bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the Earth's Polar Outflow From Mid‐Archean to Present
Authors: Kislyakova K. G. , Johnstone C. P. , Scherf M. , Holmström M. , Alexeev I. I. , Lammer H. , Khodachenko M. L. , Güdel M. 
Published: July 2020

AbstractThe development of habitable conditions on Earth is tightly connected to the evolution of its atmosphere, which is strongly influenced by atmospheric escape. We investigate the evolution of the polar ion outflow from the open field line bundle, which is the dominant escape mechanism for the modern Earth. We perform Direct Simulation Monte Carlo (DSMC) simulations and estimate the upper limits on escape rates from the Earth's open field line bundle starting from 3 gigayears ago (Ga) to present assuming the present‐day composition of the atmosphere. We perform two additional simulations with lower mixing ratios of oxygen of 1% and 15% to account for the conditions shortly after the Great Oxydation Event (GOE). We estimate the maximum loss rates due to polar outflow 3 gigayears ago of 3.3×1027 s−1 and 2.4×1027 s−1 for oxygen and nitrogen, respectively. The total integrated mass loss equals to 39% and 10% of the modern atmosphere's mass, for oxygen and nitrogen, respectively. According to our results, the main factors that governed the polar outflow in the considered time period are the evolution of the XUV radiation of the Sun and the atmosphere's composition. The evolution of the Earth's magnetic field plays a less important role. We conclude that although the atmosphere with the present‐day composition can survive the escape due to polar outflow, a higher level of CO2 between 3.0 and 2.0 Ga was likely necessary to reduce the escape.
Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer
Authors: Green Darrell , Eyre Heather , Singh Archana , Taylor Jessica T. , Chu Jason , Jeys Lee , Sumathi Vaiyapuri , Coonar Aman , Rassl Doris , Babur Muhammad , Forster Duncan , Alzabin Saba , Ponthan Frida , McMahon Adam , Bigger Brian , Reekie Tristan , Kassiou Michael , Williams Kaye , Dalmay Tamas , Fraser William D. , Finegan Katherine G. 
Published: July 2020

AbstractMetastasis is the leading cause of cancer-related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark, but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single-cell RNA-sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed mitogen-activated protein kinase 7/matrix metallopeptidase 9 (MAPK7/MMP9) signalling as a driver for primary bone cancer metastasis. RNA interference knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable.
Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer
Authors: Zhou Yang , Liu Fei , Xu Qinyang , Yang Bikang , Li Xiao , Jiang Shuheng , Hu Lipeng , Zhang Xueli , Zhu Lili , Li Qing , Zhu Xiaolu , Shao Hongfang , Dai Miao , Shen Yifei , Ni Bo , Wang Shuai , Zhang Zhigang , Teng Yincheng 
Published: July 2020

AbstractCervical cancer (CC) remains highest in the mortality of female reproductive system cancers, while cisplatin (CDDP) resistance is the one of main reasons for the lethality. Preceding evidence has supported that karyopherins are associated with chemoresistance. In this study, we simultaneously compared CDDP-incomplete responders with CDDP-complete responders of CC patients and CDDP‐insensitive CC cell lines with CDDP‐sensitive group. We finally identified that DNA-PKcs (PRKDC) was related to CDDP sensitivity after overlapping in CC sample tissues and CC cell lines. Further functional assay revealed that targeting PRKDC by shRNA and NU7026 (specific PRKDC inhibitor) could enhance CDDP sensitivity in vitro and in vivo, which was mediated by impairing DNA damage repair pathway in CC. Mechanistically, we found that PRKDC was transcriptionally upregulated by CCAAT/enhancer-binding protein delta (CEBPD), while intriguingly, CDDP treatment strengthened the transcriptional activity of CEBPD to PRKDC. We further disclosed that Importin 4 (IPO4) augmented the nuclear translocation of CEBPD through nuclear localization signals (NLS) to activate PRKDC-mediated DNA damage repair in response to CDDP. Moreover, we demonstrated that IPO4 and CEBPD knockdown improved CDDP-induced cytotoxicity in vitro and in vivo. Together, we shed the novel insight into the role of IPO4 in chemosensitivity and provide a clinical translational potential to enhance CC chemosensitivity since the IPO4-CEBPD-PRKDC axis is actionable via NU7026 (PRKDC inhibitor) or targeting IPO4 in combination with CDDP.
Why has Japan become the world’s most long-lived country: insights from a food and nutrition perspective
Authors: Tsugane Shoichiro 
Published: July 2020

AbstractIn an international comparison of recent mortality statistics among G7 countries, Japan had the longest average life expectancy, primarily due to remarkably low mortality rates from ischemic heart disease and cancer (particularly breast and prostate). As recently as the 1960s, life expectancy in Japan was the shortest among the G7 countries, owing to relatively high mortality from cerebrovascular disease—particularly intracerebral hemorrhage—and stomach cancer. Mortality rates for these diseases subsequently decreased significantly while the already low rates for ischemic heart disease and cancer also decreased, resulting in Japanese life expectancy becoming the longest. The low mortality rates from ischemic heart disease and cancer are thought to reflect the low prevalence of obesity in Japan; low intake of red meat, specifically saturated fatty acids; and high intakes of fish, specifically n-3 polyunsaturated fatty acids, plant foods such as soybeans, and nonsugar-sweetened beverages such as green tea. The decreasing mortality rates from cerebrovascular disease are thought to reflect the increases in animal foods, milk, and dairy products and consequently in saturated fatty acids and calcium, together with a decrease in salt intake which may have led to a decrease in blood pressure. This decrease in salt and highly salted foods also seems to account for the decrease in stomach cancer. The typical Japanese diet as characterized by plant food and fish as well as modest Westernized diet such as meat, milk and dairy products might be associated with longevity in Japan.
Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins
Authors: Alzahofi Noura , Welz Tobias , Robinson Christopher L. , Page Emma L. , Briggs Deborah A. , Stainthorp Amy K. , Reekes James , Elbe David A. , Straub Felix , Kallemeijn Wouter W. , Tate Edward W. , Goff Philip S. , Sviderskaya Elena V. , Cantero Marta , Montoliu Lluis , Nedelec Francois , Miles Amanda K. , Bailly Maryse , Kerkhoff Eugen , Hume Alistair N. 
Published: July 2020

AbstractCell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in opposition to microtubules. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here, we show that the SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va-dependent transport in melanocytes. Thus, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIREs to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this, we suggest a model in which organelles and force generators (motors and track assemblers) are linked, forming an organelle-based, cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm.
Gene regulatory network inference from sparsely sampled noisy data
Authors: Aalto Atte , Viitasaari Lauri , Ilmonen Pauliina , Mombaerts Laurent , Gonçalves Jorge 
Published: July 2020

AbstractThe complexity of biological systems is encoded in gene regulatory networks. Unravelling this intricate web is a fundamental step in understanding the mechanisms of life and eventually developing efficient therapies to treat and cure diseases. The major obstacle in inferring gene regulatory networks is the lack of data. While time series data are nowadays widely available, they are typically noisy, with low sampling frequency and overall small number of samples. This paper develops a method called BINGO to specifically deal with these issues. Benchmarked with both real and simulated time-series data covering many different gene regulatory networks, BINGO clearly and consistently outperforms state-of-the-art methods. The novelty of BINGO lies in a nonparametric approach featuring statistical sampling of continuous gene expression profiles. BINGO’s superior performance and ease of use, even by non-specialists, make gene regulatory network inference available to any researcher, helping to decipher the complex mechanisms of life.
Design of a MAPK signalling cascade balances energetic cost versus accuracy of information transmission
Authors: Anders Alexander , Ghosh Bhaswar , Glatter Timo , Sourjik Victor 
Published: July 2020

AbstractCellular processes are inherently noisy, and the selection for accurate responses in presence of noise has likely shaped signalling networks. Here, we investigate the trade-off between accuracy of information transmission and its energetic cost for a mitogen-activated protein kinase (MAPK) signalling cascade. Our analysis of the pheromone response pathway of budding yeast suggests that dose-dependent induction of the negative transcriptional feedbacks in this network maximizes the information per unit energetic cost, rather than the information transmission capacity itself. We further demonstrate that futile cycling of MAPK phosphorylation and dephosphorylation has a measurable effect on growth fitness, with energy dissipation within the signalling cascade thus likely being subject to evolutionary selection. Considering optimization of accuracy versus the energetic cost of information processing, a concept well established in physics and engineering, may thus offer a general framework to understand the regulatory design of cellular signalling systems.
Free space super focusing using all dielectric hyperbolic metamaterial
Authors: Salama Norhan A. , Desouky Mai , Obayya S. S. A. , Swillam Mohamed A. 
Published: July 2020

