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Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Shukla and colleagues study the genomic and transcriptomic data of exceptional responders to immunotherapy in renal cell carcinoma and find that such responses could be related to tertiary lymphoid structures, clonal neoantigen load and altered metabolism.

An in situ X-ray nanodiffraction technique allows for the real-time study of the photoinduced chemical reaction to produce Ag from AgBr, and can spatially resolve structural changes at the submicrometre scale with a time resolution of 5 ms.

Ultrafast quantum control of helium atoms is obtained by shaping the extreme ultraviolet pulses generated by a seeded free-electron laser.

Kerr frequency combs are well suited for high-capacity data transmission with phase-sensitive modulation formats. This work demonstrates error-free transmission with data rates of up to 1.44 Tbit s⁻¹, spectral efficiencies of up to 6 bit s⁻¹ Hz⁻¹ and transmission distances of up to 300 km.

Quantitative, large-scale in vivo phosphoproteomics analyses are made possible with a form of spike-in stable-isotope labeling with amino acids in cell culture (SILAC), in which SILAC-labeled cell lines act as an internal standard for mass spectrometry–based tissue phosphoproteome analysis.

This paper develops two approaches for multiplexing cortical organoids and SCanSNP, a method for deconvolving cell identities, to trace neurodevelopmental trajectories at scale.

Alzheimer’s disease is characterised by the deposition of Aβ amyloid fibrils and tau protein neurofibrillary tangles. Here the authors use cryo-EM to structurally characterise brain derived Aβ amyloid fibrils and find that they are polymorphic and right-hand twisted, which differs from in vitro generated Aβ fibrils.

Systemic amyloidosis of the ATTR is one of the most abundant forms of systemic amyloidosis and caused by misfolding of the circulating blood protein transthyretin (TTR). Here the authors present the cryo-EM structure of patient-derived Val30Met ATTR amyloid fibrils which reveals that the protofilament consists of an N-terminal and a C-terminal TTR fragment and discuss implications for the mechanism of misfolding.

Channelrhodopsins (ChRs) are algal light-gated ion channels used as optogenetic tools for manipulating neuronal activity. Here authors present a metagenomically identified family of phylogenetically distinct anion-conducting ChRs (MerMAIDs) which desensitize during continuous illumination due to accumulation of a non-conducting photointermediate.

Our perception of a speech sound tends to remain stable despite variation in people’s vocal characteristics. Here, by measuring neural activity as people listened to speech from different voices, the authors provide evidence for speaker normalization processes in the human auditory cortex.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

T cell exhaustion was thought to be strictly associated only with chronic infections and tumours, but it turns out that acute infections also generate a subset of precursor T cells with exhaustion-like phenotypes.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

Cereghetti et al. report that the glycolytic metabolite fructose-1,6-bisphosphate initiates the disassembly of amyloids formed by the yeast pyruvate kinase Cdc19 to resume ATP production during stress recovery.

High-resolution crystal structures of the rat succinate receptor SUCNR1 in an inactive confirmation, and the humanized rat SUCNR1 bound to an antagonist, provide insights into the structure of these receptors and the species selectivity of antagonist binding.

Rhizoclosmatium globosum contains three rhodopsin-guanylyl cyclases (RGCs) predicted to enable visual orientation of zoospores. Here authors show that RGC1 and 2 function as light-activated cyclases only upon heterodimerization with RGC3 (NeoR), a near-infrared absorbing, highly fluorescent rhodopsin.

A haem–carbenoid has been proposed to be involved in abiological enzymatic reactions. Now, Hilvert and co-workers provide crystallographic evidence for a haem–carbenoid intermediate as the reactive species in an olefin cyclopropanation reaction catalysed by an artificial metalloenzyme.

Using a combination of behavioral and physiological approaches, the authors show that ON and OFF motion detection pathways in Drosophila exhibit distinct temporal tuning properties. Computational modeling suggests that these asymmetric tuning properties improve the fly's ability to reliably estimate velocity in natural environments.

A class of chimeric synthetic antibiotics that bind to lipopolysaccharide and BamA shows potent activity against multidrug-resistant Gram-negative bacteria, with the potential to address life-threatening infections.

Peripheral stimuli can induce acute immune training and tolerance in the brain and lead to long-lasting epigenetic reprogramming of microglia; these changes alter pathology in mouse models of stroke and Alzheimer’s pathology .

