Evolutionary Study of COVID-19 Disease Severity in India for the Genetic Variation and Prevention of Disease Progression

Introduction:Coronaviruses (CoV) have been responsible for three epidemics in the 21st century, including Severe Acute Respiratory Syndrome (SARS) in 2003. Corona virus is a single strand ribonucleic acid which is genotypically and phenotypically diverse.Method:The phylogenetic tree and Entropy plot are used to show the strain variation with root difference or Boot strip changes among various nucleotide plots with mutational changes (19).Therefore, we would like to explain evolutionary changes in other countries compared to India and in different states of India. To evaluate the strain variation with their mutation and adaptation of the environment with the virus or may be due to several passages occurring over a period of time.Results:For phylogenetic tree analysis, we have selected 8-8 isolates from each state, Assam, Chhattisgarh, Delhi, Gujarat, Haryana, Himachal Pradesh, Karnataka, Kerala, Orissa, Maharashtra, Punjab, Telangana, Uttar Pradesh and West Bengal. Total 74 isolates were selected from given states for making of phylogenetic tree and mutational study. There were many point mutations found.Discussion:According to our study, we found a several point mutation occurred among the sequence submitted in gene bank database that is same as China which has been reported. This study was conducted to systematic analysis on the genomic data of NCBI. This work is also significant in terms of mutational research. Evolutionary changes and approach a new strain through the mutational study done by BioEdit and MEGA 6.0 software. The bioinformatics and the statistical genetic analysis may contribute for study of COVID-19 as other infection and complex disease. This study is used understand the host–pathogen interaction and to contain the COVID-19 outbreak.Conclusion:This study highlighted the evolutionary changes occurred in the COVID-19 disease severity variation in strain for the prevention and mutation. We reported the genetic study of COVID-19 disease with their association in already submitted strain of database for the study of their genetic variation as well as disease progression.

Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

Aim Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). Material and methods Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). Results There were 4 women and 3 men between 36–91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. Conclusions These data suggest different mechanisms of DLBCL development in LPL patients.

Activity-specificity trade-off gives PI5P4Kβ a nucleotide preference to function as a GTP-sensing kinase

SummaryMost kinases function with ATP. However, contrary to the prevailing dogma, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a primary phosphate donor with a unique binding mode for GTP. Although PI5P4Kβ is evolved from a primordial ATP-utilizing enzyme, PI4P5K, how PI5P4Kβ evolutionarily acquired the GTP preference to function as a cellular GTP sensor remains unclear. In this study, we show that the short nucleotide base-recognition motif, TRNVF, is responsible for the GTP binding of PI5P4Kβ, and also confers onto PI5P4Kβ an unexpected specificity that extends to inosine triphosphate (ITP) and xanthosine triphosphate (XTP). A mutational study with GTP analogues suggests that the extended specificity is an obligatory consequence to the acquisition of GTP-dependent activity. However, as the cellular concentrations of ITP and XTP are typically negligible, PI5P4Kβ can still function as a GTP sensor, suggesting that the cellular physiological conditions leave room for the functional evolution of PI5P4Kβ.

Characterization of Stackebrandtia nassauensis GH 20 Beta-Hexosaminidase, a Versatile Biocatalyst for Chitobiose Degradation

An unstudied β-N-acetylhexosaminidase (SnHex) from the soil bacterium Stackebrandtia nassauensis was successfully cloned and subsequently expressed as a soluble protein in Escherichia coli. Activity tests and the biochemical characterization of the purified protein revealed an optimum pH of 6.0 and a robust thermal stability at 50 °C within 24 h. The addition of urea (1 M) or sodium dodecyl sulfate (1% w/v) reduced the activity of the enzyme by 44% and 58%, respectively, whereas the addition of divalent metal ions had no effect on the enzymatic activity. PUGNAc (O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate) strongly inhibited the enzyme in sub-micromolar concentrations. The β-N-acetylhexosaminidase was able to hydrolyze β1,2-linked, β1,3-linked, β1,4-linked, and β1,6-linked GlcNAc residues from the non-reducing end of various tested glycan standards, including bisecting GlcNAc from one of the tested hybrid-type N-glycan substrates. A mutational study revealed that the amino acids D306 and E307 bear the catalytically relevant side acid/base side chains. When coupled with a chitinase, the β-N-acetylhexosaminidase was able to generate GlcNAc directly from colloidal chitin, which showed the potential of this enzyme for biotechnological applications.