Genomic-based characterization of Enterococcus spp.: an emerging pathogen isolated from human gut

Molecular Biology Reports - Enterococci are ubiquitous microorganisms having diverse ecological niches but most prominently in gastrointestinal tract of humans and animals. Production of enterocins...     

MITOL-dependent ubiquitylation negatively regulates the entry of PolγA into mitochondria

Mutations in mitochondrial replicative polymerase PolγA lead to progressive external ophthalmoplegia (PEO). While PolγA is the known central player in mitochondrial DNA (mtDNA) replication, it is unknown whether a regulatory process exists on the mitochondrial outer membrane which controlled its entry into the mitochondria. We now demonstrate that PolγA is ubiquitylated by mitochondrial E3 ligase, MITOL (or MARCH5, RNF153). Ubiquitylation in wild-type (WT) PolγA occurs at Lysine 1060 residue via K6 linkage. Ubiquitylation of PolγA negatively regulates its binding to Tom20 and thereby its mitochondrial entry. While screening different PEO patients for mitochondrial entry, we found that a subset of the PolγA mutants is hyperubiquitylated by MITOL and interact less with Tom20. These PolγA variants cannot enter into mitochondria, instead becomes enriched in the insoluble fraction and undergo enhanced degradation. Hence, mtDNA replication, as observed via BrdU incorporation into the mtDNA, was compromised in these PEO mutants. However, by manipulating their ubiquitylation status by 2 independent techniques, these PEO mutants were reactivated, which allowed the incorporation of BrdU into mtDNA. Thus, regulated entry of non-ubiquitylated PolγA may have beneficial consequences for certain PEO patients.

This study shows that mitochondrial entry of the replicative polymerase PolgA is regulated by ubiquitylation by the E3 ligase MITOL; however, by manipulating their ubiquitylation status, some progressive external ophthalmoplegia mutants whose PolgA is polyubiquitylated and cannot enter the mitochondrion can be reactivated and hence become functionally active.     

Insight into the binding of a non-toxic,self-assembling aromatic tripeptide with ct-DNA: Spectroscopic and viscositic studies

The report describes the synthesis, self-association and DNA binding studies of an aromatic tripeptide H-Phe-Phe-Phe-OH (FFF). The peptide backbone adopts β—sheet conformation both in solid and solution. In aqueous solution, FFF self-assembles to form nanostructured aggregates. Interactions of this peptide with calf-thymus DNA (ct-DNA) have been studied using various biophysical techniques including ultraviolet (UV) absorption spectroscopy, fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The value of mean binding constant calculated from UV and fluorescence spectroscopic data is (2.914 ± 0.74) x 10³ M^?1 which is consistent with an external binding mode. Fluorescence intercalator displacement (FID) assay, iodide quenching study, viscosity measurement and thermal denaturation study of DNA further confirm the groove binding mode of peptide, FFF with ct-DNA. MTT cell survival assay reveals very low cytotoxicity of the peptide toward human lung carcinoma cell line A549.     

Comparative Trial of Pancrex V Forte and Nutrizym in Treatment of Malabsorption in Cystic Fibrosis

A cross-over trial of pancreatic enzyme replacement therapy has been conducted on 12 children with cystic fibrosis using Pancrex V forte and Nutrizym tablets in equivalent dosage. No differences were found in the effectiveness of these products as measured by stool volume, number of bowel actions, faecal fat excretion, and urine urea excretion. Neither product eliminated the steatorrhoea. Though there was no laboratory evidence to support their choice nine patients expressed a preference for Nutrizym at the conclusion of the trial. This preference was based partly on the smaller number of tablets which are required.     

Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents

Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper.