| | Cancer: Resistance through repopulation
Bladder-cancer cells have been found to release prostaglandin E2 when they are killed by chemotherapy. Paradoxically, this molecule stimulates the proliferation of surviving cancer stem cells, leading to tumour repopulation.
| Neuroscience: A three-dimensional neural compass
The discovery that the neural navigation system of the mammalian brain acts in three dimensions sheds light on how mammals orient themselves in complex environments.
| Genomics: African dawn
The African Genome Variation Project presents genotyping and whole-genome data from individuals across sub-Saharan Africa, giving insight into population history and guiding future genomic studies on the continent.
| Architecture and conformational switch mechanism of the ryanodine receptor
Using electron cryomicroscopy, the structure of the rabbit RyR1 calcium channel is determined at 6.1 Å resolution in the closed state and 8.5 Å in the open state, revealing how calcium binding to the EF-hand of RyR1 regulates channel opening and facilitates calcium-induced calcium release.
| Structure of a mammalian ryanodine receptor
Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca2+-induced channel opening.
| The African Genome Variation Project shapes medical genetics in Africa OPEN
The African Genome Variation Project contains the whole-genome sequences of 320 individuals and dense genotypes on 1,481 individuals from sub-Saharan Africa; it enables the design and interpretation of genomic studies, with implications for finding disease loci and clues to human origins.
| Three-dimensional head-direction coding in the bat brain
A study of freely moving bats provides new insights into how the brain encodes a three-dimensional neural compass; neurons were identified encoding the three Euler rotation angles of the head (azimuth, pitch, and roll) and recordings from these head-direction cells revealed a toroidal model of spatial orientation mapped out by cells tuned to two circular variables (azimuth × pitch).
| Homo erectus at Trinil on Java used shells for tool production and engraving
Argon and luminescence dating of fossil shell infills from Trinil in Java, where Homo erectus lived, reveals that the hominin-bearing deposits are younger than previously thought; perforated shells, a shell tool and an engraved shell indicate that Homo erectus ate freshwater mussels, used their shells as tools and was able to create abstract engravings.
| Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury
Regeneration and plasticity after spinal cord injury are limited by inhibitory proteoglycans; here, modulation of a receptor for proteoglycans in rats is shown to lead to functional recovery after injury.
| Towards a therapy for Angelman syndrome by targeting a long non-coding RNA
Angelman syndrome is a neurodevelopmental disorder caused by disrupted function of the maternal copy of the imprinted UBE3A gene; here, targeting a long non-coding RNA that is responsible for silencing the paternal copy of UBE3A with antisense oligonucleotides is shown to partially restore UBE3A expression in the central nervous system and correct some cognitive deficits in a mouse model of the disease.
| Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells
The deubiquitinase enzyme DUBA is shown to act as a negative regulator of interleukin-17A (IL-17A) in TH17 cells; DUBA interacts with and stabilizes the ubiquitin ligase UBR5, which in turn targets RORγt for degradation in the proteaseome, thus limiting IL-17A production.
| Catalysts from synthetic genetic polymers
Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions.
| Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
To determine the origin of adult tissue-resident macrophages, a mouse lineage tracing study has revealed that these cells derive from erythro-myeloid progenitors in the yolk sac that are distinct from fetal and adult haematopoietic stem cells.
| Experimentally induced innovations lead to persistent culture via conformity in wild birds
How socially transmitted behaviours spread and persist is shown in a wild animal population, revealing an effect of social conformity.
| Structure of human cytoplasmic dynein-2 primed for its power stroke
The X-ray crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate is described.
| Structure of the F-actin––tropomyosin complex
Electron cryomicroscopy reveals the three-dimensional structure of F-actin at a resolution of 3.7 Å in complex with tropomyosin at a resolution of 6.5 Å; the stabilizing interactions and the effects of disease-causing mutants are also investigated.
| Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance
Using human bladder cancer xenograft models, a new mechanism involving an active proliferative response of cancer stem cells to chemotherapy-induced damage is shown, driven by prostaglandin E2 (PGE2) release in a manner similar to PGE2-induced wound repair; pharmacological inhibition of the PGE2/COX2 axis by celecoxib attenuates chemoresistance, suggesting a possible adjunctive therapy for bladder carcinomas.
| | β-catenin mediates stress resilience through Dicer1/microRNA regulation
Here β-catenin, which has been implicated in neurological and psychiatric diseases, including depression, is shown to mediate resilience to chronic stress in mice through induction of Dicer and microRNAs in nucleus accumbens, a key brain reward region.
Caroline Dias, Jian Feng, Haosheng Sun et al. | Deconstructing transcriptional heterogeneity in pluripotent stem cells
This study uses single-cell expression profiling of pluripotent stem cells after various perturbations, and uncovers a high degree of variability that can be inherited through cell divisions—modulating microRNA or external signalling pathways induces a ground state with reduced gene expression heterogeneity and a distinct chromatin profile.
Roshan M. Kumar, Patrick Cahan, Alex K. Shalek et al. | Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase
Here the structure of the membrane protein complex sodium-translocating NADH:quinone oxidoreductase (Na+-NQR) is described; as Na+-NQR is a component of the respiratory chain of various bacteria, including pathogenic ones, this structure may serve as the basis for the development of new antibiotics.
Julia Steuber, Georg Vohl, Marco S. Casutt et al. | | Stellar feedback as the origin of an extended molecular outflow in a starburst galaxy
A high-velocity outflow of molecular gas from a starburst galaxy has been observed to extend about ten kiloparsecs; its velocity is consistent with the momentum flux from stellar radiation pressure, showing that bursts of star formation can eject large amounts of cold gas from the central regions of galaxies, curtailing star formation.
