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A Galactic-scale gas wave in the solar neighbourhood 期刊论文
NATURE, 2020, 578 (7794) : 237-+
作者:  Alves, Joao;  Zucker, Catherine;  Goodman, Alyssa A.;  Speagle, Joshua S.;  Meingast, Stefan;  Robitaille, Thomas;  Finkbeiner, Douglas P.;  Schlafly, Edward F.;  Green, Gregory M.
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

The three-dimensional structure of all cloud complexes in the solar neighbourhood is revealed, showing a narrow and coherent 2.7-kpc arrangement of dense gas, in disagreement with the Gould Belt model.


For the past 150 years, the prevailing view of the local interstellar medium has been based on a peculiarity known as the Gould Belt(1-4), an expanding ring of young stars, gas and dust, tilted about 20 degrees to the Galactic plane. However, the physical relationship between local gas clouds has remained unknown because the accuracy in distance measurements to such clouds is of the same order as, or larger than, their sizes(5-7). With the advent of large photometric surveys(8) and the astrometric survey(9), this situation has changed(10). Here we reveal the three-dimensional structure of all local cloud complexes. We find a narrow and coherent 2.7-kiloparsec arrangement of dense gas in the solar neighbourhood that contains many of the clouds thought to be associated with the Gould Belt. This finding is inconsistent with the notion that these clouds are part of a ring, bringing the Gould Belt model into question. The structure comprises the majority of nearby star-forming regions, has an aspect ratio of about 1:20 and contains about three million solar masses of gas. Remarkably, this structure appears to be undulating, and its three-dimensional shape is well described by a damped sinusoidal wave on the plane of the Milky Way with an average period of about 2 kiloparsecs and a maximum amplitude of about 160 parsecs.


  
Hepatic NADH reductive stress underlies common variation in metabolic traits 期刊论文
NATURE, 2020, 583 (7814) : 122-+
作者:  Skov, Laurits;  Coll Macia, Moises;  Sveinbjoernsson, Gardar;  Mafessoni, Fabrizio;  Lucotte, Elise A.;  Einarsdottir, Margret S.;  Jonsson, Hakon;  Halldorsson, Bjarni;  Gudbjartsson, Daniel F.;  Helgason, Agnar;  Schierup, Mikkel Heide;  Stefansson, Kari
收藏  |  浏览/下载:43/0  |  提交时间:2020/07/03

The cellular NADH/NAD(+) ratio is fundamental to biochemistry, but the extent to which it reflects versus drives metabolic physiology in vivo is poorly understood. Here we report the in vivo application of Lactobacillus brevis (Lb)NOX1, a bacterial water-forming NADH oxidase, to assess the metabolic consequences of directly lowering the hepatic cytosolic NADH/NAD(+) ratio in mice. By combining this genetic tool with metabolomics, we identify circulating alpha-hydroxybutyrate levels as a robust marker of an elevated hepatic cytosolic NADH/NAD(+) ratio, also known as reductive stress. In humans, elevations in circulating alpha-hydroxybutyrate levels have previously been associated with impaired glucose tolerance(2), insulin resistance(3) and mitochondrial disease(4), and are associated with a common genetic variant in GCKR(5), which has previously been associated with many seemingly disparate metabolic traits. Using LbNOX, we demonstrate that NADH reductive stress mediates the effects of GCKR variation on many metabolic traits, including circulating triglyceride levels, glucose tolerance and FGF21 levels. Our work identifies an elevated hepatic NADH/NAD(+) ratio as a latent metabolic parameter that is shaped by human genetic variation and contributes causally to key metabolic traits and diseases. Moreover, it underscores the utility of genetic tools such as LbNOX to empower studies of '  causal metabolism'  .


The authors identify an increased hepatic NADH/NAD(+) ratio as an underlying metabolic parameter that is shaped by human genetic variation and contributes causally to key metabolic traits and diseases.


