bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semaphorin 7A modulates cytokine‐induced memory‐like responses by human natural killer cells
Authors: Ghofrani Joshua , Lucar Olivier , Dugan Haley , Reeves R. Keith , Jost Stephanie 
Published: April 2019

AbstractCytokine‐induced memory‐like (CIML) NK cells are endowed with the capacity to mediate enhanced effector functions upon cytokine or activating receptor restimulation for several weeks following short‐term preactivation with IL‐12, IL‐15, and IL‐18. Promising results from a first‐in‐human clinical trial highlighted the clinical potential of CIML NK cells as adoptive immunotherapy for patients with hematologic malignancies. However, the mechanisms underlying CIML NK cell differentiation and increased functionality remain incompletely understood. Semaphorin 7A (SEMA7A) is a potent immunomodulator expressed in activated lymphocytes and myeloid cells. In this study, we show that SEMA7A is substantially upregulated on NK cells stimulated with cytokines, and specifically marks activated NK cells with a strong potential to release IFN‐γ. In particular, preactivation of NK cells with IL‐12+IL‐15+IL‐18 resulted in greater than tenfold upregulation of SEMA7A and enhanced expression of the ligand for SEMA7A, integrin‐β1, on CIML NK cells. Strikingly, preactivation in the presence of antibodies targeting SEMA7A lead to significantly decreased IFN‐γ production following restimulation. These results imply a novel mechanism by which cytokine‐enhanced SEMA7A/integrin‐β1 interaction promotes CIML NK cell differentiation and maintenance of increased functionality. Our data suggest that targeting SEMA7A/integrin‐β1 signaling might provide a novel immunotherapeutic approach to potentiate antitumor activity of CIML NK cells.
Upstream perturbation and floodplain formation effects on chute‐cutoff‐dominated meandering river pattern and dynamics
Authors: Weisscher Steven A. H. , Shimizu Yasuyuki , Kleinhans Maarten G. 
Published: April 2019

AbstractA sustained dynamic inflow perturbation and bar–floodplain conversion are considered crucial to dynamic meandering. Past experiments, one‐dimensional modelling and linear theory have demonstrated that the initiation and persistence of dynamic meandering require a periodic transverse motion of the inflow. However, it remains unknown whether the period of the inflow perturbation affects self‐formed meander dynamics. Here, we numerically study the effect of the inflow perturbation period on the development and meander dynamics of a chute‐cutoff‐dominated river, which requires two‐dimensional modelling with vegetation forming floodplain on bars. We extended the morphodynamic model Nays2D with growth and mortality rules of vegetation to allow for meandering. We tested the effect of a transversely migrating inflow boundary by varying the perturbation period between runs over an order of magnitude around typical modelled meander periods. Following the cutoff cascade after initial meander formation from a straight channel, all runs with sufficient vegetation show series of growing meanders terminated by chute cutoffs. This generates an intricate channel belt topography with point bar complexes truncated by chutes, oxbow lakes, and scroll‐bar‐related vegetation age patterns. The sinuosity, braiding index and meander period, which emerge from the inherent biomorphological feedback loops, are unrelated to the inflow perturbation period, although the spin‐up to dynamic equilibrium takes a longer time and distance for weak and absent inflow perturbations. This explains why, in previous experimental studies, dynamic meandering was only accomplished with a sustained upstream perturbation in flumes that were short relative to the meander wavelength. Our modelling of self‐formed meander patterns is evidence that scroll‐bar‐dominated and chute‐cutoff‐dominated meanders develop from downstream convecting instabilities. This insight extends to many more fluvial, estuarine and coastal systems in morphological models and experiments, which require sustained dynamic perturbations to form complex patterns and develop natural dynamics. © 2019 The Authors. Earth Surface Processes and Landforms Published by John Wiley & Sons Ltd.
On the differences between mega‐ and meta‐imputation and analysis exemplified on the genetics of age‐related macular degeneration
Authors: Gorski Mathias , Günther Felix , Winkler Thomas W. , Weber Bernhard H. F. , Heid Iris M. 
Published: April 2019

