Dietary zinc and the control of Streptococcus pneumoniae infection

© 2019 Eijkelkamp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences

Patterns and Perceptions of Climate Change in a Biodiversity Conservation Hotspot

Quantifying local people's perceptions to climate change, and their assessments of which changes matter, is fundamental to addressing the dual challenge of land conservation and poverty alleviation in densely populated tropical regions To develop appropriate policies and responses, it will be important not only to anticipate the nature of expected changes, but also how they are perceived, interpreted and adapted to by local residents. The Albertine Rift region in East Africa is one of the world's most threatened biodiversity hotspots due to dense smallholder agriculture, high levels of land and resource pressures, and habitat loss and conversion. Results of three separate household surveys conducted in the vicinity of Kibale National Park during the late 2000s indicate that farmers are concerned with variable precipitation. Many survey respondents reported that conditions are drier and rainfall timing is becoming less predictable. Analysis of daily rainfall data for the climate normal period 1981 to 2010 indicates that total rainfall both within and across seasons has not changed significantly, although the timing and transitions of seasons has been highly variable. Results of rainfall data analysis also indicate significant changes in the intra-seasonal rainfall distribution, including longer dry periods within rainy seasons, which may contribute to the perceived decrease in rainfall and can compromise food security. Our results highlight the need for fine-scale climate information to assist agro-ecological communities in developing effective adaptive management

ZnuA and zinc homeostasis in pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and a clinically significant opportunistic human pathogen. Central to the ability of P. aeruginosa to colonise both environmental and host niches is the acquisition of zinc. Here we show that P. aeruginosa PAO1 acquires zinc via an ATP-binding cassette (ABC) permease in which ZnuA is the high affinity, zinc-specific binding protein. Zinc uptake in Gram-negative organisms predominantly occurs via an ABC permease, and consistent with this expectation a P. aeruginosa ΔznuA mutant strain showed an ~60% reduction in cellular zinc accumulation, while other metal ions were essentially unaffected. Despite the major reduction in zinc accumulation, minimal phenotypic differences were observed between the wild-type and ΔznuA mutant strains. However, the effect of zinc limitation on the transcriptome of P. aeruginosa PAO1 revealed significant changes in gene expression that enable adaptation to low-zinc conditions. Genes significantly up-regulated included non-zinc-requiring paralogs of zinc-dependent proteins and a number of novel import pathways associated with zinc acquisition. Collectively, this study provides new insight into the acquisition of zinc by P. aeruginosa PAO1, revealing a hitherto unrecognized complexity in zinc homeostasis that enables the bacterium to survive under zinc limitation.Victoria G. Pederick, Bart A. Eijkelkamp, Stephanie L. Begg, Miranda P. Ween, Lauren J. McAllister, James C. Paton, Christopher A. McDevit

Quantitative estimates of glacial refugia for chimpanzees ( Pan troglodytes ) since the Last Interglacial (120,000 BP)

Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467° (approximately 5.19 km2 grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km2 of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available

Diagnostic accuracy and clinical impact of natriuretic peptide screening for the detection of heart failure in the community: a protocol for systematic review and meta-analysis

Introduction: Patients diagnosed with heart failure in primary care have a better prognosis than those diagnosed in hospital. However, most cases are missed in the community. Recent attention has focussed on the potential of early detection through screening. Natriuretic peptides (NPs) are tested by GPs and used to rule out heart failure in patients presenting with symptoms. Evidence is now emerging that they may also have a role in screening but their accuracy in this context and the associated optimal thresholds, have not been established. The impact that NP screening would have on patients and health care systems also remains unclear. Methods: We aim to undertake a systematic search of the following sources: Ovid Medline, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. Screening, data extraction and critical appraisal will be carried out independently and in duplicate by two reviewers. We will include studies based in the community with &gt;100 participants that recruited a screened population. We will not add a study design filter and there will be no language restriction. The primary outcome will be the sensitivity and the specificity of NP screening and optimal thresholds for screening will be explored. Outcomes of interest for the impact analysis will include mortality, hospital admissions and cost effectiveness. This protocol has been developed in accordance with guidelines from the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). Discussion: This systematic review will identify how accurately NP screen for heart failure in the community and explore where NP screening thresholds should be set. It also aims to summarise the clinical impact of this strategy. Together, these results should inform future interventions that may provide an alternative pathway to facilitate improved detection of heart failure in the community. Registration: PROSPERO CRD42018087498; registered on 11 May 2018.</p

Diagnostic accuracy and clinical impact of natriuretic peptide screening for the detection of heart failure in the community: a protocol for systematic review and meta-analysis

Introduction: Patients diagnosed with heart failure in primary care have a better prognosis than those diagnosed in hospital. However, most cases are missed in the community. Recent attention has focussed on the potential of early detection through screening. Natriuretic peptides (NPs) are tested by GPs and used to rule out heart failure in patients presenting with symptoms. Evidence is now emerging that they may also have a role in screening but their accuracy in this context and the associated optimal thresholds, have not been established. The impact that NP screening would have on patients and health care systems also remains unclear. Methods: We aim to undertake a systematic search of the following sources: Ovid Medline, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. Screening, data extraction and critical appraisal will be carried out independently and in duplicate by two reviewers. We will include studies based in the community with &gt;100 participants that recruited a screened population. We will not add a study design filter and there will be no language restriction. The primary outcome will be the sensitivity and the specificity of NP screening and optimal thresholds for screening will be explored. Outcomes of interest for the impact analysis will include mortality, hospital admissions and cost effectiveness. This protocol has been developed in accordance with guidelines from the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). Discussion: This systematic review will identify how accurately NP screen for heart failure in the community and explore where NP screening thresholds should be set. It also aims to summarise the clinical impact of this strategy. Together, these results should inform future interventions that may provide an alternative pathway to facilitate improved detection of heart failure in the community. Registration: PROSPERO CRD42018087498; registered on 11 May 2018.</p