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α-synuclein aggregates cause neuronal damage, but their heterogeneity complicates studying their toxic properties. Here, the authors analyze α-synuclein aggregates in vitro and study post-mortem brain samples, providing evidence that small aggregates are the main culprit for neuronal death in Parkinson’s disease.

Sperm motility and male fertility requires function of the CatSper calcium channels. Here, using cryo-electron tomography, authors visualize the native in-cell 3D structure and higher-order organization of the CatSper as long zigzag rows along the sperm tail.

Using cryo-EM, Chung et al. investigate conformational states of mammalian respiratory complex I to reveal an ubiquinone-10 molecule occupying the full length of the Q-binding channel. Molecular dynamics simulations suggest how the charge states of key residues influence the substrate binding pose.

Recurrent absence seizures aberrantly increase activity-regulated myelination within the seizure network; this maladaptive myelination, in turn, increases network hypersynchrony and seizure burden over time.

In vivo, in vitro and in silico validation of the direct inhibition of Tyrosinase activity by the ML233 small molecule reveal a therapeutic candidate for skin disorders.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

7,8-dihydro-8-oxoguanine and 7,8-dihydro-8-oxoadenine (oxoA) are generated upon oxidative damage to DNA, but the biological effects of oxoA are not well known. Here, the authors report that only oxoA forms DNA interstrand crosslinks (ICLs) upon secondary oxidation and that these ICLs can be induced by reactive halogen species, one-electron oxidants and the myeloperoxidase/H₂O₂/Cl^- system.

SLC25A51 is identified as a transporter of intact NAD⁺ into mammalian mitochondria and is required to maintain the mitochondrial NAD⁺ pool and respiratory function.

Ultraviolet radiation (UVR) increases melanoma incidence. Here, the authors report that UVR-damaged dermal fibroblasts upregulate MMP1 to degrade collagen which inhibits melanoma invasion and that aged primary melanomas in skin with degraded collagen have a better prognosis, while new collagen synthesis restores invasion and leads to death.

Gene expression covariation can be studied by single-cell RNA sequencing. Here the authors analyze intrinsically covarying gene pairs by eliminating the confounding effects in single-cell experiments and observe covariation of proximal genes and miRNA-induced covariation of target mRNAs.

Increased perivascular fibroblast activity and vascular remodeling occurs early in ALS pathogenesis and can predict patient survival time

Zhou et al. unveil a novel role for activated microglia and macrophages during wound healing after CNS injury. Microglia promote corralling and form a protective barrier at the injury penumbra via the axon guidance receptor Plexin-B2.

Levels of the glycolytic intermediate metabolite dihydroxyacetone phosphate are shown to signal cellular glucose availability to the mTORC1 complex through an AMPK-independent route.

A chemoproteomics and protein engineering strategy to investigate metabolic activity of lipid kinases led to assignment of a key role for atypical C1 domains in directing fatty acyl specificity of diacylglycerol kinase function in live cells.

Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness.

The onset of deep water export from the North Atlantic Ocean preceded the onset of Antarctic glaciation by about one million years, according to sediment geochemistry, and may have been triggered by tectonic changes in the Atlantic basin.

In a technological tour de force, a whole-body 11.7-T MRI scanner has been developed. Here images of the human brain are presented while safety for the imaged human volunteers has been ascertained.

This Resource defines fungal diversity of Populus trees and associations with climate variables on a continental scale.

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

The function of memory CD8⁺ T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8⁺T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.

Holes in endothelial barriers, called transendothelial cell macroapertures (TEMs), are predicted to be limited by line tension of unknown origin. Here the authors identify an actomyosin cable encircling TEMs and establish a role for ezrin in stabilising F-actin bundles, allowing their crosslinking by non-muscle myosin IIa.

Globins are best known for their role in respiration, but recent studies suggest they might contribute to redox signalling as well. Here, the authors present biochemical, structural and in vivoevidence that the roundworm globin Glb-12 acts as a superoxide generator necessary for germline development.

The heart forms from combining the first with the second heart field, which in mammals creates left and right ventricle. Here transgenic zebrafish and physiology studies reveal that transcription factors controlling septation in mammals already in teleosts guide muscle coupling by controlling the relative contribution of the two fields to the heart.

Cerebellar outputs contribute to motor as well as cognitive behaviors. Here, the authors elucidate the connectivity between deep cerebellar nuclei and specific cell types in the striatum via the intralaminar thalamic nucleus and the participation of this circuit in striatum-dependent behavior.

A saposin protein–lipid nanoparticle system stabilizes diverse, fragile membrane proteins in a lipid environment for structural and functional studies.

Impaired somatostatin secretion owing to loss of β- to δ-cell electrical coupling underlies defective counter-regulatory glucagon secretion in type-1 diabetes.

Dystrophin is expressed in muscle stem cells, in which it regulates their cell division and proper repopulation.

Fecher et al. devise an approach to isolate cell-type-specific mitochondria from the mouse CNS. They demonstrate proteomic diversity of cerebellar mitochondria covering bioenergetics, calcium handling and organelle contact sites.

Peripheral inflammatory macrophages are found to modulate daytime locomotion of zebrafish via recruiting neutrophils into the brain.

Some peptoids—synthetic structural relatives of polypeptides—can assemble into two-dimensional nanometre-scale sheets; simulations and experimental measurements show that these nanosheets contain a motif unique to peptoids, namely zigzag Σ-strands, which interlock and enable the nanosheets to extend in two dimensions only.

Vector-transmission of Leishmania donovani in malnourished mice produces distinct clinical symptoms in chronic visceral leishmaniasis, enhances parasite burden and dissemination, and disrupts gut microbiota.

Covalent confinement drives symmetry breaking in macromolecular arrangements, giving rise to layered low-symmetry self-assemblies of mesh networks in the sub-10-nm scale.

In this study, the authors reveal distinct developmental programs underlying innate and learned olfactory behaviors by demonstrating that chemogenetic inactivation of neurons generated in neonatal mice impairs the behavioral response to aversive odorants, whereas inactivation of adult-born neurons impairs learning of novel food-related odors.

The My Baby Biome Study demonstrates that three gut microbiome community clusters exist in infants in the United States. These compositions vary on the prevalence and abundance of Bifidobacterium and impact risk for the development of atopic disease.

The authors describe a method for generating functional neural spheroids and assembloids for disease modeling and drug discovery by cell aggregation of differentiated human iPSC derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.

Keklikoglou et al. report that cytotoxic drugs induce tumour-derived extracellular vesicles that facilitate monocyte expansion through annexin A6 and thus lung metastasis in breast cancer.

Quasi-Love wave scattering is used to identify gradients in seismic anisotropy in the mantle beneath Australia that may represent major lithospheric boundaries between geological provinces and modified mantle flow along the ocean-continent transition.

During vertebrate embryogenesis, the pharyngeal arch arteries (PAA) connect segments of the primitive circulation. Burns and colleagues show that Nkx2.5⁺ heart precursors from the lateral plate mesoderm surprisingly give rise to the PAA angioblasts, and that Nkx2.5 is required for PAA development.

ESRP1, ESRP2 and CTNND1 operate in the periderm to regulate craniofacial morphogenesis. Using complementary in vivo and in vitro models, we tested the function of human ESRP1/2 gene variants and CTNND1 isoforms