AbstractWhile current genome‐wide association analyses often rely on meta‐analysis of study‐specific summary statistics, individual participant data (IPD) from multiple studies increase options for modeling. When multistudy IPD is available, however, it is unclear whether this data is to be imputed and modeled across all participants (mega‐imputation and mega‐analysis) or study‐specifically (meta‐imputation and meta‐analysis). Here, we investigated different approaches toward imputation and analysis using 52,189 subjects from 25 studies of the International Age‐related Macular Degeneration (AMD) Genomics Consortium including, 16,144 AMD cases and 17,832 controls for association analysis.From 27,448,454 genetic variants after 1,000‐Genomes‐based imputation, mega‐imputation yielded ~400,000 more variants with high imputation quality (mostly rare variants) compared to meta‐imputation. For AMD signal detection (P < 5 × 10−8) in mega‐imputed data, most loci were detected with mega‐analysis without adjusting for study membership (40 loci, including 34 known); we considered these loci genuine, since genetic effects and P‐values were comparable across analyses. In meta‐imputed data, we found 31 additional signals, mostly near chromosome tails or reference panel gaps, which disappeared after accounting for interaction of whole‐genome amplification (WGA) with study membership or after excluding studies with WGA‐participants.For signal detection with multistudy IPD, we recommend mega‐imputation and mega‐analysis, with meta‐imputation followed by meta‐analysis being a computationally appealing alternative.
Embracing Wobble: Exploring Novice Teachers’ Efforts to Enact Dialogic Literacy Instruction
Authors: Stewart Trevor Thomas , Coombs Dawan , Fecho Bob , Hawley Todd 
Published: April 2019

AbstractContemporary school contexts present challenges for novice teachers seeking to support students’ literacy development by bringing content into dialogue with students’ lives. These challenges, framed as wobble moments, often contribute to high rates of teacher attrition. However, dialogue with peers, colleagues, and mentors can help teachers learn from the tensions they encounter as they enact dialogic literacy instruction. The authors share the struggles of novice teachers working to enact dialogical practices and describe how an oral inquiry process framework helped them negotiate these challenges. Working from a Bakhtinian stance, the authors present three wobble moments that were connected to school structures, personal and professional identities, and conformity to demonstrate how the oral inquiry process helped the participants learn from the difficulties they faced. Findings suggest that the oral inquiry process framework can help teachers navigate difficulty through dialogue and enact pathways that empower them. Recommendations for implementing this framework are also included.
Growth‐promoting effects of low‐level butyl benzyl phthalate exposure on human neuroblastoma SH‐SY5Y cells
Authors: Zhang Fan , Zhang Juan , Shi Nian , Li Tao 
Published: April 2019

AbstractThe purpose of present study was to investigate the impact of butyl benzyl phthalate (BBP) on SH‐SY5Y neuroblastoma cells in vitro. The cell counting kit‐8 was used to measure cell proliferation and flow cytometry was utilized to study cell cycle phases and apoptosis. Western blotting and quantitative real‐time polymerase chain reaction were used to detect levels of aromatase, estrogen receptors (ERs) and some apoptosis and cell cycle‐related genes. Results showed BBP‐stimulated SH‐SY5Y cells in a dose‐dependent manner and produced a reverted U‐shaped dose‐response curve. BBP at lower concentrations (0.01 and 0.1 μm) significantly induced cell proliferation while inhibited cell growth at 300 μm. The promoting effect of estradiol could be entirely blocked by administration of ICI182 780, a pure antagonist of ERs, while the effect of BBP could be partly blocked. Additionally, we confirmed 0.1 μm BBP‐induced cell proliferation caused the arrest of cells in S phase and inhibited apoptosis, which might be partially explained by the decreased expression of p53, the increased expression of proliferating cell nuclear antigen, Bcl‐2 and cell cycle regulator cyclin‐D1, and the activation of aromatase. The addition of ICI182 780 had no effect on BBP‐induced ERβ mRNA expression, whereas ICI182 780 could effectively counteract the effect of estradiol. Moreover, pretreatment with ICI182 780 could block the induction of aromatase protein expression and activity by BBP, showing an involvement of ERs. Except for the ER pathway, these results showed there might be other pathways involved in promoting the effects of low‐level BBP on SH‐SY5Y cells, which require further investigation.
Nanofibrous antibiotic‐eluting matrices: Biocompatibility studies in a rat model
Authors: Passos Patrícia C. , Moro Juliana , Barcelos Raquel Cristine Silva , Da Rosa Higor Z. , Vey Luciana T. , Bürguer Marilise Escobar , Maciel Roberto M. , Danesi Cristiane C. , Edwards Paul C. , Bottino Marco C. , Kantorski Karla Z. 
Published: April 2019

