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Objectives The aim of this retrospective study was to assess the long-term results of root remodelling with tricuspid aortic valves and the effects of concomitant cusp repair and annuloplasty. Methods Between 10/1995 and 12/2021, 684 patients with root aneurysm and regurgitant tricuspid valves were treated by root remodelling. Mean age was 56.5(SD: 14) years, 538(77.6%) were male. Relevant aortic regurgitation was present in 68.3%. Concomitant procedures were performed in 374 patients. The long-term results were analyzed. Mean follow-up of 7.2(SD: 5.3) years (median 6.6 years); it was 95% complete (4934.4 patient-years). Results Cusps prolapse was repaired in 83%, an annuloplasty was added in 353 instances (51.6%). Hospital mortality was 2.3%, survival was 81.7% (SD: 1.2) and 55.7 (SD: 5.8) at 10 and 20 years; age and measurement of effective height were independent predictors for death. Freedom from AI II was 90.5 (SD : 1.9) at 10 years and 76.7(SD : 4.5) at 20 years. Cusp repair of all cusps showed a lower freedom from recurrent AI≥II at 10 years(p Freedom from reoperation was 95.5(SD : 1.1) and 92.8(SD: 2.8) at 10 and 20 years. The addition of an annuloplasty showed no difference(p = 0.236). Cusp repair had no effect on valve durability(p = 0.390). Conclusions Root remodelling leads to good long-term stability. The addition of cusp repair improves the valve stability over time. The addition of suture annuloplasty improve early valve competency; it showed no effect on freedom from reoperation up to 10 years.

C-di-GMP signaling can directly influence bacterial behavior by affecting the functionality of c-di-GMP-binding proteins. In addition, c-di-GMP can exert a global effect on gene transcription or translation, for example, via riboswitches or by binding to transcription factors. In this study, we investigated the effects of changes in intracellular c-di-GMP levels on gene expression and protein production in the opportunistic pathogen Pseudomonas aeruginosa. We induced c-di-GMP production via an ectopically introduced diguanylate cyclase and recorded the transcriptional, translational as well as proteomic profile of the cells. We demonstrate that rising levels of c-di-GMP under growth conditions otherwise characterized by low c-di-GMP levels caused a switch to a non-motile, auto-aggregative P. aeruginosa phenotype. This phenotypic switch became apparent before any c-di-GMP-dependent role on transcription, translation, or protein abundance was observed. Our results suggest that rising global c-di-GMP pools first affects the motility phenotype of P. aeruginosa by altering protein functionality and only then global gene transcription.

Susanne Dietrich und Julia Schulze Wessel: Zwischen Selbstorganisation und Stigmatisierung. Die Lebenswirklichkeit jüdischer Displaced Persons und die neue Gestalt des Antisemitismus in der deutschen Nachkriegsgesellschaft. (Veröffentlichungen des Archivs der Stadt Stuttgart, Band 75). Klett-Cotta Verlag Stuttgart 1998. 232 Seiten mit 18 Abbildungen. Pappband € 20,--.ISBN 3-89850-954-0

Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remains largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD. Therefore, we conducted a transcriptome study of SAD and ELA performing RNA sequencing in peripheral blood samples. Analyzing differential gene expression between individuals suffering from SAD with high or low levels of ELA and healthy individuals with high or low levels of ELA, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD while no significant differences in expression were identified with respect to ELA. The most significantly expressed gene was MAPK3 (p = 0.003) being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analysis (WGCNA) identified only modules significantly associated with ELA (p ≤ 0.05), not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3 revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD. In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.

The review essay looks at recent publications with regards to nationalism and nation as a concept of political science. By distinguishing between inclusive and exclusive nations as well as focusing on the conflicting potential of the debates on nationalism, the author opens up interpretative lines and offers new insights into this field of research.

Capsule polymers are crucial virulence factors of pathogenic bacteria and are used as antigens in glycoconjugate vaccine formulations. Some Gram-negative pathogens express poly(glycosylglycerol phosphate) capsule polymers that resemble Gram-positive wall teichoic acids and are synthesized by TagF-like capsule polymerases. So far, the biotechnological use of these enzymes for vaccine developmental studies was restricted by the unavailability of enantiopure CDP-glycerol, one of the donor substrates required for polymer assembly. Here, we use CTP:glycerol-phosphate cytidylyltransferases (GCTs) and TagF-like polymerases to synthesize the poly(glycosylglycerol phosphate) capsule polymer backbones of the porcine pathogen Actinobacillus pleuropneumoniae, serotypes 3 and 7 (App3 and App7). GCT activity was confirmed by high-performance liquid chromatography, and polymers were analyzed using comprehensive nuclear magnetic resonance studies. Solid-phase synthesis protocols were established to allow potential scale-up of polymer production. In addition, one-pot reactions exploiting glycerol-kinase allowed us to start the reaction from inexpensive, widely available substrates. Finally, this study highlights that multidomain TagF-like polymerases can be transformed by mutagenesis of active site residues into single-action transferases, which in turn can act in trans to build-up structurally new polymers. Overall, our protocols provide enantiopure, nature-identical capsule polymer backbones from App2, App3, App7, App9, and App11, Neisseria meningitidis serogroup H, and Bibersteinia trehalosi serotypes T3 and T15. IMPORTANCE Economic synthesis platforms for the production of animal vaccines could help reduce the overuse and misuse of antibiotics in animal husbandry, which contributes greatly to the increase of antibiotic resistance. Here, we describe a highly versatile, easy-to-use mix-and-match toolbox for the generation of glycerol-phosphate-containing capsule polymers that can serve as antigens in glycoconjugate vaccines against Actinobacillus pleuropneumoniae and Bibersteinia trehalosi, two pathogens causing considerable economic loss in the swine, sheep, and cattle industries. We have established scalable protocols for the exploitation of a versatile enzymatic cascade with modular architecture, starting with the preparative-scale production of enantiopure CDP-glycerol, a precursor for a multitude of bacterial surface structures. Thereby, our approach not only allows the synthesis of capsule polymers but might also be exploitable for the (chemo)enzymatic synthesis of other glycerol-phosphate-containing structures such as Gram-positive wall teichoic acids or lipoteichoic acids.

In einem als Pretest konzeptionierten Befragung von Gefluchteten in Sachsen untersuchte das Netzwerk Integrations-, Fremdenfeindlichkeits- und Rechtsextremismusforschung in Sachsen (IFRiS), welche politischen Einstellungen und Erwartungen an das Aufnahmeland vorherrschen und welche Erfahrungen bereits in Deutschland gemacht wurden. Insgesamt sind die Erfahrungen in Deutschland eher positiv, wenn einige Befragte auch durchaus uber individuelle und gruppenbezogene Diskriminierung berichteten. Die Erfassung politischer Einstellungen erwies sich als recht schwierig. Insgesamt zeigte sich aber, dass Demokratie mehrheitlich als wunschenswert empfunden wird, parallel aber Sympathien fur starke Autoritaten existieren.

© 2021 The Authors., The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., Hyun-Dong Chang is supported by the Dr. Rolf M. Schwiete Foundation. Susanne Melzer and Attila Tarnok thank De Novo Software for providing FCS Express. Enrico Lugli is supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC IG20676). Gabriele De Simone and Giovanni Galletti were supported by Fellowships from the Fondazione Italiana per la Ricerca sul Cancro-Associazione Italiana per la Ricerca sul Cancro (FIRC-AIRC). Jun Dong is supported by Deutsche Forschungsgemeinschft (DFG, German Research Foundation) Projektnummer 389687267 and Chinesisch-Deutsches Zentrum für Wissenschaftsförderung [Sino-German Center for Research Promotion (SGC)] grant C-0072. Nicola Gagliani, Samuel Huber and Franziska Muscate are supported by DFG fundings: SFB841,GA 2441/3-1, HU 1714/10-1. The tetramer APC-conjugated H-2K (d) HIV-1 gag197-205 AMQMLKETI used in TDS assay for mouse blood T cells was obtained through the NIH Tetramer Facility. Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14-1. Supported by the following grants: AIRC 5X1000 2018 id. 21147 (Lorenzo Moretta); AIRC IG 2017 id. 19920 (Lorenzo Moretta); RC-2020 OPBG (Lorenzo Moretta); AIRC and European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 800924 (Linda Quatrini). Dirk Baumjohann was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Emmy Noether Programme BA 5132/1-2 (252623821) and Germany's Excellence Strategy EXC2151 (390873048).

