Showing papers in "Nature Communications in 2020"
TL;DR: An unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states is revealed, and U1 is suggested as a potential target for their modulation.
Abstract: Stimulated cells and cancer cells have widespread shortening of mRNA 3'-untranslated regions (3'UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates' most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells' migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3'UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.
3,432 citations
TL;DR: It is shown that the SARS-CoV-2 spike protein is less stable than that of SARS -CoV, and limited cross-neutralization activities between SARS and COVID-19 patients’ sera showlimited cross- neutralization activities, suggesting that recovery from one infection might not protect against the other.
Abstract: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
2,622 citations
TL;DR: The authors show that the PHD1 controls muscle mass in a hydroxylation-independent manner and prevents the degradation of leucine sensor LRS during oxygen and amino acid depletion to ensure effective mTORC1 activation in response to leucines.
Abstract: mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity.
1,466 citations
TL;DR: Remdesivir (RDV) has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.
1,431 citations
TL;DR: Professor Arumugam Manthiram looks back at the evolution of cathode chemistry, discussing the three major categories of oxide cathode materials with an emphasis on the fundamental solid-state chemistry that has enabled these advances.
Abstract: Lithium-ion batteries have aided the portable electronics revolution for nearly three decades. They are now enabling vehicle electrification and beginning to enter the utility industry. The emergence and dominance of lithium-ion batteries are due to their higher energy density compared to other rechargeable battery systems, enabled by the design and development of high-energy density electrode materials. Basic science research, involving solid-state chemistry and physics, has been at the center of this endeavor, particularly during the 1970s and 1980s. With the award of the 2019 Nobel Prize in Chemistry to the development of lithium-ion batteries, it is enlightening to look back at the evolution of the cathode chemistry that made the modern lithium-ion technology feasible. This review article provides a reflection on how fundamental studies have facilitated the discovery, optimization, and rational design of three major categories of oxide cathodes for lithium-ion batteries, and a personal perspective on the future of this important area. The 2019 Nobel Prize in Chemistry has been awarded to a trio of pioneers of the modern lithium-ion battery. Here, Professor Arumugam Manthiram looks back at the evolution of cathode chemistry, discussing the three major categories of oxide cathode materials with an emphasis on the fundamental solid-state chemistry that has enabled these advances.
1,120 citations
TL;DR: In this paper, the authors identify more than 109,000 previously unrecognized lunar craters and date almost 19,000 craters based on transfer learning with deep neural networks, which results in the identification of 109,956 new craters, which is more than a dozen times greater than the initial number of recognized craters.
Abstract: Impact craters, which can be considered the lunar equivalent of fossils, are the most dominant lunar surface features and record the history of the Solar System. We address the problem of automatic crater detection and age estimation. From initially small numbers of recognized craters and dated craters, i.e., 7895 and 1411, respectively, we progressively identify new craters and estimate their ages with Chang’E data and stratigraphic information by transfer learning using deep neural networks. This results in the identification of 109,956 new craters, which is more than a dozen times greater than the initial number of recognized craters. The formation systems of 18,996 newly detected craters larger than 8 km are estimated. Here, a new lunar crater database for the mid- and low-latitude regions of the Moon is derived and distributed to the planetary community together with the related data analysis. Using Chang’E data, the authors here identify more than 109,000 previously unrecognized lunar craters and date almost 19,000 craters based on transfer learning with deep neural networks. A new lunar crater database is derived and distributed to the planetary community.
973 citations
TL;DR: This review summarizes the mechanisms by which the abundance of different TCA cycle metabolites controls cellular function and fate in different contexts and focuses on how these metabolites mediated signaling can affect physiology and disease.
Abstract: Mitochondria are signaling organelles that regulate a wide variety of cellular functions and can dictate cell fate. Multiple mechanisms contribute to communicate mitochondrial fitness to the rest of the cell. Recent evidence confers a new role for TCA cycle intermediates, generally thought to be important for biosynthetic purposes, as signaling molecules with functions controlling chromatin modifications, DNA methylation, the hypoxic response, and immunity. This review summarizes the mechanisms by which the abundance of different TCA cycle metabolites controls cellular function and fate in different contexts. We will focus on how these metabolites mediated signaling can affect physiology and disease. Mitochondrial metabolites contribute to more than biosynthesis, and it is clear that they influence multiple cellular functions in a variety of ways. Here, Martinez-Reyes and Chandel review key metabolites and describe their effects on processes involved in physiology and disease including chromatin dynamics, immunity, and hypoxia.
957 citations
TL;DR: A meta-analysis of 3,111,714 reported global cases shows that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission and higher odds of death compared to females.
