Showing papers by "Stockholm University published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
TL;DR: In this paper, the role of topology in non-Hermitian (NH) systems and its far-reaching physical consequences observable in a range of dissipative settings are reviewed.
Abstract: The current understanding of the role of topology in non-Hermitian (NH) systems and its far-reaching physical consequences observable in a range of dissipative settings are reviewed. In particular, how the paramount and genuinely NH concept of exceptional degeneracies, at which both eigenvalues and eigenvectors coalesce, leads to phenomena drastically distinct from the familiar Hermitian realm is discussed. An immediate consequence is the ubiquitous occurrence of nodal NH topological phases with concomitant open Fermi-Seifert surfaces, where conventional band-touching points are replaced by the aforementioned exceptional degeneracies. Furthermore, new notions of gapped phases including topological phases in single-band systems are detailed, and the manner in which a given physical context may affect the symmetry-based topological classification is clarified. A unique property of NH systems with relevance beyond the field of topological phases consists of the anomalous relation between bulk and boundary physics, stemming from the striking sensitivity of NH matrices to boundary conditions. Unifying several complementary insights recently reported in this context, a picture of intriguing phenomena such as the NH bulk-boundary correspondence and the NH skin effect is put together. Finally, applications of NH topology in both classical systems including optical setups with gain and loss, electric circuits, and mechanical systems and genuine quantum systems such as electronic transport settings at material junctions and dissipative cold-atom setups are reviewed.
758 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, National Research University – Higher School of Economics3, Columbia University4, Yale University5, University of Lagos6, Institute for Fiscal Studies7, Universidade Nova de Lisboa8, Lahore University of Management Sciences9, University of St Andrews10, Stockholm School of Economics11, Ghent University12, Alternatives13, Trinity College, Dublin14, University of Sierra Leone15, Kathmandu16, Cornell University17, University of Illinois at Chicago18, New York University Abu Dhabi19, Princeton University20, Stockholm University21, Tufts University22, University of Michigan23, Northwestern University24, London School of Economics and Political Science25
TL;DR: In this article, the authors analyzed COVID-19 vaccine acceptance across 15 survey samples covering 10 low and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals.
Abstract: Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
536 citations
TL;DR: This paper evaluated the effect of school closures on primary school performance using exceptionally rich data from The Netherlands (n ≈ 350,000) using the fact that national examinations took place before and after lockdown and compare progress during this period to the same period in the 3 previous years.
Abstract: Suspension of face-to-face instruction in schools during the COVID-19 pandemic has led to concerns about consequences for students' learning. So far, data to study this question have been limited. Here we evaluate the effect of school closures on primary school performance using exceptionally rich data from The Netherlands (n ≈ 350,000). We use the fact that national examinations took place before and after lockdown and compare progress during this period to the same period in the 3 previous years. The Netherlands underwent only a relatively short lockdown (8 wk) and features an equitable system of school funding and the world's highest rate of broadband access. Still, our results reveal a learning loss of about 3 percentile points or 0.08 standard deviations. The effect is equivalent to one-fifth of a school year, the same period that schools remained closed. Losses are up to 60% larger among students from less-educated homes, confirming worries about the uneven toll of the pandemic on children and families. Investigating mechanisms, we find that most of the effect reflects the cumulative impact of knowledge learned rather than transitory influences on the day of testing. Results remain robust when balancing on the estimated propensity of treatment and using maximum-entropy weights or with fixed-effects specifications that compare students within the same school and family. The findings imply that students made little or no progress while learning from home and suggest losses even larger in countries with weaker infrastructure or longer school closures.
534 citations
TL;DR: In this paper, the rational response to the global threat posed by accumulating and poorly reversible plastic pollution is to rapidly reduce plastic emissions through reductions in consumption of virgin plastic materials, along with internationally coordinated strategies for waste management.
Abstract: Plastic pollution accumulating in an area of the environment is considered “poorly reversible” if natural mineralization processes occurring there are slow and engineered remediation solutions are improbable. Should negative outcomes in these areas arise as a consequence of plastic pollution, they will be practically irreversible. Potential impacts from poorly reversible plastic pollution include changes to carbon and nutrient cycles; habitat changes within soils, sediments, and aquatic ecosystems; co-occurring biological impacts on endangered or keystone species; ecotoxicity; and related societal impacts. The rational response to the global threat posed by accumulating and poorly reversible plastic pollution is to rapidly reduce plastic emissions through reductions in consumption of virgin plastic materials, along with internationally coordinated strategies for waste management.
482 citations
TL;DR: In this article, the authors presented an updated global fit of neutrino oscillation data in the simplest three-neutrino framework, which showed a strong preference for the normal neutrinos mass ordering with 25σ statistical significance.