Mass cytometry is increasingly employed in larger immune profiling studies involving data acquisitions across several days and multiple sites. For gaining a maximum of information from respective data by computational analyses, several techniques have been developed to minimize noise in mass cytometric data sets, such as sample banking, standardized instrument setup, sample barcoding, and signal normalization. However, the repeated preparation of cocktails composed of isotope-tagged antibodies remained a significant source of error. We here show that premixed antibody cocktails fail to deliver expected staining patterns when stored at 4°C for 4 weeks. As a solution, we developed and tested a cryopreservation method for highly multiplexed antibody cocktails for mass cytometry including lanthanide, palladium, and platinum conjugates that yielded stable staining patterns for at least 9 months when stored at temperatures below -80°C. Using frozen aliquots of antibody cocktails is an economic and flexible approach to significantly improve data consistency in large mass cytometry studies with repetitive staining/measurement cycles spanning several days or involving multiple data acquisition sites. © 2019 International Society for Advancement of Cytometry.

Der Beitrag analysiert und diskutiert aus der Perspektive der Kommunikationswissenschaft und der Medienforschung die gesellschaftliche Rolle der klassischen Massenmedien und neu der Online-Kommunikation mit ihren vielfaltigen Funktionen und Leistungen gegenuber der Gesellschaft. Es werden relevante theoretische Perspektiven der (Medien-)Soziologie und Politologie auf der Makroebene und der Medienwirkungsforschung auf der Mikroebene dargestellt und deren Implikationen bezuglich Integration der Gesellschaft herausgearbeitet und diskutiert.

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B‑ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK‑2206 promises meticulous pan‑AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK‑2206 on B‑ALL cell lines and primary samples and investigate potential synergistic effects with BCL‑2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK‑2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK‑2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK‑2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4, 11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK‑2206. Functional assessment of BCL‑2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK‑2206 and venetoclax incubation. In summary, we demonstrate that the pan‑AKT inhibitor MK‑2206 potently blocks B‑ALL cell proliferation and for the first time characterize the synergistic effect of combined MK‑2206 and venetoclax treatment in B‑ALL.

In den gegenwartigen Debatten um die Grenzen der Demokratie wird implizit und explizit uber die Frage gestritten, wieviel Fremdheit und Diversitat moderne Demokratien tragen konnen. Diese Fragen ruhren an dem Fundament moderner Demokratien, an ihrem Selbstverstandnis und der(diskursiven) Regulation von Inklusion und Exklusion. Anhand der biblischen Figur der Ahrenleserin Ruth wird sich der Beitrag mit dem Verhaltnis von Fremdheit und demokratischer Ordnung auseinandersetzen. Mit Cynthia Ozick, Julia Kristeva und Bonnie Honig werden drei unterschiedliche Zugange zum Thema diskutiert: Wahrend Ozick und Kristeva die Fremdheit in der Assimilation oder der Selbstbestatigung der Ordnung verschwinden lassen, beharrt Honig auf dem notwendigen Bestehen der Fremdheit in demokratischen Ordnungen. Fremdheit steht bei ihr fur das demokratische Paradox, das moderne Demokratien seit ihrer Grundung begleitet.

Syphilis is often called the great imitator because of its frequent atypical clinical manifestations that make the disease difficult to recognize. Because Treponema pallidum subsp. pallidum, the infectious agent of syphilis, is yet uncultivated in vitro, diagnosis is usually made using serology; however, in cases where serology is inconclusive or in patients with immunosuppression where these tests may be difficult to interpret, the availability of a molecular tool for direct diagnosis may be of pivotal importance. Here we present a fluorescence in situ hybridization (FISH) assay that simultaneously identifies and analyzes spatial distribution of T. pallidum in histological tissue sections. For this assay the species-specific FISH probe TPALL targeting the 16S rRNA of T. pallidum was designed in silico and evaluated using T. pallidum infected rabbit testicular tissue and a panel of non-syphilis spirochetes as positive and negative controls, respectively, before application to samples from four syphilis-patients. In a HIV positive patient, FISH showed the presence of T. pallidum in inguinal lymph node tissue. In a patient not suspected to suffer from syphilis but underwent surgery for phimosis, numerous T. pallidum cells were found in preputial tissue. In two cases with oral involvement, FISH was able to differentiate T. pallidum from oral treponemes and showed infection of the oral mucosa and tonsils, respectively. The TPALL FISH probe is now readily available for in situ identification of T. pallidum in selected clinical samples as well as T. pallidum research applications and animal models.