bluuebunny/crossref_metadata_2025 huggingface dataset:
The UV/X-ray radiation fields and particle (CME) flows of M dwarf exoplanet host stars
Authors: Brown Alexander
Published: September 2020

The high energy X-ray and UV radiation fields of host stars play a crucial role in determining the atmospheric conditions and habitability of potentially-habitable exoplanets. This paper focuses on the major surveys of the UV/X-ray emissions of M- and K-type exoplanet hosts that have been undertaken by the MUSCLES and MegaMUSCLES Hubble Space Telescope (HST) Treasury programs and associated contemporaneous X-ray and ground-based observations. The quiescent and flaring radiation (both photons and implied particles) were observed from this extensive sample of relatively old, low mass, exoplanet host stars and show that, from the viewpoint of a habitable-zone exoplanet, there is no such thing as an “inactive” M dwarf star. The resulting implications are significant for planetary habitability. Extensive monitoring of the X-ray/UV emission from a representative younger M dwarf is also presented and the direct stellar effects that influence exoplanets during the earlier phases of their formation and evolution discussed.
The Genetic Architecture of the Clustering of Cardiometabolic Risk Factors: A Study of 8- to 17-Year-Old Chinese Twins
Authors: Ji Fuling , Ning Feng , Duan Haiping , Dong Liyan , Yang Feng , Liu Zhisheng , Song Xuyan , Zhang Dongfeng , Wang Shaojie , Pang Zengchang , Kaprio Jaakko , Silventoinen Karri
Published: September 2020

We explored the genetic architecture of metabolic risk factors of cardiovascular diseases (CVDs) and their clustering in Chinese boys and girls. Seven metabolic traits (body mass index [BMI], waist circumference [WC], systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol [TC], triglyceride [TG], and uric acid [UA]) were measured in a sample of 1016 twins between 8 and 17 years of age, recruited from the Qingdao Twin Registry. Cholesky, independent pathway, and common pathway models were used to identify the latent genetic structure behind the clustering of these metabolic traits. Genetic architecture of these metabolic traits was largely similar in boys and girls. The highest heritability was found for BMI (a2 = 0.63) in boys and TC (a2 = .69) in girls. Three heritable factors, adiposity (BMI and WC), blood pressure (SBP and DBP), and metabolite factors (TC, TG, and UA), which formed one higher-order latent phenotype, were identified. Latent genetic, common environmental, and unique environmental factors indirectly impacted the three factors through one single latent factor. Our results suggest that there is one latent factor influencing several metabolic traits, which are known risk factors of CVDs in young Chinese twins. Latent genetic, common environmental, and unique environmental factors indirectly imposed on them. These results inform strategies for gene pleiotropic discovery and intervening of CVD risk factors during childhood and adolescence.
Deconstructing Tectonics: Ten Animated Explorations
Authors: Scotese Christopher R. , van der Pluijm Ben A.
Published: September 2020

The configuration of continents and oceans of our tectonically active planet is ever changing. Using new, high‐resolution paleogeographic base maps, we created a set of animations that examine key elements of plate tectonics. These time‐ and space‐based paleoglobe reconstructions illustrate continental rifting, continental breakup, ocean ridges and fracture zones, hot spot tracks, arc‐backarc systems, continental collision, terrane accretion, opening‐closing of ocean basins, supercontinent formation, plate velocities, and future Earth. Each animation is supported by a narrative that offers a brief topical overview, some observations to guide a user's exploration, and key references that formulated the main ideas and concepts that became the foundations of modern plate tectonics.
Ocean Surface Currents Reconstruction: Spectral Characterization of the Transfer Function Between SST and SSH
Authors: González‐Haro Cristina , Isern‐Fontanet Jordi , Tandeo Pierre , Garello René
Published: September 2020

Knowledge of ocean surface current at high resolutions is crucial for many applications. In addition to the classic satellite altimetry retrieval from sea surface height (SSH), ocean surface currents can be retrieved from sea surface temperature (SST) observations using a transfer function between SST and SSH. Previous works showed the potential of microwave SST observations to reconstruct ocean surface currents using a synergistic approach: an optimal transfer function that combines the phase of SST with the SSH amplitude spectra. This synergistic approach revealed that surface quasi geostrophy (SQG) reconstruction can be enhanced and opened up the possibility to improve spatial resolution of ocean currents retrieved from altimeters observations if infrared SST observations are considered. However, before applying this synergistic approach to satellite observations, we need to analyze and characterize the spectral properties of the transfer function. This spectral characterization of the transfer function allows to exploit the synergy between SST and SSH observations that have different measurement topology and different spatial resolution. Here, we performed a feasibility study using the daily outputs of the operational Mercator global analysis and forecast system at (1/12)° in the western coast of Australia (27–35°S, 107–113°E) spanning from 26 November 2012 to 26 November 2016. Results showed that the mean transfer function in this region presents two well different bands: one characterized by a negative slope slightly steeper (α = −1.2) than the k−1 predicted by the SQG solution for scales smaller than 270 km and another characterized by a plateau for wavelengths larger than 270 km. In addition, the results revealed that the inhomogeneity in dynamics of the flow limits global solutions. Finally, we showed that information contained along the track is enough for a synoptic reconstruction of the flow in this region, which shows the feasibility of applying this methodology to real satellite observations.
Iron Supply by Subglacial Discharge Into a Fjord Near the Front of a Marine‐Terminating Glacier in Northwestern Greenland
Authors: Kanna Naoya , Sugiyama Shin , Fukamachi Yasushi , Nomura Daiki , Nishioka Jun
Published: September 2020

Glacial fjords in Greenland show high productivity owing to the runoff of meltwater from the glaciers. Macronutrient dynamics (of nitrate, phosphate, and silicate) associated with subglacial discharge plumes in front of marine‐terminating glaciers are widely cited as important drivers of summer phytoplankton blooms in the fjords. However, the dynamics of iron (Fe), an essential micronutrient for primary production, remain largely unstudied in glacial fjords. To investigate the role of subglacial discharge plumes in Fe supply processes in glacial fjords, a comprehensive survey of Bowdoin Fjord, adjacent to the marine‐terminating Bowdoin Glacier in northwestern Greenland, was conducted. The subglacial discharge of Fe‐rich meltwater induces a buoyancy‐driven upwelling plume in front of the glacier that entrains nutrient‐rich Arctic‐ and Atlantic‐origin waters. The plume water potentially carried 4.5–8.7 × 107 g day−1 of total dissolvable Fe out of Bowdoin Fjord in summer. The concentration of dissolved Fe (dFe) in the plume water (~15.6 nmol kg−1) was 4 times higher than that in the water in the outer part of the fjord (~3.8 nmol kg−1). The dFe:nitrate + nitrite ratio (mmol mol−1) in the plume water varied between 0.58 and 3.2, several orders of magnitude higher than the phytoplankton cellular Fe:nitrate ratio estimated using the hypothetical Fe:C ratio and observed particulate organic carbon:nitrate ratio of the fjord. Hence, the plume water is replete with Fe with respect to phytoplankton demands. Subglacial discharge drives the upwelling of Fe and macronutrients toward the euphotic zone, which is vital for the generation of summer phytoplankton growth in glacial fjords.
Applications and Limitations of Elastic Thermobarometry: Insights From Elastic Modeling of Inclusion‐Host Pairs and Example Case Studies
Authors: Cisneros M. , Befus K. S.
Published: September 2020

Elastic thermobarometry can be used to constrain the pressure and temperature conditions of mineral crystallization by exploiting the difference in the elastic evolution of a mineral inclusion and its host during cooling and decompression. In this work we examine the pressure‐temperature sensitivity of >5,000 untested inclusion‐host pairs. Hosts such as diamond and zircon are ideal host minerals because their low compressibility makes them rigid containment vessels. Highly compressible inclusions such as albite, graphite, and quartz serve as the most reliable barometers. We provide three case studies of inclusion‐host pairs from different geologic settings to demonstrate the advantages and challenges associated with these mineral pairs. Apatite inclusions in olivine from Yellowstone caldera mostly record negative residual pressures (tension) and suggest magmatic crystallization at ~0.4 GPa. Rutile inclusions in garnet from Verpeneset eclogites record near ambient conditions and do not recover reasonable metamorphic conditions of rutile entrapment. These results suggest that stiff inclusions may have a tensile strain limit, a possible limitation of elastic thermobarometry. Albite inclusions in epidote from a blueschist (Syros, Greece) record geologically reasonable entrapment pressures, but a large range of residual pressures that may be caused by the complex anisotropy of both phases. Our theoretical and applied results indicate that elastic thermobarometry has the potential to be used to understand petrologic processes in diverse geologic environments, including mantle, metamorphic, and magmatic settings but that each elastic thermobarometer requires careful evaluation.
Gravity Wave Source Spectra Appropriation for Mesosphere Lower Thermosphere Using Meteor Radar Observations and GROGRAT Model Simulations
Authors: Pramitha M. , Kumar K. Kishore , Ratnam M. Venkat , Praveen M. , Rao S. Vijaya Bhaskara
Published: September 2020

Meteor radar observations of gravity wave momentum fluxes (GWMFs) in the 82–94 km altitude region, which is a part of mesosphere lower thermosphere (MLT), are employed to identify the best fit gravity wave source spectrum using Gravity wave Regional or Global Ray Tracer (GROGRAT) model simulations over a low‐latitude location, Tirupati (13.63°N, 79.4°E). GROGRAT model is used to propagate a spectrum of gravity waves from the troposphere to the lower thermosphere. A total number of five gravity wave source spectra with various permutations and combinations are considered for the model simulations and by comparing the model simulated and radar observed gravity wave fields in the 82–94 km region, a best fit source spectrum is identified. The significance of the present study lies in appropriating the gravity wave source spectrum using meteor radar observations for the first time, which will have implications in improving gravity parameterization schemes in global models.
NOx Emissions Reduction and Rebound in China Due to the COVID‐19 Crisis
Authors: Ding J. , van der A R. J. , Eskes H. J. , Mijling B. , Stavrakou T. , van Geffen J. H. G. M. , Veefkind J. P.
Published: September 2020

During the COVID‐19 lockdown (24 January–20 March) in China low air pollution levels were reported in the media as a consequence of reduced economic and social activities. Quantification of the pollution reduction is not straightforward due to effects of transport, meteorology, and chemistry. We have analyzed the NOx emission reductions calculated with an inverse algorithm applied to daily NO2 observations from TROPOMI onboard the Copernicus Sentinel‐5P satellite. This method allows the quantification of emission reductions per city and the analysis of emissions of maritime transport and of the energy sector separately. The reductions we found are 20–50% for cities, about 40% for power plants, and 15–40% for maritime transport depending on the region. The reduction in both emissions and concentrations shows a similar timeline consisting of a sharp reduction (34–50%) around the Spring festival and a slow recovery from mid‐February to mid‐March.
Direct Assimilation of Radar Data With Ensemble Kalman Filter and Hybrid Ensemble‐Variational Method in the National Weather Service Operational Data Assimilation System GSI for the Stand‐Alone Regional FV3 Model at a Convection‐Allowing Resolution
Authors: Tong Chong‐Chi , Jung Youngsun , Xue Ming , Liu Chengsi
Published: September 2020

Capabilities to directly assimilate radar radial velocity (Vr) and reflectivity (Z) data are implemented within the operational GSI data assimilation (DA) framework and coupled with the new stand‐alone regional (SAR) FV3 model. The effectiveness and performance of 3DVar, EnKF, and hybrid En3DVar methods are evaluated with a storm cluster over the U.S. Central Plains at 3‐km grid spacing. During the DA cycles, 3DVar analyses show better fit to Z observations but fastest error growth, while EnKF and pure En3DVar lead to smaller forecast errors. For Vr, EnKF outperforms other methods in both analysis and forecast. Good correspondence with tornado reports is obtained by most experiments for probabilistic forecast of updraft helicity (UH), except for 3DVar which shows insufficient confidence in certain regions. Overall, EnKF and hybrid En3DVar show best forecast skills in terms of composite reflectivity and UH. Tests with more cases are needed to draw more general conclusions, however.
Predicting Magnetization Directions Using Convolutional Neural Networks
Authors: Nurindrawati Felicia , Sun Jiajia
Published: September 2020

Magnetic data have been widely used for understanding basin structures, mineral deposit systems, the formation history of various geological systems, and many others. Proper interpretation of magnetic data requires accurate knowledge of total magnetization directions of the source bodies in an area of study. Existing approaches for estimating magnetization directions involve either unstable data processing steps or computationally intensive processes such as 3‐D inversions. In this study, we developed a new method of automatically predicting the magnetization direction of a magnetic source body using convolutional neural networks (CNNs). CNNs have achieved great success in many other applications such as computer vision and seismic image interpretation but have not been used to extract parameters from magnetic data. We simulated many magnetic data maps with different magnetization directions from a synthetic source body, all subject to the same background field. Two CNNs were trained separately, one for predicting the inclination and the other for predicting declination. We determined the optimal CNN architectures for predicting inclinations and declinations by systematically comparing 13 different CNN architectures. In addition, we investigated the effect of having different parameters such as magnetization magnitude, source body shape, location, and depth on the performance of our predictive models. We also tested the method using field data from Black Hill Norite, Australia, and Yeshan region, China, for which prior research results are available for comparison. Our study shows that machine learning provides an effective means of automatically predicting magnetization directions based on magnetic data maps.
Benchmarking Component Analysis of Remanent Magnetization Curves With a Synthetic Mixture Series: Insight Into the Reliability of Unmixing Natural Samples
Authors: He Kuang , Zhao Xiangyu , Pan Yongxin , Zhao Xiang , Qin Huafeng , Zhang Tongwei
Published: September 2020

Geological samples often contain several magnetic components associated with different geological processes. Component analysis of remanent magnetization curves has been widely applied to decompose convoluted information. However, the reliability of commonly used methods is poorly assessed as independent verification is rarely available. For this purpose, we designed an experiment using a series of mixtures of two endmembers to benchmark unmixing methods for isothermal remanent magnetization (IRM) acquisition curves. First‐order reversal curves (FORC) diagrams were analyzed for comparison. It is demonstrated that the parametric method, which unmixes samples using specific probability distributions, may result in biased estimates. In contrast, an endmember‐based IRM unmixing approach yielded better quantitative results, which are comparable to the results obtained by FORC analysis based on principle component analysis (FORC‐PCA). We demonstrate that endmember‐based methods are in principle more suitable for unmixing a collection of samples with common endmembers; however, the level of decomposition will vary depending on the difference between the true endmembers that are associated with distinctive processes and the empirical endmembers used for unmixing. When it is desired to further decompose endmembers, the parametric unmixing approach remains a valuable means of inferring their underlying components. We illustrate that the results obtained by endmember‐based and parametric methods can be quantitatively combined to provide improved unmixing results at the level of parametric model distributions.
“Nice to Meet You”: A Quality Improvement Project to Increase Warm Handoffs
Authors: Germán Miguelina , Hsu-Walklet Teresa , Gurney Brittany A. , Parekh Jillian , Stein Berman Rachel , Herrick Jason , Briggs Rahil D. , Aviv Elizabeth C. , Faro Elissa Z.
Published: September 2020

Objective: Low rates of behavioral health (BH) engagement and poor follow-up can exacerbate youth mental health difficulties. Warm handoffs, when a primary care provider (PCP) introduces the patient to the BH care provider in an integrated setting, have been shown to improve the rate of BH follow-up appointments. This 1-year study describes a quality improvement (QI) project conducted at a large, urban pediatric primary care practice, with aims of (a) improving the percentage of warm handoffs performed for pediatric patients referred to behavioral health by 100% and (b) increasing the proportion of warm handoffs completed per primary care provider (PCP) for 60% of all PCPs. Methods: Using QI methods, a multidisciplinary team implemented tests of change via Plan-Do-Study-Act cycles (PDSAs) and completed a run chart of number of warm handoffs to assess performance. A balancing measure was used to determine impact of increased warm handoffs on behavioral health provider’s sessions. Results: The percentage of warm handoffs doubled compared to the baseline period (37% vs. 18%), and there were significant differences in follow-up rates between referred patients who received a warm handoff (73.1%) and those who did not (49.5%), regardless of whether the same BH provider conducted the warm handoff and follow-up visit, or whether two different BH providers were involved. Additionally, the number of warm handoffs per PCP increased for over 70% of total PCPs. Conclusions: This project demonstrated (a) the utility of using QI procedures to meet our aims and (b) the importance of warm handoffs in an integrated setting.

Implications for Impact Statement

This QI project focused on increasing warm handoffs in primary care because they improve behavioral health (BH) follow-up appointments. A warm handoff is a practice by which the primary care provider (PCP) introduces the patient to the BH care provider during the patient’s medical visit. Using QI methods, this project increased the percentage of warm handoffs received among referred pediatric patients to BH by over 100% and increased the proportion of warm handoffs completed per PCP for at least 60% of PCPs. Increasing warm handoffs to BH providers should be considered a best practice to help address the potentially chronic effects of untreated childhood mental health disorders.
Pediatric Integrated Primary Care as the Foundation for Healthy Development Across the Lifespan
Authors: McCabe Mary Ann , Leslie Laurel , Counts Nathaniel , Tynan William D.
Published: September 2020

Objective: Pediatric Integrated Primary Care (IPC) plays a unique and foundational role in prevention of behavioral health disorders and promotion of healthy development and positive health behaviors across the life span. Early intervention can mitigate the impact of social determinants of health (including adverse childhood experiences) and promote health equity. Yet to realize this potential for health promotion and prevention, it will be necessary for pediatric integrated primary care to shift focus upstream—ensuring a 2-generation approach (e.g., parenting programs, screening for maternal depression) and enabling effective collaboration with other sectors in communities that impact children and families (e.g., home visiting programs, schools). This will pose challenges for sharing desired outcomes and data and reconceptualizing returns on investment across sectors. Other policy changes will also be necessary, including payment reforms (e.g., value-based payment models), interprofessional training, and increased funding for IPC research in pediatrics. It will be necessary to educate policymakers that health promotion and prevention in pediatric IPC results in improved health and savings into adulthood. Conclusion: Pediatric psychology can play a leadership role in realizing the potential for pediatric IPC.

