Top 40 Priorities for Science to Inform US Conservation and Management Policy

To maximize the utility of research to decisionmaking, especially given limited financial resources, scientists must set priorities for their efforts. We present a list of the top 40 high-priority, multidisciplinary research questions directed toward informing some of the most important current and future decisions about management of species, communities, and ecological processes in the United States. The questions were generated by an open, inclusive process that included personal interviews with decisionmakers, broad solicitation of research needs from scientists and policymakers, and an intensive workshop that included scientifically oriented individuals responsible for managing and developing policy related to natural resources. The process differed from previous efforts to set priorities for conservation research in its focus on the engagement of decisionmakers in addition to researchers. The research priorities emphasized the importance of addressing societal context and exploration of trade-offs among alternative policies and actions, as well as more traditional questions related to ecological processes and functions.Keywords: Priority setting, Natural resource management, Ecosystems, Conservation, Decisionmaker

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

Multi-context genetic modeling of transcriptional regulation resolves novel disease loci

A majority of the variants identified in genome-wide association studies fall in non-coding regions of the genome, indicating their mechanism of impact is mediated via gene expression. Leveraging this hypothesis, transcriptome-wide association studies (TWAS) have assisted in both the interpretation and discovery of additional genes associated with complex traits. However, existing methods for conducting TWAS do not take full advantage of the intra-individual correlation inherently present in multi-context expression studies and do not properly adjust for multiple testing across contexts. We introduce CONTENT-a computationally efficient method with proper cross-context false discovery correction that leverages correlation structure across contexts to improve power and generate context-specific and context-shared components of expression. We apply CONTENT to bulk multi-tissue and single-cell RNA-seq data sets and show that CONTENT leads to a 42% (bulk) and 110% (single cell) increase in the number of genetically predicted genes relative to previous approaches. We find the context-specific component of expression comprises 30% of heritability in tissue-level bulk data and 75% in single-cell data, consistent with cell-type heterogeneity in bulk tissue. In the context of TWAS, CONTENT increases the number of locus-phenotype associations discovered by over 51% relative to previous methods across 22 complex traits

Global Visions : Towards a New Internationalism in the Visual Arts

This anthology includes 16 essays by as many authors on the topic of a new internationalism in art. Among the topics discussed: the problem of ethnography for the arts; the problem of creating meaning through the museum; issues of difference, curatorship, and exhibiting. Biographical notes on writers. Circa 100 bibl. ref

lentiMPRA and MPRAflow for high-throughput functional characterization of gene regulatory elements.

Massively parallel reporter assays (MPRAs) can simultaneously measure the function of thousands of candidate regulatory sequences (CRSs) in a quantitative manner. In this method, CRSs are cloned upstream of a minimal promoter and reporter gene, alongside a unique barcode, and introduced into cells. If the CRS is a functional regulatory element, it will lead to the transcription of the barcode sequence, which is measured via RNA sequencing and normalized for cellular integration via DNA sequencing of the barcode. This technology has been used to test thousands of sequences and their variants for regulatory activity, to decipher the regulatory code and its evolution, and to develop genetic switches. Lentivirus-based MPRA (lentiMPRA) produces 'in-genome' readouts and enables the use of this technique in hard-to-transfect cells. Here, we provide a detailed protocol for lentiMPRA, along with a user-friendly Nextflow-based computational pipeline-MPRAflow-for quantifying CRS activity from different MPRA designs. The lentiMPRA protocol takes ~2 months, which includes sequencing turnaround time and data processing with MPRAflow

Frail elderly patients’ experiences of information on medication. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Older patients generally have only poor knowledge about their medicines. Knowledge is important for good adherence and for participating in decisions about treatment. Patients are entitled to be informed on an individual and adequate level. The aim of the study was to explore frail elderly patients’ experiences of receiving information about their medications and their views on how the information should best be given.</p> <p>Methods</p> <p>The study was qualitative in design and was carried out in 2011. Twelve frail elderly (aged 68–88) participants taking cardiovascular medications participated in semi-structured interviews covering issues related to receiving information about prescribed medicines. The interviews were recorded, transcribed and subjected to content analysis, in which the text was analysed in five steps, inspired by Graneheim and Lundman.</p> <p>Results</p> <p>The results revealed that the experiences which the elderly participants had regarding the receiving of medical information fell into two main categories: “Comfortable with information” or “Insecure with information”. The elderly felt comfortable when they trusted their physician or their medication, when they received enough information from the prescriber or when they knew how to find out sufficient information by themselves. They felt insecure if they were anxious, if the availability of medical care was poor or if they did not receive enough information.</p> <p>Conclusions</p> <p>Factors that frequently caused insecurity about information and anxiety were too short consultations, lack of availability of someone to answer questions or of the opportunity to contact the physician if adverse effects are suspected. These factors could easily be dealt with and there must be improvements in the clinics if the patients´ feelings of security are to be increased.</p

Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression of type 1 interferon-stimulated genes (ISGs) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell type-specific expression features predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data to map cell type-specific cis-expression quantitative trait loci and to link SLE-associated variants to cell type-specific expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE