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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of nutrition, February 2002, Vol.132(2), pp.145-51
    Description: The relationship between nutritional status and insulin-like growth factor binding protein-2 (IGFBP-2) gene expression in chickens was studied. Chickens (6 wk old) were food deprived for 2 d and then refed. IGFBP-2 mRNA in the brain was significantly decreased by food deprivation and levels did not increase when birds were refed for 24 h. Gizzard and hepatic IGFBP-2 mRNA levels were significantly increased by food deprivation and decreased by refeeding. Any nutrients tested decreased hepatic IGFBP-2 gene expression. In kidney, IGFBP-2 mRNA was detected but not influenced by food deprivation and refeeding. In another study, the influence of dietary protein source [isolated soybean protein vs. casein; crude protein (CP) 20%] and the supplementation of essential amino acids on IGFBP-2 gene expression of young chickens (5 wk old) was examined. The influence of feeding a low soybean protein diet (CP 5%) on tissue IGFBP-2 gene expression was also investigated. Hepatic IGFBP-2 mRNA was not detected in any group. Feeding the low protein diet for 7 d decreased brain IGFBP-2 mRNA level and increased gizzard IGFBP-2 level compared with chickens fed 20% protein diets. A significant interaction between protein source and amino acid supplementation was observed in gizzard IGFBP-2 mRNA level. In both casein-fed groups and in chickens fed 20% soybean protein diet without supplemental amino acids, the levels did not differ from one another or from the low protein diet-fed birds. The level was lower in chickens fed the amino acid-supplemented, 20% soybean protein diet. In conclusion, the response of IGFBP-2 gene expression to variations in nutritional status was rapid and different in several tissues of young chickens, which would help modulate the growth-promoting effect of circulating IGF-I by making the IGF-IGFBP complex.
    Keywords: Gene Expression Regulation, Developmental ; Chickens -- Metabolism ; Food Deprivation -- Physiology ; Insulin-Like Growth Factor Binding Protein 2 -- Genetics
    ISSN: 0022-3166
    E-ISSN: 15416100
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  • 2
    Language: English
    In: The Journal of Allergy and Clinical Immunology, April 2016, Vol.137(4), pp.1226-1235
    Description: The circadian clock temporally gates signaling through the high-affinity IgE receptor (FcεRI) in mast cells, thereby generating a marked day/night variation in allergic reactions. Thus manipulation of the molecular clock in mast cells might have therapeutic potential for IgE-mediated allergic reactions. We determined whether pharmacologically resetting the molecular clock in mast cells or basophils to times when FcεRI signaling was reduced (ie, when core circadian protein period 2 [PER2] is upregulated) resulted in suppression of IgE-mediated allergic reactions. We examined the effects of PF670462, a selective inhibitor of the key clock component casein kinase 1δ/ε, or glucocorticoid, both of which upregulated PER2 in mast cells, on IgE-mediated allergic reactions both and . PF670462 or corticosterone (or dexamethasone) suppressed IgE-mediated allergic reactions in mouse bone marrow–derived mast cells or basophils and passive cutaneous anaphylactic reactions in mice in association with increased PER2 levels in mast cells or basophils. PF670462 or dexamethasone also ameliorated allergic symptoms in a mouse model of allergic rhinitis and downregulated allergen-specific basophil reactivity in patients with allergic rhinitis. Pharmacologically resetting the molecular clock in mast cells or basophils to times when FcεRI signaling is reduced can inhibit IgE-mediated allergic reactions. The results suggest a new strategy for controlling IgE-mediated allergic diseases. Additionally, this study suggests a novel mechanism underlying the antiallergic actions of glucocorticoids that relies on the circadian clock, which might provide a novel insight into the pharmacology of this drug in allergic patients.
    Keywords: Circadian Clock ; Mast Cells ; Basophils ; Ige ; Allergy ; Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 3
    Language: English
    In: Annals of neurology, January 2019, Vol.85(1), pp.47-58
    Description: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend 0.11). The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47-58.
