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1.
H. D. Patterson E. R. Williams L. Paterson 《Biometrical journal. Biometrische Zeitschrift》1985,27(1):75-79
KHARE and FEDERER (1981) have proposed a method for constructing resolvable incomplete-block designs with, they claim, higher efficiencies than those of the α-designs described by PATTERSON and WILLIAMS (1976a). This claim is shown here to be unfounded. The best α-designs have higher efficiencies than the Khare and Federer designs, and can be constructed straightforwardly using the concise table of generating arrays in PATTERSON , WILLIAMS and HUNTER (1978). 相似文献
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Xiaohui Yu Baoyin Jia Faqiang Wang Xiuxiu Lv Xuemei Peng Yiyang Wang Hongmei Li Yanping Wang Daxiang Lu Huadong Wang 《Journal of cellular and molecular medicine》2014,18(2):263-273
Cardiomyocyte tumour necrosis factor α (TNF‐α) production contributes to myocardial depression during sepsis. This study was designed to observe the effect of norepinephrine (NE) on lipopolysaccharide (LPS)‐induced cardiomyocyte TNF‐α expression and to further investigate the underlying mechanisms in neonatal rat cardiomyocytes and endotoxaemic mice. In cultured neonatal rat cardiomyocytes, NE inhibited LPS‐induced TNF‐α production in a dose‐dependent manner. α1‐ adrenoceptor (AR) antagonist (prazosin), but neither β1‐ nor β2‐AR antagonist, abrogated the inhibitory effect of NE on LPS‐stimulated TNF‐α production. Furthermore, phenylephrine (PE), an α1‐AR agonist, also suppressed LPS‐induced TNF‐α production. NE inhibited p38 phosphorylation and NF‐κB activation, but enhanced extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation and c‐Fos expression in LPS‐treated cardiomyocytes, all of which were reversed by prazosin pre‐treatment. To determine whether ERK1/2 regulates c‐Fos expression, p38 phosphorylation, NF‐κB activation and TNF‐α production, cardiomyocytes were also treated with U0126, a selective ERK1/2 inhibitor. Treatment with U0126 reversed the effects of NE on c‐Fos expression, p38 mitogen‐activated protein kinase (MAPK) phosphorylation and TNF‐α production, but not NF‐κB activation in LPS‐challenged cardiomyocytes. In addition, pre‐treatment with SB202190, a p38 MAPK inhibitor, partly inhibited LPS‐induced TNF‐α production in cardiomyocytes. In endotoxaemic mice, PE promoted myocardial ERK1/2 phosphorylation and c‐Fos expression, inhibited p38 phosphorylation and IκBα degradation, reduced myocardial TNF‐α production and prevented LPS‐provoked cardiac dysfunction. Altogether, these findings indicate that activation of α1‐AR by NE suppresses LPS‐induced cardiomyocyte TNF‐α expression and improves cardiac dysfunction during endotoxaemia via promoting myocardial ERK phosphorylation and suppressing NF‐κB activation. 相似文献
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Recent evidence implicates a central role for PI3K signalling in mediating cell survival during the process of neuronal differentiation. Although PI3K activity is stimulated by a wide range of growth factors and cytokines in different cell lines and tissues, activation of this pathway by insulin‐like growth factor I (IGF‐I) most likely represents the main survival signal during neuronal differentiation. IGF‐I is highly expressed during development of the central nervous system, and thus is a critical factor for the development and maturation of the cerebellum. Upon ligand binding, the IGF‐I receptor phosphorylates tyrosine residues in SHC and insulin receptor substrates (IRSs) initiating two main signalling cascades, the MAP kinase and the phosphatidylinositol 3‐kinase (PI3K) pathways. Activated PI3K is composed of a catalytic subunit (p110α or β) associated with one of a large family of regulatory subunits (p85α, p85β, p55γ, p55α, and p50α). To evaluate the contributions of these various regulatory subunits to neuronal differentiation, we have used antibodies specific for each of the PI3K subunits. Using these antisera, we now demonstrate that PI3K subunits are differentially regulated in cerebellar development, and that the expression level of the p55γ regulatory subunit reaches a maximum during postnatal development, decreasing thereafter to low levels in the adult cerebellum. Furthermore, our studies reveal that the distribution of the various PI3K regulatory subunits varies during development of the cerebellum. Interestingly, p55γ is expressed in both glial and neuronal cells; moreover, in Purkinje neurones, this subunit colocalises with the IGF‐IR. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 39–50, 2001 相似文献
