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Social cohesion among Syrian and Turkish children, adolescents, and young adults in Turkey: Data from Turkey
No full textAbstract This data set provides information about basic social-demographic characteristics and social cohesion among young Turkish nationals and Syrian refugees. Information on different dimensions of social cohesion such as belongingness, trust, altruism and social relations, along with socio-demographic information, was collected from a sample of 1305 adolescents and young adults (12–30 years), and 685 children (6–11 years). Data was collected through field interviews between November 2018 – January 2019 in Ankara, Istanbul, and in the bordering cities of Mardin, Gaziantep, Hatay and Şanlıurfa. The sample was selected using a cluster randomised design among the participants of the “Education Program for Syrian Refugees and Host Communities” (BILSY) program conducted by the German Corporation for International Cooperation (GIZ) in Turkey
Photoactivatable and photolabile pharmacophores: lessons learned from capsaicin
No full textStructurally merging light-susceptible with bioactive molecules allows to generate photolabile chromopharmacophores. Using capsaicinoids, chromopharmacophores could activate the TRPV1 channel, while no activation is observed for the photoproducts.Light-controlled molecules have become valuable tools for studying biological systems offering an unparalleled control in space and time. Specifically, the remote-controllable (de)activation of small molecules is attractive both to study molecular processes from a fundamental point of view and to develop future precision therapeutics. While pronounced changes through light-induced cleavage of photolabile protecting groups and the accompanying liberation of bioactive small molecules have become a highly successful strategy, approaches that focus solely on the revert process, i.e. the photochemical deactivation of bioactive agents, are sparse. In this work, we studied whether a given bioactive compound could be made photolability by structural design. We thus used the example of capsaicinoids, which control the transient receptor potential cation channel subfamily V member 1 (TRPV1), to generate both suitable light activation and deactivation strategies.Structurally merging light-susceptible with bioactive molecules allows to generate photolabile chromopharmacophores. Using capsaicinoids, chromopharmacophores could activate the TRPV1 channel, while no activation is observed for the photoproducts.Light-controlled molecules have become valuable tools for studying biological systems offering an unparalleled control in space and time. Specifically, the remote-controllable (de)activation of small molecules is attractive both to study molecular processes from a fundamental point of view and to develop future precision therapeutics. While pronounced changes through light-induced cleavage of photolabile protecting groups and the accompanying liberation of bioactive small molecules have become a highly successful strategy, approaches that focus solely on the revert process, i.e. the photochemical deactivation of bioactive agents, are sparse. In this work, we studied whether a given bioactive compound could be made photolability by structural design. We thus used the example of capsaicinoids, which control the transient receptor potential cation channel subfamily V member 1 (TRPV1), to generate both suitable light activation and deactivation strategies.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Vetenskapsrådet https://doi.org/10.13039/501100004359Dr. Rolf M. Schwiete Stiftung https://doi.org/10.13039/50110002002
Magenschrittmacher-Update: Relevanz bei Gastroparese
No full textZusammenfassung Die Gastroparese stellt eine Erkrankung dar, bei der die Magenentleerung in Abwesenheit einer mechanischen Obstruktion des Magenausgangs erheblich eingeschränkt ist. Neben medikamentös-konservativen Maßnahmen stellt die gastrale Elektrostimulation (GES) bei refraktären Verläufen eine mögliche Therapiealternative dar. Allerdings lässt die Datenlage aus randomisierten kontrollierten Studien zur Wirksamkeit keine uneingeschränkte Empfehlung zu. Ziel dieser Übersichtsarbeit ist neben der Einführung in das Krankheitsbild der Gastroparese inkl. der zugrunde liegenden Pathophysiologie die Einordnung der therapeutischen Rolle der GES anhand der aktuell verfügbaren Literatur. Insbesondere werden Indikationen und Limitationen der Therapie aufgezeigt, bevor mögliche Optimierungen der Therapie skizziert und ein Ausblick auf ein mögliches innovatives Therapieverfahren in der Zukunft gegeben werden
Mesozoic atmospheric CO 2 concentrations reconstructed from dinosaur tooth enamel