Implications for Impact Statement

Advances in a few key policy areas will enable pediatric integrated primary care to serve its unique and nearly universal function—promoting healthy development and preventing behavioral health conditions for better health and wellbeing throughout life.
Things must not fall apart: the ripple effects of the COVID-19 pandemic on children in sub-Saharan Africa
Authors: Coker Modupe , Folayan Morenike O. , Michelow Ian C. , Oladokun Regina E. , Torbunde Nguavese , Sam-Agudu Nadia A.
Published: September 2020

Zero to 19 year-old children in sub-Saharan Africa bear a disproportionate proportion of the global burden of communicable and non-communicable diseases. Significant public health gains have been made in the fight against these diseases, however, factors such as underequipped health systems, disease outbreaks, conflict, and political instability continue to challenge prevention and control. The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduces new challenges to public health programs in sub-Saharan Africa. Of particular concern are programs targeting major conditions among children, such as undernutrition, vaccine-preventable pneumonia and diarrhea, malaria, tuberculosis, HIV, and sickle cell disease. This article focuses on the impact of the COVID-19 pandemic on child health in sub-Saharan Africa. We review the epidemiology of major pediatric diseases and, referencing modeling projections, discuss the short- and long-term impact of the pandemic on major disease control. We deliberate on potential complications of SARS-CoV-2 co-infections/co-morbidities and identify critical social and ethical issues. Furthermore, we highlight the paucity of COVID-19 data and clinical trials in this region and the lack of child participants in ongoing studies. Lastly, approaches and interventions to mitigate the pandemic’s impact on child health outcomes are discussed.

Impact

Children in sub-Saharan Africa bear a disproportionate burden of communicable and non-communicable diseases globally; this remains true even as the COVID-19 pandemic persists.

Amidst the fast-expanding COVID-19 literature, there is little comprehensive coverage of the pandemic’s indirect impact on child health in sub-Saharan Africa.

This article comprehensively outlines the threat that the pandemic poses to major disease prevention and control for children in sub-Saharan Africa. It discusses the potential impact of SARS-CoV-2 co-infections/co-morbidities, highlights research gaps, and advocates for data and action to mitigate the ripple effects of the pandemic on this population.
Achieving similar root microbiota composition in neighbouring plants through airborne signalling
Authors: Kong Hyun Gi , Song Geun Cheol , Sim Hee-Jung , Ryu Choong-Min
Published: September 2020

The ability to recognize and respond to environmental signals is essential for plants. In response to environmental changes, the status of a plant is transmitted to other plants in the form of signals such as volatiles. Root-associated bacteria trigger the release of plant volatile organic compounds (VOCs). However, the impact of VOCs on the rhizosphere microbial community of neighbouring plants is not well understood. Here, we investigated the effect of VOCs on the rhizosphere microbial community of tomato plants inoculated with a plant growth-promoting rhizobacterium Bacillus amyloliquefaciens strain GB03 and that of their neighbouring plants. Interestingly, high similarity (up to 69%) was detected in the rhizosphere microbial communities of the inoculated and neighbouring plants. Leaves of the tomato plant treated with strain GB03-released β-caryophyllene as a signature VOC, which elicited the release of a large amount of salicylic acid (SA) in the root exudates of a neighbouring tomato seedling. The exposure of tomato leaves to β-caryophyllene resulted in the secretion of SA from the root. Our results demonstrate for the first time that the composition of the rhizosphere microbiota in surrounding plants is synchronized through aerial signals from plants.
Antibiotic use and risk of colorectal cancer: a systematic review and dose–response meta-analysis
Authors: Simin Johanna , Fornes Romina , Liu Qing , Olsen Renate Slind , Callens Steven , Engstrand Lars , Brusselaers Nele
Published: September 2020

Background

It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present.

Design

Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose–response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models.

Results

Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05–1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26–2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93–1.32). The dose–response analysis did not provide strong evidence of any particular dose–response association, and the risk patterns were rather similar for colon and rectal cancer.

Discussion

The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug–microbiome interactions.
PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers
Authors: Liu Rui , Chen Youwen , Liu Guangzhi , Li Chenxi , Song Yurong , Cao Zhiwen , Li Wen , Hu Jinghong , Lu Cheng , Liu Yuanyan
Published: September 2020

Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.
Cells of the adult human heart
Authors: Litviňuková Monika , Talavera-López Carlos , Maatz Henrike , Reichart Daniel , Worth Catherine L. , Lindberg Eric L. , Kanda Masatoshi , Polanski Krzysztof , Heinig Matthias , Lee Michael , Nadelmann Emily R. , Roberts Kenny , Tuck Liz , Fasouli Eirini S. , DeLaughter Daniel M. , McDonough Barbara , Wakimoto Hiroko , Gorham Joshua M. , Samari Sara , Mahbubani Krishnaa T. , Saeb-Parsy Kourosh , Patone Giannino , Boyle Joseph J. , Zhang Hongbo , Zhang Hao , Viveiros Anissa , Oudit Gavin Y. , Bayraktar Omer Ali , Seidman J. G. , Seidman Christine E. , Noseda Michela , Hubner Norbert , Teichmann Sarah A.
Published: September 2020

