Assessment of Plasmodium Falciparum RNA Pseudouridylate Synthase (Putative) as Novel Drug Target

Malaria is a major public health problem associated with high mortality, morbidity rates and undue economic burden in sub-Saharan countries. Presently, every year, 300 to 500 million people suffer clinically from malaria and 90% of them in sub-Saharan Africa. About 1.5 to 3 million people die of malaria every year and 85% of these occur in Africa. One child dies of malaria somewhere in Africa every 20 second, and there is one malarial death every 12 sec somewhere in the world. This is also a damaging economic burden for these sub-Saharan Africa countries as huge work force time and resources are expended for treatment. Plasmodium falciparum (hence forth Pf) is the most severe of all the human malaria parasites. This organism is continuing to develop resistance to all known drugs and therapeutic regime. One of the mechanisms of resistance in Pf is the modification of the drug target. Hence, it is expedient to continuously discover novel drug targets in Pf and to discover or develop new drugs against such targets. Drug-able signaling pathways have been shown to have inherent mechanism capable of deterring drug resistance. Using computational techniques, we have identified some proteins in the signaling pathways of Pf as putative targets for anti-plasmodia drug. RNA pseudouridylate synthase, which also plays a key role in RNA synthesis and ribosomal function, is one of such proteins. Initial virtual screening of this enzyme against drug and chemical databases has been performed to identify compounds that can inhibit this enzyme. This led us to compounds which inhibit nucleotide metabolism. This is a work in progress whose current state is hoped for presentation at this conference. In order to determine the identified compounds IC50, the identified compounds will be screened in vitro against the enzyme. We have currently completed the establishment of the enzyme functionally expression in E. coli and purification. Thereafter, the drugs will be screened for their anti-plasmodia activity using cultured Pf and the IC50 for each drug will be determined. In order to assess their safety, the selectivity index of compounds that showed in vitro anti-plasmodia activity will be determined using human cultured cell lines. The last stage of this study will involve screening the compounds in an in vivo mouse model of malaria. It is hoped that the result of this study will prove this enzyme as a novel target for antimalarial drug. And provide as input, critical drug targets in to our established Structure Based Drug Design (SBDD) pipelin

A review of coarse mineral dust in the Earth system

Mineral dust particles suspended in the atmosphere span more than three orders of magnitude in diameter, from <0.1 µm to more than 100 µm. This wide size range makes dust a unique aerosol species with the ability to interact with many aspects of the Earth system, including radiation, clouds, hydrology, atmospheric chemistry, and biogeochemistry. This review focuses on coarse and super-coarse dust aerosols, which we respectively define as dust particles with a diameter of 2.5–10 µm and 10–62.5 µm. We review several lines of observational evidence indicating that coarse and super-coarse dust particles are transported farther than previously expected and that the abundance of these particles is substantially underestimated in current global models. We synthesize previous studies that used observations, theories, and model simulations to highlight the impacts of coarse and super-coarse dust aerosols on the Earth system, including their effects on dust-radiation interactions, dust-cloud interactions, atmospheric chemistry, and biogeochemistry. Specifically, coarse and super-coarse dust aerosols produce a net positive direct radiative effect (warming) at the top of the atmosphere and can modify temperature and water vapor profiles, influencing the distribution of clouds and precipitation. In addition, coarse and super-coarse dust aerosols contribute a substantial fraction of ice-nucleating particles, especially at temperatures above –23 °C. They also contribute a substantial fraction to the available reactive surfaces for atmospheric processing and the dust deposition flux that impacts land and ocean biogeochemistry by supplying important nutrients such as iron and phosphorus. Furthermore, we examine several limitations in the representation of coarse and super-coarse dust aerosols in current model simulations and remote-sensing retrievals. Because these limitations substantially contribute to the uncertainties in simulating the abundance and impacts of coarse and super-coarse dust aerosols, we offer some recommendations to facilitate future studies. Overall, we conclude that an accurate representation of coarse and super-coarse properties is critical in understanding the impacts of dust aerosols on the Earth system