Abstract: We present an updated global fit of neutrino oscillation data in the simplest three-neutrino framework In the present study we include up-to-date analyses from a number of experiments Concerning the atmospheric and solar sectors, besides the data considered previously, we give updated analyses of IceCube DeepCore and Sudbury Neutrino Observatory data, respectively We have also included the latest electron antineutrino data collected by the Daya Bay and RENO reactor experiments, and the long-baseline T2K and NOνA measurements, as reported in the Neutrino 2020 conference All in all, these new analyses result in more accurate measurements of θ13, θ12, $$ \Delta {m}_{21}^2 $$
and $$ \left|\Delta {m}_{31}^2\right| $$
The best fit value for the atmospheric angle θ23 lies in the second octant, but first octant solutions remain allowed at ∼ 24σ Regarding CP violation measurements, the preferred value of δ we obtain is 108π (158π) for normal (inverted) neutrino mass ordering The global analysis still prefers normal neutrino mass ordering with 25σ statistical significance This preference is milder than the one found in previous global analyses These new results should be regarded as robust due to the agreement found between our Bayesian and frequentist approaches Taking into account only oscillation data, there is a weak/moderate preference for the normal neutrino mass ordering of 200σ While adding neutrinoless double beta decay from the latest Gerda, CUORE and KamLAND-Zen results barely modifies this picture, cosmological measurements raise the preference to 268σ within a conservative approach A more aggressive data set combination of cosmological observations leads to a similar preference for normal with respect to inverted mass ordering, namely 270σ This very same cosmological data set provides 2σ upper limits on the total neutrino mass corresponding to Σmν < 012 (015) eV in the normal (inverted) neutrino mass ordering scenario The bounds on the neutrino mixing parameters and masses presented in this up-to-date global fit analysis include all currently available neutrino physics inputs
402 citations
TL;DR: Aghanim et al. as mentioned in this paper used the same data set to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
Abstract: Author(s): Aghanim, N; Akrami, Y; Ashdown, M; Aumont, J; Baccigalupi, C; Ballardini, M; Banday, AJ; Barreiro, RB; Bartolo, N; Basak, S; Battye, R; Benabed, K; Bernard, JP; Bersanelli, M; Bielewicz, P; Bock, JJ; Bond, JR; Borrill, J; Bouchet, FR; Boulanger, F; Bucher, M; Burigana, C; Butler, RC; Calabrese, E; Cardoso, JF; Carron, J; Challinor, A; Chiang, HC; Chluba, J; Colombo, LPL; Combet, C; Contreras, D; Crill, BP; Cuttaia, F; De Bernardis, P; De Zotti, G; Delabrouille, J; Delouis, JM; DI Valentino, E; DIego, JM; Dore, O; Douspis, M; Ducout, A; Dupac, X; Dusini, S; Efstathiou, G; Elsner, F; Enslin, TA; Eriksen, HK; Fantaye, Y; Farhang, M; Fergusson, J; Fernandez-Cobos, R; Finelli, F; Forastieri, F; Frailis, M; Fraisse, AA; Franceschi, E; Frolov, A; Galeotta, S; Galli, S; Ganga, K; Genova-Santos, RT; Gerbino, M; Ghosh, T; Gonzalez-Nuevo, J; Gorski, KM; Gratton, S; Gruppuso, A; Gudmundsson, JE; Hamann, J; Handley, W; Hansen, FK; Herranz, D; Hildebrandt, SR; Hivon, E; Huang, Z; Jaffe, AH; Jones, WC; Karakci, A; Keihanen, E; Keskitalo, R; Kiiveri, K; Kim, J; Kisner, TS | Abstract: In the original version, the bounds given in Eqs. (87a) and (87b) on the contribution to the early-time optical depth, (15,30), contained a numerical error in deriving the 95th percentile from the Monte Carlo samples. The corrected 95% upper bounds are: τ(15,30) l 0:018 (lowE, flat τ(15, 30), FlexKnot), (1) τ(15, 30) l 0:023 (lowE, flat knot, FlexKnot): (2) These bounds are a factor of 3 larger than the originally reported results. Consequently, the new bounds do not significantly improve upon previous results from Planck data presented in Millea a Bouchet (2018) as was stated, but are instead comparable. Equations (1) and (2) give results that are now similar to those of Heinrich a Hu (2021), who used the same Planck 2018 data to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
344 citations
TL;DR: This paper recommends a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services.
