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Berlin Brandenburg

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  • 1
    In: Nature, 2011, Vol.471(7340), p.591
    Description: Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKK gamma or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin super(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1 beta was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.
    Keywords: Inflammation ; Cd40 Antigen ; 06910;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 2
    Language: English
    In: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, September 2012, Vol.16(9), pp.e687-91
    Description: The current study was conducted to use a developed framework to appraise the public primary care response to pandemic 2009 influenza A H1N1 virus in Hong Kong in 2009. A cross-sectional survey was conducted of 300 doctors working in public primary care clinics. In addition, a qualitative study was conducted in two selected general outpatient clinics (GOPCs) with 10 doctors between September and December 2009. We found that there was an increase in clinical service demand for public primary care doctors and that there was lower compliance with hand washing as compared to the wearing of masks among GOPC doctors during the study period. Since hand hygiene and influenza vaccination are effective methods to prevent the spread of influenza infection, future studies should explore the reasons for non-compliance with these preventive behaviors among doctors. More education and training in dealing with influenza A H1N1 infection may be needed.
    Keywords: Pandemics ; Physicians, Primary Care ; Hand Disinfection -- Methods ; Influenza A Virus, H1n1 Subtype -- Isolation & Purification ; Influenza, Human -- Epidemiology
    ISSN: 12019712
    E-ISSN: 1878-3511
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  • 3
    In: Hepatology, May 2015, Vol.61(5), pp.1565-1578
    Description: In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross‐sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty‐two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long‐chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH). : Well‐defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS. (H 2015;61:1565–1578)
    Keywords: Medicine;
    ISSN: 0270-9139
    E-ISSN: 1527-3350
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  • 4
    Language: English
    In: Frontiers in Pharmacology, 01 January 2018, Vol.8
    Description: Rheumatoid arthritis synovial fibroblasts (RASFs) are fundamental effector cells in RA driving the joint inflammation and deformities. Celastrol is a natural compound that exhibits a potent anti-arthritic effect promoting endoplasmic reticulum (ER) stress mediated by intracellular calcium (Ca2+)...
    Keywords: Rheumatoid Arthritis ; Rasfs ; Celastrol ; Calcium ; Inflammation ; Autoimmunity ; Pharmacy, Therapeutics, & Pharmacology
    E-ISSN: 1663-9812
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  • 5
    Language: English
    In: Journal of Virology, 2011, Vol. 85(22), p.11581
    Description: The 2009 pandemic influenza H1N1 (H1N1pdm) virus was generated by reassortment of swine influenza viruses of different lineages. This was the first influenza pandemic to emerge in over 4 decades and the first to occur after the realization that influenza pandemics arise from influenza viruses of animals. In order to understand the biological determinants of pandemic emergence, it is relevant to compare the tropism of different lineages of swine influenza viruses and reassortants derived from them with that of 2009 pandemic H1N1 (H1N1pdm) and seasonal influenza H1N1 viruses in ex vivo cultures of the human nasopharynx, bronchus, alveoli, and conjunctiva. We hypothesized that virus which can transmit efficiently between humans replicated well in the human upper airways. As previously reported, H1N1pdm and seasonal H1N1 viruses replicated efficiently in the nasopharyngeal, bronchial, and alveolar epithelium. In contrast, representative viruses from the classical swine (CS) (H1N1) lineage could not infect human respiratory epithelium; Eurasian avian-like swine (EA) (H1N1) viruses only infected alveolar epithelium and North American triple-reassortant (TRIG) viruses only infected the bronchial epithelium albeit inefficiently. Interestingly, a naturally occurring triple-reassortant swine virus, A/SW/HK/915/04 (H1N2), with a matrix gene segment of EA swine derivation (i.e., differing from H1N1pdm only in lacking a neuraminidase [NA] gene of EA derivation) readily infected and replicated in human nasopharyngeal and bronchial epithelia but not in the lung. A recombinant sw915 with the NA from H1N1pdm retained its tropism for the bronchus and acquired additional replication competence for alveolar epithelium. In contrast to H1N1pdm, none of the swine viruses tested nor seasonal H1N1 had tropism in human conjunctiva. Recombinant viruses generated by swapping the surface proteins (hemagglutinin and NA) of H1N1pdm and seasonal H1N1 virus demonstrated that these two gene segments together are key determinants of conjunctival tropism. Overall, these findings suggest that ex vivo cultures of the human respiratory tract provide a useful biological model for assessing the human health risk of swine influenza viruses.
    Keywords: Viral Tropism ; Conjunctiva -- Virology ; Influenza A Virus, H1n1 Subtype -- Pathogenicity ; Influenza A Virus, H1n2 Subtype -- Pathogenicity ; Reassortant Viruses -- Isolation & Purification ; Respiratory Mucosa -- Virology;
    ISSN: 1098-5514
    ISSN: 10985514
    ISSN: 0022538X
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  • 6
    Language: English
    In: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 February 2004, Vol.10(4), pp.1401-8
    Description: In the present study, we investigated the prognostic and diagnostic significance of beta-catenin nuclear immunostaining in 60 specimens of normal colorectal tissue; 180 specimens of colorectal polyps, adenomas, and carcinomas; and 40 specimens from patients...