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Tomas Erban Michaela Erbanova Marta Nesvorna Jan Hubert 《Archives of insect biochemistry and physiology》2009,71(3):139-158
The adaptation of nine species of mites that infest stored products for starch utilization was tested by (1) enzymatic analysis using feces and whole mite extracts, (2) biotests, and (3) inhibition experiments. Acarus siro, Aleuroglyphus ovatus, and Tyroborus lini were associated with the starch‐type substrates and maltose, with higher enzymatic activities observed in whole mite extracts. Lepidoglyphus destructor was associated with the same substrates but had higher activities in feces. Dermatophagoides farinae, Chortoglyphus arcuatus, and Caloglyphus redickorzevi were associated with sucrose. Tyrophagus putrescentiae and Carpoglyphus lactis had low or intermediate enzymatic activity on the tested substrates. Biotests on starch additive diets showed accelerated growth of species associated with the starch‐type substrates. The inhibitor acarbose suppressed starch hydrolysis and growth of the mites. We suggest that the species with higher starch hydrolytic activity in feces were more tolerant to acarbose, and α‐amylase and α‐glucosidase of synanthropic mites are suitable targets for inhibitor‐based strategies of mite control. © 2009 Wiley Periodicals, Inc. 相似文献
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Jinyoung Son Misun Kim Ilo Jou Kyoung Chan Park Hee Young Kang 《Pigment cell & melanoma research》2014,27(2):201-208
Inflammatory cytokines are closely related to pigmentary changes. In this study, the effects of IFN‐γ on melanogenesis were investigated. IFN‐γ inhibits basal and α‐MSH‐induced melanogenesis in B16 melanoma cells and normal human melanocytes. MITF mRNA and protein expressions were significantly inhibited in response to IFN‐γ. IFN‐γ inhibited CREB binding to the MITF promoter but did not affect CREB phosphorylation. Instead, IFN‐γ inhibited the association of CBP and CREB through the increased association between CREB binding protein (CBP) and STAT1. These findings suggest that IFN‐γ inhibits both basal and α‐MSH‐induced melanogenesis by inhibiting MITF expression. The inhibitory action of IFN‐γ in α‐MSH‐induced melanogenesis is likely to be associated with the sequestration of CBP via the association between CBP and STAT1. These data suggest that IFN‐γ plays a role in controlling inflammation‐ or UV‐induced pigmentary changes. 相似文献
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A conformational analysis of peptides having dipropylglycine (Dpg) or 1‐aminocycloheptanecarboxylic acid (Ac7c) within l ‐leucine (Leu) residues was conducted in solution and in a crystal state. Dpg and Ac7c had similar structures with acyclic and cyclic side chains, respectively. FTIR, 1H NMR, and CD spectra measurements revealed that the preferred conformations of Dpg‐ and Ac7c‐containing l ‐Leu peptides in solution were similar; both had a right‐handed (P) 310‐helix. The Dpg‐containing octapeptide adopted a right‐handed (P) α‐helix in the crystal state. Dpg and Ac7c homopeptides had planar and helical structures as their preferred conformations, respectively; however, Dpg‐ and Ac7c‐containing l ‐Leu peptides adopted similar structures in solution. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 210–218, 2016. 相似文献
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Nobuo Okazaki Maki Kumei Miho Manzoku Seiki Kuramitsu Mikako Shirouzu Akeo Shinkai Shigeyuki Yokoyama 《Acta Crystallographica. Section F, Structural Biology Communications》2007,63(3):173-177
TTHA0281 is a hypothetical protein from Thermus thermophilus HB8 that belongs to an uncharacterized protein family, UPF0150, in the Pfam database and to COG1598 in the National Center for Biotechnology Information Database of Clusters of Orthologous Groups. The X‐ray crystal structure of the protein was determined by a multiple‐wavelength anomalous dispersion technique and was refined at 1.9 Å resolution to a final R factor of 18.5%. The TTHA0281 monomer adopts an α‐β‐β‐β‐α fold and forms a homotetramer. Based on the properties and functions of structural homologues of the TTHA0281 monomer, the TTHA0281 protein is speculated to be involved in RNA metabolism, including RNA binding and cleavage. 相似文献
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Xue Xue Weiwei Zhang Jifeng Zhu Xiaojun Chen Sha Zhou Zhipeng Xu Gang Hu Chuan Su 《Journal of cellular and molecular medicine》2019,23(4):2568-2582
