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Toward a critical study of boundaries in and around organizations:Introduction to the Special Issue
Get PDFThis introduction to the Special Issue makes the political implications of boundaries in and around organizations the central locus of inquiry. It explores the experiences and interests of those who encounter marginalization and exclusion through processes of boundary drawing. Next to introducing the individual papers of the Special Issue and identifying overlapping themes across them, we highlight opportunities to inspire future research on the ambivalence of the enabling and constraining effects of boundaries, the role of different power positions for negotiating boundaries, how boundaries are brought in and out of consciousness and how boundaries are connected with (inter)national boundary drawing.</p
Assessing the Quality of Narrative Feedback in Entrustable Professional Activities Using the EFeCT Feedback Scoring Tool
Get PDFBackground: Competency-based medical education (CBME) is the cornerstone of undergraduate training in Canada. Entrustable professional activities (EPAs) assess competency in professional tasks, with narrative feedback being a key component. There is currently a lack of published literature on the quality of narrative feedback in EPA observations in undergraduate medical education. This study explores the quality of narrative feedback in EPA observations provided to medical students. Methods: The quality of narrative feedback in a random sample of anonymised EPA observations from Year 3 students was evaluated using the Evaluation of Feedback Captured Tool (EFeCT). The EFeCT tool explores five facets of quality feedback, with a score of five indicating high-quality feedback. Three evaluators independently assessed the quality of narrative feedback using the EFeCT tool. Any differences in score were resolved through discussion to reach consensus. Results: In the 2022–2023 academic year, 15,240 EPA observations were completed for year 3 students. A subset of 748 observations was analysed. Of these, one scored 0, seven scored 1, 33 scored 2, 115 scored 3, 151 scored 4 and 441 scored 5 on the EFeCT tool. The mean EFeCT score was 4.3. Conclusions: Overall, the majority of EPA narratives provided moderate to high-quality feedback to students. However, variability was evident, and many EPA narratives were missing one or more elements of high-quality feedback. This could result in significant implications for learner development. Addressing contextual factors such as clinical workload and creating faculty development opportunities may support faculty in providing high-quality narrative feedback.</p
The electrophilic metabolite of kynurenine, kynurenine-CKA, requires C151 in Keap1 to derepress Nrf2
Get PDFThe Kelch-like ECH-associated protein 1 / Nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) system responds to a wide array of structurally diverse small molecules, of both exogenous and endogenous origin, by inducing a robust cytoprotective program that allows adaptation during oxidative, metabolic and inflammatory stress. Here, we report that exposure to the tryptophan metabolite kynurenine and its electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA) leads to an increase in the abundance of transcription factor Nrf2 and Induction of Nrf2-target genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), in murine and human cells. Additionally, both kynurenine and Kyn-CKA activate the aryl hydrocarbon receptor (AhR). Using cellular thermal shift assays, we found that Kyn-CKA increases the thermal stability of Keap1-mCherry fusion protein, but not free mCherry, indicating target engagement of Keap1, the principal repressor of Nrf2. Critically, the ability of Kyn-CKA to increase the abundance of Nrf2 and expression of NQO1 in mouse embryonic fibroblasts (MEFs) expressing wild-type Keap1 was greatly diminished in C151S-Keap1 mutant MEFs. Furthermore, Kyn-CKA reacts with Keap1 C151 much faster in vitro than with the small molecule thiol N-acetyl cysteine, suggesting that Kyn-CKA is targeted to C151 by the surrounding active site. Experiments in wild-type, AhR-knockout, and Nrf2- knockout primary murine bone marrow-derived macrophages showed that Nrf2 is required for the acute anT-inflammatory activity of Kyn-CKA, whereas AhR is dispensable. Together, these findings demonstrate that Kyn-CKA requires C151 in Keap1 to derepress Nrf2 and reveal that Nrf2, but not AhR, is a main contributor to the anti-inflammatory activity of Kyn-CKA in macrophages
Evolutionary transcriptomics unveils rapid changes of gene expression patterns in flowering plants
Get PDFThe evolutionary history of angiosperms (flowering plants) is characterized by a highly accelerated rate of diversification. Although a number of hypotheses have been proposed to explain the ecological success and rapid rise of angiosperms, the molecular mechanisms underlying their speciation are only partially understood. In this study, we analyzed the developmental transcriptomes of seven angiosperm species spanning 160 million years of evolution. We demonstrate that angiosperm protein-coding gene expression patterns diverged rapidly. Particularly high rates of expression changes were found for genes that are involved in the response to endogenous and environmental stimuli, promoting broad ecological tolerances, adaptive evolution, and speciation. This study highlights how ecological and evolutionary dynamics are highly interrelated, shows that the rates of expression divergence differ from those previously described for mammals, and provides a comprehensive resource to perform cross-kingdom comparative studies of transcriptome evolution.</p
