Perturbations in growth trajectory due to early diet affect age-related deterioration in performance

Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence. Using three-spined sticklebacks (Gasterosteus aculeatus), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish caught up in size with controls. However, this growth acceleration influenced swimming endurance and its decline over the course of the breeding season, with a faster decline in fish that had undergone faster growth compensation. Similarly, accelerated growth led to a more pronounced reduction in the breeding period (as indicated by the duration of sexual ornamentation) over the following two breeding seasons, suggesting faster reproductive senescence. Parallel experiments showed a heightened effect of accelerated growth on these age-related declines in performance if the fish were under greater time stress to complete their compensation prior to the breeding season. Compensatory growth led to a reduction in median life span of 12% compared to steadily growing controls. While life span was independent of the eventual adult size attained, it was negatively correlated with the age-related decline in swimming endurance and sexual ornamentation. These results, complementary to those found when growth trajectories were altered by temperature rather than dietary manipulations, show that the costs of accelerated growth can last well beyond the time over which growth rates differ and are affected by the time available until an approaching life-history event such as reproduction

Effect of growth compensation on subsequent physical fitness in green swordtails Xiphophorus helleri

Early environmental conditions have been suggested to influence subsequent locomotor performance in a range of species, but most measurements have been of initial (baseline) performance. By manipulating early growth trajectories in green swordtail fish, we show that males that underwent compensatory growth as juveniles had a similar baseline swimming endurance when mature adults to ad libitum fed controls. However, they had a reduced capacity to increase endurance with training, which is more likely to relate to Darwinian fitness. Compensatory growth may thus result in important locomotor costs later in life

Supplementary Material for: Vitamin K Antagonists Predispose to Calciphylaxis in Patients with End-Stage Renal Disease

<b><i>Background/Aims:</i></b> Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. <b><i>Methods:</i></b> We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. <b><i>Results:</i></b> We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. <b><i>Conclusion:</i></b> Treatment with VKA predisposes to the development of calciphylaxis

Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and ΔF508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of ΔF508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No ΔF508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of ΔF508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and ΔF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing

Effects of pressure-sensitivity and plastic dilatancy on void growth and interaction

10.1016/j.ijsolstr.2005.10.014International Journal of Solids and Structures43216380-639