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A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 – 9 . Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units 10 ), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches 11 , 12 – 13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry 14 . These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis. Metabolomics data from germ-free and specific-pathogen-free mice reveal effects of the microbiome on host chemistry, identifying conjugations of bile acids that are also enriched in patients with inflammatory bowel disease or cystic fibrosis.

Large-scale use of the persistent and potent neonicotinoid and fipronil insecticides has raised concerns about risks to ecosystem functions provided by a wide range of species and environments affected by these insecticides. The concept of ecosystem services is widely used in decision making in the context of valuing the service potentials, benefits, and use values that well-functioning ecosystems provide to humans and the biosphere and, as an endpoint (value to be protected), in ecological risk assessment of chemicals. Neonicotinoid insecticides are frequently detected in soil and water and are also found in air, as dust particles during sowing of crops and aerosols during spraying. These environmental media provide essential resources to support biodiversity, but are known to be threatened by long-term or repeated contamination by neonicotinoids and fipronil. We review the state of knowledge regarding the potential impacts of these insecticides on ecosystem functioning and services provided by terrestrial and aquatic ecosystems including soil and freshwater functions, fisheries, biological pest control, and pollination services. Empirical studies examining the specific impacts of neonicotinoids and fipronil to ecosystem services have focused largely on the negative impacts to beneficial insect species (honeybees) and the impact on pollination service of food crops. However, here we document broader evidence of the effects on ecosystem functions regulating soil and water quality, pest control, pollination, ecosystem resilience, and community diversity. In particular, microbes, invertebrates, and fish play critical roles as decomposers, pollinators, consumers, and predators, which collectively maintain healthy communities and ecosystem integrity. Several examples in this review demonstrate evidence of the negative impacts of systemic insecticides on decomposition, nutrient cycling, soil respiration, and invertebrate populations valued by humans. Invertebrates, particularly earthworms that are important for soil processes, wild and domestic insect pollinators which are important for plant and crop production, and several freshwater taxa which are involved in aquatic nutrient cycling, were all found to be highly susceptible to lethal and sublethal effects of neonicotinoids and/or fipronil at environmentally relevant concentrations. By contrast, most microbes and fish do not appear to be as sensitive under normal exposure scenarios, though the effects on fish may be important in certain realms such as combined fish-rice farming systems and through food chain effects. We highlight the economic and cultural concerns around agriculture and aquaculture production and the role these insecticides may have in threatening food security. Overall, we recommend improved sustainable agricultural practices that restrict systemic insecticide use to maintain and support several ecosystem services that humans fundamentally depend on.

Intercropping is considered by its advocates to be a sustainable, environmentally sound, and economically advantageous cropping system. Intercropping systems are complex, with non-uniform competition between the component species within the cropping cycle, typically leading to unequal relative yields making evaluation difficult. This paper is a review of the main existing metrics used in the scientific literature to assess intercropping systems. Their strengths and limitations are discussed. Robust metrics for characterising intercropping systems are proposed. A major limitation is that current metrics assume the same management level between intercropping and monocropping systems and do not consider differences in costs of production. Another drawback is that they assume the component crops in the mixture are of equal value. Moreover, in employing metrics, many studies have considered direct and private costs and benefits only, ignoring indirect and social costs and benefits of intercropping systems per se. Furthermore, production risk and growers’ risk preferences were often overlooked. In evaluating intercropping advantage using data from field trials, four metrics are recommended that collectively take into account all important differences in private costs and benefits between intercropping and monocropping systems, specifically the Land Equivalent Ratio, Yield Ratio, Value Ratio and Net Gross Margin.

