You are hereNature
Nature
AI-controlled brain implants for mood disorders tested in people
Wed, 11/22/2017 - 01:00AI-controlled brain implants for mood disorders tested in people
Nature 551, 7682 (2017). http://www.nature.com/doifinder/10.1038/nature.2017.23031
Author: Sara Reardon
Researchers funded by the US military are developing appliances to record neural activity and automatically stimulate the brain to treat mental illness.
Categories: Literature
Mechanism of tandem duplication formation in BRCA1-mutant cells
Wed, 11/22/2017 - 01:00Mechanism of tandem duplication formation in BRCA1-mutant cells
Nature 551, 7682 (2017). doi:10.1038/nature24477
Authors: Nicholas A. Willis, Richard L. Frock, Francesca Menghi, Erin E. Duffey, Arvind Panday, Virginia Camacho, E. Paul Hasty, Edison T. Liu, Frederick W. Alt & Ralph Scully
Small, approximately 10-kilobase microhomology-mediated tandem duplications are abundant in the genomes of BRCA1-linked but not BRCA2-linked breast cancer. Here we define the mechanism underlying this rearrangement signature. We show that, in primary mammalian cells, BRCA1, but not BRCA2, suppresses the formation of tandem
Categories: Literature
Measurement of the multi-TeV neutrino interaction cross-section with IceCube using Earth absorption
Wed, 11/22/2017 - 01:00Measurement of the multi-TeV neutrino interaction cross-section with IceCube using Earth absorption
Nature 551, 7682 (2017). doi:10.1038/nature24459
Authors:
Neutrinos interact only very weakly, so they are extremely penetrating. The theoretical neutrino–nucleon interaction cross-section, however, increases with increasing neutrino energy, and neutrinos with energies above 40 teraelectronvolts (TeV) are expected to be absorbed as they pass through the Earth. Experimentally, the cross-section has been determined only at the relatively low energies (below 0.4 TeV) that are available at neutrino beams from accelerators. Here we report a measurement of neutrino absorption by the Earth using a sample of 10,784 energetic upward-going neutrino-induced muons. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the neutrino–nucleon interaction cross-section for neutrino energies 6.3–980 TeV, more than an order of magnitude higher than previous measurements. The measured cross-section is about 1.3 times the prediction of the standard model, consistent with the expectations for charged- and neutral-current interactions. We do not observe a large increase in the cross-section with neutrino energy, in contrast with the predictions of some theoretical models, including those invoking more compact spatial dimensions or the production of leptoquarks. This cross-section measurement can be used to set limits on the existence of some hypothesized beyond-standard-model particles, including leptoquarks.
Categories: Literature
Orthogonal muscle fibres have different instructive roles in planarian regeneration
Wed, 11/22/2017 - 01:00Orthogonal muscle fibres have different instructive roles in planarian regeneration
Nature 551, 7682 (2017). doi:10.1038/nature24660
Authors: M. Lucila Scimone, Lauren E. Cote & Peter W. Reddien
The ability to regenerate missing body parts exists throughout the animal kingdom. Positional information is crucial for regeneration, but how it is harboured and used by differentiated tissues is poorly understood. In planarians, positional information has been identified from study of phenotypes caused by RNA interference in which the wrong tissues are regenerated. For example, inhibition of the Wnt signalling pathway leads to regeneration of heads in place of tails. Characterization of these phenotypes has led to the identification of position control genes (PCGs)—genes that are expressed in a constitutive and regional manner and are associated with patterning. Most PCGs are expressed within planarian muscle; however, how muscle is specified and how different muscle subsets affect regeneration is unknown. Here we show that different muscle fibres have distinct regulatory roles during regeneration in the planarian Schmidtea mediterranea. myoD is required for formation of a specific muscle cell subset: the longitudinal fibres, oriented along the anterior–posterior axis. Loss of longitudinal fibres led to complete regeneration failure because of defects in regeneration initiation. A different transcription factor-encoding gene, nkx1-1, is required for the formation of circular fibres, oriented along the medial–lateral axis. Loss of circular fibres led to a bifurcated anterior–posterior axis with fused heads forming in single anterior blastemas. Whereas muscle is often viewed as a strictly contractile tissue, these findings reveal that different muscle types have distinct and specific regulatory roles in wound signalling and patterning to enable regeneration.
