Search

CRISPR–Cas tools enable genome regulation but are often too large for efficient AAV delivery. Here, authors engineer a compact enhanced TnpB–ωRNA system (enTnpB) as a versatile genome regulation platform and develop a single-AAV regimen, ImmunAct, to activate endogenous cytokines and enhance cancer immunotherapy.

The millimetre image of the Centaurus A nucleus by the Event Horizon Telescope reveals a highly collimated, asymmetrically edge-brightened jet. The source’s event horizon shadow should be visible at terahertz frequencies, consistent with the universal scale invariance of black holes.

The cellular makeup of the primate cochlea, crucial for hearing, remains poorly understood. Here, authors show a detailed map of primate cochlear cells, revealing both conserved and species-specific features.

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.

A single-cell multi-omics atlas of rice is revealed, providing insight into cell-type functions and molecular programs.

EEG-based dynamic large-scale network analysis demonstrates how the parahippocampal-insula network modulates memory reactivation and attentional prioritization during retro-cue working memory tasks.

High-performance approaches for terpenoid discovery and characterization in fungi are lacking. Now, a fully automated and high-throughput biofoundry is developed using Aspergillus oryzae as chassis for efficient genome mining and biosynthetic pathway analysis of bioactive terpenoids.

Less is known about the entire microbial pathogen profile of small mammals. Here, the authors analyse 2,408 tissue-resolved metatranscriptomes to map the infectome in small mammals, uncovering high viral, bacterial, fungal and parasitic diversity and showing how geography, hosts, and seasons shape zoonotic risk.

Chassis-independent recombinase-assisted genome engineering (CRAGE) enables the integration of plasmids encoding biosynthetic gene clusters into the chromosomes of diverse bacteria to optimize production of natural products in non-native strains.

In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.

Methionine restriction (MR) provides metabolic benefits in many organisms. Here, the authors report that MR is sensed by yeast mitochondria as a sign of SAM deprivation; in response, the mitochondria redirect carbon metabolism to fuel nitrogen anabolism in a lipoate-dependent mechanism.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

A 2.5-billion-year record of oxygen isotopes in sedimentary sulfate reveals the transitional oxygenation of the Earth’s surface and provides constraints on the dynamic, lengthy co-oxygenation of Earth’s atmosphere and oceans.

During zygotic genome activation the embryo must re-wire the regulatory network that sustains totipotency earlier during development. Here they identify ZFP352 as an essential factor that targets retrotransposon families to facilitate dissolution of the totipotency network and enable ZGA.

In the Multicellularity Long Term Evolution Experiment, diploid yeast evolve to be tetraploid under selection for larger multicellular size, revealing how whole-genome duplication can arise due to its immediate benefits, persist under selection, and fuel long-term innovations via aneuploidy.

Thyroid hormones regulate systemic glucose metabolism through incompletely understood mechanisms. Here the authors report that hepatic thyroid hormone receptor β mediates the effects of the thyroid hormone T3 on systemic glucose homeostasis by modulating GLP-1 levels through suppression of hepatic CYP8B1 expression and bile acid mediated inhibition of intestinal FXR signalling.

The WD40 domain of the SCF^Cdc4ubiquitin ligase targets substrates via multiple phosphorylated degron motifs. The authors define a second degron-binding WD40 pocket that imparts a negative allosteric effect on binding to the primary pocket, and thereby enables the dynamic exchange of bound degrons.

Aurora kinase A is a mitotic kinase that facilitates G2/M events. Here the authors show that in breast cancer cells Aurora kinase A has a kinase-independent function in the nucleus by activating the MYC promoter in cooperation with hnRNP K, enhancing the breast cancer stem cell phenotype.

Li, Li, Wu et al. use a proteomics approach, PhastID to identify protein components of nuclear condensates (NCs). They reveal crosstalk between NCs, the dynamics of condensate components and identify an NC formed by BUD13.

