Multiple prebiotic metals mediate translation.

Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution

Evaluating the Feasibility of Sustainable Seafood Labelling Programmes in Small Island Developing States: A Pilot Study of Artisanal Fisheries in Seychelles

The Republic of Seychelles is one of six African Small Island Developing States (SIDS) and has a marine-based economy reliant on fisheries and international tourism. Seychelles has been flagged by the United Nations as highly vulnerable to climate change. Climatic threats are compounded with population declines of key fishery species. A progressive national stance towards ocean sustainability and an emerging economy partially driven by tourists are two of several factors that make Seychelles a good candidate for a sustainable seafood labelling and consumption programme, which would provide market-based incentives for fishery harvesters, regulators, buyers and consumers to improve sustainable practices. To address the feasibility of such a programme, we conducted a pilot study, surveying 33 artisanal fishers and mapping supply chain structure to examine incentives and challenges. Questions addressed fishers’ years of experience, reliance on fishing for income, and flexibility in gear type and species targeted. Of the total number of respondents, 64% would like to see a programme implemented but only 34% thought it would be successful. Participants identified several barriers and benefits that primarily spanned socioeconomic and regulatory themes. Our pilot results indicate the sociocultural and economic impacts of sustainability programmes in Seychelles are as important as environmental considerations, a finding pertinent to anyone undertaking similar research efforts in other SIDS. We advocate for the necessity of thorough, location-based research and in-depth stakeholder consultation to elucidate economic, societal, behavioural and cultural factors that will affect the success of designing and implementing seafood labelling programmes in SIDS

Beyond Undetectable: Modeling the Clinical Benefit of Improved Antiretroviral Adherence in Persons With Human Immunodeficiency Virus With Virologic Suppression

BACKGROUND: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown. METHODS: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up. RESULTS: Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively. CONCLUSIONS: Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated

The untapped potential of seascape genomics in the North Pacific

Seascape genomics provides a powerful framework to evaluate the presence and strength of environmental pressures on marine organisms, as well as to forecast long term species stability under various perturbations. In the highly productive North Pacific, forage fishes, key trophic links across ecosystems, are also contending with a rapidly warming climate and a litany of associated oceanographic changes (e.g., changes in salinity, dissolved oxygen, pH, primary production, etc.). These changes can place substantial selective pressures on populations over space and time. While several population genomics studies have targeted forage fishes in the North Pacific, none have formally analyzed the interactions between genotype and environment. However, when population genomics studies provide collection location information and other critical data, it is possible to supplement a published genomic dataset with environmental data from existing public databases and perform “post hoc seascape genomics” analyses. In reviewing the literature, we find pertinent metadata (dates and locations of sample collection) are rarely provided. We identify specific factors that may impede the application of seascape genomics methods in the North Pacific. Finally, we present an approach for supplementing data in a reproducible way to allow for post hoc seascape genomics analysis, in instances when metadata are reported. Overall, our goal is to demonstrate – via literature review – the utility and importance of seascape genomics to understanding the long term health of forage fish species in the North Pacific

Trophic Garnishes: Cat–Rat Interactions in an Urban Environment

BACKGROUND:Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats (Rattus norvegicus), and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. METHODOLOGY/PRINCIPAL FINDINGS:Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6+/-12.5 rats/alley and 123.8+/-42.2 rats/alley over two years). The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley) also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g+/-17.8 g) than the trapped rats (385.0 g+/-135.6 g). Cats rarely preyed on the larger, older portion of the rat population. CONCLUSIONS/SIGNIFICANCE:The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the juvenile proportion of the rat population. The top predator in this urban ecosystem appears to have little impact on the size of the prey population, and similarly, reduction in rat populations doesn't impact the size of the cat population. However, the selected targeting of small rats may locally influence the size structure of the population which may have consequences for patterns of pathogen transmission

Emergency Department Pediatric Readiness Among US Trauma Centers: A Machine Learning Analysis of Components Associated With Survival.

OBJECTIVE: We used machine learning to identify the highest impact components of emergency department (ED) pediatric readiness for predicting in-hospital survival among children cared for in US trauma centers. BACKGROUND: ED pediatric readiness is associated with improved short-term and long-term survival among injured children and part of the national verification criteria for US trauma centers. However, the components of ED pediatric readiness most predictive of survival are unknown. METHODS: This was a retrospective cohort study of injured children below 18 years treated in 458 trauma centers from January 1, 2012, through December 31, 2017, matched to the 2013 National ED Pediatric Readiness Assessment and the American Hospital Association survey. We used machine learning to analyze 265 potential predictors of survival, including 152 ED readiness variables, 29 patient variables, and 84 ED-level and hospital-level variables. The primary outcome was in-hospital survival. RESULTS: There were 274,756 injured children, including 4585 (1.7%) who died. Nine ED pediatric readiness components were associated with the greatest increase in survival: policy for mental health care (+8.8% change in survival), policy for patient assessment (+7.5%), specific respiratory equipment (+7.2%), policy for reduced-dose radiation imaging (+7.0%), physician competency evaluations (+4.9%), recording weight in kilograms (+3.2%), life support courses for nursing (+1.0%-2.5%), and policy on pediatric triage (+2.5%). There was a 268% improvement in survival when the 5 highest impact components were present. CONCLUSIONS: ED pediatric readiness components related to specific policies, personnel, and equipment were the strongest predictors of pediatric survival and worked synergistically when combined

Norovirus and Foodborne Disease, United States, 1991–2000

Analysis of foodborne outbreaks shows how advances in viral diagnostics are clarifying the causes of foodborne outbreaks and determining the high impact of norovirus infections

Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain

Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45+ cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45+ cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain's innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants

Modulations of the Chicken Cecal Microbiome and Metagenome in Response to Anticoccidial and Growth Promoter Treatment

With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches