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On the design and performance of a hybrid-integrated high-T c superconducting C-band oscillator
(1992)
For protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter taste substances are most probably initiated by tracheal brush cells (BC). Our single-cell RNA-seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca2+](i) in BC and subsequent ACh-release. ACh-release is regulated in an autocrine manner. While the muscarinic ACh-receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca2+](i) in ciliated cells. Stimulation by denatonium or with Pseudomonas quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5- and M3R-mediated. We show that ACh-release from BC via the bitter taste cascade leads to immediate paracrine protective responses that can be boosted in an autocrine manner. This mechanism represents the initial step for the activation of innate immune responses against pathogens in the airways.
The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Although much effort is made to prevent risks arising from food, food-borne diseases are an ever present-threat to the consumers’ health. The consumption of fresh food that is contaminated with pathogens like fungi, viruses or bacteria can cause food poisoning that leads to severe health damages or even death. The outbreak of Shiga Toxin-producing enterohemorrhagic E. coli (EHEC) in Germany and neighbouring countries in 2011 has shown this dramatically. Nearly 4.000 people were reported of being affected and more than 50 people died during the so called EHEC-crisis. As a result the consumers’ trust in the safety of fruits and vegetables decreased sharply.
Although much effort is made to prevent risks arising from food, food-borne diseases are an ever-present threat to the consumers’ health. The consumption of fresh food that is contaminated with pathogens like fungi, viruses or bacteria can cause food poisoning that leads to severe health damages or even death. The outbreak of Shiga Toxin-producing enterohemorrhagic E. coli (EHEC) in Germany and neighbouring countries in 2011 has shown this dramatically. Nearly 4.000 people were reported of being affected and more than 50 people died during the so called EHEC-crisis. As a result the consumers’ trust in the safety of fruits and vegetables decreased sharply.
Large sections of the German society are able to buy and consume meat on a daily basis due to progress in the agri-food sector. However, the way meat is produced, traded and consumed increasingly has become an issue that is controversially discussed by the media, non-governmental organisations (NGOs), lobbyists, the industry itself and consumers – often with a negative connotation. The meat industry reacts to this. By creating information campaigns and animal welfare initiatives it aims to stress that it is going to take its corporate social responsibilities (CSR) for consumers and animal welfare seriously. But, the industry’s actions are still criticised as being not sufficient to improve animal welfare levels significantly. Much of this criticism can be observed in online news portals, where articles about the issue get published and commented by readers. This makes online portals a valuable source for information that is to be tapped in this study. It aims to better understand the multifaceted discussions concerning animal welfare initiatives in online portals. By applying qualitative content analysis and web mining techniques to a sample of documents taken from three major German news sites it can be shown that online discussions refer to various aspects of sustainability and corporate social responsibility. Findings also indicate that the discussions are framed by financial aspects.