The processing of RNAs transcribed by RNA polymerase II requires a cap-binding complex (CBC), consisting of NCBP1 and NCBP2. Here, the authors report an alternative CBC formed by NCBP1 and a previously uncharacterized protein, NCBP3 that is critical for RNA processing under cellular stress conditions.

The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.

Pathogen whole genome sequencing, coupled with statistical and machine learning models, offers a promising solution to multi-drug resistance diagnosis. Here, the authors present two deep convolutional neural networks that predict the antibiotic resistance phenotypes of M. tuberculosis isolates.

Grammar learning requires memory for temporally organised, rule-based patterns in speech. Here, the authors use event-related potentials to show that 6 to 8 month-old infants can form memory of dependencies between nonadjacent elements in sentences of an unknown language, regardless of whether they nap or stay awake after encoding.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Mathieson et al. carried out a genome-wide association study of reproductive success (number of children born) in humans, revealing the importance of diverse neuro-endocrine and behavioural factors.

Here, the authors probe the mechanism of secondary nucleation inhibition of the BRICHOS domain of the lung surfactant protein (proSP-C) against α-Syn aggregation and amyloid formation using NMR and super-resolution fluorescence microscopy.

Examining the spatially resolved transcriptome of tissue sections promises advances in biomedical research. Here, the authors present xDBiT, a versatile, microfluidics-based approach to cost-effectively measure the spatial transcriptome of multiple tissue sections in parallel.

Large volcanic eruptions in the first half of the nineteenth century blurred the transition from the Little Ice Age to anthropogenic warming, and led to sustained cooling, drought in Africa and weakened monsoons, suggests a combination of observations and model simulations.

Glaciers in the European Alps are strongly affected by global warming, yet there is no methodologically consistent alpine-wide analysis on glacier changes. Here the authors show significant glacier retreat and an ice mass loss of 1.3 ± 0.2 Gt a⁻¹, derived from contemporaneous measurements of glacier areas and elevations.

Microsecond infrared spectroscopy together with quantum chemistry reveal the rate-determining proton and electron movements and identify an oxygen-radical state of the manganese cluster as the S4 state.

Glucose uptake in astrocytes is thought to rely on GLUT1. Here, the authors show that adult mice tolerate astrocyte-specific GLUT1 deletion, which increases astrocytic glucose metabolism and confers neuroprotection in a model of stroke.

The human endoderm-derived organoid cell atlas (HEOCA) presents an integrative analysis of single-cell transcriptomes across different conditions, sources and protocols. It compares cell types and states between models, and harmonizes cell annotations through mapping to primary tissues.

Van Hove singularities have the potential to drive unconventional magnetic states in Kagomes. Here, the authors provide experimental and theoretical results suggesting a van Hove singularity-assisted spin density wave in the Kagome metal CeTi₃Bi₄.

Copy number alterations in stem cells impair neural crest differentiation and set the stage for neuroblastoma-like traits and tumours. This study hints at early tumourigenesis mechanisms and finds developmental gene signatures linked to prognosis.

This study presents the cryo-EM structures of polymorphic TDP-43-derived amyloid fibrils that share a common fibril protein conformation constituting an amyloid key motif. The obtained results provide a possible mechanistic explanation for the formation of this motif in amyloid fibrils.

Targeted protein degradation (TPD) has emerged as a new paradigm for modulating protein activity. Here, the authors develop bifunctional degraders combining a putative ligand of the autophagy-related LC3 protein with different protein targets, which direct proteins of interest to the proteasome by covalently targeting the DCAF11 E3 ligase substrate receptor.

In mice, a population of astrocytes in the central striatum, characterized by expression of μ-crystallin, has a role in perseveration phenotypes that are often associated with human neuropsychiatric disorders.

Systemic AA amyloidosis is caused by misfolding of the acute phase protein serum amyloid A1. Here the authors present the cryo-EM structures of murine and human AA amyloid fibrils that were isolated from tissue samples and describe how the fibrils differ in their fundamental structural properties.

Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

The function of VCP/p97 AAA-ATPase cofactor UBXD1 and its UBX domain has been elusive. Here the authors show that the extended UBXD1 UBX domain is located at the p97 pore exit where it binds ubiquitin, suggesting that UBXD1 receives unfolded substrates and hands them off for down-stream processing.

Analysis of monoclonal antibody responses to the Ebola virus vaccine rVSV-ZEBOV in human volunteers.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.