Geschlechterspezifische Auswirkungen sozialer Exklusion auf die funktionelle Konnektivität der Amygdala im Ruhezustand

Diese Arbeit widmete sich der Frage nach potenziellen Veränderungen der funktionellen Konnektivität der Amygdala im Ruhezustand (rsFC) vor vs. nach sozialer Exklusion und damit einhergehenden Geschlechterunterschieden. Um die (geschlechterspezifischen) Auswirkungen sozialer Exklusion auf die Amygdala rsFC zu untersuchen, wurden Ruhezustandsmessungen (rs-fMRT) von insgesamt 76 Probanden (40 Frauen und 36 Männer) im Alter von 19 bis 34 Jahren vor bzw. nach Durchführung des Cyberball-Paradigmas, einem Ballspiel am Computer, untersucht, unter welchem der Proband im Laufe ausgeschlossen wird. Vor und nach Durchlaufen des Experimentes wurden neben der Aufnahme des Gehirns im Ruhezustand auch die Cortisol-Konzentration im Speichel und einige Stimmungsparameter der Probanden mittels Fragebögen erhoben. Die Untersuchung der rs-fMRT-Daten erfolgte durch eine regionenbasierte („seed-based“) Analyse der Amygdala auf Ganzhirnebene unter Verwendung einer mehrfaktoriellen, messwiederholten Varianzanalyse. Während die soziale Exklusion hinsichtlich Stimmung zu einer Veränderung führte, zeigten sich für Cortisol und die Amygdala rsFC kein signifikanter Effekt des Experiments und auch keine Interaktion mit dem Geschlecht. Allerdings fanden sich allgemeine Geschlechterunterschiede sowohl in Hinblick auf Cortisol, eine höhere Konzentration bei Männern als Frauen, als auch in der Amygdala rsFC wieder: Frauen zeigten in dieser Arbeit eine stärkere Amygdala-Verbindung als Männer zu temporalen Hirnregionen (MTG, STG) sowie dem Hippocampus, Regionen, welche vor allem für die Erkennung und Verarbeitung von Gesichtsausdrücken, die Angstkonditionierung und Konsolidierung vorrangig emotionaler Gedächtnisinformationen von Bedeutung sind. Männer zeigten im Vergleich zu Frauen eine stärkere Amygdala rsFC zu parietalen Hirnregionen (IPL, IPS). Der IPL ist neben der Körperwahrnehmung, der Wahrnehmung wütender Gesichter sowie ängstlicher Körperhaltungen auch für räumlich-mathematische Fähigkeiten elementar. Während die Ergebnisse hinsichtlich subjektiver Einschätzung und auch Cortisol erfolgreich bisherige Studien replizieren, wurde erstmals eine Veränderung der Amygdala rsFC durch soziale Exklusion untersucht, allerdings ohne signifikanten Effekt. Dies könnte durch mehrere Faktoren oder einer Kombination dieser bedingt sein. Es ist denkbar, dass Veränderungen der Amygdala rsFC und eventuell auch damit einhergehende Geschlechterunterschiede unter realen Bedingungen beziehungsweise bei einer insgesamt intensiveren und naturalistischeren Umsetzung sozialer Exklusion sowie einer rs-fMRT-Messung unmittelbar im Anschluss an die Ausgrenzungserfahrung festgestellt werden könnten. Unterstützt wird diese Überlegung von der Theorie der raschen Umverteilung neuronaler Ressourcen unmittelbar nach Stress. Auch ein Übertragungseffekt des vorher durchgeführten Tasks sollte mitberücksichtigt werden. Ebenso könnten weitere Studien Fluktuationen im weiblichen Menstruationszyklus, etwa durch hormonzyklusadaptierte Messungen, zwischen den Frauen erfassen, da diese potenziell auch die Amygdala rsFC beeinflussen können. Soziale Exklusion stellt einen Risikofaktor für Depressionen und soziale Angststörungen dar. Da diese Erkrankungen mit spezifischen Veränderungen der Amygdala rsFC einhergehen, sich deren Prävalenz deutlich zwischen den Geschlechtern unterscheidet und Depressionen weiterhin auf dem Vormarsch sind, ist es von gesellschaftlicher Relevanz, diesem Thema weiterhin nachzugehen.Social exclusion can evoke negative moods and can have a sustained negative impact on our health. The resting state functional connectivity (rsFC) of the amygdala, a central structure for processing emotions, is strongly influenced by psychosocial stress. Women and men differ in their way of processing emotions and managing situations like stress and social exclusion. It is already known that there are sex-specific differences in the amygdala rsFC. To explore the (sex-specific) effects of social exclusion on amygdala rsFC, resting-state-data was analyzed from 76 subjects (40 women and 36 men) using the Cyberball paradigm, a computerized ball tossing game in which the subject is excluded from the game. A seed-based analysis of amygdala connectivity on a whole-brain level was implemented. Before and after saliva samples for cortisol and affect ratings were collected from all subjects. As hypothesized, social exclusion led to a significant effect on positive affect but showed no impact on cortisol or amygdala rsFC. Data analysis however, revealed general sex differences in amygdala rsFC: While women demonstrated significantly stronger rsFC between the amygdala and temporal brain regions (MTG, STG) and limbic system (hippocampus), men showed stronger coupling between the amygdala and parietal brain regions (IPL, IPS). This is the first study to investigate the effect of social exclusion on amygdala rsFC, however, no significant effect was observed. This might be explained by several factors or a combination thereof. It is possible that changes in the amygdala rsFC and possibly also accompanying sex differences could be experimentally accessed with a more intense and naturalistic implementation of social exclusion combined with rs-fMRI measurements immediately after the exclusion experience. This is supported by the theory of a rapid reallocation of neuronal resources. A carry-over effect from the previous task should also be taken into consideration. Future studies could further implement measurements adapted to the female menstrual cycle as it is known that sex hormones can influence amygdala rsFC. Social exclusion is a potential risk factor for the development of depression and social anxiety disorders. As these disorders seem to be associated with specific changes in the amygdala rsFC, their prevalence clearly differs between the sexes, and depression disorders are still on the rise, it is of high social relevance to explore this topic further

