Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition.

The circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1(lox/lox)/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD(+)-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition

Modelling non-linear redshift-space distortions in the galaxy clustering pattern: systematic errors on the growth rate parameter

We investigate the ability of state-of-the-art redshift-space distortions models for the galaxy anisotropic two-point correlation function \xi(r_p, \pi), to recover precise and unbiased estimates of the linear growth rate of structure f, when applied to catalogues of galaxies characterised by a realistic bias relation. To this aim, we make use of a set of simulated catalogues at z = 0.1 and z = 1 with different luminosity thresholds, obtained by populating dark-matter haloes from a large N-body simulation using halo occupation prescriptions. We examine the most recent developments in redshift-space distortions modelling, which account for non-linearities on both small and intermediate scales produced respectively by randomised motions in virialised structures and non-linear coupling between the density and velocity fields. We consider the possibility of including the linear component of galaxy bias as a free parameter and directly estimate the growth rate of structure f. Results are compared to those obtained using the standard dispersion model, over different ranges of scales.We find that the model of Taruya et al. (2010), the most sophisticated one considered in this analysis, provides in general the most unbiased estimates of the growth rate of structure, with systematic errors within 4% over a wide range of galaxy populations spanning luminosities between L > L* and L > 3L*. The scale-dependence of galaxy bias plays a role on recovering unbiased estimates of f when fitting quasi non-linear scales. Its effect is particularly severe for most luminous galaxies, for which systematic effects in the modelling might be more difficult to mitigate and have to be further investigated. [...]Comment: 17 pages, 16 figures, Accepted for publication in MNRA

The turbulent gas structure in the centers of NGC253 and the Milky Way

We compare molecular gas properties in the starbursting center of NGC253 and the Milky Way Galactic Center (GC) on scales of ~1-100 pc using dendograms and resolution-, area- and noise-matched datasets in CO (1-0) and CO (3-2). We find that the size-line width relations in NGC253 and the GC have similar slope, but NGC253 has larger line widths by factors of ~2-3. The $\sigma^2/R$ dependency on column density shows that, in the GC, on scales of 10-100 pc the kinematics of gas over $N>3\times10^{21}$ cm$^{-2}$ are compatible with gravitationally bound structures. In NGC253 this is only the case for column densities $N>3\times10^{22}$ cm$^{-2}$. The increased line widths in NGC253 originate in the lower column density gas. This high-velocity dispersion, not gravitationally self-bound gas is likely in transient structures created by the combination of high average densities and feedback in the starburst. The high densities turns the gas molecular throughout the volume of the starburst, and the injection of energy and momentum by feedback significantly increases the velocity dispersion at a given spatial scale over what is observed in the GC.Comment: 13 pages, 3 figures, 4 tables; accepted for publication in the Astrophysical Journa

The Source Regions of Whistlers.

We present a new method for identifying the source regions of lightning‐generated whistlers observed at a fixed location. In addition to the spatial distribution of causative lightning discharges, we calculate the ratio of lightning discharges transmitted into ground detectable whistlers as a function of location. Our method relies on the time of the whistlers and the time and source location of spherics from a global lightning database. We apply this method to whistlers recorded at 15 ground‐based stations in the Automatic Whistler Detector and Analyzer Network operating between 2007 and 2018 and to located lightning strokes from the World Wide Lightning Location Network database. We present the obtained maps of causative lightning and transmission rates. Our results show that the source region of whistlers corresponding to each ground station is around the magnetic conjugate point of the respective station. The size of the source region is typically less than 2,000 km in radius with a small fraction of sources extending to up to 3,500 km. The transmission ratio is maximal at the conjugate point and decreases with increasing distance from it. This conforms to the theory that whistlers detected on the ground propagated in a ducted mode through the plasmasphere, and thus, the lightning strokes of their causative spherics must cluster around the footprint of the ducts in the other hemisphere. Our method applied resolves the whistler excitation region mystery that resulted from correlation‐based analysis methods, concerning the source region of whistlers detected in Dunedin, New Zealand

The contribution of coping related variables and cardiac vagal activity on the performance of a dart throwing task under pressure.

The aims of this study were 1) to assess the predictive role of coping related variables (CRV) on cardiac vagal activity (derived from heart rate variability), and 2) to investigate the influence of CRV (including cardiac vagal activity) on a dart throwing task under low pressure (LP) and high pressure (HP) conditions. Participants (n=51) completed trait CRV questionnaires: Decision Specific Reinvestment Scale, Movement Specific Reinvestment Scale and Trait Emotional Intelligence Questionnaire. They competed in a dart throwing task under LP and HP conditions. Cardiac vagal activity measurements were taken at resting, task and during recovery for 5min. Self-reported ratings of stress were recorded at three time points via a visual analogue scale. Upon completion of the task, self-report measures of motivation, stress appraisal, attention, perceived pressure and dart throwing experience were completed. Results indicated that resting cardiac vagal activity had no predictors. Task cardiac vagal activity was predicted by resting cardiac vagal activity in both pressure conditions with the addition of a trait CRV in HP. Post task cardiac vagal activity was predicted by resting cardiac vagal activity in both conditions with the addition of a trait CRV in HP. Cardiac vagal reactivity (difference from resting to task) was predicted by a trait CRV in HP conditions. Cardiac vagal recovery (difference from task to post task) was predicted by a state CRV only in LP. Dart throwing task performance was predicted by a combination of both CRV and cardiac vagal activity. The current research suggests that coping related variables and cardiac vagal activity influence dart throwing task performance differently dependent on pressure condition

Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire

Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae

Predicting where a radiation will occur: Acoustic and molecular surveys reveal overlooked diversity in Indian Ocean Island crickets (Mogoplistinae: Ornebius)

Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra-island speciation scenario in which ecological and mating traits diverge hand-in-hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands. (Résumé d'auteur