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Long-term exposure to the ethanol-derived metabolite acetaldehyde elevates structural genomic alterations but not base substitutions.
No full textAcetaldehyde is the primary metabolite of ethanol, and routes of exposure include endogenous sources, food and cigarette smoke. To explore whether the mutagenic effect of acetaldehyde is responsible for the carcinogenicity of ethanol, we use whole genome sequencing on four human cell lines subjected to long-term, physiologically relevant, analytically validated acetaldehyde treatments. Unexpectedly, the treatments do not induce increased base substitution and short insertion/deletion mutagenesis, nor the appearance of the alcohol-associated cancer mutation signature SBS16. In contrast, we observe large genomic alterations in most cell lines, which parallel the association of 32 kb to 1 Mb deletions and duplications with alcohol consumption in a Japanese gastric cancer cohort. Observations of DNA damage response and a specific requirement for the homologous recombination pathway to tolerate acetaldehyde suggest that DNA breaks are responsible for structural genomic alterations in both cell line and tumour samples, and these may contribute to the carcinogenic effect of acetaldehyde
Genomic diversity of SARS-CoV-2 carriage in a cohort of schoolchildren in Côte d'Ivoire during COVID-19 pandemics: insights from pre-delta emergence.
No full textNo description supplie
The promise of GLP-1 receptor agonists for neurodegenerative diseases.
No full textGlucagon-like peptide-1 receptor agonists (GLP-1RAs), established therapies for type 2 diabetes and obesity, are increasingly recognized for their potential in neurodegenerative diseases. Preclinical studies across diverse neurodegenerative conditions consistently demonstrate neuroprotective effects of GLP-1RAs, including reduced protein aggregation, enhanced autophagy, improved mitochondrial function, suppression of neuroinflammation, and preservation of synaptic integrity. Epidemiological analyses further suggest reduced incidence of dementia, Parkinson disease, and multiple sclerosis among long-term GLP-1RA users. Early human trials provide signals of target engagement, such as preserved cerebral glucose metabolism, altered inflammatory biomarkers, and slowed brain atrophy, although clinical outcomes to date remain mixed and trials in rarer disorders are sparse. Translation is constrained by uncertainty around optimal molecule choice, CNS penetrance, tolerability, adherence, and heterogeneity of response. Furthermore, next-generation dual and triple agonists may offer enhanced efficacy but remain untested in neurodegeneration. Conceptually, GLP-1RAs share pleiotropic effects with exercise - one of the few interventions with proven disease-modifying potential - by enhancing insulin signaling, stabilizing mitochondria, reducing inflammation, and promoting synaptic plasticity. This overlap highlights their promise as "pharmacological analogues of exercise," and underscores the need for biomarker-driven, disease-specific trials to establish whether GLP-1RAs can deliver durable disease modification across the spectrum of neurodegenerative diseases
From Microscopes to Workflows: Supporting Research Through Imaging and Analysis
No full textThe Euro-BioImaging Scientific Ambassadors program aims to raise awareness about the services and opportunities provided by Euro-BioImaging. Our Scientific Ambassadors act as catalysts, connecting with like-minded individuals who share a common goal to impact in their communities. By effectively communicating the services offered by Euro?BioImaging, our Scientific Ambassadors play a crucial role in expanding the reach of Euro-BioImaging. Through their advocacy and engagement, Scientific Ambassadors help foster a greater understanding of Euro-BioImaging services, making imaging technologies more accessible for researchers and creating opportunities for collaboration, scientific advancement, and innovation in bioimaging.Poster presented as part of the Crick BioImage Analysis Symposium 2025.Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.</p
HepB-Boost: Implementation of free of charge healthcare worker hepatitis B testing and vaccination at Kilifi County Referral Hospital, Kenya.
No full textObjectives
Healthcare workers (HCWs) are at high risk of HBV exposure due to contact with blood and bodily fluids. In Kenya, HCWs are rarely fully vaccinated against HBV. During 2024, Kilifi County Referral Hospital (KCRH) in Kenya implemented HCW HBV testing and vaccination. We assess this implementation, including acceptability, feasibility and costs.
Methods
A technical working group was formed at KCRH, sensitisation was undertaken and vaccines procured in multi-dose vials. Clinics were run for two hours twice weekly over six-months. HBsAg testing was available, and vaccination offered at 0, 1 and 6 months.
