bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner
Authors: Li Jie , Li Xinle , Liu Daquan , Zhang Shiqi , Tan Nian , Yokota Hiroki , Zhang Ping 
Published: December 2020

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.
SOX9-activated FARSA-AS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9
Authors: Zhou Taicheng , Wu Lili , Ma Ning , Tang Fuxin , Yu Zhuomin , Jiang Zhipeng , Li Yingru , Zong Zhen , Hu Kunpeng 
Published: December 2020

AbstractSRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family, SOX9 (SRY-box transcription factor 9) has been reported to be highly expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized that SOX9 could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated that SOX9 was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation of SOX9 in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing of SOX9 suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), while FARSA-AS1 elevated SOX9 in turn by absorbing miR-18b-5p and augmented FARSA via sequestering miR-28-5p. Furthermore, loss of FARSA-AS1 hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified that FARSA-AS1 aggravated the malignancy in CRC by enhancing SOX9 and FARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSA loop in CRC, which provides some clews of promising targets for CRC.
Sirtuin 1-dependent regulation of high mobility box 1 in hypoxia–reoxygenated brain microvascular endothelial cells: roles in neuronal amyloidogenesis
Authors: Lee Young-Sun , Choi Ji-Young , Mankhong Sakulrat , Moon Sohee , Kim Sujin , Koh Young Ho , Kim Ji-Hye , Kang Ju-Hee 
Published: December 2020

AbstractHypoxia–reperfusion injury is one of the major risk factors for neurodegeneration. However, it is unclear whether ischaemic damage in brain microvascular endothelial cells plays roles in neurodegeneration, particularly in the amyloidogenic changes contributing to the development of Alzheimer’s disease (AD) pathologies. Therefore, we investigated the roles of hypoxia–reoxygenation (H/R)-induced release of high mobility group box protein 1 (HMGB1), a risk molecule for AD pathogenesis in the ischaemic damaged brain, from human brain microvascular endothelial cells (HBMVECs) in neuronal amyloid-beta (Aβ) production. H/R increased nuclear–cytosolic translocation and secretion of HMGB1 in HBMVECs, along with increased permeability and HMGB1-dependent p-c-Jun activation. In addition, H/R increased the expression of Sirtuin 1 (Sirt1), coincident with an increase of intracellular Sirt1–HMGB1 binding in HBMVECs. H/R increased the acetylation of HMGB1 and extracellular secretion, which was significantly inhibited by Sirt1 overexpression. Furthermore, Sirt1 contributed to autophagy-mediated endogenous HMGB1 degradation. More importantly, treatment of neuronal cells with conditioned medium from H/R-stimulated HBMVECs (H/R-CM) activated their amyloidogenic pathways. The neuronal amyloidogenic changes (i.e. increased levels of extracellular Aβ40 and Aβ42) by H/R-CM from HBMVECs were further increased by Sirt1 inhibition, which was significantly suppressed by neutralization of the HMGB1 in H/R-CM. Collectively, our results suggest that HMGB1 derived from H/R-stimulated HBMVECs contributes to amyloidogenic pathways in neurons playing roles in the pathogenesis of AD, which are regulated by endothelial Sirt1.
Singular magnetic anisotropy in the nematic phase of FeSe
Authors: Zhou Rui , Scherer Daniel D. , Mayaffre Hadrien , Toulemonde Pierre , Ma Mingwei , Li Yuan , Andersen Brian M. , Julien Marc-Henri 
Published: December 2020

AbstractFeSe is arguably the simplest, yet the most enigmatic, iron-based superconductor. Its nematic but non-magnetic ground state is unprecedented in this class of materials and stands out as a current puzzle. Here, our nuclear magnetic resonance measurements in the nematic state of mechanically detwinned FeSe reveal that both the Knight-shift and the spin–lattice relaxation rate 1/T1 possess an in-plane anisotropy opposite to that of the iron pnictides LaFeAsO and BaFe2As2. Using a microscopic electron model that includes spin–orbit coupling, our calculations show that an opposite quasiparticle weight ratio between the dxz and dyz orbitals leads to an opposite anisotropy of the orbital magnetic susceptibility, which explains our Knight-shift results. We attribute this property to a different nature of nematic order in the two compounds, predominantly bond type in FeSe and onsite ferro-orbital in pnictides. The T1 anisotropy is found to be inconsistent with existing neutron scattering data in FeSe, showing that the spin fluctuation spectrum reveals surprises at low energy, possibly from fluctuations that do not break C4 symmetry. Therefore, our results reveal that important information is hidden in these anisotropies and they place stringent constraints on the low-energy spin correlations as well as on the nature of nematicity in FeSe.
Efficient hybrid de novo assembly of human genomes with WENGAN
Authors: Di Genova Alex , Buena-Atienza Elena , Ossowski Stephan , Sagot Marie-France 
Published: December 2020

AbstractGenerating accurate genome assemblies of large, repeat-rich human genomes has proved difficult using only long, error-prone reads, and most human genomes assembled from long reads add accurate short reads to polish the consensus sequence. Here we report an algorithm for hybrid assembly, WENGAN, that provides very high quality at low computational cost. We demonstrate de novo assembly of four human genomes using a combination of sequencing data generated on ONT PromethION, PacBio Sequel, Illumina and MGI technology. WENGAN implements efficient algorithms to improve assembly contiguity as well as consensus quality. The resulting genome assemblies have high contiguity (contig NG50: 17.24–80.64 Mb), few assembly errors (contig NGA50: 11.8–59.59 Mb), good consensus quality (QV: 27.84–42.88) and high gene completeness (BUSCO complete: 94.6–95.2%), while consuming low computational resources (CPU hours: 187–1,200). In particular, the WENGAN assembly of the haploid CHM13 sample achieved a contig NG50 of 80.64 Mb (NGA50: 59.59 Mb), which surpasses the contiguity of the current human reference genome (GRCh38 contig NG50: 57.88 Mb).
Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
Authors: Mehta Kosha J. , Sharp Paul A. 
Published: December 2020

AbstractLiver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0–2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.
Feasibility of continuous fever monitoring using wearable devices
Authors: Smarr Benjamin L. , Aschbacher Kirstin , Fisher Sarah M. , Chowdhary Anoushka , Dilchert Stephan , Puldon Karena , Rao Adam , Hecht Frederick M. , Mason Ashley E. 
Published: December 2020

AbstractElevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported COVID-19 infections. These cases provide the first evidence that illness-associated elevations in peripheral temperature are observable using wearable devices and correlate with self-reported fever. Our analyses support the hypothesis that wearable sensors can detect illnesses in the absence of symptom recognition. Finally, these data support the hypothesis that prediction of illness onset is possible using continuously generated physiological data collected by wearable sensors. Our findings should encourage further research into the role of wearable sensors in public health efforts aimed at illness detection, and underscore the importance of integrating temperature sensors into commercially available wearables.
Opisthobranch grazing results in mobilisation of spherulous cells and re-allocation of secondary metabolites in the sponge Aplysina aerophoba
Authors: Wu Yu-Chen , García-Altares María , Pintó Berta , Ribes Marta , Hentschel Ute , Pita Lucía 
Published: December 2020

AbstractSponges thrive in marine benthic communities due to their specific and diverse chemical arsenal against predators and competitors. Yet, some animals specifically overcome these defences and use sponges as food and home. Most research on sponge chemical ecology has characterised crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about chemical dynamics in the tissue and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opisthobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry, MALDI-imaging MS). We characterised the distribution of two major brominated alkaloids in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalised wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidised compounds, causing T. perversa deterrence. During grazing, T. perversa’s way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.
Poor oral hygiene and dental caries predict high mortality rate in hemodialysis: a 3-year cohort study
Authors: Mizutani Koji , Mikami Risako , Gohda Tomohito , Gotoh Hiromichi , Aoyama Norio , Matsuura Takanori , Kido Daisuke , Takeda Kohei , Izumi Yuichi , Sasaki Yoshiyuki , Iwata Takanori 
Published: December 2020

AbstractThe aim of this study was to investigate the impact of oral hygiene, periodontal diseases, and dental caries on all-cause mortality in hemodialysis. This prospective cohort study included 266 patients with end-stage renal disease who were undergoing hemodialysis. Medical interviews, blood biochemical tests, and comprehensive dental examinations including periodontal pocket examination on all teeth and dental plaque accumulation by debris index-simplified (DI-S), were performed. Survival rates were assessed at a 3-year follow-up. Overall, 207 patients were included in the longitudinal analysis, and 38 subjects died during the follow-up period. Cox proportional hazards analysis of the multivariate model demonstrated that the highest tertile of DI-S had a significantly higher risk of all-cause mortality than the lowest two tertiles after adjustment for age, sex, smoking habit, body mass index, diabetes, prior cardiovascular disease, hemodialysis vintage, high sensitivity C-reactive protein, albumin, and number of remaining teeth (hazard ratio, 3.04; 95% confidence interval, 1.50–6.17; p = 0.002). Moreover, the number of decayed teeth significantly increased the hazard ratio to 1.21 (95% confidence interval, 1.06.1.37; p = 0.003). This study suggests that accumulated dental plaque and untreated decay, but not periodontal disease, may be independently associated with all-cause mortality in patients undergoing hemodialysis.
Biodegradation of selected hydrocarbons by novel bacterial strains isolated from contaminated Arabian Gulf sediment
Authors: Al-Thukair Assad Ahmed , Malik Karim , Nzila Alexis 
Published: December 2020

AbstractThree strains of novel bacteria were isolated from oil-contaminated sediment from the Arabian Gulf (Brevibacillus brevis T2C2008, Proteus mirabilis T2A12001, and Rhodococcus quinshengi TA13008). The isolated strains were tested for their degrading efficacy of low and high molecular hydrocarbon (naphthalene and pyrene). The efficacy of the two-hydrocarbon degradation by the isolates bacterial was determined at a temperature of 25 °C and 37 °C and pH of 5.0 and 9.0. In inoculated media at 37 °C, Rhodococcus qinshengi fully metabolized naphthalene and degrade 56% of pyrene. Brevibacillus brevis break down over 80% of naphthalene at room temperatures (25 °C). However, it was found that P. mirabilis and R. qinshengi biodegraded nearly 94% of naphthalene in the incubated media. The capacity for pyrene and naphthalene degradation in varying pH and temperature conditions was shown to be significant in Rhodococcus qinshengi because of its mineralization exceeding 50% across the tested pH and temperature. This implies that the isolated strains are ideal for biodegradation of contaminated sediment with naphthalene and pyrene.
Liquid temperature prediction in bubbly flow using ant colony optimization algorithm in the fuzzy inference system as a trainer
Authors: Babanezhad Meisam , Behroyan Iman , Nakhjiri Ali Taghvaie , Marjani Azam , Heydarinasab Amir , Shirazian Saeed 
Published: December 2020

AbstractIn the current research paper a novel hybrid model combining first-principle and artificial intelligence (AI) was developed for simulation of a chemical reactor. We study a 2-dimensional reactor with heating sources inside it by using computational fluid dynamics (CFD). The type of considered reactor is bubble column reactor (BCR) in which a two-phase system is created. Results from CFD were analyzed in two different stages. The first stage, which is the learning stage, takes advantage of the swarm intelligence of the ant colony. The second stage results from the first stage, and in this stage, the predictions are according to the previous stage. This stage is related to the fuzzy logic system, and the ant colony optimization learning framework is build-up this part of the model. Ants movements or swarm intelligence of ants lead to the optimization of physical, chemical, or any kind of processes in nature. From point to point optimization, we can access a kind of group optimization, meaning that a group of data is studied and optimized. In the current study, the swarm intelligence of ants was used to learn the data from CFD in different parts of the BCR. The learning was also used to map the input and output data and find out the complex connection between the parameters. The results from mapping the input and output data show the full learning framework. By using the AI framework, the learning process was transferred into the fuzzy logic process through membership function specifications; therefore, the fuzzy logic system could predict a group of data. The results from the swarm intelligence of ants and fuzzy logic suitably adapt to CFD results. Also, the ant colony optimization fuzzy inference system (ACOFIS) model is employed to predict the temperature distribution in the reactor based on the CFD results. The results indicated that instead of solving Navier–Stokes equations and complex solving procedures, the swarm intelligence could be used to predict a process. For better comparisons and assessment of the ACOFIS model, this model is compared with the genetic algorithm fuzzy inference system (GAFIS) and Particle swarm optimization fuzzy inference system (PSOFIS) method with regards to model accuracy, pattern recognition, and prediction capability. All models are at a similar level of accuracy and prediction ability, and the prediction time for all models is less than one second. The results show that the model’s accuracy with low computational learning time can be achieved with the high number of CIR (0.5) when the number of inputs ≥ 4. However, this finding is vice versa, when the number of inputs < 4. In this case, the CIR number should be 0.2 to achieve the best accuracy of the model. This finding could also highlight the importance of sensitivity analysis of tuning parameters to achieve an accurate model with a cost-effective computational run.
Combined PI3Kα-mTOR Targeting of Glioma Stem Cells
Authors: Eckerdt Frank D. , Bell Jonathan B. , Gonzalez Christopher , Oh Michael S. , Perez Ricardo E. , Mazewski Candice , Fischietti Mariafausta , Goldman Stewart , Nakano Ichiro , Platanias Leonidas C. 
Published: December 2020

AbstractGlioblastoma (GBM) is the most common and lethal primary intrinsic tumour of the adult brain and evidence indicates disease progression is driven by glioma stem cells (GSCs). Extensive advances in the molecular characterization of GBM allowed classification into proneural, mesenchymal and classical subtypes, and have raised expectations these insights may predict response to targeted therapies. We utilized GBM neurospheres that display GSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. The PI3Kα selective inhibitor alpelisib blocked PI3K/AKT activation and inhibited spheroid growth, suggesting an essential role for the PI3Kα catalytic isoform. p110α expression was highest in the proneural subtype and this was associated with increased phosphorylation of AKT. Further, employing the GBM BioDP, we found co-expression of PIK3CA with the neuronal stem/progenitor marker NES was associated with poor prognosis in PN GBM patients, indicating a unique role for PI3Kα in PN GSCs. Alpelisib inhibited GSC neurosphere growth and these effects were more pronounced in GSCs of the PN subtype. The antineoplastic effects of alpelisib were substantially enhanced when combined with pharmacologic mTOR inhibition. These findings identify the alpha catalytic PI3K isoform as a unique therapeutic target in proneural GBM and suggest that pharmacological mTOR inhibition may sensitize GSCs to selective PI3Kα inhibition.
Detection of oriented fractal scaling components in anisotropic two-dimensional trajectories
Authors: Seleznov Ivan , Popov Anton , Kikuchi Kazuhei , Kolosova Elena , Kolomiiets Bohdan , Nakata Akio , Kaneko Miki , Kiyono Ken 
Published: December 2020

AbstractWe propose a novel class of mixed fluctuations with different orientations and fractal scaling features as a model for anisotropic two-dimensional (2D) trajectories hypothesized to appear in complex systems. Furthermore, we develop the oriented fractal scaling component analysis (OFSCA) to decompose such mixed fluctuations into the original orientation components. In the OFSCA, the original orientations are detected based on the principle that the original angles are orthogonal to the angles with the minimum and maximum scaling exponents of the mixed fluctuations. In our approach, the angle-dependent scaling properties are estimated using the Savitzky–Golay-filter-based detrended moving-average analysis (DMA), which has a higher detrending order than the conventional moving-average-filter-based DMA. To illustrate the OFSCA, we demonstrate that the numerically generated time-series of mixed fractional Gaussian noise (fGn) processes with non-orthogonal orientations and different scaling exponents is successfully decomposed into the original fGn components. We demonstrate the existence of oriented components in the 2D trajectories by applying OFSCA to real-world time-series, such as human postural fluctuations during standing and seismic ground acceleration during the great 2011 Tohoku-oki earthquake.