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Changes in the tumour microenvironment have been associated with response and resistance to immunotherapy. Here, by performing longitudinal transcriptomic and spatial analysis, the authors report the exploratory analysis of their phase II trial of neoadjuvant chemotherapy alone or in combination with pembrolizumab (anti-PD1) in patients with advanced high-grade ovarian carcinoma.

Centrioles are broken down during oogenesis and are provided by the sperm during sexual reproduction, though how centriole numbers are regulated during asexual reproduction is unclear. Here they study two asexually reproducing nematodes and identify distinct mechanisms for maternal centrosome inheritance.

Genetically encoded voltage indicators need fast and large signals to allow widefield imaging of rapid neuronal activity. Here, the authors develop the indicator JEDI-1P and demonstrate pan-cortical voltage imaging and gamma-frequency tracking in awake mice in single trials.

With a sustainable carbohydrate core, the proposed polyamide plastic design here can compete with fossil-based alternative in terms of both performance and cost.

Claims that the end-Ordovician Earth was characterized by giant ice sheets, yet paradoxically warm oceans and elevated CO₂ levels are open to debate. Here, Ghienne et al. examine sedimentary records from low and high palaeolatitude settings and propose a revision of the mechanisms for end-Ordovician events.

Fetching an object by means of sending a wave—impossible? Not necessarily. As now demonstrated experimentally, generating waves on a water surface using a set of plungers can cause a floating particle to move counter to the general direction of wave propagation. The effect originates from vorticity creation by steep 3D waves.

Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to CRBN-PROTACs.

Here, the authors uncover that, among 92 identified host factors associated with SARS-CoV-2 virions, G3BP1 and G3BP2 are present at the assembly site, incorporated within virions, and unexpectedly promote the production of SARS-CoV-2 virions.

Quantum neural networks could help analysing the output of quantum computers and quantum simulators of growing complexity. Here, the authors use a 7-qubit superconducting quantum processor to show how a quantum convolutional neural network can correctly recognise the phase of a quantum many-body state.

Exploring the molecular mechanisms by which the blood-borne factor osteocalcin promotes cognitive resilience, Rivagorda, Romeo-Guitart et al. identify a primary cilia axis through which osteocalcin promotes autophagy in neurons.

Optimisation of production of recombinant proteins is pharmaceutically important. Here, the authors identify a state of secretion burnout for cells and report a strategy in which induction is dynamically adjusted based on the current cell stress to avoid the appearance of burnt-out cells.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

Chronic myelomonocytic leukaemia is treated with agents that modify DNA methylation but whether they have direct cytotoxic effects is unclear. Here, the authors show that cells from treated patients show marked methylation changes without altered somatic mutation burden, suggesting that cytotoxicity is not a major factor in therapeutic efficacy.

The first crystal structure of human TMPRSS2, a proteolytic driver of SARS-CoV-2 infection in airways and an antiviral target, reveals structural features of viral spike protein and protease inhibitor binding.

Principal component analysis is often used in studies of ancient DNA, but does not account for the age of the samples. Here, the authors present a factor analysis (FA) which corrects for this by including the effect of allele frequency drift over time.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A population of macrophages with exclusive molecular and functional signatures in the muscle spindles express machinery for synthesizing and releasing glutamate, and a cellular component, the muscle spindle macrophages, directly regulates neural activity and muscle contraction.

SlyB, a lipoprotein in the PhoPQ stress regulon in Gram-negative bacteria, forms stable stress-induced complexes with the outer membrane proteome.

The function and position of organelles are pivotal for tumor cell dissemination. Here the authors use melanoma patient samples and animal models to show that peripheral localization of lysosomes promotes metastasis by favoring lysosome exocytosis and cell invasion.

Disruptions in epidermal growth factor receptor (EGFR) trafficking has been linked to tumor progression. Here the authors show that sortilin limits cell proliferation and tumor growth by promoting EGFR internalization.

Single domain antibodies block tau entry into neurons, a key step in tau propagation in the brain in Alzheimer’s disease. They prevent tau from binding to surface receptors by competition. The most effective, VHH H3-2, has a unique binding mode to tau.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

Many organs and cells have complex tree-like morphologies, but how these patterns emerge during development from global guidance cues and local self-organization remains unclear. Here, the authors develop a theory for the influence of both factors and test it on neuronal branching data.

How daylight saving time shift (DST) affects mortality dynamics on a large population scale remains unknown. Here, the authors examine the impact of DST on all-cause mortality in 16 European countries for the period 1998-2012.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Axonal swellings have been found on Purkinje cell axons in the cerebellum both during development and disease. The authors show that axons with swellings propagate action potentials with higher fidelity than those without and that mice with more axonal swellings learn cerebellar-related tasks better.