Results
366/574 (64%) of staff received at least one vaccine. Of those attending, the number of fully vaccinated staff increased from 189/366 (5%) to 164/366 (45%), with 289/366 (79%) receiving at least two vaccines. 125/366 (35%) were tested for HBsAg and 4/125 (3%) tested positive. Overall cost of the vaccination programme was estimated at 25.45. A lack of HBV monovalent vaccine in multi-dose vials limited vaccination completion.
Conclusions
HBV vaccination for HCWs was feasible and acceptable at KCRH and could be offered at other similar sized hospitals. Consistent access to HBV monovalent vaccine must be a priority for Kenya
Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.
No full textCirculating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM (pTNM) stage I disease. ctDNA predicted worse clinical outcome, and patients with LUAD with </p
Chronogram: an R package for data curation and analysis of infection and vaccination cohort studies.
No full textMOTIVATION: Observational cohort studies that track vaccine and infection responses offer real-world data to inform pandemic policy. Translating biological hypotheses, such as whether different patterns of accumulated antigenic exposures confer differing antibody responses, into analysis code can be onerous, particularly when source data is dis-aggregated. RESULTS: The R package chronogram introduces the class chronogram, where metadata is seamlessly aggregated with sparse infection episode, clinical and laboratory data. Each experimental modality is added sequentially, allowing the incorporation of new data, such as specialized time-consuming research assays, or their downstream analyses. Source data can be any rectangular data format, including database tables (such as structured query language databases). This supports annotations that aggregate data types/sources, for example, combining symptoms, molecular testing, and sequencing of one or more infectious episodes in a pathogen-agnostic manner. Chronogram arranges observational data to allow the translation of biological hypotheses into their corresponding code via a shared vocabulary. AVAILABILITY AND IMPLEMENTATION: Chronogram is implemented R and available under an MIT licence at: https://www.github.com/FrancisCrickInstitute/chronogram; a user manual is available at: https://franciscrickinstitute.github.io/chronogram/
APP antisense oligonucleotides are effective in rescuing mitochondrial phenotypes in human iPSC-derived trisomy 21 astrocytes.
No full textINTRODUCTION: Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels in neurons, but their effects in astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs in astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD). METHODS: Human induced pluripotent stem cells (hiPSCs) from a healthy individual and an individual with DS were differentiated into astrocytes. Astrocytes were treated with APP ASOs for 10 days, and APP levels were quantified. Mitochondrial morphology and superoxide production in DS astrocytes were analyzed using super-resolution and confocal microscopy. RESULTS: APP ASOs significantly reduced APP levels in astrocytes from both control and DS individuals. In DS astrocytes, treatment restored mitochondrial health, increasing mitochondrial number and size while reducing superoxide production. DISCUSSION: APP ASOs effectively reduce APP levels and improve mitochondrial health in astrocytes, suggesting their potential as a therapeutic approach for DS and DS-related AD. Further in vivo studies are required to confirm these findings. HIGHLIGHTS: APP ASOs reduce APP levels in human iPSC-derived astrocytes. APP ASO treatment rescues mitochondrial phenotypes in trisomy 21 astrocytes. This study supports ASOs as a potential therapy for Down syndrome-related Alzheimer's disease
Symmetrical patterns formed when electrons from different subshells are set in motion.
No full textAnimations were prepared according to the specifications of the rotationally invariant atomic orbital model using Cinema 4D software.This media is associated with the article by R. Ogrodowicz titled 'The three-dimensional structure of an electron cloud encoded in the hydrogen spectrum aligns with the rotationally invariant atomic orbital model.', 2025.</p
Generation of a human iPSC line (UCLi025-A) from a patient with PHARC syndrome harbouring biallelic variants in ABHD12.
No full textA human induced pluripotent stem cell (hiPSC) line (UCLi025-A) was generated from dermal fibroblast cells from a 42-year-old female donor with polyneuropathy, hearing loss, retinitis pigmentosa and early-onset cataract (PHARC) syndrome carrying a homozygous nonsense variant in ABHD12 c.193C>T, p.(Arg65*). Fibroblasts were confirmed to carry the variant by Sanger sequencing and subsequently reprogrammed using non-integrating episomal plasmids generating a hiPSC line (UCLi025-A). This established cell line was validated for pluripotency markers expression, in vitro differentiation potential and normal karyotype. The utilization of this cell line will serve as a valuable resource for modelling PHARC syndrome and identification of therapeutic targets