Synthetic microplastics (≤5-mm fragments) are emerging environmental contaminants that have been found to accumulate within coastal marine sediments worldwide. The ecological impacts and fate of ...microplastic debris are only beginning to be revealed, with previous research into these topics having primarily focused on higher organisms and/or pelagic environments. Despite recent research into plastic-associated microorganisms in seawater, the microbial colonization of microplastics in benthic habitats has not been studied. Therefore, we employed a 14-day microcosm experiment to investigate bacterial colonization of low-density polyethylene (LDPE) microplastics within three types of coastal marine sediment from Spurn Point, Humber Estuary, U.K.
Bacterial attachment onto LDPE within sediments was demonstrated by scanning electron microscopy and catalyzed reporter deposition fluorescence in situ hybridisation (CARD-FISH). Log-fold increases in the abundance of 16S rRNA genes from LDPE-associated bacteria occurred within 7 days with 16S rRNA gene numbers on LDPE surfaces differing significantly across sediment types, as shown by quantitative PCR. Terminal-restriction fragment length polymorphism (T-RFLP) analysis demonstrated rapid selection of LDPE-associated bacterial assemblages whose structure and composition differed significantly from those in surrounding sediments. Additionally, T-RFLP analysis revealed successional convergence of the LDPE-associated communities from the different sediments over the 14-day experiment. Sequencing of cloned 16S rRNA genes demonstrated that these communities were dominated after 14 days by the genera Arcobacter and Colwellia (totalling 84-93% of sequences). Attachment by Colwellia spp. onto LDPE within sediments was confirmed by CARD-FISH.
These results demonstrate that bacteria within coastal marine sediments can rapidly colonize LDPE microplastics, with evidence for the successional formation of plastisphere-specific bacterial assemblages. Although the taxonomic compositions of these assemblages are likely to differ between marine sediments and the water column, both Arcobacter and Colwellia spp. have previously been affiliated with the degradation of hydrocarbon contaminants within low-temperature marine environments. Since hydrocarbon-degrading bacteria have also been discovered on plastic fragments in seawater, our data suggest that recruitment of hydrocarbonoclastic bacteria on microplastics is likely to represent a shared feature between both benthic and pelagic marine habitats.
Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with ...broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.
Safety climate research has reached a mature stage of development, with a number of meta-analyses demonstrating the link between safety climate and safety outcomes. More recently, there has been ...interest from systems theorists in integrating the concept of safety culture and to a lesser extent, safety climate into systems-based models of organizational safety. Such models represent a theoretical and practical development of the safety climate concept by positioning climate as part of a dynamic work system in which perceptions of safety act to constrain and shape employee behavior. We propose safety climate and safety culture constitute part of the enabling capitals through which organizations build safety capability. We discuss how organizations can deploy different configurations of enabling capital to exert control over work systems and maintain safe and productive performance. We outline 4 key strategies through which organizations to reconcile the system control problems of promotion versus prevention, and stability versus flexibility.
Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking ...the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein diet, but not when mice are fed a HFD with low energy density (high fiber). Furthermore, mice with an activating mutation in NLRP1, and hence increased IL-18, have decreased adiposity and are resistant to diet-induced metabolic dysfunction. Feeding these mice a HFD further increased plasma IL-18 concentrations and strikingly resulted in loss of adipose tissue mass and fatal cachexia, which could be prevented by genetic deletion of IL-18. Thus, NLRP1 is an innate immune sensor that functions in the context of metabolic stress to produce IL-18, preventing obesity and metabolic syndrome.
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•Deletion of NLRP1 in mice leads to obesity and metabolic syndrome•NLRP1 obesity phenotype is related to the energy quotient of the diet•Loss of NLRP1 decreased IL-18 production and lipolysis•NLRP1 activation increased IL-18, prevented obesity, but was fatal on the high-fat diet
Murphy et al. link the NLRP1 inflammasome to IL-18 production and show that mice lacking NLRP1 have defective lipolysis and become obese, as seen with IL-18 deficiency. NLRP1 activation prevents obesity but results in fatal fat loss and cachexia on a high-fat diet, which is rescued by deletion of IL-18.
Motivated by accelerating anthropogenic extinctions, decades of biodiversity-ecosystem function (BEF) experiments show that ecosystem function declines with species loss from local communities. Yet, ...at the local scale, changes in species' total and relative abundances are more common than species loss. The consensus best biodiversity measures are Hill numbers, which use a scaling parameter,
, to emphasize rarer versus more common species. Shifting that emphasis captures distinct, function-relevant biodiversity gradients beyond species richness. Here, we hypothesized that Hill numbers that emphasize rare species more than richness does may distinguish large, complex and presumably higher-functioning assemblages from smaller and simpler ones. In this study, we tested which values of
produce the strongest BEF relationships in community datasets of ecosystem functions provided by wild, free-living organisms. We found that
values that emphasized rare species more than richness does most often correlated most strongly with ecosystem functions. As emphasis shifted to more common species, BEF correlations were often weak and/or negative. We argue that unconventional Hill diversities that shift emphasis towards rarer species may be useful for describing biodiversity change, and that employing a wide spectrum of Hill numbers can clarify mechanisms underlying BEF relationships. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.
To summarize available data on the effectiveness and safety of single-agent misoprostol for medical abortion in the first trimester.
We searched MEDLINE, CABI, Cochrane, EMBASE, LILACS, the Web of ...Science, and ClinicalTrials.gov for English-language studies that evaluated misoprostol alone for abortion of a viable pregnancy in the first trimester.
Our search yielded 1,562 citations, of which 38 included data from 53 trial groups that met our inclusion and exclusion criteria.
We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2,536 (meta-analytic estimate 22.0%, 95% CI 18.8-25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6,359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3-8.5%) had ongoing pregnancies. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4-1.0%) were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71-85%).
Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester.
PROSPERO, CRD42018083589.
Background Studies suggest strong links between adverse childhood experiences (ACEs) and poor adult health and social outcomes. However, the use of such studies in non-US populations is relatively ...scarce. Methods Retrospective cross-sectional survey of 1500 residents and 67 substance users aged 18-70 years in a relatively deprived and ethnically diverse UK population. Results Increasing ACEs were strongly related to adverse behavioural, health and social outcomes. Compared with those with 0 ACEs, individuals with 4+ ACEs had adjusted odds ratios of the following: 3.96 95% confidence interval (CI): 2.74-5.73 for smoking; 3.72 (95% CI: 2.37-5.85) for heavy drinking; 8.83 (95% CI: 4.42-17.62) for incarceration and 3.02 (95% CI: 1.38-6.62) for morbid obesity. They also had greater risk of poor educational and employment outcomes; low mental wellbeing and life satisfaction; recent violence involvement; recent inpatient hospital care and chronic health conditions. Higher ACEs were also associated with having caused/been unintentionally pregnant aged <18 years and having been born to a mother aged <20 years. Conclusions ACEs contribute to poor life-course health and social outcomes in a UK population. That ACEs are linked to involvement in violence, early unplanned pregnancy, incarceration, and unemployment suggests a cyclic effect where those with higher ACE counts have higher risks of exposing their own children to ACEs.
Despite the development of novel drugs, the prospects for many patients with acute myeloid leukemia (AML) remain dismal. This study reveals that the selective inhibitor of RNA polymerase I (Pol I) ...transcription, CX-5461, effectively treats aggressive AML, including mixed-lineage leukemia-driven AML, and outperforms standard chemotherapies. In addition to the previously characterized mechanism of action of CX-5461 (ie, the induction of p53-dependent apoptotic cell death), the inhibition of Pol I transcription also demonstrates potent efficacy in p53null AML in vivo. This significant survival advantage in both p53WT and p53null leukemic mice treated with CX-5461 is associated with activation of the checkpoint kinases 1/2, an aberrant G2/M cell-cycle progression and induction of myeloid differentiation of the leukemic blasts. The ability to target the leukemic-initiating cell population is thought to be essential for lasting therapeutic benefit. Most strikingly, the acute inhibition of Pol I transcription reduces both the leukemic granulocyte-macrophage progenitor and leukemia-initiating cell (LIC) populations, and suppresses their clonogenic capacity. This suggests that dysregulated Pol I transcription is essential for the maintenance of their leukemia-initiating potential. Together, these findings demonstrate the therapeutic utility of this new class of inhibitors to treat highly aggressive AML by targeting LICs.
•Inhibition of RNA Pol I by CX-5461 treats aggressive AML and outperforms standard chemotherapy regimens.•CX-5461 induces p53-dependent apoptosis, p53-independent cell-cycle defects and differentiation, and reduces LICs.
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