GoM DE: interpreting structure in sequence count data with differential expression analysis allowing for grades of membership

Parts-based representations, such as non-negative matrix factorization and topic modeling, have been used to identify structure from single-cell sequencing data sets, in particular structure that is not as well captured by clustering or other dimensionality reduction methods. However, interpreting the individual parts remains a challenge. To address this challenge, we extend methods for differential expression analysis by allowing cells to have partial membership to multiple groups. We call this grade of membership differential expression (GoM DE). We illustrate the benefits of GoM DE for annotating topics identified in several single-cell RNA-seq and ATAC-seq data sets

Cultural orientations and preference for HRM policies and practices:the case of Oman

This study empirically examines the influence of cultural orientations on employee preferences of human resource management (HRM) policies and practices in Oman. Data were collected from 712 employees working in six large Omani organizations. The findings indicate that there is a number of differences among Omani employees regarding value orientations due especially to age, education and work experience. The findings show a strong orientation towards mastery, harmony, thinking and doing, and a weak orientation towards hierarchy, collectivism, subjugation and human nature-as-evil. The results demonstrate a clear link between value orientations and preferences for particular HRM policies and practices. Group-oriented HRM practices are preferred by those who scored high on collectivism and being orientations, and those who scored low on thinking and doing orientations. Hierarchy-oriented HRM practices are preferred by those scoring high on hierarchy, subjugation and human nature-as-bad orientations, and those scoring low on thinking and mastery orientations. Finally, preference for loose and informal HRM practices was positively associated with being, and negatively associated with thinking, doing and harmony orientations. The theoretical and practical implications of these findings are discussed in detail

Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

SURGE: uncovering context-specific genetic-regulation of gene expression from single-cell RNA sequencing using latent-factor models

Abstract Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, a method for unsupervised discovery of context-specific expression quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows discovery of the contexts or cell types modulating genetic regulation without prior knowledge. Applied to peripheral blood single-cell eQTL data, SURGE contexts capture continuous representations of distinct cell types and groupings of biologically related cell types. We demonstrate the disease-relevance of SURGE context-specific eQTLs using colocalization analysis and stratified LD-score regression

The role of peroxiredoxins in oxygenic photosynthesis of cyanobacteria and higher plants: peroxide detoxification or redox sensing?

Dietz K-J, Stork T, Finkemeier I, et al. The role of peroxiredoxins in oxygenic photosynthesis of cyanobacteria and higher plants: peroxide detoxification or redox sensing? In: Demmig-Adams B, Adams W, Mattoo A, eds. Photoprotection, photoinhibition, gene regulation, and environment. Advances in photosynthesis and respiration. Vol 21. Dordrecht: Kluwer Acad Press; 2006: 303-319