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, […]
Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart
The heart needs to adapt its output to the metabolic demands of the organism. Phosphorylation of the myosin motors by cardiac myosin light chain kinase (cMLCK) increases heart muscle contractile function, yet its regulation and mechanism of action have remained unclear. Here, we show that cMLCK undergoes liquid-liquid phase separation and forms biomolecular condensates associated […]
Pyrethroid Resistance Status and Multiple kdr Mutations (F1534C/L) in Aedes aegypti Populations from Zika-prone Areas in Lamu County, Kenya
Aedes aegypti mosquitoes are the primary vectors for dengue, yellow fever, chikungunya and zika virus transmission, posing significant public health risks. In Kenya, these viruses drive disease outbreaks especially, dengue and chikungunya with coastal Kenya being the most affected. Low-level circulation of the Zika virus has been reported in parts of the Kenyan coast, with […]
Analysis of multi-way chromatin interactions at sub-nucleosome resolution identifies synergistic nano-scale interactions within super-enhancers
In-depth understanding of the 3D organization of the genome and its role in the regulation of gene expression requires techniques to measure complex chromosome conformations at single alleles at high resolution. Here, we present multi-way Micro-Capture-C (mwMCC), a method to detect concurrent interactions between multiple chromatin regions at single alleles at sub-nucleosome resolution. mwMCC resolves […]
Obsessive-compulsive disorder and abstract sequence task contributions shift prefrontal cortical connectivity
Obsessive-compulsive disorder (OCD) is characterized, in part, by repetitive, sequential behaviors, such as cleaning rituals, yet underlying neural circuitry related to abstract sequencing in OCD remains poorly understood. Prior work has implicated a set of cortical regions activated during abstract sequences, which are defined by rules rather than specific stimulus features (Desrochers et al., 2022). […]
Large language model inference of macromolecular complex composition via model consensus and experimental data integration
Large language models (LLMs) are poised to reshape how biologists retrieve specialized knowledge at scale. Yet their performance on deep, domain-specific queries is poorly defined because much biological information resides in structured databases or large experimental datasets rather than in a free text format. One such gap in cellular biology lies in identifying major macromolecular […]
Flow-driven delivery boosts antibiotic effectiveness by overwhelming bacterial defenses
Physical, chemical, and biological factors collectively determine antibiotic effectiveness. However, laboratory studies often consider only one or two of these factors and fail to capture key interaction effects. Here, we use microfluidics to study the interplay of host-relevant shear flow, the antibiotic gentamicin, and the human pathogen Pseudomonas aeruginosa. We discover bacterial populations can defend […]
Layer 6 corticothalamic neurons show diverse and dynamic responses that support a role in cortical gain control in noisy environments
Listening in complex environments requires the enhancement of relevant sounds and suppression of irrelevant ones. Corticothalamic neurons (CTNs) in auditory cortex layer (L) 6 provide modulatory feedback to thalamic nuclei and to upper cortical layers and are thought to be involved in gain control. However, their role in auditory processing remains unclear. We used in […]
Cohesin collisions maintain ordered nucleosome architecture at boundaries and promoters
Abstract Cohesin is best known for its role in loop extrusion, while nucleosome phasing at regulatory elements is usually attributed to local DNA-bound factors and remodelers. Here we identify a previously unrecognized role for cohesin-mediated extrusion in maintaining local nucleosome architecture at CTCF sites and transcription start sites. Using single-molecule nano-NOMe-seq during SCC1 depletion, cell-cycle […]
Play vocalizations induce affective bias in reward learning and memory in orangutans
Affective biases, or shifts in learning and decision-making driven by affective states, are central to human cognition. Translational studies in rodents have shown that pharmacological and stress manipulations alter reward valuation, but how positive social signals shape these processes remains poorly understood. Here, we adapted the Affective Bias Test (ABT), a translational rodent assay of […]
Pyrethroid Resistance Status and Multiple kdr Mutations (F1534C/L) in Aedes aegypti Populations from Zika-prone Areas in Lamu County, Kenya
Aedes aegypti mosquitoes are the primary vectors for dengue, yellow fever, chikungunya and zika virus transmission, posing significant public health risks. In Kenya, these viruses drive disease outbreaks especially, dengue and chikungunya with coastal Kenya being the most affected. Low-level circulation of the Zika virus has been reported in parts of the Kenyan coast, with […]
Play vocalizations induce affective bias in reward learning and memory in orangutans
Affective biases, or shifts in learning and decision-making driven by affective states, are central to human cognition. Translational studies in rodents have shown that pharmacological and stress manipulations alter reward valuation, but how positive social signals shape these processes remains poorly understood. Here, we adapted the Affective Bias Test (ABT), a translational rodent assay of […]