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Here the authors report two structures of human PTH1R-Gs complex bound to ligands PTH and ABL, providing insight into the molecular mechanism of ligand duration.
Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumours. Here, the authors use single-nuclei and bulk-tissue RNA-seq to characterise PCPG tumours and their microenvironments and reveal molecular subtypes as well as expression patterns associated with metastasis.
Memory augmented neural network for lifelong on-device learning is bottlenecked by limited bandwidth in conventional hardware. Here, the authors demonstrate its efficient in-memristor realization with a close-software accuracy, supported by hashing and similarity search in crossbars.
Squalene-hopene cyclase are membrane-bound enzymes used to produce bioactive compounds at industrial scale. Here, the authors show squalene-hopene cyclase spheroplasts, obtained by removing the outer cell membrane, having a higher catalytic activity than the enzymes and the whole cells, and their cross-linking for recycling and reuse.
Here, the authors integrate measured fabrication constraints in topology optimization to design a highly optimized dielectric nanocavity. The theoretically predicted confinement of light below the diffraction limit is confirmed by near- and far-field spectroscopy.
Out of equilibrium operation of chemical reaction networks. (CRNs) enables materials to autonomously respond to their environment by activation and deactivation of intermolecular interactions but the deactivation to noninteracting building blocks remains understudied. Here, the authors develop a new, modular CRN that enables control over the deactivation kinetics.
The functions of specific lipids in autophagosome biogenesis are not entirely clear. Here, the authors show that the ER protein GRAMD1C, a cholesterol transport protein, suppresses autophagy initiation and has roles in mitochondrial cholesterol homeostasis and respiration.
The effect of geometrical confinement on the locomotion of microrobots is crucial to operating them in real-world applications. Bozuyuk et al. show that the locomotion efficiency of microrollers decreases in confined spaces at high rotation frequencies and propose a slender geometry to overcome this problem.
Altered expression of splicing factors can contribute to tumour progression. Here the authors show that splicing factor BUD31 enhances ovarian cancer progression by promoting exon inclusion in the anti-apoptotic BCL2 family member, BCL2L12.
Cost-effective methods for long-term storage of DNA are desired. Here the authors present a method for in situ cryosilicification of whole blood cells, allowing long-term and room temperature preservation of genomic information for only approximately $0.5 per sample.
Diabetes is characterized by loss or dysfunction of pancreatic β-cells. Here the authors show that the signalling protein WNT4 is heterogeneously activated by β-cells during their postnatal maturation with WNT4 positive cells being more mature, and that inactivating WNT4 in β-cells after maturation impairs beta-cell function.
A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of ALS and FTD. Here, the authors demonstrate CRISPR/Cas9 excision of the expansion results in a rescue of disease mechanisms in vivo and in vitro.
Microglia survey the parenchyma, which leads to morphology changes over time. Here the authors show using 2 photon imaging of microglia in vivo that sleep modulates microglial morphodynamics through Cx3cr1 signaling.
WbbB is a structurally unusual retaining glycosyltransferase. Here, the authors show that WbbB forms an Asp232-Kdo adduct prior to transfer to the saccharide acceptor. Therefore, unlike any previously studied glycosyltransferase, WbbB uses the double-displacement mechanism first proposed in 1953.
Information about O-glycosylation site regulation and occupancy in the human proteome is limited. Here, the authors identify GalNAc transferase-specific glycan sites in human keratinocytes and describe their occupancy.
DNA methyltransferase 3 A (DNMT3A) is involved in DNA methylation, and genetic variants in the DNMT3 locus have been associated with inflammatory bowel disease. Here the authors report that DNMT3A controls intestinal epithelial barrier function and restoration of the gut barrier function after intestinal epithelial perturbation.
Single cell RNA-sequencing of the AstTau neuron-asteroid tau assembloid model reveals excitatory neuron inflammatory signatures and an astrocytic heat shock response similar to that occurring in the brains of individuals with tauopathies, which can be ameliorated with a neuroprotective HSP90 inhibitor.
Vaccination and infection history determine the breadth of neutralizing antibody response to SARS-CoV-2 variants and other sarbecoviruses with breakthrough or natural infection combined with vaccination or booster vaccination with mRNA vaccine providing highest neutralization.
Crop wild relatives’ genetic diversity is usually not considered in conservation planning. Here, the authors introduce an approach to identify conservation areas based on evolutionary and threat processes, by developing proxies of genetic differentiation, and including taxa’s habitat preferences.
Interfacial ferroelectricity may emerge in moiré superlattices. Here, the authors find that the polarized charge is much larger than the capacity of the moiré miniband and the associated anomalous screening exists outside the band.