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A flavonoid-based approach to mitigating hyperglycaemia: in silico analysis of AMPK activation, membrane and metabolic effects of rutin in hepg2 cells
No full textHyperglycaemia exacerbates tissue damage and complications in COVID-19 and metabolic disorders. Flavonoids have shown diverse therapeutic potential in metabolic and infectious diseases, yet their molecular mechanisms remain unclear. The 5' adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor and a promising therapeutic target in diabetes and viral infections. This study investigated the binding affinity, structural stability and conformational dynamics of flavonoids with AMPK through molecular docking, molecular dynamics (MD) simulations (Maestro Schrodinger, Amber 18) carried out for 100 ns, and MM/GBSA binding free energy calculations. In vitro cytotoxicity and biochemical assays, including MTT, ATP, ΔΨm, CYP3A4, and LDH, were performed on HepG2 cells and analyzed using one-way ANOVA with Tukey's post hoc test. Rutin showed the strongest binding to AMPK (−64.87 ± 10.07 kcal/mol), indicating superior binding and potential biological effects. Computational analysis identified key residues Glu86, Glu92, Glu135 and Asp149 involved in direct hydrogen bonding and electrostatic interactions, contributing to binding affinity and stability in the AMPK binding pocket. Rutin maintained nearly 100% cell viability up to 500 µM, significantly increased ATP and CYP3A4 levels while reducing LDH without impacting ΔΨm, indicating preserved mitochondrial integrity, enhanced metabolism and bioenergetics. These findings showed rutin as a safe and potent AMPK modulator with potential for further optimization and preclinical evaluations to treat diabetes and other diseases associated with mitochondrial dysfunction and metabolic stress
Target-enriched multilocus assay on poriferan museum collections unsettles tethyid classification.
No full textMarine biodiversity collections are critical resources for understanding biodiversity and evolutionary patterns. However, their taxonomic utility is limited due to challenges in morphological identification and cryptic speciation, particularly in sponges (Porifera). This study applied a novel target-enriched multilocus assay to a decades-old unidentified collection of Tethyidae from the Queensland Museum. Target-specific baits were designed based on Tethya genome data, enabling the sequencing of nuclear ultraconserved elements (UCEs) and mitochondrial genomes, even from degraded samples. In the study, 40 specimens were sequenced, and we found up to 4,440 UCEs per sample. The phylogenies were based on up to 2,788 loci and demonstrated overall high bootstrap support. Results include robust support for earlier findings on the non-monophyly of Tethya, with lineages linking to other genera (e.g., Stellitethya, Tethycometes), suggesting that Tethya is a paraphyletic group foundational to Tethyidae. Morphological subgroupings, previously hypothesized, were validated genetically, though several novel relationships emerged. This approach highlights the suitability of target-enriched multilocus assays for archival collections, enabling detailed biodiversity assessments using collection material initially not sampled for molecular work. Our Tethya case study underlines that this methodology provides a framework for broader applications in marine biodiversity conservation, facilitating the understanding and preservation of past and present biodiversity to guide future efforts
Galenia africana extract as an alternative to typical azoles against Candida species
No full textCandidiasis is a common infection caused by Candida species, often associated with immune compromised patients. Due to the prevalence of candidal resistance to typical azole treatments, alternative forms of therapies should be investigated. The use of medicinal plants as an alternative form of therapy has become a topic of interest in the scientific community. Galenia africana has shown a lot of potential as an antimicrobial plant extract. In this study, the antifungal activity of the ethanolic and ethyl acetate extraction of Galenia africana was investigated against fluconazole-resistant and susceptible Candida species. High-performance liquid chromatography and nuclear magnetic resonance were employed to separate, isolate and purify the active compounds of Galenia africana followed by evaluating the antifungal activity using broth microdilution, synergistic and time kill assays. Three compounds were isolated from Galenia africana, identified as (S)-5,7-dihydroxy flavone (1), (E)-2',4'-dihydroxychalcone (2), and (S)-2',5,7,-trihydroxyflavanone (3). The results showed significant antifungal activity below 500μg/ml which confirms that Galenia africana can be used as a potential antifungal against fluconazole resistant strains of Candida
