Evaluation of Binding of Rosmarinic Acid with Human Transferrin and Its Impact on the Protein Structure: Targeting Polyphenolic Acid-Induced Protection of Neurodegenerative Disorders.

Rosmarinic acid (RA) is a natural compound that is gaining wide popularity owing to its broad-spectrum biological activities. RA is known for its wide range of medicinal properties and therapeutic applications in a vast range of neurodegenerative disorders thus making it a vital natural compound. Human transferrin (hTf) is a clinically significant protein that plays a pivotal role in maintaining iron homeostasis.

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy.

Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed and screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC = 5.89 μM.

High-depth African genomes inform human migration and health.

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020.

Capacity building for whole genome sequencing of Mycobacterium tuberculosis and bioinformatics in high TB burden countries.

Background: Whole genome sequencing (WGS) is increasingly used for Mycobacterium tuberculosis (Mtb) research. Countries with the highest tuberculosis (TB) burden face important challenges to integrate WGS into surveillance and research.

Methods: We assessed the global status of Mtb WGS and developed a 3-week training course coupled with long-term mentoring and WGS infrastructure building.

Multistage antiplasmodial activity of hydroxyethylamine compounds, and evaluations.

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of species. New therapeutics acting against the pathogenic asexual and sexual stages, including liver-stage malarial infection, have now attained more attention in achieving malaria eradication efforts. In this paper, two previously identified potent antiplasmodial hydroxyethylamine (HEA) compounds were investigated for their activity against the malaria parasite's multiple life stages.

Transcriptomics of the Rooibos () Species Complex.

Rooibos (), widely known as a herbal tea, is endemic to the Cape Floristic Region of South Africa (SA). It produces a wide range of phenolic compounds that have been associated with diverse health promoting properties of the plant. The species comprises several growth forms that differ in their morphology and biochemical composition, only one of which is cultivated and used commercially.

Diverse genomoviruses representing twenty-nine species identified associated with plants.

Genomoviruses (family Genomoviridae) are circular single-stranded DNA viruses that have been mainly identified through metagenomics studies in a wide variety of samples from various environments. Here, we describe 98 genomes of genomoviruses found associated with members of 19 plant families from Australia, Brazil, France, South Africa and the USA. These 98 genomoviruses represent 29 species, 26 of which are new, in the genera Gemykolovirus (n = 37), Gemyduguivirus (n = 9), Gemygorvirus (n = 8), Gemykroznavirus (n = 6), Gemycircularvirus (n = 21) and Gemykibivirus (n = 17).

Structural Comparison of Diverse HIV-1 Subtypes using Molecular Modelling and Docking Analyses of Integrase Inhibitors.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA).

Unravelling the unfolding pathway of human Fas-activated serine/threonine kinase induced by urea.

Fas-activated serine/threonine kinase (FASTK) is a mitochondria-associated nuclear protein that inhibits Fas- and UV-induced apoptosis. This protein is generally activated during Fas-mediated apoptosis by phosphorylating a nuclear RNA-binding protein T-cell intracellular antigen-1 and thus considered as a modulator of apoptosis. In the present study, we have examined the equilibrium unfolding and conformational stability of the kinase domain of FASTK (FASTK.

Short Communication: HIV-1 Drug Resistance Mutation Analyses of Cameroon-Derived Integrase Sequences.

HIV-1 integrase (IN) is a primary target for combination antiretroviral therapy. Only a limited number of studies report on the emergence of resistance-associated mutations (RAMs) in Cameroon. We observed that 1.

Genome Sequencing of a Severe Acute Respiratory Syndrome Coronavirus 2 Isolate Obtained from a South African Patient with Coronavirus Disease 2019.

As a contribution to the global efforts to track and trace the ongoing coronavirus pandemic, here we present the sequence, phylogenetic analysis, and modeling of nonsynonymous mutations for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome that was detected in a South African patient with coronavirus disease 2019 (COVID-19).

Rosmarinic Acid Exhibits Anticancer Effects via MARK4 Inhibition.

Microtubule affinity regulating kinase (MARK4) is a potential drug target for different types of cancer as it controls the early step of cell division. In this study, we have screened a series of natural compounds and finally identified rosmarinic acid (RA) as a potential inhibitor of MARK4. Molecular docking and 500 ns all-atom simulation studies suggested that RA binds to the active site pocket of MARK4, forming enough number of non-covalent interactions with critical residues and MARK4-RA complex is stable throughout the simulation trajectory.

Cellular and Molecular Targets of Waterbuck Repellent Blend Odors in Antennae of Newstead, 1910.