Intercropping using mixtures of dryland crop species for grain or seed production was investigated in southern Australia across a range of rainfall zones over three years. The objective was to understand the productivity and profitability of intercropping in extensive, high-input grain cropping systems. Previous research has shown large productivity benefits of mixtures; however, few farmers practice intercropping in Australia, and an analysis of profitability is needed to support future potential adoption. Experimental results showed strong mixture responses (in terms of yield, value and land equivalence), but not all were profitable compared to an equivalent share of monoculture crops (as measured by gross margins). The most promising mixtures were those containing high-value crops (canola) and legumes (field pea or faba bean) at the wetter sites where the additional gross margin over equivalent monoculture crops ranged from$12/ha to $ 576/ha. Mixtures containing highly competitive crops (wheat or barley) were generally unprofitable. Mixtures involving cereals were doubly disadvantaged by the aggressiveness of these lower-value crops in the mixtures we examined and the high grain separation costs post-harvest. Cost reduction in mixture systems involving high-value crops that are synergistic (grain legumes) should provide enduring opportunities for intercropping in southern Australia.

Background Geriatric collaborative care models improve postoperative outcomes for older adults. However, there are limited data exploring how preoperative geriatric assessment may affect surgical cancellations. Methods This is a single-center retrospective cohort analysis. Patients enrolled in the Perioperative Optimization of Senior Health (POSH) program from 2011 to 2016 were included. POSH is a collaborative care model between geriatrics, surgery, and anesthesiology. Baseline demographic and medical data were collected during the POSH pre-op appointment. Patients who attended a POSH pre-op visit but did not have surgery were identified, and a chart review was performed to identify reasons for surgical cancellation. Baseline characteristics of patients who did and did not undergo surgery were compared. Results Of 449 eligible POSH referrals within the study period, 33 (7.3%) did not proceed to surgery; cancellation rates within the POSH program were lower than institutional cancellation rates for adults over age 65 who did not participate in POSH. Patients who did not have surgery were significantly older, more likely to have functional limitations, and had higher rates of several comorbidities compared with those who proceeded to surgery ( P  < 0.05). Reasons for surgical cancellations included a similar number of patient- and provider-driven causes. Conclusions Many reasons for surgical cancellation were related to potentially modifiable factors, such as changes in goals of care or concerns about rehabilitation, emphasizing the importance of shared decision-making in elective surgery for older adults. These results highlight the important role geriatric collaborative care can offer to older adults with complex needs.

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h²), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10−4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

In the emerging field of implementation science, measuring the extent to which a new or modified healthcare program or practice is successfully implemented following an intervention is a critical component in understanding how evidence-based treatments become part of regular practice. This paper is intended to expand our understanding of factors that influence the successful adoption of new or modified HIV services in correctional settings. The nine-site project developed and directed an organization-level intervention designed to implement improvements in preventing, detecting, and treating HIV for persons under correctional supervision. Using semi-structured interviews to elicit perceptions from Senior Researchers and Executive Sponsors at each of the nine sites, this paper presents their views and observations regarding the success of the experimental intervention in their criminal justice setting. Within the areas of focus for implementation (either HIV prevention, testing, or linkage to community treatment) the complexity of programmatic needs was very influential with regards to perceptions of success. An organization's pre-existing characteristics, staffing, funding, and interorganizational relationships contributed to either the ease or difficulty of programmatic implementation. Results are discussed pertaining to furthering our understanding of why new or modified healthcare interventions achieve success, including whether the intervention is a modification of existing practice or is a new intervention, and the choice of implementation strategy.

The siderophore produced by Rhodococcus rhodochrous strain OFS, rhodobactin, was isolated from iron-deficient cultures and purified by a combination of XAD-7 absorptive/partition resin column and semi-preparative HPLC. The siderophore structure was characterized using 1D and 2D (1)H, (13)C and (15)N NMR techniques (DQFCOSY, TOCSY, NOESY, HSQC and LR-HSQC) and was confirmed using ESI-MS and MS/MS experiments. The structural characterization revealed that the siderophore, rhodobactin, is a mixed ligand hexadentate siderophore with two catecholate and one hydroxamate moieties for iron chelation. We further investigated the effects of Fe concentrations on siderophore production and found that Fe limiting conditions (Fe concentrations from 0.1 microM to 2.0 microM) facilitated siderophore excretion. Our interests lie in the role that siderophores may have in binding metals at mixed contamination sites (containing metals/radionuclides and organics). Given the broad metabolic capacity of this microbe and its Fe scavenging ability, R. rhodochrous OFS may have a competitive advantage over other organisms employed in bioremediation.