bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Intermodel Diversity When Simulating the Time of Emergence in CMIP5 Climate Models
Authors: Hyun Seung‐Hwon , Yeh Sang‐Wook , Song Se‐Yong , Park Hyo‐Seok , Kirtman Ben P.
Published: July 2020

Using a statistical method, we examined the time of emergence (ToE), which was defined as the year when the global mean surface temperature (GMST) trend exceeds the trend explained by internal variability, using 33 Coupled Model Intercomparison Project Phase 5 (CMIP5) climate models for 1861–2100. We found that the GMST trend explained by internal variability showed minimal changes even though the GMST trend rapidly increased under the Representative Climate Pathway 8.5 scenario. However, there was large intermodel diversity for the ToEs in CMIP5 climate models. The intensity of Arctic amplification was closely associated with intermodel diversity of the ToEs. A significant difference in the amount of Arctic sea ice extent during the reference period (1861‐1910) played a role in determining whether there was slow or fast simulation of the ToE in CMIP5 climate models. We argue that a slow or fast ToE is influenced by how the climate models initially simulate the sea ice extent during the reference period.
Origin of Electron Boomerang Stripes: Localized ULF Wave‐Particle Interactions
Authors: Zhao X. X. , Hao Y. X. , Zong Q.‐G. , Zhou X.‐Z. , Yue Chao , Chen X. R. , Liu Y. , Blake J. B. , Claudepierre S. G. , Reeves G. D.
Published: July 2020

Ultralow frequency (ULF) wave‐particle interactions play a significant role in the radiation belt dynamic process, during which drift resonance can accelerate and transport energetic electrons in the outer radiation belt. Observations of wave‐electron drift resonance are characterized by quasiperiodic straight or “boomerang‐shaped” stripes in the pitch angle spectrogram. Here we present an ULF wave event on 1 December 2015, during which both kinds stripes were observed by Van Allen Probes A and B, respectively. Using the time‐of‐flight technique based on the pitch angle dependence of electron drift velocities, the “boomerang‐shaped” stripes are inferred to originate from straight stripes at the time and location covered by Probe B. Given that straight stripes were indeed observed by Probe B, our observations strongly support the charged particle interacting with azimuthally localized ULF waves. A new method is provided to identify the location of ULF wave‐particle interaction on the basis of remote observations of electron flux modulations.
Spatiotemporal Characteristics and Propagation of Summer Extreme Precipitation Events Over United States: A Complex Network Analysis
Authors: Mondal Somnath , Mishra Ashok Kumar , Leung L. Ruby
Published: July 2020

Complex network (CN) is a graph theory‐based depiction of relation shared by various elements of a complex dynamical system such as the atmosphere. Here we apply the concept of CN to understand the directionality and topological structure of summer extreme precipitation events (SEPEs) over the conterminous United States (CONUS). The SEPEs are calculated based on the 95th percentile daily rainfall at 0.5° × 0.5° spatial resolution for CONUS to investigate the multidimensional characteristics of precipitation extremes. The derived CN coefficients (e.g., betweenness centrality, clustering coefficient, orientation, and network divergence) reveal important structural and dynamical information about the topology of the SEPEs and improve understanding of the dominant meteorological patterns. The initiation and propagation of SEPEs from the source zones to the sink zones are identified. The SEPEs are influenced by topography, dominant wind patterns, and moisture sources in terms of their topological structure and spatial dynamics.
A Unique Feature of the 2019 Extreme Positive Indian Ocean Dipole Event
Authors: Wang Guojian , Cai Wenju , Yang Kai , Santoso Agus , Yamagata Toshio
Published: July 2020

During austral spring of 2019, an extreme positive Indian Ocean Dipole (pIOD) event occurred, with cold sea surface temperature (SST) anomalies over the eastern equatorial Indian Ocean (EEIO) and warming in the west. Although the growth of the EEIO cold anomalies involves forcing by equatorial nonlinear advection, unique to the 2019 pIOD is an air‐sea heat flux that was a forcing to the EEIO cold anomalies, rather than a damping as in previous extreme events. This unique thermodynamic forcing is due to a large latent cooling, which is supported by an unusually strong wind speed contributed by a large southerly anomaly as part of a long‐term trend. The wind trend is underpinned by a mean state SST change featuring slower warming off Sumatra‐Java. Given that a similar SST trend pattern is projected under greenhouse warming, the likelihood of such thermodynamical forcing operating more frequently in the future needs to be considered.
Contributions of Greenland GPS Observed Deformation From Multisource Mass Loading Induced Seasonal and Transient Signals
Authors: Li Wenhao , Shum C. K. , Li Fei , Zhang Shengkai , Ming Feng , Chen Wei , Zhang Bao , Lei Jintao , Zhang Qingchuan
Published: July 2020

