Hydrophobic aggregation and collective absorption of dioxin into lipid membranes: insights from atomistic simulations

Dioxins are a highly toxic class of chlorinated aromatic chemicals. They have been extensively studied, but several molecular-level details of their action are still missing. Here we present molecular dynamics simulations of their absorption and diffusion through cell membranes. We show that, due to their hydrophobic character, dioxins can quickly penetrate into a lipid membrane, both as single molecules and as aggregates. We find clear evidence for their ability to accumulate in cell membranes. Our free energy calculations indicate that subsequent transport into the cell is unlikely to be a simple diffusive process

Carcinogenicity prediction of noncongeneric chemicals by augmented top priority fragment classification

Carcinogenicity prediction is an important process that can be performed to cut down experimental costs and save animal lives. The current reliability of the results is however disputed. Here, a blind exercise in carcinogenicity category assessment is performed using augmented top priority fragment classification. The procedure analyses the applicability domain of the dataset, allocates in clusters the compounds using a leading molecular fragment, and a similarity measure. The exercise is applied to three compound datasets derived from the Lois Gold Carcinogenic Database. The results, showing good agreement with experimental data, are compared with published ones. A final discussion on our viewpoint on the possibilities that the carcinogenicity modelling of chemical compounds offers is presented

One-pot Wittig reactions in water and in the presence of a surfactant

\u3b1,\u3b2-Unsaturated esters were synthesized in open atmosphere via mild and efficient one-pot Wittig reactions performed in both water and sodium dodecyl sulfate (SDS)-water solution

Integrating computational methods to predict mutagenicity of aromatic azo compounds

Azo dyes have several industrial uses. However, these azo dyes and their degradation products showed mutagenicity, inducing damage in environmental and human systems. Computational methods are proposed as cheap and rapid alternatives to predict the toxicity of azo dyes. A benchmark dataset of Ames data for 354 azo dyes was employed to develop three classification strategies using knowledge-based methods and docking simulations. Results were compared and integrated with three models from the literature, developing a series of consensus strategies. The good results confirm the usefulness of in silico methods as a support for experimental methods to predict the mutagenicity of azo compounds

‘Clinics aren’t meant for men’: Sexual health care access and seeking behaviours among men in Gauteng province, South Africa

Men may be key players in the transmission of sexually transmitted infections (STI), and it is important that STI/HIV health services reach men. The objective of this study was to explore sexual health care access and seeking behaviours in men. This study used focus groups to examine sexual health care access and seeking behaviours in men 5 years after implementation of free antiretroviral therapy (ART) in the South African public sector. Six focus groups (N=58) were conducted with men ≥18 years in an urban area of Gauteng province. Men were recruited from various locations throughout the community. Men reported several barriers and facilitators to the use of public and private clinics for sexual health services including HIV testing, and many men reported seeking care from traditional healers. Men often viewed public clinics as a place for women and reported experiences with some female nurses who were rude or judgmental of the men. Additionally, some men reported that they sought sexual health care services at public clinics; however, they were not given physical examinations by health care providers to diagnose their STI syndrome. Most men lacked knowledge about ART and avoided HIV testing because of fear of death or being abandoned by their families or friends. Study findings suggest that men still require better access to high-quality, non-judgmental sexual health care services. Future research is needed to determine the most effective method to increase men’s access to sexual health care services.Keywords: sexual health care access, men.Les hommes peuvent être des responsables dans la transmission des infections sexuellement transmissibles (IST), et il est important que les services de santé des IST/VIH les sensibilisent (les hommes). Les objectifs de cette étude étaient d’examiner l’accès aux soins de santé et les comportements sexuels des hommes pendant 5 ans après la mise en oeuvre de la thérapie antirétrovirale (ART) gratuite dans le secteur public Sud-Africain. Six groups d’hommes âgés ≥18 ans (N=58) ont menés des discussions dans la zone urbaine de la province de Gauteng. Ces hommes sont recrutés dans divers endroits dans toute la communauté. Ils ont déclarés rencontrés des obstacles et facilitateurs à l’accès des cliniques publiques et privées des services de santé sexuelle, y compris le test du VIH, et beaucoup d’hommes déclarent être à la recherche de soins vers des guérisseurs traditionnels. Les hommes ont souvent vu les cliniques publiques comme des endroits pour les femmes et se sont souvent plaint des expériences qu’ils ont eues par rapport aux infirmières qui ont un mauvais jugement sur eux. Certains d’entre eux ont déclaré qu’ils cherchaient des soins de santé dans les cliniques publiques, mais qu’ils n’étaient pas soumis à des examens physiques pour diagnostiquer leurs syndrome d’IST. La plupart d’entre eux n’avaient pas de connaissances de l’ART et évitent le test du VIH parce qu’ils ont peur de la mort ou d’être abandonné par leurs familles ou leurs amis. Cette étude suggère que les hommes doivent exiger de meilleures qualités de soins, un non-jugement des services de santé sexuelle. Les recherches futures sont nécessaires pour déterminer la méthode la plus efficace d’accroitre l’accès des hommes aux services de santé sexuelle

