Relevant microclimate for determining the development rate of malaria mosquitoes and possible implications of climate change

Background The relationship between mosquito development and temperature is one of the keys to understanding the current and future dynamics and distribution of vector-borne diseases such as malaria. Many process-based models use mean air temperature to estimate larval development times, and hence adult vector densities and/or malaria risk. Methods Water temperatures in three different-sized water pools, as well as the adjacent air temperature in lowland and highland sites in western Kenya were monitored. Both air and water temperatures were fed into a widely-applied temperature-dependent development model for Anopheles gambiae immatures, and subsequently their impact on predicted vector abundance was assessed. Results Mean water temperature in typical mosquito breeding sites was 4-6°C higher than the mean temperature of the adjacent air, resulting in larval development rates, and hence population growth rates, that are much higher than predicted based on air temperature. On the other hand, due to the non-linearities in the relationship between temperature and larval development rate, together with a marginal buffering in the increase in water temperature compared with air temperature, the relative increases in larval development rates predicted due to climate change are substantially less. Conclusions Existing models will tend to underestimate mosquito population growth under current conditions, and may overestimate relative increases in population growth under future climate change. These results highlight the need for better integration of biological and environmental information at the scale relevant to mosquito biology

Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year(1,2). Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity(2-4). Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain ( El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods ( over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods ( under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Nino Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62876/1/nature03820.pd

bioNMF: a versatile tool for non-negative matrix factorization in biology

BACKGROUND: In the Bioinformatics field, a great deal of interest has been given to Non-negative matrix factorization technique (NMF), due to its capability of providing new insights and relevant information about the complex latent relationships in experimental data sets. This method, and some of its variants, has been successfully applied to gene expression, sequence analysis, functional characterization of genes and text mining. Even if the interest on this technique by the bioinformatics community has been increased during the last few years, there are not many available simple standalone tools to specifically perform these types of data analysis in an integrated environment. RESULTS: In this work we propose a versatile and user-friendly tool that implements the NMF methodology in different analysis contexts to support some of the most important reported applications of this new methodology. This includes clustering and biclustering gene expression data, protein sequence analysis, text mining of biomedical literature and sample classification using gene expression. The tool, which is named bioNMF, also contains a user-friendly graphical interface to explore results in an interactive manner and facilitate in this way the exploratory data analysis process. CONCLUSION: bioNMF is a standalone versatile application which does not require any special installation or libraries. It can be used for most of the multiple applications proposed in the bioinformatics field or to support new research using this method. This tool is publicly available at

Temperature and Malaria Trends in Highland East Africa

There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region. We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglia's Climatic Research Unit database (CRU TS) for several relevant locations. We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996. The trends in the newer data are even more significant when post-1996 data are added to the samples. We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al. We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample. However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level. A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho

Forcing Versus Feedback: Epidemic Malaria and Monsoon Rains in Northwest India

Malaria epidemics in regions with seasonal windows of transmission can vary greatly in size from year to year. A central question has been whether these interannual cycles are driven by climate, are instead generated by the intrinsic dynamics of the disease, or result from the resonance of these two mechanisms. This corresponds to the more general inverse problem of identifying the respective roles of external forcings vs. internal feedbacks from time series for nonlinear and noisy systems. We propose here a quantitative approach to formally compare rival hypotheses on climate vs. disease dynamics, or external forcings vs. internal feedbacks, that combines dynamical models with recently developed, computational inference methods. The interannual patterns of epidemic malaria are investigated here for desert regions of northwest India, with extensive epidemiological records for Plasmodium falciparum malaria for the past two decades. We formulate a dynamical model of malaria transmission that explicitly incorporates rainfall, and we rely on recent advances on parameter estimation for nonlinear and stochastic dynamical systems based on sequential Monte Carlo methods. Results show a significant effect of rainfall in the inter-annual variability of epidemic malaria that involves a threshold in the disease response. The model exhibits high prediction skill for yearly cases in the malaria transmission season following the monsoonal rains. Consideration of a more complex model with clinical immunity demonstrates the robustness of the findings and suggests a role of infected individuals that lack clinical symptoms as a reservoir for transmission. Our results indicate that the nonlinear dynamics of the disease itself play a role at the seasonal, but not the interannual, time scales. They illustrate the feasibility of forecasting malaria epidemics in desert and semi-arid regions of India based on climate variability. This approach should be applicable to malaria in other locations, to other infectious diseases, and to other nonlinear systems under forcing

Climate Change and the Geographic Distribution of Infectious Diseases

Our ability to predict the effects of climate change on the spread of infectious diseases is in its infancy. Numerous, and in some cases conflicting, predictions have been developed, principally based on models of biological processes or mapping of current and historical disease statistics. Current debates on whether climate change, relative to socioeconomic determinants, will be a major influence on human disease distributions are useful to help identify research needs but are probably artificially polarized. We have at least identified many of the critical geophysical constraints, transport opportunities, biotic requirements for some disease systems, and some of the socioeconomic factors that govern the process of migration and establishment of parasites and pathogens. Furthermore, we are beginning to develop a mechanistic understanding of many of these variables at specific sites. Better predictive understanding will emerge in the coming years from analyses regarding how these variables interact with each other

Comparing Models for Early Warning Systems of Neglected Tropical Diseases

Early Warning Systems (EWS) are management tools to predict the occurrence of epidemics. They are based on the dependence of a given infectious disease on environmental variables. Although several neglected tropical diseases are sensitive to the effect of climate, our ability to predict their dynamics has been barely studied. In this paper, we use several models to determine if the relationship between cases and climatic variability is robust—that is, not simply an artifact of model choice. We propose that EWS should be based on results from several models that are to be compared in terms of their ability to predict future number of cases. We use a specific metric for this comparison known as the predictive R2, which measures the accuracy of the predictions. For example, an R2 of 1 indicates perfect accuracy for predictions that perfectly match observed cases. For cutaneous leishmaniasis, R2 values range from 72% to77%, well above predictions using mean seasonal values (64%). We emphasize that predictability should be evaluated with observations that have not been used to fit the model. Finally, we argue that EWS should incorporate climatic variables that are known to have a consistent relationship with the number of observed cases

A combination of three surface modifiers for the optimal generation and application of natural hybrid nanopigments in a biodegradable resin