  
Detection of metastable electronic states by Penning trap mass spectrometry 期刊论文
NATURE, 2020, 581 (7806) : 42-+
作者:  Rauch, Jennifer N.;  Luna, Gabriel;  Guzman, Elmer;  Audouard, Morgane;  Challis, Collin;  Sibih, Youssef E.;  Leshuk, Carolina;  Hernandez, Israel;  Wegmann, Susanne;  Hyman, Bradley T.;  Gradinaru, Viviana;  Kampmann, Martin;  Kosik, Kenneth S.
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

State-of-the-art optical clocks(1) achieve precisions of 10(-18) or better using ensembles of atoms in optical lattices(2,3) or individual ions in radio-frequency traps(4,5). Promising candidates for use in atomic clocks are highly charged ions(6) (HCIs) and nuclear transitions(7), which are largely insensitive to external perturbations and reach wavelengths beyond the optical range(8) that are accessible to frequency combs(9). However, insufficiently accurate atomic structure calculations hinder the identification of suitable transitions in HCIs. Here we report the observation of a long-lived metastable electronic state in an HCI by measuring the mass difference between the ground and excited states in rhenium, providing a non-destructive, direct determination of an electronic excitation energy. The result is in agreement with advanced calculations. We use the high-precision Penning trap mass spectrometer PENTATRAP to measure the cyclotron frequency ratio of the ground state to the metastable state of the ion with a precision of 10(-11)-an improvement by a factor of ten compared with previous measurements(10,11). With a lifetime of about 130 days, the potential soft-X-ray frequency reference at 4.96 x 10(16) hertz (corresponding to a transition energy of 202 electronvolts) has a linewidth of only 5 x 10(-8) hertz and one of the highest electronic quality factors (10(24)) measured experimentally so far. The low uncertainty of our method will enable searches for further soft-X-ray clock transitions(8,12) in HCIs, which are required for precision studies of fundamental physics(6).


Penning trap mass spectrometry is used to measure the electronic transition energy from a long-lived metastable state to the ground state in highly charged rhenium ions with a precision of 10(-11).


  
Implications of Organic Mass to Carbon Ratios Increasing Over Time in the Rural United States 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (5)
作者:  Malm, W. C.;  Schichtel, B. A.;  Hand, J. L.;  Prenni, A. J.
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/02
Thermal Optical Reflectance  Organic Carbon  Elemental Carbon  Organic Carbon to Carbon Ratio  Carbon Measurement Uncertainty  
An engineered PET depolymerase to break down and recycle plastic bottles 期刊论文
NATURE, 2020, 580 (7802) : 216-+
作者:  Zhao, Evan Wenbo;  Liu, Tao;  Jonsson, Erlendur;  Lee, Jeongjae;  Temprano, Israel;  Jethwa, Rajesh B.;  Wang, Anqi;  Smith, Holly;  Carretero-Gonzalez, Javier;  Song, Qilei;  Grey, Clare P.
收藏  |  浏览/下载:103/0  |  提交时间:2020/07/03

Present estimates suggest that of the 359 million tons of plastics produced annually worldwide(1), 150-200 million tons accumulate in landfill or in the natural environment(2). Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic, with almost 70 million tons manufactured annually worldwide for use in textiles and packaging(3). The main recycling process for PET, via thermomechanical means, results in a loss of mechanical properties(4). Consequently, de novo synthesis is preferred and PET waste continues to accumulate. With a high ratio of aromatic terephthalate units-which reduce chain mobility-PET is a polyester that is extremely difficult to hydrolyse(5). Several PET hydrolase enzymes have been reported, but show limited productivity(6,7). Here we describe an improved PET hydrolase that ultimately achieves, over 10 hours, a minimum of 90 per cent PET depolymerization into monomers, with a productivity of 16.7 grams of terephthalate per litre per hour (200 grams per kilogram of PET suspension, with an enzyme concentration of 3 milligrams per gram of PET). This highly efficient, optimized enzyme outperforms all PET hydrolases reported so far, including an enzyme(8,9) from the bacterium Ideonella sakaiensis strain 201-F6 (even assisted by a secondary enzyme(10)) and related improved variants(11-14) that have attracted recent interest. We also show that biologically recycled PET exhibiting the same properties as petrochemical PET can be produced from enzymatically depolymerized PET waste, before being processed into bottles, thereby contributing towards the concept of a circular PET economy.