AbstractDespite that Hyperbolic Metamaterial (HMM) has demonstrated sub-wavelength focusing inside of it, sub-wavelength imaging in free space of HMM is rarely introduced. The decay of hyperbolic momentum space outside the hyperbolic medium has hindered the realization of sub-wavelengh focusing in the near field of HMM. Furthermore, manipulating the negatively refracted waves exiting the HMM have addressed another major obstacle to realize free space sub-wavelength focusing. In this work, we report extended sub-wavelength focusing in free space based on negative refraction of light exiting the HMM. The proposed structure is composed of multilayers of doped InAs/intrinsic InAs integrated with metallic slit. We theoretically simulate the doped InAs/intrinsic InAs HMM and investigate the negative refraction behavior outside the HMM. We optimized the structure for achieving high resolution down to 0.2λ, extended to a distance of 3.2 µm in free space. Also, sub-wavelength focusing in free space has been studied at different doping concentrations showing that the small doping concentrations exhibit enhancement in resolution at short distances up to 600 nm away from the HMM. Extending the focusing distance is achieved up to distance 3.5 µm from the hyperbolic structure by manipulating the doping concentration. This proposed lens configuration is expected to find potential usage in mid IR thermal imaging and photolithography application.
Temporal clustering of prey in wildlife passages provides no evidence of a prey-trap
Authors: Martinig April Robin , Riaz Mahnoor , St. Clair Colleen Cassady 
Published: July 2020

AbstractWildlife passages are structures built across roads to facilitate wildlife movement and prevent wildlife collisions with vehicles. The efficacy of these structures could be reduced if they funnel prey into confined spaces at predictable locations that are exploited by predators. We tested the so-called prey-trap hypothesis using remote cameras in 17 wildlife passages in Quebec, Canada from 2012 to 2015 by measuring the temporal occurrence of nine small and medium-sized mammal taxa (< 30 kg) that we classified as predators and prey. We predicted that the occurrence of a prey-trap would be evidenced by greater frequencies and shorter latencies of sequences in which predators followed prey, relative to prey–prey sequences. Our results did not support the prey-trap hypothesis; observed prey–predator sequences showed no difference or were less frequent than expected, even when prey were unusually abundant or rare or at sites with higher proportions of predators. Prey–predator latencies were also 1.7 times longer than prey–prey sequences. These results reveal temporal clustering of prey that may dilute predation risk inside wildlife passages. We encourage continued use of wildlife passages as mitigation tools.
Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis
Authors: Bellafante Elena , McIlvride Saraid , Nikolova Vanya , Fan Hei Man , Manna Luiza Borges , Chambers Jenny , Machirori Mavis , Banerjee Anita , Murphy Kevin , Martineau Marcus , Schoonjans Kristina , Marschall Hanns-Ulrich , Jones Peter , Williamson Catherine 
Published: July 2020

AbstractWomen with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of developing gestational diabetes mellitus and have impaired glucose tolerance whilst cholestatic. FXR and TGR5 are modulators of glucose metabolism, and FXR activity is reduced in normal pregnancy, and further in ICP. We aimed to investigate the role of raised serum bile acids, FXR and TGR5 in gestational glucose metabolism using mouse models. Cholic acid feeding resulted in reduced pancreatic β-cell proliferation and increased apoptosis in pregnancy, without altering insulin sensitivity, suggesting that raised bile acids affect β-cell mass but are insufficient to impair glucose tolerance. Conversely, pregnant Fxr−/− and Tgr5−/− mice are glucose intolerant and have reduced insulin secretion in response to glucose challenge, and Fxr−/− mice are also insulin resistant. Furthermore, fecal bile acids are reduced in pregnant Fxr−/− mice. Lithocholic acid and deoxycholic acid, the principal ligands for TGR5, are decreased in particular. Therefore, we propose that raised serum bile acids and reduced FXR and TGR5 activity contribute to the altered glucose metabolism observed in ICP.
Whole genome re-sequencing reveals recent signatures of selection in three strains of farmed Nile tilapia (Oreochromis niloticus)
Authors: Cádiz María I. , López María E. , Díaz-Domínguez Diego , Cáceres Giovanna , Yoshida Grazyella M. , Gomez-Uchida Daniel , Yáñez José M. 
Published: July 2020

AbstractNile tilapia belongs to the second most cultivated group of fish in the world, mainly because of its favorable characteristics for production. Genetic improvement programs and domestication process of Nile tilapia may have modified the genome through selective pressure, leaving signals that can be detected at the molecular level. In this work, signatures of selection were identified using genome-wide SNP data, by two haplotype-based (iHSandRsb) and oneFSTbased method. Whole-genome re-sequencing of 326 individuals from three strains (A, B and C) of farmed tilapia maintained in Brazil and Costa Rica was carried out using Illumina HiSeq 2500 technology. After applying conventional SNP-calling and quality-control filters, ~ 1.3 M high-quality SNPs were inferred and used as input for theiHS,RsbandFSTbased methods. We detected several candidate genes putatively subjected to selection in each strain. A considerable number of these genes are associated with growth (e.g.NCAPG, KLF3, TBC1D1, TTN), early development (e.g.FGFR3, PFKFB3), and immunity traits (e.g.NLRC3,PIGR,MAP1S). These candidate genes represent putative genomic landmarks that could be associated to traits of biological and commercial interest in farmed Nile tilapia.
Examination of intestinal ultrastructure, bowel wall apoptosis and tight junctions in the early phase of sepsis
Authors: Obermüller Beate , Frisina Noemi , Meischel Martin , Singer Georg , Stanzl-Tschegg Stefanie , Lichtenegger Helga , Kolb Dagmar , Klymiuk Ingeborg , Till Holger , Castellani Christoph 
Published: July 2020

AbstractGut hyperpermeability can be caused by either apoptosis of the intestinal epithelium or altered status, permeability or porosity of tight junctions. This project aims to elucidate these mechanisms in the early phase of sepsis. Eighteen male wild type mice were randomized to two groups. All mice received one single gavage of fluorescein isothiocyanate (FITC) dextran 30 min before intervention. One group (n = 10) underwent cecal ligation and puncture to induce sepsis. The other group (n = 8) was sham operated. Septic animals exhibited significantly increased permeability for FITC 8 h post-operatively. Significantly increased serum interleukin-6, tumor-necrosis-factor-alpha and interleukin-1-beta confirmed sepsis. Septic animals showed significant bowel wall inflammation of ileum and colon samples. PCR revealed significantly increased expression of claudin-2 and decreased expressions of claudin-4, tight-junction-protein-1 and occludin-1 resembling increased permeability of tight junctions. However, these alterations could not be confirmed at the protein level. Light microscopy revealed significant dilatation of intercellular spaces at the basal sections of intestinal epithelial cells (IEC) in septic animals confirmed by increased intercellular spaces at the level of tight junctions and adherens junctions in electron microscopy (TEM). In small angle X-ray scattering no increase in number or size of nanopores could be shown in the bowel wall. HOECHST staining and PCR of ileum samples for apoptosis markers proofed no relevant differences in intestinal epithelial cell apoptosis between the groups. Intestinal hyperpermeability in septic animals was most likely caused by alterations of the intercellular contacts and not by apoptosis or increased size/number of nanopores of intestinal epithelial cells in this murine model of early sepsis.
Scarce and directly beneficial reputations support cooperation
Authors: Samu Flóra , Számadó Szabolcs , Takács Károly 
Published: July 2020

AbstractA human solution to the problem of cooperation is the maintenance of informal reputation hierarchies. Reputational information contributes to cooperation by providing guidelines about previous group-beneficial or free-rider behaviour in social dilemma interactions. How reputation information could be credible, however, remains a puzzle. We test two potential safeguards to ensure credibility: (i) reputation is a scarce resource and (ii) it is not earned for direct benefits. We test these solutions in a laboratory experiment in which participants played two-person Prisoner’s Dilemma games without partner selection, could observe some other interactions, and could communicate reputational information about possible opponents to each other. Reputational information clearly influenced cooperation decisions. Although cooperation was not sustained at a high level in any of the conditions, the possibility of exchanging third-party information was able to temporarily increase the level of strategic cooperation when reputation was a scarce resource and reputational scores were directly translated into monetary benefits. We found that competition for monetary rewards or unrestricted non-monetary reputational rewards helped the reputation system to be informative. Finally, we found that high reputational scores are reinforced further as they are rewarded with positive messages, and positive gossip was leading to higher reputations.
Measurement of optical reflection and temperature changes after blood occlusion using a wearable device
Authors: Gu Jian , Tomioka Yoko , Kida Koichi , Xiao Yingyi , Saito Itsuro , Okazaki Mutsumi , Someya Takao , Sekino Masaki 
Published: July 2020

AbstractEarly detection of compromised circulation is essential for postoperative monitoring of free flap. Hourly clinical check-ups such as inspection and palpation still result in a delay in detection. Conversely, optical reflection and temperature measurement are useful alternatives for detecting blood circulation. However, conventional methods that verify ischemia and congestion within a short period have not been reported. In this study, we measured short-term changes in optical reflection and temperature in a rat flap using a wearable flexible sensor probe previously developed in our laboratory. Five ischemia and five congestion groin flap models were measured using a sensor probe and reference devices. Curve fitting was performed on transition signals to evaluate changes in signals and their time constants. The optical reflection signal decreased after venous ligation and increased after arterial ligation. The parameters of the fitted curves indicate a significant difference between congestion and ischemia at p < 0.01 (probability value), which was detected within a few minutes after ligation. However, insufficient significance was observed in the temperature signal. Our method gives supporting information to verify ischemia and congestion, and has the potential to rapidly detect compromised circulation.