Abstract: Freshwater ecosystems provide irreplaceable services for both nature and society. The quality and quantity of freshwater affect biogeochemical processes and ecological dynamics that determine biodiversity, ecosystem productivity, and human health and welfare at local, regional and global scales. Freshwater ecosystems and their associated riparian habitats are amongst the most biologically diverse on Earth, and have inestimable economic, health, cultural, scientific and educational values. Yet human impacts to lakes, rivers, streams, wetlands and groundwater are dramatically reducing biodiversity and robbing critical natural resources and services from current and future generations. Freshwater biodiversity is declining rapidly on every continent and in every major river basin on Earth, and this degradation is occurring more rapidly than in terrestrial ecosystems. Currently, about one third of all global freshwater discharges pass through human agricultural, industrial or urban infrastructure. About one fifth of the Earth's arable land is now already equipped for irrigation, including all the most productive lands, and this proportion is projected to surpass one third by midcentury to feed the rapidly expanding populations of humans and commensal species, especially poultry and ruminant livestock. Less than one fifth of the world's preindustrial freshwater wetlands remain, and this proportion is projected to decline to under one tenth by midcentury, with imminent threats from water transfer megaprojects in Brazil and India, and coastal wetland drainage megaprojects in China. The Living Planet Index for freshwater vertebrate populations has declined to just one third that of 1970, and is projected to sink below one fifth by midcentury. A linear model of global economic expansion yields the chilling prediction that human utilization of critical freshwater resources will approach one half of the Earth's total capacity by midcentury. Although the magnitude and growth of the human freshwater footprint are greater than is generally understood by policy makers, the news media, or the general public, slowing and reversing dramatic losses of freshwater species and ecosystems is still possible. We recommend a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services. Effective management of freshwater resources and ecosystems must be ranked amongst humanity's highest priorities.
325 citations
University of California, Santa Barbara1, Oak Ridge National Laboratory2, National Renewable Energy Laboratory3, École Polytechnique Fédérale de Lausanne4, Great Lakes Bioenergy Research Center5, Imperial College London6, Massachusetts Institute of Technology7, Stockholm University8, Katholieke Universiteit Leuven9, Dalian Institute of Chemical Physics10
TL;DR: In this paper, the authors present a set of guidelines for analysing critical data from lignin-first approaches, including feedstock analysis and process parameters, with the ambition of uniting the lignIN-first research community around a common set of reportable metrics, including fractionation efficiency, product yields, solvent mass balances, catalyst efficiency, and requirements for additional reagents such as reducing, oxidising, or capping agents.
Abstract: The valorisation of the plant biopolymer lignin is now recognised as essential to enabling the economic viability of the lignocellulosic biorefining industry. In this context, the “lignin-first” biorefining approach, in which lignin valorisation is considered in the design phase, has demonstrated the fullest utilisation of lignocellulose. We define lignin-first methods as active stabilisation approaches that solubilise lignin from native lignocellulosic biomass while avoiding condensation reactions that lead to more recalcitrant lignin polymers. This active stabilisation can be accomplished by solvolysis and catalytic conversion of reactive intermediates to stable products or by protection-group chemistry of lignin oligomers or reactive monomers. Across the growing body of literature in this field, there are disparate approaches to report and analyse the results from lignin-first approaches, thus making quantitative comparisons between studies challenging. To that end, we present herein a set of guidelines for analysing critical data from lignin-first approaches, including feedstock analysis and process parameters, with the ambition of uniting the lignin-first research community around a common set of reportable metrics. These guidelines comprise standards and best practices or minimum requirements for feedstock analysis, stressing reporting of the fractionation efficiency, product yields, solvent mass balances, catalyst efficiency, and the requirements for additional reagents such as reducing, oxidising, or capping agents. Our goal is to establish best practices for the research community at large primarily to enable direct comparisons between studies from different laboratories. The use of these guidelines will be helpful for the newcomers to this field and pivotal for further progress in this exciting research area.
320 citations
University of Groningen1, Erasmus University Rotterdam2, Katholieke Universiteit Leuven3, Chinese Academy of Sciences4, University of Surrey5, King's College London6, University of Toronto7, Avera Health8, Karolinska Institutet9, University of Copenhagen10, University of Greifswald11, University of Kiel12, Yeshiva University13, Sungkyunkwan University14, University of Tartu15, Weizmann Institute of Science16, Copenhagen University Hospital17, University of Texas Health Science Center at Houston18, University of Alabama at Birmingham19, Stockholm University20, University of Michigan21, VU University Amsterdam22, University of Oxford23, University of Bristol24, University of Amsterdam25, Maastricht University26, University of California, San Diego27, University of Eastern Finland28, National Institutes of Health29, University of California, Los Angeles30, Linköping University31, Harvard University32, Radboud University Nijmegen33, University of North Carolina at Chapel Hill34, Ewha Womans University35, Fred Hutchinson Cancer Research Center36, National Research Council37
TL;DR: In this article, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts) and found high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples.
