N-acetyl-cysteinylated streptophenazines from Streptomyces

ABSTRACTHere, we describe two N-acetyl-cysteinylated streptophenazines (1 and 2) produced by soil-derived Streptomyces sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from Streptomyces sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine Streptomyces sp. CNB-091. Compounds 1 and 2 were the main streptophenazine products from Streptomyces sp. ID63040 at all cultivation times, but were not detected in Streptomyces sp. CNB-091. The lack of obvious candidates for cysteinylation in the Streptomyces sp. ID63040 biosynthetic gene cluster suggests that the N-acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example on how to leverage metabolomics for the discovery of new natural products and point out to the often-neglected contribution of house-keeping cellular functions to natural product diversification.Graphical abstract

The association of energy and macronutrient intake with all-cause mortality, cardiovascular disease, and dementia: findings from 120,963 women and men in the UK Biobank

This study aimed to investigate the association between individual, and combinations of, macronutrients with premature death, cardiovascular disease (CVD) and dementia. Sex differences were investigated. Data were utilised from a prospective cohort of 120,963 individuals (57% female) within the UK Biobank, who completed ≥two 24-hour diet recalls. The associations of macronutrients, as percentages of total energy intake, with outcomes were investigated. Combinations of macronutrients were defined using k-means cluster analysis, with clusters explored in association with outcomes. There was a higher risk of death with high carbohydrate intake (Hazard ratios (HRs), 95% confidence intervals (95% CI) upper v lowest third 1.13 (1.03, 1.23)), yet a lower risk with higher intakes of protein (upper v lowest third 0.82 (0.76, 0.89)). There was a lower risk of CVD with moderate intakes (middle v lowest third) of energy and protein (sub distribution HRs (SHR), 0.87 (0.79, 0.97) and (0.87 (0.79, 0.96)) respectively). There was a lower risk of dementia with moderate energy intake (SHR 0.71 (0.52, 0.96)). Sex differences were identified. The dietary cluster characterised by low carbohydrate, low fat and high protein was associated with a lower risk of death (HR 0.84 (0.76, 0.93)) compared to the reference cluster, and a lower risk of CVD for men (SHR 0.83 (0.71, 0.97)). Given that associations were evident, both as single macronutrients and for combinations with other macronutrients for death, and for CVD in men, we suggest that the biggest benefit from diet-related policy and interventions will be when combinations of macronutrients are targeted.

Clustering Longitudinal Blood Pressure Trajectories to Examine Heterogeneity in Outcomes Among Preeclampsia Cases and Controls

Preeclampsia is a heterogeneous disease characterized by new onset of hypertension along with signs of organ damage, affects 2% to 8% of pregnancies, and can result in serious complications to the mother and her child. There is little empirical evidence on the clinical importance of differences in blood pressure trajectories over the course of pregnancy, particularly in pregnancies affected by preeclampsia. We undertook an investigation of longitudinal changes in gestational blood pressure in a nested case-control study of preeclampsia in MoBa (Norwegian Mother, Father and Child Cohort Study). We included 1906 validated preeclampsia cases and 1413 validated controls. We derived blood pressure trajectory clusters using longitudinal k-means clustering and examined demographic and early-pregnancy predictors and birth outcomes, in relation to clusters. Maternal age, prepregnancy body mass index, and parity were substantially different across blood pressure clusters of cases. Pregnancy outcomes, including preterm birth, small for gestational age, and birthweight Z score, were meaningfully worse for individuals with a more rapid increase in blood pressure, as well as for individuals with a high starting blood pressure. For example, risk of preterm birth was 11-fold to 35-fold higher for steep and high trajectory clusters, and risk of small for gestational age was 2-fold higher compared with the reference cluster. Future studies may leverage these trajectories to differentiate preeclampsia cases in relation to circulating biomarkers, which may help in the development of preeclampsia prediction tools.

Clustering of Excess Body Weight-Related Behaviors in a Sample of Brazilian Adolescents

The aim of the study was to identify the existence of clusters in multiple lifestyle behaviors, including consumption of fruits/vegetables, sugary products/soft drinks, physical activity and sedentary behavior. The association between identified clusters and excess body weight in a sample of adolescents from Dourados, Brazil, was examined. This is a cross-sectional school-based study involving 578 participants aged 12–18 of both sexes. Anthropometric measurements were performed and a questionnaire was applied with structured questions to collect data. Excess body weight was identified through body mass index. Cluster analysis was performed to identify sex-specific clusters of multiple lifestyle behaviors. Analysis of covariance and logistic regression were used to analyze associations between clusters and excess body weight. Six clusters were identified in both sexes. Girls and boys in the cluster characterized by greater time spent in sedentary behavior were 53% (OR = 1.53 [1.06–2.26]) and 63% (OR = 1.63 [1.12–2.35]) more likely to present excess body weight compared to their peers in the reference cluster. In the case of adolescents in the cluster characterized by high consumption of sugary products/soft drinks, girls were 47% more likely to be overweight (OR = 1.47 [1.05–2.13]) and boys were 51% more likely (OR = 1.51 [1.05–2.16]). High consumption of fruits/vegetables, low consumption of sugary products/soft drinks and less sedentary behavior was considered the most effective combination for the maintenance of a healthy weight.

Unphysical properties of the rotation tensor estimated by least squares optimization with specific application to biomechanics

Analysis of the transformation of one data set into another is a ubiquitous problem in many fields of science. Many works approximate the transformation of a reference cluster of n vectors Xi (i=1,2,..,n) into another cluster of n vectors xi by a translation and a rotation using a least squares optimization to obtain the rotation tensor Q. The objective of this work is to prove that this rotation tensor Q exhibits unphysical dependence on the shape and orientation of the reference cluster. In contrast, when the transformation is approximated by a translation and a general non-singular tensor F, which includes deformations, then the associated rotation tensor R does not exhibit these unphysical properties. An example in biomechanics quantifies the errors of these unphysical properties.

MHD simulations of cool core clusters

Using Smoothed Particle Magneto Hydrodynamics (Dolag & Stasyszyn), we study the effects of magnetic fields in galaxy clusters with the aim to infer their dynamical role within the cool core region. Therefore we we investigate the role of regularization as well as divergence cleaning schemes (Stasyszyn & Dolag 2009). We run cosmological simulations of a reference cluster in order to evaluate our various implementation in a realistic scenario. The preliminary results indicate that the final magnetic field profile in the simulations depends only on the amount of artificial dissipation, but not in the amount of numerical div(B) present in the different implementation. We also present first results from simulations which are including radiative cooling and star formation. Even at the this low resolution we find a strong additional amplification of the magnetic field within the cool core region indicating that magnetic pressure could become comparable to the thermal pressure in theses regimes.