Molecular basis for gene-specific transactivation by nuclear receptors

AbstractNuclear receptors (NRs) are key transcriptional regulators of metazoan physiology and metabolism. Different NRs bind to similar or even identical core response elements; however, they regulate transcription in a highly receptor- and gene-specific manner. These differences in gene activation can most likely be accounted for by mechanisms involving receptor-specific interactions with DNA as well as receptor-specific interactions with protein complexes binding to adjacent and distant DNA sequences. Here, we review key molecular aspects of transactivation by NRs with special emphasis on the recent advances in the molecular mechanisms responsible for receptor- and gene-specific transcriptional activation. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease

A framework for implementation, education, research and clinical use of ultrasound in emergency departments by the Danish Society for Emergency Medicine

The first Danish Society for Emergency Medicine (DASEM) recommendations for the use of clinical ultrasound in emergency departments has been made. The recommendations describes what DASEM believes as being current best practice for training, certification, maintenance of acquired competencies, quality assurance, collaboration and research in the field of clinical US used in an ED

On convex conceptual regions in deep network representations

The current study of human-machine alignment aims at understanding the geometry of latent spaces and the correspondence to human representations. G\"ardenfors' conceptual spaces is a prominent framework for understanding human representations. Convexity of object regions in conceptual spaces is argued to promote generalizability, few-shot learning, and intersubject alignment. Based on these insights, we investigate the notion of convexity of concept regions in machine-learned latent spaces. We develop a set of tools for measuring convexity in sampled data and evaluate emergent convexity in layered representations of state-of-the-art deep networks. We show that convexity is robust to basic re-parametrization, hence, meaningful as a quality of machine-learned latent spaces. We find that approximate convexity is pervasive in neural representations in multiple application domains, including models of images, audio, human activity, text, and brain data. We measure convexity separately for labels (i.e., targets for fine-tuning) and other concepts. Generally, we observe that fine-tuning increases the convexity of label regions, while for more general concepts, it depends on the alignment of the concept with the fine-tuning objective. We find evidence that pre-training convexity of class label regions predicts subsequent fine-tuning performance

Point-of-care focused lung ultrasound in emergency medicine: Protocol for a scoping review

Baggrund Point-of-care fokuseret lungeultralyd er en central kompetence i akutmedicin. Meta-analyser for diagnostiske studier af point-of-care fokuseret lungeultralyd har vist lovende diagnostiske resultater for pneumothorax, pleura effusion, interstitielt syndrom, lungeemboli og pneumoni. Men manglende evidens på patient-nære endemål og et fåtal af randomiserede kontrollerede studier synes at være begrænsende for den videre implementering af point-of-care ultralyd. En metodisk kortlægning af eksisterende studier indenfor et forskningsfelt kan vejlede fremtidige forskningsindsatser. Formålet med dette review er at give et overblik over original forskning i point-of-care fokuseret lungeultralyd i akutmedicin med særlig vægt på studiedesign og patient-relevansen af endemål. Metoder Reviewet designes som et scoping review og det vil inkludere originale studier i point-of-care fokuseret lungeultralyd til voksne patienter i akutafdelinger. Reviewet vil fokusere på point-of-care fokuseret lungeultralyd; studier i fyldestgørende thorakal ultralyd er uden for denne afgrænsning (f.eks. ultralydsundersøgelser som vurderer mediastinale lymfeknuder, diafragma bevægelse, kontrast- eller procedure lunge ultralyd). Vi vil ekskludere studier uden tilgængeligt engelsk manuskript. Grå litteratur og udelukkende kvalitative studier vil ikke blive inkluderet. Reviews, protokoller, meta-analyser, case artikler, letters, og konference abstrakts vil blive ekskluderet. Dataudtrækket vil inkludere adskillige metodiske og sonografiske karakteristika (f.eks. sampling metoden [lejlighedsvis/fortløbende], diagnostisk rolle af ultralyd [triage, tillæg, erstatning], antal af sonografører, sonograførernes ekspertise [træning og erfaring] og sonograførernes rolle [behandlende læge eller forsker]. Den narrative syntese af alle inkluderede studier vil blive gennemført med særlig vægt på studie designs og patient-relevans af endemål. Figurer og diagrammer vil opsummere tidsmæssige tendenser, metode karakteristika og endemål. Diskussion Dette scoping review vil tilbyde et overblik som systematiske reviews ikke kan sammenfatte eller kortlægge. Kortlægningen af studie designs og patient-relevans af endemål vil vejlede fremtidige studier og systematiske reviews i forsøget på at vejlede klinikere og patienter til den mest hensigtsmæssige brug af point-of-care fokuseret lungeultralyd i akutmedicin. Reviewet vil også biddrage med et overblik over område-specifikke metodiske og sonografiske karakteristika, som gør det muligt for andre forskere at identificere de utilstrækkeligheder, som bør opgives, og de fremskridt som bør dyrkes

Functional traits—not nativeness—shape the effects of large mammalian herbivores on plant communities

DATA AND MATERIALS AVAILABILITY : All data and the core analysis scripts are provided in Dryad (24).Large mammalian herbivores (megafauna) have experienced extinctions and declines since prehistory. Introduced megafauna have partly counteracted these losses yet are thought to have unusually negative effects on plants compared with native megafauna. Using a meta-analysis of 3995 plot-scale plant abundance and diversity responses from 221 studies, we found no evidence that megafauna impacts were shaped by nativeness, “invasiveness,” “feralness,” coevolutionary history, or functional and phylogenetic novelty. Nor was there evidence that introduced megafauna facilitate introduced plants more than native megafauna. Instead, we found strong evidence that functional traits shaped megafauna impacts, with larger-bodied and bulk-feeding megafauna promoting plant diversity. Our work suggests that trait-based ecology provides better insight into interactions between megafauna and plants than do concepts of nativeness.EDITOR'S SUMMARY : Large herbivores shape ecosystems by consuming vegetation, dispersing seeds, and creating disturbances. Due to extirpations of many large herbivorous mammals and the spread of others by people, many ecosystems host megaherbivores that did not coevolve with the local plant species. Lundgren et al. investigated whether introduced species therefore have stronger and more negative effects on plant abundance and diversity (see the Perspective by Buckley and Torsney). In their meta-analysis of more than 200 studies, they found no differences between introduced and native megaherbivore impacts or evidence for stronger impacts of functionally novel species. Instead, large-bodied herbivores and those with selective diets had a stronger effect on vegetation (e.g., grass feeders reducing graminoid diversity), suggesting a stronger role for species’ traits than origins in determining their impacts. —Bianca LopezVILLUM FONDEN; Danish National Research Foundation; and Independent Research Fund Denmark–Natural Sciences.https://www.science.org/journal/sciadvhj2024Mammal Research InstituteSDG-15:Life on lan