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
287 citations
University of Bern1, Harvard University2, VU University Amsterdam3, University of Oxford4, Public Health Research Institute5, University of Wuppertal6, Kyoto University7, University of Amsterdam8, University of New South Wales9, University of Melbourne10, City University London11, University of Gothenburg12, Free University of Berlin13, University of Texas at Austin14, James I University15, Carlos III Health Institute16, Ohio State University17, Northwestern University18, University of Erlangen-Nuremberg19, University of Bristol20, University Hospitals Bristol NHS Foundation Trust21, Trinity College, Dublin22, University of York23, Karolinska Institutet24, Peking Union Medical College25, Linköping University26, University of Regina27, University of Sydney28, McLean Hospital29, University of Lübeck30, University of Zaragoza31, Imperial College London32, University of Nottingham33, University of Hamburg34, Oregon Research Institute35, Australian National University36, Hofstra University37, The Ohio State University Wexner Medical Center38, Stockholm University39, Hull York Medical School40, Tilburg University41, Linnaeus University42
TL;DR: In this article, the authors conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD-network meta-regression, and found that both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term.
Abstract: Importance Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures Patient Health Questionnaire–9 (PHQ-9) scores. Results Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, −0.8; 95% CI, −1.4 to −0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
Australian National University1, Max Planck Society2, University of Sydney3, University of Ljubljana4, Uppsala University5, Stockholm University6, University of New South Wales7, Monash University8, Macquarie University9, Aarhus University10, Leibniz Institute for Astrophysics Potsdam11, University of Southern Queensland12, International Space Science Institute13, Lund University14, University of Western Australia15, Kapteyn Astronomical Institute16, University of Hertfordshire17, Swinburne University of Technology18, Johns Hopkins University19, York University20, Columbia University21
TL;DR: In this paper, the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
Abstract: © 2021 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
01 Aug 2021
TL;DR: In this paper, the authors provide a toolbox for chemists in academia as well as industrial practitioners, and introduce guiding principles for the application of late-stage functionalization strategies to access new molecules of interest.
Abstract: Over the past decade, the landscape of molecular synthesis has gained major impetus by the introduction of late-stage functionalization (LSF) methodologies. C–H functionalization approaches, particularly, set the stage for new retrosynthetic disconnections, while leading to improvements in resource economy. A variety of innovative techniques have been successfully applied to the C–H diversification of pharmaceuticals, and these key developments have enabled medicinal chemists to integrate LSF strategies in their drug discovery programmes. This Review highlights the significant advances achieved in the late-stage C–H functionalization of drugs and drug-like compounds, and showcases how the implementation of these modern strategies allows increased efficiency in the drug discovery process. Representative examples are examined and classified by mechanistic patterns involving directed or innate C–H functionalization, as well as emerging reaction manifolds, such as electrosynthesis and biocatalysis, among others. Structurally complex bioactive entities beyond small molecules are also covered, including diversification in the new modalities sphere. The challenges and limitations of current LSF methods are critically assessed, and avenues for future improvements of this rapidly expanding field are discussed. We, hereby, aim to provide a toolbox for chemists in academia as well as industrial practitioners, and introduce guiding principles for the application of LSF strategies to access new molecules of interest. Late-stage C–H functionalization of complex molecules has emerged as a powerful tool in drug discovery. This Review classifies significant examples by reaction manifold and assesses the benefits and challenges of each approach. Avenues for future improvements of this fast-expanding field are proposed.
TL;DR: In this article, a priority ranking of future research avenues at the interface of microclimate ecology and global change biology, with a specific focus on three key themes: (1) disentangling the abiotic and biotic drivers and feedbacks of forest microclimates; (2) global and regional mapping and predictions, and (3) the impacts of micro-climate on forest biodiversity and ecosystem functioning in the face of climate change.
Abstract: Forest microclimates contrast strongly with the climate outside forests. To fully understand and better predict how forests' biodiversity and functions relate to climate and climate change, microclimates need to be integrated into ecological research. Despite the potentially broad impact of microclimates on the response of forest ecosystems to global change, our understanding of how microclimates within and below tree canopies modulate biotic responses to global change at the species, community and ecosystem level is still limited. Here, we review how spatial and temporal variation in forest microclimates result from an interplay of forest features, local water balance, topography and landscape composition. We first stress and exemplify the importance of considering forest microclimates to understand variation in biodiversity and ecosystem functions across forest landscapes. Next, we explain how macroclimate warming (of the free atmosphere) can affect microclimates, and vice versa, via interactions with land-use changes across different biomes. Finally, we perform a priority ranking of future research avenues at the interface of microclimate ecology and global change biology, with a specific focus on three key themes: (1) disentangling the abiotic and biotic drivers and feedbacks of forest microclimates; (2) global and regional mapping and predictions of forest microclimates; and (3) the impacts of microclimate on forest biodiversity and ecosystem functioning in the face of climate change. The availability of microclimatic data will significantly increase in the coming decades, characterizing climate variability at unprecedented spatial and temporal scales relevant to biological processes in forests. This will revolutionize our understanding of the dynamics, drivers and implications of forest microclimates on biodiversity and ecological functions, and the impacts of global changes. In order to support the sustainable use of forests and to secure their biodiversity and ecosystem services for future generations, microclimates cannot be ignored.
