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During the development of multi-cellular animals, biochemical signals control the organization of cells to set up body axes. In mouse embryonic stem cell aggregates, tissue flows are now found to amplify the formation of such body axes.

Descriptive data in biomedical research are expanding rapidly, but functional validation methods lag behind. Here, authors present Logical Synthetic cis-regulatory DNA, a framework to design reporters that mark cellular states and pathways, showcasing its applicability to complex phenotypic states.

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.

Scanning tunnelling microscopy-based H desorption lithography is used for atomic-scale patterning of quantum devices in Si, but its time-consuming nature hinders scalability. Here the authors report H desorption from Si(001):H surface using extreme-UV light and explore implications for patterning.

Protein–protein interactions specific to 11 individual tissues are presented in a comprehensive resource.

Epidemiological analysis of Mycobacterium tuberculosis genomes and public health data show that lineage-specific variation in transmission varies with the degree of host and pathogen geographical coincidence and reveals signals of a biological effect of host–pathogen coexistence.

Large language models are increasingly used for diverse tasks, yet we have limited insight into their understanding of chemistry. Now ChemBench—a benchmarking framework containing more than 2,700 question–answer pairs—has been developed to assess their chemical knowledge and reasoning, revealing that the best models surpass human chemists on average but struggle with some basic tasks.

The benefits and risks of nature to human health have been studied, however, robust empirical research on forest biodiversity and health outcomes is still lacking. Here the authors use a unique dataset from 164 European forest stands to explore the associations between forest types and well-being.

Owens et al. reported PFI-7, a selective and potent antagonist of GID4 of the CTLH E3 ligase complex, which enables identification of human GID4 targets. This study provides valuable insights into GID4 functions and a powerful tool for advancing new targeted protein degradation strategies.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Researchers use plasmonic nanofocusing of near-infrared pulses in metallic tapered gap waveguides to generate ultrashort extreme-ultraviolet pulses. They calculate that the electromagnetic field intensity is around 350 times higher than that of a reference untapered waveguide, allowing harmonics up to the 43rd to be realized at a modest incident intensity of ∼10¹¹ W cm⁻².

The authors demonstrate that cells that are deficient in H3K9 trimethylation display more compact mitotic chromosomes decorated with aberrantly high H3S10 phosphorylation and H3K27 trimethylation. By quantitative proteomics, they show that H3K9 trimethylation is essential for mitotic bookmarking by Esrrb and thus for the maintenance of epigenetic memory during cell division.

Strong lasing effects similar to those in the optical regime can occur at 1.5–2.1 Å wavelengths during high-intensity XFEL-driven Kα₁ lasing of copper and manganese.

The authors investigate spin-valley polarization in hybrid systems of Au nanoparticles and monolayer MoS₂ and observe a nearly complete quenching of the far-field circular polarization state of emission from MoS₂ at the position of the nanoparticle. This highlights the need to consider an ensemble, rather than just a single rotating dipole emitter, for precise predictions of polarization responses in these hybrid systems.

This study, together with a companion manuscript, show that, in mice, weight loss as a result of GIP receptor antagonism requires, and potentiates, functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

Physical characterisation of proteins is challenging. Here the authors report single-molecule microfluidic diffusional sizing (smMDS) to enable calibration-free single-molecule diffusional-sizing based monitoring of protein hydrodynamic radii even within heterogenous multicomponent mixtures.

Here the authors perform the reconstruction and analysis of pathological ALys amyloid fibrils extracted from fat tissue from a patient carrying the D87G variant. They reveal an intact amyloid fibril with no evidence of proteolysis and four intact disulphide bonds.

Here, the authors show that cystatin C (CST3) regulates the activity of cathepsin B during pancreatitis in a pH dependent manner. Moreover, cathepsin B activity is inhibited by monomeric CST3 but activated by dimeric CST3.

CEBPA is frequently mutated in acute myeloid leukemia (AML), but the transcriptional impact of the AML-associated isoform remains unclear. Here, the authors show that CEBPA-mutant cells have reduced inflammatory expression and higher sensitivity to ER stress due to impaired function of AP1 factors.

Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.

In this Perspective article, Huwyler, Binz and colleagues discuss the future of long-term normothermic machine perfusion for livers and propose a staged assessment approach for ex situ perfused organs.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

In this paper, the authors revealed the distinct folding motifs for irreversible and reversible amyloids derived from a single protein, by combining multiple mesoscopic and molecular techniques including AFM, cryo-EM and solid-state NMR.

