| | Cancer: Organ-seeking vesicles
An analysis reveals that cancer cells remotely prepare distant sites for tumour spread in an organ-specific manner, by deploying organ-seeking extracellular vesicles.
| Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development
Salamanders are the only tetrapod that can fully regenerate their limbs and tail, a capacity that might be linked to their unique preaxial mode of limb development; here, data from fossils reveal the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods, suggesting that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes.
| Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals
Fungal pathogens reorient hyphal growth towards their plant hosts in response to chemical signals; here, directed growth of the plant pathogen Fusarium oxysporum towards the roots of the tomato plant is shown to be triggered by class III peroxidases secreted by the tomato plant, with the fungal response requiring a sex pheromone receptor.
| Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy
Treating ovarian cancer in mouse models with inhibitors for the epigenetic regulators EZH2 and DNMT1 increases the expression of the inflammatory chemokines CXCL9 and CXCL10, resulting in enhanced tumour infiltration by effector T cells, and slowed tumour progression.
| Crystal structure of the RNA-dependent RNA polymerase from influenza C virus
The X-ray crystal structure of influenza C virus polymerase, captured in a closed, pre-activation confirmation, is solved at 3.9 Å resolution; comparison with previous RNA-bound structures reveals large conformational changes associated with RNA binding and activation, and illustrates the notable flexibility of the influenza virus RNA polymerase.
| Autophagy mediates degradation of nuclear lamina
In response to cancer-associated stress, autophagy machinery mediates degradation of nuclear lamina components in mammals, suggesting that cells might degrade nuclear components to prevent tumorigenesis.
| Methane storage in flexible metal–organic frameworks with intrinsic thermal management
Two flexible metal-organic frameworks are presented as solid adsorbents for methane that undergo reversible phase transitions at specific methane pressures, enabling greater storage capacities of usable methane than have been achieved previously, while also providing internal heat management of the system.
| In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus
This study visualizes the interior of a dsRNA virus using cryo-electron microscopy, revealing the organization of the genome of cytoplasmic polyhedrosis virus together with its transcriptional enzyme complex in both quiescent and transcribing states.
| Corrigendum: A basal ichthyosauriform with a short snout from the Lower Triassic of China
| | | Brief Communications Arising | | | | Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
CRISPR-Cas9 genome-editing screens identify gasdermin D as a substrate for inflammatory caspases, and its N-terminal cleavage fragment, as well as the equivalent regions in other gasdermins, is shown to be capable of inducing pyroptosis.
Jianjin Shi, Yue Zhao, Kun Wang et al. | Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Gasdermin D is identified as the required substrate for pyroptosis, mediating caspase-11 function in the non-canonical inflammasome pathway; the cleaved N-terminal domain is shown to trigger pyroptosis.
Nobuhiko Kayagaki, Irma B. Stowe, Bettina L. Lee et al. | Projections from neocortex mediate top-down control of memory retrieval
Here, a sparse neuronal projection from a part of the prefrontal cortex, the anterior cingulate, to the hippocampus is identified that, when activated, can elicit memory retrieval in mice.
Priyamvada Rajasethupathy, Sethuraman Sankaran, James H. Marshel et al. | Selective small-molecule inhibition of an RNA structural element
A novel drug, ribocil, is shown to mimic the binding of a natural ligand to a bacterial riboflavin riboswitch (a non-coding stretch of messenger RNA whose structure is affected by a ligand—usually one related to the function of the protein encoded by the messenger RNA) to cause inhibition of bacterial growth; the ability to target an RNA structural element with a synthetic small molecule may expand our view of the target space susceptible to therapeutic intervention.
John A. Howe, Hao Wang, Thierry O. Fischmann et al. | | Telomerase activation by genomic rearrangements in high-risk neuroblastoma
Activation of telomere maintenance mechanisms—caused by novel somatic rearrangements of TERT, by MYCN amplification, or ATRX mutations—is a hallmark of high-risk neuroblastomas.