Categories: Literature
A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage
Wed, 11/22/2017 - 01:00A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage
Nature 551, 7682 (2017). doi:10.1038/nature24620
Authors: K. Adam Bohnert & Cynthia Kenyon
Although individuals age and die with time, an animal species can continue indefinitely, because of its immortal germ-cell lineage. How the germline avoids transmitting damage from one generation to the next remains a fundamental question in biology. Here we identify a lysosomal switch that enhances germline proteostasis before fertilization. We find that Caenorhabditis elegans oocytes whose maturation is arrested by the absence of sperm exhibit hallmarks of proteostasis collapse, including protein aggregation. Remarkably, sperm-secreted hormones re-establish oocyte proteostasis once fertilization becomes imminent. Key to this restoration is activation of the vacuolar H+-ATPase (V-ATPase), a proton pump that acidifies lysosomes. Sperm stimulate V-ATPase activity in oocytes by signalling the degradation of GLD-1, a translational repressor that blocks V-ATPase synthesis. Activated lysosomes, in turn, promote a metabolic shift that mobilizes protein aggregates for degradation, and reset proteostasis by enveloping and clearing the aggregates. Lysosome acidification also occurs during Xenopus oocyte maturation; thus, a lysosomal switch that enhances oocyte proteostasis in anticipation of fertilization may be conserved in other species.
Categories: Literature
NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis
Wed, 11/22/2017 - 01:00NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis
Nature 551, 7682 (2017). doi:10.1038/nature24637
Authors: Samantha W. Alvarez, Vladislav O. Sviderskiy, Erdem M. Terzi, Thales Papagiannakopoulos, Andre L. Moreira, Sylvia Adams, David M. Sabatini, Kıvanç Birsoy & Richard Possemato
Environmental nutrient levels impact cancer cell metabolism, resulting in context-dependent gene essentiality. Here, using loss-of-function screening based on RNA interference, we show that environmental oxygen levels are a major driver of differential essentiality between in vitro model systems and in vivo tumours. Above the 3–8% oxygen concentration typical of most tissues, we find that cancer cells depend on high levels of the iron–sulfur cluster biosynthetic enzyme NFS1. Mammary or subcutaneous tumours grow despite suppression of NFS1, whereas metastatic or primary lung tumours do not. Consistent with a role in surviving the high oxygen environment of incipient lung tumours, NFS1 lies in a region of genomic amplification present in lung adenocarcinoma and is most highly expressed in well-differentiated adenocarcinomas. NFS1 activity is particularly important for maintaining the iron–sulfur co-factors present in multiple cell-essential proteins upon exposure to oxygen compared to other forms of oxidative damage. Furthermore, insufficient iron–sulfur cluster maintenance robustly activates the iron-starvation response and, in combination with inhibition of glutathione biosynthesis, triggers ferroptosis, a non-apoptotic form of cell death. Suppression of NFS1 cooperates with inhibition of cysteine transport to trigger ferroptosis in vitro and slow tumour growth. Therefore, lung adenocarcinomas select for expression of a pathway that confers resistance to high oxygen tension and protects cells from undergoing ferroptosis in response to oxidative damage.
Categories: Literature
A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Wed, 11/22/2017 - 01:00A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Nature 551, 7682 (2017). doi:10.1038/nature24661
Authors: Dylan Dodd, Matthew H. Spitzer, William Van Treuren, Bryan D. Merrill, Andrew J. Hryckowian, Steven K. Higginbottom, Anthony Le, Tina M. Cowan, Garry P. Nolan, Michael A. Fischbach & Justin L. Sonnenburg
The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.
Categories: Literature
Structural basis for the initiation of eukaryotic transcription-coupled DNA repair
Wed, 11/22/2017 - 01:00Structural basis for the initiation of eukaryotic transcription-coupled DNA repair
Nature 551, 7682 (2017). doi:10.1038/nature24658
Authors: Jun Xu, Indrajit Lahiri, Wei Wang, Adam Wier, Michael A. Cianfrocco, Jenny Chong, Alissa A. Hare, Peter B. Dervan, Frank DiMaio, Andres E. Leschziner & Dong Wang
Eukaryotic transcription-coupled repair (TCR) is an important and well-conserved sub-pathway of nucleotide excision repair that preferentially removes DNA lesions from the template strand that block translocation of RNA polymerase II (Pol II). Cockayne syndrome group B (CSB, also known as ERCC6) protein in humans (or its yeast orthologues, Rad26 in Saccharomyces cerevisiae and Rhp26 in Schizosaccharomyces pombe) is among the first proteins to be recruited to the lesion-arrested Pol II during the initiation of eukaryotic TCR. Mutations in CSB are associated with the autosomal-recessive neurological disorder Cockayne syndrome, which is characterized by progeriod features, growth failure and photosensitivity. The molecular mechanism of eukaryotic TCR initiation remains unclear, with several long-standing unanswered questions. How cells distinguish DNA lesion-arrested Pol II from other forms of arrested Pol II, the role of CSB in TCR initiation, and how CSB interacts with the arrested Pol II complex are all unknown. The lack of structures of CSB or the Pol II–CSB complex has hindered our ability to address these questions. Here we report the structure of the S. cerevisiae Pol II–Rad26 complex solved by cryo-electron microscopy. The structure reveals that Rad26 binds to the DNA upstream of Pol II, where it markedly alters its path. Our structural and functional data suggest that the conserved Swi2/Snf2-family core ATPase domain promotes the forward movement of Pol II, and elucidate key roles for Rad26 in both TCR and transcription elongation.
Categories: Literature
Re-evaluating evolution in the HIV reservoir
Wed, 11/22/2017 - 01:00Re-evaluating evolution in the HIV reservoir
Nature 551, 7681 (2017). doi:10.1038/nature24634
Authors: Daniel I. S. Rosenbloom, Alison L. Hill, Sarah B. Laskey & Robert F. Siliciano
ARISING FROMR.Lorenzo-Redondoet al. Nature530, 51–56 (2016); doi:10.1038/nature16933Despite antiretroviral therapy (ART), a latent reservoir of replication-competent HIV-1 persists in resting memory CD4+ T cells and precludes a cure. Lorenzo-Redondo et
Categories: Literature
Lorenzo-Redondo et al. reply
Wed, 11/22/2017 - 01:00Lorenzo-Redondo et al. reply
Nature 551, 7681 (2017). doi:10.1038/nature24635
Authors: Ramon Lorenzo-Redondo, Helen R. Fryer, Trevor Bedford, Eun-Young Kim, John Archer, Sergei L. Kosakovsky Pond, Yoon-Seok Chung, Sudhir Penugonda, Jeffrey G. Chipman, Courtney V. Fletcher, Timothy W. Schacker, Michael H. Malim, Andrew Rambaut, Ashley T. Haase, Angela R. McLean & Steven M. Wolinsky
REPLYING TOD. I. S.Rosenbloom, A. L.Hill, S. B.Laskey & R. F.SilicianoNature551, 10.1038/nature24634 (2017)In the accompanying Comment, Rosenbloom et al. present a model simulation that questions our report
Categories: Literature
Photonuclear reactions triggered by lightning discharge
Wed, 11/22/2017 - 01:00Photonuclear reactions triggered by lightning discharge
Nature 551, 7681 (2017). doi:10.1038/nature24630
Authors: Teruaki Enoto, Yuuki Wada, Yoshihiro Furuta, Kazuhiro Nakazawa, Takayuki Yuasa, Kazufumi Okuda, Kazuo Makishima, Mitsuteru Sato, Yousuke Sato, Toshio Nakano, Daigo Umemoto & Harufumi Tsuchiya
Lightning and thunderclouds are natural particle accelerators. Avalanches of relativistic runaway electrons, which develop in electric fields within thunderclouds, emit bremsstrahlung γ-rays. These γ-rays have been detected by ground-based observatories, by airborne detectors and as terrestrial γ-ray flashes from space. The energy of the γ-rays is sufficiently high that they can trigger atmospheric photonuclear reactions that produce neutrons and eventually positrons via β+ decay of the unstable radioactive isotopes, most notably 13N, which is generated via 14N + γ → 13N + n, where γ denotes a photon and n a neutron. However, this reaction has hitherto not been observed conclusively, despite increasing observational evidence of neutrons and positrons that are presumably derived from such reactions. Here we report ground-based observations of neutron and positron signals after lightning. During a thunderstorm on 6 February 2017 in Japan, a γ-ray flash with a duration of less than one millisecond was detected at our monitoring sites 0.5–1.7 kilometres away from the lightning. The subsequent γ-ray afterglow subsided quickly, with an exponential decay constant of 40–60 milliseconds, and was followed by prolonged line emission at about 0.511 megaelectronvolts, which lasted for a minute. The observed decay timescale and spectral cutoff at about 10 megaelectronvolts of the γ-ray afterglow are well explained by de-excitation γ-rays from nuclei excited by neutron capture. The centre energy of the prolonged line emission corresponds to electron–positron annihilation, providing conclusive evidence of positrons being produced after the lightning.
Categories: Literature
Photonic quantum state transfer between a cold atomic gas and a crystal
Wed, 11/22/2017 - 01:00Photonic quantum state transfer between a cold atomic gas and a crystal
Nature 551, 7681 (2017). doi:10.1038/nature24468
Authors: Nicolas Maring, Pau Farrera, Kutlu Kutluer, Margherita Mazzera, Georg Heinze & Hugues de Riedmatten
Interfacing fundamentally different quantum systems is key to building future hybrid quantum networks. Such heterogeneous networks offer capabilities superior to those of their homogeneous counterparts, as they merge the individual advantages of disparate quantum nodes in a single network architecture. However, few investigations of optical hybrid interconnections have been carried out, owing to fundamental and technological challenges such as wavelength and bandwidth matching of the interfacing photons. Here we report optical quantum interconnection of two disparate matter quantum systems with photon storage capabilities. We show that a quantum state can be transferred faithfully between a cold atomic ensemble and a rare-earth-doped crystal by means of a single photon at 1,552 nanometre telecommunication wavelength, using cascaded quantum frequency conversion. We demonstrate that quantum correlations between a photon and a single collective spin excitation in the cold atomic ensemble can be transferred to the solid-state system. We also show that single-photon time-bin qubits generated in the cold atomic ensemble can be converted, stored and retrieved from the crystal with a conditional qubit fidelity of more than 85 per cent. Our results open up the prospect of optically connecting quantum nodes with different capabilities and represent an important step towards the realization of large-scale hybrid quantum networks.
Categories: Literature
Ligand-accelerated non-directed C–H functionalization of arenes
Wed, 11/22/2017 - 01:00Ligand-accelerated non-directed C–H functionalization of arenes
Nature 551, 7681 (2017). doi:10.1038/nature24632
Authors: Peng Wang, Pritha Verma, Guoqin Xia, Jun Shi, Jennifer X. Qiao, Shiwei Tao, Peter T. W. Cheng, Michael A. Poss, Marcus E. Farmer, Kap-Sun Yeung & Jin-Quan Yu
The directed activation of carbon–hydrogen bonds (C–H) is important in the development of synthetically useful reactions, owing to the proximity-induced reactivity and selectivity that is enabled by coordinating functional groups. Palladium-catalysed non-directed C–H activation could potentially enable further useful reactions, because it can reach more distant sites and be applied to substrates that do not contain appropriate directing groups; however, its development has faced substantial challenges associated with the lack of sufficiently active palladium catalysts. Currently used palladium catalysts are reactive only with electron-rich arenes, unless an excess of arene is used, which limits synthetic applications. Here we report a 2-pyridone ligand that binds to palladium and accelerates non-directed C–H functionalization with arene as the limiting reagent. This protocol is compatible with a broad range of aromatic substrates and we demonstrate direct functionalization of advanced synthetic intermediates, drug molecules and natural products that cannot be used in excessive quantities. We also developed C–H olefination and carboxylation protocols, demonstrating the applicability of our methodology to other transformations. The site selectivity in these transformations is governed by a combination of steric and electronic effects, with the pyridone ligand enhancing the influence of sterics on the selectivity, thus providing complementary selectivity to directed C–H functionalization.