Global Positioning System (GPS) provides critical geodetic constraints on Earth's elastic response induced by ice and other mass loadings in Greenland. Previous studies focused on long‐term ice mass changes, with relatively fewer studies on transient signals and had used fewer GPS stations. Here we reconstructed 44 Greenland‐wide coastal decadal GPS time series using multichannel singular spectral analysis and quantified the origins of spatiotemporal patterns of transient to seasonal signals. We used an exhaustive list of geophysical processes, including surface mass balance (SMB), atmospheric pressure, continental hydrology, nontidal ocean loading, bedrock thermal expansion, precipitation, runoff, and ice discharge, and identified that most of Greenland's GPS sites exhibit SMB‐induced transient signals during 2012–2015, with maximum displacement reaching 20.45 mm. Analyses of differenced time series between adjacent GPS stations near peripheral glaciers reveal that locally varying seasonal signals are primarily attributable to SMB, followed by atmosphere.
Surface Chlorophyll Enhancement in Mesoscale Eddies by Submesoscale Spiral Bands
Authors: Zhang Zhengguang , Qiu Bo
Published: July 2020

Oceanic submesoscale processes (with scales ~1–10 km and approximately days) have been progressively recognized as an important upwelling mechanism to close the upper ocean nutrient budget and sustain the primary production in euphotic layer. Spiral band is one of the most typical submesoscale structures of mesoscale eddies, characterized with enhancement of surface chlorophyll concentration. By combining satellite ocean‐color, satellite‐altimetry, and surface drifter data, we find that the oceanic spiral chlorophyll bands emerge globally and share a series of structural and kinematic features with atmospheric spiral rain bands of tropical cyclones, which indicate that they are footprints of the vertical motions induced by vortex Rossby waves embedded in eddies. As vortex Rossby waves are closely related to eddy evolution under background deformation, further observational analysis indicates that an intense eddy energy variation and a strong background deformation field constitute the favorable conditions for the emergence of the spiral chlorophyll bands.
Efficient Vertical Transport of Black Carbon in the Planetary Boundary Layer
Authors: Liu Dantong , Hu Kang , Zhao Delong , Ding Shuo , Wu Yunfei , Zhou Chang , Yu Chenjie , Tian Ping , Liu Quan , Bi Kai , Wu Yangzhou , Hu Bo , Ji Dongsheng , Kong Shaofei , Ouyang Bin , He Hui , Huang Mengyu , Ding Deping
Published: July 2020

Vertical distribution of black carbon (BC) determines the layer where its heating impacts exert. This study presents continuous and simultaneous measurements at surface and on a mountain site above the wintertime planetary boundary layer influenced by uplifted surface anthropogenic emissions. BC was observed efficiently transported upwards by daytime convective mixing. However, this vertical transport was less for other particulate masses. An about twofold higher BC mass fraction was thus present at mountain than surface, hereby a lowered single‐scattering albedo (SSA) by 0.06. This may be caused by the evaporative loss of condensed semivolatile materials, prevailing the secondary particulate formation, in a cleaner environment containing less precursors. The elevated BC mass corresponded with the most intensive solar radiation at midday, wielding more heating impacts over the planetary boundary layer (PBL). This phenomenon may apply to other remote regions where a reduced SSA will introduce more positive radiative effects.
Continuous Isoprene Measurements in a UK Temperate Forest for a Whole Growing Season: Effects of Drought Stress During the 2018 Heatwave
Authors: Ferracci Valerio , Bolas Conor G. , Freshwater Ray A. , Staniaszek Zosia , King Thomas , Jaars Kerneels , Otu‐Larbi Frederick , Beale John , Malhi Yadvinder , Waine Toby William , Jones Roderic L. , Ashworth Kirsti , Harris Neil R. P.
Published: July 2020

Isoprene concentrations were measured at four heights below, within, and above the forest canopy in Wytham Woods (United Kingdom) throughout the summer of 2018 using custom‐built gas chromatographs (the iDirac). These observations were complemented with selected ancillary variables, including air temperature, photosynthetically active radiation, occasional leaf gas exchange measurements, and satellite retrievals of normalized difference vegetation and water indices. The campaign overlapped with a long and uninterrupted heatwave accompanied by moderate drought. Peak isoprene concentrations during the heatwave‐drought were up to a factor of 4 higher than those before or after. Higher temperatures during the heatwave could not account for all the observed isoprene; the enhanced abundances correlated with drought stress. Leaf‐level emissions confirmed this and also included compounds associated with ecosystem stress. This work highlights that a more in‐depth understanding of the effects of drought stress is required to better characterize isoprene emissions.
Assessment of InSight Landing Site Predictions
Authors: Golombek M. , Kass D. , Williams N. , Warner N. , Daubar I. , Piqueux S. , Charalambous C. , Pike W. T.
Published: July 2020