Available enzymatic CO2 reduction strategies are not suitable for aerobic microorganisms and many industrial settings. Here, the authors design a new metabolic pathway that can operate under fully aerobic conditions, ambient CO2 levels, and seamlessly integrate with well-established C1-assimilation pathways.

Cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNA ribonucleoprotein complexes bound to the transcription–export complex reveal how mRNAs are packaged and recognized for nuclear export.

The efficient excitation of atoms using photons is a fundamental step in the control of photon-atom interaction and quantum information protocols. Here the authors show that photons with an exponentially rising envelope excite a single atom efficiently compared to a decaying temporal shape.

Diamond colour centres are of interest for solid-state quantum technologies but obtaining an efficient spin-photon interface remains challenging. Here, the authors use resonant excitation under magnetic fields to optically access the electronic spin sublevels of silicon-vacancy centres in diamond.

Raman microscopes suffer from the compromise between speed and spectral information and are often unsuited for fibre beam delivery. Karpf et al.overcome these limitations using continuous-wave rapidly wavelength-swept probe lasers and a short-duty-cycle actively modulated pump laser in an all-fibre setup.

Neurostimulation has been proposed as a potential approach for treatment-resistant PTSD. Here in a pilot study the authors show that amygdala theta activity is heightened during aversive and symptomatic experiences in patients with treatment-resistant post-traumatic stress disorder, and reduced following significant clinical improvement associated with closed-loop stimulation.

Protein biosynthesis is a major target of existing antibiotics that inhibit the efficiency or fidelity of the bacterial ribosome. Here, the authors show that a synthetic peptide displays bactericidal activity through a different mechanism, inducing co-translational aggregation of nascent peptidic chains.

The unification of the theory of relativity and quantum mechanics is a long-standing challenge in physics. Here the authors investigate the effects of a wide range of accelerations on an entangled photon pair, providing an upper bound for the effects of non-inertial frames on quantum systems.

This paper introduces msiFlow, an open-source software for scalable and reproducible end-to-end multimodal image analysis. Using msiFlow, the authors explore the molecular heterogeneity of leukocytes in infected tissues.

High sensitivity in quantum sensing comes often at the expense of other figures of merit, usually resulting in distortion. Here, the authors propose a protocol with good sensitivity, readout linearity and high frequency resolution, and benchmark it through signal measurements at audio bands with NV centers.

Distributed networks in visual cortex precisely link the fine-scale functional architecture with distant network elements and appear early in development, when heterogeneous local connections may seed long-range network interactions.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

A single-cell ex vivo screening of repurposable drugs in glioblastoma and machine learning of drug–target networks show that anti-tumor neuroactive drugs converge on the AP-1/BTG pathway, based on which prediction models and experimental in vivo and in silico validation identify the anti-depressant vortioxetine as a potential therapeutic agent.

The cryo-EM structure of phage φTE is presented, revealing a distinct neck topology, tail sheath baseplate organization and oligomeric state of the tape measure protein. These features suggest a mechanism linking base plate conformational changes to sheath contraction and genome ejection.

KirBac channels are the bacterial homologs of mammalian inwardly rectifying potassium (Kir) channels. All available structures are closed at the helix bundle crossing, but the crystal structure of an open-state KirBac channel now indicates how opening of the primary activation gate may be physically coupled to a rotational twist in the cytoplasmic domain.

The neural mechanisms that underlie temporal predictions remain unclear. Here the authors show that humans estimate the probability density of anticipated sensory events and represent this key variable in posterior parietal and motor cortical areas.

A non-destructive DNA isolation method for the stepwise release of DNA trapped in ancient tooth and bone artefacts is developed.

An exome wide association study of UK Biobank data revealed 158 variants and 105 genes significantly associated with kidney function traits and disease. The findings are supported by functional evidence for a previously unreported mutation in CLDN10.

Assessing tumour microenvironment-targeted drug candidates remains challenging. Here, the authors develop a comprehensive screening platform that allows for monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumour spheroids.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.

An autonomous system is described that combines deep reinforcement learning with onboard sensors collecting data from the physical world, enabling it to fly faster than human world champion drone pilots around a race track.