Categories: Literature
Hydrogen-bearing iron peroxide and the origin of ultralow-velocity zones
Wed, 11/22/2017 - 01:00Hydrogen-bearing iron peroxide and the origin of ultralow-velocity zones
Nature 551, 7681 (2017). doi:10.1038/nature24461
Authors: Jin Liu, Qingyang Hu, Duck Young Kim, Zhongqing Wu, Wenzhong Wang, Yuming Xiao, Paul Chow, Yue Meng, Vitali B. Prakapenka, Ho-Kwang Mao & Wendy L. Mao
Ultralow-velocity zones (ULVZs) at Earth’s core–mantle boundary region have important implications for the chemical composition and thermal structure of our planet, but their origin has long been debated. Hydrogen-bearing iron peroxide (FeO2Hx) in the pyrite-type crystal structure was recently found to be stable under the conditions of the lowermost mantle. Using high-pressure experiments and theoretical calculations, we find that iron peroxide with a varying amount of hydrogen has a high density and high Poisson ratio as well as extremely low sound velocities consistent with ULVZs. Here we also report a reaction between iron and water at 86 gigapascals and 2,200 kelvin that produces FeO2Hx. This would provide a mechanism for generating the observed volume occupied by ULVZs through the reaction of about one-tenth the mass of Earth’s ocean water in subducted hydrous minerals with the effectively unlimited reservoir of iron in Earth’s core. Unlike other candidates for the composition of ULVZs, FeO2Hx synthesized from the superoxidation of iron by water would not require an extra transportation mechanism to migrate to the core–mantle boundary. These dense FeO2Hx-rich domains would be expected to form directly in the core–mantle boundary region and their properties would provide an explanation for the many enigmatic seismic features that are observed in ULVZs.
Categories: Literature
Graduate students face alarming tax hike
Tue, 11/21/2017 - 19:00Graduate students face alarming tax hike
Nature 551, 7680 (2017). doi:10.1038/d41586-017-05925-6
Author:
Adding to PhD students’ woes will undermine US research and economy.
Categories: Literature
Chemists get faster on the draw
Tue, 11/21/2017 - 19:00Chemists get faster on the draw
Nature 551, 7680 (2017). doi:10.1038/d41586-017-05898-6
Author:
A Nature journals guide to drawing the structures of molecules should aid expert and casual chemists alike.
Categories: Literature
How China could make the most of its beamlines
Tue, 11/21/2017 - 19:00How China could make the most of its beamlines
Nature 551, 7680 (2017). doi:10.1038/d41586-017-05924-7
Author:
More international collaboration could build capacity at big physics facilities especially in the south.
Categories: Literature
Immunization needs a technology boost
Tue, 11/21/2017 - 19:00Immunization needs a technology boost
Nature 551, 7680 (2017). http://www.nature.com/doifinder/10.1038/d41586-017-05923-8
Author: Seth Berkley
Tracking who receives vaccines is essential, but will be impossible without innovations in digital technologies, says Seth Berkley.
Categories: Literature
New Delhi smog, death-sentence appeal and a porpoise setback
Tue, 11/21/2017 - 19:00New Delhi smog, death-sentence appeal and a porpoise setback
Nature 551, 7680 (2017). http://www.nature.com/doifinder/10.1038/d41586-017-05926-5
Author:
The week in science: 11–16 November 2017.
Categories: Literature
Biology’s beloved amphibian — the axolotl — is racing towards extinction
Tue, 11/21/2017 - 19:00Biology’s beloved amphibian — the axolotl — is racing towards extinction
Nature 551, 7680 (2017). http://www.nature.com/doifinder/10.1038/d41586-017-05921-w
Author: Erik Vance
Although abundant in captivity, the salamander has nearly disappeared from its natural habitat, and that’s a problem.
Categories: Literature