Reduced Amino Acid Specificity of Mammalian Tyrosyl-tRNA Synthetase is Associated with Elevated Mistranslation of Tyr Codons

Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNATyr with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control

Tropical Cyclones and Climate Change

Trabajo presentado en: 10th International Worskshop Cyclones Tropicales, celebrado del 5 al 9 de diciembre de 2022 en Bali, Indonesia.A substantial number of studies have been published since the IWTC-9 in 2018, improving our understanding of the effect of climate change on tropical cyclones (TCs) and associated hazards and risks. They reinforced the robustness of increases in TC intensity and associated TC hazards and risks due to anthropogenic climate change. New modeling and observational studies suggested the potential influence of anthropogenic climate forcings, including greenhouse gases and aerosols, on global and regional TC activity at the decadal and century time scale. However, there is still substantial uncertainty owing to model uncertainty in simulating historical TC decadal variability in the Atlantic and owing to limitations of observed TC records. The projected future change in the global number of TCs has become more uncertain since IWTC-9 due to projected increases in TC frequency by a few climate models. A new paradigm, TC seeds, has been proposed, and there is currently a debate on whether seeds can help explain the physical mechanism behind the projected changes in global TC frequency. New studies also highlighted the importance of large-scale environmental fields on TC activity, such as snow cover and air-sea interactions. Future projections on TC translation speed and Medicanes are new additional focus topics in our report. Recommendations and future research are proposed relevant to the remaining scientific questions and assisting policymakers

Statistical Analysis of Rainfall Data using non-parametric methods of Solapur District, Maharashtra, India

India being a Tropical country, experiences variety Rainfall. The Rainfall is the prime input required for Design of Hydraulic structures like culverts and bridges, Irrigation canals, storm water and road drainage system, etc. To estimate the detailed design and planning of crops, statistical analysis is required. In the present study, annual rainfall data for a period of 20 years (2000 to 2019) is used to understand the statistical behavior of the rainfall in last two decades for Solapur district. Also return period by various plotting position formulae is evaluated from the annual rainfall. The rainfall variability is checked by calculating the mean, standard deviation and coefficient of variation. From the study results, the rainfall pattern is found to be irregular. The best fitted probability distribution was identified based on the minimum deviation between actual and estimated values

Use of a weather forecast model to identify suitable sites for new wind power plants in Karnataka

The wind speed forecast by a weather forecast model (with a resolution of 3 km) has been used to identify regions with high wind speed in Karnataka. The correlation between daily wind speed predicted by the model and the measured wind speed at three stations in Karnataka has been shown to be high. Based on this model, new locations have been suggested for the installation of new wind power plants in Karnataka

Impact of a narrow coastal Bay of Bengal sea surface temperature front on an Indian summer monsoon simulation

A dry bias in climatological Central Indian rainfall plagues Indian summer monsoon (ISM) simulations in multiple generations of climate models. Here, using observations and regional climate modeling, we focus on a warm coastal Bay of Bengal sea surface temperature (SST) front and its impact on Central Indian rainfall. The SST front, featuring sharp gradients as large as 0.5 °C/100 km, is colocated with a mixed layer depth (MLD) front, in a region where salinity variations are known to control MLD. Regional climate simulations coupling a regional atmospheric model with an ocean mixed layer model are performed. A simulation with observed MLD climatology reproduces SST, rainfall, and atmospheric circulation associated with ISM reasonably well; it also eliminates the dry bias over Central India significantly. Perturbing MLD structure in the simulations, we isolate the SST front’s impact on the simulated ISM climate state. This experiment offers insights into ISM climatological biases in the coupled NCEP Climate Forecast System version-2. We suggest that the warm SST front is essential to Central Indian rainfall as it helps to sustain deep and intense convection in its vicinity, which may be a source for the vortex cores seeding the monsoon low-pressure systems.Published versio

An update on the influence of natural climate variability and anthropogenic climate change on tropical cyclones

A substantial number of studies have been published since the Ninth International Workshop on Tropical Cyclones (IWTC-9) in 2018, improving our understanding of the effect of climate change on tropical cyclones (TCs) and associated hazards and risks. These studies have reinforced the robustness of increases in TC intensity and associated TC hazards and risks due to anthropogenic climate change. New modeling and observational studies suggested the potential influence of anthropogenic climate forcings, including greenhouse gases and aerosols, on global and regional TC activity at the decadal and century time scales. However, there are still substantial uncertainties owing to model uncertainty in simulating historical TC decadal variability in the Atlantic, and the limitations of observed TC records. The projected future change in the global number of TCs has become more uncertain since IWTC-9 due to projected increases in TC frequency by a few climate models. A new paradigm, TC seeds, has been proposed, and there is currently a debate on whether seeds can help explain the physical mechanism behind the projected changes in global TC frequency. New studies also highlighted the importance of large-scale environmental fields on TC activity, such as snow cover and air-sea interactions. Future projections on TC translation speed and medicanes are new additional focus topics in our report. Recommendations and future research are proposed relevant to the remaining scientific questions and assisting policymakers.</p

Reduced Amino Acid Specificity of Mammalian Tyrosyl-tRNA Synthetase Is Associated with Elevated Mistranslation of Tyr Codons

Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNA(Tyr) with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control