bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA
Authors: Sakata Dousatsu , Belov Oleg , Bordage Marie-Claude , Emfietzoglou Dimitris , Guatelli Susanna , Inaniwa Taku , Ivanchenko Vladimir , Karamitros Mathieu , Kyriakou Ioanna , Lampe Nathanael , Petrovic Ivan , Ristic-Fira Aleksandra , Shin Wook-Geun , Incerti Sebastien 
Published: November 2020

AbstractIonising radiation induced DNA damage and subsequent biological responses to it depend on the radiation’s track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic “fully integrated” MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of $$\gamma$$
γ
-H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.
Record high Pacific Arctic seawater temperatures and delayed sea ice advance in response to episodic atmospheric blocking
Authors: Kodaira Tsubasa , Waseda Takuji , Nose Takehiko , Inoue Jun 
Published: November 2020

AbstractArctic sea ice is rapidly decreasing during the recent period of global warming. One of the significant factors of the Arctic sea ice loss is oceanic heat transport from lower latitudes. For months of sea ice formation, the variations in the sea surface temperature over the Pacific Arctic region were highly correlated with the Pacific Decadal Oscillation (PDO). However, the seasonal sea surface temperatures recorded their highest values in autumn 2018 when the PDO index was neutral. It is shown that the anomalous warm seawater was a rapid ocean response to the southerly winds associated with episodic atmospheric blocking over the Bering Sea in September 2018. This warm seawater was directly observed by the R/V Mirai Arctic Expedition in November 2018 to significantly delay the southward sea ice advance. If the atmospheric blocking forms during the PDO positive phase in the future, the annual maximum Arctic sea ice extent could be dramatically reduced.
Two pursuit strategies for a single sensorimotor control task in blowfly
Authors: Varennes Leandre , Krapp Holger G. , Viollet Stephane 
Published: November 2020

AbstractEffective visuomotor coordination is a necessary requirement for the survival of many terrestrial, aquatic, and aerial animal species. We studied the kinematics of aerial pursuit in the blowfly Lucilia sericata using an actuated dummy as target for freely flying males. We found that the flies perform target tracking in the horizontal plane and target interception in the vertical plane. Our behavioural data suggest that the flies’ trajectory changes are a controlled combination of target heading angle and of the rate of change of the bearing angle. We implemented control laws in kinematic models and found that the contributions of proportional navigation strategy are negligible. We concluded that the difference between horizontal and vertical control relates to the difference in target heading angle the fly keeps constant: 0° in azimuth and 23° in elevation. Our work suggests that male Lucilia control both horizontal and vertical steerings by employing proportional controllers to the error angles. In horizontal plane, this controller operates at time delays as small as 10 ms, the fastest steering response observed in any flying animal, so far.
The double fascicular variations of the anterior talofibular ligament and the calcaneofibular ligament correlate with interconnections between lateral ankle structures revealed on magnetic resonance imaging
Authors: Szaro Paweł , Ghali Gataa Khaldun , Polaczek Mateusz , Ciszek Bogdan 
Published: November 2020

AbstractThe anterior talofibular ligament and the calcaneofibular ligament are the most commonly injured ankle ligaments. This study aimed to investigate if the double fascicular anterior talofibular ligament and the calcaneofibular ligament are associated with the presence of interconnections between those two ligaments and connections with non-ligamentous structures. A retrospective re-evaluation of 198 magnetic resonance imaging examinations of the ankle joint was conducted. The correlation between the double fascicular anterior talofibular ligament and calcaneofibular ligament and connections with the superior peroneal retinaculum, the peroneal tendon sheath, the tibiofibular ligaments, and the inferior extensor retinaculum was studied. The relationships between the anterior talofibular ligament’s and the calcaneofibular ligament’s diameters with the presence of connections were investigated. Most of the connections were visible in a group of double fascicular ligaments. Most often, one was between the anterior talofibular ligament and calcaneofibular ligament (74.7%). Statistically significant differences between groups of single and double fascicular ligaments were visible in groups of connections between the anterior talofibular ligament and the peroneal tendon sheath (p < 0.001) as well as the calcaneofibular ligament and the posterior tibiofibular ligament (p < 0.05), superior peroneal retinaculum (p < 0.001), and peroneal tendon sheath (p < 0.001). Differences between the thickness of the anterior talofibular ligament and the calcaneofibular ligament (p < 0.001), the diameter of the fibular insertion of the anterior talofibular ligament (p < 0.001), the diameter of calcaneal attachment of the calcaneofibular ligament (p < 0.05), and tibiocalcaneal angle (p < 0.01) were statistically significant. The presence of the double fascicular anterior talofibular ligament and the calcaneofibular ligament fascicles correlate with connections to adjacent structures.
Quantifying the contribution of established risk factors to cardiovascular mortality differences between Russia and Norway
Authors: Trias-Llimós Sergi , Pennells Lisa , Tverdal Aage , Kudryavtsev Alexander V. , Malyutina Sofia , Hopstock Laila A. , Iakunchykova Olena , Nikitin Yuri , Magnus Per , Kaptoge Stephen , Di Angelantonio Emanuele , Leon David A. 
Published: November 2020

AbstractSurprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40–69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1–40.1) among men and 22.1% (10.4–31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9–10 to 7–8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.
Increased TRPV4 expression in non-myelinating Schwann cells is associated with demyelination after sciatic nerve injury
Authors: Feng Xiaona , Takayama Yasunori , Ohno Nobuhiko , Kanda Hirosato , Dai Yi , Sokabe Takaaki , Tominaga Makoto 
Published: November 2020

AbstractTransient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system. Schwann cells (SCs) are primary glia cells that wrap around axons to form the myelin sheath in the peripheral nervous system. However, whether TRPV4 is expressed and functions in SCs is unclear. Here, we demonstrate functional expression of TRPV4 in mouse SCs and investigated its physiological significance. Deletion of TRPV4 did not affect normal myelin development for SCs in sciatic nerves in mice. However, after sciatic nerve cut injury, TRPV4 expression levels were remarkably increased in SCs following nerve demyelination. Ablation of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury.
Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells
Authors: Stoddart Leigh A. , Kindon Nicholas D. , Otun Omolade , Harwood Clare R. , Patera Foteini , Veprintsev Dmitry B. , Woolard Jeanette , Briddon Stephen J. , Franks Hester A. , Hill Stephen J. , Kellam Barrie 
Published: November 2020

AbstractTo study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the receptor or the limitations of dissociable fluorescent ligands, here we describe rational design of a compound that covalently and selectively labels a GPCR in living cells with a fluorescent moiety. We designed a fluorescent antagonist, in which the linker incorporated between pharmacophore (ZM241385) and fluorophore (sulfo-cyanine5) is able to facilitate covalent linking of the fluorophore to the adenosine A2A receptor. We pharmacologically and biochemically demonstrate irreversible fluorescent labelling without impeding access to the orthosteric binding site and demonstrate its use in endogenously expressing systems. This offers a non-invasive and selective approach to study function and localisation of native GPCRs.
An inducible CRISPR interference library for genetic interrogation of Saccharomyces cerevisiae biology
Authors: Momen-Roknabadi Amir , Oikonomou Panos , Zegans Maxwell , Tavazoie Saeed 
Published: November 2020

AbstractGenome-scale CRISPR interference (CRISPRi) is widely utilized to study cellular processes in a variety of organisms. Despite the dominance of Saccharomyces cerevisiae as a model eukaryote, an inducible genome-wide CRISPRi library in yeast has not yet been presented. Here, we present a genome-wide, inducible CRISPRi library, based on spacer design rules optimized for S. cerevisiae. We have validated this library for genome-wide interrogation of gene function across a variety of applications, including accurate discovery of haploinsufficient genes and identification of enzymatic and regulatory genes involved in adenine and arginine biosynthesis. The comprehensive nature of the library also revealed refined spacer design parameters for transcriptional repression, including location, nucleosome occupancy and nucleotide features. CRISPRi screens using this library can identify genes and pathways with high precision and a low false discovery rate across a variety of experimental conditions, enabling rapid and reliable assessment of genetic function and interactions in S. cerevisiae.
The PAR2 inhibitor I-287 selectively targets Gαq and Gα12/13 signaling and has anti-inflammatory effects
Authors: Avet Charlotte , Sturino Claudio , Grastilleur Sébastien , Gouill Christian Le , Semache Meriem , Gross Florence , Gendron Louis , Bennani Youssef , Mancini Joseph A. , Sayegh Camil E. , Bouvier Michel 
Published: November 2020

AbstractProtease-activated receptor-2 (PAR2) is involved in inflammatory responses and pain, therefore representing a promising therapeutic target for the treatment of immune-mediated inflammatory diseases. However, as for other GPCRs, PAR2 can activate multiple signaling pathways and those involved in inflammatory responses remain poorly defined. Here, we describe a new selective and potent PAR2 inhibitor (I-287) that shows functional selectivity by acting as a negative allosteric regulator on Gαq and Gα12/13 activity and their downstream effectors, while having no effect on Gi/o signaling and βarrestin2 engagement. Such selective inhibition of only a subset of the pathways engaged by PAR2 was found to be sufficient to block inflammation in vivo. In addition to unraveling the PAR2 signaling pathways involved in the pro-inflammatory response, our study opens the path toward the development of new functionally selective drugs with reduced liabilities that could arise from blocking all the signaling activities controlled by the receptor.
N-Heterocyclic carbene-catalyzed enantioselective hetero-[10 + 2] annulation
Authors: Peng Qiupeng , Li Shi-Jun , Zhang Bei , Guo Donghui , Lan Yu , Wang Jian 
Published: November 2020

AbstractHigher-order cycloadditions are a powerful strategy for the construction of polycycles in one step. However, an efficient and concise version for the induction of asymmetry is lacking. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and could be an ideal choice for enantioselective higher-order cycloadditions. Here, we report an enantioselective [10 + 2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields, and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory calculations provide an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol.
FAM225A promotes sorafenib resistance in hepatocarcinoma cells through modulating miR-130a-5p–CCNG1 interaction network
Authors: Liu Yan-Tong , Liu Guo-Qing , Huang Jing-Min 
Published: November 2020

Abstract
Chemotherapy resistance is still a key hurdle in current hepatocellular carcinoma (HCC) treatment. Therefore, clarifying the molecular mechanisms contributing to this acquired resistance is urgent for the effective treatment of liver cancer. In this research, we observed that lncRNA FAM225A expression is dramatically up-regulated not only in HCC tissues and cell lines but also in sorafenib-resistant HepG2/SOR cells. Moreover, FAM225A knockdown significantly weakened HepG2/SOR cells resistance to sorafenib treatment by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Similar results were obtained from the tumor xenograft model in mice. Further mechanistic researches revealed that the direct interaction between FAM225A and miR-130a-5p, while miR-130a-5p negatively modulated Cyclin G1 (CCNG1) expression by targeting 3′UTR of CCNG1. MiR-130a-5p inhibition or CCNG1 overexpression could partially offset FAM225A knockdown-induced increased viability of HepG2/SOR cells in response to sorafenib challenge. Collectively, our findings provide evidence that FAM225A/miR-130a-5p/CCNG1 interaction network regulates the resistance of HCC cells to sorafenib treatment and could supply a possible strategy for restoring sorafenib sensitivity in HCC therapy.
Contrasting association of Leptin receptor polymorphisms and haplotypes with polycystic ovary syndrome in Bahraini and Tunisian women: a case–control study
Authors: Dallel Meriem , Douma Zeineb , Finan Ramzi R. , Hachani Feten , Letaifa Dhafer B. , Mahjoub Touhami , Almawi Wassim Y. 
Published: November 2020

Abstract
Background: The present study examined the contribution of ethnicity to the association of leptin receptor gene (LEPR) gene variants with polycystic ovary syndrome (PCOS) in Tunisian and Bahraini Arabic-speaking women.
Methods: Subjects consisted of 320 women with PCOS, and 446 eumenorrhic women from Tunisia, and 242 women with PCOS and 238 controls from Bahrain. Genotyping of (exonic) rs1137100 and rs1137101 and (intronic) rs2025804 LEPR variants was done by allelic exclusion.
Results: The minor allele frequencies (MAFs) of rs1137100 and rs1137101 were significantly different between PCOS cases and control women from Bahrain but not Tunisia, and LEPR rs1137101 was associated with increased PCOS susceptibility only in Bahraini subjects. Furthermore, rs1137100 was associated with decreased PCOS risk among Bahrainis under codominant and recessive models; rs1137100 was negatively associated with PCOS in Tunisians after controlling for testosterone. In addition, rs2025804 was associated with increased PCOS risk among Tunisian but not Bahraini women, after adjusting for key covariates. Negative correlation was seen between rs1137101 and triglycerides in Tunisians, while homeostasis model assessment of insulin resistance (HOMA-IR) and insulin correlated with rs2025804 and rs1137101 among Bahraini subjects, and rs1137101 correlated with estradiol and prolactin. Taking TAG haplotype as common, positive association of TAA and negative association of TGG haplotype with PCOS was seen among Bahraini women; no three-locus PCOS-associated haplotypes were found in Tunisians.
Conclusions: The present study is the first to demonstrate the contribution of ethnicity to the association of LEPR gene variants with PCOS, thereby highlighting the significance of controlling for ethnicity in gene association investigations.
FRZBas a key molecule in abdominal aortic aneurysm progression affecting vascular integrity
Authors: Oh Chang-Kyu , Ko Yeji , Park Jeong Jun , Heo Hye Jin , Kang Junho , Kwon Eun Jung , Kang Ji Wan , Lee Yoonsung , Myung Kyungjae , Kang Jin Mo , Ko Dai Sik , Kim Yun Hak 
Published: November 2020

AbstractAbdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell–cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.
Geometric modeling of M87* as a Kerr black hole or a non-Kerr compact object
Authors: Vincent F. H. , Wielgus M. , Abramowicz M. A. , Gourgoulhon E. , Lasota J.-P. , Paumard T. , Perrin G. 
Published: November 2020

Context. The Event Horizon Telescope (EHT) collaboration recently obtained the first images of the surroundings of the supermassive compact object M87* at the center of the galaxy M87. This provides a fascinating probe of the properties of matter and radiation in strong gravitational fields. It is important to determine from the analysis of these results what can and cannot be inferred about the nature of spacetime around M87*
Aims. We want to develop a simple analytic disk model for the accretion flow of M87*. Compared to general-relativistic magnetohydrodynamic models, this new approach has the advantage that it is independent of the turbulent character of the flow and is controlled by only a few easy-to-interpret, physically meaningful parameters. We want to use this model to predict the image of M87*, assuming that it is either a Kerr black hole or an alternative compact object.
Methods. We computed the synchrotron emission from the disk model and propagate the resulting light rays to the far-away observer by means of relativistic ray tracing. Such computations were performed assuming different spacetimes, such as Kerr, Minkowski, nonrotating ultracompact star, rotating boson star, or Lamy spinning wormhole. We performed numerical fits of these models to the EHT data.
Results. We discuss the highly lensed features of Kerr images and show that they are intrinsically linked to the accretion-flow properties and not only to gravitation. This fact is illustrated by the notion of the secondary ring, which we introduce. Our model of a spinning Kerr black hole predicts mass and orientation consistent with the EHT interpretation. The non-Kerr images result in a similar quality of numerical fits and may appear very similar to Kerr images, once blurred to the EHT resolution. This implies that a strong test of the Kerr spacetime may be out of reach with the current data. We note that future developments of the EHT could alter this situation.
Conclusions. Our results show the importance of studying alternatives to the Kerr spacetime to be able to test the Kerr paradigm unambiguously. More sophisticated treatments of non-Kerr spacetimes and more advanced observations are needed to proceed further in this direction.