Systematic transcriptomics analysis reveals the synergistic interaction of calorie restriction and rapamycin in extending cellular lifespan, identifying unique and overlapping gene regulation patterns in both yeast and human cells.

Long-distance V(D)J recombination is facilitated by contraction of the Igh locus and linear RAG scanning along chromatin, both driven by cohesin-mediated loop extrusion, which allows recombination of widely separated gene segments to occur.

Chromosomal inversions can promote speciation. Here, the authors identify a young inversion that has captured ecologically important genetic variants in a hybrid zone of the plant Boechera stricta, promoting local adaptation and incipient speciation.

Anna Andersson, Tanja Gruber, James Downing and colleagues report a genomic analysis of infant acute lymphoblastic leukemias with MLL rearrangements. They identify recurrent activating mutations in tyrosine kinase, phosphatidylinositol 3-kinase and RAS pathway genes but find that these mutations were often present in minor subclones and lost at the time of relapse.

Chromothripsis, a chromosomal shattering event, can be elicited by micronuclei and chromosome bridges formed by CRISPR–Cas9-generated double-stranded breaks. Extensive chromosomal rearrangements may thus be an on-target effect of genome editing.

The genetic changes that occur in late stage metastatic melanoma are not well delineated. Here, the authors use rapid autopsy samples from metastatic melanoma patients and show that the late stage in the disease is characterised by whole genome doubling and aneuploidy.

The development of new methodologies to convert plastics into fuels without relying on noble metal-based catalysts is desirable. Now it is shown that a layered self-pillared zeolite enables the conversion of polyethylene to gasoline with a selectivity of 99% and yields of >80% without the need to use external hydrogen.

Microtubule asters originate from centrosomes but their role during interphase remains largely unknown. Here, the authors find that microtubule asters anchored by previously-uncharacterized FSD1 play a role in ciliogenesis by maintaining the dynamic localization of centriolar satellites.

Inspired by human brain for multi-task continual learning, a generalized photonic neuromorphic architecture (L²ONN) is proposed to model physical-driven light sparsity and parallelism, towards reconfigurable and scalable lifelong learning.

The medial prefrontal cortex (mPFC) is implicated in pain regulation, yet the underlying mechanisms are poorly understood. Here the authors establish a critical role for mPFC in regulating pain sensation and pain-related anxiety, mediated by activation of the cyclin-dependent kinase 5 signalling pathway.

ZTF J1406+1222 is a wide hierarchical triple system that hosts a low-metallicity subdwarf star and a ‘black widow’ millisecond pulsar that has a highly varying optical flux and a 62-minute period.

The neutron star birth-mass function, based on 90 mass measurements, shows a unimodal turn-on power-law shape peaking at 1.27 solar masses. This model links supernova progenitors and binary evolution to observed mass constraints.

Single-electron transistors are written at the heterointerface of two oxides using an atomic force microscope tip, and the electrons in the device can be controlled by gating and the ferroelectric state of the heterostructure.

Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

A recombinant vaccine that targets the receptor-binding domain of the spike protein of SARS-CoV-2 induces a potent antibody response in immunized mice, rabbits and non-human primates, and protects primates from infection with the virus.

Understanding of the structures and roles of catalyst promoters markedly lags behind the understanding of the structures and roles of catalytic sites. Here, the authors address this challenge by incorporating a single-site promoter—tin—on a TiO₂ surface to enhance the catalytic activity of various metals on the TiO₂ in selective hydrogenation of nitroarenes.

Researchers report rewritable nanoscale photodetectors that exploit 2–3 nm nanowire junctions. Large electromagnetic fields in the gap region aid the detector response, which is electric-field-tunable and spans the visible to near-infrared regime.

Small molecule NIR-II fluorophores are of interest for a range of applications but can suffer from chemical and photostability issues. Here, the authors report on the development of an acceptor molecule with improved stability in alkaline conditions expanding the range of possible applications.