Naphthenic acids are amphipathic compounds whose toxicity has primarily been attributed to narcosis toxicity to cell membranes. However, few methods exist that specifically study the membrane disruption and toxicity of this complex family of cyclic, polycyclic and acyclic alkyl-substituted carboxylic acids. Here we describe a whole cell biosensor approach that relies on the ability of […]

Nipah virus (NiV) is a highly pathogenic emerging henipavirus for which there are no licensed vaccines or therapeutics currently available. Viral entry is mediated by the coordinated action of the attachment (NiVG) and fusion (NiVF) glycoproteins yet the organisation of NiVF on viral particles and its influence on antibody neutralisation is not completely understood. Using […]

C. elegans, a bacterivore living in microbially-complex environments, harbors a characteristic community of gut bacteria that contribute to its health and fitness. What determines which environmental bacteria end up as commensals is largely unknown in C. elegans, as in other animals. Previous work found that gut Pantoea isolates supported rapid worm development and infection resistance, […]

Introduction: Impaired motile cilia function contributes to many respiratory disorders, but therapies targeting this cellular defect are currently lacking. Personalized airway epithelial models combined with quantitative, complementary ciliary assays can pave the way for the development of such therapies. However, existing airway epithelial cultures often show variable ciliogenesis, and ciliary function is frequently assessed using […]

OXA-232, an OXA-48 like carbapenemase stands amongst newly identified beta-lactamases that causes of the extensive of beta-lactam resistance. While active-site residues are well characterised, the contributions of conserved non-active-site residues in exerting enzymatic activity remain unexplored, limiting our understanding about the roles of these residues in the overall OXA-232 function. To address these gaps, the […]

How regenerative capacity originates during development remains poorly understood, even in vertebrates with exceptional adult regenerative ability. Using the axolotl, we identify a defined embryonic window between stages 30 and 34 during which the tail region transitions from a regeneration-incompetent to a regeneration-competent state. Amputations across staged embryos reveal that earlier embryos entirely fail to […]

Protein evolutionary rates vary widely across proteins and among sites within proteins, reflecting multiple molecular, cellular, and functional constraints. While protein-level properties, such as expression and essentiality, and site-level structural and functional constraints, are known to influence evolutionary rates, how these constraints combine across scales to determine site-specific evolutionary rates remains unclear. Moreover, because many […]

During infection, bacterial populations need to overcome low levels of host-generated H2O2. However, experiments almost always use high H2O2 levels that are rarely found in hosts. Here, we use microfluidics to investigate how host-relevant H2O2 impacts populations of the human pathogen Pseudomonas aeruginosa in flow. Using long-channel microfluidic devices, we establish that cells at the […]

Codon optimality promotes efficient translation and, as recent research has shown, also extends mRNA lifetimes. However, how control is distributed between translation and mRNA degradation remains unclear. We show that this relative impact depends strongly on the measurement approach. Using fluorescent protein reporters can underestimate codon-optimality-dependent increases in translation efficiency. Conversely, analyses based on poly(A)-selected […]

Long-read sequencing technologies offer the potential to capture multiple RNA processing events within single molecules, but standard protocols suffer from quantification biases and sequencing errors that limit their utility for precise analysis. Here, we describe Long-read 3′ RACE-seq (L3R-seq), a targeted long-read sequencing method that ligates a unique molecular identifier (UMI)-containing adapter to the 3′ […]

Alternative splicing of mRNA precursors is an important step in gene regulation and a major mechanism by which genetic variants cause human disease. However, changes in splicing have only been quantified for a tiny fraction of possible variants in the human genome, limiting our ability to interpret clinical variants, evaluate and develop machine learning models, […]

Mosaic loss of chromosome Y (LOY) is a common age-associated somatic alteration in men and is typically measured from DNA-based assays. Many cohorts, however, contain bulk RNA-seq data without matched DNA-based LOY measurements. We developed a Bayesian framework to estimate the fraction of cells with LOY from male bulk RNA-seq by modeling reduced Y-linked gene […]