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.
P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
Authors: Wisniewski Laura , French Vanessa , Lockwood Nicola , Valdivia Leonardo E. , Frankel Paul
Published: September 2020

P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We characterise here a novel deletion model of P130CAS in zebrafish. Using in vivo microscopy and transgenic vascular reporters, we observed that while bcar1−/− zebrafish showed no arterial angiogenic or heart defects during development, they strikingly failed to form the caudal vein plexus (CVP). Endothelial cells (ECs) within the CVP of bcar1−/− embryos produced fewer filopodial structures and did not detach efficiently from neighbouring cells, resulting in a significant reduction in ventral extension and overall CVP area. Mechanistically, we show that P130Cas mediates Bmp2b-induced ectopic angiogenic sprouting of ECs in the developing embryo and provide pharmacological evidence for a role of Src family kinases in CVP development.
Inhibition of enteric methanogenesis in dairy cows induces changes in plasma metabolome highlighting metabolic shifts and potential markers of emission
Authors: Yanibada Bénédict , Hohenester Ulli , Pétéra Mélanie , Canlet Cécile , Durand Stéphanie , Jourdan Fabien , Boccard Julien , Martin Cécile , Eugène Maguy , Morgavi Diego P. , Boudra Hamid
Published: September 2020

There is scarce information on whether inhibition of rumen methanogenesis induces metabolic changes on the host ruminant. Understanding these possible changes is important for the acceptance of methane-reducing practices by producers. In this study we explored the changes in plasma profiles associated with the reduction of methane emissions. Plasma samples were collected from lactating primiparous Holstein cows fed the same diet with (Treated, n = 12) or without (Control, n = 13) an anti-methanogenic feed additive for six weeks. Daily methane emissions (CH4, g/d) were reduced by 23% in the Treated group with no changes in milk production, feed intake, body weight, and biochemical indicators of health status. Plasma metabolome analyses were performed using untargeted [nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC–MS)] and targeted (LC–MS/MS) approaches. We identified 48 discriminant metabolites. Some metabolites mainly of microbial origin such as dimethylsulfone, formic acid and metabolites containing methylated groups like stachydrine, can be related to rumen methanogenesis and can potentially be used as markers. The other discriminant metabolites are produced by the host or have a mixed microbial-host origin. These metabolites, which increased in treated cows, belong to general pathways of amino acids and energy metabolism suggesting a systemic non-negative effect on the animal.
Functional analysis of sandstone ground stone tools: arguments for a qualitative and quantitative synergetic approach
Authors: Zupancich Andrea , Cristiani Emanuela
Published: September 2020

In the last few years, the application of quantitative methods in the field of use wear analysis has grown considerably, involving the use of different techniques. A development in surface measurements approaches has become necessary as standard assessments based upon qualitative functional analysis are often affected by a degree of subjectivity and a limited reproducibility. To advance the current methodological debate on functional analysis of ground stone technology, we present a combined methodological approach, including qualitative and quantitative analyses, applied to the study of experimental sandstone ground stone tools. We test surface quantification at a macro and micro-scale, paired with the observation and description of residue and use wear connected to the processing of plant, animal and mineral matters. Our results provide an exhaustive quantitative dataset concerning surface modifications associated with different uses and suggest an analytical workflow for the functional analysis of both experimental and archaeological ground stone assemblages. We also highlight the limitation and pitfalls of an exclusive adoption of quantitative methods in the study of ancient tool use demonstrating how a synergetic approach can enhance the quality, reproducibility and comparability of functional data.
Publisher Correction: 3D Magnetic Resonance Spirometry
Authors: Boucneau Tanguy , Fernandez Brice , Larson Peder , Darrasse Luc , Maître Xavier
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Connectivity and population structure of albacore tuna across southeast Atlantic and southwest Indian Oceans inferred from multidisciplinary methodology
Authors: Nikolic Natacha , Montes Iratxe , Lalire Maxime , Puech Alexis , Bodin Nathalie , Arnaud-Haond Sophie , Kerwath Sven , Corse Emmanuel , Gaspar Philippe , Hollanda Stéphanie , Bourjea Jérôme , West Wendy , Bonhommeau Sylvain
Published: September 2020

