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Naked mole rats are remarkable in combining extreme longevity with virtually complete resistance to cancer. Now a novel glycosaminoglycan variant that may have evolved to provide the creatures with the tough, flexible skin needed for a subterranean lifestyle has been identified as a key contributor to their cancer resistance. Hyaluronan, or hyaluronic acid, is a ubiquitous component of the extracellular matrix. Xiao Tian et al. observed that the culture media of naked mole-rat fibroblasts becomes viscous owing to the accumulation of a thick gooey substance and identified it as a high-molecular-mass hyaluronan (HMM-HA), more than five times larger than mouse and human equivalents. It accumulates in naked mole-rat tissues owing to low hyaluronidase activity and a unique form of hyaluronan synthase 2. HMM-HA acts through the CD44 receptor and removal of HMM-HA makes naked mole-rat cells more susceptible to transformation. This unusual model of cancer protection suggests potential new avenues of research into anticancer and life-extension strategies. Cover: Joel Sartore/National Geographic Image Collection/Alamy
Two huge projects have the potential to revolutionize neuroscience, as long as they don’t drain money from other work and are monitored to keep them on target.
The United States and Europe are both planning billion-dollar investments to understand how the brain works. But the technological challenges are vast.
Massive open online courses can make higher education more accessible, immersive and comprehensive — if they are deployed with due caution, says Michael M. Crow.
Giving scientists greater access to conceptual and technical tuition through massive open online courses will aid interdisciplinary research, say Hazel Sive and Sanjay Sarma.
John Whitfield finds resonance with today's behavioural sciences in Niccolò Machiavelli's great Renaissance political treatise, begun five centuries ago this month.
The Andreev bound states are a hallmark of the theory of superconducting weak links. Using the versatile Josephson effect as source, device and detector, these spin-1/2 states have been directly observed. See Letter p.312
Plants are expected to respond to rising levels of atmospheric carbon dioxide by using water more efficiently. Direct evidence of this has been obtained from forests, but the size of the effect will prompt debate. See Letter p.324
How do pathogens survive temperature variations? At a molecular level, one bacterial species seems to regulate gene expression in response to temperature through structural equilibria in corresponding RNA sequences. See Letter p.355
A phenomenon known as CP asymmetry, which explains our very existence, has been observed in the decays of Bs0 mesonic particles. The finding represents yet another triumph of the standard model of particle physics.
Mathematical modelling linked with patient data suggests that combination therapy is more effective than sequential treatment at preventing drug resistance in cancer. This predictive approach may pave the way for personalized therapies.
Analyses of the toxin produced by Salmonella Typhi bacteria reveal an unusual assembly of toxin subunits, and show that most symptoms of typhoid fever can be linked to one subunit's DNA-damaging activity. See Letter p.350
Sensitive protein sensors of calcium have been created; these new tools are shown to report neural activity in cultured neurons, flies and zebrafish and can detect single action potentials and synaptic activation in the mouse visual cortex in vivo.
A muscle-specific membrane protein called myomaker is transiently expressed during myogenesis and is both necessary and sufficient to drive myoblast fusion in vivo and in vitro.
LRG1 is identified as a new regulator of TGF-β signalling that promotes angiogenesis via a TβRII–ALK1–ENG–Smad1/5/8 signalling pathway; antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury.
A fundamental and previously unobserved aspect of the Josephson effect is revealed through spectroscopic measurements of the excited Andreev states in superconducting atomic contacts.
A method of producing perovskite-sensitized solar cells by sequential — as opposed to single-step — deposition of the perovskite’s components onto a nanoporous titanium oxide film allows for greater reproducibility of device performance and a record power conversion efficiency of 15 per cent.
Synchrotron-based nuclear resonance vibrational spectroscopy is used to characterize the reactive Fe(iv)=O intermediate of the halogenase SyrB2; the substrate directs the orientation of this intermediate, presenting specific frontier molecular orbitals that can activate the selective halogenation.
Present-day forests use water more efficiently, probably owing to the effect of increased atmospheric carbon dioxide on leaf stomata, which partially close to maintain a near-constant level of carbon dioxide inside the leaves despite increasing atmospheric levels.
Newly determined ratios and abundances of sulphur, selenium and tellurium in mantle peridotites are consistent with the view that a ‘late veneer’ of slightly volatile-depleted, carbonaceous-chondrite-like material supplied between 20 and 100 per cent of the silicate Earth’s highly volatile elements, such as hydrogen and carbon.
An autosomal chromosome pair in Drosophila, the dot chromosome, is shown to have evolved from an ancestral X chromosome: these findings explain several previously puzzling aspects of dot chromosome biology and challenge the view that differentiated sex chromosomes represent a terminal evolutionary stage.
In the mouse whisker region of primary somatosensory cortex (S1), neurons projecting to secondary somatosensory cortex (S2) and primary motor cortex (M1), respectively, are differentially activated during distinct whisker-based behavioural tasks; sensory stimulus features alone do not elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.
Rett syndrome is caused by mutations in MeCP2, and this study identifies a site on MeCP2, T308, whose phosphorylation is regulated by neuronal activity: phosphorylation of T308 blocks the interaction of MeCP2 with the NCoR co-repressor complex, suppressing MeCP2's ability to repress transcription, and mice carrying mutations of MeCP2 T308 show Rett-syndrome-related symptoms.
Naked mole rats seem almost entirely protected from developing cancer, and this can now, at least in part, be explained by the production of a unique high-molecular-mass form of hyaluronan, a component of the extracellular matrix; together with an increased sensitivity of naked mole-rat cells to hyaluronan signalling, this form protects its cells from oncogenic transformation.
Unlike most salmonellae, Salmonellaenterica serovar Typhi causes life-threatening systemic infections known as typhoid fever, for which the molecular basis is unknown; here administration of typhoid toxin produced by S. Typhi reproduces many of the acute symptoms of typhoid fever, carbohydrates on cell surface glycoproteins are identified as receptors for typhoid toxin and the toxin’s crystal structure is determined, providing insights into these interactions.
In the human pathogen Vibrio vulnificus, the riboswitch regulating gene expression of the adenosine deaminase is shown to exist in three distinct stable conformational states; this three-state mechanism allows control of gene expression over a broad temperature range, which is essential for Vibrio adaptation.
Asymmetric sequence determinants flanking gene transcription start sites are shown to control directionality of transcription elongation in mammalian cells by regulating promoter-proximal cleavage and polyadenylation.
The X-ray crystal structure of a member of the glucose-specific phosphotransferase system (EIIAGlc) bound to the MalFGK2 maltose transporter is presented, revealing that two EIIAGlcproteins bind to the cytoplasmic ATPase subunits of the maltose transporter to stabilize it in an inward-facing conformation that prevents ATP hydrolysis.