Nef Alleles from All Major HIV-1 Clades Activate Src-Family Kinases and Enhance HIV-1 Replication in an Inhibitor-Sensitive Manner

The HIV-1 accessory factor Nef is essential for high-titer viral replication and AIDS progression. Nef function requires interaction with many host cell proteins, including specific members of the Src kinase family. Here we explored whether Src-family kinase activation is a conserved property of Nef alleles from a wide range of primary HIV-1 isolates and their sensitivity to selective pharmacological inhibitors. Representative Nef proteins from the major HIV-1 subtypes A1, A2, B, C, F1, F2, G, H, J and K strongly activated Hck and Lyn as well as c-Src to a lesser extent, demonstrating for the first time that Src-family kinase activation is a highly conserved property of primary M-group HIV-1 Nef isolates. Recently, we identified 4-amino substituted diphenylfuropyrimidines (DFPs) that selectively inhibit Nef-dependent activation of Src-family kinases as well as HIV replication. To determine whether DFP compounds exhibit broad-spectrum Nef-dependent antiretroviral activity against HIV-1, we first constructed chimeric forms of the HIV-1 strain NL4-3 expressing each of the primary Nef alleles. The infectivity and replication of these Nef chimeras was indistinguishable from that of wild-type virus in two distinct cell lines (U87MG astroglial cells and CEM-T4 lymphoblasts). Importantly, the 4-aminopropanol and 4-aminobutanol derivatives of DFP potently inhibited the replication of all chimeric forms of HIV-1 in both U87MG and CEM-T4 cells in a Nef-dependent manner. The antiretroviral effects of these compounds correlated with inhibition of Nef-dependent activation of endogenous Src-family kinases in the HIV-infected cells. Our results demonstrate that the activation of Hck, Lyn and c-Src by Nef is highly conserved among all major clades of HIV-1 and that selective targeting of this pathway uniformly inhibits HIV-1 replication

QSAR studies on 4-thiazolidinones and 2-azetidinones bearing benzothiophene nucleus as potential anti-tubercular agents

586-591Quantitative structure-activity relationships (QSAR) study on a series of (substituted 1, 2-dihydro)4–thiazolidinones and 2-azetidinones bearing benzothiophene nucleus with anti-tubercular activity has been carried out using a combination of various physicochemical descriptors. Several significant equations with good co-efficient of correlation (>0.860) have been obtained. The two models are selected using internal predictive power discerned by cross-validated coefficient q². Both models highlight some common important feature, i.e., bulky substitution and the high nucleophilicity nature of the molecules, favorable for anti-tubercular activity

Varietal Screening and Management of Basal Rot Disease of Onion

Onion (Allium cepa L.) belongs to the family Amaryllidaceae. It is known as common onion, bulb onion or biennial herb, and is one of the most important vegetable crops in India. However, the crop faces numerous diseases attack, resulting in losses to both quantity and quality. Among the diseases, the basal rot caused by Fusarium oxysporum f. sp. cepae, is one of the most significant soil-borne diseases. This work aimed to screen various onion varieties for resistance against basal rot in pots under glasshouse condition as well as to assess the efficacy of fungicides against the pathogen under both in vitro and in vivo conditions. It was observed that all onion varieties screened were highly susceptible while Bhima red was just susceptible; none of the varieties were resistant to basal rot. Under in vitro conditions the Fungicides Carbendazim and Tebuconazole, of the given concentration, were cent per cent effective in inhibiting mycelial growth of Fusarium oxysporum f. sp. cepae. For the field condition, the module of [carbendazim (2 g/kg) followed by tebuconazole (0.1 %) followed by azoxystrobin (0.1 %)] was the most effective.&nbsp

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