Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life

Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring

Arbeitsleben im demografischen Wandel: Fallstudie Kraftunterstützungssystem für Handwerker

Der Trend 'Alternde Gesellschaft' wirkt auf sämtliche Bereiche des täglichen Lebens und bedingt zum Beispiel eine zunehmende Lebensarbeitszeit, die gepaart mit stetig steigenden Anforderungen an Qualität und Effizienz neue Technologien, Arbeitsprozesse und Assistenzsysteme erfordert. Für Letztere, angewendet auf die Domäne 'Hand- und Heimwerker' erscheinen Systeme zweckmäßig, die eine Kraftunterstützung, Augmentierung, Sicherheitssteigerung und/oder Führungsfunktion darstellen. Die erforderlichen wissenschaftlichen Technologiebausteine zur Umsetzung dieser Funktionen sind größtenteils bereits heute vorhanden. Dieser Artikel widmet sich der Kraftunterstützung und beschreibt ein elektromechanisches System - den Demonstrator eines so genannten '3. Armes' - welches den Anwender aktiv beim Umgang mit schweren Elektrowerkzeugen unterstützt. Der '3. Arm' besteht weitestgehend aus kosteneffektiven massenmarkt-tauglichen Komponenten. Er ist an einem Gürtel um die Hüfte des Handwerkers befestigt und entlastet den Handwerker bei schweren oder ermüdenden Arbeiten. Zwei Funktionen wurden implementiert und erprobt. Dies ist einerseits die Kompensation der Gewichtskraft des Werkzeugs mit einer geeigneten Kraftregelung und dem Ziel, ein möglichst transparentes Verhalten des Systems zu erreichen. Andererseits wurde mit Hilfe so genannter 'Virtual Fixtures' eine Positionierungs-Hilfsfunktion dargestellt für wiederkehrende Arbeitsschritte in definierten Arbeitshöhen

Cathepsin B promotes collagen biosynthesis driving Bronchiolitis Obliterans Syndrome.

Bronchiolitis obliterans syndrome (BOS) is a major complication after lung transplantation (LTx). BOS is characterised by massive peribronchial fibrosis, leading to air trapping induced pulmonary dysfunction. Cathepsin B, a lysosomal cysteine-protease, was shown to enforce fibrotic pathways in several diseases. However, the relevance of Cathepsin B in BOS progression has not yet been addressed. The aim of the study was to elucidate the function of Cathepsin B in BOS pathogenesis.We determined Cathepsin B levels in BAL fluid and lung tissue from healthy donors (HD) and BOS LTx patients. Furthermore, Cathepsin B activity was assessed via a FRET-based assay and protein expression was determined using Western blotting, ELISA, and immunostaining. To investigate the impact of Cathepsin B in the pathophysiology of BOS, we used an in-vivo orthotopic left-LTx mouse model. Mechanistic studies were performed in-vitro using macrophage and fibroblast cell lines.We found a significant increase of Cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis (LB). Moreover, Cathepsin B activity was associated with an increased biosynthesis of collagen, and negatively affected lung function. Interestingly, we observed that Cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived Cathepsin B contributed to TGF-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype.Infiltrating macrophages release active Cathepsin B promoting fibroblast-activation and subsequent collagen deposition, driving BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS

Binding of NUFIP2 to Roquin promotes recognition and regulation of <em>ICOS</em> mRNA.

The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3&#39;-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen similar to 1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay. NUFIP2 binds directly and with high affinity to Roquin, which stabilizes NUFIP2 in cells. Post-transcriptional repression of human ICOS by endogenous Roquin proteins requires two neighboring non-canonical stem-loops in the ICOS 3&#39;-UTR. This unconventional cis-element as well as another tandem loop known to confer Roquin-mediated regulation of the Ox40 3&#39;-UTR, are bound cooperatively by Roquin and NUFIP2. NUFIP2 therefore emerges as a cofactor that contributes to mRNA target recognition by Roquin