AbstractThis study evaluated the biocompatibility of degradable polydioxanone (PDS) electrospun drug delivery systems (hereafter referred as matrices) containing metronidazole (MET) or ciprofloxacin (CIP) after subcutaneous implantation in rats. Sixty adult male rats were randomized into six groups: SHAM (sham surgery); PDS (antibiotic‐free matrix); 1MET (one 25 wt% MET matrix); 1CIP (one 25 wt% CIP matrix); 2MET (two 25 wt% MET matrices); and 2CIP (two 25 wt% CIP matrices). At 3 and 30 days, animals were assessed for inflammatory cell response (ICR), collagen fibers degradation, and oxidative profile (reactive oxygen species [ROS]; lipid peroxidation [LP]; and protein carbonyl [PC]). At 3 days, percentages of no/discrete ICR were 100, 93.3, 86.7, 76.7, 50, and 66.6 for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP, respectively. At 30 days, percentages of no/discrete ICR were 100% for SHAM, PDS, 1MET, and 1CIP and 93.3% for 2MET and 2CIP. Between 3 and 30 days, SHAM, 1CIP, and 2CIP produced collagen, while 1MET and 2MET were unchanged. At 30 days, the collagen fiber means percentages for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP were 63.7, 60.7, 56.6, 62.6, 51.8, and 61.7, respectively. Antibiotic‐eluting matrices showed similar or better oxidative behavior when compared to PDS, except for CIP‐eluting matrices, which showed higher levels of PC compared to SHAM or PDS at 30 days. Collectively, our findings indicate that antibiotic‐eluting matrices may be an attractive biocompatible drug delivery system to fight periodontopathogens. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.
microRNA‐messenger RNA regulatory network of esophageal squamous cell carcinoma and the identification of miR‐1 as a biomarker of patient survival
Authors: Wei Qiao , Li Xiyi , Yu Weiwei , Zhao Kuaile , Qin Guangqi , Chen Huan , Gu Yanzi , Ding Fei , Zhu Zhengfei , Fu Xiaolong , Sun Menghong 
Published: April 2019

AbstractEmerging evidence indicates that microRNAs (miRNAs) play an important role in tumor carcinogenesis and progression by targeting gene expression. The goal of this study was to comprehensively analyze the vital functional miRNAs and their target genes in esophageal squamous cell carcinoma (ESCC) and to explore the clinical significance and mechanisms of miR‐1 in ESCC. First, the miRNA and messenger RNA (mRNA) expression profiles of ESCC were determined with microarray technology. Using an integrated analysis of miRNAs and their target genes with multistep bioinformatics methods, the miRNA‐mRNA regulatory network in ESCC was constructed. Next, miR‐1 expression in 292 ESCC patients and its relationship with clinicopathological features and prognosis were detected by in situ hybridization. Furthermore, the biological functions of miR‐1 were determined with in vitro and in vivo functional experiments. Finally, real‐time quantitative reverse transcription polymerase chain reaction, Western blot analysis, and luciferase reporter assays were performed to verify the target genes of miR‐1. In this study, 67 miRNAs and 2992 genes were significantly differentially expressed in ESCC tissues compared with their expression in adjacent normal tissues, and an miRNA‐mRNA regulatory network comprising 59 miRNAs and 162 target mRNAs was identified. Low miR‐1 expression was correlated with pathological T stage, lymph node metastasis, vessel invasion, and poor clinical outcome. miR‐1 suppressed ESCC cell proliferation and invasion and promoted ESCC cell apoptosis. Fibronectin 1 (FN1) was verified as a direct target of miR‐1. Taken together, the present results suggest that miR‐1 may be a valuable prognostic predictor for ESCC, and the miR‐1/FN1 axis may be a therapeutic target.
Differential expression of Ets‐1 in breast cancer among North Indian population
Authors: Nazir Sheeraz Un , Kumar Ramesh , Dil‐Afroze  , Rasool Ishrat , Bondhopadhyay Banashree , Singh Ankita , Tripathi Richa , Singh Neha , Khan Asiya , Tanwar Pranay , Agrawal Usha , Mehrotra Ravi , Hussain Showket 
Published: April 2019

