Epigenetic regulation of centromeric chromatin: old dogs, new tricks?

The assembly of just a single kinetochore at the centromere of each sister chromatid is essential for accurate chromosome segregation during cell division. Surprisingly, despite their vital function, centromeres show considerable plasticity with respect to their chromosomal locations and activity. The establishment and maintenance of centromeric chromatin, and therefore the location of kinetochores, is epigenetically regulated. The histone H3 variant CENP-A is the key determinant of centromere identity and kinetochore assembly. Recent studies have identified many factors that affect CENP-A localization, but their precise roles in this process are unknown. We build on these advances and on new information about the timing of CENP-A assembly during the cell cycle to propose new models for how centromeric chromatin is established and propagated

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The magnitude and character of resistance-training-induced increase in tendon stiffness at old age is gender specific

Human tendon mechanical properties are modified with loading. Moreover, there are indications that the training response in the tendon is gender specific. The aim of the current study was to examine whether in vivo patella tendon stiffness (K) differentially alters with training in older males compared with females. We also aimed to identify which endocrine pathway underlies the responses. Maximal knee extensor forces were also monitored to determine the training effect on muscle function. Fourteen healthy, habitually active older persons (seven males aged 74.0 ± 1.2 years (mean±SEM) and seven females aged 76.7 ± 1.2 years) were tested at baseline and after 12 weeks of weekly, progressive resistance training. With training, percentage increase in quadriceps maximum voluntary isometric force (MVC) was similar in males (2,469.6 ± 168.0 to 3,097.3 ± 261.9 N; +25.3 ± 6.1% (p < 0.01)) and females (1,728.8 ± 136.3 to 2,166.5 ± 135.8 N; +30.4 ± 15.1% (p < 0.05)), respectively. K increased more in males (338.0 ± 26.6 to 616.9 ± 58.7 N/mm; 79.8 ± 4.2% (p < 0.001)) compared to females (338.9 ± 31.0 to 373.2 ± 25.8 N/mm; +13.0 ± 3.7% (p < 0.001)). Interestingly, a pattern was found whereby below ~40% MVC, the females showed their greatest degree of K changes, whereas the males showed their greatest degree of K change above this relative force level. This gender contrast was also true at a standardised force level (1,200 N), with 5.8 ± 0.4% vs. 82.5 ± 1.8% increments in the females (i.e. value change from 380.3 ± 14.1 to 402.4 ± 13.3 N/mm) and the males (i.e. value change from 317.8 ± 13.8 to 580.2 ± 30.9 N/mm), respectively (p < 0.001). While circulating levels of both IGF-I and IL-6 did not alter with training, IGFBP-3 showed a significant training effect (19.1 ± 4.8%, p < 0.001) and only in the male sub-group (p = 0.038). We show here that with training, in vivo older females' tendon is less dramatically modulated than that of males'. We also show that the relative forces, at which the greatest adaptations are exhibited, differ by gender, with a suggestion of endocrine adaptations in males only. We thus propose that both training and rehabilitation regimens should consider gender-specific tendon responsiveness, at least in older persons