Two medical-technology companies illustrate the ups and downs of innovation.
The UK government’s decision to subsidize a nuclear power station while cutting support for renewables is short-sighted.
The problem of abandoned fishing gear and its effects on marine life deserve greater attention.
World Health Organization advisory committee endorses use of the RTS,S vaccine in small-scale demonstrations.
Next-generation machines can penetrate kilometres below surface in days rather than years.
Loss prompts rethink about design of future cradle-to-grave studies.
The plummeting success rates in grant applications in the last decade are linked to flat budgets and more resubmitted proposals.
Astronomers prepare to observe an impact off the coast of Sri Lanka.
US regulators clear a viral melanoma therapy, paving the way for a promising field with a chequered past.
The island nation of Kiribati is one of the world's most vulnerable to rising sea levels. But residents may have to leave well before the ocean claims their homes.
Researchers hope to show that using the gas as a raw material could make an impact on climate change.
News & Views
Inflammatory caspase proteins help to control pathogen replication by triggering pyroptotic cell death. It now emerges that cleavage of the caspase substrate gasdermin D is sufficient to induce pyroptosis. See Articles p.660 & p.666
A clever approach has been used to imprint a phase pattern on a laser beam. The pattern is not only random at each point, but also depends on information stored elsewhere in the pattern.
In plant cells, the pigment anthocyanin is transported to a membrane-bounded organelle called the vacuole for storage. A previously unidentified transport pathway involving vacuolar-membrane extensions mediates this process.
Organometallic reagents have been developed that chemically modify proteins and peptides specifically at cysteine amino-acid residues — potentially offering a general route to making therapeutically useful compounds. See Letter p.687
A discovery in southern China of human teeth dated to more than 80,000 years old indicates that Homo sapiens was present in the region considerably earlier than had previously been suspected. See Letter p.696
A fundamental scientific assumption called local realism conflicts with certain predictions of quantum mechanics. Those predictions have now been verified, with none of the loopholes that have compromised earlier tests. See Letter p.682
A screen for compounds that block a bacterial biosynthetic pathway has uncovered an antibiotic lead that shuts off pathogen growth by targeting a molecular switch in a regulatory RNA structure. See Article p.672
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.
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.
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.
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.
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 Bell experiment that is ‘loophole’ free—leaving no room for explanations based on experimental imperfections—reveals a statistically significant conflict with local realism
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.
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.
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.
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.
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.
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.
The gut epithelium has remarkable self-renewal capacity that under homeostatic conditions is driven by Wnt signalling in Lgr5+ intestinal stem cells (ISCs). However, the mechanisms underlying ISC regeneration after injury remain poorly understood. The Hippo signalling pathway mediates tissue growth and is important for regeneration. Here we demonstrate in mice that Yap, a downstream transcriptional effector of Hippo, is critical for recovery of intestinal epithelium after exposure to ionizing radiation. Yap transiently reprograms Lgr5+ ISCs by suppressing Wnt signalling and excessive Paneth cell differentiation, while promoting cell survival and inducing a regenerative program that includes Egf pathway activation. Accordingly, growth of Yap-deficient organoids is rescued by the Egfr ligand epiregulin, and we find that non-cell-autonomous production of stromal epiregulin may compensate for Yap loss in vivo. Consistent with key roles for regenerative signalling in tumorigenesis, we further demonstrate that Yap inactivation abolishes adenomas in the ApcMin mouse model of colon cancer, and that Yap-driven expansion of Apc−/− organoids requires the Egfr module of the Yap regenerative program. Finally, we show that in vivo Yap is required for progression of early Apc mutant tumour-initiating cells, suppresses their differentiation into Paneth cells, and induces a regenerative program and Egfr signalling. Our studies reveal that upon tissue injury, Yap reprograms Lgr5+ ISCs by inhibiting the Wnt homeostatic program, while inducing a regenerative program that includes activation of Egfr signalling. Moreover, our findings reveal a key role for the Yap regenerative pathway in driving cancer initiation.
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.
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.