SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. Here, serum of Beta-infected patients revealed reduced cross-neutralization of wildtype virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wildtype-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics

Making trade sustainable impact assessment more relevant to trade negotiations

While trade sustainability impact assessments (trade SIAs) have generated much useful information about the potential impacts of trade liberalisation, they have made very limited impact on trade negotiations, which generate unresolved controversy, if not deadlock. This paper contends that one reason for this is that trade SIAs do not explicitly recognise the motives for countries to resist free trade. Five such motives are identified, with very different characteristics and validity from the perspective of social welfare enhancement and sustainable development. The paper suggests revisions to the trade SIA methodology to help decision-makers better understand the obstacles to trade liberalisation negotiations and whether it is likely that these obstacles will, and desirable that they should, be overcome

Umweltschutzfinanzierung in Mittel- und Osteuropa (MOE) und den Neuen Unabhaengigen Staaten (NUS). Teilbericht 1: Evaluation der westlichen multi- und bilateralen Unterstuetzungsleistungen sowie der Finanzierungen der IFIs

Available from TIB Hannover: RN 8908(2000,271,1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany)DEGerman

Gesundheit und Fitness von deutschen Schulkindern

<jats:title>Zusammenfassung</jats:title><jats:sec> <jats:title>Hintergrund</jats:title> <jats:p>Übergewicht und Bewegungsmangel stellen bei Kindern ein Risiko für kardiovaskuläre Erkrankungen dar. Das Ziel der Studie war, den kardiovaskulären Gesundheitsstatus und die Fitness deutscher Grund- und Gesamtschülerinnen und -schüler sowie mögliche Einflussfaktoren zu erfassen.</jats:p> </jats:sec><jats:sec> <jats:title>Methodik</jats:title> <jats:p>In einer prospektiven Querschnittsstudie wurden 357 Kinder (9,6 ± 1,7 Jahre) auf kardiovaskuläre Risikofaktoren untersucht. Die Pulswellengeschwindigkeit (PWV) als Maß für die arterielle Gefäßelastizität sowie die Fahrradergometrie zur Einschätzung der Fitness wurden bestimmt.</jats:p> </jats:sec><jats:sec> <jats:title>Ergebnisse</jats:title> <jats:p>24 % der Kinder waren übergewichtig (Body-Mass-Index, BMI >90. Perzentile) oder adipös (BMI >97. Perzentile). Nahezu alle diese Kinder litten an einer viszeralen Adipositas (99 %). Bei Kindern mit Übergewicht/Adipositas war häufiger eine geringere Gefäßelastizität nachweisbar (PWV „standard deviation score“, SDS 0,8 ± 1,0 vs. 0,2 ± 0,9 bei Kindern ohne Übergewicht, <jats:italic>p</jats:italic> < 0,001; PWV-Werte >95. Perzentile 24 % vs. 3 %). Das Vorliegen von Übergewicht/Adipositas, Grundschulalter, höherer Blutdruck und niedrigeres „High Density Lipoprotein“(HDL)-Cholesterin waren unabhängige Prädiktoren für geringere Gefäßelastizität. Zudem zeigten Kinder mit Übergewicht/Adipositas einen höheren systolischen Blutdruck, ein nachteiligeres Fettstoffwechselprofil, höhere Harnsäure- und Glutamat-Pyruvat-Transaminase(GPT)-Werte sowie schlechtere körperliche Fitness und einen höheren Medienkonsum. Es bestand eine signifikante Assoziation von BMI und glomerulärer Filtrationsrate.</jats:p> </jats:sec><jats:sec> <jats:title>Diskussion</jats:title> <jats:p>Das mit erhöhtem BMI und reduzierter Fitness einhergehende kardiovaskuläre Risiko wird durch weitere Risikofaktoren für die Entwicklung eines metabolischen Syndroms verstärkt. Zusätzlich finden sich Hinweise, dass bereits strukturelle Veränderungen an den Gefäßen vorliegen. Unsere Daten legen eine umfassende Beurteilung des individuellen kardiovaskulären Risikos bei Kindern mit Übergewicht nahe und unterstreichen die Notwendigkeit, Präventionsmaßnahmen früh in den Alltag von Kindern zu implementieren, um die kardiovaskuläre Morbidität im Erwachsenenalter zu verringern.</jats:p> </jats:sec&gt

Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells

Anti-NMDA receptor (NMDAR) autoantibodies cause NMDAR encephalitis, the most common autoimmune encephalitis, leading to psychosis, seizures, and autonomic dysfunction. Current treatments comprise broad immunosuppression or non-selective antibody removal. We developed NMDAR-specific chimeric autoantibody receptor (NMDAR-CAAR) T cells to selectively eliminate anti-NMDAR B cells and disease-causing autoantibodies. NMDAR-CAARs consist of an extracellular multi-subunit NMDAR autoantigen fused to intracellular 4-1BB/CD3ζ domains. NMDAR-CAAR T cells recognize a large panel of human patient-derived autoantibodies, release effector molecules, proliferate, and selectively kill antigen-specific target cell lines even in the presence of high autoantibody concentrations. In a passive transfer mouse model, NMDAR-CAAR T cells led to depletion of an anti-NMDAR B cell line and sustained reduction of autoantibody levels without notable off-target toxicity. Treatment of patients may reduce side effects, prevent relapses, and improve long-term prognosis. Our preclinical work paves the way for CAAR T cell phase I/II trials in NMDAR encephalitis and further autoantibody-mediated diseases

Insights from the 4C-T Study suggest increased cardiovascular burden in girls with end stage kidney disease before and after kidney transplantation

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred-thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4ml/min/1.73m(2) per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m(2) per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure