Probable Mechanism(s) of Antifungal Activity of SJA-95, a Heptaene Polyene Antibiotic

A new strain, streptomyces sp. S. 24 was isolated from a soil sample collected from Japan. The strain produced heptaene polyene antibiotic, SJA-95, in submerged culture and found to elicit promising antifungal activity against yeasts, filamentous fungi and clinical isolates, both in vitro and in vivo. Experimental studies were carried out using biological methods to understand the probable mechanism(s) of antifungal activity of SJA-95. Our experimental findings suggest that SJA-95 binds more avidly to ergosterol, the sterol in fungal cell membranes, than to cholesterol found in mammalian cell membranes. Such preferential binding of SJA-95 to ergosterol might help to establish its usefulness as a chemotherapeutic agent with lesser adverse reactions.     

Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Platelet spreading on the subendothelium in response to vascular injury is fundamental to the regulation of physiologic hemostasis. Previously, we have shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regulates platelet spreading on immobilized fibrinogen (Fg). In this study, we investigated the signaling events that occur downstream of CIB in the absence of signaling that occurs as a result of granular secretion. Using Chinese hamster ovary (CHO) cells as a model, we demonstrate that CIB induces cell migration. Immunofluorescence analysis of CIB localization indicates that endogenous CIB accumulates in areas of focal adhesions, and its overexpression up-regulates the formation of focal adhesion complexes compared with control cells. Immunoprecipitation analysis indicates that CIB associates with focal adhesion kinase (FAK), a key regulator in focal complex formation, and up-regulates its activity. Overexpression of dominant-negative FAK, FRNK, along with CIB in CHO cells completely inhibits CIB-induced cell migration. Further, confirmation of these data in the platelet system indicates that CIB and FAK associate throughout all stages of platelet spreading but only on Fg binding to GPIIb/IIIa. Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation.     

Molecular epidemiology of human picobirnaviruses among children of a slum community in Kolkata, India

Picobirnaviruses are a group of unclassified, non-enveloped, small spherical viruses, 35-41 nm in diameter without any apparent surface morphology. They have characteristic bisegmented double stranded RNA genome of two types namely large profile (2.3-2.6 kbp for the larger and 1.5-1.9 kbp for the smaller segment, respectively) or small profile (1.75 and 1.55 kbp for segments 1 and 2, respectively). Human picobirnaviruses (n=12 positives; 2/56 diarrhoeic children and 10/607 non-diarrhoeic children) with large (n=11) or small (n=1) genome pattern were observed in faecal specimens of children from a slum community by silver stained PAGE gels. Faecal specimen from four asymptomatic cases (P597_02_IND, K135_02_IND, A373_03_IND, A356_03_IND) and one diarrhoeic case (K135_03_IND) had genogroup I picobirnaviruses (1-CHN-97 like) showing amplicons within the 201 bp region, with primers PicoB25-PicoB43, targeting the conserved domain of RNA-dependent RNA polymerase (RdRp) gene. It was interesting to note that only the PBV strain P597_02_IND from Kolkata with large genome was closely related to a reported strain (similarity with 2-GA-91 from USA was 87% at the nucleotide level and 90% at the amino acid level). Sequence analysis showed three conserved amino acid domains as well as a highly conserved D-S-D motif, characteristic of RNA-dependent RNA polymerase gene of bisegmented, double stranded RNA viruses. Sequence data of the picobirnavirus A356_03_IND indicated strong heterogeneity with all other picobirnavirus strains sequenced till date. After nearly a decade a genogroup II picobirnavirus strain (R227_03_IND) was isolated from a diarrhoea case in the community, with small genome profile and amplified with specific primers PicoB23-PicoB24; but the sequence data showed that it was divergent from the hitherto reported prototype strain 4-GA-91 of genogroup II human picobirnaviruses.     

Clinical significance of lipid profile in cancer patients

In the present study, we have examined lipid profile in normal healthy age matched control and patients with various malignancies. Analysis of data revealed that total lipids, cholesterol and HDL cholesterol levels are inversely associated with incidence of cancer where as triglycerides levels were significantly elevated in cancer patients. Electrophoretic separation of lipoproteins revealed a significant decrease in the mean values of alpha fraction in patients with malignancy when compared with the corresponding control group. The other fractions beta and pre-beta did not show any change in the mean values in patients with cancer as compared to the normal corresponding control group.