A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1b immunohistochemistry, and tumor necrosis factor (TNF)-a and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (Po0.05). Higher hepatic TNF-a (Po0.001) and IL-10 (Po0.01) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells (presumably Kupffer cells) were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA-I mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity

Direct Measurement of Nuclear Dependence of Charged Current Quasielastic-like Neutrino Interactions using MINERvA

Charged-current $\nu_{\mu}$ interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielastic-like interactions. The transfered four-momentum squared to the target nucleus, $Q^2$, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus $Q^2$ and the cross-section ratios of iron, lead and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on atomic number. While the quasielastic-like scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments

Physical characterisation of an alginate/lysozyme nano-laminate coating and its evaluation on ‘coalho’ cheese shelf life

This work aimed at the characterisation of a nanolaminate coating produced by the layer-by-layer methodology and its evaluation on the preservation of ‘Coalho’ cheese. Initially, five alternate layers of alginate and lysozyme were assembled in an aminolysed/charged polyethylene terephthalate (A/C PET) and physically characterised by UV/VIS spectroscopy, contact angle, water vapour (WVTR) and oxygen (OTR) transmission rates and scanning electron microscopy. Afterwards, the same methodology was used to apply the nano-laminate coating in ‘Coalho’ cheese and its shelf life was evaluated during 20 days in terms of mass loss, pH, lipid peroxidation, titratable acidity and microbial count. UV/VIS spectroscopy and contact angle analyses confirmed the layers’ deposition and the successful assembly of nano-laminate coating on A/C PET surface. The coating presented WVTR and OTR values of 1.03×10−3 and 1.28× 10−4 g m−2 s−1, respectively. After 20 days, coated cheese showed lower values of mass loss, pH, lipidic peroxidation, microorganisms’ proliferation and higher titratable acidity in comparison with uncoated cheese. These results suggest that gas barrier and antibacterial properties of alginate/lysozyme nanocoating can be used to extend the shelf life of ‘Coalho’ cheese.The author Bartolomeu G. de S. Medeiros is recipient of a scholarship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-Brazil). The author Marthyna P. Souza is recipient of a scholarship from Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE, Brazil) and was recipient of a scholarship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/PDEE-Brazil). The authors Ana C. Pinheiro, Ana I. Bourbon and Miguel A. Cerqueira are recipients of a fellowship (SFRH/BD/48120/2008, SFRH/BD/73178/2010 and SFRH/BPD/72753/2010, respectively), supported by Fundacao para a Ciencia e Tecnologia, POPH-QREN and FSE (FCT, Portugal). Maria G. Carneiro-da-Cunha express is gratitude to the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) for research grant. The present work was supported by CAPES/PROCAD/NF/1415/2007. The support of EU Cost Action FA0904 is gratefully acknowledged

Modelling the Protective Efficacy of Alternative Delivery Schedules for Intermittent Preventive Treatment of Malaria in Infants and Children

BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy. METHODS AND FINDINGS: A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone. CONCLUSION: Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria

Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC

Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer’s desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples

Seasonality of Plasmodium falciparum transmission: a systematic review

This article is fully open access and the published version is available free of charge from the jounal website.http://www.malariajournal.com/content/14/1/343Background Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has “strongly seasonal” transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized. Methods The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts. Results and discussion 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both). Discussion Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location. Conclusions The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales. Keywords: Plasmodium falciparum ; Seasonality; Climatic driversAcknowledgements This work was supported by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, and Fogarty International Center, National Institutes of Health. DLS is funded by a grant from the Bill & Melinda Gates Foundation (OPP1110495), which also supports RCR. PMA is grateful to the University of Utrecht for supporting him with The Belle van Zuylen Chair. PWG is a Career Development Fellow (K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and receives support from the Bill and Melinda Gates Foundation (OPP1068048, OPP1106023)

