Browse Articles
Discover research articles across all indexed journals
SDC4 identified as an oncogenic target gene of NF-κB in TNFα-Induced tumor cells
Curiosity, drive, willingness to learn: three qualities to display at science job interviews
Ideal antiferroelectricity with large digital electrostrain in PbZrO3 epitaxial thin films
A seasonal strategy for pollen tube growth and ovule development to overcome winter in Japanese stone oak (Lithocarpus edulis)
Author Correction: Development and evolution of Drosophila chromatin landscape in a 3D genome context
The effect of non-local coupling of fibroblasts on pacing dynamics in a 2D tissue: a simulation study
Abstract Although myocytes in healthy hearts are usually coupled to nearest neighbours via gap junctions, under conditions such as fibrosis, in scar tissue, or across ablation lines, myocytes can uncouple from their neighbours. However it has been experimentally observed that electrical conduction can still occur across these uncoupled regions via fibroblasts. In this paper we propose a novel model of non-local coupling between myocytes and fibroblasts in a 2D tissue, and hypothesise that such long-range coupling can give rise to pro-arrhythmic re-entrant wave dynamics. We have simulated the scar and the surrounding border zone via simultaneous coupling of fibroblasts with both proximal and distal regions of myocardium. We find that in this setup the border zone itself is a dynamical outcome of the coupling between cells within and outside the scar. We have determined the effect of the border zone on the stability of waves generated by rapid pacing. Furthermore we have identified key parameters that determine wave dynamics in this geometry, and have also described the mechanism underlying the complex wave dynamics. These findings are of significance for our understanding of cardiac arrhythmias associated with regions of myocardial scar.
How quickly do humans mutate? Four generations help answer the question
A mathematical model of H5N1 influenza transmission in US dairy cattle
Abstract 2024 saw a novel outbreak of H5N1 avian influenza in US dairy cattle. Limited surveillance data has made determining the true scale of the epidemic difficult. We present a stochastic metapopulation transmission model that simulates H5N1 influenza transmission through individual dairy cows in 35,974 herds in the continental US. Transmission is enabled through the movement of cattle between herds, as indicated from Interstate Certificates of Veterinary Inspection data. We estimate the rates of under-reporting by state and present the anticipated rates of positivity for cattle tested at the point of exportation over time. We investigate the impact of intervention methods on the underlying epidemiological dynamics, demonstrating that current interventions have had insufficient impact, preventing only a mean 175.2 reported outbreaks. Our model predicts that the majority of the disease burden is, as of January 2025, concentrated within West Coast states. We quantify the uncertainty in the scale of the epidemic, highlighting the most pressing data streams to capture, and which states are expected to see outbreaks emerge next, with Arizona and Wisconsin at greatest risk. Our model suggests that dairy outbreaks will continue to occur in 2025, and that more urgent, farm-focused, biosecurity interventions and targeted surveillance schemes are needed.
Attention as the primary cognitive domain affected in post-myocardial infarction cognitive impairment: a prospective multicenter study
How skunk cabbages and other smelly plants brew their foul odour
Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors
Abstract Current cancer gene therapies rely primarily on antitumor immunity, but the exploration of alternative mRNA cargoes for direct antitumor effects is crucial to expand cancer gene therapies. Here we show that lipid nanoparticles (LNPs) carrying mRNA encoding a viral 3 C protease can efficiently suppress tumors by selectively inducing tumor cell apoptosis. In various solid tumor models, intracranial injection of LNPs carrying mRNA encoding the 3 C protease (3C-LNPs) significantly inhibits tumor growth and prolongs survival in glioblastoma models. Similarly, subcutaneous injection reduces tumor volume and inhibits angiogenesis in a breast cancer model, while intravenous injection inhibits tumor growth and angiogenesis and prolongs survival in hepatocellular carcinoma models. Mass spectrometry and cleavage site prediction assays identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as the main target degraded by the 3 C protease. This study suggests that viral protease mRNA could be a promising broad-spectrum antitumor therapeutic.
RNA demethylase ALKBH5 regulates cell cycle progression in DNA damage response
Abstract RNA N6-methyladenosine (m6A) modification plays a crucial role in the DNA damage response, while the detailed mechanisms remain to be explored. In this study, we report the involvement of the m6A demethylase ALKBH5 in X-ray-induced DNA damage response. Depletion of ALKBH5 reduces X-ray-induced DNA damage, induces G2/M phase arrest and reduces cell apoptosis. RNA sequencing and m6A sequencing analysis reveal that ALKBH5 removes m6A modifications from its target mRNAs and suppresses their expression. A subset of mRNAs encoding cyclin dependent kinase inhibitors, such as CDKN1A and CDKN2B, show increased stability and expression upon ALKBH5 knockdown. Subsequently, the upregulation of CDKN1A and CDKN2B contributes to G2/M phase arrest to facilitate DNA repair. Our findings unveil the epigenetic regulation of cell cycle checkpoint by ALKBH5 in X-ray-induced DNA damage, offering potential targets for DNA damage-based therapy for cancers.