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University of Göttingen1, Osaka University2, KAIST3, National Chemical Laboratory4, Academy of Scientific and Innovative Research5, University of British Columbia6, Emory University7, University of Upper Alsace8, University of California, Berkeley9, University of Auckland10, Stockholm University11, AstraZeneca12
TL;DR: In this paper, the authors provide an overview of the best practices for C-H activation as well as key advances in asymmetric, photoinduced and electrocatalytic-mediated catalysis for this synthetic platform.
Abstract: Transition metal-catalysed C–H activation has emerged as an increasingly powerful platform for molecular syntheses, enabling applications to natural product syntheses, late-stage modification, pharmaceutical industries and material sciences, among others. This Primer summarizes representative best practices for the experimental set-up and data deposition for C–H activation, as well as discussing key developments including recent advances in asymmetric, photoinduced and electrocatalytic C–H activation. Likewise, strategies for applications of C–H activation towards the assembly of structurally complex (bio)polymers and drugs in academia and industry are discussed. In addition, current limitations in C–H activation and possible approaches for overcoming these shortcomings are reviewed. This Primer provides an overview of the best practices for C–H activation as well as key advances in asymmetric, photoinduced and electrocatalytic-mediated catalysis for this synthetic platform. An overview of how C–H activation facilitates the synthesis of molecules such as structurally complex (bio)polymers and drugs is provided along with the current challenges and priorities for the next decade.
TL;DR: In this article, the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions are discussed.
Abstract: This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.
TL;DR: In this article, the authors present an overview of a next-generation instrument, IceCube-Gen2, which will sharpen our understanding of the processes and environments that govern the Universe at the highest energies.
Abstract: The observation of electromagnetic radiation from radio to γ-ray wavelengths has provided a wealth of information about the Universe. However, at PeV (1015 eV) energies and above, most of the Universe is impenetrable to photons. New messengers, namely cosmic neutrinos, are needed to explore the most extreme environments of the Universe where black holes, neutron stars, and stellar explosions transform gravitational energy into non-thermal cosmic rays. These energetic particles havemillions of times higher energies than those produced in the most powerful particle accelerators on Earth. As neutrinos can escape from regions otherwise opaque to radiation, they allow an unique view deep into exploding stars and the vicinity of the event horizons of black holes. The discovery of cosmic neutrinos with IceCube has opened this new window on the Universe. IceCube has been successful in finding first evidence for cosmic particle acceleration in the jet of an active galactic nucleus. Yet, ultimately, its sensitivity is too limited to detect even the brightest neutrino sources with high significance, or to detect populations of less luminous sources. In thiswhite paper, we present an overview of a next-generation instrument, IceCube-Gen2, which will sharpen our understanding of the processes and environments that govern the Universe at the highest energies. IceCube-Gen2 is designed to: (a) Resolve the high-energy neutrino sky from TeV to EeV energies (b) Investigate cosmic particle acceleration through multi-messenger observations (c) Reveal the sources and propagation of the highest energy particles in the Universe (d) Probe fundamental physics with high-energy neutrinos IceCube-Gen2 will enhance the existing IceCube detector at the South Pole. It will increase the annual rate of observed cosmic neutrinos by a factor of ten compared to IceCube, and will be able to detect sources five times fainter than its predecessor. Furthermore, through the addition of a radio array, IceCube- Gen2 will extend the energy range by several orders of magnitude compared to IceCube. Construction will take 8 years and cost about $350M. The goal is to have IceCube-Gen2 fully operational by 2033. IceCube-Gen2 will play an essential role in shaping the new era of multimessenger astronomy, fundamentally advancing our knowledge of the highenergy Universe. This challenging mission can be fully addressed only through the combination of the information from the neutrino, electromagnetic, and gravitational wave emission of high-energy sources, in concert with the new survey instruments across the electromagnetic spectrum and gravitational wave detectors which will be available in the coming years.
Stockholm University1, Swedish Museum of Natural History2, Purdue University3, Met Office4, University of Exeter5, George Mason University6, University of Southern California7, University of Bristol8, Uppsala University9, University of Kiel10, Boise State University11, Alfred Wegener Institute for Polar and Marine Research12, University of Oslo13, Cardiff University14, University of Bremen15, Northumbria University16, ETH Zurich17, University of Washington18
TL;DR: A review of the state-of-the-art in Miocene climate, ocean circulation, biogeochemical cycling, ice sheet dynamics, and biotic adaptation research can be found in this article.