Our purpose was to improve the thermal, mechanical and optimal properties of an epoxy bioresin using optimum hybrid natural pigments previously synthesised in our lab. Next, we searched for the best combinations of factors in the synthesis of natural hybrid nanopigments and then incorporated them into the bioresin. We combined three structural modifiers in the nanopigment synthesis, surfactant, coupling agent (silane) and a mordant salt (alum), selected to replicate mordant textile dyeing with natural dyes. We used Taguchi s design L8 to seek final performance optimisation. We selected three natural dyes, chlorophyll, beta-carotene and beetroot extract, and used two laminar nanoclay types, montmorillonite and hydrotalcite. The thermal, mechanical and colorimetric characterisation of the composite obtained by mixing natural hybrid nanopigments (bionanocomposite) was made. The natural dye interactions with both nanoclays improved the thermal stabilities, colour performance and UV VIS light exposure stability of natural dyes and bioresins. The best bionanocomposite materials were found in an acidic pH [3, 4] environment and by modifying nanoclays with mordant and surfactant during the nanopigment synthesis processWe thank the Spanish Ministry of Economy and Competitiveness for funding Projects DPI2011-30090-C02-02 and DPI2015-68514-R.Micó Vicent, B.; Jordán Núñez, J.; Martinez Verdu, FM.; Balart Gimeno, RA. (2017). A combination of three surface modifiers for the optimal generation and application of natural hybrid nanopigments in a biodegradable resin. Journal of Materials Science. 52(2):889-898. https://doi.org/10.1007/s10853-016-0384-8S889898522Majdzadeh-Ardakani K, Nazari B (2010) Improving the mechanical properties of thermoplastic starch/poly(vinyl alcohol)/clay nanocomposites. Compos Sci Technol 70(10):1557–1563. doi: 10.1016/j.compscitech.2010.05.022Najafi N, Heuzey MC, Carreau PJ (2012) Polylactide (PLA)-clay nanocomposites prepared by melt compounding in the presence of a chain extender. Compos Sci Technol 72(5):608–615. doi: 10.1016/j.compscitech.2012.01.005Acharya H, Srivastava SK, Bhowmick AK (2007) Synthesis of partially exfoliated EPDM/LDH nanocomposites by solution intercalation: structural characterization and properties. Compos Sci Technol 67(13):2807–2816. doi: 10.1016/j.compscitech.2007.01.030Marras SI, Zuburtikudis I, Panayiotou C (2007) Nanostructure vs. microstructure: morphological and thermomechanical characterization of poly(L-lactic acid)/layered silicate hybrids. Eur Polymer J 43(6):2191–2206. doi: 10.1016/j.eurpolymj.2007.03.013Leszczyńska A, Njuguna J, Pielichowski K, Banerjee JR (2007) Polymer/montmorillonite nanocomposites with improved thermal properties: Part I. Factors influencing thermal stability and mechanisms of thermal stability improvement. Thermochim Acta 453(2):75–96. doi: 10.1016/j.tca.2006.11.002Park HM, Lee WK, Park CY, Cho WJ, Ha CS (2003) Environmentally friendly polymer hybrids Part I Mechanical, thermal, and barrier properties of thermoplastic starch/clay nanocomposites. J Mater Sci 38(5):909–915. doi: 10.1023/a:1022308705231Porter D, Metcalfe E, Thomas MJK (2000) Nanocomposite fire retardants—a review. Fire Mater 24(1):45–52. doi: 10.1002/(sici)1099-1018(200001/02)24:13.0.co;2-sRay SS, Okamoto M (2003) Polymer/layered silicate nanocomposites: a review from preparation to processing. Prog Polym Sci 28(11):1539–1641. doi: 10.1016/j.progpolymsci.2003.08.002Gao D, Li R, Lv B, Ma J, Tian F, Zhang J (2015) Flammability, thermal and physical-mechanical properties of cationic polymer/montmorillonite composite on cotton fabric. Compos B Eng 77:329–337. doi: 10.1016/j.compositesb.2015.03.061LeBaron PC, Wang Z, Pinnavaia TJ (1999) Polymer-layered silicate nanocomposites: an overview. Appl Clay Sci 15(1–2):11–29. doi: 10.1016/s0169-1317(99)00017-4Karuntarut Sermsantiwanita SP (2012) Preparation of bio-based nanocomposite emulsions: effect of clay type. Prog Org Coat 74:660–666Pascual J, Fages E, Fenollar O, Garcia D, Balart R (2009) Influence of the compatibilizer/nanoclay ratio on final properties of polypropylene matrix modified with montmorillonite-based organoclay. Polym Bull 