Quanitifzierung der Herzratenvariabilität und der motorischen Aktivität über den Migräne-Zyklus

Migräne stellt eine der häufigsten Formen der primären Kopfschmerzen dar. Neben dem charakteristischen Schmerz an sich beschreiben Migränepatienten regelmäßig Begleitsymptome, die eine Beteiligung des autonomen Nervensystems vermuten lassen. Daher zielte die vorliegende Studie auf die Quantifizierung der autonomen Aktivität ab, um migräneassoziierte, möglicherweise zyklische Abläufe des sympathischen und/oder parasympathischen Nervensystems zu identifizieren. Hierzu wurde eine monozentrische, prospektive Studie durchgeführt, an der 15 Patientinnen und fünf Patienten mit episodischer Migräne im Alter von 19 bis 35 Jahren teilnahmen. Diese trugen zur kontinuierlichen Vitalparameteraufzeichnung das E4 Wristband der Firma Empatica (Italien) über eine mittlere Dauer von 28,2 Tagen. Für die akquirierte Herzschlagrate (normaltonormal(NN)Intervalle) wurde die Standardabweichung (SDNN) als Indikator der Herzratenvariabilität (HRV) und somit des kardialen autonomen Nervensystems, aus den Beschleunigungsdaten die Signal Magnitude Area (SMA) als Indikator der motorischen Aktivität berechnet. Um migräneassoziierte, zyklische Abläufe von SDNN und SMA zu eruieren, wurden diese für präiktale, iktale, postiktale und migränefreie Perioden betrachtet (über das Patientenkollektiv gemittelt und intraindividuell). Zudem wurden die Änderungen der autonomen und der motorischen Aktivität (ΔSDNN und ΔSMA) für Migräne (vor, während und nach) und migränefreie Tage gegenübergestellt. SDNN zeigte gemittelt über das Patientenkollektiv keine statistisch signifikanten Unterschiede; innerhalb der Individuen variierte die Richtung (parasympathische oder sympathische Aktivierung), in welche sich SDNN für konsekutive Migräneattacken verschob. ΔSDNN war in den vor, während und nach einer Migräneattacke berechneten Blöcken signifikant höher als an migränefreien Tagen; am deutlichsten trat ΔSDNN dabei in der Prämigränephase hervor. SMA und ΔSMA verhielten sich analog zu SDNN und ΔSDNN. Mittels des Parameters SDNN konnte keine eine Migräneattacke begleitende zyklische Regulation der autonomen Aktivität identifiziert werden, da eine derartige aufgrund der inkonsistenten, intraindividuellen Verschiebungen von SDNN zu negieren ist. Wurde dagegen die Änderung des Parameters SDNN (ΔSDNN) betrachtet, ergaben sich statistisch signifikante Anhaltspunkte auf Migräneassoziierte Instabilitäten im autonomen Nervensystem. Die Höhe von ΔSDNN und damit der Instabilitäten ist von migränefreien Zeitpunkten wie auch für die einzelnen Blöcke einer Migräneattacke verschieden. Dabei eröffnet der sprunghafte Anstieg von ΔSDNN in der Prämigränephase die Möglichkeit, einen Biomarker für die Erkennung einer sich anbahnenden Migräneattacke zu etablieren. Diese präiktalen Veränderungen sind vereinbar mit einer primär hypothalamischen Störung zu diesem Zeitpunkt, wie es neuere Daten aus der Bildgebung nahelegen. Die Bewegungsdaten (SMADaten) und deren Änderung (ΔSMA) legen ferner nahe, dass der Umfang der motorischen Aktivität in den Phasen einer Migräneattacke unterschiedlich starken Schwankungen unterliegt und nicht generell vermindert ist.Objective Migraine is known as a common primary headache disorder. In addition to the characteristic pain itself, migraine subjects often describe accompanying symptoms which suggest an involvement of the autonomic nervous system in episodic migraine. Advancing the understanding of the pathophysiology behind, the study quantified the autonomic nervous system in order to investigate migraineassociated, possibly cyclic processes. Methods A monocentric, prospective study was conducted. 20 patients with episodic migraine aged between 19 and 35 years wore the E4 wristband for an average of 28.2 days to measure blood volume pulse (BVP) and motionbased activity continuously. In consequence, computing the standard deviation of normaltonormalintervals (SDNN), heart rate variability (HRV) could be derived as a sign of the autonomic nervous system. Signal Magnitude Area (SMA) computed from the accelerometric data additionally captured the degree of movement. SDNN and SMA were calculated before, during and after a migraine as well as in migrainefree time slots (both intraindividually and averaged over all patients). Besides, the hourly variations of SDNN and SMA (ΔSDNN and ΔSMA) were compared for migraine (before, during, after) and migrainefree days. Results Averaged over all patients, no significant differences were found for SDNN. Concerning SDNN intraindividually, the shift of SDNN (towards parasympathetic or sympathetic hyperactivation) varied for consecutive migraine attacks. In contrast, ΔSDNN was significantly higher before, during and after migraine than on migrainefree days, with ΔSDNN being most evident in the pre and postmigraine phase. SMA and ΔSMA displayed similar results as SDNN and ΔSDNN. Conclusion Using SDNN, no cyclic regulation related to a migraine attack could be identified due to the inconsistent, intraindividual changes in SDNN. However, with regard to ΔSDNN, there were statistically significant differences of migraineassociated instabilities in the cardial autonomic nervous system. During the phases of a migraine attack, the level of ΔSDNN and thus of the autonomic instabilities is higher than on migrainefree days, with the significant change of ΔSDNN in the premigraine phase offering the opportunity of a biomarker for advanced attack recognition. Furthermore, the SMA and ΔSMA data suggest that the extent of physical activity changes depending on the phases of a migraine attack

