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Kimberly G. Norman Jeffrey A. Canter Mingjian Shi Ginger L. Milne Jason D. Morrow James E. Sligh 《Mitochondrion》2010,10(2):94-101
Transplant recipients have an elevated risk of skin cancer, with a 65- to 250-fold increase in squamous cell carcinoma. Usage of the immunosuppressant cyclosporine A (CsA) is associated with the development of skin cancer. We hypothesized that the increased incidence of skin cancer was due to the action of CsA within keratinocyte mitochondria where it can inhibit mitochondrial permeability transition pore (MPTP) opening. Normally, MPTP opening is induced by oxidative stress such as that caused by UV light and leads to cell death, thereby eliminating a cell that has been exposed to genotoxic insult. However, in the presence of CsA, damaged cells may survive and consequently form tumors. To test this hypothesis, we treated keratinocytes with levels of CsA used therapeutically in transplant patients and assessed their viability following UVA-irradiation. CsA prevented cell death by inhibiting MPTP opening, even though the levels of oxidative stress were increased markedly. Nim811, a non-immunosuppressive drug that can block the MPTP had a similar effect while the immunosuppressive drug tacrolimus that does not interact with the mitochondria had no effect. These findings suggest that CsA may promote skin cancer in transplant patients by allowing keratinocyte survival under conditions of increased genotoxic stress. 相似文献
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? Premise of the study: One potential threat to rare species is genetic swamping caused by hybridization, but few studies have quantified this threat. Rhododendron cyanocarpum is a narrow endemic species that occurs sympatrically with potentially interfertile congeners throughout its range within Yunnan, China. We searched the entire distribution of R. cyanocarpum for hybrids and examined the patterns of hybridization to assess potential threat from hybridization. ? Methods: In a comprehensive field survey, we detected only one instance of hybridization involving R. cyanocarpum, with R. delavayi, at Huadianba near Dali. Material of both species and putative hybrids was examined using morphology, chloroplast DNA, nuclear ribosomal DNA, and Bayesian analysis of AFLP profiles. ? Key results: Of 10 putative hybrids, two were F(1)(')s and at least seven were F(2)(')s. Four backcrosses to R. delavayi were detected among material with R. delavayi-like morphology within the hybrid zone. Backcrosses to R. cyanocarpum were not detected. Therefore F(2)(')s outnumbered all other classes within the hybrid zone, a situation not previously confirmed for plants and extremely rare generally. Hybridization was asymmetrical, with R. delavayi as the maternal parent in all but one of the hybrids detected. ? Conclusions: Although natural hybridization is common in Rhododendron, it is rare in R. cyanocarpum and is apparently not accompanied by backcrossing toward R. cyanocarpum. Hence, there is no immediate risk of genetic swamping, unless habitat disturbance increases and changes the patterns of hybridization. Our study is the first to report a plant hybrid zone dominated by F(2) hybrids. This pattern might contribute to species barrier maintenance. 相似文献
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Cecilie?M?MejdellEmail author Grete?HM?J?rgensen Therese?Rehn Kjersti?Fremstad Linda?Keeling Knut?E?B?e 《Acta veterinaria Scandinavica》2010,52(1):68
Background
The risk of injuries is of major concern when keeping horses in groups and there is a need for a system to record external injuries in a standardised and simple way. The objective of this study, therefore, was to develop and validate a system for injury recording in horses and to test its reliability and feasibility under field conditions.Methods
Injuries were classified into five categories according to severity. The scoring system was tested for intra- and inter-observer agreement as well as agreement with a 'golden standard' (diagnosis established by a veterinarian). The scoring was done by 43 agricultural students who classified 40 photographs presented to them twice in a random order, 10 days apart. Attribute agreement analysis was performed using Kendall's coefficient of concordance (Kendall's W), Kendall's correlation coefficient (Kendall's τ) and Fleiss' kappa. The system was also tested on a sample of 100 horses kept in groups where injury location was recorded as well.Results
Intra-observer agreement showed Kendall's W ranging from 0.94 to 0.99 and 86% of observers had kappa values above 0.66 (substantial agreement). Inter-observer agreement had an overall Kendall's W of 0.91 and the mean kappa value was 0.59 (moderate). Agreement for all observers versus the 'golden standard' had Kendall's τ of 0.88 and the mean kappa value was 0.66 (substantial). The system was easy to use for trained persons under field conditions. Injuries of the more serious categories were not found in the field trial.Conclusion
The proposed injury scoring system is easy to learn and use also for people without a veterinary education, it shows high reliability, and it is clinically useful. The injury scoring system could be a valuable tool in future clinical and epidemiological studies.66.
Background
Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. 相似文献67.
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Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献69.
P K Weech P Provost N M Tremblay R N Camato R W Milne Y L Marcel E Rassart 《Progress in lipid research》1991,30(2-3):259-266
The structure of ApoD and its sites of synthesis have been discovered. These characteristics differ from those of the other apolipoproteins. The role of ApoD in the plasma lipoprotein system remains to be discovered, but the recent, rapid increase in our knowledge of this protein suggests that it plays an important role in the homeostasis or housekeeping of probably all organs. One of its functions is likely to be the transport of a hydrophobic ligand (a lipid) in a one-to-one molar ratio with itself. This transport is likely to occur unidirectionally between neighboring cells in an organ, and between perivascular cells and the blood circulation. The chemical structure of the natural ligand, or ligands, of ApoD in normal cells in vivo or in culture is not known, but ApoD has been shown to bind some steroids and bilirubin. Remarkable upregulation of synthesis of ApoD has been observed during regeneration of injured peripheral nerves. Perhaps the physiologic role of ApoD will prove to be more interesting and of equal importance in biology to the roles of the other apolipoproteins in cardiovascular disease. 相似文献
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