New insights into the FLS2 trafficking and signaling pathway revealing a role for late defense responses in Arabidopsis immunity

Pathogen-associated molecular pattern (PAMP) triggered immunity (PTI) enables plants to efficiently defend themselves against most pathogens. PTI is initiated by plasma membrane pattern recognition receptors like Flagellin Sensitive 2 (FLS2), which detects flg22 peptides derived from bacterial flagellin. Flg22 triggers cellular trafficking of FLS2 to endosomal compartments and several defense responses, including early responses such as closure of stomatal apertures or gene activation and late responses such as seedling growth arrest or callose deposition. Cellular trafficking is often regulated by ubiquitination. In order to find factors modulating FLS2 endosomal trafficking, we used the Pseudomonas syringe pv. tomato (Pto) DC3000 effector AvrPtoB to identify residues in FLS2, which are ubiquitinated by AvrPtoB. Using tandem mass-spectrometry we identified one ubiquitination site in the juxtamembrane domain of FLS2. FLS2 mutated in all juxtamembrane located lysines showed reduced ubiquitination in vitro, enhanced resistance to Pto DC3000 and increased FLS2 endosome numbers upon flg22 treatment. Ubiquitinated plasma membrane proteins are targeted to late endosomal compartments by the Endosomal Sorting Complex Required for Transport (ESCRT) in yeast and animals. Using confocal microscopy we observed flg22-dependent co-localization of FLS2 with ESCRT-1 positive vesicles. Furthermore, ESCRT-1 mutants vps28-2 and vps37-1 showed reduced flg22-triggered defense gene activation, loss of flg22-dependent stomatal closure and decreased numbers of FLS2 endosomes. Both mutants showed higher susceptibility to biotrophic pathogens, indicating a role of ESCRT-1 components in plant immunity. A second approach aimed to genetically dissect flg22 responses by analyzing a previously isolated flagellin insensitive 1 (fli1) mutant. Fli1 mutants were similar susceptible to Pto DC3000 than fls2-17 receptor mutants. Increased susceptibility of fli1 to Pto DC3000 correlated with higher expression of sugar starvation responsive genes during infections and reduced late flg22 responses. Early flg22 responses and transcriptional profiles three hours post infection resembled wild-type plants, suggesting a positive role of late PAMP responses in plant immunity. Genetic analysis showed that fli1 is recessive inherited and co-segregated with markers on the upper arm of chromosome 5. Sequence differences in fli1 predicted by whole genome sequence analysis were, however, shared with Ler wild-type plants, leaving the designation of fli1 to one gene open. In conclusion, these data provide good evidences for a role of late FLS2 endosomal trafficking and late flg22-repsonses as critical components of plant immunity against Pto DC3000

CalloseMeasurer: a novel software solution to measure callose deposition and recognise spreading callose patterns

BACKGROUND: Quantification of callose deposits is a useful measure for the activities of plant immunity and pathogen growth by fluorescence imaging. For robust scoring of differences, this normally requires many technical and biological replicates and manual or automated quantification of the callose deposits. However, previously available software tools for quantifying callose deposits from bioimages were limited, making batch processing of callose image data problematic. In particular, it is challenging to perform large-scale analysis on images with high background noise and fused callose deposition signals. RESULTS: We developed CalloseMeasurer, an easy-to-use application that quantifies callose deposition, a plant immune response triggered by potentially pathogenic microbes. Additionally, by tracking identified callose deposits between multiple images, the software can recognise patterns of how a given filamentous pathogen grows in plant leaves. The software has been evaluated with typical noisy experimental images and can be automatically executed without the need for user intervention. The automated analysis is achieved by using standard image analysis functions such as image enhancement, adaptive thresholding, and object segmentation, supplemented by several novel methods which filter background noise, split fused signals, perform edge-based detection, and construct networks and skeletons for extracting pathogen growth patterns. To efficiently batch process callose images, we implemented the algorithm in C/C++ within the AcapellaTM framework. Using the tool we can robustly score significant differences between different plant genotypes when activating the immune response. We also provide examples for measuring the in planta hyphal growth of filamentous pathogens. CONCLUSIONS: CalloseMeasurer is a new software solution for batch-processing large image data sets to quantify callose deposition in plants. We demonstrate its high accuracy and usefulness for two applications: 1) the quantification of callose deposition in different genotypes as a measure for the activity of plant immunity; and 2) the quantification and detection of spreading networks of callose deposition triggered by filamentous pathogens as a measure for growing pathogen hyphae. The software is an easy-to-use protocol which is executed within the Acapella software system without requiring any additional libraries. The source code of the software is freely available at https://sourceforge.net/projects/bioimage/files/Callose