High performance data analysis via coordinated caches

With the second run period of the LHC, high energy physics collaborations will have to face increasing computing infrastructural needs. Opportunistic resources are expected to absorb many computationally expensive tasks, such as Monte Carlo event simulation. This leaves dedicated HEP infrastructure with an increased load of analysis tasks that in turn will need to process an increased volume of data. In addition to storage capacities, a key factor for future computing infrastructure is therefore input bandwidth available per core. Modern data analysis infrastructure relies on one of two paradigms: data is kept on dedicated storage and accessed via network or distributed over all compute nodes and accessed locally. Dedicated storage allows data volume to grow independently of processing capacities, whereas local access allows processing capacities to scale linearly. However, with the growing data volume and processing requirements, HEP will require both of these features. For enabling adequate user analyses in the future, the KIT CMS group is merging both paradigms: popular data is spread over a local disk layer on compute nodes, while any data is available from an arbitrarily sized background storage. This concept is implemented as a pool of distributed caches, which are loosely coordinated by a central service. A Tier 3 prototype cluster is currently being set up for performant user analyses of both local and remote data

Functional diversification of Argonautes in nematodes:an expanding universe

In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism

Biparental inheritance of plastidial and mitochondrial DNA and hybrid variegation in Pelargonium

Plastidial (pt) and mitochondrial (mt) genes usually show maternal inheritance. Non-Mendelian, biparental inheritance of plastids was first described by Baur (Z Indukt Abstamm Vererbungslehre 1:330–351, 1909) for crosses between Pelargonium cultivars. We have analyzed the inheritance of pt and mtDNA by examining the progeny from reciprocal crosses of Pelargoniumzonale and P. inquinans using nucleotide sequence polymorphisms of selected pt and mt genes. Sequence analysis of the progeny revealed biparental inheritance of both pt and mtDNA. Hybrid plants exhibited variegation: our data demonstrate that the inquinans chloroplasts, but not the zonale chloroplasts bleach out, presumably due to incompatibility of the former with the hybrid nuclear genome. Different distribution of maternal and paternal sequences could be observed in different sectors of the same leaf, in different leaves of the same plant, and in different plants indicating random segregation and sorting-out of maternal and paternal plastids and mitochondria in the hybrids. The substantial transmission of both maternal and paternal mitochondria to the progeny turns Pelargonium into a particular interesting subject for studies on the inheritance, segregation and recombination of mt genes

Developmentally early and late onset of Rps10 silencing in Arabidopsis thaliana: genetic and environmental regulation

Transgene dosage, silencing competence of the transgene loci, and photoperiod conditions were found to regulate the onset and efficiency of Rps10 silencing in two independent transgenic lines of Arabidopsis thaliana. The Rps10 gene encodes the S10 protein which is part of the small subunit of mitochondrial ribosomes. Homozygous plants presented developmentally early onset of silencing, a very efficient decrease in the level of Rps10 transcripts, as well as a severe and uniform phenotype called P1. P1 plants either died during the vegetative growth phase or were rescued by reversion resulting from inactivation of silencing. A wide variety of morphological and developmental abnormalities observed within the hemizygous transformants allowed their classification into three categories P2, P3, and P4. The most severe and early was the P2 phenotype found in only one transgenic line and most probably resulting from high competence of the transgene loci. Developmentally late onset of silencing occurred only in the short day photoperiod and was characteristic for the P3 and P4 plants. This phenomenon was attributed to conditions favourable to silencing achieved in the short day photoperiod, e.g. a greatly prolonged vegetative phase accompanied by a gradual increase of the level of Rps10 transcripts. To the best of our knowledge, this is the first report indicating that the onset of silencing depends on the photoperiod conditions in A. thaliana

Planting the Seeds of a New Paradigm

RNA-mediated gene silencing has emerged in recent years as an important mechanism for regulating gene expression. Some of the key discoveries have been made in plant

Chemical PARP Inhibition Enhances Growth of Arabidopsis and Reduces Anthocyanin Accumulation and the Activation of Stress Protective Mechanisms

Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through the addition of ADP-ribose polymers, yet its role in modulating plant development and stress responses is only poorly understood. The experiments presented here address some of the gaps in our understanding of its role in stress tolerance and thereby provide new insights into tolerance mechanisms and growth. Using a combination of chemical and genetic approaches, this study characterized phenotypes associated with PARP inhibition at the physiological level. Molecular analyses including gene expression analysis, measurement of primary metabolites and redox metabolites were used to understand the underlying processes. The analysis revealed that PARP inhibition represses anthocyanin and ascorbate accumulation under stress conditions. The reduction in defense is correlated with enhanced biomass production. Even in unstressed conditions protective genes and molecules are repressed by PARP inhibition. The reduced anthocyanin production was shown to be based on the repression of transcription of key regulatory and biosynthesis genes. PARP is a key factor for understanding growth and stress responses of plants. PARP inhibition allows plants to reduce protection such as anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high energy levels likely enabling the observed enhancement of biomass production under stress, opening interesting perspectives for increasing crop productivity