Non-adherence, discontinuation, and seroconversion among people on daily HIV pre-exposure prophylaxis (PrEP) in Brazil: a nationwide cohort study.

The goal of this study was to evaluate characteristics associated with Pre-exposure Prophylaxis for HIV infection (PrEP) non-adherence or discontinuation in Brazil and assess the association between these outcomes and HIV seroconversion. We used linked national dispensing and pathology data to identify people aged 14+ years initiating PrEP in 2018. We estimated non-adherence using the proportion of days covered (PDC), defining non-adherence as PDC < 60%.

Inhibition of 3-Hydroxykynurenine Transaminase from and : A Mosquito-Specific Target to Combat the Transmission of Arboviruses.

Arboviral infections such as Zika, chikungunya, dengue, and yellow fever pose significant health problems globally. The population at risk is expanding with the geographical distribution of the main transmission vector of these viruses, the mosquito. The global spreading of this mosquito is driven by human migration, urbanization, climate change, and the ecological plasticity of the species.

Advances in the phytochemical screening and biological potential of propolis.

Propolis is a natural resinous product collected from different parts of plants by bees and mixed with their salivary secretions. The occurrence of more than 180 different chemotypes has flavonoids, phenolic acids, esters, and phenolic aldehydes, as well as balsamic resins, beeswax, pollen, and essential and aromatic oils, among others. Its biological potential documented throughout the world justifies the need, from time to time, to organize reviews on the subject, with the intention of gathering and informing about the update on propolis.

An artificial neural network model to predict structure-based protein-protein free energy of binding from Rosetta-calculated properties.

The prediction of the free energy (Δ) of binding for protein-protein complexes is of general scientific interest as it has a variety of applications in the fields of molecular and chemical biology, materials science, and biotechnology. Despite its centrality in understanding protein association phenomena and protein engineering, the Δ of binding is a daunting quantity to obtain theoretically. In this work, we devise a novel Artificial Neural Network (ANN) model to predict the Δ of binding for a given three-dimensional structure of a protein-protein complex with Rosetta-calculated properties.

Association strength of E6 to E6AP/p53 complex correlates with HPV-mediated oncogenesis risk.

Human papillomavirus (HPV) is recognized as the causative agent of cervical cancer in women, and it is associated with other anogenital and head/neck cancers. More than 120 types of HPV have been identified and many classified as high- or low-risk according to their oncogenic potential. One of its proteins, E6, has evolved to overcome the oncosuppressor functions of p53 by targeting this protein for degradation via interaction with the human ubiquitin-ligase E6AP.

Identification of potential dihydrofolate reductase inhibitors using QSAR, molecular docking, dynamics simulations and free energy calculation.

Herein we describe the use of molecular docking simulations, quantitative structure-activity relationships studies and ADMETox predictions to analyse the molecular recognition of a series of 7-aryl-2,4-diaminoquinazoline derivatives on the inhibition of dihydrofolate reductase and conducted a virtual screening to discover new potential inhibitors. A quantitative structure-activity relationship model was developed using 40 compounds and two selected descriptors. These descriptors indicated the importance of pKa and molar refractivity for the inhibitory activity against DHFR.

Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil.

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein.

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.

Immune evasion of SARS-CoV-2 variants of concern is driven by low affinity to neutralizing antibodies.

SARS-CoV-2 VOC immune evasion is mainly due to lower cross-reactivity from previously elicited class I/II neutralizing antibodies, while increased affinity to hACE2 plays a minor role. The affinity between antibodies and VOCs is impacted by remodeling of the electrostatic surface potential of the Spike RBDs. The P.

Cooperative UAV-UGV Autonomous Power Pylon Inspection: An Investigation of Cooperative Outdoor Vehicle Positioning Architecture.

Realizing autonomous inspection, such as that of power distribution lines, through unmanned aerial vehicle (UAV) systems is a key research domain in robotics. In particular, the use of autonomous and semi-autonomous vehicles to execute the tasks of an inspection process can enhance the efficacy and safety of the operation; however, many technical problems, such as those pertaining to the precise positioning and path following of the vehicles, robust obstacle detection, and intelligent control, must be addressed. In this study, an innovative architecture involving an unmanned aircraft vehicle (UAV) and an unmanned ground vehicle (UGV) was examined for detailed inspections of power lines.

Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular -Protonation Event.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration.

The influence of biotinylation on the ability of a computer designed protein to detect B-cells producing anti-HIV-1 2F5 antibodies.

Antibodies against the HIV-1 2F5 epitope are known as one of the most powerful and broadly protective anti-HIV antibodies. Therefore, vaccine strategies that include the 2F5 epitope in their formulation require a robust method to detect specific anti-2F5 antibody production by B cells. Towards this goal, we have biotinylated a previously reported computer-designed protein carrying the HIV-1 2F5 epitope aiming the further development of a platform to detect human B-cells expressing anti-2F5 antibodies through flow cytometry.