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Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at very high rates. However, certain individuals who initially achieve viral suppression to undetectable levels may eventually suffer treatment failure mainly due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration. GRL-142 forms optimum polar, van der Waals, and halogen bond interactions with HIV-1 protease and strongly blocks protease dimerization, demonstrating that combined multiple optimizing elements significantly enhance molecular and atomic interactions with a target protein and generate unprecedentedly potent and practically favorable agents.

In a radical departure from the classical E1-E2-E3 three-enzyme mediated ubiquitination of eukaryotes, the recently described bacterial enzymes of the SidE family of Legionella pneumophila effectors utilize NAD+ to ligate ubiquitin onto target substrate proteins. This outcome is achieved via a two-step mechanism involving (1) ADP ribosylation of ubiquitin followed by (2) phosphotransfer to a target serine residue. Here, using fluorescent NAD+ analogues as well as synthetic substrate mimics, we have developed continuous assays enabling real-time monitoring of both steps of this mechanism. These assays are amenable to biochemical studies and high-throughput screening of inhibitors of these effectors, and the discovery and characterization of putative enzymes similar to members of the SidE family in other organisms. We also show their utility in studying enzymes that can reverse and inhibit this post-translational modification.

Capsicum annuum L., also known as bell or sweet pepper, is a globally significant horticultural crop in the Solanaceae family. India’s red and yellow colored capsicum holds 13th rank in export. In India, color capsicum is a valuable crop, yielding 2.34 times more per square meter in protected cultivation comparing open field. Tamil Nadu contributes 16,689 tonnes on 284 hectares, comprising 5.13% of India’s total. Modern agriculture benefits from automation and robotics, especially in protected cultivation for selective, high-quality capsicum harvesting, reducing labor fatigue. In consideration to the issues like timely and repetitive harvestings and shortage of labour a study was focused to develop a robotic harvester. The study evaluated the engineering attributes of red and yellow capsicum during protected cultivation, classified into size categories A, B and C. Moisture content ranged from 83.6% to 87.12%. Capsicum dimensions spanned 57 mm to 110 mm in length, 52 mm to 98 mm in width, and 51 mm to 96 mm in thickness. Red capsicum had slightly larger arithmetic, geometric, square mean, and equivalent diameters, with sphericity ranging from 0.89 to 0.93. Surface area varied from 87 cm² to 316 cm², volume from 108 cm³ to 363 cm³, and mass from 67 g to 226 g, with red capsicum slightly larger. The highest static friction coefficient was with aluminum, at 0.61 to 0.66. Using the CIELAB model for color estimation, the significant color difference for red and yellow capsicum were 79.26 and 70.28 respectively. Moisture content was negatively correlated with aspect ratio and sphericity, and other attributes had positive correlations. This data is valuable for potential capsicum harvesting mechanization in robotics and protected cultivation. [ABSTRACT FROM AUTHOR]