Abstract: Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease. Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.
957 citations
TL;DR: A human monoclonal antibody is reported capable of neutralizing both authentic SARS-CoV and SARS -CoV-2 by targeting a common epitope on these viruses.
Abstract: The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.
948 citations
TL;DR: Evidence of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise is reported.
Abstract: SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.
771 citations
TL;DR: This review focuses on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumours' extracellular matrix (ECM).
Abstract: Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients.
TL;DR: Pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614, and D614G may increase infectivity by assembling more functional S protein into the virion.
Abstract: SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (SG614) with the original (SD614). We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion.
TL;DR: Immunotherapy using immune-checkpoint modulators revolutionizes the oncology field far beyond their remarkable clinical efficacy in some patients with a more holistic vision of the patient with cancer.
Abstract: Immunotherapy using immune-checkpoint modulators revolutionizes the oncology field far beyond their remarkable clinical efficacy in some patients. It creates radical changes in the evaluation of treatment efficacy and toxicity with a more holistic vision of the patient with cancer.
TL;DR: This study shows that Sars-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-Cov-2.
Abstract: The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.
TL;DR: While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.
Abstract: Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.
TL;DR: TiO2/perovskite (CsPbBr3) S-scheme heterojunctions synthesized by a facile electrostatic-driven self-assembling approach are developed which greatly promotes the separation of electron-hole pairs to foster efficient CO2 photoreduction.
Abstract: Exploring photocatalysts to promote CO2 photoreduction into solar fuels is of great significance. We develop TiO2/perovskite (CsPbBr3) S-scheme heterojunctions synthesized by a facile electrostatic-driven self-assembling approach. Density functional theory calculation combined with experimental studies proves the electron transfer from CsPbBr3 quantum dots (QDs) to TiO2, resulting in the construction of internal electric field (IEF) directing from CsPbBr3 to TiO2 upon hybridization. The IEF drives the photoexcited electrons in TiO2 to CsPbBr3 upon light irradiation as revealed by in-situ X-ray photoelectron spectroscopy analysis, suggesting the formation of an S-scheme heterojunction in the TiO2/CsPbBr3 nanohybrids which greatly promotes the separation of electron-hole pairs to foster efficient CO2 photoreduction. The hybrid nanofibers unveil a higher CO2-reduction rate (9.02 μmol g–1 h–1) comparing with pristine TiO2 nanofibers (4.68 μmol g–1 h–1). Isotope (13CO2) tracer results confirm that the reduction products originate from CO2 source. Rational design and fabrication of high-performance photocatalyst is of great importance for CO2 reduction into solar fuel. Here, the authors demonstrate that S-scheme heterojunction TiO2/CsPbBr3 photocatalyst exhibits enhanced CO2 photoreduction activity.
University of Göttingen1, University of Hohenheim2, German Institute of Global and Area Studies3, International Maize and Wheat Improvement Center4, University of Bern5, Magister6, University of Waikato7, University of Jena8, Bogor Agricultural University9, University of Kiel10, Leipzig University11, University of the Philippines Los Baños12, Russian Academy of Sciences13, Tadulako University14
TL;DR: Landscape compositions that can mitigate trade-offs under optimal land-use allocation but also show that intensive monocultures always lead to higher profits are identified, suggesting that targeted landscape planning is needed to increase land- use efficiency while ensuring socio-ecological sustainability.
Abstract: Land-use transitions can enhance the livelihoods of smallholder farmers but potential economic-ecological trade-offs remain poorly understood. Here, we present an interdisciplinary study of the environmental, social and economic consequences of land-use transitions in a tropical smallholder landscape on Sumatra, Indonesia. We find widespread biodiversity-profit trade-offs resulting from land-use transitions from forest and agroforestry systems to rubber and oil palm monocultures, for 26,894 aboveground and belowground species and whole-ecosystem multidiversity. Despite variation between ecosystem functions, profit gains come at the expense of ecosystem multifunctionality, indicating far-reaching ecosystem deterioration. We identify landscape compositions that can mitigate trade-offs under optimal land-use allocation but also show that intensive monocultures always lead to higher profits. These findings suggest that, to reduce losses in biodiversity and ecosystem functioning, changes in economic incentive structures through well-designed policies are urgently needed.
TL;DR: Air and surfaces in hospital rooms of COVID-19 patients are sampled, SARS-CoV-2 RNA is detected in air samples of two of three tested airborne infection isolation rooms, and surface contamination is found in 66.7% of tested rooms during the first week of illness and 20% beyond the first month of illness.
Abstract: Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.