A review of coarse mineral dust in the Earth system

Mineral dust particles suspended in the atmosphere span more than three orders of magnitude in diameter, from <0.1 µm to more than 100 µm. This wide size range makes dust a unique aerosol species with the ability to interact with many aspects of the Earth system, including radiation, clouds, hydrology, atmospheric chemistry, and biogeochemistry. This review focuses on coarse and super-coarse dust aerosols, which we respectively define as dust particles with a diameter of 2.5–10 µm and 10–62.5 µm. We review several lines of observational evidence indicating that coarse and super-coarse dust particles are transported farther than previously expected and that the abundance of these particles is substantially underestimated in current global models. We synthesize previous studies that used observations, theories, and model simulations to highlight the impacts of coarse and super-coarse dust aerosols on the Earth system, including their effects on dust-radiation interactions, dust-cloud interactions, atmospheric chemistry, and biogeochemistry. Specifically, coarse and super-coarse dust aerosols produce a net positive direct radiative effect (warming) at the top of the atmosphere and can modify temperature and water vapor profiles, influencing the distribution of clouds and precipitation. In addition, coarse and super-coarse dust aerosols contribute a substantial fraction of ice-nucleating particles, especially at temperatures above –23 °C. They also contribute a substantial fraction to the available reactive surfaces for atmospheric processing and the dust deposition flux that impacts land and ocean biogeochemistry by supplying important nutrients such as iron and phosphorus. Furthermore, we examine several limitations in the representation of coarse and super-coarse dust aerosols in current model simulations and remote-sensing retrievals. Because these limitations substantially contribute to the uncertainties in simulating the abundance and impacts of coarse and super-coarse dust aerosols, we offer some recommendations to facilitate future studies. Overall, we conclude that an accurate representation of coarse and super-coarse properties is critical in understanding the impacts of dust aerosols on the Earth system

Water demand modelling using evolutionary computation techniques: integrating water equity and justice for realization of the sustainable development goals

The purpose of this review is to establish and classify the diverse ways in which evolutionary computation (EC) techniques have been employed in water demand modelling and to identify important research challenges and future directions. This review also investigates the potentials of conventional EC techniques in influencing water demand management policies beyond an advisory role while recommending strategies for their use by policy-makers with the sustainable development goals (SDGs) in perspective. This review ultimately proposes a novel integrated water demand and management modelling framework (IWDMMF) that enables water policy-makers to assess the wider impact of water demand management decisions through the principles of egalitarianism, utilitarianism, libertarianism and sufficientarianism. This is necessary to ensure that water policy decisions incorporate equity and justice. Environmental science; Applied computing; Computing methodology; Civil engineering; Process modeling; Hydrology; evolutionary computation; water justice; water demand; Artificial intelligence; water equity; Sustainable development goal

Functional properties and predicted glycemic index of gluten free cereal, pseudocereal and legume flours

Most of gluten free (GF) bakery products available on the market are made by a restricted number of grains. Flours and starches from rice and maize are mainly used. For this reason, people affected by celiac disease frequently suffer of nutritional deficiencies and have high intake of some nutrients. The use of a wider range of GF flours, rich in nutrients and phytochemicals, may improve the nutritional quality of GF products. This study aimed at the characterization of twelve GF flours obtained from cereals, pseudocereals and legumes for what concerns their functional properties, starch composition, phenolic and flavonoid content, and their effect on glycemic index (GI), that was estimated in vitro. In particular, starch composition had an influence on predicted glycemic index (pGI). pGI and damaged starch were positively related, whereas flavonoid, amylose and resistant starch (RS) contents were negatively related to pGI. In general, for all the parameters considered, cereals, except for rice flour, showed similar behavior, so as legumes. On the contrary, pseudocereals presented quite different characteristics between each other, due to their different botanical origin. The knowledge of starch composition, its relationship with GI, and functional properties could contribute to the selection of flours for healthier GF bakery products

