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Religiosität von Jugendlichen und jungen Erwachsenen stellt ein äußerst plurales Phänomen dar, wobei bei vielen christlichen Jugendlichen zudem mit einer hohen Offenheit für religiösen Pluralismus zu rechnen ist. Zugleich sind – in einem kleinen Segment – verstärkt religiöse Ausdrucksformen und -stile anzutreffen, die traditionalistisch geprägt sind und die von Außenstehenden daher als fundamentalistisch gedeutet werden können. Aufgabe von Religionspädagogik ist es, die Vielfalt der Ausdrucksformen jugendlicher Religiosität wahrzunehmen und auf dieser Grundlage Konzepte religiöser Bildung zu entwerfen. Dieser Beitrag interessiert sich deshalb für Ausdrucksformen der Religiosität junger Erwachsener in ‚neuen‘ religiösen Bewegungen, die zur Zeit des Social Distancing angesichts der Corona-Pandemie ihre Aktivitäten in sozialen Netzwerken intensiviert und ihr Angebot virtuell erweitert haben. Als Beispiel für die Präsenz katholischer (Jugend-)Bewegungen wurde die HOME Church Salzburg, die ein Teil der Loretto-Bewegung ist, gewählt, welche durch ihren professionellen Auftritt auf verschiedenen Social Media- Kanälen hohe Reichweiten erzielt. Auf Grundlage ihres Sunday Morning- Konzeptes werden Spezifika der dort wahrnehmbaren religiösen Äußerungen, Überzeugungen, Einstellungen, Haltungen und Ausdrucksformen analysiert. Dafür wurden zwölf Sunday Mornings, die zwischen Mitte März und Pfingsten 2020 gefeiert und via YouTube gestreamt wurden, genauer untersucht. In Anlehnung an die Religious Fundamentalism Scale (Altemeyer/ Hunsberger 2005) werden zunächst spezifische Parameter entwickelt, anhand derer eine Kategorisierung und Einordnung von Inhalten und Ausdrucksformen in Bezug auf Fundamentalismus ermöglicht wird. Ziel ist es, einen Beitrag zu einem religionspädagogisch differenzierten Blick auf neue religiöse (Jugend-)Bewegungen zu leisten, der Polarisierungen Widerstand bietet, und damit nach Herausforderungen und Anknüpfungspunkten für religiöse Bildung zu suchen.

Tumours exhibit notable metabolic alterations compared with their corresponding normal tissue counterparts. These metabolic alterations can support anabolic growth, enable survival in hostile environments and regulate gene expression programmes that promote malignant progression. Whether these metabolic changes are selected for during malignant transformation or can themselves be drivers of tumour initiation is unclear. However, intriguingly, many of the major bottlenecks for tumour initiation - control of cell fate, survival and proliferation - are all amenable to metabolic regulation. In this article, we review evidence demonstrating a critical role for metabolic pathways in processes that support the earliest stages of tumour development. We discuss how cell-intrinsic factors, such as the cell of origin or transforming oncogene, and cell-extrinsic factors, such as local nutrient availability, promote or restrain tumour initiation. Deeper insight into how metabolic pathways control tumour initiation will improve our ability to design metabolic interventions to limit tumour incidence. [ABSTRACT FROM AUTHOR]

Aberrant innate immune responses to the gut microbiota are causally involved in the pathogenesis of inflammatory bowel diseases (IBD). The exact triggers and main signaling pathways activating innate immune cells and how they modulate adaptive immunity in IBD is still not completely understood. Here, we report that the PI3K/PTEN signaling pathway in dendritic cells enhances IL-6 production in a model of DSS-induced colitis. This results in exacerbated Th1 cell responses and increased mortality in DC-specific PTEN knockout (PTENΔDC) animals. Depletion of the gut microbiota using antibiotics as well as blocking IL-6R signaling rescued mortality in PTENΔDC mice, whereas adoptive transfer of Flt3L-derived PTEN-/- DCs into WT recipients exacerbated DSS-induced colitis and increased mortality. Taken together, we show that the PI3K signaling pathway in dendritic cells contributes to disease pathology by promoting IL-6 mediated Th1 responses. [ABSTRACT FROM AUTHOR]

Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health. [ABSTRACT FROM AUTHOR]

Bone loss is one of the consequences of aging, leading to diseases such as osteoporosis and increased susceptibility to fragility fractures and therefore considerable morbidity and mortality in humans. Here, we identify microRNA‐146a (miR‐146a) as an essential epigenetic switch controlling bone loss with age. Mice deficient in miR‐146a show regular development of their skeleton. However, while WT mice start to lose bone with age, animals deficient in miR‐146a continue to accrue bone throughout their life span. Increased bone mass is due to increased generation and activity of osteoblasts in miR‐146a‐deficient mice as a result of sustained activation of bone anabolic Wnt signaling during aging. Deregulation of the miR‐146a target genes Wnt1 and Wnt5a parallels bone accrual and osteoblast generation, which is accompanied by reduced development of bone marrow adiposity. Furthermore, miR‐146a‐deficient mice are protected from ovariectomy‐induced bone loss. In humans, the levels of miR‐146a are increased in patients suffering fragility fractures in comparison with those who do not. These data identify miR‐146a as a crucial epigenetic temporal regulator which essentially controls bone homeostasis during aging by regulating bone anabolic Wnt signaling. Therefore, miR‐146a might be a powerful therapeutic target to prevent age‐related bone dysfunctions such as the development of bone marrow adiposity and osteoporosis. [ABSTRACT FROM AUTHOR]

