Influence of fluid accumulation on major adverse kidney events in critically ill patients - an observational cohort study.

BACKGROUND: Fluid accumulation (FA) is known to be associated with acute kidney injury (AKI) during intensive care unit (ICU) stay but data on mid-term renal outcome is scarce. The aim of this study was to investigate the association between FA at ICU day 3 and major adverse kidney events in the first 30 days after ICU admission (MAKE30). METHODS: Retrospective, single-center cohort study including adult ICU patients with sufficient data to compute FA and MAKE30. We defined FA as a positive cumulative fluid balance greater than 5% of bodyweight. The association between FA and MAKE30, including its sub-components, as well as the serum creatinine trajectories during ICU stay were examined. In addition, we performed a sensitivity analysis for the stage of AKI and the presence of chronic kidney disease (CKD). RESULTS: Out of 13,326 included patients, 1,100 (8.3%) met the FA definition. FA at ICU day 3 was significantly associated with MAKE30 (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI] 1.67-2.30; p < 0.001) and all sub-components: need for renal replacement therapy (aOR 3.83; 95%CI 3.02-4.84), persistent renal dysfunction (aOR 1.72; 95%CI 1.40-2.12), and 30-day mortality (aOR 1.70; 95%CI 1.38-2.09), p all < 0.001. The sensitivity analysis showed an association of FA with MAKE30 independent from a pre-existing CKD, but exclusively in patients with AKI stage 3. Furthermore, FA was independently associated with the creatinine trajectory over the whole observation period. CONCLUSIONS: Fluid accumulation is significantly associated with MAKE30 in critically ill patients. This association is independent from pre-existing CKD and strongest in patients with AKI stage 3.

Entomopathogenic nematodes as an effective and sustainable alternative to control the fall armyworm in Africa.

The recent invasion of the fall armyworm (FAW), a voracious pest, into Africa and Asia has resulted in unprecedented increases in insecticide applications, especially in maize cultivation. The health and environmental hazards posed by these chemicals have prompted a call for alternative control practices. Entomopathogenic nematodes are highly lethal to the FAWs, but their application aboveground has been challenging. In this study, we report on season-long field trials with an innocuous biodegradable gel made from carboxymethyl cellulose containing local nematodes that we specifically developed to target the FAW. In several Rwandan maize fields with distinct climatic conditions and natural infestation rates, we compared armyworm presence and damage in control plots and plots that were treated with either our nematode gel formulation, a commercial liquid nematode formulation, or the commonly used contact insecticide cypermethrin. The treatments were applied to the whorl of each plant, which was repeated three to four times, at 2-week intervals, starting when the plants were still seedlings. Although all three treatments reduced leaf damage, only the gel formulation decreased caterpillar infestation by about 50% and yielded an additional ton of maize per hectare compared with untreated plots. Importantly, we believe that the use of nematodes can be cost-effective, since we used nematode doses across the whole season that were at least 3-fold lower than their normal application against belowground pests. The overall results imply that precisely formulated and easy-to-apply nematodes can be a highly effective, affordable, and sustainable alternative to insecticides for FAW control.

The impact of religion on changes in end-of-life practices in European intensive care units: a comparative analysis over 16 years.

PURPOSE: Religious beliefs affect end-of-life practices in intensive care units (ICUs). Changes over time in end-of-life practices were not investigated regarding religions. METHODS: Twenty-two European ICUs (3 regions: Northern, Central, and Southern Europe) participated in both Ethicus-1 (years 1999-2000) and Ethicus-2 studies (years 2015-2016). Data of ICU patients who died or had limitations of life-sustaining therapy were analysed regarding changes in end-of-life practices and patient/physician religious affiliations. Frequencies, timing of decision-making, and religious affiliations of physicians/patients were compared using the same definitions. RESULTS: In total, 4592 adult ICU patients (n = 2807 Ethicus-1, n = 1785 Ethicus-2) were analysed. In both studies, patient and physician religious affiliations were mostly Catholic, Greek Orthodox, Jewish, Protestant, or unknown. Treating physicians (but not patients) commonly reported no religious affiliation (18%). Distribution of end-of-life practices with respect to religion and geographical regions were comparable between the two studies. Withholding [n = 1143 (40.7%) Ethicus-1 and n = 892 (50%) Ethicus-2] and withdrawing [n = 695 (24.8%) Ethicus-1 and n = 692 (38.8%) Ethicus-2] were most commonly decided. No significant changes in end-of-life practices were observed for any religion over 16 years. The number of end-of-life discussions with patients/ families/ physicians increased, while mortality and time until first decision decreased. CONCLUSIONS: Changes in end-of-life practices observed over 16 years appear unrelated to religious affiliations of ICU patients or their treating physicians, but the effects of religiosity and/or culture could not be assessed. Shorter time until decision in the ICU and increased numbers of patient and family discussions may indicate increased awareness of the importance of end-of-life decision-making in the ICU.