62(3):367–380. doi: 10.1007/s00289-008-0018-7Beltrán MI, Benavente V, Marchante V, Marcilla A (2013) The influence of surfactant loading level in a montmorillonite on the thermal, mechanical and rheological properties of EVA nanocomposites. Appl Clay Sci 83–84:153–161. doi: 10.1016/j.clay.2013.08.028Bitinis N, Verdejo R, Maya EM, Espuche E, Cassagnau P, Lopez-Manchado MA (2012) Physicochemical properties of organoclay filled polylactic acid/natural rubber blend bionanocomposites. Compos Sci Technol 72(2):305–313. doi: 10.1016/j.compscitech.2011.11.018Sanchez-Garcia MD, Lopez-Rubio A, Lagaron JM (2010) Natural micro and nanobiocomposites with enhanced barrier properties and novel functionalities for food biopackaging applications. Trends Food Sci Technol 21(11):528–536. doi: 10.1016/j.tifs.2010.07.008Huskić M, Žigon M, Ivanković M (2013) Comparison of the properties of clay polymer nanocomposites prepared by montmorillonite modified by silane and by quaternary ammonium salts. Appl Clay Sci 85:109–115. doi: 10.1016/j.clay.2013.09.004Osman MA, Rupp JEP, Suter UW (2005) Effect of non-ionic surfactants on the exfoliation and properties of polyethylene-layered silicate nanocomposites. Polymer 46(19):8202–8209. doi: 10.1016/j.polymer.2005.06.101Wang H, Fang P, Chen Z, Wang S, Xu Y, Fang Z (2008) Effect of silane grafting on the microstructure of high-density polyethylene/organically modified montmorillonite nanocomposites. Polym Int 57(1):50–56. doi: 10.1002/pi.2310Montgomery DC (2008) Design and analysis of experiments. Wiley, HobokenBaena-Murillo E, Micó-Vicent B, Martínez-Verdú FM (2013) Method for the synthesis of nanostructured hybrid pigments having properties that can be syntonized. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2013110841&recNum=229&docAn=ES2013070026&queryString=(ANA:ES)&maxRec=25813Kohno Y, Inagawa M, Ikoma S, Shibata M, Matsushima R, Fukuhara C, Tomita Y, Maeda Y, Kobayashi K (2011) Stabilization of a hydrophobic natural dye by intercalation into organo-montmorillonite. Appl Clay Sci 54(3):202–205. doi: 10.1016/j.clay.2011.09.001Kaneko Y, Iyi N, Bujdak J, Sasai R, Fujita T (2004) Effect of layer charge density on orientation and aggregation of a cationic laser dye incorporated in the interlayer space of montmorillonites. J Colloid Interface Sci 269(1):22–25. doi: 10.1016/s0021-9797(03)00602-7Silva AA, Dahmouche K, Soares BG (2011) Nanostructure and dynamic mechanical properties of silane-functionalized montmorillonite/epoxy nanocomposites. Appl Clay Sci 54(2):151–158. doi: 10.1016/j.clay.2011.08.002Park S-J, Kim B-J, Seo D-I, Rhee K-Y, Lyu Y-Y (2009) Effects of a silane treatment on the mechanical interfacial properties of montmorillonite/epoxy nanocomposites. Mater Sci Eng A 526(1–2):74–78. doi: 10.1016/j.msea.2009.07.023Khraisheh MAM, Al-Ghouti MA, Allen SJ, Ahmad MN (2005) Effect of OH and silanol groups in the removal of dyes from aqueous solution using diatomite. Water Res 39(5):922–932. doi: 10.1016/j.watres.2004.12.008Fahn R, Fenderl K (1983) Reaction-products of organic-dye molecules with acid-treated montmorillonite. Clay Miner 18(4):447–458. doi: 10.1180/claymin.1983.018.4.10Kohno Y, Totsuka K, Ikoma S, Yoda K, Shibata M, Matsushima R, Tomita Y, Maeda Y, Kobayashi K (2009) Photostability enhancement of anionic natural dye by intercalation into hydrotalcite. J Colloid Interface Sci 337(1):117–121. doi: 10.1016/j.jcis.2009.04.065Capilla P, Pujol J (2002) Fundamentos de Colorimetría. Universitat de ValenciaGilabert EJ, Verdú FMM (2007) Medida de la luz y el color. Editorial de la UPV. In: Color psicofísico, pp 185–221Zhao H, Nagy KL (2004) Dodecyl sulfate–hydrotalcite nanocomposites for trapping chlorinated organic pollutants in water. J Colloid Interface Sci 274(2):613–624. doi: 10.1016/j.jcis.2004.03.05

Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α-hydroxy-4-cholesten-3-one. Terminal ileal farnesoid X receptor (FXR)-mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole-genome sequencing and ultra-performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase-producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15-mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia