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Ecological macroeconomics in the open economy: Sustainability, unequal exchange and policy coordination in a center-periphery model 期刊论文
ECOLOGICAL ECONOMICS, 2020, 172
作者:  Althouse, Jeffrey;  Guarini, Giulio;  Gabriel Porcile, Jose
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/02
Ecological macroeconomics  Green growth  Ecologically unequal exchange  Balance of payments constraint  Environmental policy coordination  Center-periphery model  
Population flow drives spatio-temporal distribution of COVID-19 in China 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:69/0  |  提交时间:2020/07/03

Sudden, large-scale and diffuse human migration can amplify localized outbreaks of disease into widespread epidemics(1-4). Rapid and accurate tracking of aggregate population flows may therefore be epidemiologically informative. Here we use 11,478,484 counts of mobile phone data from individuals leaving or transiting through the prefecture of Wuhan between 1 January and 24 January 2020 as they moved to 296 prefectures throughout mainland China. First, we document the efficacy of quarantine in ceasing movement. Second, we show that the distribution of population outflow from Wuhan accurately predicts the relative frequency and geographical distribution of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until 19 February 2020, across mainland China. Third, we develop a spatio-temporal '  risk source'  model that leverages population flow data (which operationalize the risk that emanates from epidemic epicentres) not only to forecast the distribution of confirmed cases, but also to identify regions that have a high risk of transmission at an early stage. Fourth, we use this risk source model to statistically derive the geographical spread of COVID-19 and the growth pattern based on the population outflow from Wuhan  the model yields a benchmark trend and an index for assessing the risk of community transmission of COVID-19 over time for different locations. This approach can be used by policy-makers in any nation with available data to make rapid and accurate risk assessments and to plan the allocation of limited resources ahead of ongoing outbreaks.


Modelling of population flows in China enables the forecasting of the distribution of confirmed cases of COVID-19 and the identification of areas at high risk of SARS-CoV-2 transmission at an early stage.


  
Potential circadian effects on translational failure for neuroprotection 期刊论文
NATURE, 2020
作者:  Sakai, Akito;  Minami, Susumu;  Koretsune, Takashi;  Chen, Taishi;  Higo, Tomoya;  Wang, Yangming;  Nomoto, Takuya;  Hirayama, Motoaki;  Miwa, Shinji;  Nishio-Hamane, Daisuke;  Ishii, Fumiyuki;  Arita, Ryotaro;  Nakatsuji, Satoru
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans(1,2) may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger alpha-phenyl-butyl-tert-nitrone (alpha PBN), and the N-methyl-d-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in '  active-phase'  than in '  inactive-phase'  rodent neurons. alpha PBN and MK801 reduced neuronal death only in '  inactive-phase'  neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.


Studies in rats and mice at different times of day suggest that the failure of neuroprotective strategies for stroke in translational studies might be related to the difference in circadian cycles between humans and rodents.


  
A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes 期刊论文
NATURE, 2020, 582 (7811) : 271-+
作者:  Waszak, Sebastian M.;  Robinson, Giles W.;  Gudenas, Brian L.;  Smith, Kyle S.;  Forget, Antoine;  Kojic, Marija;  Garcia-Lopez, Jesus;  Hadley, Jennifer;  Hamilton, Kayla V.;  Indersie, Emilie;  Buchhalter, Ivo;  Kerssemakers, Jules;  Jaeger, Natalie;  Sharma, Tanvi;  Rausch, Tobias
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Hoxb13 acts as a cofactor of Meis1 in regulating cardiomyocyte maturation and cell cycle, and knockout of both proteins enables regeneration of postnatal cardiac tissue in a mouse model of heart injury.


A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes(1,2) and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest(3). Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.


  
Ionic solids from common colloids 期刊论文
NATURE, 2020, 580 (7804) : 487-+
作者:  Delord, T.;  Huillery, P.;  Nicolas, L.;  Hetet, G.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

Oppositely charged colloidal particles are assembled in water through an approach that allows electrostatic interactions to be precisely tuned to generate macroscopic single crystals.


From rock salt to nanoparticle superlattices, complex structure can emerge from simple building blocks that attract each other through Coulombic forces(1-4). On the micrometre scale, however, colloids in water defy the intuitively simple idea of forming crystals from oppositely charged partners, instead forming non-equilibrium structures such as clusters and gels(5-7). Although various systems have been engineered to grow binary crystals(8-11), native surface charge in aqueous conditions has not been used to assemble crystalline materials. Here we form ionic colloidal crystals in water through an approach that we refer to as polymer-attenuated Coulombic self-assembly. The key to crystallization is the use of a neutral polymer to keep particles separated by well defined distances, allowing us to tune the attractive overlap of electrical double layers, directing particles to disperse, crystallize or become permanently fixed on demand. The nucleation and growth of macroscopic single crystals is demonstrated by using the Debye screening length to fine-tune assembly. Using a variety of colloidal particles and commercial polymers, ionic colloidal crystals isostructural to caesium chloride, sodium chloride, aluminium diboride and K4C60 are selected according to particle size ratios. Once fixed by simply diluting out solution salts, crystals are pulled out of the water for further manipulation, demonstrating an accurate translation from solution-phase assembly to dried solid structures. In contrast to other assembly approaches, in which particles must be carefully engineered to encode binding information(12-18), polymer-attenuated Coulombic self-assembly enables conventional colloids to be used as model colloidal ions, primed for crystallization.


  
Asynchronous carbon sink saturation in African and Amazonian tropical forests 期刊论文
NATURE, 2020, 579 (7797) : 80-+
作者:  Wannes Hubau;  Simon L. Lewis;  Oliver L. Phillips;  Kofi Affum-Baffoe;  Hans Beeckman;  Aida Cuní;  -Sanchez;  Armandu K. Daniels;  Corneille E. N. Ewango;  Sophie Fauset;  Jacques M. Mukinzi;  Douglas Sheil;  Bonaventure Sonké;  Martin J. P. Sullivan;  Terry C. H. Sunderland;  Hermann Taedoumg;  Sean C. Thomas;  Lee J. T. White;  Katharine A. Abernethy;  Stephen Adu-Bredu;  Christian A. Amani;  Timothy R. Baker;  Lindsay F. Banin;  Fidè;  le Baya;  Serge K. Begne;  Amy C. Bennett;  Fabrice Benedet;  Robert Bitariho;  Yannick E. Bocko;  Pascal Boeckx;  Patrick Boundja;  Roel J. W. Brienen;  Terry Brncic;  Eric Chezeaux;  George B. Chuyong;  Connie J. Clark;  Murray Collins;  James A. Comiskey;  David A. Coomes;  Greta C. Dargie;  Thales de Haulleville;  Marie Noel Djuikouo Kamdem;  Jean-Louis Doucet;  Adriane Esquivel-Muelbert;  Ted R. Feldpausch;  Alusine Fofanah;  Ernest G. Foli;  Martin Gilpin;  Emanuel Gloor;  Christelle Gonmadje;  Sylvie Gourlet-Fleury;  Jefferson S. Hall;  Alan C. Hamilton;  David J. Harris;  Terese B. Hart;  Mireille B. N. Hockemba;  Annette Hladik;  Suspense A. Ifo;  Kathryn J. Jeffery;  Tommaso Jucker;  Emmanuel Kasongo Yakusu;  Elizabeth Kearsley;  David Kenfack;  Alexander Koch;  Miguel E. Leal;  Aurora Levesley;  Jeremy A. Lindsell;  Janvier Lisingo;  Gabriela Lopez-Gonzalez;  Jon C. Lovett;  Jean-Remy Makana;  Yadvinder Malhi;  Andrew R. Marshall;  Jim Martin;  Emanuel H. Martin;  Faustin M. Mbayu;  Vincent P. Medjibe;  Vianet Mihindou;  Edward T. A. Mitchard;  Sam Moore;  Pantaleo K. T. Munishi;  Natacha Nssi Bengone;  Lucas Ojo;  Fidè;  le Evouna Ondo;  Kelvin S.-H. Peh;  Georgia C. Pickavance;  Axel Dalberg Poulsen;  John R. Poulsen;  Lan Qie;  Jan Reitsma;  Francesco Rovero;  Michael D. Swaine;  Joey Talbot;  James Taplin;  David M. Taylor;  Duncan W. Thomas;  Benjamin Toirambe;  John Tshibamba Mukendi;  Darlington Tuagben;  Peter M. Umunay;  Geertje M. F. van der Heijden;  Hans Verbeeck;  Jason Vleminckx;  Simon Willcock;  Hannsjö;  rg Wö;  ll;  John T. Woods;  Lise Zemagho
收藏  |  浏览/下载:23/0  |  提交时间:2020/05/13

Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions(1-3). Climate-driven vegetation models typically predict that this tropical forest '  carbon sink'  will continue for decades(4,5). Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53-0.79), in contrast to the long-term decline in Amazonian forests(6). Therefore the carbon sink responses of Earth'  s two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature(7-9). Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth'  s intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass(10) reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth'  s climate.


  
Population growth and land development: Investigating the bi-directional interactions 期刊论文
ECOLOGICAL ECONOMICS, 2020, 169
作者:  Tong, Qingmeng;  Qiu, Feng
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/02
Population growth  Land development  Spatial spillovers  Spatial regression model  
CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities 期刊论文
NATURE, 2020
作者:  Yang, Jianfeng;  Faccenda, Manuele
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

Cancer genomics studies have identified thousands of putative cancer driver genes(1). Development of high-throughput and accurate models to define the functions of these genes is a major challenge. Here we devised a scalable cancer-spheroid model and performed genome-wide CRISPR screens in 2D monolayers and 3D lung-cancer spheroids. CRISPR phenotypes in 3D more accurately recapitulated those of in vivo tumours, and genes with differential sensitivities between 2D and 3D conditions were highly enriched for genes that are mutated in lung cancers. These analyses also revealed drivers that are essential for cancer growth in 3D and in vivo, but not in 2D. Notably, we found that carboxypeptidase D is responsible for removal of a C-terminal RKRR motif(2) from the alpha-chain of the insulin-like growth factor 1 receptor that is critical for receptor activity. Carboxypeptidase D expression correlates with patient outcomes in patients with lung cancer, and loss of carboxypeptidase D reduced tumour growth. Our results reveal key differences between 2D and 3D cancer models, and establish a generalizable strategy for performing CRISPR screens in spheroids to reveal cancer vulnerabilities.


