31 research outputs found
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
Recommended from our members
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 ”m to more than 100 ”m. 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 2.5â10 ”m and 10â62.5 ”m. 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 â23 °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 ”m to more than 100 ”m. 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 2.5â10 ”m and 10â62.5 ”m. 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 â23 °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 ”m to more than 100 ”m. 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 2.5â10 ”m and 10â62.5 ”m. 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 â23 °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
Recommended from our members
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 ”m to more than 100 ”m. 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 2.5â10 ”m and 10â62.5 ”m. 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 â23 °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