Comprehensive analysis of remote sensing data used to select the Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) landing site correctly predicted the atmospheric temperature and pressure profile during entry and descent, the safe landing surface, and the geologic setting of the site. The smooth plains upon which the InSight landing site is located were accurately predicted to be generally similar to the Mars Exploration Rover Spirit landing site with relatively low rock abundance, low slopes, and a moderately dusty surface with a 3–10 m impact fragmented regolith over Hesperian to Early Amazonian basaltic lava flows. The deceleration profile and surface pressure encountered by the spacecraft during entry, descent, and landing compared well (within 1σ) of the envelope of modeled temperature profiles and the expected surface pressure. Orbital estimates of thermal inertia are similar to surface radiometer measurements, and materials at the surface are dominated by poorly consolidated sand as expected. Thin coatings of bright atmospheric dust on the surface were as indicated by orbital albedo and dust cover index measurements. Orbital estimates of rock abundance from shadow measurements in high‐resolution images and thermal differencing indicated very low rock abundance and surface counts show 1–4% area covered by rocks. Slopes at 100 to 5 m length scale measured from orbital topographic and radar data correctly indicated a surface comparably smooth and flat as the two smoothest landing sites (Opportunity and Phoenix). Thermal inertia and radar data indicated the surface would be load bearing as found.
Anthropogenic dissolved organic carbon and marine microbiomes
Authors: Vila-Costa Maria , Cerro-Gálvez Elena , Martínez-Varela Alicia , Casas Gemma , Dachs Jordi
Published: July 2020

Thousands of synthetic chemicals and hydrocarbons are released to the marine environment composing the anthropogenic dissolved organic carbon (ADOC). Most ADOC is disproportionally hydrophobic, and consequently, its concentrations in the cell membranes are between a thousand and hundred million fold higher than those in the dissolved phase. Marine microorganisms respond to ADOC by multiple strategies ranging from ADOC degradation to detoxifying metabolisms. We argue that the increasing concentrations of ADOC in the oceans deriving from rivers, atmospheric deposition, and plastic leachates can have an effect on the health of the oceans and influence the major biogeochemical cycles, thus influencing the Earth system during the Anthropocene.
Aberrantly expressed HORMAD1 disrupts nuclear localization of MCM8–MCM9 complex and compromises DNA mismatch repair in cancer cells
Authors: Liu Kang , Wang Yifan , Zhu Quanfeng , Li Peng , Chen Jiyuan , Tang Zhenghui , Shen Yuanming , Cheng Xiaodong , Lu Lin-Yu , Liu Yidan
Published: July 2020

HORMAD1 is a meiosis-specific protein that promotes synapsis and recombination of homologous chromosomes in meiotic prophase. Originally identified as a cancer/testis antigen, HORMAD1 is also aberrantly expressed in several cancers. However, the functions of HORMAD1 in cancer cells are still not clear. Here, we show that HORMAD1 is aberrantly expressed in a wide variety of cancers and compromises DNA mismatch repair in cancer cells. Mechanistically, HORMAD1 interacts with MCM8–MCM9 complex and prevents its efficient nuclear localization. As a consequence, HORMAD1-expressing cancer cells have reduced MLH1 chromatin binding and DNA mismatch repair defects. Consistently, HORMAD1 expression is associated with increased mutation load and genomic instability in many cancers. Taken together, our study provides mechanistic insights into HORMAD1’s functions in cancer cells, which can potentially be exploited for targeted therapy of HORMAD1-expressing cancers.
Development of A4 antibody for detection of neuraminidase I223R/H275Y-associated antiviral multidrug-resistant influenza virus
Authors: Guk Kyeonghye , Kim Hyeran , Lee Miyeon , Choi Yoon-Aa , Hwang Seul Gee , Han Gaon , Kim Hye-Nan , Kim Hongki , Park Hwangseo , Yong Dongeun , Kang Taejoon , Lim Eun-Kyung , Jung Juyeon
Published: July 2020

The emergence and spread of antiviral drug-resistant viruses have been a worldwide challenge and a great concern for patient care. We report A4 antibody specifically recognizing and binding to the mutant I223R/H275Y neuraminidase and prove the applicability of A4 antibody for direct detection of antiviral multidrug-resistant viruses in various sensing platforms, including naked-eye detection, surface-enhanced Raman scattering-based immunoassay, and lateral flow system. The development of the A4 antibody enables fast, simple, and reliable point-of-care assays of antiviral multidrug-resistant influenza viruses. In addition to current influenza virus infection testing methods that do not provide information on the antiviral drug-resistance of the virus, diagnostic tests for antiviral multidrug-resistant viruses will improve clinical judgment in the treatment of influenza virus infections, avoid the unnecessary prescription of ineffective drugs, and improve current therapies.
Author Correction: Repurposing type I–F CRISPR–Cas system as a transcriptional activation tool in human cells
Authors: Chen Yuxi , Liu Jiaqi , Zhi Shengyao , Zheng Qi , Ma Wenbin , Huang Junjiu , Liu Yizhi , Liu Dan , Liang Puping , Songyang Zhou
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Potential of MMP-9 based nanoparticles at optimizing the cow dry period: pulling apart the effects of MMP-9 and nanoparticles
Authors: Gifre-Renom L. , Carratalá J. V. , Parés S. , Sánchez-García L. , Ferrer-Miralles N. , Villaverde A. , Bach A. , Garcia-Fruitós Elena , Arís Anna
Published: July 2020