CRISPR screens in a 3D spheroid cancer model system more accurately recapitulate cancer phenotypes than existing 2D models and were used to identify carboxypeptidase D, acting via the IGF1R, as a 3D-specific driver of cancer growth.


  
Global-scale human impact on delta morphology has led to net land area gain 期刊论文
NATURE, 2020, 577 (7791) : 514-+
作者:  Nienhuis, J. H.;  Ashton, A. D.;  Edmonds, D. A.;  Hoitink, A. J. F.;  Kettner, A. J.;  Rowland, J. C.;  Tornqvist, T. E.
收藏  |  浏览/下载:8/0  |  提交时间:2020/05/13

River deltas rank among the most economically and ecologically valuable environments on Earth. Even in the absence of sea-level rise, deltas are increasingly vulnerable to coastal hazards as declining sediment supply and climate change alter their sediment budget, affecting delta morphology and possibly leading to erosion(1-3). However, the relationship between deltaic sediment budgets, oceanographic forces of waves and tides, and delta morphology has remained poorly quantified. Here we show how the morphology of about 11,000 coastal deltas worldwide, ranging from small bayhead deltas to mega-deltas, has been affected by river damming and deforestation. We introduce a model that shows that present-day delta morphology varies across a continuum between wave (about 80 per cent), tide (around 10 per cent) and river (about 10 per cent) dominance, but that most large deltas are tide- and river-dominated. Over the past 30 years, despite sea-level rise, deltas globally have experienced a net land gain of 54 +/- 12 square kilometres per year (2 standard deviations), with the largest 1 per cent of deltas being responsible for 30 per cent of all net land area gains. Humans are a considerable driver of these net land gains-25 per cent of delta growth can be attributed to deforestation-induced increases in fluvial sediment supply. Yet for nearly 1,000 deltas, river damming(4) has resulted in a severe (more than 50 per cent) reduction in anthropogenic sediment flux, forcing a collective loss of 12 +/- 3.5 square kilometres per year (2 standard deviations) of deltaic land. Not all deltas lose land in response to river damming: deltas transitioning towards tide dominance are currently gaining land, probably through channel infilling. With expected accelerated sea-level rise(5), however, recent land gains are unlikely to be sustained throughout the twenty-first century. Understanding the redistribution of sediments by waves and tides will be critical for successfully predicting human-driven change to deltas, both locally and globally.


A global study of river deltas shows a net increase in delta area by about 54 km(2) yr(-1) over the past 30 years, in part due to deforestation-induced sediment delivery increase.


  
Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling 期刊论文
NATURE, 2020, 578 (7796) : 582-+
作者:  Faraco, Giuseppe;  Hochrainer, Karin;  Segarra, Steven G.;  Schaeffer, Samantha;  Santisteban, Monica M.;  Menon, Ajay;  Jiang, Hong;  Holtzman, David M.;  Anrather, Josef;  Iadecola, Costantino
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Addressing the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are capable of treating drug-resistant infections(1). Many antibiotics are sourced from specialized metabolites produced by bacteria, particularly those of the Actinomycetes family(2). Although actinomycete extracts have traditionally been screened using activity-based platforms, this approach has become unfavourable owing to the frequent rediscovery of known compounds. Genome sequencing of actinomycetes reveals an untapped reservoir of biosynthetic gene clusters, but prioritization is required to predict which gene clusters may yield promising new chemical matter(2). Here we make use of the phylogeny of biosynthetic genes along with the lack of known resistance determinants to predict divergent members of the glycopeptide family of antibiotics that are likely to possess new biological activities. Using these predictions, we uncovered two members of a new functional class of glycopeptide antibiotics-the known glycopeptide antibiotic complestatin and a newly discovered compound we call corbomycin-that have a novel mode of action. We show that by binding to peptidoglycan, complestatin and corbomycin block the action of autolysins-essential peptidoglycan hydrolases that are required for remodelling of the cell wall during growth. Corbomycin and complestatin have low levels of resistance development and are effective in reducing bacterial burden in a mouse model of skin MRSA infection.


The glycopeptide antibiotic-related compounds complestatin and corbomycin function by binding to peptidoglycan and blocking the action of autolysins-peptidoglycan hydrolase enzymes that remodel the cell wall during growth.