Ubiquitination is an important post‐translational event responsible for half‐life and turnover of proteins inside the cell. Proteins are ubiquitinated by forming an iso‐peptide bond between their lysine residue and C‐terminal glycine residue of ubiquitin leading to rapid degradation of proteins by 26S proteosome complex. Deregulation of ubiquitination is manifested by aberrant expression of E3‐ligase activity or mutation in the surroundings of ubiquitination sites. Many new experimentally validated ubiquitinated lysines have been recently identified that motivated the study of the environments surrounding the ubiquitinated lysines. With the help of known ubiquitinated proteins, here we present a comprehensive study of sequence and spatial environment of ubiquitination sites of human and yeast proteins. To identify position‐specific features, this work distinguishes the spatial environments as proximity and distal regions. Certain amino acids specific to these regions, well differentiate the ubiquitination sites from non‐ubiquitination sites are revealed. Additionally, amino acid signatures that contribute for protein disordered regions and solvent accessibility of amino acids are found to be contributing factors in ubiquitination sites. These results suggest that the ubiquitination site environment of the substrate determines the recognition and unfolding of substrate to facilitate the entry into 26S proteosomal complex. We believe that these findings will help in better prediction of ubiquitination sites using the sequence and spatial information.

Background Archaea belong to the domain Euryarchaeota, represents only 3-5% of the rumen microbiota; however, they play a central role in maintaining the H2 pressure. Host species in conjunction with geographical regions may lead to the variable distribution of rumen methanogens. Indian cattle and buffaloes represent 13 and 53% of the global population, respectively. However, the influence of host species (bovine) and geographical regions on the methanogens distribution has not been investigated in Indian subcontinent. Therefore, the present study was undertaken to explore the rumen methanogens diversity in the cattle and buffaloes native to the two distinct geographical regions of India. Results Next generation sequencing of 16S rRNA gene from 36 rumen fluid samples corresponding to cattle and buffaloes revealed that Methanobrevibacter (Mbr.) genus constituted largest fraction (55-62%) of the rumen archaeal community. Furthermore, Methanobrevibacter gottschalkii was the most prominent methanogens with the significantly higher abundance in cattle. Methanomassiliicoccales represented <10% of the total archaeal community and was found to be the most variable between these two host species. In north region, the distribution of Methanomassiliicoccales, such as Methanosphaera sp., Group 4, Group 8, Group 12 sp. and Group 9 sp. was significantly higher in cattle. The distribution of prominent methanogens, such as Mbr. gottschalkii and Mbr. ruminantium did not differ between two host species in the north region. However, Mbr. gottschalkii was significantly higher in buffaloes as compared to cattle in south region. Mbr. wolinii was exclusively detected in the cattle. Inter-region comparison established that Methanomassiliicoccales were the most variable between the two regions. Conclusions Host species did not affect the distribution of hydrogenotrophic methanogens except for Mbr. gottschalkii. Methylotrophic methanogens, in spite of their limited representation, were most influenced by the host species and geographical regions. Overall, the Methanomassiliicoccales distribution was higher in cattle, and the environmental conditions in north region were conducive for their higher distribution. The variable distribution of methanogens indicated that host and geographical region oriented strategies needs to be developed for the reduction of enteric methane emission. Further studies are warranted to explore the impact of diet on the distribution of rumen methanogens between the host species within and across different environmental conditions.

Background The rising number of trials on repurposed dugs in COVID-19 has led to duplication and a need for curation of available outcomes from treatments that have been followed across the world. We have conducted a systematic review and meta-analysis that focus on evaluating the clinical outcomes of repurposed interventions against COVID-19. Methods Random effects model was adopted to estimate overall treatment effect and heterogeneity. Meta-regression was performed to study the correlation between comorbid conditions and non-invasive or invasive ventilation requirement. Results Twenty-nine articles met our eligibility criteria. In subgroup analysis, Tocilizumab was highly significant with lower mortality rate (OR 27.50; 95%CI [5.39-140.24]) of severe COVID-19 patients. Hydroxychloroquine and Lopinavir-ritonavir was found to be inefficacious in severe patients (OR 0.64; 95%CI [0.47-0.86] and 1.40 [0.71-2.76]). Dexamethasone had marginal effect on overall mortality rate (OR 1.19; 95%CI [1.05-1.35]). The meta-regression shows a positive correlation between prevalence of patients on Tocilizumab in non invasive support and hypertension condition (P = 0.02), whereas a negative correlation was identified with patients having lung disease (P = 0.03). Conclusion Overall, our study confirmed that tocilizumab may probably reduce the mortality rate (<10%) of severe COVID-19 patients than other interventions. Further, reduce the risk of requiring non-invasive ventilator support in patients with comorbid condition of lung disease. Hydroxychloroquine and Lopinavir-ritonavir has no clinical benefits in severe COVID-19. A high quality evidence is required to evaluate the usage of Serpin + Favipiravir combination in severe or critical COVID-19.