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Novel gene regulatory networks identified in response to nitro-conjugated linoleic acid in human endothelial cells
No full textA distinct transcriptome regulated by NO2-CLA was revealed in primary human coronary artery endothelial cells (HCAECs) through RNA sequencing. </p
Promoting the adoption of best practices and standards to enhance quality and reproducibility of stem cell research
No full textAdvancing the use of human stem cell-based models on preclinical and regulatory testing fields requires the performance of rigorous and reproducible research. Quality standards and reporting best practices should be promoted to ensure the reliability and translatability of stem cell models and results. Strategies to increase awareness and implementation of best practices and standards will require training initiatives and collaboration across relevant stakeholders. Overall, improving the quality and reproducibility of stem cell-based models and methods through best practices and standards will accelerate their adoption in industrial and regulatory contexts and ultimately drive the development of effective therapies and safer chemicals
Vocalisations as a potential indicator of parturition in C57BL/6J mice.
No full textBreeding management in laboratory rodents is challenging, particularly around parturition and the neonatal period, where cage disturbance is often avoided in an attempt to limit neonatal mortality. Nevertheless, cage-side observations and single daily checks frequently underestimate pup numbers born and miss parturition complications. Home Cage Monitoring (HCM) systems are gaining popularity in animal facilities, detecting critical events such as food availability and activity levels. Parturition is a complex event involving specific patterns of behaviour, activity and vocalisations. In this study, audio and video data were collected from parturition events of single-housed C57BL/6J females and breeding pairs housed in a prototype rack with integrated microphones. Vocalisations were detected during parturition in both housing conditions, with minimal vocalisations observed prior to parturition, except for ultrasonic sounds in pair-housed mice (Mus musculus). After parturition, all vocalisations gradually decreased. Despite limitations such as the need for post-event analysis and the focus on a single mouse strain, this study suggests that detecting vocalisations can be a promising basis for developing automated parturition detection. This highlights the potential of HCM systems for improving breeding management and welfare in laboratory rodent colonies
High-throughput drug screening in a cellular model of KRAS-driven arteriovenous malformations.
No full textNo description supplie
S-phase checkpoint protects from aberrant replication fork processing and degradation.
No full textReplication stress, a hallmark of cancer cells, is detected by checkpoint mechanisms that trigger a range of cellular responses. Among these, the preservation of replication fork integrity is crucial for ensuring survival in the presence of DNA damage. In budding yeast checkpoint mutants, DNA damage leads to irreversible replication fork arrest and subsequent cell death, though the underlying mechanism remains unclear. Our study reveals that several DNA processing factors, including Rad51, the Rad5 HIRAN and helicase domains, and the catalytic activity of Mus81, contribute to this lethality. Nevertheless, their roles are masked by their essential functions in cell survival after damage removal. Additionally, we show that these factors, along with Exo1, drive the gradual degradation of nascent DNA at replication forks upon DNA damage. Notably, this degradation can be mitigated by expression of human PrimPol, which is absent in yeast. These findings suggest that the essential role of S-phase checkpoints upon DNA damage is to safeguard stalled replication forks from aberrant processing, thereby preserving nascent DNA integrity
nuTCRacker: Predicting the recognition of HLA-I-peptide complexes by αβTCRs for unseen peptides.
No full textThe ability to predict which antigenic peptide(s) the αβTCR of a given CD8+ T-cell clone can recognise would represent a quantum leap in the understanding of T-cell repertoire selection and development of targeted cell-mediated immunotherapies. Current methods fail to make accurate predictions for antigenic peptides not present in the training dataset. Here, we propose a novel deep learning method called nuTCRacker that makes accurate predictions for a subset of unseen peptides, with an AUC > 0.7 for around a third of peptides evaluated using a large dataset compiled from curated public resources. An additional evaluation was undertaken using a small cellula-validated dataset of αβTCR peptides associated with cancer. Our analysis suggests that it is possible to make useful predictions for an unseen peptide provided the training dataset contains: many samples with the same HLA class I molecule as that bound to the peptide; at least one peptide that is similar to the target peptide; and a small number of αβTCRs that are similar to those bound to the unseen peptide of interest
Structures and mechanisms of AAA+ protein complexes in DNA processing.
No full textAAA+ proteins are a large family of ATPases involved in a myriad of cellular activities. Recent advances in AAA+ proteins, especially cryoEM structures of these proteins in complex with their substrates, have provided key insights into how they function. Here we review recent progress in structural studies and mechanistic understanding of AAA+ proteins involved in DNA processing, including gene transcription, DNA replication, repair/recombination and transposition. Using a few selected examples, we show how AAA+ proteins act on both DNA and protein peptides, which are often enclosed in the pores of AAA+ hexamers. We propose that using AAA+ proteins to translocate a peptide to partially unfold a substrate is an effective strategy in disassembling an assembled complex. Further, several studies show that although they often act as asymmetric hexamers in their active form, AAA+ proteins adopt a range of oligomers for their functions
PrEP programmes as a framework for tackling HBV infection in adolescents and young adults in KwaZulu-Natal, South Africa
No full textThese materials have been presented at the Global Hepatitis Summit (GHS) 2025 in Los Angeles, to support the new Evaluation of Vukuzazi LiVEr disease - Hepatitis B 'EVOLVE-HBV' study based at the Africa Health Research Institute (AHRI) in KwaZulu Natal, South Africa.‘EVOLVE-HBV’ research programme explored the PrEP uptake and retention cascade amongst adolescents and youth aged 15-30-year-olds and living with HBV through decentralized sexual health /HIV services of the ‘Thetha nami ngithethe nawe’ and the Long-acting HIV Pre-Exposure Prophylaxis (LAPIS) study.Specific AimAim: We set out to use data from PrEP studies to determine results of HBV screening, treatment uptake and retention amongst adolescents and young adults aged 15-30 years.Ethics and governanceThis work has been approved under the terms of the EVOLVE-HBV project ethics: University of KwaZulu Natal (UKZN) Biomedical Research Ethics Committee (BREC, ref. 00004495/2022) and University College London, UK ethics committee (ref. 23221/001 EVOLVE-HBV).PrEP HIV studies: (BREC/00000473/2019 and BREC/00003735/2021).</p
Hepatitis B Core-Related Antigen Point-of-Care Tests as a Risk Stratification Tool for Treatment Eligibility: Experience From Kenya.
No full textWe undertook a point-of-care test for hepatitis B core-related antigen in adults with hepatitis B virus in Kilifi, Kenya. A positive test identified all individuals with a hepatitis B viral load >200 000 IU/mL and who were hepatitis B e antigen positive. It also correlated with a higher alanine aminotransferase (ALT) level (P = .03), raised aspartate transaminase-to-platelet ratio index (APRI) (P < .001), and higher elastography scores (P = .03)
Science, education, leadership, and politics: An interview with Bruce Alberts and Paul Nurse.
No full textScience is often portrayed as the objective search for knowledge. However, science is also part of complex societies that shape science and in turn are shaped by scientific findings. In this interview, Bruce Alberts, former president of the US National Academy of Sciences, and Paul Nurse, former and future president of the Royal Society, discuss the roles of science and scientists in society. They share their passion to understand the natural world and the joy of discovery. They emphasize the importance of leadership in building institutions that support science and evidence-based decision-making. They share their frustration that current science education falls short in teaching the way science arrives at a better but incomplete understanding of the world. They urge scientists to organize and make their case to the public and fight misinformation and mistruths