BackgroundEndothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced P. falciparum and P. vivax infection.MethodsParticipants were enrolled in Induced Blood Stage Malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2 and von Willebrand Factor (vWF) were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry (PAT) and near infrared spectroscopy (NIRS), and the endothelial glycocalyx by sublingual video-microscopy and measurement of biomarkers of degradation.ResultsForty-five healthy, malaria-naïve participants were recruited from 5 studies. Osteoprotegerin and vWF increased in participants following inoculation with P. vivax (n=16), or P. falciparum (n=15), with angiopoietin-2 also increasing in P. falciparum For both species, the most pronounced increase was seen in osteoprotegerin. This was particularly marked in P. vivax, where osteoprotegerin correlated with parasitemia and malaria clinical score. There were no changes in measures of endothelial gylcocalyx or microvascular function.ConclusionsPlasma biomarkers of endothelial activation increase in early P. falciparum and P. vivax infection, and precede changes in the endothelial glycocalyx or microvascular function. The more pronounced increase in osteoprotegerin suggests that this biomarker may play a role in disease pathogenesis. Copyright © 2020 American Society for Microbiology.Interdisciplinary healthcare providers (HCPs) receive only minimal training in identifying, referring for and treating eating disorders and may feel ill-prepared to manage them. There is a need for brief interventions that prepare HCPs for work with people with eating disorders, particularly when they do not fit stereotypes about who might experience an eating disorder. One method for enacting brief interventions that make change in this realm is using digital stories (short videos) to generate awareness and knowledge. In this article, we discuss the results of a pilot study exploring the impact of viewing digital stories created by people in eating disorder recovery and their supporters on an interdisciplinary group of HCPs. We showed five stories to 22 HCPs who filled out qualitative prequestionnaires and postquestionnaires about their experiences of viewing the films and how they conceptualised recovery. Providers found the stories evocative; the stories appear to have complexified their perspectives on recovery. HCPs desired more diverse, detailed and lengthy stories, indicating that pursuing digital storytelling for HCP education and awareness may hold promise. Through centring the voices of people with eating disorders and in recovery, digital stories may also provide new ways of talking about recovery that open up possibilities for embracing difference. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The Hippo pathway is an evolutionary conserved signalling network that regulates organ size, cell fate control and tumorigenesis. In the context of organ size control, the pathway incorporates a large variety of cellular cues such as cell polarity and adhesion into an integrated transcriptional response. The central Hippo signalling effector is the transcriptional co-activator Yorkie, which controls gene expression in partnership with different transcription factors, most notably Scalloped. When it is not activated by Yorkie, Scalloped can act as a repressor of transcription, at least in part due to its interaction with the corepressor protein Tgi. The mechanism by which Tgi represses transcription is incompletely understood and therefore we sought to identify proteins that potentially operate together with it. Using an affinity purification and mass-spectrometry approach we identified Pits and CtBP as Tgi-interacting proteins, both of which have been linked to transcriptional repression. Both Pits and CtBP were required for Tgi to suppress the growth of the Drosophila melanogaster eye and CtBP loss suppressed the undergrowth of yorkie mutant eye tissue. Furthermore, as reported previously for Tgi, overexpression of Pits repressed transcription of Hippo pathway target genes. These findings suggest that Tgi might operate together with Pits and CtBP to repress transcription of genes that normally promote tissue growth. The human orthologues of Tgi, CtBP and Pits (VGLL4, CTBP2 and IRF2BP2) have previously been shown to physically and functionally interact to control transcription, implying that the mechanism by which these proteins control transcriptional repression is conserved throughout evolution. Copyright © 2020, Genetics.In eukaryotic genomes, ribosomal RNA (rRNA) genes exist as tandemly repeated clusters, forming ribosomal DNA (rDNA) loci. Each rDNA locus typically contains hundreds of rRNA genes to meet the high demand of ribosome biogenesis. Nucleolar dominance is a phenomenon, whereby individual rDNA loci are entirely silenced or transcribed, and is believed to be a mechanism to control rRNA dosage. Nucleolar dominance was originally noted to occur in interspecies hybrids, and has been shown to occur within a species (i.e. non-hybrid context). However, studying nucleolar dominance within a species has been challenging due to the highly homogenous sequence across rDNA loci. By utilizing single nucleotide polymorphisms (SNPs) between X rDNA vs. Y rDNA loci in males, as well as sequence variations between two X rDNA loci in females, we conducted a thorough characterization of nucleolar dominance throughout development of D. melanogaster We demonstrate that nucleolar dominance is a developmentally-regulated program that occurs in non-hybrid, wild type D. melanogaster, where Y rDNA dominance is established during male embryogenesis, whereas females normally do not exhibit dominance between two X rDNA loci. By utilizing various chromosomal complements (e.g. X/Y, X/X, X/X/Y) and a chromosome rearrangement, we show that the short arm of the Y chromosome including the Y rDNA likely contains information that instructs the state of nucleolar dominance.  https://www.selleckchem.com/products/ulonivirine.html  Our study begins to reveal the mechanisms underlying the selection of rDNA loci for activation/silencing in nucleolar dominance in the context of non-hybrid D. melanogaster. Copyright © 2020, Genetics.