bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordance of children’s intake of selected food groups as reported by parents via 24-h dietary recall and ecological momentary assessment
Authors: Loth Katie A , Fertig Angela , Trofholz Amanda , Harnack Lisa , Crosby Ross , Neumark-Sztainer Dianne , Berge Jerica M
Published: June 2020

Objective:

To understand how dietary intake data collected via a brief ecological momentary assessment (EMA) measure compares to that of data collected via interviewer-administered 24-h dietary recalls, and explore differences in level of concordance between these two assessment types by individual- and meal-level characteristics.

Design:

Parents completed three 24-h dietary recalls and 8 d of brief EMA surveys on behalf of their child; in total, there were 185 d where dietary intake data from both EMA and 24-h recall were available. The EMA measure asked parents to indicate whether (yes/no) their child had consumed any of the nine total food items (e.g. fruit, vegetable, etc.) at eating occasions where both the child and parent were present.

Setting:

Twenty-four-hour dietary recalls were completed in person in the study participant’s home; participants completed EMA surveys using a study provided in iPad or their personal cell phone.

Participants:

A diverse, population-based sample of parent–child dyads (n 150).

Results:

Among meals reported in both the EMA and dietary recalls, concordance of reporting of specific types of food ranged from moderate agreement for meat (kappa = 0·55); fair agreement for sweets (kappa = 0·38), beans/nuts (kappa = 0·37), dairy (kappa = 0·31), fruit (kappa = 0·31) and vegetables (kappa = 0·27); and little to no agreement for refined grains, whole grains and sweetened beverages (73 % overall agreement; kappa = 0·14). Concordance of reporting was highest for breakfast and snacks, as compared with other eating occasions. Higher concordance was observed between the two measures if the meal occurred at home.

Conclusions:

Data suggest that among meals reported in both the EMA and dietary recalls, concordance in reporting was reasonably good for some types of food but only fair or poor for others.
Brazilian immigrant fathers’ perspectives on child’s eating and feeding practices: a qualitative study conducted in the United States
Authors: Lindsay Ana Cristina , Vianna Gabriela Vasconcellos de Barros , Arruda Carlos André Moura , Alves Amanda De Sá Melo , Hasselmann Maria Helena , Machado Márcia MT , Greaney Mary L
Published: June 2020

Objectives:

Brazilians comprise a rapidly growing immigrant Latino group in the USA, yet little research has focused on health issues affecting Brazilian children in immigrant families. As increasing evidence is documenting fathers’ influential role in their children’s eating behaviours and ultimately weight status, the current study sought to explore the Brazilian immigrant fathers’ perspectives and practices related to child’s feeding practices and their preschool-aged children’s eating.

Design:

Qualitative study using in-depth, semi-structured interviews. Interviews were conducted in Portuguese by native Brazilian research staff using a semi-structured interview guide. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed thematically using a hybrid approach that incorporated deductive and inductive analytical approaches.

Setting:

Massachusetts.

Participants:

Twenty-one Brazilian immigrant fathers who had at least one child aged 2–5 years.

Results:

Results revealed fathers’ awareness of the importance of healthy eating for their children, their influence as role models and their involvement in feeding routines of their preschool-aged children. Moreover, fathers were receptive to participating in family interventions to promote their children’s healthy eating. Nearly all fathers reported wanting to learn more and to do ‘what’s right’ for their children.

Conclusions:

The current study provides new information about Brazilian immigrant fathers’ views about factors influencing their children’s healthy eating behaviours and paternal feeding practices. Future research should quantify fathers’ feeding styles and practices and solicit fathers’ input in the design of culturally appropriate family interventions targeting the home environment of preschool-aged children of Brazilian immigrant families.
When Do Voters Sanction Corrupt Politicians?
Authors: Klašnja Marko , Lupu Noam , Tucker Joshua A.
Published: June 2020

A growing body of research explores the factors that affect when corrupt politicians are held accountable by voters. Most studies, however, focus on one or few factors in isolation, leaving incomplete our understanding of whether they condition each other. To address this, we embedded rich conjoint candidate choice experiments into surveys in Argentina, Chile, and Uruguay. We test the importance of two contextual factors thought to mitigate voters’ punishment of corrupt politicians: how widespread corruption is and whether it brings side benefits. Like other scholars, we find that corruption decreases candidate support substantially. But, we also find that information that corruption is widespread does not lessen the sanction applied against corruption, whereas information about the side benefits from corruption does, and does so to a similar degree as the mitigating role of permissible attitudes toward bribery. Moreover, those who stand to gain from these side benefits are less likely to sanction corruption.
Rewetting Offers Rapid Climate Benefits for Tropical and Agricultural Peatlands But Not for Forestry‐Drained Peatlands
Authors: Ojanen Paavo , Minkkinen Kari
Published: June 2020

