| Structural biology: Signalling under the microscope G-protein-coupled receptors are biological targets for drug discovery. Developments in cryo-electron microscopy have enabled the solution of the structure of a class B receptor in complex with its signalling protein. Two biologists and a microscopist explain the exciting implications of this work. | Structural Biology: An ion-transport enzyme that rocks Previous crystal structures of membrane-spanning enzymes called ATPases have revealed that the enzymes undergo complex movements. The movements, it now emerges, involve rocking in place in the membrane. | Whole-genome landscapes of major melanoma subtypes The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites. | Maintenance of persistent activity in a frontal thalamocortical loop Thalamic neurons show selective persistent activity that predicts movement direction, and their photoinhibition decreases activity in the anterior lateral motor cortex, and vice versa, suggesting that persistent activity requires reciprocal excitation in a thalamocortical loop. | Protein–phospholipid interplay revealed with crystals of a calcium pump Solvent contrast modulation reveals how the lipid bilayer actively participates in the conformational switches of Ca2+-ATPase through the actions of tryptophan, arginine and lysine residues, which function as membrane floats and anchors. | Experimental evidence that thrust earthquake ruptures might open faults Earthquake rupture experiments and mathematical modelling reveal the existence of a torquing mechanism of thrust fault ruptures near the free surface that causes them to dynamically unclamp, open and slip large distances. | The concurrent emergence and causes of double volcanic hotspot tracks on the Pacific plate The emergence of geographically and geochemically distinct double volcanic chains on the Pacific plate coincides with a recent azimuthal change in the motion of the plate. | Thalamic amplification of cortical connectivity sustains attentional control The mediodorsal nucleus of the thalamus amplifies the functional connectivity of the prefrontal cortex, thereby sustaining cortical representations of rule sets without relaying categorical information. | Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling The authors describe water-soluble surrogate Wnt agonists, with specificity towards some frizzled (FZD) receptors, which can maintain human intestinal organoid cultures and have effects on the mouse liver in vivo. | Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal R-spondin and Wnt ligand families act non-redundantly and cooperatively within the same molecular pathway in the intestinal stem-cell niche to maintain stem-cell competency and drive stem-cell expansion. | FGF-dependent metabolic control of vascular development Fibroblast growth factor receptor (FGFR) signalling is a crucial regulator of endothelial metabolism and vascular development. | Core Mediator structure at 3.4 Å extends model of transcription initiation complex The 3.4 Å crystal structure of the 15-subunit core Mediator complex in yeast. | Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells The molecular mechanism of Goodpasture disease is modelled to mechanistically determine how a human leukocyte antigen (HLA) allele can exert its dominant protective effect in autoimmune disease. | Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein | Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin | Corrigendum: An intermediate-mass black hole in the centre of the globular cluster 47 Tucanae | | | | npj 2D Materials and Applications is an online-only, open access journal that aims to become a top-tier interdisciplinary platform for scientists to share research on 2D materials and their applications. Part of the Nature Partner Journals series, npj 2D Materials and Applications is published in partnership with FCT NOVA, Lisbon, with the support of the European Materials Research Society (E-MRS). The journal is now open for submissions. Find out more >> | | | | | | | | | | | Cell diversity and network dynamics in photosensitive human brain organoids Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light. Giorgia Quadrato, Tuan Nguyen, Evan Z. Macosko et al. | Assembly of functionally integrated human forebrain spheroids Human pluripotent stem cells were used to develop dorsal and ventral forebrain 3D spheroids, which can be assembled to study interneuron migration and to derive a functionally integrated forebrain system with cortical interneurons and glutamatergic neurons. Fikri Birey, Jimena Andersen, Christopher D. Makinson et al. | T-cell invigoration to tumour burden ratio associated with anti-PD-1 response The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient. Alexander C. Huang, Michael A. Postow, Robert J. Orlowski et al. | Visualizing multistep elevator-like transitions of a nucleoside transporter Multiple crystallographic structures of a concentrative nucleoside transporter show how it uses an ‘elevator’ mechanism to move its transport domain across the membrane. Marscha Hirschi, Zachary Lee Johnson, Seok-Yong Lee | | Observation of the frozen charge of a Kondo resonance In a quantum dot in the Kondo regime, electrical charges are effectively frozen, but the quantum dot remains electrically conducting owing to strong electron–electron correlations. M. M. Desjardins, J. J. Viennot, M. C. Dartiailh et al. | Observed quantization of anyonic heat flow Quasiparticles in strongly interacting fractional quantum Hall systems carry heat according to the same quantization of thermal conductance as for particles in non-interacting systems. Mitali Banerjee, Moty Heiblum, Amir Rosenblatt et al. | Dual-phase nanostructuring as a route to high-strength magnesium alloys Combining the benefits of nanocrystals with those of amorphous metallic glasses leads to a dual-phase material—comprising sub-10-nanometre-sized nanocrystalline grains embedded in amorphous glassy shells—that exhibits a strength approaching the ideal theoretical limit. Ge Wu, Ka-Cheung Chan, Linli Zhu et al. | Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide A nickel catalyst that promotes carboxylation of halogenated hydrocarbons at remote aliphatic sites with carbon dioxide via tunable and controllable chain-walking is described. Francisco Juliá-Hernández, Toni Moragas, Josep Cornella et al. | Burgess Shale fossils illustrate the origin of the mandibulate body plan Tokummia katalepsis from the Burgess Shale had a pair of mandibles and maxilliped claws, showing that large bivalved arthropods from the Cambrian period are forerunners of myriapods and pancrustaceans, thereby providing a basis for the origin of the hyperdiverse mandibulate body plan. Cédric Aria, Jean-Bernard Caron | The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability Conditional deletion of the mitochondrial Na+/Ca2+ exchanger NCLX in adult mouse hearts causes sudden death due to mitochondrial calcium overload, whereas its overexpression limits cell death elicited by ischaemia reperfusion injury and heart failure. Timothy S. Luongo, Jonathan P. Lambert, Polina Gross et al. | Tumour ischaemia by interferon-γ resembles physiological blood vessel regression Interferon-γ acts on tumour endothelial cells to drive vascular regression, inducing ischaemia that leads to tumour collapse. Thomas Kammertoens, Christian Friese, Ainhoa Arina et al. | Transmission of cytokinesis forces via E-cadherin dilution and actomyosin flows Under physiological forces, resulting from cytokinesis, the mechanosensitivity of adherens junction arises from a local decrease in E-cadherin concentration and results in actomyosin flows. Diana Pinheiro, Edouard Hannezo, Sophie Herszterg et al. | Polyglutamine tracts regulate beclin 1-dependent autophagy The polyglutamine domain in ataxin 3, which is expanded in spinocerebellar ataxia type 3, allows normal ataxin 3 to interact with and deubiquitinate beclin 1 and thereby to promote autophagy. Avraham Ashkenazi, Carla F. Bento, Thomas Ricketts et al. | Structural insight into allosteric modulation of protease-activated receptor 2 Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design. Robert K. Y. Cheng, Cédric Fiez-Vandal, Oliver Schlenker et al. | | | | |
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