AbstractBreast cancer is a highly aggressive disease contributing to high mortality rate among females across the globe owing to wide geographical variations, change in lifestyle along with rapid tumor growth, drug resistance, and high metastasis rate. To understand the molecular and genetic basis of breast cancer progression; we studied the role of E26 transformation‐specific‐1 (Ets‐1) transcription factor which is implicated to have a role in carcinogenesis like invasion, metastasis, angiogenesis, etc. Our findings revealed an overexpression of Ets‐1 gene in 75 breast cancer tumors as compared with their normal adjacent tissues. The findings significantly established a co‐relation between Ets‐1 expression in breast cancer tissue with hormonal receptor profiles and ductal‐lobular histological subtypes in Indian population. In addition, a differential expression pattern of Ets‐1 was observed between high, moderate, and low grades of breast cancer patients. The present study demonstrates a crucial role of Ets‐1 transcription factor which may serve as a potential biomarker for breast carcinogenesis.
LINC00473/miR‐374a‐5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy
Authors: Chen Weizuo , Zhang Yanshan , Wang Huijuan , Pan Tingting , Zhang Yinguo , Li Chao 
Published: April 2019

AbstractEsophageal squamous cell carcinoma (ESCC) is the most prevalent type in esophageal cancers. Despite accumulating achievements in treatments of ESCC, patients still suffer from recurrence because of the treatment failures, one of the reasons for which is radioresistance. Therefore, it is a necessity to explore the molecular mechanism underlying ESCC radioresistance. Long intergenic noncoding RNA 473 (LINC00473) has been reported to be aberrantly expressed in several human malignancies. However, its biological function in radiosensitivity of ESCC remains to be fully understood. This study explored the role of LINC00473 in radiosensitivity of ESCC cells and whether LINC00473 acted as a competing endogenous RNA to realize its modulation on radioresistance. We found that LINC00473 was markedly upregulated in ESCC tissues and cell lines, and its expression was remarkably related to cellular response to irradiation. In addition, knockdown of LINC00473 could sensitize ESCC cells to radiation in vitro. As for the underlying mechanism, we uncovered that there was a mutual inhibition between LINC00473 and miR‐374a‐5p. Spindlin1 (SPIN1) was verified as a downstream target of miR‐374a‐5p, and LINC00473 upregulated SPIN1 expression through negatively modulating miR‐374a‐5p expression. Furthermore, we revealed that SPIN1 could aggravate the radioresistance of ESCC cells. Finally, overexpression of SPIN1 reversed the LINC00473 silencing‐enhanced radiosensitivity in ESCC cells. To sum up, we demonstrated that LINC00473 facilitated radioresistance by regulating the miR‐374a‐5p/SPIN1 axis in ESCC.
LncRNA LEF1‐AS1 regulates the migration and proliferation of vascular smooth muscle cells by targeting miR‐544a/PTEN axis
Authors: Zhang Lina , Zhou Changyong , Qin Qiaoji , Liu Zhenfang , Li Peng 
Published: April 2019