Putting Queens in Carry Chains

This paper describes an FPGA implementation of a solution-counting solver for the N-Queens Puzzle. The proposed algorithmic mapping utilizes the fast carrychain logic found on modern FPGA architectures in order to achieve a regular and efficient design. From an initial full chessboard mapping, several optimization strategies are explored. Also, the infrastructure is described, which we have constructed for the computation of the currently unknown solution count of the 26- Queens Puzzle. Finally, we compare the performance of our used concrete FPGA device mappings also in contrast to general-purpose CPUs

An Embedded Garbage Collection Module with Support for Multiple Mutators and Weak References

This report details the design of a garbage collection (GC) module, which introduces modern GC features to the domain of embedded implementations. The described design supports weak references and feeds reference queues. Its architecture allows multiple concurrent application cores operating as mutators on the shared memory managed by the GC module. The garbage collection is exact and fully concurrent so as to enable the uninterrupted computational progress of the mutators. It combines a distributed root marking with a centralized heap scan of the managed memory. It features a novel mark-and-copy GC strategy on a segmented memory, which thereby overcomes both the tremendous space overhead of two-space copying and the compaction race of mark-and-compact approaches. The proposed GC architecture has been practically implemented and proven using the embedded bytecode processor SHAP as a sample testbed. The synthesis results for settings up to three SHAP mutator cores are given and online functional measurements are presented. Basic performance dependencies on the system configuration are evaluated

Neue Mitbestimmungspraktiken in der digitalen Transformation der "Industrie 4.0": Befunde aus dem gewerkschaftlichen Projekt "Arbeit 2020 in NRW"

Die Bezeichnung "Industrie 4.0" hat sich als Synonym für den digitalen Wandel im deutschen Industriesektor etabliert. Die damit verbundenen Umbrüche werden jedoch nicht technisch vorgegeben, sondern sind in den Betrieben arbeitspolitisch gestaltbar - und damit Gegenstand der Mitbestimmung der Betriebsräte. Eine Antwort auf diese Herausforderungen ist das gewerkschaftliche Projekt "Arbeit 2020 in NRW" als eines der aktuell avanciertesten betriebspolitischen Projekte deutscher Gewerkschaften. Im Rahmen des Projekts sollen in den Betrieben das Wissen um Veränderungen erhöht, arbeitspolitische Themen erschlossen und schließlich auch Vereinbarungen mit der Unternehmensseite ausgehandelt werden. Die Befunde zeigen, dass auf diese Weise die Ressourcen und die Handlungsfähigkeit der Betriebsräte gestärkt, beteiligungsorientierte Mitbestimmungspraktiken eingeübt und strategische Orientierungen der Betriebsräte gefördert werden können. Insgesamt lässt sich folgern, dass das "duale" Zusammenspiel von Betriebsräten und Gewerkschaften im Betrieb als Grundlage einer handlungsmächtigen Interessenvertretung immer mehr an Bedeutung gewinnt

Moderating or mediating effects of family characteristics on socioeconomic inequalities in child health in high-income countries – a scoping review

Background: By explaining the development of health inequalities, eco-social theories highlight the importance of social environments that children are embedded in. The most important environment during early childhood is the family, as it profoundly influences children’s health through various characteristics. These include family processes, family structure/size, and living conditions, and are closely linked to the socioeconomic position (SEP) of the family. Although it is known that the SEP contributes to health inequalities in early childhood, the effects of family characteristics on health inequalities remain unclear. The objective of this scoping review is to synthesise existing research on the mediating and moderating effects of family characteristics on socioeconomic health inequalities (HI) during early childhood in high-income countries. Methods: This review followed the methodology of “Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews”. To identify German and English scientific peer-reviewed literature published from January 1st, 2000, to December 19th, 2019, the following search term blocks were linked with the logical operator “AND”: (1) family structure/size, processes, living conditions, (2) inequalities, disparities, diversities, (3) income, education, occupation, (4) health and (5) young children. The search covered the electronic databases PubMed, PsycINFO, and Scopus. Results: The search yielded 7,089 records. After title/abstract and full-text screening, only ten peer-reviewed articles were included in the synthesis, which analysed the effects of family characteristics on HI in early childhood. Family processes (i.e., rules /descriptive norms, stress, parental screen time, parent–child conflicts) are identified to have mediating or moderating effects. While families’ living conditions (i.e., TVs in children’s bedrooms) are suggested as mediating factors, family structure/size (i.e., single parenthood, number of children in the household) appear to moderate health inequalities. Conclusion: Family characteristics contribute to health inequalities in early childhood. The results provide overall support of models of family stress and family investment. However, knowledge gaps remain regarding the role of family health literacy, regarding a wide range of children’s health outcomes (e.g., oral health, inflammation parameters, weight, and height), and the development of health inequalities over the life course starting at birth.Peer Reviewe