Abstract: The Miocene epoch (23.03–5.33 Ma) was a time interval of global warmth, relative to today. Continental configurations and mountain topography transitioned towards modern conditions, and many flora and fauna evolved into the same taxa that exist today. Miocene climate was dynamic: long periods of early and late glaciation bracketed a ∼2 Myr greenhouse interval – the Miocene Climatic Optimum (MCO). Floras, faunas, ice sheets, precipitation, pCO2, and ocean and atmospheric circulation mostly (but not ubiquitously) covaried with these large changes in climate. With higher temperatures and moderately higher pCO2 (∼400–600 ppm), the MCO has been suggested as a particularly appropriate analogue for future climate scenarios, and for assessing the predictive accuracy of numerical climate models – the same models that are used to simulate future climate. Yet, Miocene conditions have proved difficult to reconcile with models. This implies either missing positive feedbacks in the models, a lack of knowledge of past climate forcings, or the need for re‐interpretation of proxies, which might mitigate the model‐data discrepancy. Our understanding of Miocene climatic, biogeochemical, and oceanic changes on broad spatial and temporal scales is still developing. New records documenting the physical, chemical, and biotic aspects of the Earth system are emerging, and together provide a more comprehensive understanding of this important time interval. Here we review the state‐of‐the‐art in Miocene climate, ocean circulation, biogeochemical cycling, ice sheet dynamics, and biotic adaptation research as inferred through proxy observations and modelling studies.
Stockholm University1, Royal Swedish Academy of Sciences2, Potsdam Institute for Climate Impact Research3, University of Waterloo4, Harvard University5, Wageningen University and Research Centre6, University of Wisconsin-Madison7, University of Alaska Fairbanks8, Yale University9, Princeton University10, Stanford University11, University of Cambridge12, Oregon State University13, Australian National University14, Commonwealth Scientific and Industrial Research Organisation15
TL;DR: A systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic is provided in this paper.
Abstract: The COVID-19 pandemic has exposed an interconnected and tightly coupled globalized world in rapid change. This article sets the scientific stage for understanding and responding to such change for global sustainability and resilient societies. We provide a systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic; humanity has become the major force in shaping the future of the Earth system as a whole; and the scale and pace of the human dimension have caused climate change, rapid loss of biodiversity, growing inequalities, and loss of resilience to deal with uncertainty and surprise. Taken together, human actions are challenging the biosphere foundation for a prosperous development of civilizations. The Anthropocene reality—of rising system-wide turbulence—calls for transformative change towards sustainable futures. Emerging technologies, social innovations, broader shifts in cultural repertoires, as well as a diverse portfolio of active stewardship of human actions in support of a resilient biosphere are highlighted as essential parts of such transformations.
Stockholm University1, Sun Yat-sen University2, Ghent University3, Eastern Virginia Medical School4, University of Greifswald5, University of Pittsburgh6, University of Copenhagen7, University of Barcelona8, University of Crete9, Sapienza University of Rome10, Guy's and St Thomas' NHS Foundation Trust11, Katholieke Universiteit Leuven12
TL;DR: EUFOREA, the European Forum for Research and Education in Allergy and Airway Diseases, here proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinic.
Abstract: Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug–exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.
TL;DR: A new bound on the ultralight axion (ULA) dark matter mass m_{a), using the Lyman-alpha forest to look for suppressed cosmic structure growth is presented: a 95% lower limit m_{ a}>2×10^{-20} eV.
Abstract: We present a new bound on the ultralight axion (ULA) dark matter mass ${m}_{\mathrm{a}}$, using the Lyman-alpha forest to look for suppressed cosmic structure growth: a 95% lower limit ${m}_{\mathrm{a}}g2\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}20}\text{ }\text{ }\mathrm{eV}$. This strongly disfavors ($g99.7%$ credibility) the canonical ULA with ${10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}l{m}_{\mathrm{a}}l{10}^{\ensuremath{-}21}\text{ }\text{ }\mathrm{eV}$, motivated by the string axiverse and solutions to possible tensions in the cold dark matter model. We strengthen previous equivalent bounds by about an order of magnitude. We demonstrate the robustness of our results using an optimized emulator of improved hydrodynamical simulations.
University of London1, Stockholm University2, National Institutes of Health3, French Institute of Health and Medical Research4, University of Washington5, Utrecht University6, Aristotle University of Thessaloniki7, Masaryk University8, Finnish Environment Institute9, Harvard University10, University of Exeter11, University of Montpellier12, Imperial College London13
TL;DR: COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs and the mechanisms of these interactions deserve additional scrutiny.
Texas A&M University1, University of Exeter2, University of Helsinki3, Université du Québec à Montréal4, Tanjungpura University5, University of Hawaii at Manoa6, University of Bristol7, Bowdoin College8, Chulalongkorn University9, University of California, Los Angeles10, Max Planck Society11, University of Nottingham12, University of Magallanes13, Oeschger Centre for Climate Change Research14, Université de Montréal15, Northeast Normal University16, Lehigh University17, Mount Holyoke College18, McGill University19, Stockholm University20, University of Leicester21, Katholieke Universiteit Leuven22, University of St Andrews23, Florida State University24, Aarhus University25, University of Toronto26, University of New Hampshire27, University of Łódź28, Centre national de la recherche scientifique29, Cranfield University30, University of Alberta31, Stockholm Environment Institute32, Lawrence Berkeley National Laboratory33, United States Geological Survey34, Texas A&M University at Galveston35, University of Victoria36, Adam Mickiewicz University in Poznań37, Finnish Meteorological Institute38, Royal Holloway, University of London39, University of Queensland40, Lamont–Doherty Earth Observatory41, National Park Service42, University of York43, Hope College44, University of Reading45, Uva Wellassa University46, Queen's University Belfast47, University of California, Berkeley48, Memorial University of Newfoundland49
TL;DR: In this article, the authors define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future.