Albacore tuna (Thunnus alalunga) is an important target of tuna fisheries in the Atlantic and Indian Oceans. The commercial catch of albacore is the highest globally among all temperate tuna species, contributing around 6% in weight to global tuna catches over the last decade. The accurate assessment and management of this heavily exploited resource requires a robust understanding of the species’ biology and of the pattern of connectivity among oceanic regions, yet Indian Ocean albacore population dynamics remain poorly understood and its level of connectivity with the Atlantic Ocean population is uncertain. We analysed morphometrics and genetics of albacore (n = 1,874) in the southwest Indian (SWIO) and southeast Atlantic (SEAO) Oceans to investigate the connectivity and population structure. Furthermore, we examined the species’ dispersal potential by modelling particle drift through major oceanographic features. Males appear larger than females, except in South African waters, yet the length–weight relationship only showed significant male–female difference in one region (east of Madagascar and Reunion waters). The present study produced a genetic differentiation between the southeast Atlantic and southwest Indian Oceans, supporting their demographic independence. The particle drift models suggested dispersal potential of early life stages from SWIO to SEAO and adult or sub-adult migration from SEAO to SWIO.
Active open-loop control of elastic turbulence
Authors: van Buel Reinier , Stark Holger
Published: September 2020

We demonstrate through numerical solutions of the Oldroyd-B model in a two-dimensional Taylor–Couette geometry that the onset of elastic turbulence in a viscoelastic fluid can be controlled by imposed shear-rate modulations, one form of active open-loop control. Slow modulations display rich and complex behavior where elastic turbulence is still present, while it vanishes for fast modulations and a laminar response with the Taylor–Couette base flow is recovered. We find that the transition from the laminar to the turbulent state is supercritical and occurs at a critical Deborah number. In the state diagram of both control parameters, Weissenberg versus Deborah number, we identify the region of elastic turbulence. We also quantify the transition by the flow resistance, for which we derive an analytic expression in the laminar regime within the linear Oldroyd-B model. Finally, we provide an approximation for the transition line in the state diagram introducing an effective critical Weissenberg number in comparison to constant shear. Deviations from the numerical result indicate that the physics behind the observed laminar-to-turbulent transition is more complex under time-modulated shear flow.
Caries severity and socioeconomic inequalities in a nationwide setting: data from the Italian National pathfinder in 12-years children
Authors: Campus Guglielmo , Cocco Fabio , Strohmenger Laura , Cagetti Maria Grazia
Published: September 2020

This study presents the result of the second National pathfinder conducted in Italy on children’s oral health, reporting the prevalence and severity of caries in 12-year old children and describing the caries figure related to the socioeconomic inequalities, both at individual level and macroeconomic level. The two-digit codes related to ICDAS (International Caries Detection and Assessment System) for each tooth and the gingival bleeding score were recorded at school on 7,064 children (48.97% males and 51.03% females). The Gross National Product (GNP) per capita, the Gini Index and Unemployment rate in each Italian section, parents’ educational levels, working status, smoking habit and their ethnic background were recorded. Zero-inflated-negative-binomial (ZINB) models were run, using caries-free teeth, teeth with enamel lesions, cavitated lesions and restorations as functions of socioeconomic explanatory variables, to evaluate the effects of justifiable economic factors of geographical distribution. The mean number of enamel lesions, cavitated lesions and filled per teeth were statistically significant (p < 0.01) dissimilar among the Italian section. GNP per capita, Gini Index and Unemployment rate were significantly correlated to ICDAS scores and filled teeth. Important differences in ICDAS score values remain among children from different socioeconomic backgrounds. Efforts should be made to improve awareness and knowledge regarding oral health practice and to implement preventive programs and access to dental services in Southern Italy where the disease is still unresolved.
The neuropathic phenotype of the K/BxN transgenic mouse with spontaneous arthritis: pain, nerve sprouting and joint remodeling
Authors: Gonçalves dos Santos Gilson , Jimenéz-Andrade Juan Miguel , Woller Sarah A. , Muñoz-Islas Enriqueta , Ramírez-Rosas Martha Beatriz , Ohashi Nobuko , Ferreira Catroli Glaucilene , Fujita Yuya , Yaksh Tony L. , Corr Maripat
Published: September 2020

The adult K/BxN transgenic mouse develops spontaneous autoimmune arthritis with joint remodeling and profound bone loss. We report that both males and females display a severe sustained tactile allodynia which is reduced by gabapentin but not the potent cyclooxygenase inhibitor ketorolac. In dorsal horn, males and females show increased GFAP+ astrocytic cells; however, only males demonstrate an increase in Iba1+ microglia. In dorsal root ganglia (DRG), there is an increase in CGRP+, TH+, and Iba1+ (macrophage) labeling, but no increase in ATF3+ cells. At the ankle there is increased CGRP+, TH+, and GAP-43+ fiber synovial innervation. Thus, based on the changes in dorsal horn, DRG and peripheral innervation, we suggest that the adult K/BxN transgenic arthritic mice display a neuropathic phenotype, an assertion consistent with the analgesic pharmacology seen in this animal. These results indicate the relevance of this model to our understanding of the nociceptive processing which underlies the chronic pain state that evolves secondary to persistent joint inflammation.
Asymmetry induced suppression of chaos
Authors: Biswas Animesh , Chaurasia Sudhanshu Shekhar , Parmananda P. , Sinha Sudeshna
Published: September 2020