Aquaporin‐4 (AQP4), the main water‐selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced Parkinson's disease (PD) model, AQP4‐deficient (AQP4?/?) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+)‐positive neurons than did wild‐type AQP4 (AQP4+/+) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor‐β1 (TGF‐β1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4?/? mice after MPTP treatment. Furthermore, the lower level of TGF‐β1 in AQP4?/? mice partially resulted from impairment of its generation by astrocytes; reduced TGF‐β1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH+ neurons in AQP4?/? mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4‐mediated immune regulation. 相似文献
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Tien‐Chye Tan Yvette Y. Yien Bharat K. C. Patel Benjamin N. Mijts Kunchithapadam Swaminathan 《Acta Crystallographica. Section D, Structural Biology》2003,59(12):2257-2258
This is a report on the structure determination of AmyB, the second α‐amylase from Halothermothrix orenii, by X‐ray crystallography. This bacterium was isolated from saltpans where conditions consisted of both high temperatures and high NaCl content. AmyB is a 599‐residue protein which is stable and significantly active at 358 K in starch solution containing up to 10%(w/v) NaCl. The purified recombinant AmyB protein crystallizes in the monoclinic space group C2, with unit‐cell parameters a = 225.85, b = 77.16, c = 50.13 Å, β = 99.32°, using the hanging‐drop vapour‐diffusion method. The crystal diffracts X‐rays to a resolution limit of 1.97 Å. 相似文献
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《Peptide Science》2017,108(3)
The conformational characteristics of protected homo‐oligomeric Boc‐[β3(R)Val]n‐OMe, n = 1, 2, 3, 4, 6, 9, and 12 have been investigated in organic solvents using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) absorption spectroscopy and circular dichroism (CD) methods. The detailed 1H NMR analysis of Boc‐[β3(R)Val]12‐OMe reveals that the peptide aggregates extensively in CDCl3, but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl3 and in CD3OH. Limited assignment of the N‐terminus NH groups, together with solvent dependence of NH chemical shifts and temperature coefficients provides evidence for 14‐helix conformation in the 12‐residue peptide. FTIR analysis in CHCl3 establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm−1 (intramolecular) and 3285 cm−1 (intermolecular), begins at the level of the tetrapeptide. The observed CD bands, 214 nm (negative) and 198 nm (positive), support 14‐helix formation in the 9 and 12 residue sequences. The folding and aggregation tendencies of homo‐oligomeric α‐, β‐, and γ‐ residues is compared in the model peptides Boc‐[ωVal]n‐NHMe, ω = α, β, and γ and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl3, establish that the tendency to aggregate at the di and tripeptide level follows the order β > α∼γ, while the tendency to fold follows the order γ > β > α. 相似文献
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Zhiguang Ping Yi Shi Yanling Sun Liping Ma Ming Wang 《Acta Crystallographica. Section F, Structural Biology Communications》2012,68(1):41-44
The activity of interferon‐γ (IFN‐γ) relies on signal transduction, which is triggered by combination with the receptors interferon‐γ receptor α chain (IFNGR1) and β chain (IFNGR2). Native recombinant chicken IFNGR1 (chIFNGR1; residues 25–237) was overexpressed in Escherichia coli, purified by refolding and crystallized using the vapour‐diffusion technique. The crystals belonged to space group P6522, with unit‐cell parameters a = b = 64.1, c = 216.3 Å, α = β = 90, γ = 120°. The Matthews coefficient and solvent content were calculated as 2.67 Å3 Da−1 and 53.97%, respectively. X‐ray diffraction data for chIFNGR1 were collected to 2.0 Å resolution at a synchrotron source. 相似文献
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Anna Roujeinikova Carsten Raasch Svetlana Sedelnikova Wolfgang Liebl David W. Rice 《Acta Crystallographica. Section D, Structural Biology》2001,57(7):1046-1047
Thermotoga maritima 4‐α‐glucanotransferase (GTase), a 52 kDa molecular‐weight amylolytic enzyme, has been crystallized by the hanging‐drop vapour‐diffusion method using PEG monomethylether 5000 as a precipitating agent. A complete data set has been collected to 2.6 Å resolution using cryocooling conditions and synchrotron radiation. The crystals belong to space group I222 or I212121, with unit‐cell parameters a = 92.6, b = 180.3, c = 199.2 Å. 相似文献
18.