Abstract: The carbon balance of peatlands is predicted to shift from a sink to a source this century. However, peatland ecosystems are still omitted from the main Earth system models that are used for future climate change projections, and they are not considered in integrated assessment models that are used in impact and mitigation studies. By using evidence synthesized from the literature and an expert elicitation, we define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future. We also identify uncertainties and knowledge gaps in the scientific community and provide insight towards better integration of peatlands into modelling frameworks. Given the importance of the contribution by peatlands to the global carbon cycle, this study shows that peatland science is a critical research area and that we still have a long way to go to fully understand the peatland–carbon–climate nexus. Peatlands are impacted by climate and land-use changes, with feedback to warming by acting as either sources or sinks of carbon. Expert elicitation combined with literature review reveals key drivers of change that alter peatland carbon dynamics, with implications for improving models.
TL;DR: In this article, the ATLAS particle-flow reconstruction method is used to reconstruct the topo-clusters of the proton-proton collision data with a center-of-mass energy of 13$ TeV collected by the LHC.
Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.
TL;DR: In this article, the authors investigated the nutrient fluxes and physiological as well as molecular responses of the widespread coral Stylophora pistillata to heat stress prior to the onset of bleaching to identify processes involved in the breakdown of the coral-algal symbiosis.
Abstract: Recurrent mass bleaching events are pushing coral reefs worldwide to the brink of ecological collapse. While the symptoms and consequences of this breakdown of the coral-algal symbiosis have been extensively characterized, our understanding of the underlying causes remains incomplete. Here, we investigated the nutrient fluxes and the physiological as well as molecular responses of the widespread coral Stylophora pistillata to heat stress prior to the onset of bleaching to identify processes involved in the breakdown of the coral-algal symbiosis. We show that altered nutrient cycling during heat stress is a primary driver of the functional breakdown of the symbiosis. Heat stress increased the metabolic energy demand of the coral host, which was compensated by the catabolic degradation of amino acids. The resulting shift from net uptake to release of ammonium by the coral holobiont subsequently promoted the growth of algal symbionts and retention of photosynthates. Together, these processes form a feedback loop that will gradually lead to the decoupling of carbon translocation from the symbiont to the host. Energy limitation and altered symbiotic nutrient cycling are thus key factors in the early heat stress response, directly contributing to the breakdown of the coral-algal symbiosis. Interpreting the stability of the coral holobiont in light of its metabolic interactions provides a missing link in our understanding of the environmental drivers of bleaching and may ultimately help uncover fundamental processes underpinning the functioning of endosymbioses in general.
TL;DR: In this article, a ligand core rebalances the in-plane and out-of-plane interactions that define anisotropic crystal growth, and a family of 2D π-conjugated metal-organic frameworks (MOFs) is derived from large single crystals of sizes up to 200 µm.
Abstract: Electrically conducting 2D metal–organic frameworks (MOFs) have attracted considerable interest, as their hexagonal 2D lattices mimic graphite and other 2D van der Waals stacked materials. However, understanding their intrinsic properties remains a challenge because their crystals are too small or of too poor quality for crystal structure determination. Here, we report atomically precise structures of a family of 2D π-conjugated MOFs derived from large single crystals of sizes up to 200 μm, allowing atomic-resolution analysis by a battery of high-resolution diffraction techniques. A designed ligand core rebalances the in-plane and out-of-plane interactions that define anisotropic crystal growth. We report two crystal structure types exhibiting analogous 2D honeycomb-like sheets but distinct packing modes and pore contents. Single-crystal electrical transport measurements distinctively demonstrate anisotropic transport normal and parallel to the π-conjugated sheets, revealing a clear correlation between absolute conductivity and the nature of the metal cation and 2D sheet packing motif. Two-dimensional MOFs can possess porosity and electrical conductivity but are difficult to grow as single crystals. Here, by balancing in-plane and out-of-plane interactions, single crystals of sizes up to 200 µm are grown, allowing in-plane transport measurements and atomic-resolution analysis.
