Dienoyl-CoA reductase (DECR) deficiency with hyperlysinemia is a rare disorder affecting the metabolism of polyunsaturated fatty acids and lysine. The molecular basis of this condition is currently unknown. We describe a new case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy suggestive of a mitochondrial disorder. Exome sequencing revealed a causal mutation in NADK2. NADK2 encodes the mitochondrial NAD kinase, which is crucial for NADP biosynthesis evidenced by decreased mitochondrial NADP(H) levels in patient fibroblasts. DECR and also the first step in lysine degradation are performed by NADP-dependent oxidoreductases explaining their in vivo deficiency. DECR activity was also deficient in lysates of patient fibroblasts and could only be rescued by transfecting patient cells with functional NADK2. Thus NADPH is not only crucial as a cosubstrate, but can also act as a molecular chaperone that activates and stabilizes enzymes. In addition to polyunsaturated fatty acid oxidation and lysine degradation, NADPH also plays a role in various other mitochondrial processes. We found decreased oxygen consumption and increased extracellular acidification in patient fibroblasts, which may explain why the disease course is consistent with clinical criteria for a mitochondrial disorder. We conclude that DECR deficiency with hyperlysinemia is caused by mitochondrial NADP(H) deficiency due to a mutation in NADK2.

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a posttranscriptional level and play a crucial role in the development of cells of the immune system. Macrophages are essential for generating inflammatory reactions upon tissue damage and encountering of invading pathogens, yet modulation of their immune responses is critical for maintaining tissue homeostasis. Macrophages can present different phenotypes, depending on the cytokine environment they encounter in the affected tissues. In this study, we have identified expression signatures of miRNAs that are differentially regulated during maturation of monocytes and polarization of macrophages by cytokines. We present a comprehensive characterization of miRNA expression in human monocytes and M1, M2a, and M2c polarized macrophages, using next-generation sequencing. Furthermore, we show that miRNA expression signatures are closely related to the various immune functions of polarized macrophages and therefore are involved in shaping the diverse phenotypes of these cells. The miRNAs identified here serve as markers for identification of inflammatory macrophages involved in the development of immune responses. Our findings contribute to understanding the role of miRNAs in determining the macrophage function in healthy and diseased tissues.

This study aims were to determine the positional physical requirements of English domestic women’s rugby union match-play. Global positioning system data (Catapult Minimax S4) were collected at 10 Hz of 129 competitive player games from the Tyrrells Premier15 league. Players were classified according to broad (Forwards, Backs) and specific positions (front-, second-, back-row, scrum-half, inside-, and outside-backs). Total distances, maximum speed, and player loads were calculated. Mean total distance was 4982 m and was similar between the Forwards and Backs, with second-row players covering the most (5297 m) and outside-backs the least (4701 m). Inside- and outside-backs covered a significantly greater distance at high speed running (134 m; 178 m) and sprinting (74 m; 92 m) speeds, respectively, whereas the second- and back-row covered greater distances jogging (1966 m; 1976 m) and the front-row spent the greatest overall distance walking (2613 m). Outside-backs reached greater maximum speed than all other positions (24.9 km.h-1). The mean player load was highest in the back-row (562 AU) and second-row (555 AU) and these were higher than the outside-backs (476 AU). These findings indicate that the demands placed on female rugby players are position specific and differ from male players. Additionally, the data are the first obtained from the 10 Hz GPS and from within English domestic women’s rugby, thus adding to the overall limited data available on women’s rugby union.