Martin Peifer, Falk Hertwig, Frederik Roels et al. | Thalamic control of sensory selection in divided attention
The authors trained mice to attend to or suppress vision based on behavioral context and show, through novel and established techniques, that changes in visual gain rely on tunable feedforward inhibition of visual thalamus via innervating thalamic reticular neurons; these findings introduce a subcortical model of attention in which modality-specific thalamic reticular subnetworks mediate top-down and context-dependent control of sensory selection.
Ralf D. Wimmer, L. Ian Schmitt, Thomas J. Davidson et al. | The earliest unequivocally modern humans in southern China
A collection of 47 unequivocally modern human teeth from a cave in southern China shows that modern humans were in the region at least 80,000 years ago, and possibly as long as 120,000 years ago, which is twice as long as the earliest known modern humans in Europe; the population exhibited more derived features than contemporaneous hominins in northern and central China, adding to the complexity of the human story.
Wu Liu, María Martinón-Torres, Yan-jun Cai et al. | Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer
Acetyl-CoA carboxylases (ACCs) are large, multi-domain enzymes with crucial functions in fatty acid metabolism and are potential drug targets; here the X-ray crystal structure of the full-length, 500-kDa holoenzyme dimer of the ACC from Saccharomyces cerevisiae is solved and reveals an organization quite different from that of other biotin-dependent carboxylases.
Jia Wei, Liang Tong | Organometallic palladium reagents for cysteine bioconjugation
Palladium(ii) complexes can be used in efficient and highly selective cysteine conjugation reactions that are rapid and robust, and the resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles.
Ekaterina V. Vinogradova, Chi Zhang, Alexander M. Spokoyny et al. | Decadal slowdown of a land-terminating sector of the Greenland Ice Sheet despite warming
Whether or not an increase in meltwater will make ice sheets move more quickly has been contentious, because water lubricates the ice–rock interface and speeds up the ice, but also stimulates the development of efficient drainage; now, a long-term and large-area study of a land-terminating margin of the Greenland Ice Sheet finds that more meltwater does not equal higher velocity.
Andrew J. Tedstone, Peter W. Nienow, Noel Gourmelen et al. | Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract
The authors develop a mouse model of Enterococcus faecalis colonization to show that enterococci harbouring the bacteriocin-expressing plasmid pPD1 replace indigenous enterococci and have the ability to transfer the plasmid to other enterococci, which enhances the stability of the bacteriocin-expressing bacteria in the gut; this result suggests a therapeutic approach that leverages niche-specificity to eliminate antibiotic-resistant bacteria from infected individuals.
Sushma Kommineni, Daniel J. Bretl, Vy Lam et al. | Abundant molecular oxygen in the coma of comet 67P/Churyumov–Gerasimenko
In situ measurement of O2 in the coma of comet 67P/Churyumov–Gerasimenko shows local abundances ranging from one per cent to ten per cent relative to H2O; the spatial and temporal uniformity of the O2/H2O ratio suggests that primordial O2 was incorporated into the nucleus during the comet's formation.
A. Bieler, K. Altwegg, H. Balsiger et al. | Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer
This study finds that the Hippo pathway is essential for gut epithelial regeneration and tumour initiation; the Hippo component Yap holds off differentiation of intestinal stem cells to Paneth cells to promote a survival and self-renewal regenerative program through activation of the Egfr pathway.
Alex Gregorieff, Yu Liu, Mohammad R. Inanlou et al. | CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase
Charcot–Marie–Tooth diseases are hereditary peripheral neuropathies for which there are currently no effective therapies; here the type 2D subtype of these diseases is shown to be caused by mutations impeding a signalling pathway necessary for motor neuron survival.
Weiwei He, Ge Bai, Huihao Zhou et al. | Loophole-free Bell inequality violation using electron spins separated by 1.3 kilometres
A Bell experiment that is 'loophole' free—leaving no room for explanations based on experimental imperfections—reveals a statistically significant conflict with local realism
B. Hensen, H. Bernien, A. E. Dréau et al. | | | | |
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