Phylogenetic Predictions on Grids

A phylogenetic or evolutionary tree is constructed from a set of species or DNA sequences and depicts the relatedness between the sequences. Predictions of future sequences in a phylogenetic tree are important for a variety of applications including drug discovery, pharmaceutical research and disease control. In this work, we predict future DNA sequences in a phylogenetic tree using cellular automata. Cellular automata are used for modeling neighbor-dependent mutations from an ancestor to a progeny in a branch of the phylogenetic tree. Since the number of possible ways of transformations from an ancestor to a progeny is huge, we use computational grids and middleware techniques to explore the large number of cellular automata rules used for the mutations. We use the popular and recurring neighbor-based transitions or mutations to predict the progeny sequences in the phylogenetic tree. We performed predictions for three types of sequences, namely, triose phosphate isomerase, pyruvate kinase, and polyketide synthase sequences, by obtaining cellular automata rules on a grid consisting of 29 machines in 4 clusters located in 4 countries, and compared the predictions of the sequences using our method with predictions by random methods. We found that in all cases, our method gave about 40% better predictions than the random methods.

Benzothiophene Carboxamide Derivatives as Novel Antimalarials

Bromo-benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl-ACP reductase. Here, we report bromo-benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood-stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials.(C) 2011 IUBMB IUBMB Life, 63(12): 1111-1115, 2011

Progress in tuberculosis vaccine development and host-directed therapies-a state of the art review

Tuberculosis continues to kill 1.4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.