The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma

Deubiquitylases (DUBs) are therapeutically amenable components of the ubiquitin machinery that stabilize substrate proteins. Their inhibition can destabilize oncoproteins that may otherwise be undruggable. Here, we screened for DUB vulnerabilities in multiple myeloma, an incurable malignancy with dependency on the ubiquitin proteasome system and identified OTUD6B as an oncogene that drives the G1/S-transition. LIN28B, a suppressor of microRNA biogenesis, is specified as a bona fide cell cycle-specific substrate of OTUD6B. Stabilization of LIN28B drives MYC expression at G1/S, which in turn allows for rapid S-phase entry. Silencing OTUD6B or LIN28B inhibits multiple myeloma outgrowth in vivo and high OTUD6B expression evolves in patients that progress to symptomatic multiple myeloma and results in an adverse outcome of the disease. Thus, we link proteolytic ubiquitylation with post-transcriptional regulation and nominate OTUD6B as a potential mediator of the MGUS-multiple myeloma transition, a central regulator of MYC, and an actionable vulnerability in multiple myeloma and other tumors with an activated OTUD6B-LIN28B axis.</p

Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19

Progressive respiratory failure and hyperinflammatory response is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. Despite mounting evidence of disruption of the hypothalamus-pituitary-adrenal axis in COVID-19, relatively little is known about the tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adrenal glands and associated changes. Here we demonstrate adrenal viral tropism and replication in COVID-19 patients. Adrenal glands showed inflammation accompanied by inflammatory cell death. Histopathologic analysis revealed widespread microthrombosis and severe adrenal injury. In addition, activation of the glycerophospholipid metabolism and reduction of cortisone intensities were characteristic for COVID-19 specimens. In conclusion, our autopsy series suggests that SARS-CoV-2 facilitates the induction of adrenalitis. Given the central role of adrenal glands in immunoregulation and taking into account the significant adrenal injury observed, monitoring of developing adrenal insufficiency might be essential in acute SARS-CoV-2 infection and during recovery.</p

Rehabilitative Versorgung und gesundheitsbedingte Frühberentung von Personen mit Migrationshintergrund in Deutschland: Abschlussbericht

Dieser Abschlussbericht stellt die Ergebnisse des Projektes "Rehabilitative Versorgung und gesundheitsbedingte Frühberentung von Personen mit Migrationshintergrund in Deutschland" vor. Auf Basis eines quantitativen und qualitativen Forschungszugangs wurde untersucht, inwiefern sich einzelne Gruppen von ausländischen Staatsangehörigen bzw. Menschen mit Migrationshintergrund hinsichtlich der Häufigkeit von Arbeitsunfällen und Berufskrankheiten, der Inanspruchnahme beruflicher und medizinischer Rehabilitationsmaßnahmen, des Rehabilitationserfolges und der Frühberentung von Deutschen bzw. Menschen ohne Migrationshintergrund unterscheiden. Unter Bezugnahme auf Prozess- und Individualdaten unterschiedlicher Rehabilitationsträger zeigt der Bericht, dass Menschen mit Migrationshintergrund im Durchschnitt weniger häufig Maßnahmen der medizinischen Rehabilitation in Anspruch nehmen sowie einen geringeren Rehabilitationserfolg und höhere Frühberentungsquoten aufweisen als die Mehrheitsbevölkerung. Auf Basis einer systematischen Literaturrecherche und mittels qualitativer Experten- und Fokusgruppeninterviews werden darüber hinaus unterschiedliche Zugangs-, Durchführungs- und Wirksamkeitsbarrieren in der Rehabilitation von Menschen mit Migrationshintergrund identifiziert, welche die quantitativen Ergebnisse zumindest teilweise erklären können. Handlungsempfehlungen für die Verbesserung der rehabilitativen Versorgung von Menschen mit Migrationshintergrund werden abgeleitet