No full textAir-breathing vertebrates incorporate a fraction of isotopically anomalous air O 2 in their body water. The 17 O isotope anomaly of air O 2 (expressed as Δ’ 17 O air ) is related to atmospheric CO 2 concentrations ( p CO 2 ) and gross primary production (GPP). Tooth enamel records the Δ’ 17 O of body water and can thus preserve such paleo- p CO 2 or paleo-GPP information over geological time periods. Here, we demonstrate the potential of respective reconstructions of atmospheric p CO 2 or GPP from the triple oxygen isotope composition of fossil dinosaur tooth enamel. The data from unaltered enamel samples, along with an assumed modern GPP t /GPP 0 ratio of 1 for the Mesozoic, suggest a mean Late Jurassic p CO 2 = 1,200 ± 150 ppmv and Late Cretaceous p CO 2 = 750 ± 200 ppmv. These estimates are in good agreement with other p CO 2 proxy data for the same time intervals. When utilizing a p CO 2 inferred from other proxies, tooth enamel Δ’ 17 O PO4 may also serve as a proxy for GPP. Using published p CO 2 data, we reconstructed GPP t /GPP 0 ratios with 1.20 ± 0.17 for the Late Jurassic and 2.24 ± 0.96 for the Late Cretaceous, which would imply a 20 to 120% higher GPP in the Mesozoic than today. Overall, triple oxygen isotope analysis of fossil teeth of terrestrial amniotes can provide insights into past atmospheric greenhouse gas content and global primary productivity.German science foundationDFG Heisenberg grantVeWA consortium LOEWE progra
Exploiting algal strains for robust cross‐domain phytoplankton classification via deep learning
No full textAbstract Phytoplankton species are essential bioindicators for evaluating the status of freshwater ecosystems in accordance with the EU Water Framework Directive. However, manual identification of phytoplankton is time‐consuming and requires taxonomic expertise. Deep learning (DL) offers promising tools for automating the identification, but challenges remain due to imaging biases, morphological diversity, and the lack of validated benchmark datasets. In this study, we trained a DL model on microphotographs of controlled laboratory strains from 20 phytoplankton species and tested its performance on independent environmental image datasets. We assessed which species are suitable for cross‐dataset classification and explored whether computer vision–based image representations (DL features) reflect species similarity across datasets. Additionally, we combined shape analysis with DL features to determine whether feature‐based species distances correspond to morphological similarity. The model trained on strain images achieved reliable cross‐dataset classification for over half of the species. Classification performance declined with increasing feature/domain shifts between training and test images but improved when environmental images enriched the training set. Morphologically distinctive species, such as star‐like forms and those with lobes or bristles, exhibited higher classification rates, whereas rectangular or roundish forms posed greater challenges. DL features consistently clustered species across datasets, and the distances in DL feature space aligned with those in simplified shape space. Our findings demonstrate that using strains as references in DL models enables effective cross‐dataset classification while capturing morphological patterns. Integrating taxonomic expertise with computer vision is crucial for developing robust, interpretable phytoplankton bioindicator systems for ecological monitoring and biodiversity research.Bundesministerium für Umwelt, Naturschutz, nukleare Sicherheit und Verbraucherschutz https://doi.org/10.13039/501100013549Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
Mutual reinforcement of lymphotoxin-driven myositis and impaired autophagy in murine muscle
No full textAbstract Inclusion body myositis (IBM) is a progressive muscle disorder characterized by inflammation and degeneration with altered proteostasis. To better understand the interrelationship between these two features, we aimed at establishing a novel preclinical mouse model. First, we used quantitative PCR to determine expression of pro-inflammatory chemo- and cytokines including lymphotoxin (LT)-signaling pathway components in human skeletal muscle tissue diagnosed with myositis. Based on these results we generated a mouse model that we analyzed at the histological, ultrastructural, transcriptional, biochemical, and behavioral level. Lastly, we subjected this model to anti-inflammatory treatments. After confirming and extending previous data on activation of lymphotoxin (LT)-signaling in human myositis, we generated distinct transgenic mouse lines co-expressing LTα and -β in skeletal muscle fibers. Transgenic mice displayed chronic myositis accompanied by dysregulated proteostasis, including an altered autophagolysosomal pathway that initially shows signs of activation and later exhaustion and decreased flux. To enhance the latter, we genetically impaired autophagy in skeletal muscle cells. Autophagy impairment alone induced a pro-inflammatory transcriptional state, but no obvious cellular inflammation. However, the combination of LT-driven myositis with autophagy impairment induced the full spectrum of characteristic molecular and pathological features of IBM in skeletal muscle, including protein inclusions with typical ultrastructural morphology and mild mitochondrial pathology. Our attempts to treat the pathology by subjecting these mice to corticosteroids or anti-Thy1.2 antibodies mirrored recent treatment failures in humans, i.e., none of these treatments resulted in significant clinical improvement of motor performance or the transcriptional profile of muscle pathology. In summary, these data provide evidence that inflammation and autophagy disruption play a synergistic role in the development of IBM-like muscular pathology. Furthermore, once established, IBM-like pathology in these mice, as in human IBM patients cannot be reverted or prevented from progression by conventional means of immunosuppression. We expect that this novel mouse model will help to identify future treatment modalities for IBM
Translocations can drive expression changes of multiple genes in regulons covering entire chromosome arms
No full textAbstract Chromosomal translocations have largely been implicated in tumor development. However, beyond the consequences of aberrant gene expression near the breakpoint, their effects remain underexplored. In this work, we characterize the interplay between translocations, chromatin organization and gene expression using mantle cell lymphoma (MCL) as a model. We show by in vitro genomic engineering and in MCL patient samples that translocations can drive transcriptional changes at entire chromosome arms affecting multiple genes in a regulon-like fashion. Moreover, we demonstrate a clear link between the translocation-induced transcriptional alterations and genome organization, with genes most susceptible to change expression forming pre-existing ultra-long-range interactions spanning 50 megabases. The translocation involves the strong immunoglobulin enhancer into this 3D interaction, allowing the spread of its regulatory potential over the entire affected chromosome arm. Finally, we show that translocation-induced effects mainly represent expression enhancement of genes already active prior to translocation formation, highlighting the importance of the epigenetic state of the cell in which this initial hit occurs. In summary, by studying genome organization principles in the context of translocations, we describe a new principle of gene regulation, showing that strong enhancers can induce substantial gene expression enhancement through ultra-long-range interactions affecting entire chromosome arms, representing an important new mechanism in health and disease
Adolescent Schooling and Adult Labor Supply: Evidence from COVID-19 School Closures and Reopenings in Kenya
No full textAbstract This study identifies the impact of a shock to adolescent school availability—potentially affecting both household childcare burdens and child labor—on adult labor supply in the context of COVID-19-related school closures in Kenya. Using nationally representative bi-monthly panel data, the analysis compares changes in outcomes after schools partially reopened in October 2020 for households with children in a grade eligible to return against those with children in adjacent grades. An adolescent returning to school increases adults’ weekly work by 4.3 hours (27 percent) in the short run, concentrated among the most flexible margins of adjustment and particularly household agriculture. Contrary to evidence from high-income settings, overall effects are not gendered. There are no effects of the partial reopening on respondent childcare hours and heterogeneity in labor-supply effects by household characteristics does not align with predictions based on a childcare mechanism. Instead, the results indicate that increased adult work hours substitute for reduced child work in household agriculture as a child goes back to school. Impacts on labor supply are driven by less wealthy households with children engaged in household agriculture, while wealthier agricultural households substitute child labor with increased hired labor. The results show that adolescent schooling has important consequences for household production and labor-supply decisions. Poor agricultural households face particularly high opportunity costs for children’s education
GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function
No full textAbstract Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RAs) ameliorate mitochondrial health by increasing mitochondrial turnover in metabolically relevant tissues. Mitochondrial adaptation to metabolic stress is crucial to maintain pancreatic β-cell function and prevent type 2 diabetes (T2D) progression. While the GLP-1R is well-known to stimulate cAMP production leading to Protein Kinase A (PKA) and Exchange Protein Activated by cyclic AMP 2 (Epac2) activation, there is a lack of understanding of the molecular mechanisms linking GLP-1R signalling with mitochondrial and β-cell functional adaptation. Here, we present a comprehensive study in β-cell lines and primary islets that demonstrates that, following GLP-1RA stimulation, GLP-1R-positive endosomes associate with the endoplasmic reticulum (ER) membrane contact site (MCS) tether VAPB at ER-mitochondria MCSs (ERMCSs), where active GLP-1R engages with SPHKAP, an A-kinase anchoring protein (AKAP) previously linked to T2D and adiposity risk in genome-wide association studies (GWAS). The inter-organelle complex formed by endosomal GLP-1R, ER VAPB and SPHKAP triggers a pool of ERMCS-localised cAMP/PKA signalling via the formation of a PKA-RIα biomolecular condensate which leads to changes in mitochondrial contact site and cristae organising system (MICOS) complex phosphorylation, mitochondrial remodelling, and β-cell functional adaptation, with important consequences for the regulation of β-cell insulin secretion and survival to stress