Peat soils drained for agriculture and forestry are important sources of carbon dioxide and nitrous oxide. Rewetting effectively reduces these emissions. However, rewetting also increases methane emissions from the soil and, on forestry‐drained peatlands, decreases the carbon storage of trees. To analyze the effect of peatland rewetting on the climate, we built radiative forcing scenarios for tropical peat soils, temperate and boreal agricultural peat soils, and temperate and boreal forestry‐drained peat soils. The effect of tree and wood product carbon storage in boreal forestry‐drained peatlands was also estimated as a case study for Finland. Rewetting of tropical peat soils resulted in immediate cooling. In temperate and boreal agricultural peat soils, the warming effect of methane emissions offsets a major part of the cooling for the first decades after rewetting. In temperate and boreal forestry‐drained peat soils, the effect of rewetting was mostly warming for the first decades. In addition, the decrease in tree and wood product carbon storage further delayed the onset of the cooling effect for decades. Global rewetting resulted in increasing climate cooling, reaching −70 mW (m2 Earth)−1 in 100 years. Tropical peat soils (9.6 million ha) accounted for approximately two thirds and temperate and boreal agricultural peat soils (13.0 million ha) for one third of the cooling. Forestry‐drained peat soils (10.6 million ha) had a negligible effect. We conclude that peatland rewetting is beneficial and important for mitigating climate change, but abandoning tree stands may instead be the best option concerning forestry‐drained peatlands.
A Kalman Filter Time Series Analysis Method for InSAR
Authors: Dalaison M. , Jolivet R.
Published: June 2020

Earth orbiting satellites, such as Sentinel 1A‐B, build up an ever‐growing set of synthetic aperture radar images of the ground. This conceptually allows for real‐time monitoring of ground displacements using Interferometric Synthetic Aperture Radar (InSAR), notably in tectonically active regions such as fault zones or over volcanoes. We propose a Kalman filter for InSAR time series analysis (KFTS), an efficient method to rapidly update preexisting time series of displacement with data as they are made available, with limited computational cost. KFTS solves together for the evolution of phase change with time and for a parametrized model of ground deformation. Synthetic tests of the KFTS reveal exact agreement with the equivalent weighted least squares solution and a convergence of descriptive model parameter after the assimilation of about 1 year of data. We include the impact of sudden deformation events such as earthquakes or slow slip events on the time series of displacement. First tests of the KFTS on ENVISAT data over Mt. Etna (Sicily) and Sentinel 1 data around the Chaman fault (Afghanistan, Pakistan) show precise (±0.05 mm) retrieval of phase change when data are sufficient. Otherwise, the optimized parametrized model is used to forecast phase change. Good agreement is found with classic time series analysis solution and GPS‐derived time series. Accurate estimates are conditioned to the proper parametrization of errors so that models and observations can be combined with their respective uncertainties. This new tool is freely available to process ongoing InSAR time series.
Lifting the Veil on Martian Dust Storms
Authors: M��tt�nen Anni , Newman Claire
Published: June 2020

A special collection in JGR Planets presents insights from a long-awaited global dust storm on Mars in 2018 that was closely scrutinized by five orbiting and two landed spacecraft.
Why Did Great Apes Disappear from Southwestern China?
Authors: Stanley Sarah
Published: June 2020

Periodic pulses of cooler temperatures may have disrupted the warm, humid, late Miocene climate that sustained the region’s great apes long after most species disappeared elsewhere.
Uranium Isotope Fractionation in Non‐sulfidic Anoxic Settings and the Global Uranium Isotope Mass Balance
Authors: Cole Devon B. , Planavsky Noah J. , Longley Martha , Böning Philipp , Wilkes Daniel , Wang Xiangli , Swanner Elizabeth D. , Wittkop Chad , Loydell David K. , Busigny Vincent , Knudsen Andrew C. , Sperling Erik A.
Published: June 2020

