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51.
Rana Begum Karin Calaza Jaimie Hoh Kam Thomas E. Salt Chris Hogg Glen Jeffery 《Biology letters》2015,11(3)
Ageing is an irreversible cellular decline partly driven by failing mitochondrial integrity. Mitochondria accumulate DNA mutations and reduce ATP production necessary for cellular metabolism. This is associated with inflammation. Near-infrared exposure increases retinal ATP in old mice via cytochrome c oxidase absorption and reduces inflammation. Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and reduced inflammation with age. Critically, there was a significant increase in average lifespan: 100–175% more flies survived into old age following 670 nm exposure and these had significantly improved mobility. This may be a simple route to extending lifespan and improving function in old age. 相似文献
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Ellman MB Kim JS An HS Chen D KC R An J Dittakavi T van Wijnen AJ Cs-Szabo G Li X Xiao G An S Kim SG Im HJ 《Gene》2012,505(2):283-290
MyD88 is an adapter protein that links toll-like receptors (TLRs) and Interleukin-1 receptors (IL-1Rs) with downstream signaling molecules. The MyD88 has been found to be an essential mediator in the development of osteoarthritis in articular cartilage. However, the role of the MyD88 pathway has yet to be elucidated in the intervertebral disk (IVD). Using in vitro techniques, we analyzed the effect of MyD88 pathway-specific inhibition on the potent inflammatory and catabolic mediator LPS and IL-1 in bovine and human nucleus pulposus (NP) cells by assessing matrix-degrading enzyme expression, including matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family). We also analyzed inhibition of MyD88 in the regulation of inducible nitric oxide synthase and TLR-2. Finally, we used an ex vivo organ culture model to assess the effects of MyD88 inhibitor (MyD88i) on catabolic factor-induced disk degeneration in mice lumbar disks. In bovine NP cells, MyD88i potently antagonizes LPS- or IL-1-mediated induction of cartilage-degrading enzyme production, including MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. MyD88i also attenuates the LPS- or IL-1-mediated induction of iNOS and TLR-2 gene expression. Our ex vivo findings reveal inhibition of MyD88 via counteraction of IL-1-mediated proteoglycan depletion. The findings from this study demonstrate the potent anti-inflammatory and anti-catabolic effects of inhibition of MyD88 pathway inhibition on IVD homeostasis, suggesting a potential therapeutic benefit of a MyD88i in degenerative disk disease in the future. 相似文献
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Heather A Harrington Kenneth L Ho Samik Ghosh KC Tung 《Theoretical biology & medical modelling》2008,5(1):26
Background
A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. 相似文献55.
Aida Ferreiro-Iglesias Manuel Calaza Eva Perez-Pampin Francisco J Lopez Longo Jose L Marenco Francisco J Blanco Javier Narvaez Federico Navarro Juan D Ca?ete Arturo R de la Serna Isidoro Gonzalez-Alvaro Gabriel Herrero-Beaumont Jose L Pablos Alejandro Balsa Benjamin Fernandez-Gutierrez Rafael Caliz Juan J Gomez-Reino Antonio Gonzalez 《Arthritis research & therapy》2014,16(5)
Introduction
Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti–cyclic citrullinated peptide–positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies.Methods
A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described.Results
Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term—the originally reported finding—or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods.Conclusions
None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists. 相似文献56.
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Characterization of EST-derived microsatellites for gene mapping and evolutionary genomics in turbot
Bouza C Hermida M Millán A Vilas R Vera M Fernández C Calaza M Pardo BG Martínez P 《Animal genetics》2008,39(6):666-670
The detection of microsatellite sequences within expressed sequence tags (ESTs) connects potential markers with specific genes, generating type I markers. We have developed and mapped by linkage analysis a set of EST-derived microsatellites in the turbot, Scophthalmus maximus. One hundred and ninety-one microsatellites were identified from 9256 turbot ESTs. Primer design was possible with 98 microsatellites. After genotyping 25 wild turbot and the parents of two reference families for linkage analysis, 43 EST-derived microsatellites were selected because they met technical and polymorphism criteria. A final set of 31 EST-derived microsatellites could be mapped to 17 linkage groups of the turbot consensus map based on 242 anonymous microsatellites. Twenty-four microsatellite-containing ESTs were functionally annotated, confirming them as type I markers. Nineteen were mapped in the turbot consensus map. These EST-derived microsatellites constitute useful tools for genome scanning of turbot populations, marker-assisted selection programmes and comparative mapping. 相似文献
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Paola Fatás Ana M. Gil M. Isabel Calaza Ana I. Jiménez Carlos Cativiela 《Chirality》2012,24(12):1082-1091
The preparation of all four stereoisomers of the proline analog that bears a phenyl group attached to the β carbon either cis or trans to the carboxylic acid (cis‐ and trans‐β‐phenylproline, respectively) has been addressed. The methodology developed allows access to multigram quantities of the target amino acids in enantiomerically pure form and suitably protected for use in peptide synthesis. Racemic precursors of cis‐β‐phenylproline and trans‐β‐phenylproline were prepared from easily available starting materials and subjected to high‐performance liquid chromatography enantioseparation. Semipreparative columns (250 × 20 mm) containing chiral stationary phases based on amylose (Chiralpak IA) (Daicel‐Chiral Technologies Europe, Illkirch, France) or cellulose (Chiralpak IC) were used respectively for the resolution of the cis‐ and trans‐β‐phenylproline precursors. Chirality, 24:1082‐1091, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
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Optical tweezers (infrared laser-based optical traps) have emerged as a powerful tool in molecular and cell biology. However, their usefulness has been limited, particularly in vivo, by the potential for damage to specimens resulting from the trapping laser. Relatively little is known about the origin of this phenomenon. Here we employed a wavelength-tunable optical trap in which the microscope objective transmission was fully characterized throughout the near infrared, in conjunction with a sensitive, rotating bacterial cell assay. Single cells of Escherichia coli were tethered to a glass coverslip by means of a single flagellum: such cells rotate at rates proportional to their transmembrane proton potential (. J. Mol. Biol. 138:541-561). Monitoring the rotation rates of cells subjected to laser illumination permits a rapid and quantitative measure of their metabolic state. Employing this assay, we characterized photodamage throughout the near-infrared region favored for optical trapping (790-1064 nm). The action spectrum for photodamage exhibits minima at 830 and 970 nm, and maxima at 870 and 930 nm. Damage was reduced to background levels under anaerobic conditions, implicating oxygen in the photodamage pathway. The intensity dependence for photodamage was linear, supporting a single-photon process. These findings may help guide the selection of lasers and experimental protocols best suited for optical trapping work. 相似文献
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