TL;DR: In this paper, the authors assess the impact of artificial intelligence on the achievement of the Sustainable Development Goals (SDGs) by using Artificial Intelligence (AI) and its progressively wider impact on many sectors.
Abstract: The emergence of artificial intelligence (AI) and its progressively wider impact on many sectors requires an assessment of its effect on the achievement of the Sustainable Development Goals. Using ...
TL;DR: The authors highlight the role of bottom-up movements to overcome structural economic growth imperatives spurring consumption by changing structures and culture towards safe and just systems.
Abstract: For over half a century, worldwide growth in affluence has continuously increased resource use and pollutant emissions far more rapidly than these have been reduced through better technology The affluent citizens of the world are responsible for most environmental impacts and are central to any future prospect of retreating to safer environmental conditions We summarise the evidence and present possible solution approaches Any transition towards sustainability can only be effective if far-reaching lifestyle changes complement technological advancements However, existing societies, economies and cultures incite consumption expansion and the structural imperative for growth in competitive market economies inhibits necessary societal change
TL;DR: Compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1 + CD57 + exhausted T cells, and significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors.
Abstract: The immune system of patients infected by SARS-CoV-2 is severely impaired Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naive, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19 COVID-19 is a serious pandemic threat to public health, but insights on the pathophysiological and immunological conditions are only emerging Here the authors use multi-color flow cytometry to characterize CD4+ and CD8+ T cells in peripheral blood from 39 COVID-19 patients in Italy to report altered T cell activation, function and polarization
TL;DR: It is reported that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6.
Abstract: The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.
TL;DR: The challenge of interpreting observational evidence from non-representative samples used to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes is highlighted.
Abstract: Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challenge of interpreting observational evidence from such non-representative samples. Collider bias can induce associations between two or more variables which affect the likelihood of an individual being sampled, distorting associations between these variables in the sample. Analysing UK Biobank data, compared to the wider cohort the participants tested for COVID-19 were highly selected for a range of genetic, behavioural, cardiovascular, demographic, and anthropometric traits. We discuss the mechanisms inducing these problems, and approaches that could help mitigate them. While collider bias should be explored in existing studies, the optimal way to mitigate the problem is to use appropriate sampling strategies at the study design stage. Many published studies of the current SARS-CoV-2 pandemic have analysed data from non-representative samples from populations. Here, using UK BioBank samples, Gibran Hemani and colleagues discuss the potential for such studies to suffer from collider bias, and provide suggestions for optimising study design to account for this.
TL;DR: An optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen is generated, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs, and these initial results support further development of this vaccine candidate.
Abstract: The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.
TL;DR: In this paper, the authors report the results of agent-based modelling using a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia, and compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures.
Abstract: There is a continuing debate on relative benefits of various mitigation and suppression strategies aimed to control the spread of COVID-19. Here we report the results of agent-based modelling using a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia. This model is calibrated to match key characteristics of COVID-19 transmission. An important calibration outcome is the age-dependent fraction of symptomatic cases, with this fraction for children found to be one-fifth of such fraction for adults. We apply the model to compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures. School closures are not found to bring decisive benefits unless coupled with high level of social distancing compliance. We report several trade-offs, and an important transition across the levels of social distancing compliance, in the range between 70% and 80% levels, with compliance at the 90% level found to control the disease within 13-14 weeks, when coupled with effective case isolation and international travel restrictions.
TL;DR: The notion of “sampling fraction” is defined and a methodology called Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC), which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples is introduced.
Abstract: Differential abundance (DA) analysis of microbiome data continues to be a challenging problem due to the complexity of the data. In this article we define the notion of “sampling fraction” and demonstrate a major hurdle in performing DA analysis of microbiome data is the bias introduced by differences in the sampling fractions across samples. We introduce a methodology called Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC), which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples. The absolute abundance data are modeled using a linear regression framework. This formulation makes a fundamental advancement in the field because, unlike the existing methods, it (a) provides statistically valid test with appropriate p-values, (b) provides confidence intervals for differential abundance of each taxon, (c) controls the False Discovery Rate (FDR), (d) maintains adequate power, and (e) is computationally simple to implement. Differential abundance analysis of microbiome data continues to be challenging due to data complexity. The authors propose a method which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples.
TL;DR: The authors provide a comprehensive assessment of regional changes and show that most heat indicaters have increased since the 1950s, on spatial and temporal scales necessary for understanding impacts.