The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.

What is the origin of the methane detected in Enceladus’s plumes? A Bayesian approach to the problem shows that abiotic serpentinization of rocks cannot explain the methane abundance by itself, and biotic methane production gets the highest likelihood—provided the probability of life emerging at Enceladus is high.

Cyclophilins play a key role in the life cycle of many viruses and represent important drug targets for broad-spectrum antiviral therapies. Here, the authors use fragment-based drug discovery to develop non-peptidic inhibitors of human cyclophilins with high activity against replication of a number of viral families.

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

CLYBL has a role beyond itaconate catabolism to degrade malyl-CoA, a noncanonical metabolite and methylmalonyl-CoA mutase inhibitor that depletes coenzyme B₁₂, implying that malyl-CoA contributes to the B₁₂ deficiency observed in individuals with CLYBL loss of function.

Hybridizations between different wild species and subspecies within Musa genus lead to the origin of current banana cultivars with different ploidy level and constitution. Here, the authors assemble seven genomes from different ancestral genetic groups and show the speciation process is accompanied by chromosome rearrangements.

Cryo-EM structure of the human PAC1R receptor bound to its neuropeptide ligand PACAP and to an engineered G_s complex reveals the mode of PACAP recognition and suggests functional diversity of the extracellular domains in class B GPCRs.

Graphene oxide is a promising material for molecular separation technologies. Here, the authors propose a realistic staggered stacking structure that plays a crucial role in H/D recognition in water adsorption, as well as high mobilities of water.

Modelling of the evolution of atmospheric methane emissions from the 2022 Nord Stream subsea pipeline leaks shows that the event emitted the largest recorded amount of methane from a single transient event.

The RNA-binding protein SRSF7 autoregulates its protein levels through an intricate negative feedback mechanism that involves translation of two distinct protein halves, termed Split-ORFs; the potential to encode Split-ORFs is also seen in other targets of nonsense-mediated decay.

Structures of human 5-HT_2AR in complex with several drugs reveal a side-extended cavity that is unique for this receptor, while molecular docking suggests that a highly 5-HT_2AR-selective antagonist binds residues within this cavity.

Exposing cerebral organoids and post-mortem brain explants to SARS-CoV-2 virus particles alters expression of synaptic proteins and potentially affects synaptic function by blocking LPHN3 and FLRT3 synapses.

Structural and biochemical analysis of propionyl-CoA synthase reveals that it forms a reaction chamber containing three active sites, which sequesters the reactive intermediate acrylyl-CoA during the conversion of 3-hydroxypropionate to propionyl-CoA.

Wildlife hunting can support diets and socio-economic well-being in communities around the world, but overexploitation can have cascading ecosystem effects. This study examines socio-cultural, economic and landscape factors associated with wildlife hunting in tropical forests in Africa.

Porous framework material DUT-49 was recently demonstrated to exhibit a unique counterintuitive negative gas adsorption (NGA) behaviour. Here the authors identify framework DUT-50 as an additional pressure amplifying material that features distinct NGA transitions, and suggest structural design criteria to access other such materials.

Single-stranded DNA viruses are almost ubiquitous and highly diverse. Here, the authors focus on small DNA viruses possessing chimeric genomes with RNA virus-like capsids, disentangling their complex evolutionary history, which challenges the current borders between major groups of eukaryotic ssDNA viruses.

This study shows that a multitrophic community model jointly recapitulates diel rhythms in abundances of Prochlorococcus picocyanobacteria, as well as viral infection, viral abundances and grazer abundances. Model-data integration implies that grazing predominantly controls Prochlorococcus abundances in surface waters of the North Pacific Subtropical Gyre, despite high viral densities.

Here the authors report 20 novel genomic risk loci for calcific aortic valve stenosis, the most common heart valve disorder. Using RNA sequencing in 500 human aortic valves, they prioritize candidate causal genes including TWIST1, a gene involved in endothelial-mesenchymal transition.

Hsc70 disassembles the coats of clathrin-coated vesicles, remodels a number of other protein complexes, and facilitates protein folding. The dynamics of clathrin uncoating promoted by Hsc70 have now been monitored with single-particle fluorescence imaging. The results suggest that disassembly is driven by trapping of small conformational fluctuations.

Interpenetration of metal–organic frameworks (MOFs) is a common phenomenon, in which a structure consists of two or more identical, entangled sub-lattices. Now, MOFs with variable, fractional degrees of occupancy of one of two sub-lattices have been prepared. The extent of interpenetration can be controlled either during synthesis or by autocatenation, a framework rearrangement process.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.