Non-linear, bivariate stochastic modelling of power-grid frequency applied to islands

Mitigating climate change requires a transition away from fossil fuels towards renewable energy. As a result, power generation becomes more volatile and options for microgrids and islanded power-grid operation are being broadly discussed. Therefore, studying the power grids of physical islands, as a model for islanded microgrids, is of particular interest when it comes to enhancing our understanding of power-grid stability. In the present paper, we investigate the statistical properties of the power-grid frequency of three island systems: Iceland, Ireland, and the Balearic Islands. We utilise a Fokker-Planck approach to construct stochastic differential equations that describe market activities, control, and noise acting on power-grid dynamics. Using the obtained parameters we create synthetic time series of the frequency dynamics. Our main contribution is to propose two extensions of stochastic power-grid frequency models and showcase the applicability of these new models to non-Gaussian statistics, as encountered in islands

Enhanced genome assembly and a new official gene set for Tribolium castaneum

Background. The red flour beetle Tribolium castaneum has emerged as an important model organism for the study of gene function in development and physiology, for ecological and evolutionary genomics, for pest control and a plethora of other topics. RNA interference (RNAi), transgenesis and genome editing are well established and the resources for genome-wide RNAi screening have become available in this model. All these techniques depend on a high quality genome assembly and precise gene models. However, the first version of the genome assembly was generated by Sanger sequencing, and with a small set of RNA sequence data limiting annotation quality. Results. Here, we present an improved genome assembly (Tcas5.2) and an enhanced genome annotation resulting in a new official gene set (OGS3) for Tribolium castaneum, which significantly increase the quality of the genomic resources. By adding large-distance jumping library DNA sequencing to join scaffolds and fill small gaps, the gaps in the genome assembly were reduced and the N50 increased to 4753kbp. The precision of the gene models was enhanced by the use of a large body of RNA-Seq reads of different life history stages and tissue types, leading to the discovery of 1452 novel gene sequences. We also added new features such as alternative splicing, well defined UTRs and microRNA target predictions. For quality control, 399 gene models were evaluated by manual inspection. The current gene set was submitted to Genbank and accepted as a RefSeq genome by NCBI. Conclusions. The new genome assembly (Tcas5.2) and the official gene set (OGS3) provide enhanced genomic resources for genetic work in Tribolium castaneum. The much improved information on transcription start sites supports transgenic and gene editing approaches. Further, novel types of information such as splice variants and microRNA target genes open additional possibilities for analysis

Cardiac Rac1 overexpression in mice creates a substrate for atrial arrhythmias characterized by structural remodelling

The small GTPase Rac1 seems to play a role in the pathogenesis of atrial fibrillation (AF). The aim of the present study was to characterize the effects of Rac1 overexpression on atrial electrophysiology. In mice with cardiac overexpression of constitutively active Rac1 (RacET), statin-treated RacET, and wild-type controls (age 6 months), conduction in the right and left atrium (RA and LA) was mapped epicardially. The atrial effective refractory period (AERP) was determined and inducibility of atrial arrhythmias was tested. Action potentials were recorded in isolated cells. Left ventricular function was measured by pressure-volume analysis. Five of 11 RacET hearts showed spontaneous or inducible atrial tachyarrhythmias vs. 0 of 9 controls (P <0.05). In RacET, the P-wave duration was significantly longer (26.8 +/- 2.1 vs. 16.7 +/- 1.1 ms, P = 0.001) as was total atrial activation time (RA: 13.6 +/- 4.4 vs. 3.2 +/- 0.5 ms; LA: 7.1 +/- 1.2 vs. 2.2 +/- 0.3 ms, P <0.01). Prolonged local conduction times occurred more often in RacET (RA: 24.4 +/- 3.8 vs. 2.7 +/- 2.1%; LA: 19.1 +/- 6.3 vs. 1.2 +/- 0.7%, P <0.01). The AERP and action potential duration did not differ significantly between both groups. RacET demonstrated significant atrial fibrosis but only moderate systolic heart failure. RacET and statin-treated RacET were not significantly different regarding atrial electrophysiology. The substrate for atrial arrhythmias in mice with Rac1 overexpression is characterized by conduction disturbances and atrial fibrosis. Electrical remodelling (i.e. a shortening of AERP) does not play a role. Statin treatment cannot prevent the structural and electrophysiological effects of pronounced Rac1 overexpression in this model