Uranium isotopes (238U/235U) have been used widely over the last decade as a global proxy for marine redox conditions. The largest isotopic fractionations in the system occur during U reduction, removal, and burial. Applying this basic framework, global U isotope mass balance models have been used to predict the extent of ocean floor anoxia during key intervals throughout Earth's history. However, there are currently minimal constraints on the isotopic fractionation that occurs during reduction and burial in anoxic and iron‐rich (ferruginous) aquatic systems, despite the consensus that ferruginous conditions are thought to have been widespread through the majority of our planet's history. Here we provide the first exploration of δ238U values in natural ferruginous settings. We measured δ238U in sediments from two modern ferruginous lakes (Brownie Lake and Lake Pavin), the water column of Brownie Lake, and sedimentary rocks from the Silurian‐Devonian boundary that were deposited under ferruginous conditions. Additionally, we provide new δ238U data from core top sediments from anoxic but nonsulfidic settings in the Peru Margin oxygen minimum zone. We find that δ238U values from sediments deposited in all of these localities are highly variable but on average are indistinguishable from adjacent oxic sediments. This forces a reevaluation of the global U isotope mass balance and how U isotope values are used to reconstruct the evolution of the marine redox landscape.
Antarctic Ozone Enhancement During the 2019 Sudden Stratospheric Warming Event
Authors: Safieddine Sarah , Bouillon Marie , Paracho Ana‐Claudia , Jumelet Julien , Tencé Florent , Pazmino Andrea , Goutail Florence , Wespes Catherine , Bekki Slimane , Boynard Anne , Hadji‐Lazaro Juliette , Coheur Pierre‐François , Hurtmans Daniel , Clerbaux Cathy
Published: June 2020

We analyze the 2019 sudden stratospheric warming event that occurred in the Southern Hemisphere through its impact on the Antarctic ozone. Using temperature, ozone, and nitric acid data from the Infrared Atmospheric Sounding Interferometer (IASI), our results show that the average increase in stratospheric temperature reached a maximum of 34.4° on 20 September in the [60–90]°S latitude range when compared to the past 3 years. Dynamical parameters suggest a locally reversed and weakened zonal winds and a shift in the location of the polar jet vortex. This led to air masses mixing, to a reduced polar stratospheric clouds formation detected at a ground station, and as such to lower ozone and nitric acid depletion. 2019 total ozone columns for the months of September, October, and November were on average higher by 29%, 28%, and 26%, respectively, when compared to the 11‐year average of the same months.
Large‐Scale Industrial Cloud Perturbations Confirm Bidirectional Cloud Water Responses to Anthropogenic Aerosols
Authors: Trofimov Heido , Bellouin Nicolas , Toll Velle
Published: June 2020

Aerosols offset a poorly quantified fraction of anthropogenic greenhouse gas warming, and the aerosol impact on clouds is the most uncertain mechanism of anthropogenic climate forcing. Here observations of a relatively weak average response of liquid cloud water to aerosol perturbations are extended to much larger areas than in previous studies, with the polluted cloud areas covering hundreds by hundreds of kilometers. Polluted clouds detected in satellite images at the global anthropogenic air pollution hot spot of Norilsk, Russia, and at other various major aerosol source regions show close compensation between aerosol‐induced cloud water increases and decreases. In the sampled Norilsk cloud perturbations the decrease in liquid water path offsets 3% of the radiative forcing through the Twomey effect on average. Weak cloud water response on average in large polluted areas is in very good agreement with previous results based on observations of small‐scale ship‐track‐like industrial cloud perturbations, helping to reduce the uncertainty associated with the anthropogenic aerosol impacts on clouds.
Geomagnetically Induced Current Model Validation From New Zealand's South Island
Authors: Divett T. , Mac Manus D. H. , Richardson G. S. , Beggan C. D. , Rodger C. J. , Ingham M. , Clarke E. , Thomson A. W. P. , Dalzell M. , Obana Y.
Published: June 2020

Geomagnetically induced currents (GICs) during a space weather event have previously caused transformer damage in New Zealand. During the 2015 St. Patrick's Day Storm, Transpower NZ Ltd has reliable GIC measurements at 23 different transformers across New Zealand's South Island. These observed GICs show large variability, spatially and within a substation. We compare these GICs with those calculated from a modeled geolectric field using a network model of the transmission network with industry‐provided line, earthing, and transformer resistances. We calculate the modeled geoelectric field from the spectra of magnetic field variations interpolated from measurements during this storm and ground conductance using a thin‐sheet model. Modeled and observed GIC spectra are similar, and coherence exceeds the 95% confidence threshold, for most valid frequencies at 18 of the 23 transformers. Sensitivity analysis shows that modeled GICs are most sensitive to variation in magnetic field input, followed by the variation in land conductivity. The assumption that transmission lines follow straight lines or getting the network resistances exactly right is less significant. Comparing modeled and measured GIC time series highlights that this modeling approach is useful for reconstructing the timing, duration, and relative magnitude of GIC peaks during sudden commencement and substorms. However, the model significantly underestimates the magnitude of these peaks, even for a transformer with good spectral match. This is because of the limited range of frequencies for which the thin‐sheet model is valid and severely limits the usefulness of this modeling approach for accurate prediction of peak GICs.
Precision weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis
Authors: Haarsma J. , Fletcher P. C. , Griffin J. D. , Taverne H. J. , Ziauddeen H. , Spencer T. J. , Miller C. , Katthagen T. , Goodyer I. , Diederen K. M. J. , Murray G. K.
Published: June 2020

Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
New insights into the distributions of nitrogen fixation and diazotrophs revealed by high-resolution sensing and sampling methods
Authors: Tang Weiyi , Cerdán-García Elena , Berthelot Hugo , Polyviou Despo , Wang Seaver , Baylay Alison , Whitby Hannah , Planquette Hélène , Mowlem Matthew , Robidart Julie , Cassar Nicolas
Published: June 2020

Nitrogen availability limits marine productivity across large ocean regions. Diazotrophs can supply new nitrogen to the marine environment via nitrogen (N2) fixation, relieving nitrogen limitation. The distributions of diazotrophs and N2 fixation have been hypothesized to be generally controlled by temperature, phosphorus, and iron availability in the global ocean. However, even in the North Atlantic where most research on diazotrophs and N2 fixation has taken place, environmental controls remain contentious. Here we measure diazotroph composition, abundance, and activity at high resolution using newly developed underway sampling and sensing techniques. We capture a diazotrophic community shift from Trichodesmium to UCYN-A between the oligotrophic, warm (25–29 °C) Sargasso Sea and relatively nutrient-enriched, cold (13–24 °C) subpolar and eastern American coastal waters. Meanwhile, N2 fixation rates measured in this study are among the highest ever recorded globally and show significant increase with phosphorus availability across the transition from the Gulf Stream into subpolar and coastal waters despite colder temperatures and higher nitrate concentrations. Transcriptional patterns in both Trichodesmium and UCYN-A indicate phosphorus stress in the subtropical gyre. Over this iron-replete transect spanning the western North Atlantic, our results suggest that temperature is the major factor controlling the diazotrophic community structure while phosphorous drives N2 fixation rates. Overall, the occurrence of record-high UCYN-A abundance and peak N2 fixation rates in the cold coastal region where nitrate concentrations are highest (~200 nM) challenges current paradigms on what drives the distribution of diazotrophs and N2 fixation.
Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins
Authors: Yang Yushan , Ma Lulu , Xu Yiming , Liu Yun , Li Wenya , Cai Jianchun , Zhang Yiyao
Published: June 2020

5-Fluorouracil (5-FU) is one of the most effective drugs for the treatment of colorectal cancer (CRC). However, there is an urgent need in reducing its systemic side effects and chemoresistance to make 5-FU-based chemotherapy more effective and less toxic in the treatment of CRC. Here, enalapril, a clinically widely used antihypertensive and anti-heart failure drug, has been verified as a chemosensitizer that extremely improves the sensitivity of CRC cells to 5-FU. Enalapril greatly augmented the cytotoxicity of 5-FU on the cell growth in both established and primary CRC cells. The combination of enalapril and 5-FU synergistically suppressed the cell migration and invasion in both 5-FU-sensitive and -resistant CRC cells in vitro, and inhibited angiogenesis, tumor growth, and metastasis of 5-FU-resistant CRC cells in vivo without increased systemic toxicity at concentrations that were ineffective as individual agents. Furthermore, combined treatment cooperatively inhibited NF-κB/STAT3 signaling pathway and subsequently reduced the expression levels of NF-κB/STAT3-regulated proteins (c-Myc, Cyclin D1, MMP-9, MMP-2, VEGF, Bcl-2, and XIAP) in vitro and in vivo. This study provides the first evidence that enalapril greatly sensitized CRC cells to 5-FU at clinically achievable concentrations without additional toxicity and the synergistic effect may be mainly by cooperatively suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins.
Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice
Authors: Hadadi Eva , Taylor William , Li Xiao-Mei , Aslan Yetki , Villote Marthe , Rivière Julie , Duvallet Gaelle , Auriau Charlotte , Dulong Sandrine , Raymond-Letron Isabelle , Provot Sylvain , Bennaceur-Griscelli Annelise , Acloque Hervé
Published: June 2020

Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography
Authors: Kneller Daniel W. , Phillips Gwyndalyn , O’Neill Hugh M. , Jedrzejczak Robert , Stols Lucy , Langan Paul , Joachimiak Andrzej , Coates Leighton , Kovalevsky Andrey
Published: June 2020

The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL Mpro due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL Mpro, revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.
Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
Authors: Yagi Masaki , Kabata Mio , Tanaka Akito , Ukai Tomoyo , Ohta Sho , Nakabayashi Kazuhiko , Shimizu Masahito , Hata Kenichiro , Meissner Alexander , Yamamoto Takuya , Yamada Yasuhiro
Published: June 2020

De novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.
Oncolytic virus-derived type I interferon restricts CAR T cell therapy
Authors: Evgin Laura , Huff Amanda L. , Wongthida Phonphimon , Thompson Jill , Kottke Tim , Tonne Jason , Schuelke Matthew , Ayasoufi Katayoun , Driscoll Christopher B. , Shim Kevin G. , Reynolds Pierce , Monie Dileep D. , Johnson Aaron J. , Coffey Matt , Young Sarah L. , Archer Gary , Sampson John , Pulido Jose , Perez Luis Sanchez , Vile Richard
Published: June 2020

The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNβ. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.
Single-atom Ni-N4 provides a robust cellular NO sensor
Authors: Zhou Min , Jiang Ying , Wang Guo , Wu Wenjie , Chen Wenxing , Yu Ping , Lin Yuqing , Mao Junjie , Mao Lanqun
Published: June 2020

Nitric oxide (NO) has been implicated in a variety of physiological and pathological processes. Monitoring cellular levels of NO requires a sensor to feature adequate sensitivity, transient recording ability and biocompatibility. Herein we report a single-atom catalysts (SACs)-based electrochemical sensor for the detection of NO in live cellular environment. The system employs nickel single atoms anchored on N-doped hollow carbon spheres (Ni SACs/N-C) that act as an excellent catalyst for electrochemical oxidation of NO. Notably, Ni SACs/N-C shows superior electrocatalytic performance to the commonly used Ni based nanomaterials, attributing from the greatly reduced Gibbs free energy that are required for Ni SACs/N-C in activating NO oxidation. Moreover, Ni SACs-based flexible and stretchable sensor shows high biocompatibility and low nanomolar sensitivity, enabling the real-time monitoring of NO release from cells upon drug and stretch stimulation. Our results demonstrate a promising means of using SACs for electrochemical sensing applications.
Fast and sensitive flow-injection mass spectrometry metabolomics by analyzing sample-specific ion distributions
Authors: Sarvin Boris , Lagziel Shoval , Sarvin Nikita , Mukha Dzmitry , Kumar Praveen , Aizenshtein Elina , Shlomi Tomer
Published: June 2020

Mass spectrometry based metabolomics is a widely used approach in biomedical research. However, current methods coupling mass spectrometry with chromatography are time-consuming and not suitable for high-throughput analysis of thousands of samples. An alternative approach is flow-injection mass spectrometry (FI-MS) in which samples are directly injected to the ionization source. Here, we show that the sensitivity of Orbitrap FI-MS metabolomics methods is limited by ion competition effect. We describe an approach for overcoming this effect by analyzing the distribution of ion m/z values and computationally determining a series of optimal scan ranges. This enables reproducible detection of ~9,000 and ~10,000 m/z features in metabolomics and lipidomics analysis of serum samples, respectively, with a sample scan time of ~15 s and duty time of ~30 s; a ~50% increase versus current spectral-stitching FI-MS. This approach facilitates high-throughput metabolomics for a variety of applications, including biomarker discovery and functional genomics screens.
Author Correction: Human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation
Authors: Bertin Aurélie , de Franceschi Nicola , de la Mora Eugenio , Maity Sourav , Alqabandi Maryam , Miguet Nolwen , di Cicco Aurélie , Roos Wouter H. , Mangenot Stéphanie , Weissenhorn Winfried , Bassereau Patricia
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Streptococcus mutans adhesion force sensing in multi-species oral biofilms
Authors: Wang Can , van der Mei Henny C. , Busscher Henk J. , Ren Yijin
Published: June 2020