Computer-aided engineering produces improvements to an enzyme that breaks down poly(ethylene terephthalate) (PET) into its constituent monomers, which are used to synthesize PET of near-petrochemical grade that can be further processed into bottles.


  
Late-stage oxidative C(sp(3))-H methylation 期刊论文
NATURE, 2020, 580 (7805) : 621-+
作者:  Fessler, Evelyn;  Eckl, Eva-Maria;  Schmitt, Sabine;  Mancilla, Igor Alves;  Meyer-Bender, Matthias F.;  Hanf, Monika;  Philippou-Massier, Julia;  Krebs, Stefan;  Zischka, Hans;  Jae, Lucas T.
收藏  |  浏览/下载:71/0  |  提交时间:2020/07/03

Frequently referred to as the '  magic methyl effect'  , the installation of methyl groups-especially adjacent (alpha) to heteroatoms-has been shown to dramatically increase the potency of biologically active molecules(1-3). However, existing methylation methods show limited scope and have not been demonstrated in complex settings(1). Here we report a regioselective and chemoselective oxidative C(sp(3))-H methylation method that is compatible with late-stage functionalization of drug scaffolds and natural products. This combines a highly site-selective and chemoselective C-H hydroxylation with a mild, functional-group-tolerant methylation. Using a small-molecule manganese catalyst, Mn(CF3PDP), at low loading (at a substrate/catalyst ratio of 200) affords targeted C-H hydroxylation on heterocyclic cores, while preserving electron-neutral and electron-rich aryls. Fluorine- or Lewis-acid-assisted formation of reactive iminium or oxonium intermediates enables the use of a mildly nucleophilic organoaluminium methylating reagent that preserves other electrophilic functionalities on the substrate. We show this late-stage C(sp(3))-H methylation on 41 substrates housing 16 different medicinally important cores that include electron-rich aryls, heterocycles, carbonyls and amines. Eighteen pharmacologically relevant molecules with competing sites-including drugs (for example, tedizolid) and natural products-are methylated site-selectively at the most electron rich, least sterically hindered position. We demonstrate the syntheses of two magic methyl substrates-an inverse agonist for the nuclear receptor RORc and an antagonist of the sphingosine-1-phosphate receptor-1-via late-stage methylation from the drug or its advanced precursor. We also show a remote methylation of the B-ring carbocycle of an abiraterone analogue. The ability to methylate such complex molecules at late stages will reduce synthetic effort and thereby expedite broader exploration of the magic methyl effect in pursuit of new small-molecule therapeutics and chemical probes.


A manganese-catalysed oxidative C(sp(3))-H methylation method allows a methyl group to be selectively installed into medicinally important heterocycles, providing a way to improve pharmaceuticals and better understand the '  magic methyl effect'  .


  
Collisional cooling of ultracold molecules 期刊论文
NATURE, 2020, 580 (7802) : 197-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Since the original work on Bose-Einstein condensation(1,2), the use of quantum degenerate gases of atoms has enabled the quantum emulation of important systems in condensed matter and nuclear physics, as well as the study of many-body states that have no analogue in other fields of physics(3). Ultracold molecules in the micro- and nanokelvin regimes are expected to bring powerful capabilities to quantum emulation(4) and quantum computing(5), owing to their rich internal degrees of freedom compared to atoms, and to facilitate precision measurement and the study of quantum chemistry(6). Quantum gases of ultracold atoms can be created using collision-based cooling schemes such as evaporative cooling, but thermalization and collisional cooling have not yet been realized for ultracold molecules. Other techniques, such as the use of supersonic jets and cryogenic buffer gases, have reached temperatures limited to above 10 millikelvin(7,8). Here we show cooling of NaLi molecules to micro- and nanokelvin temperatures through collisions with ultracold Na atoms, with both molecules and atoms prepared in their stretched hyperfine spin states. We find a lower bound on the ratio of elastic to inelastic molecule-atom collisions that is greater than 50-large enough to support sustained collisional cooling. By employing two stages of evaporation, we increase the phase-space density of the molecules by a factor of 20, achieving temperatures as low as 220 nanokelvin. The favourable collisional properties of the Na-NaLi system could enable the creation of deeply quantum degenerate dipolar molecules and raises the possibility of using stretched spin states in the cooling of other molecules.