The cow dry period is a non-milking interval where the mammary gland involutes and regenerates to guarantee an optimal milk production in the subsequent lactation. Important bottlenecks such as the high risk of intramammary infections complicate the process. Antibiotics have been routinely used as a preventive treatment but the concerns about potential antibiotic resistance open a new scenario in which alternative strategies have to be developed. Matrix metalloproteinase-9 (MMP-9) is an enzyme able to degrade the extracellular matrix, triggering the involution and immune function of cow mammary gland. We have studied the infusion into the mammary gland of MMP-9 inclusion bodies as protein-based nanoparticles, demonstrating that 1.2 mg of MMP-9 enhanced the involution and immune function of the cow mammary gland. However, the comparison of the effects triggered by the administration of an active and an inactive form of MMP-9 led to conclude that the response observed in the bovine mammary gland was mainly due to the protein format but not to the biological activity of the MMP-9 embedded in the inclusion body. This study provides relevant information on the future use of protein inclusion bodies in cow mammary gland and the role of MMP-9 at dry-off.
Behavioral tests assessing neuropsychiatric phenotypes in adolescent mice reveal strain- and sex-specific effects
Authors: Eltokhi Ahmed , Kurpiers Barbara , Pitzer Claudia
Published: July 2020

In humans, infancy and adolescence are associated with major changes in synaptic functions and ongoing maturation of neural networks, which underlie the major behavioral changes during these periods. Among adult cases with neuropsychiatric disorders including autism spectrum disorder, schizophrenia, attention deficit hyperactivity, and bipolar disorders, 50% have developed behavioral symptoms and received a diagnosis before 15 years of age. However, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we explored which behavioral experiments assessing neuropsychiatric phenotypes can be performed during a specific window of development in adolescent male and female C57BL/6N, DBA/2, and FVB/N mice that are typically used as background strains for generating genetically-modified mouse models. The three wild-type strains were evaluated across anxiety, social behaviors, and cognitive functions in order to cover the main behavioral impairments that occur in neuropsychiatric disorders. During adolescence, the three strains displayed significant differences under certain behavioral paradigms. In addition, C57BL/6N and FVB/N, but not DBA/2 mice revealed some sex-related differences. Our results provide new insights into discrete behaviors during development and emphasize the crucial importance of the genetic background, sex, and experimental settings in the age-dependent regulation of different behaviors.
The earliest domestic cat on the Silk Road
Authors: Haruda A. F. , Ventresca Miller A. R. , Paijmans J. L. A. , Barlow A. , Tazhekeyev A. , Bilalov S. , Hesse Y. , Preick M. , King T. , Thomas R. , Härke H. , Arzhantseva I.
Published: July 2020

We present the earliest evidence for domestic cat (Felis catus L., 1758) from Kazakhstan, found as a well preserved skeleton with extensive osteological pathologies dating to 775–940 cal CE from the early medieval city of Dzhankent, Kazakhstan. This urban settlement was located on the intersection of the northern Silk Road route which linked the cities of Khorezm in the south to the trading settlements in the Volga region to the north and was known in the tenth century CE as the capital of the nomad Oghuz. The presence of this domestic cat, presented here as an osteobiography using a combination of zooarchaeological, genetic, and isotopic data, provides proxy evidence for a fundamental shift in the nature of human-animal relationships within a previously pastoral region. This illustrates the broader social, cultural, and economic changes occurring within the context of rapid urbanisation during the early medieval period along the Silk Road.
Extreme subsidence in a populated city (Mashhad) detected by PSInSAR considering groundwater withdrawal and geotechnical properties
Authors: Khorrami Mohammad , Abrishami Saeed , Maghsoudi Yasser , Alizadeh Babak , Perissin Daniele
Published: July 2020

Ground deformation can cause serious environmental issues such as infrastructure damage, ground compaction, and reducing the ground capacity to store water. Mashhad, as one of the largest and most populated cities in the Middle East, has been suffering from extreme subsidence. In the last decade, some researchers have been interested in measuring land subsidence rates in the Mashhad valley by InSAR techniques. However, most of those studies were based on inaccurate measurements introducing uncertainties in the resulting subsidence rates. These researches used a small number of EnviSat data with long perpendicular and inhomogeneous temporal baseline. This paper seeks to determine the subsidence rate in urban areas of Mashhad in recent years, the threat that was neglected by the city managers and decision-makers. For this purpose, the Persistent Scatterer InSAR technique was applied in the study area using two time-series of descending and ascending Sentinel-1A acquisitions between 2014 and 2017. The results demonstrated the maximum line-of-sight deformation rate of 14.6 cm/year and maximum vertical deformation (subsidence) rate about 19.1 cm/year which could have irreversible consequences. The results were assessed and validated using piezometric data, GPS stations, and geotechnical properties. This assessment confirms that the main reason for subsidence in the interested area is groundwater over-extraction. Also, investigation of geotechnical properties shows that thick fine-grained layers in the northwest of the city could strongly affect the results. At the end of this paper, a new simplified method was proposed to estimate specific storage in special cases to predict the subsidence rate.
Pilot study of neurologic toxicity in mice after proton minibeam therapy
Authors: Eley John G. , Chadha Awalpreet S. , Quini Caio , Vichaya Elisabeth G. , Zhang Cancan , Davis James , Sahoo Narayan , Waddell Jaylyn , Leiser Dominic , Dilmanian F. Avraham , Krishnan Sunil
Published: July 2020

Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.
dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye
Authors: Angileri Krista M. , Gross Jeffrey M.
Published: July 2020

The ciliary marginal zone (CMZ) of the zebrafish retina contains a population of actively proliferating resident stem cells, which generate retinal neurons throughout life. The maintenance methyltransferase,dnmt1, is expressed within the CMZ. Loss of dnmt1 function results in gene misregulation and cell death in a variety of developmental contexts, however, its role in retinal stem cell (RSC) maintenance is currently unknown. Here, we demonstrate that zebrafishdnmt1s872mutants possess severe defects in RSC maintenance within the CMZ. Using a combination of immunohistochemistry, in situ hybridization, and a transgenic reporter assay, our results demonstrate a requirement for dnmt1 activity in the regulation of RSC proliferation, gene expression and in the repression of endogenous retroelements (REs). Ultimately, cell death is elevated in thednmt1−/−CMZ, but in ap53-independent manner. Using a transgenic reporter for RE transposition activity, we demonstrate increased transposition in thednmt1−/−CMZ. Taken together our data identify a critical role for dnmt1 function in RSC maintenance in the vertebrate eye.
Echocardiographic two-dimensional speckle tracking identifies acute regional myocardial edema and sub-acute fibrosis in pediatric focal myocarditis with normal ejection fraction: comparison with cardiac magnetic resonance
Authors: Chinali Marcello , Franceschini Alessio , Ciancarella Paolo , Lisignoli Veronica , Curione Davide , Ciliberti Paolo , Esposito Claudia , Del Pasqua Alessia , Rinelli Gabriele , Secinaro Aurelio
Published: July 2020

The aim here was to describe the role of speckle tracking echocardiography (STE), in identifying impairment in systolic function in children and adolescents with focal myocarditis and without reduction in ejection fraction. We describe data from 33 pediatric patients (age 4–17 years) admitted for focal myocarditis, confirmed by cardiac magnetic resonance (CMR), and without impaired ejection fraction and/or wall motion abnormalities. All children underwent Doppler echocardiography examination with analysis of global (G) and segmental longitudinal strain (LS) and CMR for the quantification of edema and myocardial fibrosis. Reduction in LS was defined according to age-specific partition values. At baseline, impaired GLS was present in 58% of patients (n = 19), albeit normal ejection fraction. LS was also regionally impaired, according to the area of higher edema at CMR (i.e. most impaired at the level of the infero-lateral segments as compared to other segments (p < 0.05). GLS impairment was also moderately correlated with the percentage edema at CMR (r = − 0.712; p = 0.01). At follow-up, GLS improved in all patients (p < 0.001), and normal values were found in 13/19 patients with baseline reduction. Accordingly persistent global and regional impairment was still observed in 6 patients. Patients with persistent LS reduction demonstrated residual focal cardiac fibrosis at follow-up CMR. Both global and regional LS is able to identify abnormalities in systolic longitudinal mechanics in children and adolescents with focal myocarditis and normal ejection fraction. The reduction in LS is consistent with edema amount and localization at CMR. Furthermore, LS identifies regional recovery or persistent cardiac function impairment, possibly related to residual focal fibrosis.
Stem cell factor produced by tumor cells expands myeloid-derived suppressor cells in mice
Authors: Lee Wei-Chen , Hsu Pao-Yueh , Hsu Hsiu-Ying
Published: July 2020

Immunotherapy is a novel treatment approach for cancers; however, its therapeutic effects are impeded by myeloid-derived suppressor cells (MDSCs). This study aimed to determine how MDSCs are expanded in cancer hosts. MDSCs were positive for Gr-1 and CD11b. Hepa1-6 hepatoma cells, EL4 lymphoma cells, and mice bearing Hepa1-6 hepatoma or lymphoma were examined. Following the inoculation of Hepa1-6 cells into the flanks of mice, a linear correlation was evident between the frequency of MDSCs in the spleen and tumor sizes. MDSC numbers diminished gradually and returned to the normal level within 3 weeks if the tumors were excised. To identify the cytokines produced by tumor cells that allowed expansion of MDSCs, cytokines in Hepa1-6 cell culture medium and murine serum were examined using a cytokine array. Stem cell factor (SCF) was implicated as the relevant cytokine. When recombinant SCF was added to the spleen cell culture medium, MDSC expansion could occur. In the presence of c-kit blockade, this effect of SCF was partially reversed. In conclusion, MDSCs can be expanded in tumor cells in a process that involves SCF released by tumor cells.
Expanding the eggshell colour gamut: uroerythrin and bilirubin from tinamou (Tinamidae) eggshells
Authors: Hamchand Randy , Hanley Daniel , Prum Richard O. , Brückner Christian
Published: July 2020

To date, only two pigments have been identified in avian eggshells: rusty-brown protoporphyrin IX and blue-green biliverdin IXα. Most avian eggshell colours can be produced by a mixture of these two tetrapyrrolic pigments. However, tinamou (Tinamidae) eggshells display colours not easily rationalised by combination of these two pigments alone, suggesting the presence of other pigments. Here, through extraction, derivatization, spectroscopy, chromatography, and mass spectrometry, we identify two novel eggshell pigments: yellow–brown tetrapyrrolic bilirubin from the guacamole-green eggshells of Eudromia elegans, and red–orange tripyrrolic uroerythrin from the purplish-brown eggshells of Nothura maculosa. Both pigments are known porphyrin catabolites and are found in the eggshells in conjunction with biliverdin IXα. A colour mixing model using the new pigments and biliverdin reproduces the respective eggshell colours. These discoveries expand our understanding of how eggshell colour diversity is achieved. We suggest that the ability of these pigments to photo-degrade may have an adaptive value for the tinamous.
Computational study of the water-driven graphene wrinkle life-cycle towards applications in flexible electronics
Authors: Kashyap Jatin , Yang Eui-Hyeok , Datta Dibakar
Published: July 2020

The ubiquitous presence of wrinkles in two-dimensional materials alters their properties significantly. It is observed that during the growth process of graphene, water molecules, sourced from ambient humidity or transferred method used, can get diffused in between graphene and the substrate. The water diffusion causes/assists wrinkle formation in graphene, which influences its properties. The diffused water eventually dries, altering the geometrical parameters and properties of wrinkled graphene nanoribbons. Our study reveals that the initially distributed wrinkles tend to coalesce to form a localized wrinkle whose configuration depends on the initial wrinkle geometry and the quantity of the diffused water. The movement of the localized wrinkle is categorized into three modes—bending, buckling, and sliding. The sliding mode is characterized in terms of velocity as a function of diffused water quantity. Direct bandgap increases linearly with the initial angle except the highest angle considered (21°), which can be attributed to the electron tunneling effect observed in the orbital analysis. The system becomes stable with an increase in the initial angle of wrinkle as observed from the potential energy plots extracted from MD trajectories and confirmed with the DOS plot. The maximum stress generated is less than the plastic limit of the graphene.
Internet searches offer insight into early-season pollen patterns in observation-free zones
Authors: Hall Jane , Lo Fiona , Saha Shubhayu , Vaidyanathan Ambarish , Hess Jeremy
Published: July 2020

Tracking concentrations of regional airborne pollen is valuable for a variety of fields including plant and animal ecology as well as human health. However, current methods for directly measuring regional pollen concentrations are labor-intensive, requiring special equipment and manual counting by professionals leading to sparse data availability in select locations. Here, we use publicly available Google Trends data to evaluate whether searches for the term “pollen” can be used to approximate local observed early-season pollen concentrations as reported by the National Allergy Bureau across 25 U.S. regions from 2012–2017, in the context of site-specific characteristics. Our findings reveal that two major factors impact the ability of internet search data to approximate observed pollen: (1) volume/availability of internet search data, which is tied to local population size and media use; and (2) signal intensity of the seasonal peak in searches. Notably, in regions and years where internet search data was abundant, we found strong correlations between local search patterns and observed pollen, thus revealing a potential source of daily pollen data across the U.S. where observational pollen data are not reliably available.
Validation of a prognostic model for adverse perinatal health outcomes
Authors: Lagendijk Jacqueline , Steyerberg Ewout W. , Daalderop Leonie A. , Been Jasper V. , Steegers Eric A. P. , Posthumus Anke G.
Published: July 2020

There is a strong association between social deprivation and adverse perinatal health outcomes, but related risk factors receive little attention in current antenatal risk selection. To increase awareness of healthcare professionals for these risk factors, a model for antenatal risk surveillance and care was developed in The Netherlands, called the ‘Rotterdam Reproductive Risk Reduction’ (R4U) scorecard. The aim of this study was to validate the R4U-scorecard. This study was conducted using external, prospective data from thirty-two midwifery practices, and fifteen hospitals in The Netherlands. The main outcome measures were the discrimination of the prognostic models for the probability of a pregnant woman developing adverse pregnancy outcomes (babies born preterm or small for gestational age), and calibration. We performed cross-validation and updated the model using statistical re-estimation of all predictors. 1752 participants were included, of whom 282 (16%) had one of the predefined adverse outcomes. The discriminative value of the original scoring system was poor [area under the curve (AUC) of 0.58 (95% CI 0.53–0.64)]. The model showed moderate calibration. The updated R4U-scorecard showed good generalisability to the validation set but did not alter the predictive value [AUC 0.61 (95% CI 0.56–0.66)]. By using external data and by updating the prognostic model, we have provided a comprehensive evaluation of the R4U-scorecard. Further improvement in classification of high-risk pregnancies is important considering the necessity of early risk detection for healthcare professionals to take appropriate actions to prevent these risks from becoming manifest problems.
Electro-acupuncture regulates glucose metabolism in chronic stress model rats
Authors: Ma Fu-qiang , Sun Chan-juan , Wei Jun-jie , Wang Ya-dong , Shen Jia-cheng , Chang Jin-jian
Published: July 2020

Studies have shown that acupuncture is very effective in treating chronic stress depression. However, little is known about the therapeutic mechanism of electro-acupuncture. Metabolomics, on the other hand, is a technology that determines the metabolic changes of organisms caused by various interventions as a whole and is related to the overall effect of electro-acupuncture (EA). 1HNMR, serum sample analysis, and histopathology and molecular biology analysis were used to evaluate the effects of EA. The results show that electro-acupuncture points can regulate the heat pain threshold of chronic stress model rats and change the morphology of adrenal cortex cells Structure, and regulate the contents of corticotropin-releasing hormone, Corticosterone (CORT), glucose, alanine and valine in the samples. These findings help to clarify the therapeutic mechanism of electro-acupuncture on heterologous chronic stress model rats. The effect of electro-acupuncture on improving chronic stress is likely to be achieved by regulating glucose metabolism, which can provide a reference for clinical acupuncture treatment of chronic stress depression.
Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
Authors: Derenne Aline , Tassin Alexandra , Nguyen Thuy Hang , De Roeck Estelle , Jenart Vincianne , Ansseau Eugénie , Belayew Alexandra , Coppée Frédérique , Declèves Anne-Emilie , Legrand Alexandre
Published: July 2020

Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy. DUX4 encodes a potent transcription factor causing a large deregulation cascade. Its high toxicity but sporadic expression constitutes major issues for testing emerging therapeutics. The IMEP method appeared as a convenient technique to locally express DUX4 in mouse muscles. Histological analyses revealed well delineated muscle lesions 1-week after DUX4 IMEP. We have therefore developed a convenient outcome measure by quantification of the damaged muscle area using color thresholding. This method was used to characterize lesion distribution and to assess plasmid recirculation and dose–response. DUX4 expression and activity were confirmed at the mRNA and protein levels and through a quantification of target gene expression. Finally, this study gives a proof of concept of IMEP model usefulness for the rapid screening of therapeutic strategies, as demonstrated using antisense oligonucleotides against DUX4 mRNA.
Adaptive time scales in recurrent neural networks
Authors: Quax Silvan C. , D’Asaro Michele , van Gerven Marcel A. J.
Published: July 2020

Recent experiments have revealed a hierarchy of time scales in the visual cortex, where different stages of the visual system process information at different time scales. Recurrent neural networks are ideal models to gain insight in how information is processed by such a hierarchy of time scales and have become widely used to model temporal dynamics both in machine learning and computational neuroscience. However, in the derivation of such models as discrete time approximations of the firing rate of a population of neurons, the time constants of the neuronal process are generally ignored. Learning these time constants could inform us about the time scales underlying temporal processes in the brain and enhance the expressive capacity of the network. To investigate the potential of adaptive time constants, we compare the standard approximations to a more lenient one that accounts for the time scales at which processes unfold. We show that such a model performs better on predicting simulated neural data and allows recovery of the time scales at which the underlying processes unfold. A hierarchy of time scales emerges when adapting to data with multiple underlying time scales, underscoring the importance of such a hierarchy in processing complex temporal information.
Non-backtracking walks reveal compartments in sparse chromatin interaction networks
Authors: Polovnikov K. , Gorsky A. , Nechaev S. , Razin S. V. , Ulianov S. V.
Published: July 2020

Chromatin communities stabilized by protein machinery play essential role in gene regulation and refine global polymeric folding of the chromatin fiber. However, treatment of these communities in the framework of the classical network theory (stochastic block model, SBM) does not take into account intrinsic linear connectivity of the chromatin loci. Here we propose the polymer block model, paving the way for community detection in polymer networks. On the basis of this new model we modify the non-backtracking flow operator and suggest the first protocol for annotation of compartmental domains in sparse single cell Hi-C matrices. In particular, we prove that our approach corresponds to the maximum entropy principle. The benchmark analyses demonstrates that the spectrum of the polymer non-backtracking operator resolves the true compartmental structure up to the theoretical detectability threshold, while all commonly used operators fail above it. We test various operators on real data and conclude that the sizes of the non-backtracking single cell domains are most close to the sizes of compartments from the population data. Moreover, the found domains clearly segregate in the gene density and correlate with the population compartmental mask, corroborating biological significance of our annotation of the chromatin compartmental domains in single cells Hi-C matrices.
Temporal variations in ambient air quality indicators in Shanghai municipality, China
Authors: Chen Yuanyuan , Bai Yang , Liu Hongtao , Alatalo Juha M. , Jiang Bo
Published: July 2020

