bluuebunny/crossref_metadata_2025_split huggingface dataset:
A FRET-based high-throughput screening platform for the discovery of chemical probes targeting the scaffolding functions of human tankyrases
Authors: Sowa Sven T. , Vela-Rodríguez Carlos , Galera-Prat Albert , Cázares-Olivera Mariana , Prunskaite-Hyyryläinen Renata , Ignatev Alexander , Lehtiö Lari 
Published: July 2020

AbstractTankyrases catalyse poly-ADP-ribosylation of their binding partners and the modification serves as a signal for the subsequent proteasomal degradation of these proteins. Tankyrases thereby regulate the turnover of many proteins involved in multiple and diverse cellular processes, such as mitotic spindle formation, telomere homeostasis and Wnt/β-catenin signalling. In recent years, tankyrases have become attractive targets for the development of inhibitors as potential therapeutics against cancer and fibrosis. Further, it has become clear that tankyrases are not only enzymes, but also act as scaffolding proteins forming large cellular signalling complexes. While many potent and selective tankyrase inhibitors of the poly-ADP-ribosylation function exist, the inhibition of tankyrase scaffolding functions remains scarcely explored. In this work we present a robust, simple and cost-effective high-throughput screening platform based on FRET for the discovery of small molecule probes targeting the protein–protein interactions of tankyrases. Validatory screening with the platform led to the identification of two compounds with modest binding affinity to the tankyrase 2 ARC4 domain, demonstrating the applicability of this approach. The platform will facilitate identification of small molecules binding to tankyrase ARC or SAM domains and help to advance a structure-guided development of improved chemical probes targeting tankyrase oligomerization and substrate protein interactions.
First-line cetuximab improves the efficacy of subsequent bevacizumab for RAS wild-type left-sided metastatic colorectal cancer: an observational retrospective study
Authors: Liu Shousheng , Jiang Chang , Yang Lin , Huang Jinsheng , Peng Roujun , Wang Xiaopai , He Wenzhuo , Bai Long , Zhou Yixin , Zhang Bei , Xia Liangping 
Published: July 2020

AbstractThe optimal targeted therapy sequence in patients of RAS wild-type left-sided metastatic colorectal cancer (mCRC) remains controversial, and few studies focus on the impact of first-line targeted agents on second-line ones. We enrolled 101 left-sided mCRC patients with RAS wild-type status, of which 50 cases received bevacizumab plus chemotherapy in both first-line and second-line therapies (Group A) and 51 cases received first-line cetuximab plus chemotherapy followed by second-line bevacizumab-containing regimens (Group B). The progression free survival (PFS) and overall survival (OS) from start of first-line (PFS 1nd and OS 1nd) and second-line (PFS 2nd and OS 2nd) therapy were compared between the two groups. PFS 1nd was comparable (10.0 vs 10.4 months; p = 0.402), while PFS 2nd (4.6 vs 7.9 months; p = 0.002), OS 1nd (26.8 vs 40.0 months; p = 0.011), and OS 2nd (15.2 vs 22.3 months; p = 0.006) were all poorer in group A compared with group B. Our study in combination with previous clinical data suggest that first-line application of cetuximab may provide a favorable condition for promoting the effect of subsequent bevacizumab, thus representing the optimal targeted therapy sequence in patients of RAS wild-type left-sided mCRC.
Sodium-glucose co-transporter (SGLT) inhibitor restores lost axonal varicosities of the myenteric plexus in a mouse model of high-fat diet-induced obesity
Authors: Shimo Satoshi , Saitoh Sei , Nguyen Huy Bang , Thai Truc Quynh , Ikutomo Masako , Muramatsu Ken , Ohno Nobuhiko 
Published: July 2020

AbstractDiabetes impairs enteric nervous system functions; however, ultrastructural changes underlying the pathophysiology of the myenteric plexus and the effects of sodium-glucose co-transporter (SGLT) inhibitors are poorly understood. This study aimed to investigate three-dimensional ultrastructural changes in axonal varicosities in the myenteric plexus and the effect thereon of the SGLT inhibitor phlorizin in mice fed a high-fat diet (HFD). Three-dimensional ultrastructural analysis using serial block-face imaging revealed that non-treated HFD-fed mice had fewer axonal varicosities and synaptic vesicles in the myenteric plexus than did normal diet-fed control mice. Furthermore, mitochondrial volume was increased and lysosome number decreased in the axons of non-treated HFD-fed mice when compared to those of control mice. Phlorizin treatment restored the axonal varicosities and organelles in HFD-fed mice. Although HFD did not affect the immunolocalisation of PGP9.5, it reduced synaptophysin immunostaining in the myenteric plexus, which was restored by phlorizin treatment. These results suggest that impairment of the axonal varicosities and their synaptic vesicles underlies the damage to the enteric neurons caused by HFD feeding. SGLT inhibitor treatment could restore axonal varicosities and organelles, which may lead to improved gastrointestinal functions in HFD-induced obesity as well as diabetes.
Structural health monitoring of metal-to-glass–ceramics penetration during thermal cycling aging using femto-laser inscribed FBG sensors
Authors: Fan Zhichun , Diao Xingzhong , Hu Kangjia , Zhang Yong , Huang Zhiyong , Kang Yanbo , Yan He 
Published: July 2020

AbstractMaintaining the mechanical strength and hermetic reliability of metal-to-glass–ceramics electrical penetration assembly (MTGC-EPA) is a key concern for ensuring the pressure boundaries of nuclear power plants. The transient temperature change caused by power adjusting or accidents in High Temperature Reactor Pebble-bed Modules may affect the structural health of sealing glass–ceramics, even leading to radiation leakage. To evaluate whether the function could survive temperature variations during the service life, thermal cycling aging experiments were imposed to MTGC-EPA. A grating length-mismatched sensing method to monitor the residual strain, an important factor of glass–ceramics structural health, was demonstrated in real-time by femto-laser inscribed fiber Bragg grating (FBG) sensor during the curing process and thermal cycling aging. Scanning electron microscope (SEM) and leakage rate tests were carried out to obtain the comparisons of microstructure and hermeticity before and after the thermal cycling. The residual strain showed a slight growth trend with thermal cycles repetition and it persisted a high value (~ 4,000 με) reflected by both Bragg wavelength shift and spectrum shape. The grating length mismatched single FBG embedded in glass–ceramics was feasible to demodulate the temperature and strain simultaneously, and the embedded FBG method achieved the structural health monitoring of MTGC-EPA during thermal cycling aging with good accuracy and reliability. Combining with the results of SEM and leakage rate detecting, the structural health of MTGC-EPA was demonstrated to be capable to endure the severe thermal conditions in nuclear reactors.
Investigation of fluoride evaporation from CaF2–CaO–Al2O3–MgO–TiO2–(Li2O) slag for electroslag remelting
Authors: Ju Jiantao , Ji Guangheng , Tang Chenmei , Yang Kangshuai , Zhu Zhihong 
Published: July 2020

AbstractThe isothermal kinetics of fluoride evaporation from CaF2–CaO–Al2O3–MgO–TiO2–(Li2O) slag with varying Li2O content were investigated in the temperature range 1743–1803 K by thermogravimetric analysis. Thermodynamic calculations and viscosity measurements were applied for studying the evaporation mechanism of fluoride. The results showed that the evaporation ratio increases with increasing Li2O content and temperature. The volatile constituents from the molten slags, mainly LiF and CaF2, were detected and their concentrations calculated. The fluoride evaporation is primarily affected by the vapour pressure of LiF and CaF2, viscosity of the slags, and melt-component activities under given experimental conditions. On the other hand, mass transfer of the gas is not the rate-controlling step that affects fluoride evaporation from the slags. The activation energy for fluoride evaporation gradually decreased from 193 ± 11 to 113 ± 3 kJ mol−1 as the Li2O content in the slags increases from 0 to 5.48 wt%. These results hold great theoretical significance for developing low-fluoride slags for electroslag remelting.
Identification of candidate miRNAs in early-onset and late-onset prostate cancer by network analysis
Authors: Parra-Medina Rafael , López-Kleine Liliana , Ramírez-Clavijo Sandra , Payán-Gómez César 
Published: July 2020