The synthesis of antibacterial ZnO nanoparticle incorporated polyethersulfone (PES) membranes through green chemistry
Get PDFIn conventional fabrication methods of polymer membranes, toxic solvents are widely used that result in significant water pollution, additionally, membrane function can be enhanced by the incorporation of nanoparticles (NP) to impart properties into them such as antimicrobial activity. To identify if a more environmentally friendly solvent can replace toxic solvents whilst enhancing membrane functionally by NPs, N,N-dimethyl lactamide (DML) was employed in the synthesis of polyethersulfone (PES) membranes and its performance was compared with the traditionally used toxic solvent of N-methyl-2-pyrrolidone (NMP). The successful synthesis of PES by DML and NMP with varying concentrations of Zinc Oxide (ZnO) NPs were achieved and were systematically characterized via different techniques to evaluate their structure, morphology, and performance. The results show that the DML-based PES–ZnO membranes exhibit a more uniform pore size distribution and higher porosity than the NMP-based PES membranes. Antibacterial tests further demonstrated that, at the same ZnO NPs concentration, the DML-based PES membrane offers a superior antimicrobial activity, highlighting DML to be a promising green chemical to replace NMP for sustainable synthesis of NP enhanced PES membranes
A transcriptomic and proteomic map of primary human cell types
Get PDFMolecular profiling of human primary cell types is essential for understanding human biology. We present a transcriptome and proteome map of 28 primary human cell types. Three major clusters of epithelial, endothelial, and mesenchymal cell types were observed in both the transcriptome and proteome levels along with the discovery of cell type enriched molecules including GRAP and C1orf116. The epithelial cell specific protein C1orf116 was further validated using immunohistochemistry across various human tissues. An exhaustive protein database search considering 39 post-translational modifications (PTMs) revealed novel insights into the PTM landscape including identification of understudied PTMs such as serine O-acetylation and histidine methylation. This also enabled comprehensive characterization of proteins with diverse PTMs. Interestingly, an unexpectedly higher frequency of dioxidation on tryptophan compared to methionine led to the identification of oxidative mitochondria complex subunit proteins. Further, a search strategy accounting for alternative translational start sites, splice junctions and translational readthrough refined genome annotation using proteomic evidence. For example, peptides from translational readthrough including extended sequence of LDHB and MDH1 were detected representing the first peptide-level evidence of these protein readthrough isoforms. Our comprehensive transcriptome and proteome data revealed cell type-specific molecular cues and heterogeneity, offering new insights into disease mechanisms often overlooked by tissue proteomics.</p
European Code Against Cancer, 5th edition – tobacco and nicotine containing products, second-hand smoke, alcohol and cancer
Get PDFTobacco use, second-hand tobacco smoke (SHS) exposure and alcohol consumption are well-established carcinogens and major public health concerns. In the European Union (EU), tobacco and alcohol use are the leading preventable causes of cancer and four other major noncommunicable diseases (NCDs), significantly contributing to NCD-related morbidity and mortality. Despite declining prevalence, consumption of these substances is still high in the region, especially among the most deprived. There is strong evidence that quitting smoking, minimising exposure to SHS and eliminating or reducing alcohol intake substantially lowers the risk of cancer. Comprehensive public health strategies at both the individual and population level are crucial to prevent cancer and other NCDs. Scientific evidence leads to two recommendations for individual action on tobacco in the European Code Against Cancer, 5th edition: (1) ‘Do not smoke. Do not use any form of tobacco, or vaping products. If you smoke, you should quit’; and (2) ‘Keep your home and car free of tobacco smoke’; and one on alcohol: (3) ‘Avoid alcoholic drinks’.</p
The Voice and Lived Experiences of Young People (YP) with Special Educational Needs and Disability (SEND), during Primary - Secondary School Transitions
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Toward a critical study of boundaries in and around organizations:Introduction to the Special Issue
Get PDFThis introduction to the Special Issue makes the political implications of boundaries in and around organizations the central locus of inquiry. It explores the experiences and interests of those who encounter marginalization and exclusion through processes of boundary drawing. Next to introducing the individual papers of the Special Issue and identifying overlapping themes across them, we highlight opportunities to inspire future research on the ambivalence of the enabling and constraining effects of boundaries, the role of different power positions for negotiating boundaries, how boundaries are brought in and out of consciousness and how boundaries are connected with (inter)national boundary drawing.</p
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