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: Tertiary alkylamines of different chain lengths have been used as primers for adhesive bonding strength promotion for polyolefinic surfaces with cyanoacrylate (CA) adhesives. A combination of the construction of model polyolefin surfaces and advanced molecular-sensitive analysis tools has been employed for understanding the promoter/polyolefin interaction at the interface. Characterization of primer structure and interfacial properties has been carried out using grazing angle reflection-absorption Fourier transform infrared spectroscopy (GA/FTIR), ellipsometry, x-ray photoelectron spectroscopy (XPS) and contact angle titration using different pH probe liquids. Our work has focused on the design and construction of a model polyolefin surface using a new in situ polyethylene (PE) polymerization technique to form a controllable thickness (〈400 Å) of PE film on a reflective metal surface. The new technique of in situ PE polymerization is based on diazomethane chemistry. Both protonated and deuterated PE films have been successfully prepared. The results of spectroscopic investigations of these model deuterated and non-deuterated PE surfaces are disclosed. Molecular parameters that affect adhesion promotion have been studied. The parameters studied include molecular structure and alkyl chain length of tertiary alkylamines.
    Additional Material: 10 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Surface and Interface Analysis 23 (1995), S. 276-288 
    ISSN: 0142-2421
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: We have observed that methacrylic acid (MA) is far more corrosive than acrylic acid (AA) on copper surfaces when copper was exposed to the vapor of these two acids at ambient temperature and environment. With the aid of modern surface-sensitive instrumentation, which included grazing angle Fourier transform infrared (FTIR), XPS, x-ray-induced Auger electron and SEM/energy-dispersive spectroscopies and white light stereo and metallurgical microscopy, we are reporting our results of an extensive study of the roles that MA and AA have in this unusual phenomenon of copper corrosion.By grazing angle FTIR analysis we demonstrated that copper carboxylate salt formation is very rapid upon short contact with the vapor of both acids, and the acids showed no evidence of polymerization. We have also demonstrated by XPS and x-ray-induced Auger electron spectroscopy that copper surfaces exposed to the MA vapor contains mainly Cu(II) species. However, the oxidation state of the copper exposed to AA vapor will depend on exposure time and environment. With limited exposure to the air, the copper surface remained shiny for up to 12 months test time. The spectrum obtained from the shiny area of the AA/Cu surface shows that it contains mainly Cu(I) mixed with some copper (II). When the spectrum was taken from a dull area of AA/Cu surfaces, the Cu(II) state was found to be predominant. These results strongly indicate that when the shiny AA/Cu surface changed to a dull color, the oxidation state of the copper also changed from +1 to +2. The molecular structure of the Cu(II)-AA salt is also believed to be altered.Both stereo microscopic and SEM/energy-dispersive spectroscopy techniques were also used to perform the visual and microanalysis of the surface texture and elemental compositions of the corroded surfaces, respectively. The presence of oxygen was also found to play an important role in the overall corrosion processes. The differences in molecular structure of copper carboxylate salts of different oxidation states are discussed and are believed to be responsible for this unusual phenomenon. We believe that this finding will provide a good explanation for the cause of drastic differences of copper corrosion by acrylic and methacrylic acids.
    Additional Material: 15 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Acta Polymerica 47 (1996), S. 285-289 
    ISSN: 0323-7648
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Epitaxial crystallization behavior of HDPE/iPP double layers under quenching and annealing conditions has been studied by means of transmission electron microscopy (TEM). The results obtained from bright field TEM observations indicate that in the as-quenched state the HDPE that is in direct contact with the surface of the oriented iPP substrate recrystallizes in the form of oriented crystallites dispersed on the iPP substrate. The electron diffraction results show that besides the two normally observed epitaxial orientations between HDPE and iPP, there is also a special orientation with [001]HDPE ‖ [001]iPP. The HDPE which is in contact with the clean surface of a glass slide crystallizes in small lamellae with random orientation. In the boundary region, the epitaxially crystallized HDPE small lamellae stop right on the boundary of the oriented iPP film. If the quenched samples are annealed at 128°C (below Tm of HDPE) for 2 h, the small HDPE crystals grow to thick lamellae in both areas. But only the epitaxial orientation of HDPE with [001]HDPE ‖ [101]iPP has been observed.
    Additional Material: 8 Ill.
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