Bacteria utilize chemical and mechanical mechanisms to sense their environment, to survive hostile conditions. In mechanical sensing, intra-bilayer pressure profiles change due to deformation induced by the adhesion forces bacteria experience on a surface. Emergent properties in mono-species Streptococcus mutans biofilms, such as extracellular matrix production, depend on the adhesion forces that streptococci sense. Here we determined whether and how salivary-conditioning film (SCF) adsorption and the multi-species nature of oral biofilm influence adhesion force sensing and associated gene expression by S. mutans. Hereto, Streptococcus oralis, Actinomyces naeslundii, and S. mutans were grown together on different surfaces in the absence and presence of an adsorbed SCF. Atomic force microscopy and RT-qPCR were used to measure S. mutans adhesion forces and gene expressions. Upon SCF adsorption, stationary adhesion forces decreased on a hydrophobic and increased on a hydrophilic surface to around 8 nN. Optical coherence tomography showed that triple-species biofilms on SCF-coated surfaces with dead S. oralis adhered weakly and often detached as a contiguous sheet. Concurrently, S. mutans displayed no differential adhesion force sensing on SCF-coated surfaces in the triple-species biofilms with dead S. oralis, but once live S. oralis were present S. mutans adhesion force sensing and gene expression ranked similar as on surfaces in the absence of an adsorbed SCF. Concluding, live S. oralis may enzymatically degrade SCF components to facilitate direct contact of biofilm inhabitants with surfaces and allow S. mutans adhesion force sensing of underlying surfaces to define its appropriate adaptive response. This represents a new function of initial colonizers in multi-species oral biofilms.
RNA sequencing analysis of the human retina and associated ocular tissues
Authors: Schumacker Scott T. , Coppage Krista R. , Enke Ray A.
Published: June 2020

The retina is a stratified layer of sensory neurons lining the posterior portion of the eye. In humans, fine detail and color vision are enabled by the macula, a central region of the retina dense in cone photoreceptors (PRs). Achromatic low light and peripheral vision are facilitated by rod PRs found with increasing density outside the macula in the peripheral retina. The outer retina is nourished by choroidal blood flow regulated by a single layer of intervening retinal pigment epithelial (RPE) cells. Existing human retinal transcriptome projects have been critical for studying aspects of retinal development and disease however, there are currently no publicly available data sets accurately describing the aging human central retina, peripheral retina, and supporting RPE/choroid. Here we used Illumina RNA sequencing (RNA-seq) analysis to characterize the mRNA transcriptome of rod and cone PR-enriched human retina as well as supporting macular RPE/choroid tissue. These data will be valuable to the vision research community for characterizing global changes in gene expression in clinically relevant ocular tissues.
Vortex phases and glassy dynamics in the highly anisotropic superconductor HgBa2CuO4+δ
Authors: Eley Serena , Willa Roland , Chan Mun K. , Bauer Eric D. , Civale Leonardo
Published: June 2020

We present an extensive study of vortex dynamics in a high-quality single crystal of HgBa2CuO4+δ, a highly anisotropic superconductor that is a model system for studying the effects of anisotropy. From magnetization M measurements over a wide range of temperatures T and fields H, we construct a detailed vortex phase diagram. We find that the temperature-dependent vortex penetration field Hp(T), second magnetization peak Hsmp(T), and irreversibility field Hirr(T) all decay exponentially at low temperatures and exhibit an abrupt change in behavior at high temperatures T/Tc >~ 0.5. By measuring the rates of thermally activated vortex motion (creep) S(T, H) = |dlnM(T, H)/dlnt|, we reveal glassy behavior involving collective creep of bundles of 2D pancake vortices as well as temperature- and time-tuned crossovers from elastic (collective) dynamics to plastic flow. Based on the creep results, we show that the second magnetization peak coincides with the elastic-to-plastic crossover at low T, yet the mechanism changes at higher temperatures.
Performance comparison of modified ComBat for harmonization of radiomic features for multicenter studies
Authors: Da-ano R. , Masson I. , Lucia F. , Doré M. , Robin P. , Alfieri J. , Rousseau C. , Mervoyer A. , Reinhold C. , Castelli J. , De Crevoisier R. , Rameé J. F. , Pradier O. , Schick U. , Visvikis D. , Hatt M.
Published: June 2020

Multicenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the “batch effect” in gene expression microarray data and was used in radiomics studies to deal with the “center-effect”. Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models.
Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals
Authors: Brunner Jesse L.
Published: June 2020

The regional and international trade of live animals facilitates the movement, spillover, and emergence of zoonotic and epizootic pathogens around the world. Detecting pathogens in trade is critical for preventing their continued movement and introduction, but screening a sufficient fraction to ensure rare infections are detected is simply infeasible for many taxa and settings because of the vast numbers of animals involved—hundreds of millions of live animals are imported into the U.S.A. alone every year. Batch processing pools of individual samples or using environmental DNA (eDNA)—the genetic material shed into an organism’s environment—collected from whole consignments of animals may substantially reduce the time and cost associated with pathogen surveillance. Both approaches, however, lack a framework with which to determine sampling requirements and interpret results. Here I present formulae for pooled individual samples (e.g,. swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. While empirical validation is key, these formulae illustrate the potential for eDNA-based detection in particular to reduce sample sizes and help bring clean trade into reach for a greater number of taxa, places, and contexts.
The association between Single Nucleotide Polymorphisms of Klotho Gene and Mortality in Elderly Men: The MrOS Sweden Study
Authors: Wu Ping-Hsun , Westerberg Per-Anton , Kindmark Andreas , Tivesten Åsa , Karlsson Magnus K. , Mellström Dan , Ohlsson Claes , Fellström Bengt , Linde Torbjörn , Ljunggren Östen
Published: June 2020

The Klotho (KL) gene is involved in phosphate homeostasis. Polymorphisms in this gene have been reported to be associated with the risk of cardiovascular disease. Here we used computational tools to predict the damage-associated single nucleotide polymorphisms (SNPs) in the human KL gene. We further investigated the association of SNPs in the KL gene and mortality in the Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort. This study included 2921 men (aged 69–81 years) with mean 4.49 ± 1.03 years follow-up. 18 SNPs in the KL gene were genotyped using Sequenom. These SNPs were identified by in silico tools for the coding and noncoding genome to predict the damaging SNPs. After quality analyses, SNPs were analyzed for mortality risk using two steps approach on logistic regression model screening and then Cox regression model confirmation. Two non-synonymous SNPs rs9536314 and rs9527025 were found to be potentially damaging SNPs that affect KL protein stability and expression. However, these two SNPs were not statistically significantly associated with all-cause mortality (crude Hazard ratio [HR] 1.72, 95% confidence interval [CI] 0.96–3.07 in rs9536314; crude HR 1.82, 95% CI 0.998–3.33 in rs9527025) or cardiovascular mortality (crude HR 1.52, 95% CI 0.56–4.14 in rs9536314; crude HR 1.54, 95% CI 0.55–4.33 in rs9527025) in additive model using Cox regression analysis. In conclusion, these two potentially damaging SNPs (rs9536314 and rs9527025) in the KL gene were not associated with all-cause mortality or cardiovascular mortality in MrOs cohort. Larger scales studies and meta-analysis are needed to confirm the correlation between polymorphisms of the KL gene and mortality.
Lifestyle risk score and mortality in Korean adults: a population-based cohort study
Authors: Lee Dong Hoon , Nam Jin Young , Kwon Sohyeon , Keum NaNa , Lee Jong-Tae , Shin Min-Jeong , Oh Hannah
Published: June 2020

Individual lifestyle risk factors have been associated with an increased risk of mortality. However, limited evidence is available on the combined association of lifestyle risk factors with mortality in non-Western populations. The analysis included 37,472 participants (aged ≥19 years) in the Korea National Health and Nutrition Examination Surveys (2007–2014) for whom the data were linked to death certificates/medical records through December 2016. A lifestyle risk score was created using five unhealthy behaviors: current smoking, high-risk alcohol drinking, unhealthy weight, physical inactivity, and insufficient/prolonged sleep. Cox proportional hazards models were used to estimate hazard ratio (HR) and 95% confidence interval (CI). During up to 9 years of follow-up, we documented 1,057 total deaths. Compared to individuals with zero lifestyle risk factor, those with 4–5 lifestyle risk factors had 2.01 times (HR = 2.01, 95% CI = 1.43–2.82) and 2.59 times (HR = 2.59, 95% CI = 1.24–5.40) higher risk of all-cause and cardiovascular mortality, respectively. However, higher lifestyle risk score was not significantly associated with cancer mortality (p-trend >0.05). In stratified analyses, the positive associations tended to be stronger in adults aged <65 years, unemployed, and those with lower levels of education. In conclusion, combined unhealthy lifestyle behaviors were associated with substantially increased risk of total and cardiovascular mortality in Korean adults.
Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes
Authors: Tomizawa Nobuo , Chou Shengpu , Fujino Yusuke , Matsuoka Satoshi , Yamamoto Kodai , Inoh Shinichi , Nojo Takeshi , Kumamaru Kanako K. , Fujimoto Shinichiro , Nakamura Sunao
Published: June 2020

