Patterns of secondary variants, influenced by cohort, phenotype, and primary-variant ascertainment, alter phenotypic outcomes in individuals with disease-associated primary variants.

A study by Dorothy P. Schafer, PhD, and Travis E. Faust, PhD, explains how two different cell types in the brain communicate in response to changes in sensory input.

(Cell 188, ◼◼◼–◼◼◼.e1–e14; November 26, 2025)

Structures of the solute carrier transporters MCT8 and OATP1C1 reveal mechanisms of thyroid hormone transport into the brain and identify a conserved extracellular allosteric site in OATP1C1.

While targeting glucose metabolism shows potential in cancer therapy, its clinical implications remain unclear. This study finds that low-carbohydrate diets or impaired glucose metabolism in cancer ce...

Competition between transcription factors and mismatch repair machinery drives localized hypermutation at regulatory elements, with implications for cancer and genome evolution.

In gravistimulated roots, gravity perception in the columella redirects the flow of the plant hormone auxin toward the lower root side, where it inhibits cell elongation for downward root bending. This local auxin accumulation activates the cell-surface ABP1/ABL3-TMK1 auxin perception module, which phosphorylates and thus stabilizes the PIN2 auxin exporter for further auxin efflux in a positive feedback loop.

A genome-wide analysis of 8,105 soybean accessions reveals its stepwise domestication process, in which black soybean acts as an evolutionary intermediate, and identifies region- and era-specific selected genes that have shaped its global adaptation and breeding priorities.

RAEFISH delivers whole-transcriptome (>20,000 genes) imaging at single-molecule resolution in cells and tissues and enables direct gRNA detection for high-content, image-based CRISPR screens.

Mycobacterium tuberculosis isolates have a complex phylogenetic structure and vary in clinical phenotypes. Combining high-throughput RNA-seq and global population genomics reveals gene expression as an axis of variation in host interaction. Underscoring this, variants in a regulator of a key virulence pathway are associated with increased transmission and drug resistance.

(Cell 188, 4567–4585.e1–e32; August 21, 2025)

Identification of TranC systems reveals evolutionary intermediates bridging from transposon-encoded TnpBs and CRISPR-Cas12 effectors. Evolutionary, structural, and functional analyses show that RNA splitting into tracrRNA and crRNA was a pivotal step in the emergence of type V CRISPR systems.

scFLUENT-seq is a single-cell method that sensitively captures nascent nuclear transcriptomes to reveal mRNA and ncRNA dynamics, heterogeneity across chromatin compartments, and transcriptional diversity linked to cellular plasticity.

An antibody-based spatial proteomics screen on human primary cilia explores 715 proteins across single cilia of different cell types and reveals extensive cell-type specificity, single-cilium heterogeneity, ciliary microdomains, CFAP300 as a new cilium marker protein, 91 novel proteins including CREB3, and a CREB3 variant associated to ciliopathy phenotypes.

Targeting tumor-associated carbohydrate antigens, the most abundant and widespread cancer antigens known, via “velcro-like” binding of lectins allows immunosuppression-resistant pan-cancer killing while ignoring normal tissues.

Multiscale proteomic network modeling of Alzheimer's disease integrates large-scale proteomic and genetic data from vulnerable brain regions and reveals key driver proteins such as AHNAK within a glia-neuron subnetwork. These findings offer valuable insights into disease mechanisms and highlight potential therapeutic targets.

Volumetric high-resolution electron microscopy reveals thin astrocyte leaflets form gap-junction-interconnected domains that contain minuscule endoplasmic reticulum saccules and enwrap synapses in clusters. Two-photon calcium imaging reveals how leaflets integrate incoming neuronal inputs occurring at different spatiotemporal scales, thereby contributing to an additional layer of circuit computations.

(Cell 151, 289–303; October 12, 2012)

A family of rationally designed time-resolved fluorescent proteins with controllable lifetimes across the visible spectrum enables simultaneous multiplexed live imaging, super-resolution microscopy, and protein stoichiometry quantification, offering a transformative toolset for advancing biological research with enhanced complexity and quantitative precision.