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RNA polymerase III limits longevity downstream of TORC1

Nature - Wed, 11/29/2017 - 01:00

RNA polymerase III limits longevity downstream of TORC1

Nature 552, 7684 (2017). doi:10.1038/nature25007

Authors: Danny Filer, Maximillian A. Thompson, Vakil Takhaveev, Adam J. Dobson, Ilektra Kotronaki, James W. M. Green, Matthias Heinemann, Jennifer M. A. Tullet & Nazif Alic

Three distinct RNA polymerases transcribe different classes of genes in the eukaryotic nucleus. RNA polymerase (Pol) III is the essential, evolutionarily conserved enzyme that generates short, non-coding RNAs, including tRNAs and 5S rRNA. The historical focus on transcription of protein-coding genes has left the roles of Pol III in organismal physiology relatively unexplored. Target of rapamycin kinase complex 1 (TORC1) regulates Pol III activity, and is also an important determinant of longevity. This raises the possibility that Pol III is involved in ageing. Here we show that Pol III limits lifespan downstream of TORC1. We find that a reduction in Pol III extends chronological lifespan in yeast and organismal lifespan in worms and flies. Inhibiting the activity of Pol III in the gut of adult worms or flies is sufficient to extend lifespan; in flies, longevity can be achieved by Pol III inhibition specifically in intestinal stem cells. The longevity phenotype is associated with amelioration of age-related gut pathology and functional decline, dampened protein synthesis and increased tolerance of proteostatic stress. Pol III acts on lifespan downstream of TORC1, and limiting Pol III activity in the adult gut achieves the full longevity benefit of systemic TORC1 inhibition. Hence, Pol III is a pivotal mediator of this key nutrient-signalling network for longevity; the growth-promoting anabolic activity of Pol III mediates the acceleration of ageing by TORC1. The evolutionary conservation of Pol III affirms its potential as a therapeutic target.

Categories: Literature

A transfer-RNA-derived small RNA regulates ribosome biogenesis

Nature - Wed, 11/29/2017 - 01:00

A transfer-RNA-derived small RNA regulates ribosome biogenesis

Nature 552, 7683 (2017). doi:10.1038/nature25005

Authors: Hak Kyun Kim, Gabriele Fuchs, Shengchun Wang, Wei Wei, Yue Zhang, Hyesuk Park, Biswajoy Roy-Chaudhuri, Pan Li, Jianpeng Xu, Kirk Chu, Feijie Zhang, Mei-Sze Chua, Samuel So, Qiangfeng Cliff Zhang, Peter Sarnow & Mark A. Kay

Transfer-RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are an abundant class of small non-coding RNAs whose biological roles are not well understood. Here we show that inhibition of a specific tsRNA, LeuCAG3′tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a

Categories: Literature

Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons

Nature - Wed, 11/29/2017 - 01:00

Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons

Nature 552, 7683 (2017). doi:10.1038/nature24475

Authors:

High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly during their propagation, provide a probe of Galactic high-energy processes and may enable the observation of phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been measured directly up to approximately 2 teraelectronvolts in previous balloon- or space-borne experiments, and indirectly up to approximately 5 teraelectronvolts using ground-based Cherenkov γ-ray telescope arrays. Evidence for a spectral break in the teraelectronvolt energy range has been provided by indirect measurements, although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range 25 gigaelectronvolts to 4.6 teraelectronvolts by the Dark Matter Particle Explorer (DAMPE) with unprecedentedly high energy resolution and low background. The largest part of the spectrum can be well fitted by a ‘smoothly broken power-law’ model rather than a single power-law model. The direct detection of a spectral break at about 0.9 teraelectronvolts confirms the evidence found by previous indirect measurements, clarifies the behaviour of the CRE spectrum at energies above 1 teraelectronvolt and sheds light on the physical origin of the sub-teraelectronvolt CREs.

Categories: Literature

Reconciling taxon senescence with the Red Queen’s hypothesis

Nature - Wed, 11/29/2017 - 01:00

Reconciling taxon senescence with the Red Queen’s hypothesis

Nature 552, 7683 (2017). doi:10.1038/nature24656

Authors: Indrė Žliobaitė, Mikael Fortelius & Nils C. Stenseth

In the fossil record, taxa exhibit a regular pattern of waxing and waning of occupancy, range or diversity between their origin and extinction. This pattern appears to contradict the law of constant extinction, which states that the probability of extinction in a given taxon is independent of that taxon’s age. It is nevertheless well established for species, genera and higher taxa of terrestrial mammals, marine invertebrates, marine microorganisms, and recent Hawaiian clades of animals and plants. Here we show that the apparent contradiction between a stochastically constant extinction rate and the seemingly deterministic waxing and waning pattern of taxa disappears when we consider their peak of expansion rather than their final extinction. To a first approximation, we find that biotic drivers of evolution pertain mainly to the peak of taxon expansion, whereas abiotic drivers mainly apply to taxon extinction. The Red Queen’s hypothesis, which emphasizes biotic interactions, was originally proposed as an explanation of the law of constant extinction. Much effort has since been devoted to determining how this hypothesis, emphasizing competition for resources, relates to the effects of environmental change. One proposed resolution is that biotic and abiotic processes operate at different scales. By focusing attention on taxon expansion rather than survival, we resolve an apparent contradiction between the seemingly deterministic waxing and waning patterns over time and the randomness of extinction that the Red Queen’s hypothesis implies.

Categories: Literature

Genetic diversity of the African malaria vector Anopheles gambiae

Nature - Wed, 11/29/2017 - 01:00

Genetic diversity of the African malaria vector Anopheles gambiae

Nature 552, 7683 (2017). doi:10.1038/nature24995

Authors:

The sustainability of malaria control in Africa is threatened by the rise of insecticide resistance in Anopheles mosquitoes, which transmit the disease. To gain a deeper understanding of how mosquito populations are evolving, here we sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa, and identified over 50 million single nucleotide polymorphisms within the accessible genome. These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size. Strong signals of recent selection were observed in insecticide-resistance genes, with several sweeps spreading over large geographical distances and between species. The design of new tools for mosquito control using gene-drive systems will need to take account of high levels of genetic diversity in natural mosquito populations.

Categories: Literature

Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

Nature - Wed, 11/29/2017 - 01:00

Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

Nature 552, 7683 (2017). doi:10.1038/nature24994

Authors: Fumiji Saito, Kouyuki Hirayasu, Takeshi Satoh, Christian W. Wang, John Lusingu, Takao Arimori, Kyoko Shida, Nirianne Marie Q. Palacpac, Sawako Itagaki, Shiroh Iwanaga, Eizo Takashima, Takafumi Tsuboi, Masako Kohyama, Tadahiro Suenaga, Marco Colonna, Junichi Takagi, Thomas Lavstsen, Toshihiro Horii & Hisashi Arase

Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths each year. Plasmodium falciparum causes most life-threatening cases of malaria. Acquired immunity to malaria is inefficient, even after repeated exposure to P. falciparum, but the immune regulatory mechanisms used by P. falciparum remain largely unknown. Here we show that P. falciparum uses immune inhibitory receptors to achieve immune evasion. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150–200 genes per parasite genome that are expressed on the surface of infected erythrocytes. We found that a subset of RIFINs binds to either leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibit activation of LILRB1-expressing B cells and natural killer (NK) cells. Furthermore, P. falciparum-infected erythrocytes isolated from patients with severe malaria were more likely to interact with LILRB1 than erythrocytes from patients with non-severe malaria, although an extended study with larger sample sizes is required to confirm this finding. Our results suggest that P. falciparum has acquired multiple RIFINs to evade the host immune system by targeting immune inhibitory receptors.

Categories: Literature

Maternal age generates phenotypic variation in Caenorhabditis elegans

Nature - Wed, 11/29/2017 - 01:00

Maternal age generates phenotypic variation in Caenorhabditis elegans

Nature 552, 7683 (2017). doi:10.1038/nature25012

Authors: Marcos Francisco Perez, Mirko Francesconi, Cristina Hidalgo-Carcedo & Ben Lehner

Genetically identical individuals that grow in the same environment often show substantial phenotypic variation within populations of organisms as diverse as bacteria, nematodes, rodents and humans. With some exceptions, the causes are poorly understood. Here we show that isogenic Caenorhabditis

Categories: Literature

Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth

Nature - Wed, 11/29/2017 - 01:00

Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth

Nature 552, 7683 (2017). doi:10.1038/nature24673

Authors: Giovanni Germano, Simona Lamba, Giuseppe Rospo, Ludovic Barault, Alessandro Magrì, Federica Maione, Mariangela Russo, Giovanni Crisafulli, Alice Bartolini, Giulia Lerda, Giulia Siravegna, Benedetta Mussolin, Roberta Frapolli, Monica Montone, Federica Morano, Filippo de Braud, Nabil Amirouchene-Angelozzi, Silvia Marsoni, Maurizio D’Incalci, Armando Orlandi, Enrico Giraudo, Andrea Sartore-Bianchi, Salvatore Siena, Filippo Pietrantonio, Federica Di Nicolantonio & Alberto Bardelli