The clustering of active galactic nuclei and star-forming galaxies in the LoTSS Deep Fields
No full textUsing deep observations across three of the LOFAR Two-metre Sky Survey Deep Fields, this work measures the angular clustering of star-forming galaxies (SFGs) and low-excitation radio galaxies (LERGs) to 1.5 for faint sources, 200 Jy. We measure the angular auto-correlation of LOFAR sources in redshift bins and their cross-correlation with multiwavelength sources to measure the evolving galaxy bias for SFGs and LERGs. Our work shows the bias of the radio-selected SFGs increases from = at 0.2 to = at 1.2; faster than the assumed models adopted in previous LOFAR cosmology studies (at sensitivities where active galactic nuclei dominate), but in broad agreement with previous work. We further study the luminosity dependence of bias for SFGs and find little evidence for any luminosity dependence at fixed redshift, although uncertainties remain large for the sample sizes available. The LERG population instead shows a weaker redshift evolution with = at 0.7 to = at 1.2, though it is also consistent with the assumed bias evolution model () within the measured uncertainties. For those LERGs that reside in quiescent galaxies, there is weak evidence that they are more biased than the general LERG population and evolve from = at 0.7 to = at 1.2. This suggests the halo environment of radio sources may be related to their properties. These measurements can help constrain models for the bias evolution of these source populations, and can help inform multi-tracer analyses
Enhancing target crop discrimination: a novel shadow detection technique for RGB datasets in mixed agricultural environments
No full textShadows pose significant challenges in smallholder farming systems, where mixed cropping is common. This study introduces two novel techniques: the Hue-Intensity-Green-Blue (HIGB) difference method for shadow detection and the Light Intensity Ratio-Based (LIRB) method for shadow compensation. Their performance was tested against the C3 and NSVDI models using five accuracy metrics on RGB imagery. HIGB consistently achieved superior accuracies (77–95%) compared to NSVDI (63–84%) and C3 (69–81%) in five different crop mixtures. Both the models, HIGB and LIRB, provide an integrated, robust solution for shadow detection and compensation in heterogeneous agricultural environments
Network topology similarities across cancer types: identifying central protein hubs for drug discovery
No full textA molecular-level understanding of cancer is essential for the development of effective therapies. Constructing protein-protein interaction (PPI) networks offers a valuable approach to identifying dysregulated driver genes and potential therapeutic targets. In this study, we modeled cancer PPI networks as metric spaces and applied mathematical and computational algorithms to analyze their structural and functional properties. Our findings reveal that these networks share a conserved architecture across different cancer types, with central zones enriched in essential proteins and critical regulatory pathways. Notably, zones 1 and 2 of the cancer PPI networks are uniquely enriched in specific pathways, underscoring their importance in the progression of cancer. These results highlight the potential of metric-based analysis of PPI networks to uncover key molecular targets and accelerate drug discovery in oncolog
Ethical transgressions among healthcare professionals in South Africa from 2014 to 2023
No full textBackground: Patients have become more comfortable lodging complaints with professional regulatory bodies over the last several years, likely influenced by the trending nature of patient-centred care and consumerism in healthcare and increased access to information through social media. Aim: To analyse the frequency and nature of reported ethical transgressions and penalties among registered South African healthcare professionals from 2014 to 2023. Setting: The study took place in South Africa. Methods: A list of all sanctioned cases was obtained from the Health Professions Council of South Africa (HPCSA) (data were unavailable for 2019). A mixed-methods approach of quantitative and qualitative content analyses was followed. Results: The study analysed 1012 ethical transgressions among 452 registered medical practitioners, physiotherapists, psychologists, dietitians, dentists and occupational therapists. Fraudulent conduct accounted for the largest number (n = 507 [50.1%]) of transgressions across all professions. The most common penalty imposed was a fine of R1000 to R10000 (26% of total penalties). Both a fine and a suspension were imposed in 82% of cases. Completion of an ethics-based educational course accounted for only 3%. Conclusion: Fraudulent conduct remains the highest reported ethical transgression among registered healthcare professionals in South Africa. Individualised education that remediates deficiencies in ethical behaviours through analysis and reflection could be beneficial in mitigating ethical misconduct among healthcare professionals. Contribution: This study provides a comparative analysis of ethical transgressions and penalties among healthcare professionals in South Africa. It also offers insights into necessary areas of improvement of education and training and suggests a different approach to disciplinary actio