Anopheles mosquitoes reveal new principles of 3D genome organization in insects.

Chromosomes are hierarchically folded within cell nuclei into territories, domains and subdomains, but the functional importance and evolutionary dynamics of these hierarchies are poorly defined. Here, we comprehensively profile genome organizations of five Anopheles mosquito species and show how different levels of chromatin architecture influence each other. Patterns observed on Hi-C maps are associated with known cytological structures, epigenetic profiles, and gene expression levels. Evolutionary analysis reveals conservation of chromatin architecture within synteny blocks for tens of millions of years and enrichment of synteny breakpoints in regions with increased genomic insulation. However, in-depth analysis shows a confounding effect of gene density on both insulation and distribution of synteny breakpoints, suggesting limited causal relationship between breakpoints and regions with increased genomic insulation. At the level of individual loci, we identify specific, extremely long-ranged looping interactions, conserved for ~100 million years. We demonstrate that the mechanisms underlying these looping contacts differ from previously described Polycomb-dependent interactions and clustering of active chromatin.

Functional Constraints on Insect Immune System Components Govern Their Evolutionary Trajectories.

Roles of constraints in shaping evolutionary outcomes are often considered in the contexts of developmental biology and population genetics, in terms of capacities to generate new variants and how selection limits or promotes consequent phenotypic changes. Comparative genomics also recognizes the role of constraints, in terms of shaping evolution of gene and genome architectures, sequence evolutionary rates, and gene gains or losses, as well as on molecular phenotypes. Characterizing patterns of genomic change where putative functions and interactions of system components are relatively well described offers opportunities to explore whether genes with similar roles exhibit similar evolutionary trajectories. Using insect immunity as our test case system, we hypothesize that characterizing gene evolutionary histories can define distinct dynamics associated with different functional roles. We develop metrics that quantify gene evolutionary histories, employ these to characterize evolutionary features of immune gene repertoires, and explore relationships between gene family evolutionary profiles and their roles in immunity to understand how different constraints may relate to distinct dynamics. We identified three main axes of evolutionary trajectories characterized by gene duplication and synteny, maintenance/stability and sequence conservation, and loss and sequence divergence, highlighting similar and contrasting patterns across these axes amongst subsets of immune genes. Our results suggest that where and how genes participate in immune responses limit the range of possible evolutionary scenarios they exhibit. The test case study system of insect immunity highlights the potential of applying comparative genomics approaches to characterize how functional constraints on different components of biological systems govern their evolutionary trajectories.

Genus-Wide Characterization of Bumblebee Genomes Provides Insights into Their Evolution and Variation in Ecological and Behavioral Traits.

Bumblebees are a diverse group of globally important pollinators in natural ecosystems and for agricultural food production. With both eusocial and solitary life-cycle phases, and some social parasite species, they are especially interesting models to understand social evolution, behavior, and ecology. Reports of many species in decline point to pathogen transmission, habitat loss, pesticide usage, and global climate change, as interconnected causes. These threats to bumblebee diversity make our reliance on a handful of well-studied species for agricultural pollination particularly precarious. To broadly sample bumblebee genomic and phenotypic diversity, we de novo sequenced and assembled the genomes of 17 species, representing all 15 subgenera, producing the first genus-wide quantification of genetic and genomic variation potentially underlying key ecological and behavioral traits. The species phylogeny resolves subgenera relationships, whereas incomplete lineage sorting likely drives high levels of gene tree discordance. Five chromosome-level assemblies show a stable 18-chromosome karyotype, with major rearrangements creating 25 chromosomes in social parasites. Differential transposable element activity drives changes in genome sizes, with putative domestications of repetitive sequences influencing gene coding and regulatory potential. Dynamically evolving gene families and signatures of positive selection point to genus-wide variation in processes linked to foraging, diet and metabolism, immunity and detoxification, as well as adaptations for life at high altitudes. Our study reveals how bumblebee genes and genomes have evolved across the Bombus phylogeny and identifies variations potentially linked to key ecological and behavioral traits of these important pollinators.

