Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma

Polymorphisms in the interleukin-4 receptor α chain (IL-4Rα) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4Rα has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target– and tissue-specific manner to mediate heightened expression of a subset of IL-4– and IL-13–responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rα–dependent signaling

Digitalisierung: Perspektiven für Arbeitsmodelle der Zukunft in Wirtschaft und Verwaltung

Die Digitalisierung ist derzeit einer der wichtigsten Wandlungstreiber in Wirtschaft und Gesellschaft. Die aus den neuen technischen Möglichkeiten resultierenden Veränderungen wirken sich auch auf das Verhalten von Kunden und Mitarbeitenden aus. In Bezug auf die Zusammenarbeit in Unternehmen und Organisationen sind bestehende Arbeitsmodelle für administrative Arbeit anzupassen und neue Formen digitaler Kollaboration einzuführen. Hiermit verbunden sind Änderungen der Arbeitszeitmodelle, der Organisation der Mitarbeitenden, der Art der Zusammenarbeit und Führung sowie der Gestaltung von Büroräumlichkeiten. In einem vergleichenden Case-Study-Ansatz von zwei Schweizer Großunternehmen und einer großen Verwaltungseinheit des Bundes werden die existierenden Arbeitsmodelle für Büroarbeit analysiert und auf Entwicklungsperspektiven hin untersucht. Ein derzeit vorhandener Mix aus traditionellen und agilen Arbeitsmodellen wird sich in Zukunft im digitalen Kontext voraussichtlich unternehmensspezifisch stärker in Richtung einer höheren Agilität weiterentwickeln

Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy

It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000 CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive to acute exercise demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/memory

Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone

Prey consumption of Orius similis Zheng (Het., Anthocoridae) with different aphid species as prey

The laboratory experiments showed that the predatory bug Orius similis Zheng, originally from China, is able to prey on different aphid species. It consumed significantly higher Aphis gossypii Glover and Aphis pomi (De Geer) than other aphid species during its entire nymphal development and adult stage as females (mated and unmated) and males. There were no significant differences in the mean daily and total prey consumption of females and males during the nymphal development. The mean daily prey consumption of adult O. similis was significantly higher by mated females than unmated females and males. No significant differences in the mean daily prey consumption of unmated females and males were detected. When A. gossypii and A. pomi were offered, the mean total prey consumption was significantly higher by females (mated and unmated) than by males. It was significantly higher by mated females than unmated females and males with Acyrthosiphon pisum (Harris) and Myzus persicae (Sulzer) as prey. O. similis adapted smoothly to fluctuating prey availability that increasing or decreasing prey consumption of the predator is depended on prey population density. The results showed that O. similis seems to be a promising predator for biological control against different aphid species

A Block Adaptive Vector Quantization for Optimized SAR Raw Data Reduction.

This paper proposes a new approach for efficient SAR raw data compression which consists of first compressing the raw data with the block adaptive quantizer (BAQ) approach and then performing a compression with the vector quantizer (VQ). Further improvements are possible selecting different compression ratios with fuzzy control systems whereby the mean data rate is nearly maintained

A Comparison of Several Algorithms for on-Board SAR Raw-Data Reduction.

This paper shows a comparison of different SAR raw data reduction algorithms applied to air- and spaceborne SAR data. A signal-to-noise ratio up to 12 dB is achieved by the Block Adaptive Vector Quantizer (BAVQ)