NaLi molecules are cooled to micro- and nanokelvin temperatures through collisions with ultracold Na atoms by using molecules and atoms in stretched hyperfine spin states and applying two evaporation stages.


  
WHY MALE ALLIGATORS CAN'T TAKE THE HEAT 期刊论文
NATURE, 2020, 581 (7806) : 11-11
作者:  Hegelich, Simon
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Climate change could wreak havoc on the male-female sex ratio in certain alligator populations.


Climate change could wreak havoc on the male-female sex ratio in certain alligator populations.


  
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis 期刊论文
NATURE, 2020, 579 (7798) : 279-+
作者:  Liu, Xiaomeng;  Gao, Hongyan;  Ward, Joy E.;  Liu, Xiaorong;  Yin, Bing;  Fu, Tianda;  Chen, Jianhan;  Lovley, Derek R.;  Yao, Jun
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

Although it is well-established that reductions in the ratio of insulin to glucagon in the portal vein have a major role in the dysregulation of hepatic glucose metabolism in type-2 diabetes(1-3), the mechanisms by which glucagon affects hepatic glucose production and mitochondrial oxidation are poorly understood. Here we show that glucagon stimulates hepatic gluconeogenesis by increasing the activity of hepatic adipose triglyceride lipase, intrahepatic lipolysis, hepatic acetyl-CoA content and pyruvate carboxylase flux, while also increasing mitochondrial fat oxidation-all of which are mediated by stimulation of the inositol triphosphate receptor 1 (INSP3R1). In rats and mice, chronic physiological increases in plasma glucagon concentrations increased mitochondrial oxidation of fat in the liver and reversed diet-induced hepatic steatosis and insulin resistance. However, these effects of chronic glucagon treatment-reversing hepatic steatosis and glucose intolerance-were abrogated in Insp3r1 (also known as Itpr1)-knockout mice. These results provide insights into glucagon biology and suggest that INSP3R1 may represent a target for therapies that aim to reverse nonalcoholic fatty liver disease and type-2 diabetes.


  
Bacterial coexistence driven by motility and spatial competition 期刊论文
NATURE, 2020, 578 (7796) : 588-+
作者:  Micke, P.;  Leopold, T.;  King, S. A.;  Benkler, E.;  Spiess, L. J.;  Schmoeger, L.;  Schwarz, M.;  Crespo Lopez-Urrutia, J. R.;  Schmidt, P. O.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Elucidating elementary mechanisms that underlie bacterial diversity is central to ecology(1,2) and microbiome research(3). Bacteria are known to coexist by metabolic specialization(4), cooperation(5) and cyclic warfare(6-8). Many species are also motile(9), which is studied in terms of mechanism(10,11), benefit(12,13), strategy(14,15), evolution(16,17) and ecology(18,19). Indeed, bacteria often compete for nutrient patches that become available periodically or by random disturbances(2,20,21). However, the role of bacterial motility in coexistence remains unexplored experimentally. Here we show that-for mixed bacterial populations that colonize nutrient patches-either population outcompetes the other when low in relative abundance. This inversion of the competitive hierarchy is caused by active segregation and spatial exclusion within the patch: a small fast-moving population can outcompete a large fast-growing population by impeding its migration into the patch, while a small fast-growing population can outcompete a large fast-moving population by expelling it from the initial contact area. The resulting spatial segregation is lost for weak growth-migration trade-offs and a lack of virgin space, but is robust to population ratio, density and chemotactic ability, and is observed in both laboratory and wild strains. These findings show that motility differences and their trade-offs with growth are sufficient to promote diversity, and suggest previously undescribed roles for motility in niche formation and collective expulsion-containment strategies beyond individual search and survival.


In mixed bacterial populations that colonize nutrient patches, a growth-migration trade-off can lead to spatial exclusion that provides an advantage to populations that become rare, thereby stabilizing the community.