Marc A.

Abstract To explore the mental and physical health (MH, PH) on individuals living with brain aneurysms and to profile their differences in disease experience.

α,β-Unsaturated carbonyl functionality- those with connected carbon-carbon and carbon-oxygen double bonds- are commonly found in bioactive compounds. Late-stage functionalization of these compounds could involve oxidation of methylene (2°) C—H bonds while leaving the C—C double bonds that are important for biological activity intact1–3. Catalytic systems have been developed for selective oxidation of methylenes in the presence aromatics4 and N-heterocycles5, however olefins remain an unsolved problem. Here we show that replacing the carboxylic acid with a H-bond donor solvent in sterically hindered manganese PDP catalysts changes the active oxidant to one that accelerates electron rich methylene oxidation and significantly slows epoxidation of electron deficient olefins (kC-H[O]/kepox = 38.5). Chemoselective methylene oxidation is demonstrated in forty-five molecules housing α,β-unsaturated carbonyl functionality where all previous methods afforded allylic oxidation or epoxidation. Mechanistic studies support that the new oxidant proceeds via a more charged pathway that disfavors electron deficient bonds, demonstrating that highly reactive metal oxidants can be tuned to achieve chemoselectivity. These discoveries enable the first late-stage oxidations in complex natural products and derivatives housing these pharmacophoric substructures to furnish novel analogues and known metabolites.

Deaminases of the APOBEC3 family contribute to the mutagenesis of various cancers, including urothelial carcinoma (UC) of the bladder. Here, the authors use functional studies and transcriptomics to demonstrate that APOBEC3 promotes tumour progression and squamous trans-differentiation in UC through IL-1α and downstream activation of the AP-1 transcription factor.

Research with BSL-4 viruses such as Ebola, Marburg, and Nipah presents significant challenges due to their high virulence and the stringent containment measures required. This study establishes human airway organoids as a robust model for investigating BSL-4 pathogens. In contrast to conventional cell lines, airway organoids enable investigation of virus-host interactions within a human tissue context, providing insights that are more directly translatable to human disease. We generated airway organoids from both clinical donor tissues and commercially available nasal epithelial cells and showed in comparative analyses with whole lung tissue that these organoids are comparable in terms of cell composition. Despite biological variations, airway organoids derived from different sources and donors exhibit a remarkably similar cellular make-up. We further demonstrated that organoids derived from nasal swabs can effectively replicate BSL-4 viruses. This establishes them as a standardized 3D model for broader research applications including infection kinetics, immune evasion, and tissue-specific tropism within a controlled environment. This platform provides a powerful tool for antiviral testing and studying virus-host interactions, thus helping bridge critical gaps in high containment virus research and advancing our understanding of these pathogens, bypassing some of the challenges of animal models.

SWI/SNF complexes are mutated in 20% of cancers, yet the underlying mechanisms are poorly understood. Here, the authors identify a compensatory mechanism of chromatin regulation that becomes essential in cancers carrying mutations that broadly inactivate SWI/SNF.

Targeting cells for ablation, gene therapy or drug delivery is an ongoing challenge in development of therapeutics. With the goal of efficiently labeling cell surfaces based on target recognition, we linked the well-established engineered ultraID biotin ligase to cell-surface affinity reagents to enable catalytic installation of tags on the surface of cells. Biotin ligase conjugated to nanobodies against cell surface proteins exhibited an order of magnitude increase in cell labeling compared to nanobody alone. Biotin labeling of cells remained efficient at low nanomolar concentrations of the conjugate, and was stable for at least 4 h. By testing a swath of antibody-biotin ligase conjugates against various targets and cell types, we confirmed the feasibility and generalizability of this approach. Administration of biotin ligase-conjugated antibodies into animals efficiently biotinylated the expected target cells. Biotinylated target cells were subsequently detectable with fluorescent streptavidin injected into the same mice. Enzyme mediated cell targeting thus provides an efficient and modular platform for biotinylation and detection of cells expressing specific surface targets with potential applications for research and therapeutics.

Advances in molecular epidemiology and computational modeling have improved our ability to track pathogen evolution, but accurate reconstruction of...

Iron is a primary constituent of terrestrial planetary cores. Through direct measurements of Fe strength at 310-430 GPa and 3700-5800 K, and simulations, the authors study rheological properties of iron under conditions approaching those of Earth's inner core.

This Review discusses global approaches to infectious disease analysis and modeling, focusing on federated methods and addressing long-standing challenges in data interoperability, equity and trust.