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The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Thomas Mann und Otto Dix hätten die Kriegsjahre von 1914 bis 1918 nicht unterschiedlicher erleben können: Der Schriftsteller Mann, der mit 25 schon nach kurzer Zeit wegen eines Plattfußes und einer Sehnenscheidenentzündung aus dem Pflichtwehrdienst entlassen wurde, meldete sich 1914 zum Landsturm, wurde aber 1916 endgültig wegen Magenproblemen und Nervosität für untauglich erklärt und war so nie an der Front. Der Künstler Dix hingegen wurde als Ersatz-Reservist schon drei Wochen nach Kriegsausbruch zur Ausbildung eingezogen und kämpfte von September 1915 bis zum Kriegsende an der West- und Ostfront. Als Schütze und Führer eines Maschinengewehrzuges stand er dabei immer an vorderster Front.
Während der Kriegsjahre und der Weimarer Republik spielten der Konflikt und seine Auswirkungen auf die deutsche Gesellschaft eine zentrale Rolle in den Werken von Dix und Mann. Ein Vergleich von Dix' Triptychon 'Der Krieg' (1928-1932, Staatliche Kunstsammlungen Dresden) und der Kriegsszene am Ende von Manns Roman 'Der Zauberberg', die der Autor erst kurz vor dessen Veröffentlichung 1924 schrieb, zeigt, dass die beiden Werke sowohl in der Motivik als auch in dem die Darstellungen bestimmenden Verständnis von Krieg als einem Phänomen der menschlichen Existenz übereinstimmen. Beide Werke werden gewöhnlich als realistische Schilderungen der grausamen, entindividualisierenden und entmenschlichenden Kräfte des Krieges verstanden.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.