Malaria risk factors in north-east Tanzania

BACKGROUND: Understanding the factors which determine a household's or individual's risk of malaria infection is important for targeting control interventions at all intensities of transmission. Malaria ecology in Tanzania appears to have reduced over recent years. This study investigated potential risk factors and clustering in face of changing infection dynamics. METHODS: Household survey data were collected in villages of rural Muheza district. Children aged between six months and thirteen years were tested for presence of malaria parasites using microscopy. A multivariable logistic regression model was constructed to identify significant risk factors for children. Geographical information systems combined with global positioning data and spatial scan statistic analysis were used to identify clusters of malaria. RESULTS: Using an insecticide-treated mosquito net of any type proved to be highly protective against malaria (OR 0.75, 95% CI 0.59-0.96). Children aged five to thirteen years were at higher risk of having malaria than those aged under five years (OR 1.71, 95% CI 1.01-2.91). The odds of malaria were less for females when compared to males (OR 0.62, 95% CI 0.39-0.98). Two spatial clusters of significantly increased malaria risk were identified in two out of five villages. CONCLUSIONS: This study provides evidence that recent declines in malaria transmission and prevalence may shift the age groups at risk of malaria infection to older children. Risk factor analysis provides support for universal coverage and targeting of long-lasting insecticide-treated nets (LLINs) to all age groups. Clustering of cases indicates heterogeneity of risk. Improved targeting of LLINs or additional supplementary control interventions to high risk clusters may improve outcomes and efficiency as malaria transmission continues to fall under intensified control

Emergence of terpene cyclization in Artemisia annua

The emergence of terpene cyclization was critical to the evolutionary expansion of chemical diversity yet remains unexplored. Here we report the first discovery of an epistatic network of residues that controls the onset of terpene cyclization in Artemisia annua. We begin with amorpha-4,11-diene synthase (ADS) and (E)-b-farnesene synthase (BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of B27,000 enzymes is generated by breeding combinations of natural amino-acid substitutions from the cyclic into the linear producer. We discover one dominant mutation is sufficient to activate cyclization, and together with two additional residues comprise a network of strongly epistatic interactions that activate, suppress or reactivate cyclization. Remarkably, this epistatic network of equivalent residues also controls cyclization in a BFS homologue from Citrus junos. Fitness landscape analysis of mutational trajectories provides quantitative insights into a major epoch in specialized metabolism

Centrifugal melt spinning of polyvinylpyrrolidone (PVP)/triacontene copolymer fibres

Polyvinylpyrrolidone/1-triacontene (PVP/TA) copolymer fibre webs produced by centrifugal melt spinning were studied to determine the influence of jet rotation speed on morphology and internal structure as well as their potential utility as adsorbent capture media for disperse dye effluents. Fibres were produced at 72 C with jet head rotation speeds from 7000 to 15,000 r min-1. The fibres were characterised by means of SEM, XRD and DSC. Adsorption behaviour was investigated by means of an isothermal bottle point adsorption study using a commercial disperse dye, Dianix AC-E. Through centrifugal spinning nanofibers and microfibers could be produced with individual fibres as fine as 200–300 nm and mean fibre diameters of ca. 1–2 lm. The PVP/TA fibres were mechanically brittle with characteristic brittle tensile fracture regions observed at the fibre ends. DSC and XRD analyses suggested that this brittleness was linked to the graft chain crystallisation where the PVP/TA was in the form of a radial brush copolymer. In this structure, the triacontene branches interlock and form small lateral crystals around an amorphous backbone. As an adsorbent, the PVP/TA fibres were found to adsorb 35.4 mg g-1 compared to a benchmark figure of 30.0 mg g-1 for a granular-activated carbon adsorbent under the same application conditions. PVP/TA is highly hydrophobic and adsorbs disperse dyes through the strong ‘‘hydrophobic bonding’’ interaction. Such fibrous assemblies may have applications in the targeted adsorption and separation of non-polar species from aqueous or polar environments