Selective enzymatic reduction of aldehydes

Highly selective enzymatic reductions of aldehydes to the corresponding alcohols was performed using an E. coli JM109 whole cell biocatalyst. A selective enzymatic method for the reduction of aldehydes could provide an eco-compatible alternative to chemical methods. The simplicity, fairly wide scope and the very high observed chemoselectivity of this approach are its most unique features

Polyphenol polymerization by an alternative oxidative microbial enzyme and characterization of the biological activity of oligomers

The recombinant catalase-peroxidase HPI from E. coli was used as an alternative enzyme in polymerization reactions for the production of ( 12) epicatechin oligomers and their biological activity was characterized.The enzyme was prepared in two forms: a purified and an immobilized form. Both were tested for their activity in oxidative polymerization reactions, and their stability and reusability were assessed. The polymerization reactions were followed by SEC-HPLC analyses, and the substrate was completely converted into one or more polymerization products depending on the reactions conditions. Results showed that the utilized conditions allowed for the isolation of some oligomers of different molecular weight: the oligomers containing 6 and 7 units of epicatechin substrate are the heaviest ones. Epicatechin was also used in reactions catalyzed by HRP in the same reaction conditions for comparison. In addition, one selected oligomer obtained by HPI enzyme catalysis was shown to act as in vitro inhibitor of tumor cell growth, like one oligomer deriving from epicatechin by HRP catalysis. These data confirm that epicatechin oligomeric form is more effective than its monomer in biological activity and suggest the use of HPI as an alternative enzyme in reactions for the production of epicatechin oligomers

Identification of a bacteriocin-like compound from Lactobacillus plantarum with antimicrobial activity and effects on normal and cancerogenic human intestinal cells

In this paper, we demonstrate that the antimicrobial activity of L. plantarum PBS067 strain against antagonist microorganisms was mediated by the production of a bacteriocin-like compound secreted at the stationary phase of the growth. The novel bacteriocin-like compound, designed plantaricin P1053, was identified by using sorption\u2013desorption method, butanol extraction and SEC-HPLC. The molecular mass of plantaricin P1053 was shown to be 1053 Da by ESI-MS analysis. Plantaricin P1053 exhibited a broad-spectrum antimicrobial activity against Gram-positive bacteria as S. aureus and Gram-negative bacteria as E. coli. In addition to the antimicrobial activity, the isolated bacteriocin-like compound showed effects on normal and cancerogenic epithelial intestinal cell lines through an enhancing of viability of healthy cells and a proliferation reduction of cancer cells. Moreover, in this paper we demonstrate that the isolated bacteriocin-like compound acts on healthy cells through the epidermal growth factor receptor (EGFR) pathways. In conclusion, plantaricin P1053 isolated from L. plantarum PBS067 strain could represent one of the first multifunctional bacteriocin-like compound acting on human epithelial intestinal cells

Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations

CITATION: Mikasi, S. G., et al. 2021. Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. BMC Infectious Diseases, 21:379, doi:10.1186/s12879-021-06059-x.The original publication is available at https://bmcinfectdis.biomedcentral.comBackground: The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG containing regimens have shown a high genetic barrier against HIV-1 isolates carrying specific resistance mutations when compared with other class of regimens. Methods: We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistanceassociated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences (n = 20) and (n = 287) sequences data derived from HIV Los Alamos National Laboratory database. The possible impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a 3D model of the HIV-1 IN complex and interaction analysis was performed using PyMol to validate DTG binding to the Wild type and seven mutant structures. Results: We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. NOPs occurred at a frequency of 66% on the central core domain (CCD) position, 44% on the C-terminal domain (CTD) position and 35% of the Nterminal domain (NTD) position. The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure. Except for accessory mutant structure E157Q, only one MG contact was made with DTG, while DTG had no MG ion contacts and no DDE motif residue contacts for structure D232N. Conclusions: Our analysis indicated that all RAM’s that resulted in a change in the number of interactions with encompassing residues does not affect DTG binding, while accessory mutations E157Q and D232N could affect DTG binding leading to possible DTG resistance. However, further experimental validation is required to validate the in silico findings of our study.https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06059-xPublisher's versio