AbstractLong noncoding RNAs (lncRNAs) play important roles in endothelium development. A lncRNA, LEF1‐AS1, is recently emerging as a potent mediator of the proliferation and migration of a number of cells, including smooth muscle cells. However, the effects of LEF1‐AS1 in atherosclerosis remains largely unknown. Specimens from patients with coronary artery atherosclerosis were collected. The quantitative real‐time polymerase chain reaction was used to analyze levels of LEF1‐AS1 and microRNA‐544a (miR‐544a). Western blot analysis was used to assess PTEN, P‐Akt, and T‐Akt protein expression. Proliferation, migration, and invasion of cells were analyzed by cell counting kit‐8 assay, scratch wound assay, and transwell assay, respectively. The interaction between LEF1‐AS1, miR‐544a, and PTEN was probed using bioinformatical analysis and dual‐luciferase assay. In plasma and tissue of patients with coronary artery atherosclerosis, LEF1‐AS1 was upregulated and miR‐544a was downregulated. A negative correlation was found between LEF1‐AS1 and miR‐544a. miR‐544a overexpression reversed the inhibition of LEF1‐AS1 in smooth muscle cell proliferation and invasion, which were mediated through the PTEN pathway. LEF1‐AS1 regulates smooth muscle cell proliferation and migration through the miR‐544a/PTEN axis, indicating that LEF1‐AS1 may be a potential therapeutic target in atherosclerosis.
Kallikarein‐related peptidase 3 common genetic variant and the risk of prostate cancer
Authors: Motamedi Rouhollah K. , Sarhangi Negar , Afshari Mahdi , Sattari Mahshid , Jamaldini Seyed H. , Samzadeh Mohammad , Mohsen Ziaei Seyed A. , Pourmand Gholam R. , Hasanzad Mandana 
Published: April 2019

AbstractKallikarein‐related peptidase 3 (KLK3) gene polymorphisms seem to play a role in susceptibility to prostate cancer (PC). The purpose of this study was to investigate the association between rs2735839 polymorphism of KLK3 gene and risk of PC in an Iranian population. In this case‐control study, rs2735839 was genotyped in 532 patients with PC and 602 controls with benign prostate hyperplasia (BPH) using polymerase chain reaction‐restriction fragment length polymorphism assay. The frequency of GG, AG, and AA genotypes of KLK3 polymorphism was 24.6% and 76.2%, 46.6% and 21.7%, and 28.8% and 2.1%, in patients with BPH and PC, respectively (P < 0.001). The frequency of G allele in patients with BPH and PC was 47.9% and 87%, respectively (odds ratio: 7.31; confidence interval: 5.88‐9.10; P < 0.001). Patients with AG and GG genotypes had a higher total serum level of prostate‐specific antigen (PSA) compared to those with AA genotype (P < 0.001). Patients with this polymorphism had higher risk of tumor with higher grade (P = 0.23), advanced stage (P = 0.11), perineural invasion (P = 0.07), and vascular invasion (P = 0.07) compared to those without it but this difference was not statistically significant. Based on our results, KLK3 gene polymorphism was associated with the risk of PC. Higher levels of PSA in the presence of KLK3 polymorphism in patients with PC indicated that rs2735839 polymorphism could be a risk factor for increased levels of PSA.
TWIST1, MMP‐21, and HLAG‐1 co‐overexpression is associated with ESCC aggressiveness
Authors: Golyan Fatemeh Fardi , Abbaszadegan Mohammad Reza , Forghanifard Mohammad Mahdi 
Published: April 2019

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of cancer, requiring reliable biomarkers for prognosis and therapeutic responsiveness. TWIST1, as an important factor responsible for metastasis of several cancers, is involved in tumor invasion and metastasis through indirectly regulation of MMP‐21 expression. On the other hand, NF‐ĸβ which is a regulator of HLAG‐1 has direct interaction with TWIST1 protein. In this retrospective study we investigated the clinical significance of TWIST1, MMP‐21, and HLAG‐1 expression in ESCC, and the possible correlation between these genes and progression of the disease. The gene expression analyses of TWIST1, MMP‐21, and HLA‐G1 were performed by relative comparative real‐time polymerase chain reaction in 58 ESCCs compared with corresponding margin‐normal esophageal tissues. Significant overexpression of HLAG‐1, TWIST1, and MMP‐21 messenger RNA was observed in 22.4%, 41.4%, and 60.3% of tumor samples, respectively. Concomitant overexpression of TWIST1/MMP‐21 and TWIST1/HLAG‐1 were significantly correlated to each other in various clinicopathological features, including depth of tumor invasion, stage of tumor progression, lymphatic invasion, and grade of tumor cell differentiation (
P < 0.05). The current study is the first report of coexpression of TWIST1, MMP‐21, and HLAG‐1 in ESCC. Such findings suggest an oncogenic role for concomitant expression of these genes in ESCC invasion and metastasis.