New York University1, University of Maryland, College Park2, University of California, Santa Cruz3, Goddard Space Flight Center4, Liverpool John Moores University5, Stockholm University6, Radboud University Nijmegen7, California Institute of Technology8, University of Washington9, Humboldt University of Berlin10, Kavli Institute for Theoretical Physics11, Adler Planetarium12, Northwestern University13, Weizmann Institute of Science14, Lawrence Berkeley National Laboratory15
TL;DR: In this paper, a homogeneous analysis of the optical/UV light curves, including 22 previously known TDEs from the literature, reveals a clean separation of light-curve properties with spectroscopic class.
Abstract: While tidal disruption events (TDEs) have long been heralded as laboratories for the study of quiescent black holes, the small number of known TDEs and uncertainties in their emission mechanism have hindered progress toward this promise. Here we present 17 new TDEs that have been detected recently by the Zwicky Transient Facility along with Swift UV and X-ray follow-up observations. Our homogeneous analysis of the optical/UV light curves, including 22 previously known TDEs from the literature, reveals a clean separation of light-curve properties with spectroscopic class. The TDEs with Bowen fluorescence features in their optical spectra have smaller blackbody radii, lower optical luminosities, and higher disruption rates compared to the rest of the sample. The small subset of TDEs that show only helium emission lines in their spectra have the longest rise times, the highest luminosities, and the lowest rates. A high detection rate of Bowen lines in TDEs with small photometric radii could be explained by the high density that is required for this fluorescence mechanism. The stellar debris can provide a source for this dense material. Diffusion of photons through this debris may explain why the rise and fade timescale of the TDEs in our sample are not correlated. We also report, for the first time, the detection of soft X-ray flares from a TDE on ~day timescales. Based on the fact that the X-ray flares peak at a luminosity similar to the optical/UV blackbody luminosity, we attribute them to brief glimpses through a reprocessing layer that otherwise obscures the inner accretion flow.
Science for Life Laboratory1, Swedish Museum of Natural History2, University of Copenhagen3, Stockholm University4, Francis Crick Institute5, University of California, Santa Cruz6, University of Potsdam7, Middle East Technical University8, Natural History Museum9, China Agricultural University10, Russian Academy of Sciences11
TL;DR: In this paper, the authors report the recovery of genome-wide data from three mammoth specimens dating to the Early and Middle Pleistocene subepochs, two of which are more than one million years old.
Abstract: Temporal genomic data hold great potential for studying evolutionary processes such as speciation. However, sampling across speciation events would, in many cases, require genomic time series that stretch well back into the Early Pleistocene subepoch. Although theoretical models suggest that DNA should survive on this timescale1, the oldest genomic data recovered so far are from a horse specimen dated to 780–560 thousand years ago2. Here we report the recovery of genome-wide data from three mammoth specimens dating to the Early and Middle Pleistocene subepochs, two of which are more than one million years old. We find that two distinct mammoth lineages were present in eastern Siberia during the Early Pleistocene. One of these lineages gave rise to the woolly mammoth and the other represents a previously unrecognized lineage that was ancestral to the first mammoths to colonize North America. Our analyses reveal that the Columbian mammoth of North America traces its ancestry to a Middle Pleistocene hybridization between these two lineages, with roughly equal admixture proportions. Finally, we show that the majority of protein-coding changes associated with cold adaptation in woolly mammoths were already present one million years ago. These findings highlight the potential of deep-time palaeogenomics to expand our understanding of speciation and long-term adaptive evolution. Siberian mammoth genomes from the Early and Middle Pleistocene subepochs reveal adaptive changes and a key hybridization event, highlighting the value of deep-time palaeogenomics for studies of speciation and long-term evolutionary trends.
TL;DR: In this article, the transition from traditional teaching into distance teaching in Swedish schools enforced by covid-19 was explored, and four distinct pedagogical activities central for distance education in a crisis, and many challenges faced during the transition were revealed.
Abstract: This study represents the first research effort to explore the transition from traditional teaching into distance teaching in Swedish schools enforced by covid-19. Governments made gradual and injudicious decisions to impede the spread of the pandemic (covid-19) in 2020. The enactment of new measures affected critical societal functions and included travel restrictions, closing of borders, school closures and lockdowns of entire countries worldwide. Social distancing became the new reality for many, and for many teachers and students, the school closure prompted a rapid transition from traditional to distance education. This study aims to capture the early stages of that transition. We distributed a questionnaire to teachers’ (n = 153) to gain insights into teacher and school preparedness, plans to deliver distance education, and teachers’ experience when making this transition. Results show that the school preparedness was mainly related to technical aspects, and that teachers lack pedagogical strategies needed in the emerging learning landscape of distance education. Findings reveal four distinct pedagogical activities central for distance education in a crisis, and many challenges faced during the transition. While preparedness to ensure continuity of education was halting, schools and teachers worked with tremendous effort to overcome the challenges. Results expand on previous findings on school closure during virus outbreaks and may in the short-term support teachers and school leaders in making informed decisions during the shift into distance education. The study may also inform the development of preparedness plans for schools, and offers a historical documentation.