Svenskt terminologiarbete - en resurs for svenska myndigheter och EUoversåttare

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TNCs arbete med Eurodicautom, Europeiska kommissionens termdatabas

The paper gives a brief orientation of the goals and activities of The Swedish Centre for Technical Terminology (TNC) and the reasons why subject field specialists feel the need of determining and describing subject field related concepts and terms. The principles and methods of terminology work are described, and the importance of having subject field specialists participating in the work is particularly emphasized.Since Sweden's membership in the EU in 1995, TNC's activities have been dominated to a !arge extent by the comprehensive task from the European Commission of updating the terminologic database Eurodicautom with Swedish terminology in various fields. In four different projects, each running for twelve months, TNC has been supplementing approximately 140 000 term records with Swedish terms and references, and to some extent also with definitions and comments. The working principles in some respects diverge from the traditional methods of terminology work. In other respects, e.g. the close cooperation with subject field specialists, it has been possible to retain the principles. However, TNC has had to adapt some of the working methods to the specific conditions of these projects. The last part of the paper is a report from one of the specialists, a biologist. She decribes her motives for applying for a job within this project, and her experiences after having been involved in the work for more than a year

Large-Signal RF Modeling with the EKV3 MOSFET Model, Journal of Telecommunications and Information Technology, 2010, nr 1

This paper presents a validation of the EKV3 MOSFET model under load-pull conditions with high input power at 5.8 GHz, as well as S-parameter measurements with low input power up to 20 GHz. The EKV3 model is able to represent coherently the large- and small-signal RF characteristics in advanced 90 nm CMOS technology. Multifinger devices with nominal drawn gate length of 70 nm are used