Evolutionary superscaffolding and chromosome anchoring to improve Anopheles genome assemblies.

BACKGROUND: New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from 'finished'. Updating multi-scaffold drafts to chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) to predict scaffold neighbours (adjacencies) offers a potentially useful complementary method for improving draft assemblies. RESULTS: We evaluated and employed 3 gene synteny-based methods applied to 21 Anopheles mosquito assemblies to produce consensus sets of scaffold adjacencies. For subsets of the assemblies, we integrated these with additional supporting data to confirm and complement the synteny-based adjacencies: 6 with physical mapping data that anchor scaffolds to chromosome locations, 13 with paired-end RNA sequencing (RNAseq) data, and 3 with new assemblies based on re-scaffolding or long-read data. Our combined analyses produced 20 new superscaffolded assemblies with improved contiguities: 7 for which assignments of non-anchored scaffolds to chromosome arms span more than 75% of the assemblies, and a further 7 with chromosome anchoring including an 88% anchored Anopheles arabiensis assembly and, respectively, 73% and 84% anchored assemblies with comprehensively updated cytogenetic photomaps for Anopheles funestus and Anopheles stephensi. CONCLUSIONS: Experimental data from probe mapping, RNAseq, or long-read technologies, where available, all contribute to successful upgrading of draft assemblies. Our evaluations show that gene synteny-based computational methods represent a valuable alternative or complementary approach. Our improved Anopheles reference assemblies highlight the utility of applying comparative genomics approaches to improve community genomic resources.

Draft Genome Assembly and Population Genetics of an Agricultural Pollinator, the Solitary Alkali Bee (Halictidae: Nomia melanderi).

Alkali bees (Nomia melanderi) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research.

Of Genes and Genomes: Mosquito Evolution and Diversity.

Mosquitoes are widely despised for their exasperating buzzing and irritating bites, and more poignantly because, during blood-feeding, females may transmit pathogens that cause devastating diseases. However, the ability to transmit such viruses, filarial worms, or malaria parasites varies greatly amongst the ∼3500 recognised mosquito species. Applying omics technologies to sample this diversity and explore the biology underlying these variations is bringing increasingly greater resolution that enhances our understanding of mosquito evolution. Here we review the current status of mosquito omics, or 'mozomics', resources and recent advances in their applications to characterise mosquito biology and evolution, with a focus on the intersection of evolutionary and functional genomics to understand the putative links between gene and genome dynamism and mosquito diversity.

Genome Sequence of the Wheat Stem Sawfly, Cephus cinctus, Representing an Early-Branching Lineage of the Hymenoptera, Illuminates Evolution of Hymenopteran Chemoreceptors.

The wheat stem sawfly, Cephus cinctus, is a major pest of wheat and key ecological player in the grasslands of western North America. It also represents the distinctive Cephoidea superfamily of sawflies (Symphyta) that appeared early during the hymenopteran radiation, but after three early-branching eusymphytan superfamilies that form the base of the order Hymenoptera. We present a high-quality draft genome assembly of 162 Mb in 1,976 scaffolds with a scaffold N50 of 622 kb. Automated gene annotation identified 11,210 protein-coding gene models and 1,307 noncoding RNA models. Thirteen percent of the assembly consists of ∼58,000 transposable elements partitioned equally between Class-I and Class-II elements. Orthology analysis reveals that 86% of Cephus proteins have identifiable orthologs in other insects. Phylogenomic analysis of conserved subsets of these proteins supports the placement of the Cephoidea between the Eusymphyta and the parasitic woodwasp superfamily Orussoidea. Manual annotation and phylogenetic analysis of families of odorant, gustatory, and ionotropic receptors, plus odorant-binding proteins, shows that Cephus has representatives for most conserved and expanded gene lineages in the Apocrita (wasps, ants, and bees). Cephus has also maintained several insect gene lineages that have been lost from the Apocrita, most prominently the carbon dioxide receptor subfamily. Furthermore, Cephus encodes a few small lineage-specific chemoreceptor gene family expansions that might be involved in adaptations to new grasses including wheat. These comparative analyses identify gene family members likely to have been present in the hymenopteran ancestor and provide a new perspective on the evolution of the chemosensory gene repertoire.