Whole Genome Sequencing of Field Isolates Reveals a Common Duplication of the Duffy Binding Protein Gene in Malagasy Plasmodium vivax Strains

Background

Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes.

Methods/Principal Findings

Through recent whole genome sequencing we obtained ≥70× coverage of the P. vivax genome from five field-isolates, resulting in ≥93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported.

Conclusions/Significance

The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations.     

Intake of Farmed Atlantic Salmon Fed Soybean Oil Increases Insulin Resistance and Hepatic Lipid Accumulation in Mice

Background

To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice.

Methodology/principal findings

Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n−3 polyunsaturated fatty acid (PUFA) content and increased n−6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver.

Conclusion/Significance

Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.     

Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

Seasonal plasticity of Ludwigia grandiflora under light and water depth gradients: An outdoor mesocosm experiment

Abiotic factors in the introduced area can limit the establishment of exotic species. Adaptation to new abiotic parameters through plastic responses is important for their establishment and distribution pattern. Survival and growth of exotic hydrophytes are related to their plasticity and their ability to adapt to local conditions. Light and water depth are two of the predominant factors determining survival, growth, distribution and abundance of aquatic plants. Although many studies have been carried out on the effect of water level and light on plant performance, their potential interactions are poorly understood. Here, we carried out an outdoor mesocosm experiment, in order to test the role of water depth, light intensity and their potential interactions on the growth and vigour of the invasive macrophyte species Ludwigia grandiflora. Three light intensities (100%, 70% and 50% of sunlight) and three water depths (30, 50 and 80 cm) were tested over a 6-week period, in spring, summer and autumn 2011. We showed that the mortality, biomass, apical and lateral growth of L. grandiflora, as well as its biomass allocation, varied according to the season and responded to both light intensity and water depth. Interactions between water depth and light intensity can have an amplifying effect on the growth of L. grandiflora. Similarities between shade and deep water adaptation responses were observed. A higher biomass and a high morphological plasticity in response to these factors were found particularly at the beginning of the life cycle. Although the invasive amphibious L. grandiflora shows a high tolerance to different water levels and light intensities, the optimal growth conditions for L. grandiflora in our experiment seem to be under full sunlight and in 30 cm of water. Colonization of light or low shade aquatic habitats, as well as shallow environments, can occur due to the high plasticity of L. grandiflora. These results may be important relative to increasing level of water bodies under climatic changes.     

Do stream fish track climate change? Assessing distribution shifts in recent decades

Understanding the ability of species to shift their distribution ranges in response to climate change is crucial for conservation biologists and resources managers. Although freshwater ecosystems include some of the most imperilled fauna worldwide, such range shifts have been poorly documented in streams and rivers and have never been compared to the current velocity of climate change. Based on national monitoring data, we examined the distributional changes of 32 stream fish species in France and quantified potential time lags in species responses, providing a unique opportunity to analyze range shifts over recent decades of warming in freshwater environments. A multi‐facetted approach, based on several range measures along spatial gradients, allowed us to quantify range shifts of numerous species across the whole hydrographic network between an initial period (1980–1992) and a contemporary one (2003–2009), and to contrast them to the rates of isotherm shift in elevation and stream distance. Our results highlight systematic species shifts towards higher elevation and upstream, with mean shifts in range centre of 13.7 m decade^?1 and 0.6 km decade^?1, respectively. Fish species displayed dispersal‐driven expansions along the altitudinal gradient at their upper range limit (61.5 m decade^?1), while substantial range contractions at the lower limit (6.3 km decade^?1) were documented for most species along the upstream–downstream gradient. Despite being consistent with the geographic variation in climate change velocities, these patterns reveal that the majority of stream fish have not shifted at a pace sufficient to track changing climate, in particular at their range centre where range shifts lag far behind expectation. Our study provides evidence that stream fish are currently responding to recent climate warming at a greater rate than many terrestrial organisms, although not as much as needed to cope with future climate modifications.     

Anthropogenic subsidies mitigate environmental variability for insular rodents

The exogenous input of nutrients and energy into island systems fuels a large array of consumers and drives bottom-up trophic cascades in island communities. The input of anthropogenic resources has increased on islands and particularly supplemented non-native consumers with extra resources. We test the hypothesis that the anthropogenic establishments of super-abundant gulls and invasive iceplants Carpobrotus spp. have both altered the dynamics of an introduced black rat Rattus rattus population. On Bagaud Island, two habitats have been substantially modified by the anthropogenic subsidies of gulls and iceplants, in contrast to the native Mediterranean scrubland with no anthropogenic inputs. Rats were trapped in all three habitats over two contrasting years of rainfall patterns to investigate: (1) the effect of anthropogenic subsidies on rat density, age-ratio and growth rates, and (2) the role of rainfall variability in modulating the effects of subsidies between years. We found that the growth rates of rats dwelling in the non-subsidized habitat varied with environmental fluctuation, whereas rats dwelling in the gull colony maintained high growth rates during both dry and rainy years. The presence of anthropogenic subsidies apparently mitigated environmental stress. Age ratio and rat density varied significantly and predictably among years, seasons, and habitats. While rat densities always peaked higher in the gull colony, especially after rat breeding in spring, higher captures of immature rats were recorded during the second year in all habitats, associated with higher rainfall. The potential for non-native rats to benefit from anthropogenic resources has important implications for the management of similar species on islands.     

