Genome subtraction for novel target definition in Salmonella typhi

Large genomic sequencing projects of pathogens as well as human genome leads to immense genomic and proteomic data which would be very beneficial for the novel target identification in pathogens. Subtractive genomic approach is one of the most useful strategies helpful in identification of potential targets. The approach works by subtracting the genes or proteins homologous to both host and the pathogen and identify those set of gene or proteins which are essential for the pathogen and are exclusively present in the pathogen. Subtractive genomic approach is employed to identify novel target in salmonella typhi. The pathogen has 4718 proteins out of which 300 are found to be essential (“ indispensable to support cellular life”) in the pathogen with no human homolog. Metabolic pathway analyses of these 300 essential proteins revealed that 149 proteins are exclusively involved in several metabolic pathway of S. typhi. 8 metabolic pathways are found to be present exclusively in the pathogen comprising of 27 enzymes unique to the pathogen. Thus, these 27 proteins may serve as prospective drug targets. Sub-cellular localization prediction of the 300 essential proteins was done which reveals that 11 proteins lie on the outer membrane of the pathogen which could be probable vaccine candidates.     

Flow cytometric evaluation of yeast–bacterial cell–cell interactions

Synthetic cell–cell interaction systems can be useful for understanding multicellular communities or for screening binding molecules. We adapt a previously characterized set of synthetic cognate nanobody–antigen pairs to a yeast–bacteria coincubation format and use flow cytometry to evaluate cell–cell interactions mediated by binding between surface-displayed molecules. We further use fluorescence-activated cell sorting to enrich a specific yeast-displayed nanobody within a mixed yeast-display population. Finally, we demonstrate that this system supports the characterization of a therapeutically relevant nanobody–antigen interaction: a previously discovered nanobody that binds to the intimin protein expressed on the surface of enterohemorrhagic Escherichia coli. Overall, our findings indicate that the yeast–bacteria format supports efficient evaluation of ligand–target interactions. With further development, this format may facilitate systematic characterization and high-throughput discovery of bacterial surface-binding molecules.     

Anilide tertiary carbinols: A new structural class of potent potassium channel openers

A new structural class of anilide tertiary carbinol potassium channel openers (PCOs) is described.     

Synthetic glucagon antagonists and partial agonists.

This paper reports the synthesis and the biological activities of six new glucagon analogues. In these compounds N-terminal modifications of the glucagon sequence were made, in most cases combined with changes in the C-terminal region which had been shown previously to enhance receptor affinity. The design of these analogues was based on [Lys17,18,Glu21]glucagon,1 a superagonist, which binds five times better than glucagon to the glucagon receptor, and on the potent glucagon antagonist [D-Phe4,Tyr5,Arg12]glucagon, which does not stimulate adenylate cyclase system even at very high concentrations. The N-terminal modifications involved substitution of His1 by the unnatural conformationally constrained residue, 4,5,6,7-tetrahydro-1H-imidazo[c]pyridine-6-carboxylic acid (Tip) and by desaminohistidine (dHis). In addition we prepared two analogues (6 and 7), in which we deleted the Phe6 residue, which was suggested to be part of a hydrophobic patch and involved in receptor binding. The following compounds were synthesized: [Tip1, Lys17,18,Glu21]glucagon (2); [Tip1,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21]glucagon (3); [dHis1,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21]glucagon (4); [dHis1,Asp3,D-Phe4,Tyr5,Arg12,Lys17,18,Glu21+ ++]glucagon (5); des-Phe6-[Tip1,D-Phe4,Tyr5,Arg12,Glu21]glucagon (6); des-Phe6-[Asp3,D-Phe4,Tyr5,Arg12,Glu21]glucagon (7). The binding potencies of these new analogues relative to glucagon (= 100) are 3.2 (2), 2.9 (3), 10.0 (4), 1.0 (5), 8.5 (6), and 1.7 (7). Analogue 2 is a partial agonist (maximum stimulation of adenylate cyclase (AC) approximately 15% and a potency 8.9% that of glucagon, while the remaining compounds 3-7 are antagonists unable to activate the AC system even at concentrations as high as 10(-5) M. In addition, in competition experiments, analogues 3-7 caused a right-shift of the glucagon stimulated adenylate cyclase dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytological studies in some species of Momordica

In the genus Momordica three species M. charantia, M. balsamina and M. dioica, have been cytologically investigated. M. dioica has a more asymmetrical karyotype than the other two species.Meiosis in the three species is regular. The strictly monoecious M. charantia and M. balsamina show similarity in the range and frequency of bivalents and chiasmata, whereas M. dioica, a dioecious species, has fewer half chiasmata per chromosome. The evolutionary significance of perennial and annual habits along with allogamous and autogamous breeding systems is discussed. The incompatibility between 2n=22 and 2n=28 species in this genus is strongly indicated by the negative results of crossings between M. charantia and M. balsamina on one side and M. dioica on the other. The possible origin of M. dioica from M. charantia is discussed.This research has been financed in part by a grant made by the United States Department of Agriculture under PL 480.     

Synthesis,Computational Insights,and Anticancer Activity of Novel Indole–Schiff Base Derivatives

Russian Journal of Bioorganic Chemistry - Synthetic and naturally available compounds with indole moiety are known to show significant biological activity. This paper describes computational...     

Physiological responses of the green microalga Acutodesmus dimorphus to temperature induced oxidative stress conditions

Temperature is the most critical factor that directly affects the physiological functioning and metabolic activities of any organism. With rising global temperature, understanding the heat stress response of an organism is critically important. In the present study, we investigated differences in the early changes occurring upon heat stress in the green microalga Acutodesmus dimorphus, a potential strain for biofuel production. The cells were heat-stressed at 45 and 50°C for 24 h and the temporal response of cells in terms of growth, pigments content, levels of oxidative stress biomarkers i.e., reactive oxygen species (ROS) and the response of enzymatic and non-enzymatic antioxidant scavengers were evaluated. The results revealed that after 24 h of heat stress at 45°C, the accumulations of chlorophyll a and carotenoids remained stable; all three ROS increased with the higher activities of various enzymatic and non-enzymatic antioxidants. On the contrary, at a higher temperature of 50°C, the accumulations of chlorophyll a, carotenoids and non-enzymatic antioxidants reduced drastically while the accumulations of all three ROS and the response of enzymatic antioxidants were significantly higher than those at 45°C. These results suggest that the cells utilize several stress acclimatization mechanisms to cope up the heat stress. There was a dramatic difference in the physiological changes and cellular antioxidant mechanism upon heat stress at 45 and 50°C. The cellular defense response of A. dimorphus gets impaired after heat stress at 50°C but remains active at 45°C, exhibiting the heat resistance and, thus, the thermotolerance.