    Keywords: Aged–Blood ; Aged, 80 and Over–Blood ; Biomarkers–Diagnosis ; Dementia–Epidemiology ; Female–Epidemiology ; Follow-Up Studies–Biosynthesis ; Gene Expression–Blood ; Humans–Genetics ; Incidence–Metabolism ; Japan–Biosynthesis ; Longitudinal Studies–Blood ; Male–Genetics ; Membrane Glycoproteins–Genetics ; Middle Aged–Genetics ; Myeloid Cells–Genetics ; Prospective Studies–Genetics ; Receptors, Immunologic–Genetics ; Risk Factors–Genetics ; Biomarkers ; Membrane Glycoproteins ; Receptors, Immunologic ; Trem2 Protein, Human;
    ISSN: 03645134
    E-ISSN: 1531-8249
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  • 4
    In: Nature Genetics, 2016
    Description: Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.
    Keywords: Adrenal Insufficiency -- Genetics ; Chromosomes, Human, Pair 7 -- Genetics ; Growth Disorders -- Genetics ; Mutation -- Genetics ; Myelodysplastic Syndromes -- Genetics ; Proteins -- Genetics;
    ISSN: 1061-4036
    E-ISSN: 15461718
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  • 5
    Language: English
    In: Extremophiles, 2016, Vol.20(3), pp.275-282
    Description: TTHA0829 from Thermus thermophilus HB8 has a molecular mass of 22,754 Da and is composed of 210 amino acid residues. The expression of TTHA0829 is remarkably elevated in the latter half of logarithmic growth phase. TTHA0829 can form either a tetrameric or dimeric structure, and main-chain folding provides an N-terminal cystathionine-β-synthase (CBS) domain and a C-terminal aspartate-kinase chorismate-mutase tyrA (ACT) domain. Both CBS and ACT are regulatory domains to which a small ligand molecule can bind. The CBS domain is found in proteins from organisms belonging to all kingdoms and is observed frequently as two or four tandem copies. This domain is considered as a small intracellular module with a regulatory function and is typically found adjacent to the active (or functional) site of several enzymes and integral membrane proteins. The ACT domain comprises four β-strands and two α-helices in a βαββαβ motif typical of intracellular small molecule binding domains that help control metabolism, solute transport and signal transduction. We discuss the possible role of TTHA0829 based on its structure and expression pattern. The results imply that TTHA0829 acts as a cell-stress sensor or a metabolite acceptor.
    Keywords: Hypothetical protein ; Thermus thermophilus HB8 ; Crystal structure ; CBS domain ; ACT domain ; Gene-annotation
    ISSN: 1431-0651
    E-ISSN: 1433-4909
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  • 6
    Language: English
    In: Genes & development, May 2010, Vol.24(9), pp.887-92
    Description: VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI2-deficient male germ cells due to defective de novo DNA methylation, which is presumably caused by impaired piRNA expression. Here, we report that essentially the same abnormalities are observed in MVH (mouse VASA homolog)-deficient mice. Comprehensive analysis of piRNAs in MVH-deficient fetal male germ cells showed that MVH plays crucial roles in the early phase of the ping-pong amplification cycle.
    Keywords: Gene Silencing ; Dead-Box RNA Helicases -- Genetics ; Genes, Intracisternal A-Particle -- Genetics ; Long Interspersed Nucleotide Elements -- Genetics ; RNA, Small Interfering -- Metabolism
    ISSN: 08909369
    E-ISSN: 1549-5477
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  • 7
    Language: English
    In: The Journal of biological chemistry, 25 February 2005, Vol.280(8), pp.6721-30
    Description: Aldosterone synthase (CYP11B2) is involved in the final steps of aldosterone biosynthesis and expressed exclusively in the adrenal zona glomerulosa cells. Using an electrophoretic mobility shift assay, we demonstrate that COUP-TFI binds to the -129/-114 element (Ad5) of human CYP11B2 promoter. Transient transfection in H295R adrenal cells demonstrated that COUP-TFI enhanced CYP11B2 reporter activity. However, the reporter construct with mutated Ad5 sequences showed reduced basal and COUP-TFI-enhanced activity, suggesting that binding of COUP-TFI to Ad5 is important for CYP11B2 transactivation. To elucidate molecular mechanisms of COUP-TFI-mediated activity, we subsequently screened for COUP-TFI-interacting proteins from a human adrenal cDNA library using a yeast two-hybrid system and identified Ubc9 and PIAS1, which have small ubiquitin-related modifier-1 (SUMO-1) conjugase and ligase activities, respectively. The coimmunoprecipitation assays confirmed that COUP-TFI forms a complex with Ubc9 and PIAS1 in mammalian cells. Immunohistochemistry showed that Ubc9 and PIAS1 are markedly expressed in rat adrenal glomerulosa cells. Coexpression of Ubc9 and PIAS1 synergistically enhanced the COUP-TFI-mediated CYP11B2 reporter activity, indicating that both proteins function as coactivators of COUP-TFI. However, sumoylation-defective mutants, Ubc9 (C93S) and PIAS1 (C351S), continued to function as coactivators of COUP-TFI, indicating that sumoylation activity are separable from coactivator ability. In addition, chromatin immunoprecipitation assays demonstrated that ectopically expressed COUP-TFI, Ubc9, and PIAS1 were recruited to an endogenous CYP11B2 promoter. Moreover, reduction of Ubc9 or PIAS1 protein levels by small interfering RNA inhibited the CYP11B2 transactivation by COUP-TFI. Our data support a physiological role of Ubc9 and PIAS1 as transcriptional coactivators in COUP-TFI-mediated CYP11B2 transcription.
