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Using cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles, a V-ATPase–synaptophysin interface was found to regulate synaptic vesicle biogenesis and alter seizure susceptibility.

Recent studies unexpectedly indicate involvement of ventral tegmental area dopamine neurons in Alzheimer’s disease (AD). Here, the authors identified the enzyme casein kinase 2 as a mechanistic link between abnormal firing activity and AD pathology.

Researchers used a fracture mechanics approach with on-chip nanomechanical testing and a large number of samples to establish a definitive fracture toughness of graphene of 4.4 MPa m^1/2, with fracture controlled by unavoidable 1.4 nm-size defects.

Cryo-electron microscopy structures of the mouse class M immunoglobulin B cell receptor complex provide insight into B cell receptor subunit assembly, domain architecture and signalling mechanism.

Autophagy in CD11c⁺ phagocytes prevents myeloid-derived suppressor cell recruitment and promotes protective T cell responses during high-dose Mycobacterium tuberculosis infection in mice.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Regions of the subducting oceanic crust are often considered to be overpressured, owing to fluid trapped beneath an impermeable seal along the overlying inter-plate boundary. Here, the authors show that slow slip earthquakes at the Cascadia subduction zone occur immediately below a 6-10 km-thick shear zone, in which slab-derived fluids are likely trapped at near-lithostatic pore pressures.

Promoter-proximal pausing by RNA Pol II is a key aspect of how gene expression is transcriptionally regulated in higher eukaryotes. Here the authors show that only NELF-mediated pausing enforces a strict early checkpoint for Cdk9 by efficiently shutting down gene transcription following loss of Cdk9.

Adaptation transcends scale in both natural and artificial systems, but the factors driving the cause of this phenomenon are unclear. Herein, the authors describe the molecular requirements for adaptation and establish a link to rationalize adaptive behavior on a self-assembled level.

Using light-sheet microscopy to image tissue flows, Weijer and colleagues demonstrate that myosin-II-driven changes in cell shape and cell intercalation contribute to primitive streak formation in chick embryos.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.

Davidson et al. visualize ferroptosis-like cell death using three-colour live imaging in vivo and demonstrate its role in triggering macrophage recruitment but delaying resolution of inflammation during wounding in the Drosophila embryo.

Organs develop unique vascular architectures to support physiological functions. Here, authors show that organo-typical vascular networks may arise from specific parenchymal cues activating unique endothelial subtypes and angiogenic sprouting processes.

Optoacoustic super-resolution at millimeter-scale depths has been impeded by the strong background absorption from blood cells. Here, the authors use dichloromethane microdroplets with high optical absorption and demonstrate 3D microangiography of the mouse brain via optoacoustic localization.

North Pacific dust flux and modelling results provide new evidence for long-term land-atmosphere-ocean interactions associated with the onset and intensification of the Northern Hemisphere Glaciation.

Neural activity is recorded at the cellular level, throughout the brain of larval zebrafish, while the animals interact with a virtual environment and adapt their motor output to changes in visual feedback; this is used to derive candidates of functional elements driving motor learning.

Understanding the microscopic variability of CMOS spin qubits is crucial for developing scalable quantum processors. Here the authors report a combined experimental and numerical study of the effect of interface roughness on variability of quantum dot spin qubits formed at the Si/SiO₂ interface.

The Musashi family of RNA binding proteins are found in an oligomeric state in the brains of patients with Alzheimer’s disease. Here the authors show that Mushashi1 and Musashi2 interact with tau protein in patient tissue and in models of tauopathy.

Molecules arranged in close proximity to a surface form molecular layers, exhibiting distinct properties. However, the creation of these layers is challenging. Here, the authors present a technique for generating molecular layers through crystallization induced by gas blowing onto a surface.

Βeta-cells have recently been shown to be heterogeneous with regard to morphology and function. Here, the authors show that β-cells in zebrafish switch from proliferative to functional states with increasing time since β-cell birth, leading to functional and proliferative heterogeneity.