It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL- 6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL- 6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice. [ABSTRACT FROM AUTHOR]

MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as autoimmune processes. Importantly, it has been shown to regulate several antiviral responses, but its contribution to the immune response against cytopathic viruses such as vesicular stomatitis virus (VSV) infections is not known. Using transgenic/recombinant VSV expressing ovalbumin, we show that miR-155 is crucially involved in regulating the T helper cell response against this virus. Our experiments indicate that miR-155 in CD4+ T cells controls their activation, proliferation, and cytokine production in vitro and in vivo upon immunization with OVA as well as during VSV viral infection. Using intravital multiphoton microscopy we analyzed the interaction of antigen presenting cells (APCs) and T cells after OVA immunization and found impaired complex formation when using miR-155 deficient CD4+ T cells compared to wildtype CD4+ T cells ex vivo. In contrast, miR-155 was dispensable for the maturation of myeloid APCs and for their T cell stimulatory capacity. Our data provide the first evidence that miR-155 is required for efficient CD4+ T cell activation during anti-viral defense by allowing robust APC-T cell interaction required for activation and cytokine production of virus specific T cells. [ABSTRACT FROM AUTHOR]

Objectives: Bone destruction in rheumatoid arthritis is mediated by osteoclasts (OC), which are derived from precursor cells of the myeloid lineage. The role of the two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2) and non-classical monocytes (which are CD115 positive, but low in Ly6C and CCR2), in serving as precursors for OC in arthritis is still elusive.Methods: We investigated CCR2-/- mice, which lack circulating classical monocytes, crossed into hTNFtg mice for the extent of joint damage. We analysed monocyte subsets in hTNFtg and K/BxN serum transfer arthritis by flow cytometry. We sorted monocyte subsets and analysed their potential to differentiate into OC and their transcriptional response in response to RANKL by RNA sequencing. With these data, we performed a gene ontology enrichment analysis and gene set enrichment analysis.Results: We show that in hTNFtg arthritis local bone erosion and OC generation are even enhanced in the absence of CCR2. We further show the numbers of non-classical monocytes in blood are elevated and are significantly correlated with histological signs of joint destruction. Sorted non-classical monocytes display an increased capacity to differentiate into OCs. This is associated with an increased expression of signal transduction components of RANK, most importantly TRAF6, leading to an increased responsiveness to RANKL.Conclusion: Therefore, non-classical monocytes are pivotal cells in arthritis tissue damage and a possible target for therapeutically intervention for the prevention of inflammatory joint damage. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy. Methods: Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed. Results: 646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p<0.001), parity (p<0.001), use of assisted reproduction techniques (p = 0.018), maternal and paternal migration background (p<0.001), and maternal and paternal education level (p<0.001). ROC evaluation of the selected prediction model revealed an area under the curve of 0.83 (95%CI: 0.8–0.86), yielding sensitivity and specificity values of 0.69 and 0.86, respectively. Conclusion: We identified predictors of maternal CMV serostatus in early pregnancy and developed a risk-predicting model based on baseline epidemiological characteristics. Our findings provide easy accessible information that can influence the counseling of pregnant woman in terms of their CMV-associated risk. [ABSTRACT FROM AUTHOR]

The PI3K signaling cascade in APCs has been recognized as an essential pathway to initiate, maintain, and resolve immune responses. In this study, we demonstrate that a cell type-specific loss of the PI3K antagonist phosphatase and tensin homolog (PTEN) in myeloid cells renders APCs toward a regulatory phenotype. APCs deficient for PTEN exhibit reduced activation of p38 MAPK and reduced expression of T cell-polarizing cytokines. Furthermore, PTEN deficiency leads to upregulation of markers for alternative activation, such as Arginase 1, with concomitant downregulation of inducible NO synthase in APCs in vitro and in vivo. As a result, T cell polarization was dysfunctional in PTEN-/- APCs, in particular affecting the Th17 cell subset. Intriguingly, mice with cell type-specific deletions of PTEN-targeting APCs were protected from experimental autoimmune encephalomyelitis, which was accompanied by a pronounced reduction of IL-17- and IL-22-producing autoreactive T cells and reduced CNS influx of classically activated monocytes/macrophages. These observations support the notion that activation of the PI3K signaling cascade promotes regulatory APC properties and suppresses pathogenic T cell polarization, thereby reducing the clinical symptoms and pathology of experimental autoimmune encephalomyelitis. [ABSTRACT FROM AUTHOR]

Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tract infections is unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM) and explored the function of TREM-2 in the innate immune response to pneumococcal infection in vivo. Unexpectedly, we found Trem-2−/− AM to display augmented bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically, we detected that in the absence of TREM-2, pulmonary macrophages selectively produced elevated complement component 1q (C1q) levels. We found that these increased C1q levels depended on peroxisome proliferator-activated receptor-δ (PPAR-δ) activity and were responsible for the enhanced phagocytosis of bacteria. Upon infection with S. pneumoniae, Trem-2−/− mice exhibited an augmented bacterial clearance from lungs, decreased bacteremia and improved survival compared to their WT counterparts. This work is the first to disclose a role for TREM-2 in clinically relevant respiratory tract infections and demonstrates a previously unknown link between TREM-2 and opsonin production within the lungs. [ABSTRACT FROM AUTHOR]

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes. [ABSTRACT FROM AUTHOR]

Background: Spermidine is the most abundant polyamine in the human body, but its intracellular concentrations decrease with ageing. Spermidine supplementation reportedly protected against age‐related changes in cognition and brain structures in fruit flies (Gupta et al, 2013), and increased memory performance in older human adults (Wirth et al, 2018). However, the effects of dietary spermidine intake on brain‐related outcomes are unclear. Therefore, we evaluated whether and how dietary spermidine is cross‐sectionally associated with cognitive function and brain structures in a population‐based sample. Methods: We based our analyses on participants from the Rhineland study with complete nutritional and cognitive assessment (n=2906, age 54.8±13.5 years), and with complete nutritional assessment and T1‐MRI scans (n=2264, age 54.1±13.4 years). Habitual dietary spermidine intake was estimated through a validated food frequency questionnaire. Cognitive performance was measured using eight cognitive tests that assessed performance in multiple domains (processing speed, executive functions, working and episodic verbal memory). These domains were summarized using z‐score averaging, producing a global cognitive function score. Brain volumetric measures (total brain, white and grey matter, cortex and hippocampus) were obtained using Freesurfer (Fischl et al, 2002). We quantified the relation between spermidine intake and the outcomes with multivariate linear models adjusted for age, sex and education. For brain volumes, models were additionally adjusted for estimated total intracranial volume. Results: The mean dietary intake of spermidine was 55.1±21.4 μmol/day. Higher spermidine intake (per SD increase) was associated with better global cognitive performance (ß=0.02, 95%CI=0.001 ‐ 0.03), and processing speed (ß=0.03, 95%CI=0.004 ‐ 0.05) and episodic verbal memory (ß=0.03, 95%CI=0.001 ‐ 0.06) domains. Conversely, dietary spermidine intake was not or inversely associated with brain volumetric measures (cortex: ß =‐0.91, 95%CI=‐1.82 – ‐0.02; left hippocampus: ß =‐0.01, 95%CI=‐0.03 – ‐0.002). Conclusions: Our results confirmed a positive association between dietary spermidine intake and better global cognitive function. However, we also found higher dietary spermidine intake to be associated with smaller cortical and left hippocampal volume. These seemingly contradictory results underscore the need for further research to better understand the effects of spermidine in cognition and brain related outcomes as well as the biological mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Metabolic networks support cancer cell survival, proliferation, and malignant progression. Cancer cells take up large amounts of nutrients such as glucose and glutamine whose metabolism provides the energy, reducing equivalents, and biosynthetic precursors required to meet the biosynthetic demands of proliferation. Intermediates of glycolysis and the tricarboxylic acid (TCA) cycle provide critical building blocks for synthesis of non-essential amino acids, nucleotides, and fatty acids. To view this SnapShot, open or download the PDF. [ABSTRACT FROM AUTHOR]

The activation of innate immune cells triggers numerous intracellular signaling pathways, which require tight control to mount an adequate immune response. The PI3K signaling pathway is intricately involved in innate immunity, and its activation dampens the expression and release of proinflammatory cytokines in myeloid cells. These signaling processes are strictly regulated by the PI3K antagonist, the lipid phosphatase, PTEN, a known tumor suppressor. Importantly, PTEN is responsible for the elevated production of cytokines such as IL-6 in response to TLR agonists, and deletion of PTEN results in diminished inflammatory responses. However, the mechanisms by which PI3K negatively regulates TLR signaling are only partially resolved. We observed that Arginase I expression and secretion were markedly induced by PTEN deletion, suggesting PTEN 7' macrophages were alternatively activated. This was mediated by increased expression and activation of the transcription factors C/EBPβ and STAT3. Genetic and pharmacologic experimental approaches in vitro, as well as in vivo autoimmunity models, provide convincing evidence that PI3K/ PTEN-regulated extracellular Arginase .1 acts as a paracrine regulator of inflammation and immunity. [ABSTRACT FROM AUTHOR]