A background Ca 2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling

Aims: Pathological cardiac hypertrophy is a major predictor for the development of cardiac diseases. It is associated with chronic neurohumoral stimulation and with altered cardiac Ca2+ signalling in cardiomyocytes. TRPC proteins form agonist-induced cation channels, but their functional role for Ca2+ homeostasis in cardiomyocytes during fast cytosolic Ca2+ cycling and neurohumoral stimulation leading to hypertrophy is unknown. Methods and results: In a systematic analysis of multiple knockout mice using fluorescence imaging of electrically paced adult ventricular cardiomyocytes and Mn2+-quench microfluorimetry, we identified a background Ca2+ entry (BGCE) pathway that critically depends on TRPC1/C4 proteins but not others such as TRPC3/C6. Reduction of BGCE in TRPC1/C4-deficient cardiomyocytes lowers diastolic and systolic Ca2+ concentrations both, under basal conditions and under neurohumoral stimulation without affecting cardiac contractility measured in isolated hearts and in vivo. Neurohumoral-induced cardiac hypertrophy as well as the expression of foetal genes (ANP, BNP) and genes regulated by Ca2+-dependent signalling (RCAN1-4, myomaxin) was reduced in TRPC1/C4 knockout (DKO), but not in TRPC1- or TRPC4-single knockout mice. Pressure overload-induced hypertrophy and interstitial fibrosis were both ameliorated in TRPC1/C4-DKO mice, whereas they did not show alterations in other cardiovascular parameters contributing to systemic neurohumoral-induced hypertrophy such as renin secretion and blood pressure. Conclusions: The constitutively active TRPC1/C4-dependent BGCE fine-tunes Ca2+ cycling in beating adult cardiomyocytes. TRPC1/C4-gene inactivation protects against development of maladaptive cardiac remodelling without altering cardiac or extracardiac functions contributing to this pathogenesis.Fil: Camacho Londoño, Juan E.. Pharmakologisches Institut; Alemania. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania. German Centre for Cardiovascular Research; AlemaniaFil: Tian, Qinghai. Institut fur Molekulare Zellbiologie; AlemaniaFil: Hammer, Karin. Institut fur Molekulare Zellbiologie; AlemaniaFil: Schröder, Laura. Institut fur Molekulare Zellbiologie; AlemaniaFil: Camacho Londoño, Julia. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Reil, Jan C.. Universitat des Saarlandes; AlemaniaFil: He, Tao. German Centre for Cardiovascular Research; Alemania. Research Unit Cardiac Epigenetics; Alemania. Tongji Hospital; ChinaFil: Oberhofer, Martin. Institut fur Molekulare Zellbiologie; AlemaniaFil: Mannebach, Stefanie. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Mathar, Ilka. Pharmakologisches Institut; Alemania. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Philipp, Stephan E.. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Tabellion, Wiebke. Institut fur Molekulare Zellbiologie; AlemaniaFil: Schweda, Frank. Universitat Regensburg; AlemaniaFil: Dietrich, Alexander. Walther-Straub-Institut fur Pharmakologie und Toxikologie; AlemaniaFil: Kaestner, Lars. Institut fur Molekulare Zellbiologie; AlemaniaFil: Laufs, Ulrich. Universitat des Saarlandes; AlemaniaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Transmembrane Signaling Group; AlemaniaFil: Flockerzi, Veit. Experimentelle und Klinische Pharmakologie und Toxikologie; AlemaniaFil: Freichel, Marc. Pharmakologisches Institut; Alemania. Experimentelle und Klinische Pharmakologie und Toxikologie; Alemania. German Centre for Cardiovascular Research; AlemaniaFil: Lipp, Peter. Institut fur Molekulare Zellbiologie; Alemani