The objective of this study was to investigate the incremental prognostic value for adverse events of myocardial blood flow (MBF) derived from stress computed tomography perfusion (CTP) at remote myocardium over cardiac risk factors and ischemia. We prospectively analyzed 242 patients who underwent dynamic CTP and CT angiography. Adverse events were defined as a composite of all-cause mortality, non-fatal myocardial infarction, unstable angina, heart failure requiring hospitalization, peripheral artery disease, and stroke. MBF value was calculated in each myocardial segment and ischemia was defined as mild decrease in MBF in two consecutive segments or moderate decrease in a single segment accompanied with a coronary stenosis ≥50%. The mean MBF of the non-ischemic segments was defined as remote MBF. We divided the patients into two groups by median MBF value of 1.15 ml/min/g. During a median follow-up of 18 months, 18 patients had adverse events. Annual event rate showed a significant difference between patients with low (≤1.15 ml/min/g) and high (>1.15 ml/min/g) MBF (6.1% vs 1.8%, p = 0.02). Univariate analysis showed that low MBF was a significant predictor of events (hazard ratio (HR): 3.4; 95% confidence interval (CI): 1.2 to 12.0; p = 0.02). This relationship maintained significant after adjusted for the presence of ischemia and cardiac risk factors (HR: 3.0; 95%CI: 1.1 to 11.1; p = 0.04). In conclusion, MBF value ≤1.15 ml/min/g derived from dynamic CTP in remote myocardium is significantly related with poor outcome and this relationship was independent of myocardial ischemia and cardiac risk factors.
Hydrogel-based milliwell arrays for standardized and scalable retinal organoid cultures
Authors: Decembrini S. , Hoehnel S. , Brandenberg N. , Arsenijevic Y. , Lutolf M. P.
Published: June 2020

The development of improved methods to culture retinal organoids is relevant for the investigation of mechanisms of retinal development under pathophysiological conditions, for screening of neuroprotective compounds, and for providing a cellular source for clinical transplantation. We report a tissue-engineering approach to accelerate and standardize the production of retinal organoids by culturing mouse embryonic stem cells (mESC) in optimal physico-chemical microenvironments. Arrayed round-bottom milliwells composed of biomimetic hydrogels, combined with an optimized medium formulation, promoted the rapid generation of retina-like tissue from mESC aggregates in a highly efficient and stereotypical manner: ∼93% of the aggregates contained retinal organoid structures. 26 day-old retinal organoids were composed of ∼80% of photoreceptors, of which ∼22% are GNAT2-positive cones, an important and rare sensory cell type that is difficult to study in rodent models. The compartmentalization of retinal organoids into predefined locations on a two-dimensional array not only allowed us to derive almost all aggregates into retinal organoids, but also to reliably capture the dynamics of individual organoids, an advantageous requirement for high-throughput experimentation. Our improved retinal organoid culture system should be useful for applications that require scalability and single-organoid traceability.
Lysosomal perturbations in human dopaminergic neurons derived from induced pluripotent stem cells with PARK2 mutation
Authors: Okarmus Justyna , Bogetofte Helle , Schmidt Sissel Ida , Ryding Matias , García-López Silvia , Ryan Brent James , Martínez-Serrano Alberto , Hyttel Poul , Meyer Morten
Published: June 2020

Mutations in the PARK2 gene encoding parkin, an E3 ubiquitin ligase, are associated with autosomal recessive early-onset Parkinson’s disease (PD). While parkin has been implicated in the regulation of mitophagy and proteasomal degradation, the precise mechanism leading to neurodegeneration in both sporadic and familial PD upon parkin loss-of-function remains unknown. Cultures of isogenic induced pluripotent stem cell (iPSC) lines with and without PARK2 knockout (KO) enable mechanistic studies of the effect of parkin deficiency in human dopaminergic neurons. We used such cells to investigate the impact of PARK2 KO on the lysosomal compartment and found a clear link between parkin deficiency and lysosomal alterations. PARK2 KO neurons exhibited a perturbed lysosomal morphology with enlarged electron-lucent lysosomes and an increased lysosomal content, which was exacerbated by mitochondrial stress and could be ameliorated by antioxidant treatment. We also found decreased lysosomal enzyme activity and autophagic perturbations, suggesting an impairment of the autophagy-lysosomal pathway in parkin-deficient cells. Interestingly, activity of the GBA-encoded enzyme, β-glucocerebrosidase, was increased, suggesting the existence of a compensatory mechanism. In conclusion, our data provide a unique characterization of the morphology, content, and function of lysosomes in PARK2 KO neurons and reveal an important new connection between mitochondrial dysfunction and lysosomal dysregulation in PD pathogenesis.