As part of the first anniversary issue of Nature Chemical Engineering, we present a collection of opinions from 40 researchers within the field on what they think are the most exciting opportunities that lie ahead for their respective topics.

MAP1B is bound and regulated by fragile X protein FMRP. Here, the authors show that elevated levels of MAP1B reduce the morphological and physiological maturation of human neurons and impair social behavior in mice.

AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

Abnormal CSF accumulation in the brain can lead to hydrocephalus. The mechanisms regulating CSF clearance during early development are unclear. Here, the authors show that NKCC1 regulates the clearance of both CSF K⁺ and fluid volume through the choroid plexus during postnatal development in mice.

Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

Lysosomal integral membrane protein-2 (LIMP-2) is a glucocerebrosidase receptor, which is linked to kidney failure and other diseases. Here the authors show that LIMP-2 is also a phospholipid receptor and present the lipid-bound structure of the LIMP-2 luminal domain dimer and discuss its lipid trafficking mechanism.

The authors map thalamic synapses onto layer 2/3 mouse visual cortex neurons, showing they are sparse, small and heterogeneously distributed. Modeling these data suggests that a few neurons could together reliably decode thalamic visual input.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

Quantitative live-cell imaging provides a dynamic protein atlas of mitosis.

Here, the authors show the amyloid formation of a low-complexity domain of NCAP, and its potential for guiding the design of antiviral agents.

Dynamic windows can reduce a building’s energy demand, yet the control of light and heat transmission remains challenging. Strand et al. show that polymer inhibitors improve the morphology of metal films allowing a wide modulation of light and heat flow in windows based on reversible metal electrodeposition.

Temporal lobe epilepsy (TLE) can be unresponsive to treatment. Here, the authors show that treatment with D-Serine mitigates TLE and acts on neurons and glia, attenuating neuronal loss and reducing astro- and microgliosis in rodents.

Infection with SARS-CoV-2 has been linked with substantive inflammation, lung pathology and development of COVID-19. Here the authors spatially associate CCL18 and CCL21 in distinct tissue niches with lung pathology of severe COVID-19.

Intense extreme UV and X-ray coherent sources are set to revolutionize numerous research areas, yet characterization of their polarization remains elusive. Here, Mazza et al.measure the polarization state of circularly polarized extreme UV light from a free-electron laser using circular dichroism.

Gene editing strategies are typically designed to correct mutant genes, but most neurodegenerative diseases are sporadic. Here the authors describe a strategy to selectively edit the C-terminus of APP and attenuate amyloid-β production, while upregulating neuroprotective α-cleavage.

Bone marrow endothelial cells have dual roles in the regulation of haematopoietic stem cell maintenance and in the trafficking of blood cells between the bone marrow and the blood circulatory system; this study shows that these different functions are regulated by distinct types of endothelial blood vessels with different permeability properties, affecting the metabolic state of their neighbouring stem cells.

A hierarchical model of melanoma tumour growth mirrors the cellular and molecular logic of cell-fate specification and differentiation of the underlying embryonic neural crest, and suggests that the ability to support growth and metastasis are limited to distinct pools of cells.

Comparing spatial omics data across samples remains elusive. Here, the authors develop a quantitative spatial framework, termed as colocatome analysis, by combining pairwise cell-cell colocalization, spatial permutation and normalization approaches for comparing features across conditions and studies.

The mitochondrial symbiont, Candidatus Midichloria mitochondrii, exists in the hard tick Ixodus ricinus, the main vector for Lyme disease. Here, the authors use FIB-SEM to characterise mitochondrial morphology and bacterial interactions in the context of oocyte maturation and endosymbiosis.

A recurrent, transformer-based neural network, called AlphaQubit, learns high-accuracy error decoding to suppress the errors that occur in quantum systems, opening the prospect of using neural-network decoders for real quantum hardware.

Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

The role of astrocyte NMDA receptor signaling in cortical circuits is unclear. Here, the authors show that NMDA receptors contribute to astrocyte calcium events and support neuronal processing of sensory information that maintains sensory activity in mice.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.