Official data on daily PM2.5, PM10, SO2, NO2, CO, and maximum 8-h average O3 (O3_8h) concentrations from January 2015 to December 2018 were evaluated and air pollution status and dynamics in Shanghai municipality were examined. Factors affecting air quality, including meteorological factors and socio-economic indicators, were analyzed. The main findings were that: (1) Overall air quality status in Shanghai municipality has improved and number of days meeting ‘Chinese ambient air quality standards’ (CAAQS) Grade II has increased. (2) The most frequent major pollutant in Shanghai municipality is O3 (which exceeded the standard on 110 days in 2015, 84 days in 2016, 126 days in 2017, 113 days in 2018), followed by PM2.5 (120days in 2015, 104 days in 2016, 67 days in 2017, 61 days in 2018) and NO2 (50 days in 2015, 67 days in 2016, 79 days in 2017, 63 days in 2018). (3) PM2.5 pollution in winter and O3 pollution in summer are the main air quality challenges in Shanghai municipality. (4) Statistical analysis suggested that PM2.5, PM10, SO2 and NO2 concentrations were significantly negatively associated with precipitation (Prec) and atmosphere temperature (T) (p < 0.05), while the O3 concentration was significantly positively associated with Prec and T (p < 0.05). Lower accumulation of PM, SO2, NO2, and CO and more serious O3 pollution were revealed during months with higher temperature and more precipitation in Shanghai. The correlation between the socio-economic factors and the air pollutants suggest that further rigorous measures are needed to control PM2.5 and that further studies are needed to identify O3 formation mechanisms and control strategies. The results provide scientific insights into meteorological factors and socio-economic indicators influencing air pollution in Shanghai.
An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica
Authors: Scrivo Rossana , Silvestri Valeria , Ciciarello Francesco , Sessa Paola , Rutigliano Iolanda , Sestili Cristina , La Torre Giuseppe , Barbati Cristiana , Altobelli Alessio , Alessandri Cristiano , Ceccarelli Fulvia , Di Franco Manuela , Priori Roberta , Riccieri Valeria , Sili Scavalli Antonio , Spinelli Francesca Romana , Agati Luciano , Fedele Francesco , Gossetti Bruno , Conti Fabrizio , Valesini Guido
Published: July 2020

The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p < 0.0001) and APAD values (21.15/18.1–25.6 vs 18/16–22; p = 0.0013) was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r2 = 0.845 and r2 = 0.556, respectively; p < 0.01) was found. Leptin levels (pg/mL; median/25th–75th percentile) were higher in PMR than in MCVRF subjects (145.1/67–398.6 vs 59.5/39.3–194.3; p = 0.04). Serum levels of adiponectin (ng/mL) were higher in PMR patients (15.9/10.65–24.1 vs 6.1/2.8–22.7; p = 0.01), while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16–0.66 vs 0.26/0.14–1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.
Phosphorylation of steroid receptor coactivator-3 (SRC-3) at serine 857 is regulated by the p38MAPK-MK2 axis and affects NF-κB-mediated transcription
Authors: Shrestha Anup , Bruckmueller Henrike , Kildalsen Hanne , Kaur Gurjit , Gaestel Matthias , Wetting Hilde Ljones , Mikkola Ingvild , Seternes Ole-Morten
Published: July 2020

Steroid receptor coactivator-3 (SRC-3) regulates the activity of both nuclear hormone receptors and a number of key transcription factors. It is implicated in the regulation of cell proliferation, inflammation and in the progression of several common cancers including breast, colorectal and lung tumors. Phosphorylation is an important regulatory event controlling the activities of SRC-3. Serine 857 is the most studied phospho-acceptor site, and its modification has been reported to be important for SRC-3-dependent tumor progression. In this study, we show that the stress-responsive p38MAPK-MK2 signaling pathway controls the phosphorylation of SRC-3 at S857 in a wide range of human cancer cells. Activation of the p38MAPK-MK2 pathway results in the nuclear translocation of SRC-3, where it contributes to the transactivation of NF-kB and thus regulation of IL-6 transcription. The identification of the p38MAPK-MK2 signaling axis as a key regulator of SRC-3 phosphorylation and activity opens up new possibilities for the development and testing of novel therapeutic strategies to control both proliferative and metastatic tumor growth.
Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis
Authors: John Sarah , Rolnick Kevin , Wilson Leslie , Wong Silishia , Van Gelder Russell N. , Pepple Kathryn L.
Published: July 2020

This study reports the use of cell-type-specific in vivo bioluminescence to measure intraocular immune cell population dynamics during the course of inflammation in a mouse model of uveitis. Transgenic lines expressing luciferase in inflammatory cell subsets (myeloid cells, T cells, and B cells) were generated and ocular bioluminescence was measured serially for 35 days following uveitis induction. Ocular leukocyte populations were identified using flow cytometry and compared to the ocular bioluminescence profile. Acute inflammation is neutrophilic (75% of ocular CD45 + cells) which is reflected by a significant increase in ocular bioluminescence in one myeloid reporter line on day 2. By day 7, the ocular T cell population increases to 50% of CD45 + cells, leading to a significant increase in ocular bioluminescence in the T cell reporter line. While initially negligible (< 1% of CD45 + cells), the ocular B cell population increases to > 4% by day 35. This change is reflected by a significant increase in the ocular bioluminescence of the B cell reporter line starting on day 28. Our data demonstrates that cell-type-specific in vivo bioluminescence accurately detects changes in multiple intraocular immune cell populations over time in experimental uveitis. This assay could also be useful in other inflammatory disease models.