Insects that transmit many of the world's deadliest animal diseases, for instance trypanosomosis, find their suitable hosts and avoid non-preferred hosts mostly through olfactory cues. The waterbuck repellent blend (WRB) comprising geranylacetone, guaiacol, pentanoic acid, and δ-octalactone derived from waterbuck skin odor is a repellent to some savannah-adapted tsetse flies and reduces trap catches of riverine species. However, the cellular and molecular mechanisms associated with detection and coding of the repellent odors remain to be elucidated.

Ellagic Acid Controls Cell Proliferation and Induces Apoptosis in Breast Cancer Cells via Inhibition of Cyclin-Dependent Kinase 6.

Cyclin-Dependent Kinase 6 (CDK6) plays an important role in cancer progression, and thus, it is considered as an attractive drug target in anticancer therapeutics. This study presents an evaluation of dietary phytochemicals, capsaicin, tocopherol, rosmarinic acid, ursolic acid, ellagic acid (EA), limonene, caffeic acid, and ferulic acid for their potential to inhibit the activity of CDK6. Molecular docking and fluorescence binding studies revealed appreciable binding affinities of these compounds to the CDK6.

Organizing and running bioinformatics hackathons within Africa: The H3ABioNet cloud computing experience.

The need for portable and reproducible genomics analysis pipelines is growing globally as well as in Africa, especially with the growth of collaborative projects like the Human Health and Heredity in Africa Consortium (H3Africa). The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for portable, reproducible pipelines adapted to heterogeneous computing environments, and for the nurturing of technical expertise in workflow languages and containerization technologies. Building on the network's Standard Operating Procedures (SOPs) for common genomic analyses, H3ABioNet arranged its first Cloud Computing and Reproducible Workflows Hackathon in 2016, with the purpose of translating those SOPs into analysis pipelines able to run on heterogeneous computing environments and meeting the needs of H3Africa research projects.

Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding.

Resistance associated mutations (RAMs) threaten the long-term success of combination antiretroviral therapy (cART) outcomes for HIV-1 treatment. HIV-1 Integrase (IN) strand transfer inhibitors (INSTIs) have proven to be a viable option for highly specific HIV-1 therapy. The INSTI, Dolutegravir is recommended by the World Health Organization for use as first-line cART.

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.

The South African national combination antiretroviral therapy (cART) roll-out program started in 2006, with over 4.4 million people accessing treatment since it was first introduced. HIV-1 drug resistance can hamper the success of cART.

A population model for the 2017/18 listeriosis outbreak in South Africa.

We introduce a compartmental model of ordinary differential equations for the population dynamics of listeriosis, and we derive a model for analysing a listeriosis outbreak. The model explicitly accommodates neonatal infections. Similarly as is common in cholera modeling, we include a compartment to represent the reservoir of bacteria.

Rooibos () Genome Size Estimation Using Flow Cytometry and K-Mer Analyses.

Plant genomes provide information on biosynthetic pathways involved in the production of industrially relevant compounds. Genome size estimates are essential for the initiation of genome projects. The genome size of rooibos ( species complex) was estimated using DAPI flow cytometry and k-mer analyses.

Modelling the impact of maternal HIV on uninfected children: correcting current estimates.

A mathematical model, populated primarily with data from South Africa, was developed to model the numbers of children affected by maternal HIV, and the number who will experience long-term negative developmental consequences. A micro-simulation model generated two scenarios. The first simulated a cohort of women whose HIV status mimicked that of a target population, and mother-child dyads by way of age- and disease-specific fertility rates.

Differential Diagnosis of Malignant Lymphadenopathy Using Flow Cytometry on Fine Needle Aspirate: Report on 269 Cases.

Introduction: Fine needle aspiration (FNA) is frequently the first noninvasive test used for the diagnostic workup of lymphadenopathy. There have been many studies showing its usefulness, especially in conjunction with other techniques for the diagnosis of lymphoma, but it remains inferior to histological examination. The data regarding this subject have mostly been reported mostly from first-world countries, but are scarce for emerging economies.

Symptom evolution following the emergence of maize streak virus.

For pathogens infecting single host species evolutionary trade-offs have previously been demonstrated between pathogen-induced mortality rates and transmission rates. It remains unclear, however, how such trade-offs impact sub-lethal pathogen-inflicted damage, and whether these trade-offs even occur in broad host-range pathogens. Here, we examine changes over the past 110 years in symptoms induced in maize by the broad host-range pathogen, maize streak virus (MSV).