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In this work, functional antibodies against the cancer-related GPCR NTS1 were generated by immunizing chickens with in silico-designed 3D peptides, offering a strategy for GPCR targeting with potential diagnostic and therapeutic applications.

Synaptic extracellular proteins increasingly emerge as key organizers of neurotransmitter receptors. Here, authors show that an IgLON family cell adhesion molecule directly traps a nicotinic receptor through extracellular interactions.

The netrin receptor UNC-40/DCC is required to recruit GABA_AR at neuromuscular junctions in C. elegans. Here, the authors show that UNC-40/DCC assembles an intracellular synaptic scaffold, regulating the content of GABA_AR and inhibitory neurotransmission.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Broadly applicable genetically encoded probes and peptide-based compounds specifically inhibit Gα_s, the prototypical signal transducer of G-protein-coupled receptors, providing new mechanistic insights into signaling at the subcellular scale.

Glasses are known for their intrinsic structural disorder. Here, Wu et al. uncover the hidden spatial organization of topological defects embedded in vibrational eigenmodes, and reveal how these defects govern the emergence of plastic flow under shear.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

We propose that synapses compute probability distributions over weights, not just point estimates. Using probabilistic inference, we derive a new set of synaptic learning rules and show that they speed up learning in neural networks.

Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4⁺ macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Zhu et al. find that aging causes region-specific myelin damage in the spinal cord, which is counteracted by enhanced TGFβ signaling in microglia, revealing a protective mechanism for healthy aging.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

ARMH2 is identified as a previously unknown cytosolic component of the sperm-specific CatSper channel, critical for its normal assembly and pH/calcium sensitivity. Loss of ARMH2 impairs sperm hyperactivation and causes severe subfertility.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Single-cell multi-omic analyses show that chronic inflammation contributes to myeloproliferative neoplasm transformation to secondary acute myeloid leukemia by enhancing tumor protein 53 (TP53) mutant cell fitness and genetic evolution.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Gfi1b regulates cellularity of haematopoietic stem cells (HSCs) and megakaryocytes (MKs) as well as spreading of MKs on matrix. Here the authors show that Gfi1b regulates this behaviour by recruiting LSD1 and β-catenin to Wnt/β-catenin signalling targets.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Retrograde signalling co-ordinates nuclear gene expression in response to stress perceived in the chloroplast. Here Guo et al. show that a MAPK cascade acting downstream of a plastid derived Ca²⁺signal contributes to the regulation of nuclear gene expression by phosphorylation of ABI4 during retrograde signalling.

An extensive phylogenomics study based on hundreds of genomes and transcriptomes provides a new interpretation of the evolution of different types of symbiotic associations in land plants, and reveals a conserved ancestral symbiosis pathway.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

In oocytes of most species atypical spindles assembled in the absence of centrosomes drive chromosome segregation, however the forces driving this process are unclear. Here the authors found that spindle poles are largely dispensable and that inter-chromosomal microtubules of the central spindle control chromosomal segregation.

The tumor suppressor PTEN antagonizes the PI3K signalling pathway and is frequently inactivated in haematological malignancies. Here, the authors unravel the main contribution of the PI3K isoform p110ß to leukemic transformation driven by PTEN-loss.

Re-exposure to a high-fat diet in mice led to emergency myelopoiesis and increased neutrophils in the blood, which infiltrated plaques and released neutrophil extracellular traps, exacerbating atherosclerosis.

Primary immunodeficiency can predispose patients to mycobacterial disease. Casanova and colleagues identify novel human mutations in the enzyme SPPL2A that result in selective accumulation of CD74 in a dendritic cell subset and lead to their death and the failure to mount effective T_H1 responses.

A series of early-time, multiwavelength observations of an optical transient, AT2022cmc, indicate that it is a relativistic jet from a tidal disruption event originating from a supermassive black hole.

The mechanical behaviour of gold nanojunctions is investigated at the atomic scale using tuning-fork atomic-force microscopy, revealing a fluidic state at high strains with signatures of viscous-like dissipation and capillary-like adhesion.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A multilevel pattern-learning framework investigates the effects of genome-wide protein-coding mutations on brain organization and behaviour in the Adolescent Brain Cognitive Development cohort.

Understanding molecular arrangements in mechanistic studies of complex materials is critical but challenging. Here, the authors develop a hierarchical incremental learning protocol to uncover microscopic patterns, improving mechanistic insights obtained

Sperm motility and male fertility requires function of the CatSper calcium channels. Here, using cryo-electron tomography, authors visualize the native in-cell 3D structure and higher-order organization of the CatSper as long zigzag rows along the sperm tail.

This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The authors reveal that even within a few-nanometre thin films, ultrafast all-optical magnetisation switching is spatially inhomogeneous along the depth and driven by the picosecond propagation of a transient domain boundary.

Single-layer graphene, owing to its impermeability, is a promising candidate to prevent transmembrane ion transport. Here, the authors report a covalent functionalization method that enables centimeter-sized graphene to function as a proton exchange membrane in a direct methanol fuel cell.

Ordered corundum oxides offer promising alternatives to traditional perovskites in functional oxide thin films. Here, the authors utilize layer-by-layer growth to fabricate CrVO3 superlattice thin films, achieving atomic-scale precision and stabilizing the ilmenite phase, potentially expanding the range of customizable rhombohedral oxides with unique properties.

The amber deposits from Kachin, Myanmar have provided numerous insights into life in the Cretaceous ~99 million years ago. Here, Zheng and colleagues describe a new Late Cretaceous amber biota from Tilin, Myanmar, dating from ~72 million years ago and preserving a diverse insect assemblage.

Digital information can be stored in monomer sequences of non-natural macromolecules, but only short chains can be read. Here the authors show long multi-byte digital polymers sequenced in a moderate resolution mass spectrometer. Full sequence coverage can be attained without pre-analysis digestion or the help from sequence databases.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.