Detection and benchmarking of somatic mutations in cancer genomes using RNA-seq data

To detect functional somatic mutations in tumor samples, whole-exome sequencing (WES) is often used for its reliability and relative low cost. RNA-seq, while generally used to measure gene expression, can potentially also be used for identification of somatic mutations. However there has been little systematic evaluation of the utility of RNA-seq for identifying somatic mutations. Here, we develop and evaluate a pipeline for processing RNA-seq data from glioblastoma multiforme (GBM) tumors in order to identify somatic mutations. The pipeline entails the use of the STAR aligner 2-pass procedure jointly with MuTect2 from genome analysis toolkit (GATK) to detect somatic variants. Variants identified from RNA-seq data were evaluated by comparison against the COSMIC and dbSNP databases, and also compared to somatic variants identified by exome sequencing. We also estimated the putative functional impact of coding variants in the most frequently mutated genes in GBM. Interestingly, variants identified by RNA-seq alone showed better representation of GBM-related mutations cataloged by COSMIC. RNA-seq-only data substantially outperformed the ability of WES to reveal potentially new somatic mutations in known GBM-related pathways, and allowed us to build a high-quality set of somatic mutations common to exome and RNA-seq calls. Using RNA-seq data in parallel with WES data to detect somatic mutations in cancer genomes can thus broaden the scope of discoveries and lend additional support to somatic variants identified by exome sequencing alone

RarERN Path: a methodology towards the optimisation of patients’ care pathways in rare and complex diseases developed within the European Reference Networks

Background: In 2017, the European Commission has launched the European Reference Networks (ERNs), virtual networks involving healthcare providers across Europe. The aim of the ERNs is to tackle complex and rare diseases and conditions that require highly specialized treatment and a concentration of knowledge and resources. The ERN on rare and complex connective tissue and musculoskeletal diseases (ERN ReCONNET) is one of the 24 ERNs approved that aims to improve the management of Rare and Complex Connective Tissue and Musculoskeletal Diseases. Objective: The RarERN Path methodology aims to create a single reference organisational model for patients’ care pathways which, if applied in different contexts, helps to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases. Methods: Starting from existing standard methods for the creation and elaboration of patients’ care pathways, a specific methodology was created in order to take advantage of the distinctive and peculiar characteristics of the ERNs. Specifically, the development of the RarERN Path methodology involved different stakeholders: health economists, clinicians and researchers expert in rare and complex diseases, communication experts, experts in patients’ involvement and narrative medicine and policy-makers. Results: The RarERN Path methodology foresees six consecutive phases, each with different and specific aims. Specifically, the six phases are represented by: Phase 1—mapping of existing patients’ care pathways and patients’ stories; Phase 2—design of an optimised common patients’ care pathway; Phase 3—consensus on an optimised common patients’ care pathway; Phase 4—key performance indicators definition; Phase 5—refinement; Phase 6—pilot phase (optional). Conclusion: The application of RarERN Path to the different disease-specific and geographical contexts would help to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases across Europe as well as a possible tangible action towards the integration of ERNs into the different European healthcare systems

A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare

Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source

Single particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). RDV was chosen as it is a wellcharacterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, was aerosolized and injected into the approximately 0.1 mu m diameter focused hard X-ray beam at the CXI instrument of LCLS. Diffraction patterns from RDV with signal to 5.9 angstrom ngstrom were recorded. The diffraction data are available through the Coherent X-ray Imaging Data Bank (CXIDB) as a resource for algorithm development, the contents of which are described here.11Ysciescopu

Medullary Norepinephrine Neurons Modulate Local Oxygen Concentrations in the Bed Nucleus of the Stria Terminalis

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. Here we investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat by measuring O2, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O2 were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O2 levels followed by a brief dip below baseline. Supporting the role of a hyperemic response, the O2 increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O2 is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O2 influx in a deep brain region