Abstract: Heatwaves have increased in intensity, frequency and duration, with these trends projected to worsen under enhanced global warming. Understanding regional heatwave trends has critical implications for the biophysical and human systems they impact. Until now a comprehensive assessment of regional observed changes was hindered by the range of metrics employed, underpinning datasets, and time periods examined. Here, using the Berkeley Earth temperature dataset and key heatwave metrics, we systematically examine regional and global observed heatwave trends. In almost all regions, heatwave frequency demonstrates the most rapid and significant change. A measure of cumulative heat shows significant increases almost everywhere since the 1950s, mainly driven by heatwave days. Trends in heatwave frequency, duration and cumulative heat have accelerated since the 1950s, and due to the high influence of variability we recommend regional trends are assessed over multiple decades. Our results provide comparable regional observed heatwave trends, on spatial and temporal scales necessary for understanding impacts. Heatwaves are expected to become more frequent and more intense under global warming, but how these trends differ on a regional scale is not well known. Here, the authors provide a comprehensive assessment of regional changes and show that most heat indicaters have increased since the 1950s.
Helmholtz Centre for Environmental Research - UFZ1, University of Girona2, Catalan Institute for Water Research3, University of Barcelona4, University of Potsdam5, Leibniz Association6, Griffith University7, Abant Izzet Baysal University8, Universidade Federal de Juiz de Fora9, Charles Sturt University10, Aarhus University11, Radboud University Nijmegen12, Uppsala University13, University of Innsbruck14, University of Murcia15, Federal University of Rio Grande do Norte16, Estonian University of Life Sciences17, Ewha Womans University18, Chinese Academy of Sciences19, National Scientific and Technical Research Council20, University of the Basque Country21, UNESCO-IHE Institute for Water Education22, IRSA23, Umeå University24
TL;DR: A global survey covering 196 dry inland waters shows that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters, increasing current inland water carbon flux estimates by 6%.
Abstract: Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sedim ...
TL;DR: A practical implementation of the polyploid-aware mixture model that quickly and accurately infers genome properties across thousands of simulated and several real datasets spanning a broad range of complexity is described and evaluated.
Abstract: An important assessment prior to genome assembly and related analyses is genome profiling, where the k-mer frequencies within raw sequencing reads are analyzed to estimate major genome characteristics such as size, heterozygosity, and repetitiveness. Here we introduce GenomeScope 2.0 (https://github.com/tbenavi1/genomescope2.0), which applies combinatorial theory to establish a detailed mathematical model of how k-mer frequencies are distributed in heterozygous and polyploid genomes. We describe and evaluate a practical implementation of the polyploid-aware mixture model that quickly and accurately infers genome properties across thousands of simulated and several real datasets spanning a broad range of complexity. We also present a method called Smudgeplot (https://github.com/KamilSJaron/smudgeplot) to visualize and estimate the ploidy and genome structure of a genome by analyzing heterozygous k-mer pairs. We successfully apply the approach to systems of known variable ploidy levels in the Meloidogyne genus and the extreme case of octoploid Fragaria × ananassa. Prior to genome assembly, the raw sequencing reads must be analyzed for assessment of major genome characteristics such as genome size, heterozygosity, and repetitiveness. For this purpose, the authors introduce GenomeScope 2.0, an extension of GenomeScope for polyploid genomes, and Smudgeplot, which can estimate a genome’s ploidy.
TL;DR: The flexible electronic structure of the surface Fe sites, and their synergy with nearest-neighbor M sites through formation of O-bridged Fe-M reaction centers, stabilize OER intermediates that are unfavorable on pure M-M centers and single Fe Sites, fundamentally accounting for the high catalytic activity of MFe LDHs.
Abstract: NiFe and CoFe (MFe) layered double hydroxides (LDHs) are among the most active electrocatalysts for the alkaline oxygen evolution reaction (OER). Herein, we combine electrochemical measurements, operando X-ray scattering and absorption spectroscopy, and density functional theory (DFT) calculations to elucidate the catalytically active phase, reaction center and the OER mechanism. We provide the first direct atomic-scale evidence that, under applied anodic potentials, MFe LDHs oxidize from as-prepared α-phases to activated γ-phases. The OER-active γ-phases are characterized by about 8% contraction of the lattice spacing and switching of the intercalated ions. DFT calculations reveal that the OER proceeds via a Mars van Krevelen mechanism. The flexible electronic structure of the surface Fe sites, and their synergy with nearest-neighbor M sites through formation of O-bridged Fe-M reaction centers, stabilize OER intermediates that are unfavorable on pure M-M centers and single Fe sites, fundamentally accounting for the high catalytic activity of MFe LDHs. NiFe and CoFe layered double hydroxides are among the most active electrocatalysts for the alkaline oxygen evolution reaction. Here, by combining operando experiments and rigorous DFT calculations, the authors unravel their active phase, the reaction center and the catalytic mechanism.