We explore the dynamics of a group of unconnected chaotic relaxation oscillators realized by mercury beating heart systems, coupled to a markedly different common external chaotic system realized by an electronic circuit. Counter-intuitively, we find that this single dissimilar chaotic oscillator manages to effectively steer the group of oscillators on to steady states, when the coupling is sufficiently strong. We further verify this unusual observation in numerical simulations of model relaxation oscillator systems mimicking this interaction through coupled differential equations. Interestingly, the ensemble of oscillators is suppressed most efficiently when coupled to a completely dissimilar chaotic external system, rather than to a regular external system or an external system identical to those of the group. So this experimentally demonstrable controllability of groups of oscillators via a distinct external system indicates a potent control strategy. It also illustrates the general principle that symmetry in the emergent dynamics may arise from asymmetry in the constituent systems, suggesting that diversity or heterogeneity may have a crucial role in aiding regularity in interactive systems.
Honey-inspired antimicrobial hydrogels resist bacterial colonization through twin synergistic mechanisms
Authors: Zhang Tiffany , Qu Yue , Gunatillake Pathiraja A. , Cass Peter , Locock Katherine E. S. , Blackman Lewis D.
Published: September 2020

Inspired by the interesting natural antimicrobial properties of honey, biohybrid composite materials containing a low-fouling polymer hydrogel network and an encapsulated antimicrobial peroxide-producing enzyme have been developed. These synergistically combine both passive and active mechanisms for reducing microbial bacterial colonization. The mechanical properties of these materials were assessed using compressive mechanical analysis, which revealed these hydrogels possessed tunable mechanical properties with Young’s moduli ranging from 5 to 500 kPa. The long-term enzymatic activities of these materials were also assessed over a 1-month period using colorimetric assays. Finally, the passive low-fouling properties and active antimicrobial activity against a leading opportunistic pathogen, Staphylococcus epidermidis, were confirmed using bacterial cell counting and bacterial adhesion assays. This study resulted in non-adhesive substrate-permeable antimicrobial materials, which could reduce the viability of planktonic bacteria by greater than 7 logs. It is envisaged these new biohybrid materials will be important for reducing bacterial adherence in a range of industrial applications.
In vivo 31P magnetic resonance spectroscopy study of mouse cerebral NAD content and redox state during neurodevelopment
Authors: Skupienski Radek , Do Kim Q. , Xin Lijing
Published: September 2020

Nicotinamide adenine dinucleotide (NAD) is an important cofactor of energy-producing pathways. The redox ratio (NAD+/NADH) reflects the cellular oxidoreductive state. Oxidative stress and redox dysregulation have been suggested to contribute to various neurological diseases. The assessment of NAD content has been recently demonstrated in large animals and human brains by 31P magnetic resonance spectroscopy. However, its measurement in small rodents has never been attempted. The purpose of this study was to investigate, in vivo, the NAD content during mouse brain neurodevelopment. 31P-MR-spectra were acquired in the mouse brain at postnatal days P20, P40, P90 and P250 at 14.1 T using a 3D-localization sequence. High spectral quality was achieved at 14.1 T. NAD+ and NADH were quantified with mean Cramér-Rao lower bound of 10% and 14%, respectively. An increase in NAD+/NADH was observed from P20 to P250 due to a decrease in [NADH]. The intracellular pH was significantly reduced with age, while the free [Mg2+] in the brain was significantly increased. This study demonstrates for the first time the feasibility of the measurement of NAD content in vivo in mouse brains during development, which opens the prospect of longitudinally studying energy metabolism and redox dysfunction in mouse models of brain pathology.
Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST
Authors: Chekli Yankel , Peron-Cane Caroline , Dell’Arciprete Dario , Allemand Jean-François , Li Chenge , Ghigo Jean-Marc , Gautier Arnaud , Lebreton Alice , Desprat Nicolas , Beloin Christophe
Published: September 2020

Bacterial proteins exported to the cell surface play key cellular functions. However, despite the interest to study the localisation of surface proteins such as adhesins, transporters or hydrolases, monitoring their dynamics in live imaging remains challenging, due to the limited availability of fluorescent probes remaining functional after secretion. In this work, we used the Escherichia coli intimin and the Listeria monocytogenes InlB invasin as surface exposed scaffolds fused with the recently developed chemogenetic fluorescent reporter protein FAST. Using both membrane permeant (HBR-3,5DM) and non-permeant (HBRAA-3E) fluorogens that fluoresce upon binding to FAST, we demonstrated that fully functional FAST can be exposed at the cell surface and used to specifically tag the external side of the bacterial envelop in both diderm and monoderm bacteria. Our work opens new avenues to study the organization and dynamics of the bacterial cell surface proteins.