    Keywords: Cytochrome P-450 Cyp11b2 -- Genetics ; DNA-Binding Proteins -- Physiology ; Proteins -- Metabolism ; Transcription Factors -- Physiology ; Ubiquitin-Conjugating Enzymes -- Metabolism
    ISSN: 0021-9258
    E-ISSN: 1083351X
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  • 8
    Language: English
    In: The Journal of biological chemistry, 22 July 2005, Vol.280(29), pp.27244-50
    Description: The Nrf2-Keap1 system coordinately regulates cytoprotective gene expression via the antioxidant responsive element (ARE). The expression of several ARE-regulated genes was found to be up-regulated in endothelial cells by laminar shear stress, suggesting that Nrf2 contributes to the anti-atherosclerosis response via the ARE. To gain further insight into the roles that Nrf2 plays in the development of atherosclerosis, we examined how Nrf2 regulates gene expression in response to anti-atherogenic laminar flow (L-flow) or pro-atherogenic oscillatory flow (O-flow). Exposure of human aortic endothelial cells (HAECs) to L-flow, but not to O-flow, induced the expression of cytoprotective genes, such as NAD(P)H quinone oxidoreductase 1 (NQO1) by 5-fold and heme oxygenase-1 by 8-fold. The critical contribution of Nrf2 to the expression induced by L-flow was ascertained in siRNA-mediated knock-down experiments. Two cyclooxygenase-2 (COX-2) specific inhibitors attenuated Nrf2 nuclear accumulation in the acute phase of L-flow exposure. A downstream product of COX-2, 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), activated the Nrf2 regulatory pathway in HAECs through binding to the cysteines of Keap1. These results demonstrate that 15d-PGJ2 is essential for L-flow to activate Nrf2 and induce anti-atherosclerotic gene expression. Whereas both L-flow and O-flow induced the nuclear accumulation of Nrf2 to comparable levels, chromatin immunoprecipitation analysis revealed that Nrf2 binding to the NQO1 ARE was significantly diminished in the case of O-flow compared with that of L-flow. These results suggest that O-flow inhibits Nrf2 activity at the DNA binding step, thereby suppressing athero-protective gene expression and hence predisposing the blood vessels to the formation of atherosclerosis.
    Keywords: DNA-Binding Proteins -- Physiology ; Endothelium, Vascular -- Cytology ; Proteins -- Physiology ; Trans-Activators -- Physiology
    ISSN: 0021-9258
    E-ISSN: 1083351X
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  • 9
    In: Nature, 2002, Vol.420(6913), p.312
    Description: The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.
    Keywords: Genome, Plant ; Physical Chromosome Mapping ; Chromosomes, Plant -- Genetics ; Oryza -- Genetics;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 10
    Language: English
    In: Oncology letters, June 2019, Vol.17(6), pp.5139-5146
    Description: The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 〈10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP 〈0.12 mg/dl (P〈0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.
    Keywords: Crp ; Il-6 ; Os ; Rfs ; Breast Cancer
    ISSN: 1792-1074
    E-ISSN: 17921082
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