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Marieke Rienks Anna Papageorgiou Kristiaan Wouters Wouter Verhesen Rick van Leeuwen Paolo Carai Georg Summer Dirk Westermann Stephane Heymans 《Cellular and molecular life sciences : CMLS》2017,74(8):1511-1525
Background
Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. SLRP’s may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown.Methods and results
This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. This immune cell activation by OGN occurred via MyD88 and increased phosphorylation of c-jun. Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation.Conclusion
The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. This variant is able to bind and activate TLR4. The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis.73.
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Rothman N Garcia-Closas M Chatterjee N Malats N Wu X Figueroa JD Real FX Van Den Berg D Matullo G Baris D Thun M Kiemeney LA Vineis P De Vivo I Albanes D Purdue MP Rafnar T Hildebrandt MA Kiltie AE Cussenot O Golka K Kumar R Taylor JA Mayordomo JI Jacobs KB Kogevinas M Hutchinson A Wang Z Fu YP Prokunina-Olsson L Burdett L Yeager M Wheeler W Tardón A Serra C Carrato A García-Closas R Lloreta J Johnson A Schwenn M Karagas MR Schned A Andriole G Grubb R Black A Jacobs EJ Diver WR Gapstur SM 《Nature genetics》2010,42(11):978-984
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?11) and a tag SNP for NAT2 acetylation status (P = 4 × 10?11), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis. 相似文献
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Anna Maria Frassanito Laura Barsanti Vincenzo Passarelli Valtere Evangelista Paolo Gualtieri 《Cellular and molecular life sciences : CMLS》2010,67(6):965-971
Here, we report the DNA sequence of the rhodopsin gene in the alga Cyanophora paradoxa (Glaucophyta). The primers were designed according to the conserved regions of prokaryotic and eukaryotic rhodopsin-like
proteins deposited in the GenBank. The sequence consists of 1,272 bp comprised of 5 introns. The correspondent protein, named
Cyanophopsin, showed high identity to rhodopsin-like proteins of Archea, Bacteria, Fungi, and Algae. At the N-terminal, the
protein is characterized by a region with no transmembrane α-helices (80 aa), followed by a region with 7α-helices (219 aa)
and a shorter 35-aa C-terminal region. The DNA sequence of the N-terminal region was expressed in E. coli and the recombinant purified peptide was used as antigen in hens to obtain polyclonal antibodies. Indirect immunofluorescence
in C. paradoxa cells showed a marked labeling of the muroplast (aka cyanelle) membrane. 相似文献
76.
Madhuri Kalathur Silvia Baiguera Paolo Macchiarini 《Cellular and molecular life sciences : CMLS》2010,67(24):4185-4196
There are a variety of airway diseases with different clinical settings, which may extend from a surgical approach to total
organ replacement. Tissue engineering involves modifying cells or tissues in order to repair, regenerate, or replace tissue
in the body and seems to be a promising approach for airway replacement. The successful implantation of stem-cell-based tissue-engineered
trachea in a young woman with end-stage post-tuberculosis left main bronchus collapse serves as a prototype for the airway
tissue-engineered-based approach. The trachea indeed could represent a perfect model system to investigate the translational
aspects of tissue engineering, largely due to its low-oxygen needs. This review highlights the anatomy of the airways, the
various disease conditions that cause damage to the airways, elaborates on the essential components of the tissue-engineering
approach, and discusses the success of the revolutionary trachea transplantation approach. 相似文献
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Submillimetre galaxies reside in dark matter haloes with masses greater than 3 × 10(11) solar masses
Amblard A Cooray A Serra P Altieri B Arumugam V Aussel H Blain A Bock J Boselli A Buat V Castro-Rodríguez N Cava A Chanial P Chapin E Clements DL Conley A Conversi L Dowell CD Dwek E Eales S Elbaz D Farrah D Franceschini A Gear W Glenn J Griffin M Halpern M Hatziminaoglou E Ibar E Isaak K Ivison RJ Khostovan AA Lagache G Levenson L Lu N Madden S Maffei B Mainetti G Marchetti L Marsden G Mitchell-Wynne K Nguyen HT O'Halloran B Oliver SJ Omont A Page MJ Panuzzo P Papageorgiou A Pearson CP 《Nature》2011,470(7335):510-512
The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year. These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes. Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. A previous attempt at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model. Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500?μm. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M(min), such that log(10)[M(min)/M(⊙)] = 11.5(+0.7)(-0.2) at 350?μm, where M(⊙) is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe, and is lower than that predicted by semi-analytical models for galaxy formation. 相似文献