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Chronic kidney disease patients present with metabolic and functional muscle abnormalities, called uremic myopathy, whose mechanisms have not yet been fully elucidated. We investigated whether chronic renal insufficiency (CRI) affects skeletal muscle contractile properties at the cellular level. CRI was induced surgically in New Zealand rabbits (UREM), with sham-operation for controls (CON), and samples were collected at 3 months post-surgery, following euthanasia. All protocols had University Ethics approval following national and European guidelines. Sample treatments and evaluations were blinded. Maximal isometric force was assessed in 382 permeabilized psoas fibers (CON, n = 142, UREM, n = 240) initially at pH7, 10 °C (‘standard’ conditions), in subsets of fibers in acidic conditions (pH6.2, 10 °C) but also at near physiological temperature (pH7, 30 °C and pH6.2, 30 °C). CRI resulted in significant smaller average cross sectional areas (CSAs) by ∼11% for UREM muscle fibers (vs CON, P < 0.01). At standard conditions, UREM fibers produced lower absolute and specific forces (i.e. normalized force per fiber CSA) (vs CON, P < 0.01); force increased in 30 °C for both groups (P < 0.01), but the disparity between UREM and CON remained significant. Acidosis significantly reduced force (vs pH7, 10 °C P < 0.01), similarly in both groups (in UREM by −48% and in CON by −43%, P > 0.05). For the first time, we give evidence that CRI can induce significant impairments in single psoas muscle fibers force generation, only partly explained by fiber atrophy, thus affecting muscle mechanics at the cellular level. 相似文献
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Jan-Willem Taanman 《Journal of bioenergetics and biomembranes》1997,29(2):151-163
As the terminal component of the mitochondrial respiratory chain, cytochrome c oxidase plays a vital role in cellular energy transformation. Human cytochrome c oxidase is composed of 13 subunits. The three major subunits form the catalytic core and are encoded by mitochondrial DNA (mtDNA). The remaining subunits are nuclear-encoded. The primary sequence is known for all human subunits and the crystal structure of bovine heart cytochrome c oxidase has recently been reported. However, despite this wealth of structural information, the role of the nuclear-encoded subunits is still poorly understood. Yeast cytochrome c oxidase is a close model of its human counterpart and provides a means of studying the effects of mutations on the assembly, structure, stability and function of the enzyme complex. Defects in cytochrome c oxidase function are found in a clinically heterogeneous group of disorders. The molecular defects that underlie these diseases may arise from mutations of either the mitochondrial or the nuclear genomes or both. A significant number of cytochrome c oxidase deficiencies, often associated with other respiratory chain enzyme defects, are attributed to mutations of mtDNA. Mutations of mtDNA appear, nonetheless, uncommon in early childhood. Pedigree analysis and cell fusion experiments have demonstrated a nuclear involvement in some infantile cases but a specific nuclear genomic lesion has not yet been reported. Detailed analyses of the many steps involved in the biogenesis of cytochrome c oxidase, often pioneered in yeast, offer several starting points for further molecular characterizations of cytochrome c oxidase deficiencies observed in clinical practice. 相似文献
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Tayler N. LaSharr Samantha P. H. Dwinnell Brittany L. Wagler Hall Sawyer Rhiannon P. Jakopak Anna C. Ortega Luke R. Wilde Matthew J. Kauffman Katey S. Huggler Patrick W. Burke Miguel Valdez Patrick Lionberger Douglas G. Brimeyer Brandon Scurlock Jill Randall Rusty C. Kaiser Mark Thonhoff Gary L. Fralick Kevin L. Monteith 《The Journal of wildlife management》2023,87(1):e22333
Capture and handling techniques for individual-based, long-term research that tracks the life history of animals by recapturing the same individuals for several years has vastly improved study inferences and our understanding of animal ecology. Yet there are corresponding risks to study animals associated with physical trauma or capture myopathy that can occur during or following capture events. Rarely has empirical evidence existed to guide decisions associated with understanding the magnitude of capture-related risks, how to reduce these risks when possible, and implications for mortality censoring and survival estimates. We used data collected from 2,399 capture events of mule deer (Odocoileus hemionus) via helicopter net-gunning to compare daily survival probabilities within a 10-week period centered on a capture event and evaluated how animal age, nutritional condition (body fat), and various handling methods influenced survival before, during, and following a capture event. Direct mortality resulting from capture efforts was 1.59%. Mean daily survival was 0.9993 ± 0.0001 (SE) during the 5-week pre-capture window, was depressed the day of capture at 0.9841 ± 0.0004, and rebounded to 0.9990 ± 0.0008 during the 5-week post-capture window. Neither capture nor handling had a detectable effect on post-capture survival, including handling time ( = 13.30 ± 1.87 min), capture time of year (i.e., Dec or Mar), tooth extraction, and the number of times an animal had been recaptured (2–17 times). Although mortality rate was slightly elevated during capture (resulting from physical trauma associated with capture), age and nutritional condition did not influence the probability of mortality during a capture event. Following a capture event, nutritional condition influenced survival; however, that relationship was consistent with expected effects of nutritional condition on winter survival and independent of capture and handling. Overall survival rates 5 weeks before capture and 5 weeks after capture were not different. A specified window of time with depressed survival following capture and handling was not evident, which contradicts the implementation of a predetermined window often used by researchers and managers for censoring mortalities that occur after capture. Previous notions that censorship of all mortality data in the 2 weeks following capture is unwarranted and risks removal of meaningful data. With previous evidence guiding our protocols for capture (e.g., reduced chase time) and handling (e.g., temperature mitigation), low direct mortality and almost undetectable indirect mortality post capture reinforces the efficacy of helicopter net-gunning for capture and recapture of mule deer in long-term, individual-based studies. 相似文献