Molecular alterations in genes involved in DNA mismatch repair (MMR) promote cancer initiation and foster tumour progression. Cancers deficient in MMR frequently show favourable prognosis and indolent progression. The functional basis of the clinical outcome of patients with tumours that are deficient in MMR is not clear. Here we genetically inactivate MutL homologue 1 (MLH1) in colorectal, breast and pancreatic mouse cancer cells. The growth of MMR-deficient cells was comparable to their proficient counterparts in vitro and on transplantation in immunocompromised mice. By contrast, MMR-deficient cancer cells grew poorly when transplanted in syngeneic mice. The inactivation of MMR increased the mutational burden and led to dynamic mutational profiles, which resulted in the persistent renewal of neoantigens in vitro and in vivo, whereas MMR-proficient cells exhibited stable mutational load and neoantigen profiles over time. Immune surveillance improved when cancer cells, in which MLH1 had been inactivated, accumulated neoantigens for several generations. When restricted to a clonal population, the dynamic generation of neoantigens driven by MMR further increased immune surveillance. Inactivation of MMR, driven by acquired resistance to the clinical agent temozolomide, increased mutational load, promoted continuous renewal of neoantigens in human colorectal cancers and triggered immune surveillance in mouse models. These results suggest that targeting DNA repair processes can increase the burden of neoantigens in tumour cells; this has the potential to be exploited in therapeutic approaches.

Categories: Literature

Genetically programmed chiral organoborane synthesis

Nature - Wed, 11/29/2017 - 01:00

Genetically programmed chiral organoborane synthesis

Nature 552, 7683 (2017). doi:10.1038/nature24996

Authors: S. B. Jennifer Kan, Xiongyi Huang, Yosephine Gumulya, Kai Chen & Frances H. Arnold

Recent advances in enzyme engineering and design have expanded nature’s catalytic repertoire to functions that are new to biology. However, only a subset of these engineered enzymes can function in living systems. Finding enzymatic pathways that form chemical bonds that are not found in biology is particularly difficult in the cellular environment, as this depends on the discovery not only of new enzyme activities, but also of reagents that are both sufficiently reactive for the desired transformation and stable in vivo. Here we report the discovery, evolution and generalization of a fully genetically encoded platform for producing chiral organoboranes in bacteria. Escherichia coli cells harbouring wild-type cytochrome c from Rhodothermus marinus (Rma cyt c) were found to form carbon–boron bonds in the presence of borane–Lewis base complexes, through carbene insertion into boron–hydrogen bonds. Directed evolution of Rma cyt c in the bacterial catalyst provided access to 16 novel chiral organoboranes. The catalyst is suitable for gram-scale biosynthesis, providing up to 15,300 turnovers, a turnover frequency of 6,100 h–1, a 99:1 enantiomeric ratio and 100% chemoselectivity. The enantiopreference of the biocatalyst could also be tuned to provide either enantiomer of the organoborane products. Evolved in the context of whole-cell catalysts, the proteins were more active in the whole-cell system than in purified forms. This study establishes a DNA-encoded and readily engineered bacterial platform for borylation; engineering can be accomplished at a pace that rivals the development of chemical synthetic methods, with the ability to achieve turnovers that are two orders of magnitude (over 400-fold) greater than those of known chiral catalysts for the same class of transformation. This tunable method for manipulating boron in cells could expand the scope of boron chemistry in living systems.

Categories: Literature

Cells make proteins using ‘alien’ DNA

Nature - Wed, 11/29/2017 - 01:00

Cells make proteins using ‘alien’ DNA

Nature 551, 7682 (2017). http://www.nature.com/doifinder/10.1038/nature.2017.23040

Author: Ewen Callaway

Expanded genetic alphabet could allow for the production of new protein-based drugs.

Categories: Literature

China to roll back regulations for traditional medicine despite safety concerns

Nature - Wed, 11/29/2017 - 01:00

China to roll back regulations for traditional medicine despite safety concerns

Nature 551, 7682 (2017). http://www.nature.com/doifinder/10.1038/nature.2017.23038

Author: David Cyranoski

Scientists fear plans to abandon clinical trials of centuries-old remedies will put people at risk.

Categories: Literature

Corrections

Nature - Wed, 11/29/2017 - 01:00

Corrections

Nature 551, 7682 (2017). http://www.nature.com/doifinder/10.1038/551553a

The News story ‘Hungary rewards success’ (Nature 551, 425–426; 2017) understated the funding for the Hungarian Brain Research Programme. It received 18.5 billion forints, not 18.5 million.And the News story ‘Science scrambles after storm’ (Nature551, 282–283; 2017) erred in its

Categories: Literature

Probing many-body dynamics on a 51-atom quantum simulator

Nature - Wed, 11/29/2017 - 01:00

Probing many-body dynamics on a 51-atom quantum simulator

Nature 551, 7682 (2017). doi:10.1038/nature24622

Authors: Hannes Bernien, Sylvain Schwartz, Alexander Keesling, Harry Levine, Ahmed Omran, Hannes Pichler, Soonwon Choi, Alexander S. Zibrov, Manuel Endres, Markus Greiner, Vladan Vuletić & Mikhail D. Lukin

Controllable, coherent many-body systems can provide insights into the fundamental properties of quantum matter, enable the realization of new quantum phases and could ultimately lead to computational systems that outperform existing computers based on classical approaches. Here we demonstrate a method for creating controlled many-body

Categories: Literature

Observation of a many-body dynamical phase transition with a 53-qubit quantum simulator

Nature - Wed, 11/29/2017 - 01:00

Observation of a many-body dynamical phase transition with a 53-qubit quantum simulator

Nature 551, 7682 (2017). doi:10.1038/nature24654

Authors: J. Zhang, G. Pagano, P. W. Hess, A. Kyprianidis, P. Becker, H. Kaplan, A. V. Gorshkov, Z.-X. Gong & C. Monroe

A quantum simulator is a type of quantum computer that controls the interactions between quantum bits (or qubits) in a way that can be mapped to certain quantum many-body problems. As it becomes possible to exert more control over larger numbers of qubits, such simulators will be able to tackle a wider range of problems, such as materials design and molecular modelling, with the ultimate limit being a universal quantum computer that can solve general classes of hard problems. Here we use a quantum simulator composed of up to 53 qubits to study non-equilibrium dynamics in the transverse-field Ising model with long-range interactions. We observe a dynamical phase transition after a sudden change of the Hamiltonian, in a regime in which conventional statistical mechanics does not apply. The qubits are represented by the spins of trapped ions, which can be prepared in various initial pure states. We apply a global long-range Ising interaction with controllable strength and range, and measure each individual qubit with an efficiency of nearly 99 per cent. Such high efficiency means that arbitrary many-body correlations between qubits can be measured in a single shot, enabling the dynamical phase transition to be probed directly and revealing computationally intractable features that rely on the long-range interactions and high connectivity between qubits.

Categories: Literature

Mild oxidation of methane to methanol or acetic acid on supported isolated rhodium catalysts

Nature - Wed, 11/29/2017 - 01:00

Mild oxidation of methane to methanol or acetic acid on supported isolated rhodium catalysts

Nature 551, 7682 (2017). doi:10.1038/nature24640

Authors: Junjun Shan, Mengwei Li, Lawrence F. Allard, Sungsik Lee & Maria Flytzani-Stephanopoulos

An efficient and direct method of catalytic conversion of methane to liquid methanol and other oxygenates would be of considerable practical value. However, it remains an unsolved problem in catalysis, as typically it involves expensive or corrosive oxidants or reaction media that are not amenable to commercialization. Although methane can be directly converted to methanol using molecular oxygen under mild conditions in the gas phase, the process is either stoichiometric (and therefore requires a water extraction step) or is too slow and low-yielding to be practical. Methane could, in principle, also be transformed through direct oxidative carbonylation to acetic acid, which is commercially obtained through methane steam reforming, methanol synthesis, and subsequent methanol carbonylation on homogeneous catalysts. However, an effective catalyst for the direct carbonylation of methane to acetic acid, which might enable the economical small-scale utilization of natural gas that is currently flared or stranded, has not yet been reported. Here we show that mononuclear rhodium species, anchored on a zeolite or titanium dioxide support suspended in aqueous solution, catalyse the direct conversion of methane to methanol and acetic acid, using oxygen and carbon monoxide under mild conditions. We find that the two products form through independent pathways, which allows us to tune the conversion: three-hour-long batch-reactor tests conducted at 150 degrees Celsius, using either the zeolite-supported or the titanium-dioxide-supported catalyst, yield around 22,000 micromoles of acetic acid per gram of catalyst, or around 230 micromoles of methanol per gram of catalyst, respectively, with selectivities of 60–100 per cent. We anticipate that these unusually high activities, despite still being too low for commercial application, may guide the development of optimized catalysts and practical processes for the direct conversion of methane to methanol, acetic acid and other useful chemicals.

Categories: Literature

Halogens in chondritic meteorites and terrestrial accretion

Nature - Wed, 11/29/2017 - 01:00

Halogens in chondritic meteorites and terrestrial accretion

Nature 551, 7682 (2017). doi:10.1038/nature24625

Authors: Patricia L. Clay, Ray Burgess, Henner Busemann, Lorraine Ruzié-Hamilton, Bastian Joachim, James M. D. Day & Christopher J. Ballentine

Volatile element delivery and retention played a fundamental part in Earth’s formation and subsequent chemical differentiation. The heavy halogens—chlorine (Cl), bromine (Br) and iodine (I)—are key tracers of accretionary processes owing to their high volatility and incompatibility, but have low abundances in most geological and planetary materials. However, noble gas proxy isotopes produced during neutron irradiation provide a high-sensitivity tool for the determination of heavy halogen abundances. Using such isotopes, here we show that Cl, Br and I abundances in carbonaceous, enstatite, Rumuruti and primitive ordinary chondrites are about 6 times, 9 times and 15–37 times lower, respectively, than previously reported and usually accepted estimates. This is independent of the oxidation state or petrological type of the chondrites. The ratios Br/Cl and I/Cl in all studied chondrites show a limited range, indistinguishable from bulk silicate Earth estimates. Our results demonstrate that the halogen depletion of bulk silicate Earth relative to primitive meteorites is consistent with the depletion of lithophile elements of similar volatility. These results for carbonaceous chondrites reveal that late accretion, constrained to a maximum of 0.5 ± 0.2 per cent of Earth’s silicate mass, cannot solely account for present-day terrestrial halogen inventories. It is estimated that 80–90 per cent of heavy halogens are concentrated in Earth’s surface reservoirs and have not undergone the extreme early loss observed in atmosphere-forming elements. Therefore, in addition to late-stage terrestrial accretion of halogens and mantle degassing, which has removed less than half of Earth’s dissolved mantle gases, the efficient extraction of halogen-rich fluids from the solid Earth during the earliest stages of terrestrial differentiation is also required to explain the presence of these heavy halogens at the surface. The hydropilic nature of halogens, whereby they track with water, supports this requirement, and is consistent with volatile-rich or water-rich late-stage terrestrial accretion.

Categories: Literature

A semi-synthetic organism that stores and retrieves increased genetic information

Nature - Wed, 11/29/2017 - 01:00

A semi-synthetic organism that stores and retrieves increased genetic information

Nature 551, 7682 (2017). doi:10.1038/nature24659

Authors: Yorke Zhang, Jerod L. Ptacin, Emil C. Fischer, Hans R. Aerni, Carolina E. Caffaro, Kristine San Jose, Aaron W. Feldman, Court R. Turner & Floyd E. Romesberg

Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Previous efforts to generate such semi-synthetic organisms culminated in the creation of a strain of Escherichia coli that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum tricornutum, imports the requisite unnatural triphosphates from its medium and then uses them to replicate a plasmid containing the unnatural base pair dNaM–dTPT3. Although the semi-synthetic organism stores increased information when compared to natural organisms, retrieval of the information requires in vivo transcription of the unnatural base pair into mRNA and tRNA, aminoacylation of the tRNA with a non-canonical amino acid, and efficient participation of the unnatural base pair in decoding at the ribosome. Here we report the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with two different unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient decoding at the ribosome to direct the site-specific incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein. The results demonstrate that interactions other than hydrogen bonding can contribute to every step of information storage and retrieval. The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions.

Categories: Literature

Shell To Double Green Energy Investments, Halve Carbon Footprint

Yale Environment 360 - Tue, 11/28/2017 - 10:56

Royal Dutch Shell announced it will double its spending on green energy between now and 2020, investing $2 billion to develop wind, biofuels, and electric car infrastructure, among other technologies. The energy giant also outlined a new goal of halving the carbon footprint of the energy it sells by 2050, with an interim goal of a 20 percent reduction by 2035.

Read more on E360 →

Categories: Environmental News

Where Corn Is King, the Stirrings of a Renaissance in Small Grains

Yale Environment 360 - Tue, 11/28/2017 - 04:00

Breaking with the industrial model of growing corn and soybeans, a growing number of Iowa farmers are putting oats, rye, and other small grains into their crop rotation, a switch that is regenerating soils, cleaning up waters, and providing benefits to family farms.

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Categories: Environmental News

Fracking Activity Linked to Increase in Texas Quakes, According to New Study

Yale Environment 360 - Mon, 11/27/2017 - 14:03

Using recent seismic data and studies of ancient fault lines, scientists have concluded that an increase in earthquake activity in parts of the United States is directly tied to hydraulic fracturing, which results in the disposal of pressurized wastewater deep into cracks in the earth’s crust.

Read more on E360 →

Categories: Environmental News

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