Acidic biphenyl derivatives: Synthesis and biological activity of a new series of potent 5-HT4 receptor antagonists

Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT₄ receptors in the atrium and ventricle of the heart. Recent investigations have revealed increased expression of the 5-HT_4(b) isoform in cardiomyocytes of chronic arrhythmic and failing hearts, and that the use of 5-HT₄ receptor antagonists may be beneficial for treating these conditions. The 5-HT₄ receptor possesses a transmembrane (TM) binding site important for ligand affinity and recognition, as well as a capacity to accommodate bulky ligands. A new series of peripherally-acting 5-HT₄ receptor antagonists were prepared by combining the acidic biphenyl group from the class of angiotensin II receptor blockers (ARBs) with the SB207266 (piboserod) scaffold. The new compounds were pharmacologically evaluated and carboxylic acid 21 was identified as a potent and promising 5-HT₄ receptor antagonist with moderate affinity for the AT₁ receptor. The permeability of carboxylic acid 21 in a Caco-2 assay was low and the corresponding prodrug esters 23a–f were therefore prepared. The pharmacokinetics of methyl ester 20 and n-butyl ester 23c were evaluated in a rat model, revealing incomplete metabolism to carboxylic acid 21. However, methyl ester 20 is a potent 5-HT₄ receptor antagonist with binding affinities in the low picomolar range. Methyl ester 20 has promising oral bioavailability and pharmacokinetics and may target 5-HT₄ receptors in both CNS and peripheral organs.     

Eumelanin‐based colouration reflects local survival of juvenile feral pigeons in an urban pigeon house

Urbanisation introduces deep changes in habitats, eventually creating new urban ecosystems where ecological functions are driven by human activities. The higher frequency of some phenotypes in urban vs rural/wild areas has led to the assumption that directional selection in urban habitats occurs, which may thereby favour some behavioural and physiological traits in urban animal populations compared to rural ones. However, empirical evidence of directional selection on phenotypic traits in urban areas remains scarce. In this study we tested whether eumelanin‐based colouration could be linked to survival in two urban populations of the feral pigeon Columba livia. A number of studies in different cities pointed out a higher frequency of darker individuals in more urbanised areas compared to rural ones. To investigate whether directional selection through survival on this highly heritable trait could explain such patterns, we conducted mark–recapture studies on two populations of feral pigeons in highly urbanized areas. We predicted that darker coloured individuals would exhibit higher survival and/or philopatry (integrated into ‘local survival’) than paler coloured ones. No difference in local survival was found between adults of different colouration intensities. However, on one site, we found that darker juveniles had a higher local survival probability than light ones. Juvenile local survival on that site was also negatively correlated with the number of chicks born. This suggests the existence of colour‐ and/or density‐dependent selection processes acting on juvenile feral pigeons in urban environments, acting through differential mortality and/or dispersal.     

High Burden of Human Papillomavirus (HPV) Infection among Young Women in KwaZulu-Natal,South Africa

Objectives

HPV infection causes cervical cancer, yet information on prevalence and risk factors for HPV in Africa remain sparse. This study describes the prevalence of HPV genotypes and risk factors associated with HPV among young women ≤ 30 years of age in KwaZulu-Natal (KZN), South Africa.

Methods

Cervicovaginal lavage samples were tested for HPV genotypes in 224 women enrolled in a prospective cohort study. Clinical, behavioural and demographic data were collected. We measured prevalence of HPV genotypes and using logistic regression, examined for factors associated with HPV.

Results

Median age of participants was 21 years [interquartile range (IQR):18–23]. The overall prevalence of HPV was 76.3% (171/224) with multiple and single genotypes prevalent in 56.3% and 20.1% of women respectively. Proportion of women with high-risk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56 and 58) was 54.5%. Women not living with their partner [adjusted odds ratio (aOR)] = 3.42 95% CI1.22–9.60; p = 0.019), was significantly associated with HPV infection and high-risk HPV genotype infection.

Conclusion

The high burden of HPV and associated risk behaviours highlight the need to intensify behavioural interventions to prevent HPV acquisition in young women. The large scale delivery of HPV vaccine should be prioritised to prevent HPV acquisition and reduce HPV-related morbidity.