AbstractThe incidence of patients under 55 years old diagnosed with Prostate Cancer (EO-PCa) has increased during recent years. The molecular biology of PCa cancer in this group of patients remains unclear. Here, we applied weighted gene coexpression network analysis of the expression of miRNAs from 24 EO-PCa patients (38–45 years) and 25 late-onset PCa patients (LO-PCa, 71–74 years) to identify key miRNAs in EO-PCa patients. In total, 69 differentially expressed miRNAs were identified. Specifically, 26 and 14 miRNAs were exclusively deregulated in young and elderly patients, respectively, and 29 miRNAs were shared. We identified 20 hub miRNAs for the network built for EO-PCa. Six of these hub miRNAs exhibited prognostic significance in relapse‐free or overall survival. Additionally, two of the hub miRNAs were coexpressed with mRNAs of genes previously identified as deregulated in EO-PCa and in the most aggressive forms of PCa in African-American patients compared with Caucasian patients. These genes are involved in activation of immune response pathways, increased rates of metastasis and poor prognosis in PCa patients. In conclusion, our analysis identified miRNAs that are potentially important in the molecular pathology of EO-PCa. These genes may serve as biomarkers in EO-PCa and as possible therapeutic targets.
Ecofriendly biodegradation of Reactive Black 5 by newly isolated Sterigmatomyces halophilus SSA1575, valued for textile azo dye wastewater processing and detoxification
Authors: Al-Tohamy Rania , Sun Jianzhong , Fareed Mervat F. , Kenawy El-Refaie , Ali Sameh S. 
Published: July 2020

AbstractA total of seven yeast strains from 18 xylanolytic and/or xylose-fermenting yeast species isolated from the wood-feeding termite Reticulitermes chinenesis could efficiently decolorize various azo dyes under high-salt conditions. Of these strains, a novel and unique azo-degrading and halotolerant yeast, Sterigmatomyces halophilus SSA1575, has been investigated in this study. This strain could significantly decolorize four combinations of a mixture of dyes. It showed a high capability for decolorizing Reactive Black 5 (RB5) even at 1,500 mg L−1. The strain SSA1575 still showed a high capability for decolorizing a 50 mg L−1 RB5 with a salt mixing at a NaCl concentration of up to 80 g L−1. It also exhibited significant ability to decolorize repeated additions of dye aliquots, with a reduction in time of up to 18 h. Most of the tested carbon and nitrogen sources could significantly enhance a RB5 decolorization. However, this process was inhibited by the addition of sucrose and sodium nitrate. NADH-dichlorophenol indophenol (NADH-DCIP) reductase and lignin peroxidase were determined as the key reductase and oxidase of S. halophilus SSA1575. Finally, strain SSA1575, can effectively detoxify RB5 into non-toxic products. Overall, S. halophilus SSA1575, might be a promising halotolerant yeast valued for the treatment of various textile effluents with high salinity.
Expression patterns of seven key genes, including β-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a and miR-93 in gastric cancer
Authors: Jafari Narjes , Abediankenari Saeid , Hosseini-Khah Zahra , Valizadeh Seyed Mohammad , Torabizadeh Zhila , Zaboli Ehsan , Ghasemi Maryam , Fakheri Hafez , Hosseini Vahid , Shekarriz Ramin , Rafiei Alireza , Asgarian-Omran Hossein , Abedian Fatemeh 
Published: July 2020

AbstractGastric cancer (GC) is one of the most prevalent cancers and a major cause of cancer related mortality worldwide. Incidence of GC is affected by various factors, including genetic and environmental factors. Despite extensive research has been done for molecular characterization of GC, it remains largely unknown. Therefore, further studies specially conducted among various ethnicities in different geographic locations, are required to know the precise molecular mechanisms leading to tumorigenesis and progression of GC. The expression patterns of seven candidate genes, including β-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a, and miR-93 were determined in 24 paired GC tissues and corresponding non-cancerous tissues by quantitative Real-Time PCR. The association between the expression of these genes and clinicopathologic factors were also investigated. Our results demonstrated that overall mRNA levels of GATA6 were significantly decreased in the tumor samples in comparison with the non-cancerous tissues (median fold change (FC) = 0.3143; P = 0.0003). Overall miR-93 levels were significantly increased in the tumor samples relative to the non-cancerous gastric tissues (FC = 2.441; P = 0.0002). β-catenin mRNA expression showed a strong positive correlation with miR-34a (r = 0.5784; P = 0.0031), and miR-181a (r = 0.5652; P = 0.004) expression. miR-34a and miR-181a expression showed a significant positive correlation (r = 0.4862; P = 0.016). Moreover, lower expression of Notch1 was related to distant metastasis in GC patients with a borderline statistical significance (p = 0.0549). These data may advance our understanding of the molecular biology that drives GC as well as provide potential targets for defining novel therapeutic strategies for GC treatment.
Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis
Authors: Pascottini O. Bogado , Van Schyndel S. J. , Spricigo J. F. W . , Rousseau J. , Weese J. S. , LeBlanc S. J. 
Published: July 2020