J. E. Geach, R. C. Hickox, A. M. Diamond-Stanic et al. | Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules
In roots and dark-grown hypocotyls of Arabidopsis thaliana, ABP1-mediated auxin signalling induces swift re-orientation of the microtubule cytoskeleton from transverse to longitudinal, thus inhibiting cell expansion.
Xu Chen, Laurie Grandont, Hongjiang Li et al. | Nonlinear lattice dynamics as a basis for enhanced superconductivity in YBa2Cu3O6.5
Femtosecond X-ray diffraction and ab initio density functional theory calculations are used to determine the crystal structure of YBa2Cu3O6.5 undergoing optically driven, nonlinear lattice excitation above the transition temperature of 52 kelvin, under which conditions the electronic structure of the material changes in such a way as to favour superconductivity.
R. Mankowsky, A. Subedi, M. Först et al. | Centriole amplification by mother and daughter centrioles differs in multiciliated cells
Using advanced microscopy techniques, the process of centriole amplification in multiciliated cells is explored, and the daughter centriole identified as the primary nucleation site of more than 90% of the new centrioles, contesting existing de novo theories of centriolar amplification and highlighting a new centrosome asymmetry.
Adel Al Jord, Anne-Iris Lemaître, Nathalie Delgehyr et al. | Nutrient-sensing nuclear receptors coordinate autophagy
The nuclear receptors FXR and PPARα are shown to regulate autophagy by competing for binding to shared sites in the promoters of autophagic genes; in the fed state FXR suppresses hepatic autophagy, whereas in the fasted state PPARα is activated and reverses the normal suppression of autophagy.
Jae Man Lee, Martin Wagner, Rui Xiao et al. | Business culture and dishonesty in the banking industry
According to popular opinion, unethical business practices are common in the financial industry; here, the employees of a large, international bank are shown to behave, on average, honestly in a laboratory game to reveal dishonest behaviour, but when their professional identity as bank employees was rendered salient, the prevalence of dishonest behaviour increased.
Alain Cohn, Ernst Fehr, Michel André Maréchal | TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein
The RING finger protein TRIM37 is encoded by a gene that is amplified in certain breast cancers, but its function is unknown; here, it is shown to mono-ubiquitinate histone H2A and repress gene expression, and to function as a breast cancer oncoprotein.
Sanchita Bhatnagar, Claude Gazin, Lynn Chamberlain et al. | An enteric virus can replace the beneficial function of commensal bacteria
Commensal bacteria are known to have an important role in keeping the host healthy, but the role of eukaryotic viruses has been unknown; now, persistent infection in mice with various strains of enteric norovirus is shown to provide similar host protection.
Elisabeth Kernbauer, Yi Ding, Ken Cadwell | Single-shot compressed ultrafast photography at one hundred billion frames per second
A technique based on compressed imaging with a streak camera is reported that can videotape transient events in two dimensions with temporal resolution down to tens of picoseconds, and its usefulness is demonstrated using single laser shots applied to a variety of physical phenomena.
Liang Gao, Jinyang Liang, Chiye Li et al. | Conductive two-dimensional titanium carbide 'clay' with high volumetric capacitance
Two-dimensional titanium carbide has been produced by etching out aluminium in a lithium fluoride and hydrochloric acid mixture; it is hydrophilic and mouldable like clay and has excellent volumetric capacitance and cyclability, properties that are desirable for portable electronics.
Michael Ghidiu, Maria R. Lukatskaya, Meng-Qiang Zhao et al. | The ESCRT machinery regulates the secretion and long-range activity of Hedgehog
A new role for the endosomal sorting complex required for transport (ESCRT) is identified in fly larvae, where it is shown to be essential for the secretion and long-range signalling of the embryonic development morphogen Hedgehog.
Tamás Matusek, Franz Wendler, Sophie Polès et al. | Transcriptional regulation of autophagy by an FXR–CREB axis
The FXR–CREB axis is identified as a key physiological switch that regulates autophagy during feeding/fasting cycles; in the fed state, the nuclear receptor FXR is shown to suppress autophagy in the liver by inhibiting autophagy-associated lipid breakdown triggered under fasting conditions by the transcriptional activator CREB.
Sunmi Seok, Ting Fu, Sung-E Choi et al. | Eastern Pacific tropical cyclones intensified by El Niño delivery of subsurface ocean heat
El Niño events can transfer subsurface heat to the eastern North Pacific with a delay of several months, causing the intensification of tropical cyclones; the mechanism may lead to insights into past variations in tropical cyclone intensity and enhance seasonal predictions.
F.-F. Jin, J. Boucharel, I.-I. Lin | Piezo2 is the major transducer of mechanical forces for touch sensation in mice
Mice lacking the mechanically activated ion channel Piezo2 in both sensory neurons and Merkel cells are almost totally incapable of light-touch sensation while other somatosensory functions, such as mechanical nociception, remain intact, implying that other mechanically activated ion channels must now be identified to account for painful touch sensation.
Sanjeev S. Ranade, Seung-Hyun Woo, Adrienne E. Dubin et al. | Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel
X-ray structures of the human TRAAK mechanosensitive potassium channel reveal how build-up of tension in the lipid membrane can convert the channel from a non-conducting wedge shape associated with an inserted lipid acyl chain that blocks the pore to an expanded cross-sectional shape that prevents lipid entry and thus permits ion conduction.
Stephen G. Brohawn, Ernest B. Campbell, Roderick MacKinnon | | | | |
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