A review of coarse mineral dust in the Earth system

Mineral dust particles suspended in the atmosphere span more than three orders of magnitude in diameter, from <0.1 µm to more than 100 µm. This wide size range makes dust a unique aerosol species with the ability to interact with many aspects of the Earth system, including radiation, clouds, hydrology, atmospheric chemistry, and biogeochemistry. This review focuses on coarse and super-coarse dust aerosols, which we respectively define as dust particles with a diameter of 2.5–10 µm and 10–62.5 µm. We review several lines of observational evidence indicating that coarse and super-coarse dust particles are transported farther than previously expected and that the abundance of these particles is substantially underestimated in current global models. We synthesize previous studies that used observations, theories, and model simulations to highlight the impacts of coarse and super-coarse dust aerosols on the Earth system, including their effects on dust-radiation interactions, dust-cloud interactions, atmospheric chemistry, and biogeochemistry. Specifically, coarse and super-coarse dust aerosols produce a net positive direct radiative effect (warming) at the top of the atmosphere and can modify temperature and water vapor profiles, influencing the distribution of clouds and precipitation. In addition, coarse and super-coarse dust aerosols contribute a substantial fraction of ice-nucleating particles, especially at temperatures above –23 °C. They also contribute a substantial fraction to the available reactive surfaces for atmospheric processing and the dust deposition flux that impacts land and ocean biogeochemistry by supplying important nutrients such as iron and phosphorus. Furthermore, we examine several limitations in the representation of coarse and super-coarse dust aerosols in current model simulations and remote-sensing retrievals. Because these limitations substantially contribute to the uncertainties in simulating the abundance and impacts of coarse and super-coarse dust aerosols, we offer some recommendations to facilitate future studies. Overall, we conclude that an accurate representation of coarse and super-coarse properties is critical in understanding the impacts of dust aerosols on the Earth system

A review of coarse mineral dust in the Earth system

International audiencerepresentation of coarse and super-coarse properties is critical in understanding the impacts of dust aerosols on the Earth system

A review of coarse mineral dust in the Earth system

Mineral dust particles suspended in the atmosphere span more than three orders of magnitude in diameter, from <0.1 µm to more than 100 µm. This wide size range makes dust a unique aerosol species with the ability to interact with many aspects of the Earth system, including radiation, clouds, hydrology, atmospheric chemistry, and biogeochemistry. This review focuses on coarse and super-coarse dust aerosols, which we respectively define as dust particles with a diameter of 2.5–10 µm and 10–62.5 µm. We review several lines of observational evidence indicating that coarse and super-coarse dust particles are transported farther than previously expected and that the abundance of these particles is substantially underestimated in current global models. We synthesize previous studies that used observations, theories, and model simulations to highlight the impacts of coarse and super-coarse dust aerosols on the Earth system, including their effects on dust-radiation interactions, dust-cloud interactions, atmospheric chemistry, and biogeochemistry. Specifically, coarse and super-coarse dust aerosols produce a net positive direct radiative effect (warming) at the top of the atmosphere and can modify temperature and water vapor profiles, influencing the distribution of clouds and precipitation. In addition, coarse and super-coarse dust aerosols contribute a substantial fraction of ice-nucleating particles, especially at temperatures above –23 °C. They also contribute a substantial fraction to the available reactive surfaces for atmospheric processing and the dust deposition flux that impacts land and ocean biogeochemistry by supplying important nutrients such as iron and phosphorus. Furthermore, we examine several limitations in the representation of coarse and super-coarse dust aerosols in current model simulations and remote-sensing retrievals. Because these limitations substantially contribute to the uncertainties in simulating the abundance and impacts of coarse and super-coarse dust aerosols, we offer some recommendations to facilitate future studies. Overall, we conclude that an accurate representation of coarse and super-coarse properties is critical in understanding the impacts of dust aerosols on the Earth system