Evidence that a positive feedback loop drives centrosome maturation in fly embryos.

Centrosomes are formed when mother centrioles recruit pericentriolar material (PCM) around themselves. The PCM expands dramatically as cells prepare to enter mitosis (a process termed centrosome maturation), but it is unclear how this expansion is achieved. In flies, Spd-2 and Cnn are thought to form a scaffold around the mother centriole that recruits other components of the mitotic PCM, and the Polo-dependent phosphorylation of Cnn at the centrosome is crucial for scaffold assembly. Here, we show that, like Cnn, Spd-2 is specifically phosphorylated at centrosomes. This phosphorylation appears to create multiple phosphorylated S-S/T(p) motifs that allow Spd-2 to recruit Polo to the expanding scaffold. If the ability of Spd-2 to recruit Polo is impaired, the scaffold is initially assembled around the mother centriole, but it cannot expand outwards, and centrosome maturation fails. Our findings suggest that interactions between Spd-2, Polo and Cnn form a positive feedback loop that drives the dramatic expansion of the mitotic PCM in fly embryos

The Influence of Recovery and Training Phases on Body Composition, Peripheral Vascular Function and Immune System of Professional Soccer Players

Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4±4.2 kg to 72.2±3.9 kg was observed, but an increase of fat mass from 10.3±5.6 kg to 11.1±5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3±3.4 and 26.0±6.3 ml/100 ml/min) respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0±2.7 and 33.9±7.6 ml/100 ml/min) during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by iNOS and HO-1 activation, as well as IL-8 release. The data provided from this study suggest that the immune system is not able to function fully during periods of high physical stress. The implications of this study are that recuperation should be carefully monitored in athletes who undergo intensive training over extended periods, but that these parameters may also prove useful for determining an individual's risk of tissue stress and possibly their susceptibility to progressive tissue damage or injury

Centriole distal-end proteins CP110 and Cep97 influence centriole cartwheel growth at the proximal end

Centrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that in Drosophila embryos an oscillation of Polo-like kinase 4 (Plk4) helps to initiate and time the growth of the cartwheel at the proximal end. Here, in the same model, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels rise and fall as the new centriole MTs grow, in a manner that appears to be entrained by the core cyclin-dependent kinase (Cdk)–Cyclin oscillator that drives the nuclear divisions in these embryos. These CP110 and Cep97 dynamics, however, do not appear to time the period of centriole MT growth directly. Instead, we find that changing the levels of CP110 and Cep97 appears to alter the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected potential crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which might help to coordinate centriole growth

Isolation, biosynthesis and chemical modifications of Rubterolones A-F:rare tropolone alkaloids from <i>Actinomadura </i>sp 5-2

The discovery of six new, highly substituted tropolone alkaloids, rubterolones A–F, from Actinomadura sp. 5-2, isolated from the gut of the fungus-growing termite Macrotermes natalensis is reported. Rubterolones were identified by using fungus-bacteria challenge assays and a HRMS-based dereplication strategy, and characterised by NMR and HRMS analyses and by X-ray crystallography. Feeding experiments and subsequent chemical derivatisation led to a first library of rubterolone derivatives (A–L). Genome sequencing and comparative analyses revealed their putative biosynthetic pathway, which was supported by feeding experiments. This study highlights how gut microbes can present a prolific source of secondary metabolites.The Daimler Benz foundation to C.B., the Villum Kann Rasmussen Foundation for a Young Investigator Fellowship (VKR10101) to M.P. R.B., the International Leibniz Research School for Microbial and Biomolecular Interactions (ILRS) and School for Microbial Communication (JSMC, DFG).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-37652018-07-12hj2017Forestry and Agricultural Biotechnology Institute (FABI)Microbiology and Plant Patholog

The effect of menstrual cycle on 2000-m rowing ergometry performance

The aim of this study was to examine the effect of menstrual cycle phase on 2000-m rowing ergometry performance. Since high concentrations of oestrogen, indicative of the mid-luteal phase of the menstrual cycle, tend to decrease glycogen utilization and reduce blood lactate concentration, it was predicted that time taken to complete a 2000-m rowing trial would be shorter in the mid-luteal phase. Ten eumenorrhoeic, recreationally trained, female volunteers (mean age 33.0 years, s=7.1) completed 2000-m time trials on a Concept 2 rowing ergometer, in both the mid-follicular and mid-luteal phases of their menstrual cycle. In each phase, a 3-min incremental rowing protocol was used to determine a blood lactate concentration of 4 mmol • l−1 (T lac-4mM) and maximum oxygen consumption (VO2max); a five-stroke maximal test was used to establish maximal power. Order of testing was randomized for menstrual cycle phase. Variables (T lac-4mM, VO2max, maximal power) were correlated with speed in the 2000-m time trials, and the effect of menstrual cycle phase on these variables was examined. A blood lactate concentration of 4 mmol • l−1 occurred at a significantly higher mean exercise intensity (mid-luteal vs. mid-follicular: 169.1 W, s=39.1 vs. 159.0 W, s=38.3; P=0.033), heart rate (179 beats • min−1, s=9 vs. 173 beats • min−1, s=11; P=0.0047), and oxygen consumption (2.64 litres • min−1, s=0.66 vs. 2.42 litres • min−1, s=0.62; P=0.04) in the mid-luteal phase than in the mid-follicular phase. There was no significant difference (P=0.11) in 2000-m time trial speed according to menstrual cycle phase. In conclusion, although T lac-4mM differed due to menstrual cycle phase, 2000-m rowing performance was unaffected. Further research into the effects of menstrual cycle on rowing performance of a longer duration, among a more homogenous group of females, is recommended

Poly‐GP in cerebrospinal fluid links C9orf72‐associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD

Abstract The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). Non‐conventional repeat translation results in five dipeptide repeat proteins (DPRs), but their clinical utility, overall significance, and temporal course in the pathogenesis of c9ALS/FTD are unclear, although animal models support a gain‐of‐function mechanism. Here, we established a poly‐GP immunoassay from cerebrospinal fluid (CSF) to identify and characterize C9orf72 patients. Significant poly‐GP levels were already detectable in asymptomatic C9orf72 mutation carriers compared to healthy controls and patients with other neurodegenerative diseases. The poly‐GP levels in asymptomatic carriers were similar to symptomatic c9ALS/FTD cases. Poly‐GP levels were not correlated with disease onset, clinical scores, and CSF levels of neurofilaments as a marker for axonal damage. Poly‐GP determination in CSF revealed a C9orf72 mutation carrier in our cohort and may thus be used as a diagnostic marker in addition to genetic testing to screen patients. Presymptomatic expression of poly‐GP and likely other DPR species may contribute to disease onset and thus represents an alluring therapeutic target