Interaction of mitochondrial voltage-dependent anion channel from rat brain with plasminogen protein leads to partial closure of the channel

Voltage-dependent anion channel (VDAC) is reported to be the receptor for plasminogen kringle5. In this paper, the interaction of VDAC from rat brain mitochondria with plasminogen protein has been investigated through bilayer electrophysiological studies. We report for the first time that interaction of plasminogen with VDAC leads to partial closure of the channel on a lipid bilayer. This could be a mechanism of modulation of VDAC gating in a cellular system.     

A model for cooperative ligand binding at complementary sites of DNA

The process of cooperative binding of ligands to DNA has been classified into different modes. An additional mode of cooperative interaction amongst ligands binding at sites on complementary strands has been emphasised. A statistical mechanical method has been applied to obtain an analytical expression for the fraction of nucleotide sites bound. Theoretical Scatchard plots have been drawn and analysed.     

Exploring dual inhibitory role of febrifugine analogues against Plasmodium utilizing structure-based virtual screening and molecular dynamic simulation

Malaria is an endemic disease caused by the protozoan parasite Plasomodium falciparum. Febrifugine analogues are natural compound obtained from the traditional Chinese herbs have shown significant antimalarial and anticancerous efficacy in experimental model. Development of resistance against the existing antimalarial drug has alarmed the scientific innovators to find a potential antimalarial molecule which can be further used by endemic countries for the elimination of this disease. In this study, structure-based virtual screening and molecular dynamics (MD) base approaches were used to generate potential antimalarial compound against plasmepsin II and prolyl-tRNA synthetase of Plasmodium. Here, we have docked series of febrifugine analogues (n = 11,395) against plasmepsin II in three different docking modes and then it was compared with previously reported target prolyl-tRNA synthetase. Extra precision docking resulted into 235 ligands having better docking score were subject for QikProp analysis. Better ligands (n = 39) obtained from QikProp analysis were subject for ADMET prediction and docking protocol validation through the estimation of receiver operator characteristics. In the later stage, 24 ligands obtained from ADMET study were subject for the estimation of binding energy through MM-GBSA and same were also docked against prolyl-tRNA synthetase to get compounds with dual inhibitor role. Finally, MD simulation and 2D fingerprint MACCS study of two best ligands have shown significant interaction with plasmepsin II and homology against known active ligand with noteworthy MACCS index, respectively. This study concludes that FA12 could be potential drug candidate to fight against Plasmodium falciparum parasites.     

Foraging strategies of black kites (<Emphasis Type="Italic">Milvus migrans govinda</Emphasis>) in urban garbage dumps

Large numbers of black kites (Milvus migrans govinda) forage with house crows (Corvus splendens) at garbage dumps in many Indian cities. Such aggregation of many individuals results in aggressiveness where adoption of a suitable behavioral approach is crucial. We studied foraging behavior of black kites in dumping sites adjoining two major corporation markets of Kolkata, India. Black kites used four different foraging tactics which varied and significantly influenced foraging attempts and their success rates. Kleptoparasitism was significantly higher than autonomous foraging events; interspecific kleptoparasitism was highest in occurrence with a low success rate, while ‘autonomous-ground’ was least adopted but had the highest success rate.     

Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily

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Aluminium toxicity induced poikilocytosis in an air-breathing teleost, Clarias batrachus (Linn.)

The present study was undertaken to assess the toxicity of acid alone and two different sublethal concentrations of aluminium, (25% and 75% dose of 96 hr LC50 value in acidified soft water of pH 5) on red blood cells of a stenohaline catfish, C. batrachus for an acute exposure of 5 days. The scanning electron microscopic studies on all the three treated groups revealed several kinds of erythrocyte alterations and modifications with abnormal morphology. These included abnormal surface-wrinkling accompanied with excessive roughness on the membrane, erythrocytes with surface granulation in higher dose and finally the appearance of morphologically abnormal forms, the codocyte (target cell) and the stomatocyte. The results suggest that abnormality in the shape of erythrocytes could be linked to altered surface membrane area to volume ratio, decrease in cytoplasmic volume owing to reduced Hb content or increase in the amount of water content within the cell resulting from osmotic disequilibrium. In this context, the abnormal surface membrane morphology could be attributed to cytoskeleton fragility and defects in structural proteins. Further, the acid group exhibited a striking behavior of cellular adhesion and bonding to adjoining cell surfaces, culminating in several bunches which thereby reduces the surface area for gaseous exchange and could produce blocking effect while flowing through microcirculation.     

Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio

We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O₂)₂(H₂O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb^R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.     

Investigating interaction of ligands with voltage dependent anion channel through noise analyses

Ion channel-protein complexes inserted in the membrane act as molecular gates for transport across the membrane. The opening and closing of these gates can be controlled by one or more variables like ligands (small molecules, proteins, etc.), transmembrane voltage, and the concentration gradient of a chemical across the membrane. We have shown how current noise profile of voltage dependent anion channel can be used to monitor change in the gating of the channel after its modulation by various ligands. This is being proposed as a novel method to probe the interaction of ion channels with ligands.