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We asked if transfer RNA (tRNA) ever got an opportunity of translating its own sequence during evolution, what would have been the function of such tRNA-encoded peptides (tREPs)? If not, could one artificially synthesize tREPs to study the corresponding functional outcomes? Here, we report a novel, first-in-the-class, chemically synthesized tREP-18 molecule originating from the

Malaria infection caused by Plasmodium falciparum is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent ...

Malaria infection caused by

Background Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Methods Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. Results 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. Conclusion These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.

In the last few years, the expanding energy utilization has imposed the formation of solutions for saving electricity. Of many solutions, one is generating a power saving policies which is defined as prediction of energy in smart environments. This model is built, based on the idea that the building residences are provided with smart meters to monitor energy consumption and can be managed accordingly. Recent prediction models focuses on performance of the prediction, but for developing a reliable energy system, it is required to predict the demand taking into account different scenarios. In this paper we propose a model for predicting future demand for energy according to different conditions using advanced machine learning framework. In this system we have a projector that builds proper state for a particular condition and using that defined state a future power demand is forecasted by the predictor. The proposed model generates utilization predictions for every 2 hours. Demonstrating the electricity consumption data for 5 years, the proposed system achieves a better performance.

MicroRNAs (miRNAs), are small non-coding RNAs of approximately 22 nucleotides in length, playing an important role in regulating gene expression post-transcriptionally. Understanding the effect of miRNA regulation in a pathway-specific manner unravels the approaches adopted to apprehend biological mechanisms, the information, which is scanty for researchers, not primed already for miR related research. Here, we describe a quick perspective in 5 steps with probable approaches and assays at every level to unravel the specific role of a microRNA, miR-145a-5p, as an example. This perspective as a guide would help in identifying novel targets for a microRNA, as shown for miR-145a-5p, which down-regulated the mRNA expression of ADD3 and BRCA2, using bioinformatic tools and experimental assays.

Drug-resistance in plasmodium parasites is manifested at large scale, putting all the malaria control efforts in vain with an urgent need of complementary strategies. A deeper understanding of mechanism of action of drugs, drug resistance and cross-resistance between drugs will pave a way to design an effective individualized drug for malaria-affected regions. This chapter summarizes the molecular mechanism of all currently available anti-malarial drugs and the factors playing significant role in the development and spread of resistance against the antimalarials.

Additional file 1: Table S1. Antimalarial Screening of compounds. Figure S1. Molecular structure of all the compounds (n =30) used in this study. Figure S2. Antimalarial effect of galactal fused pyrano-pyranone carbohybrid 12 in chloroquine resistant RKL 9 strain.

MicroRNAs (miRNAs) are small non-coding RNA molecules of around 22 nucleotides in length. They are crucially involved in the post transcriptional regulation and thus play a significant role in the modulation of different diseases. Several studies have suggested that miRNA expression is dysregulated in various cancers through different mechanisms and the dysregulated miRNA in return affects different cancer hallmarks including cell proliferation, cell death suppression, metastasis and angiogenesis. Compilation of the available miRNA data can be a stimulator for proper understanding of the correlation between the miRNA expression and cancer progression. In this review, we have focussed on the role of miR-760 in the progression of different cancer. MicroRNA-760 (miR-760) has been found to be down regulated in various cancers, thus it can be utilized as a possible prognostic marker for cancer detection. Here, we have tried to fill a gap regarding the role of miR-760 in relation to cervical cancer also. Moreover, unravelling the role of miR-760 in different cancers will enlighten the researchers with proper understanding of biology of miR-760 in regulation of different cancers.