Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin

Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients

Probing the close environment of young stellar objects with interferometry

The study of Young Stellar Objects (YSOs) is one of the most exciting topics that can be undertaken by long baseline optical interferometry. The magnitudes of these objects are at the edge of capabilities of current optical interferometers, limiting the studies to a few dozen, but are well within the capability of coming large aperture interferometers like the VLT Interferometer, the Keck Interferometer, the Large Binocular Telescope or 'OHANA. The milli-arcsecond spatial resolution reached by interferometry probes the very close environment of young stars, down to a tenth of an astronomical unit. In this paper, I review the different aspects of star formation that can be tackled by interferometry: circumstellar disks, multiplicity, jets. I present recent observations performed with operational infrared interferometers, IOTA, PTI and ISI, and I show why in the next future one will extend these studies with large aperture interferometers.Comment: Review to be published in JENAM'2002 proceedings "The Very Large Telescope Interferometer Challenges for the future

FAIRagro: Ein Konsortium in der Nationalen Forschungsdateninfrastruktur (NFDI) für Forschungsdaten in der Agrosystemforschung : Herausforderungen und Lösungsansätze für den Aufbau einer FAIRen Forschungsdateninfrastruktur

FAIRagro ist ein Konsortium in der Nationalen Forschungsdateninfrastruktur (NFDI) in Deutschland um Forschungsdaten der Agrosystemforschung FAIR – d. h. auffindbar (F), zugänglich (A), interoperabel (I) und für andere Forschende domänenübergreifend nachnutzbar (R) zu machen. In der deutschen Forschungslandschaft rund um nachhaltige Agrosysteme werden heterogene Forschungsdaten erhoben und nur zum Teil in existierenden Forschungsdatenrepositorien veröffentlicht. Das Spektrum der Datenformate erstreckt sich beispielsweise von Laborergebnissen, über Satellitenbilder bis hin zu qualitativen Interviews mit Landwirt:innen. Um diese Daten zukünftig für Forschende verschiedener Disziplinen besser auffindbar und nachnutzbar zu machen, wird FAIRagro eine Forschungsdateninfrastruktur (FDI) für die Agrosystemforschung einrichten, in der disziplinäre Dateninfrastrukturen miteinander verknüpft werden. Spezifische Herausforderungen im Forschungsdatenmanagement (FDM) fachlicher Disziplinen wie Pflanzenzüchtung, integrierter Pflanzenschutz oder Agrarrobotik werden als Use Cases in FAIRagro adressiert und für diese Lösungen entwickelt. Darüber hinaus wird FAIRagro ein Netzwerk aus direkten Ansprechpersonen für Fragen zum Forschungsdatenmanagement in der Agrosystem-Community bereitstellen. In Übereinstimmung mit den Zielsetzungen der NFDI und der European Open Science Cloud ist FAIRagro aktiv an der konzeptionellen Implementierung eines interoperablen Datenraums beteiligt

Theta_13: phenomenology, present status and prospect

The leptonic mixing angle theta_13 is currently a high-priority topic in the field of neutrino physics, with five experiments under way, searching for neutrino oscillations induced by this angle. We review the phenomenology of theta_13 and discuss the information from present global oscillation data. A description of the upcoming reactor and accelerator experiments searching for a non-zero value of theta_13 is given, and we evaluate the sensitivity reach within the next few years.Comment: Topical review, 55 pages, 23 figures, v2: various minor improvements, references added, new section 6, matches version to appear in J. Phys.

Diagnosis and treatment of urticaria and angioedema: a worldwide perspective

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations