Machtvolle Räume. Räume für Inklusion und Teilhabe am Arbeitsmarkt, reflektiert vor dem Hintergrund sozialer Ungleichheitslagen

Tomke S. Gerdes befasst sich mit der wichtigen Frage der sozialen Teilhabe im Lebensraum „Arbeit“. Dabei fokussiert die Autorin auf Menschen mit psychischen Beeinträchtigungen, greift jedoch ebenfalls „soziale Ungleichheitslagen“ in Form verschiedener intersektionaler Perspektiven auf. (DIPF/Orig.

Zincation of 4,4-dimethyloxazoline using TMPZnCl·LiCl

Various functionalized aryl and heteroaryl aluminum reagents were obtained by performing I-Li or Br-Li exchange reactions with the corresponding unsaturated organic halides in the presence of i-Bu2AlCl. By means of an appropriate catalyst, the resulting new aluminum species were directly acylated, allylated or arylated. 1,4-Michael additions to enones have also been achieved

A polysaccharide utilization locus from the gut bacterium dysgonomonas mossii encodes functionally distinct carbohydrate esterases

The gut microbiota plays a central role in human health by enzymatically degrading dietary fiber and concomitantly excreting short chain fatty acids that are associated with manifold health benefits. The polysaccharide xylan is abundant in dietary fiber but noncarbohydrate decorations hinder efficient cleavage by glycoside hydrolases (GHs) and need to be addressed by carbohydrate esterases (CEs). Enzymes from carbohydrate esterase families 1 and 6 (CE1 and 6) perform key roles in xylan degradation by removing feruloyl and acetate decorations, yet little is known about these enzyme families especially with regard to their diversity in activity. Bacteroidetes bacteria are dominant members of the microbiota and often encode their carbohydrate-active enzymes in multigene polysaccharide utilization loci (PULs). Here we present the characterization of three CEs found in a PUL encoded by the gut Bacteroidete Dysgonomonas mossii. We demonstrate that the CEs are functionally distinct, with one highly efficient CE6 acetyl esterase and two CE1 enzymes with feruloyl esterase activities. One multidomain CE1 enzyme contains two CE1 domains: an N-terminal domain feruloyl esterase, and a C-terminal domain with minimal activity on model substrates. We present the structure of the C-terminal CE1 domain with the carbohydrate-binding module that bridges the two CE1 domains, as well as a complex of the same protein fragment with methyl ferulate. The investment of D. mossii in producing multiple CEs suggests that improved accessibility of xylan for GHs and cleavage of covalent polysaccharide-polysaccharide and lignin-polysaccharide bonds are important enzyme activities in the gut environment

MRI radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models

BackgroundRadiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy.MethodsMice orthotopically implanted with a patient-derived grade 3 endometrioid endometrial cancer organoid model (O-PDX) were allocated to chemotherapy (combined paclitaxel/carboplatin, n=11) or saline/control (n=13). During tumor progression, the mice underwent weekly T2-weighted (T2w) magnetic resonance imaging (MRI). Segmentation of primary tumor volume (vMRI) allowed extraction of radiomic features from whole-volume tumor masks. A radiomic model for predicting treatment response was derived employing least absolute shrinkage and selection operator (LASSO) statistics at endpoint images in the orthotopic O-PDX (RS_O), and subsequently applied on the earlier study timepoints (RS_O at baseline, and week 1-3). For external validation, the radiomic model was tested in a separate T2w-MRI dataset on segmented whole-volume subcutaneous tumors (RS_S) from the same O-PDX model, imaged at three timepoints (baseline, day 3 and day 10/endpoint) after start of chemotherapy (n=8 tumors) or saline/control (n=8 tumors).ResultsThe RS_O yielded rapidly increasing area under the receiver operating characteristic (ROC) curves (AUCs) for predicting treatment response from baseline until endpoint; AUC=0.38 (baseline); 0.80 (week 1), 0.85 (week 2), 0.96 (week 3) and 1.0 (endpoint). In comparison, vMRI yielded AUCs of 0.37 (baseline); 0.69 (w1); 0.83 (week 2); 0.92 (week 3) and 0.97 (endpoint). When tested in the external validation dataset, RS_S yielded high accuracy for predicting treatment response at day10/endpoint (AUC=0.85) and tended to yield higher AUC than vMRI (AUC=0.78, p=0.18). Neither RS_S nor vMRI predicted response at day 3 in the external validation set (AUC=0.56 for both).ConclusionsWe have developed and validated a radiomic signature that was able to capture chemotherapeutic treatment response both in an O-PDX and in a subcutaneous endometrial cancer mouse model. This study supports the promising role of preclinical imaging including radiomic tumor profiling to assess early treatment response in endometrial cancer models

Whole-brain annotation and multi-connectome cell typing of Drosophila

The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics

The making of European society: contesting methodological nationalism

The paper is concerned with the problem of ‘society’ and in particular with the notion of ‘European society.’ Rather than reject the possibility of society, it draws on theories of the social as networks. The thesis proposed is that the concept of society should rather be understood as a relational field of interconnections. It is argued that this is highly relevant to the analysis of Europe conceived of in terms of a society. This approach can be seen as an alternative to methodological nationalism. The paper applies a network conception of society to Europe with the emphasis on the on the nineteenth century. In this account, European society is not something that was produced by European integration. Rather than see European society as a recent development, it is argued that the field of tensions between capitalism and democracy constituted the major elements that shaped a European model of society

Information flow, cell types and stereotypy in a full olfactory connectome

Funder: Howard Hughes Medical Institute; FundRef: http://dx.doi.org/10.13039/100000011The hemibrain connectome provides large-scale connectivity and morphology information for the majority of the central brain of Drosophila melanogaster. Using this data set, we provide a complete description of the Drosophila olfactory system, covering all first, second and lateral horn-associated third-order neurons. We develop a generally applicable strategy to extract information flow and layered organisation from connectome graphs, mapping olfactory input to descending interneurons. This identifies a range of motifs including highly lateralised circuits in the antennal lobe and patterns of convergence downstream of the mushroom body and lateral horn. Leveraging a second data set we provide a first quantitative assessment of inter- versus intra-individual stereotypy. Comparing neurons across two brains (three hemispheres) reveals striking similarity in neuronal morphology across brains. Connectivity correlates with morphology and neurons of the same morphological type show similar connection variability within the same brain as across two brains

An observation station for culture and tourism in Vietnam: A Forum for World Heritage and Public Participation

Special Issue The Politics of World Heritage: Negotiating Tourism and Conservation (David Harrison, Michael Hitchcock (eds.))info:eu-repo/semantics/publishe

Exploring the working conditions of disabled employees: a scoping review

Abstract Purpose Disabled people are often overlooked in considerations about work design, which contributes to their exclusion from the labor market. This issue also reflects within research, as the body of knowledge on the working conditions of disabled employees remains relatively limited. Methods A scoping review was conducted to assess the research landscape concerning the working conditions of disabled employees. Five databases have been searched, focusing on relevant studies published between 2017 and 2022. Results One hundred fourteen studies were included in the review. It was found that social aspects of work appeared within a substantial portion of the examined studies. Furthermore, it became evident that the interplay of accessibility and flexibility provides an important dynamic to make work design both inclusive and feasible. Conclusion The recurrent prominence of social aspects, accessibility, and flexibility across the studies shows common challenges and potentials within the work situation of disabled employees. This suggests avenues for future research and inclusive work design