Ryanodine receptor (RyR)-mediated calcium-induced calcium release (CICR) is a regenerative trigger-to-release mechanism used in diverse cell types. RyRs amplify small calcium signals into large, localized surges that drive autonomous oscillation, excitation-contraction coupling, pulsatile secretion, neurotransmitter release, or memory formation. Robust RyR function depends on the probability of RyR recruitment remaining within an operating range as […]

Parkinson’s disease (PD) exhibits substantial genetic heterogeneity, yet how combinations of rare variants converge on disease-relevant cellular mechanisms remains unclear. Here, we generated human induced pluripotent stem cell-derived dopaminergic neurons from PD patients carrying rare variants in recently implicated genes and performed integrated electrophysiological, proteomic, lipidomic, and genetic analyses. Patient-derived neurons showed reduced membrane capacitance […]

Object-based tasks are widely used in rodent behavioral research, yet object selection remains largely unsystematic. We present a paired-object validation protocol in which objects differ along one researcher-defined feature, allowing assessment of whether that feature is salient to the animal. Using six object pairs varying in height, color, shape, or aperture presence, we tested two […]

Background: Higher-quality diets have been associated with lower levels of ectopic fat deposited in the viscera and liver, which is hypothesized to be mediated in part by the gut microbiota. Objectives: We tested this hypothesis in a multi-ethnic imaging study using global (microbiome-wide) testing as well as a high-dimensional multiple-mediators regression framework to identify bacterial […]

Humans are just another species on Earth, but modern telecoupled societies and their socioeconomies impose immense consumption demands on the biosphere, detaching from common ecological rules. Starting from a simple ecological consumer/resource model, with humans as the consumers and terrestrial organic carbon (i.e., the biosphere) as the resource, we assume that technology modulates both human […]

Neocortex has the largest volume, while cerebellar cortex houses most neurons of the mammalian brain, underscoring paramount functions for interactions between them. Neocortex projects to the cerebellum via both the mossy fibre and climbing fibre system; whereas the mossy fibres find their origin in the pons, the climbing fibres are relayed via the subnuclei of […]

Anaerobic carbon transformation in freshwater sediments drives substantial methane emissions globally, yet the microbial taxa linking complex carbon degradation to methane production remain poorly characterized. Here, we combined metagenomics with the first metatranscriptomic dataset from the anoxic sediments of meromictic Lake Cadagno (Swiss Alps) to identify the active microbial clades, metabolic pathways, and extrachromosomal elements […]

Cnidocytes (stinging cells), unique to cnidarians (corals, anemones, jellyfish), have diversified into distinct types with variable forms and functions. Nematocytes, cnidocytes found in all cnidarians, are used for prey capture and defense. When triggered, a pressurized capsule inside the nematocyte releases a harpoon-like structure attached to a hollow tubule that pierces prey and delivers venom. […]

The Norman Conquest of 1066 CE reshaped the political and cultural landscape of England, yet its demographic consequences remain poorly understood, particularly outside elite and urban contexts where historical evidence is concentrated. Here, we investigate the population history of a rural English community spanning the Conquest using genome-wide ancient DNA from the Priory Orchard site, […]

The cerebellum plays a central role in generating temporal predictions from past sensory regularities, yet the temporal boundaries of this predictive capacity remain unclear. Using magnetoencephalography (MEG), we investigated somatosensory and cerebellar responses to omissions within rhythmic somatosensory stimulation trains across six inter-stimulus intervals (ISIs) ranging from 0.5 to 5.5 seconds. We hypothesised that cerebellar […]

Isoprenoid biosynthesis in E. coli is a promising source of high-value natural products. However, isoprenoid production imposes a substantial metabolic burden on cellular carbon and cofactor metabolism. Optimizing yields thus requires rebalancing gene expression throughout metabolism. To systematically identify the genes in E. coli central metabolism shaping isoprenoid yield, we established a high-throughput CRISPR interference […]

Animal venoms represent a major source of chemical novelty, yet how venom compounds originate, diversify, and are maintained across deep evolutionary timescales remains poorly understood. This gap is especially pronounced in cephalopods, which evolved venom systems used in predation, defense, and sexual competition, but whose venom genetic architectures, secretory cell types, and venom-producing glands remain […]