    Keywords: Cell Nucleus -- Metabolism ; Colorectal Neoplasms -- Metabolism ; Cytoskeletal Proteins -- Metabolism ; Trans-Activators -- Metabolism
    ISSN: 1078-0432
    E-ISSN: 15573265
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  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 17 October 2006, Vol.103(42), pp.15582-7
    Description: Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids. A targeted insertion methodology was developed to determine the telomeric sequences. RHA1's 9,145 predicted protein-encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many of the oxygenases occur in the numerous pathways predicted to degrade aromatic compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes, providing evidence that rhodococci harbor an extensive secondary metabolism. Among sequenced genomes, RHA1 is most similar to those of nocardial and mycobacterial strains. The genome contains few recent gene duplications. Moreover, three different analyses indicate that RHA1 has acquired fewer genes by recent horizontal transfer than most bacteria characterized to date and far fewer than Burkholderia xenovorans LB400, whose genome size and catabolic versatility rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically similar bacteria can evolve large genomes by different means. Overall, RHA1 appears to have evolved to simultaneously catabolize a diverse range of plant-derived compounds in an O(2)-rich environment. In addition to establishing RHA1 as an important model for studying actinomycete physiology, this study provides critical insights that facilitate the exploitation of these industrially important microorganisms.
    Keywords: Bacterial Proteins ; Genome, Bacterial ; Metabolism ; Rhodococcus
    ISSN: 0027-8424
    E-ISSN: 10916490
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  • 8
    Language: English
    In: American Journal of Pathology, April 2010, Vol.176(4), pp.1828-40
    Description: The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited...
    Keywords: Animals ; Bronchi ; Pandemics ; Pneumocytes ; Respiratory System ; Seasons ; Species Specificity ; Conjunctiva ; Cytokines ; Dogs ; Epithelial Cells ; Humans ; Influenza A Virus, H1n1 Subtype ; Influenza, Human ; Orthomyxoviridae ; Life Sciences ; Microbiology and Parasitology ; Virology ; Medicine
    ISSN: 0002-9440
    E-ISSN: 1525-2191
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  • 9
    Language: English
    In: Journal of Pathology, May 2001, Vol.194(1), pp.35-42
    Description: In order to understand the intricate relationship of cell proliferation and apoptosis in tumour development, proliferation markers (Ki‐67 and c‐), apoptosis, cell‐cycle inducers cyclin D1 and D3, and cell‐cycle inhibitors p16, p21, and p27 were evaluated in ductal breast carcinoma. The heterogeneous nature of breast tumours provides a system by which the changes in cell‐cycle genes can be explored under a wide range of proliferation and apoptotic indices. To address the above issues, immunohistochemical studies were conducted in 40 pairs of tumours and adjacent normal ductal tissues. The TUNEL method was used to identify apoptotic cells. Except for p27/KIP1, the proliferation (Ki‐67, c‐) and the apoptotic indexes together with levels of p16/INK4a, p21/CIP1, cyclin D1, and cyclin D3, were clearly elevated among tumour tissues, while absent in the adjacent normal tissues. Spearman correlation analysis indicated strong associations among apoptotic index, Ki‐67, c‐, and tumour grade. In addition, p21/CIP1 and cyclin D3 were positively correlated, while p16/INK4a, p27/KIP1, and cyclin D1 were negatively correlated with tumour grade. There was clear decoupling between p21 and p27, as well as decoupling between cyclin D1 and cyclin D3, in terms of their relationship to cell proliferation and apoptosis, indicating differential roles in tumour progression. Copyright © 2001 John Wiley & Sons, Ltd.
    Keywords: Breast ; Ductal Carcinoma ; Apoptosis ; Ki‐67 ; C‐ ; Cdk Inhibitors ; P21 ; P27 ; P16 ; Cyclin D1 ; Cyclin D3
    ISSN: 0022-3417
    E-ISSN: 1096-9896
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  • 10
    Language: English
    In: Biological chemistry, August 2003, Vol.384(8), pp.1147-54
    Description: Frizzled-related protein (Frp) is a newly identified family of secreted proteins involved in the Wnt signaling pathway. To date, little is known about the underlying mechanisms regulating Frp expression. In this study the promoter region of mouse frizzled related protein 4 (sFrp4) gene was cloned, sequenced, and analyzed using transient reporter assays along with site-directed mutagenesis. Two clusters of cis-acting elements, STAT3/Lyf-1/MZF1 (site 1) and C/EBP-beta/ GATA-1/CREB (site 2) located in the promoter region from -238 to -144 were found to be essential for the promoter activity of sFrp4. In addition to sites 1 and 2, putative transcriptional factor binding sites for TFIID, SP1/GC and ATF/CREB exhibited positive, while the site for NRSE exhibited negative regulatory functions, as determined by the alkaline phosphatase activities of the reporter assay. We also demonstrate that the ATF/CREB site may cooperatively interact with the NRSF-like element in regulating sFrp4 promoter activity. The data of our study, which is the first promoter analysis of mouse Frp genes, provide the basis for understanding the functions and the regulation of Frp and its role in regulating Wnt signals.
    Keywords: Promoter Regions, Genetic ; Proteins -- Genetics
    ISSN: 1431-6730
    E-ISSN: 14374315
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