Bacteriophage-encoded depolymerases: their diversity and biotechnological applications

Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell surface, such as polysaccharides, or are produced by bacteria when they are living in biofilm communities, the most common bacterial lifestyle. Consequently, phages with depolymerase activity have a facilitated access to the host receptors, by degrading the capsular polysaccharides, and are believed to have a better performance against bacterial biofilms, since the degradation of extracellular polymeric substances by depolymerases might facilitate the access of phages to the cells within different biofilm layers. Since the diversity of phage depolymerases is not yet fully explored, this is the first review gathering information about all the depolymerases encoded by fully sequenced phages. Overall, in this study, 160 putative depolymerases, including sialidases, levanases, xylosidases, dextranases, hyaluronidases, peptidases as well as pectate/pectin lyases, were found in 143 phages (43 Myoviridae, 47 Siphoviridae, 37 Podoviridae, and 16 unclassified) infecting 24 genera of bacteria. We further provide information about the main applications of phage depolymerases, which can comprise areas as diverse as medical, chemical, or food-processing industry.DPP acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BD/76440/2011. SS is an FCT investigator (IF/01413/2013). The authors also thank FCT for the Strategic Project of the UID/BIO/04469/2013 unit, FCT and European Union funds (FEDER/COMPETE) for the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER027462)

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Enhancing Electron Transfer and Stability of Screen-Printed Carbon Electrodes Modified with AgNP-Reduced Graphene Oxide Nanocomposite

This paper presents a reliable solution to enhance the electron transfer and stability of screen-printed carbon electrodes (SPCEs) for the direct detection of pathogenic bacteria. A nanocomposite of silver nanoparticles (AgNPs) and reduced graphene oxide (rGO) was used to modify the SPCEs. Herein, the nanocomposite was synthesized via a hydrothermal method and then characterized by physicochemical methods. The electron transfer rate and electrochemical properties of the AgNP-rGO nanocomposite-modified SPCEs were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy. Measurements were performed for the detection of Salmonella bacteria without any labels. Results showed that the nanocomposite firmly adhered to the surfaces of the SPCEs, led to an increase of approximately 160% in the peak current, and decreased the charge transfer resistance to 0.45 kΩ. Electrochemical stability was found in 30 CV cycles. The modified SPCEs could detect Salmonella bacteria directly at concentrations of 10–105 CFU/mL, with a limit of detection (LoD) of as low as 22 CFU/mL. A possible mechanism was proposed to explain the enhanced electron transfer on the surface and the stability of the AgNP-rGO nanocomposite-modified SPCEs. The biosensor showed high stability, cost-effectiveness, and simplicity for the direct detection of pathogenic bacteria. Graphical Abstract: [Figure not available: see fulltext.

Pharmacogenomic Analysis of CYP3A5*3 and Tacrolimus Trough Concentrations in Vietnamese Renal Transplant Outcomes

Thi Van Anh Nguyen,1,&ast; Ba Hai Le,2,&ast; Minh Thanh Nguyen,2,&ast; Viet Thang Le,3,&ast; Viet Tien Tran,4,&ast; Dinh Tuan Le,5,&ast; Duong Anh Minh Vu,2,&ast; Quy Kien Truong,3,&ast; Trong Hieu Le,2,&ast; Huong Thi Lien Nguyen2,&ast; 1Department of Pharmacy, 103 Military Hospital, Hanoi, Vietnam; 2Department of Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam; 3Department of Nephrology and Dialysis, 103 Military Hospital, Hanoi, Vietnam; 4Department of Infectious Diseases, 103 Military Hospital, Hanoi, Vietnam; 5Department of Rheumatology and Endocrinology, 103 Military Hospital, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Huong Thi Lien Nguyen, Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hoan Kiem, Hanoi, Vietnam, Tel +84904308406, Email [email protected]: CYP3A5 polymorphisms have been associated with variations in the pharmacokinetics of tacrolimus (Tac) in kidney transplant patients. Our study aims to quantify how the CYP3A5 genotype influences tacrolimus trough concentrations (C0) in a Vietnamese outpatient population by selecting an appropriate population pharmacokinetic model of Tac for our patients.Patients and Methods: The external dataset was obtained prospectively from 54 data of adult kidney transplant recipients treated at the 103 Military Hospital. All published Tac population pharmacokinetic models were systematically screened from PubMed and Scopus databases and were selected based on our patient’s available characteristics. Mean absolute prediction error (MAPE), mean prediction error, and goodness-of-fit plots were used to identify the appropriate model for finding the formula that identifies the influence of CYP3A5 genotype on the pharmacokinetic data of Vietnamese patients.Results: The model of Zhu et al had a good predictive ability with MAPE of 19.29%. The influence of CYP3A5 genotype on tacrolimus clearance was expressed by the following formulas: . The simulation result showed that Tac C0 was significantly higher in patients not expressing CYP3A5 (p< 0.001).Conclusion: The incorporation of the CYP3A5 phenotype into Zhu’s structural model has significantly enhanced our ability to predict Tacrolimus trough levels in the Vietnamese population. This study’s results underscore the valuable role of CYP3A5 phenotype in optimizing the forecast of Tac concentrations, offering a promising avenue to assist health-care practitioners in their clinical decision-making and ultimately advance patient care outcomes.Keywords: tacrolimus, population pharmacokinetic, CYP3A5, Vietna