The stress response neuropeptide CRF increases amyloid‐β production by regulating γ‐secretase activity 
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下载免费PDF全文 Hyo‐Jin Park Yong Ran Joo In Jung Oliver Holmes Ashleigh R Price Lisa Smithson Carolina Ceballos‐Diaz Chul Han Michael S Wolfe Yehia Daaka Andrey E Ryabinin Seong‐Hun Kim Richard L Hauger Todd E Golde Kevin M Felsenstein 《The EMBO journal》2015,34(12):1674-1686
The biological underpinnings linking stress to Alzheimer's disease (AD) risk are poorly understood. We investigated how corticotrophin releasing factor (CRF), a critical stress response mediator, influences amyloid‐β (Aβ) production. In cells, CRF treatment increases Aβ production and triggers CRF receptor 1 (CRFR1) and γ‐secretase internalization. Co‐immunoprecipitation studies establish that γ‐secretase associates with CRFR1; this is mediated by β‐arrestin binding motifs. Additionally, CRFR1 and γ‐secretase co‐localize in lipid raft fractions, with increased γ‐secretase accumulation upon CRF treatment. CRF treatment also increases γ‐secretase activity in vitro, revealing a second, receptor‐independent mechanism of action. CRF is the first endogenous neuropeptide that can be shown to directly modulate γ‐secretase activity. Unexpectedly, CRFR1 antagonists also increased Aβ. These data collectively link CRF to increased Aβ through γ‐secretase and provide mechanistic insight into how stress may increase AD risk. They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ‐secretase. 相似文献
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Stefanie Kobus Pablo Perez-Garcia Astrid Hoeppner Nicholas Holzscheck Filip Kovacic Wolfgang R. Streit Karl-Erich Jaeger Jennifer Chow Sander H. J. Smits 《Acta Crystallographica. Section F, Structural Biology Communications》2019,75(4):307-311
The hyperthermophilic crenarchaeon Ignicoccus hospitalis KIN4/I possesses at least 35 putative genes encoding enzymes that belong to the α/β‐hydrolase superfamily. One of those genes, the metallo‐hydrolase‐encoding igni18, was cloned and heterologously expressed in Pichia pastoris. The enzyme produced was purified in its catalytically active form. The recombinant enzyme was successfully crystallized and the crystal diffracted to a resolution of 2.3 Å. The crystal belonged to space group R32, with unit‐cell parameters a = b = 67.42, c = 253.77 Å, α = β = 90.0, γ = 120.0°. It is suggested that it contains one monomer of Igni18 within the asymmetric unit. 相似文献
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Larry R. Masterson Marcus A. Etienne Fernando Porcelli George Barany Robert P. Hammer Gianluigi Veglia 《Peptide Science》2007,88(5):746-753
The use of α,α‐disubstituted amino acids represents a valuable strategy to exercise conformational control in peptides. Incorporation of the nonstereogenic α‐aminoisobutyryl‐glycyl (Aib‐Gly) dipeptidyl sequence into i + 1 and i + 2 positions of an acyclic peptide sequence, originally designed and investigated by Gellman and coworkers, [H‐Arg‐Tyr‐Val‐Glu‐Val‐Yyy‐Xxx‐Orn‐Lys‐Ile‐Leu‐Gln‐NH2] nucleates a stable [2:4] left‐handed type I′ β‐turn in water. NMR spectra show that this newly designed β‐hairpin does not aggregate in water up to a concentration of ∼1 mM, and that its backbone conformation is superimposable on corresponding hairpins containing the D Pro‐Gly (literature) and Aib‐D Ala (this work) sequences. The Aib‐Gly turn‐inducer sequence eliminates complications because of cis–trans isomerization of Zzz‐Pro bonds, and constitutes an attractive alternative to the proteogenic Asn‐Gly and nonproteogenic D Pro‐Gly motifs previously suggested as turn‐inducer sequences. These design principles could be exploited to prepare water‐soluble β‐hairpin peptides with robust structures and novel function. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 746–753, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献