Bayesian estimation of HIV acquisition dates for prevention trials
No full textAccurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, “true DDA” was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2–7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days)
Carbon dynamics in termite mounds: the effect of land use on microbial oxalotrophy
No full textThe semi-arid western region of South Africa hosts extensive earthen mounds known as heuweltjies, which are inhabited by Microhodotermes viator termites and play a critical role in soil biogeochemical cycling. These mounds accumulate significant stores of soil organic and inorganic carbon (C), including pedogenic calcium carbonate, which may form through microbially induced calcite precipitation. In this study, the effects of land use change on C dynamics in heuweltjie soils were assessed by examining soil biogeochemistry and apparent respiratory quotient (ARQ, based on soil pore gas composition). We investigated the oxalate-carbonate pathway (OCP) as a potential mechanism of C sequestration. Topsoils were collected from one pristine and one cultivated termite mound in a semi-arid region of South Africa and incubated for one week. The carbon dioxide (CO2) and oxygen concentrations of soil pore gas as well as chemical properties of soils treated with termite frass (excrement) or calcium oxalate (CaOx) were monitored. Increases in pH and the calcite saturation index in both CaOx- and frass-treated soils suggested the potential occurrence of the OCP. The ARQ values did not reflect geochemical changes associated with OCP due to competing metabolic pathways, such as potential lignin degradation in frass-treated soils. Higher ARQ values in uncultivated versus cultivated CaOx-treated soils may indicate higher carbon use efficiency in uncultivated soils or destabilization of existing C in cultivated soils. Respiration in frass-treated soils was higher than control and CaOx-treated soils and resulted in production of bicarbonate (via dissociation of carbonic acid formed by dissolution of respired CO2 in water). This implies that termite-affected landscapes may sequester C in inorganic form. Increased total C in both cultivated and uncultivated soils treated with frass suggests that microbial CO2-fixation may occur in termite-affected landscapes, necessitating further investigation of pathways responsible for this process
Midwives’ competence in interpretation of the intrapartum cardiotocograph at public hospitals in Gauteng: An explanatory sequential mixed-methods study
No full textBackground: Cardiotocograph (CTG) tracing is a routine intrapartum care procedure for women who have been diagnosed with high-risk pregnancy. The aim of the CTG is to identify fetuses that are at risk in order to expedite delivery. Purpose: To asssess midwives’ competence in the interpretation of the intrapartum cardiotocograph at public hospitals in Gauteng. Methods: An explanatory sequential mixed-methods approach was used. During phase one, 122 midwives in Johannesburg and Tshwane District filled in self-administered questionnaires, and during phase two, 30 midwives took part in semi-structured qualitative interviews. The data from both phases was analyzed separately and then integrated using the Pillar Integration Process. Results: The Pillar Integration Process led to the identification of six pillars: 1) substandard CTG interpretation training leads to a lack of understanding of key concepts; 2) absence of norms and standards pertaining to CTG interpretation training; 3) Essential Steps in Managing Obstetric Emergencies (ESMOE) training does not result in improved CTG interpretation scores; 4) lack of standardization of CTG interpretation guidelines causes confusion among interpreters; 5) level of knowledge of foundational concepts of CTG interpretation affects clinical judgment; and 6) CTG interpretation skill is a combination of understanding of CTG characteristics, fetal heart rate pattern, fetal physiology and clinical context. Conclusion: The results highlighted a knowledge deficit in CTG interpretation and shortfalls in the current CTG training programs. This can be remediated by the development of a CTG training program which is benchmarked with existing programs which have demonstrated good knowledge scores of participants over a long period