AbstractOur objectives were to describe and compare the uterine bacterial composition of postpartum Holstein cows diagnosed as healthy (n = 8), subclinical endometritis (SCE; n = 8), or clinical endometritis (CE; n = 5) in the fifth week postpartum. We did metagenomic analyses of 16S rRNA gene sequences from endometrial cytobrush samples at 10, 21, and 35 days in milk (DIM), and endometrial bacterial culture at 35 DIM. Uterine bacterial composition in healthy, SCE, and CE was stable at 10, 21, and 35 DIM. Alpha and beta diversities showed a different uterine microbiome from CE compared to healthy or SCE, but no differences were found between healthy and SCE cows. At the phylum level, the relative abundance of Bacteroidetes and Fusobacteria, and at genera level, of Trueperella was greater in CE than healthy or SCE cows. Trueperella pyogenes was the predominant bacteria cultured in cows with CE, and a wide variety of bacterial growth was found in healthy and SCE cows. Bacteria that grew in culture were represented within the most abundant bacterial genera based on metagenomic sequencing. The uterine microbiota was similar between SCE and healthy, but the microbiome in cows with CE had a loss of bacterial diversity.
Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population
Authors: Ishibashi Kyota , Sasaki Eiji , Ota Seiya , Chiba Daisuke , Yamamoto Yuji , Tsuda Eiichi , Yoshikuni Sugimura , Ihara Kazushige , Ishibashi Yasuyuki 
Published: July 2020

AbstractTo investigate synovitis’ influence on early knee osteoarthritis (EKOA) by serum biomarkers and magnetic resonance imaging (MRI) findings in Japanese women. We enrolled 255 women aged 30–70 without radiographic abnormalities (Kellgren–Lawrence grade ≥ 2). Knee injury, OA outcome scores (KOOS), clinical examinations, and standing radiograph were used for classification criteria of EKOA. Participants were classified into normal knee group and EKOA group. All participants underwent MRIs of their right knee. The amount of effusion-synovitis volume was quantified. We compared serum matrix metalloproteinases-3 levels (MMP-3), high-sensitivity C-reactive protein, interleukin-6, and adiponectin between the groups. The relationship between synovitis and EOKA was investigated using multiple linear regression. Fifty-four participants (21%) were classified as EKOA. Serum MMP-3 concentration and effusion-synovitis volume were higher in patients with EKOA (p = 0.025 and p = 0.001, respectively). Effusion-synovitis volume negatively correlated with all KOOS subscales and positively correlated with serum MMP-3 concentration. Serum MMP-3 concentration was associated with effusion-synovitis volume β = 0.60, p < 0.001). There was mildly active but definitive synovitis in EKOA. This was an observational study so that no conclusions can be drawn regarding cause-effect for synovitis and symptoms. Future studies should conduct follow-up of participants with synovitis to assess the progression of knee OA.
Genetic interaction between central pair apparatus genes CFAP221, CFAP54, and SPEF2 in mouse models of primary ciliary dyskinesia
Authors: McKenzie Casey W. , Lee Lance 
Published: July 2020

AbstractPrimary ciliary dyskinesia (PCD) is a genetically heterogeneous syndrome that results from defects in motile cilia. The ciliary axoneme has a 9 + 2 microtubule structure consisting of nine peripheral doublets surrounding a central pair apparatus (CPA), which plays a critical role in regulating proper ciliary function. We have previously shown that mouse models with mutations in CPA genes CFAP221, CFAP54, and SPEF2 have a PCD phenotype with defects in ciliary motility. In this study, we investigated potential genetic interaction between these CPA genes by generating each combination of double heterozygous and double homozygous mutants. No detectable cilia-related phenotypes were observed in double heterozygotes, but all three double homozygous mutant lines exhibit early mortality and typically develop severe PCD-associated phenotypes of hydrocephalus, mucociliary clearance defects in the upper airway, and abnormal spermatogenesis. Double homozygous cilia are generally intact and display a normal morphology and distribution. Spermiogenesis is aborted in double homozygotes, with an absence of mature flagella on elongating spermatids and epididymal sperm. These findings identify genetic interactions between CPA genes and genetic mechanisms regulating the CPA and motile cilia function.
Fetal cardiac MRI: a single center experience over 14-years on the potential utility as an adjunct to fetal technically inadequate echocardiography
Authors: Dong Su-Zhen , Zhu Ming , Ji Hui , Ren Jing-Ya , Liu Ke 
Published: July 2020

AbstractUnlike ultrasound (US) imaging, foetal magnetic resonance imaging (MRI) is not significantly limited by maternal obesity, oligohydramnios, uterine myoma, twins, and foetal lie, which impair US visualization of the foetus. The present study aimed to introduce our foetal cardiac MRI scanning technology and over 14-years of experience on the potential utility of foetal cardiac MRI examination as an adjunct to foetal technically inadequate echocardiography (Echo). This retrospective review included 1,573 pregnant women [1,619 foetuses (46 twins)] referred for a foetal cardiac MRI because of technically limited Echo. Foetal cardiac MRI was performed using two 1.5 T units. Among the 1,619 foetuses referred for cardiac MRI, 1,379 (85.2%) cases were followed up using postnatal imaging and/or surgery, 240 (14.8%), including three twins, had no follow-up confirmation because of pregnancy termination without autopsy or loss to follow-up. The results of the present study indicated that foetal cardiac MRI examinations can be a useful adjunct to foetal echocardiography when the technical limitations of echocardiography make it inadequate for diagnosis.
Photodynamic exposure of Rose-Bengal inhibits Tau aggregation and modulates cytoskeletal network in neuronal cells
Authors: Dubey Tushar , Gorantla Nalini Vijay , Chandrashekara Kagepura Thammaiah , Chinnathambi Subashchandrabose 
Published: July 2020

AbstractThe intracellular Tau aggregates are known to be associated with Alzheimer’s disease. The inhibition of Tau aggregation is an important strategy for screening of therapeutic molecules in Alzheimer's disease. Several classes of dyes possess a unique property of photo-excitation, which is applied as a therapeutic measure against numerous neurological dysfunctions. Rose Bengal is a Xanthene dye, which has been widely used as a photosensitizer in photodynamic therapy. The aim of this work was to study the protective role of Rose Bengal against Tau aggregation and cytoskeleton modulations. The aggregation inhibition and disaggregation potency of Rose Bengal and photo-excited Rose Bengal were observed by in-vitro fluorescence, circular dichroism, and electron microscopy. Rose Bengal and photo-excited Rose Bengal induce minimal cytotoxicity in neuronal cells. In our studies, we observed that Rose Bengal and photo-excited Rose Bengal modulate the cytoskeleton network of actin and tubulin. The immunofluorescence studies showed the increased filopodia structures after photo-excited Rose Bengal treatment. Furthermore, Rose Bengal treatment increases the connections between the cells. Rose Bengal and photo-excited Rose Bengal treatment-induced actin-rich podosome-like structures associated with cell membranes. The in-vivo studies on UAS E-14 Tau mutant Drosophila suggested that exposure to Rose Bengal and photo-excited Rose Bengal efficiency rescues the behavioural and memory deficit in flies. Thus, the overall results suggest that Rose Bengal could have a therapeutic potency against Tau aggregation.
Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets
Authors: Hartman Robin J. G. , Kapteijn Daniek M. C. , Haitjema Saskia , Bekker Mireille N. , Mokry Michal , Pasterkamp Gerard , Civelek Mete , den Ruijter Hester M. 
Published: July 2020

AbstractSex differences in endothelial cell (EC) biology may reflect intrinsic differences driven by chromosomes or sex steroid exposure and gender differences accumulated over life. We analysed EC gene expression data from boy–girl twins at birth and in non-twin adults to detect sex differences at different stages of life, and show that 14–25% of the EC transcriptome is sex-biased. By combining data from both stages of life, we identified sex differences that are present at birth and maintained throughout life, and those that are acquired over life. Promisingly, we found that genes that present with an acquired sex difference in ECs are more likely to be targets of sex steroids. Annotating both gene sets with data from multiple genome-wide association studies (GWAS) revealed that genes with an intrinsic sex difference in ECs are enriched for coronary artery disease GWAS hits. This study underscores the need for treating sex as a biological variable.