bluuebunny/crossref_metadata_2025_split huggingface dataset:
The feasibility of using dielectrophoresis for isolation of glioblastoma subpopulations with increased stemness
Authors: Alinezhadbalalami Nastaran , Douglas Temple A. , Balani Nikita , Verbridge Scott S. , Davalos Rafael V. 
Published: May 2019

AbstractCancer stem cells (CSCs) are aggressive subpopulations with increased stem‐like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers. Antigen‐based sorting of CSCs usually requires staining with multiple markers, making the experiments complicated, expensive, and sometimes unreliable. Here, we study the feasibility of using dielectrophoresis (DEP) for isolation of glioblastoma cells with increased stemness. We culture a glioblastoma cell line in the form of neurospheres as an in vitro model for glioblastoma stem cells. We demonstrate that spheroid forming cells have higher expression of stem cell marker, nestin. Next, we show that dielectric properties of neurospheres change as a result of changing culture conditions. Our results indicate that spheroid forming cells need higher voltages to experience the same DEP force magnitude compared to normal monolayer cultures of glioblastoma cell line. This study confirms the possibility of using DEP to isolate glioblastoma stem cells.
Baseline separation of α and β‐acids homologues and isomers in hop (Humulus lupulus L.) by CD‐MEKC‐UV
Authors: Duarte Lucas M. , Amorim Tatiane L. , Adriano Luiz H. C. , de Oliveira Marcone A. L. 
Published: May 2019

AbstractAn alternative method for simultaneous baseline separation of α and β‐acids homologues and isomers in hop by CD‐MEKC with UV detection was proposed. The optimized background electrolyte was composed of 30 mmol/L sodium tetraborate solution, 45 mmol/L sodium dodecyl sulfate, 20 mmol/L β‐cyclodextrin and 10% v/v acetonitrile. The instrumental conditions were evaluated by using a 33 Box‐Benhken experimental design. In order to demonstrate the applicability of the method, 21 hop samples from different varieties were analyzed. The repeatability intra‐ and interday tests were performed and relative standard deviations lower than 7% for area and migration times were observed. The present method comprehended 8 min analysis time and revealed to be faster and more efficient when compared to previous reports from literature.
Capillary electrophoresis‐based enzyme assays for β‐lactamase enzymes
Authors: Chen Chunyang , Kramer Jan S. , Brunst Steffen , Proschak Ewgenij , Scriba Gerhard K.E. 
Published: May 2019

AbstractGeneric in‐capillary as well as offline CE‐based enzyme assays were developed for serine‐β‐lactamases and metallo‐β‐lactamases. The hydrolysis of benzylpenicillin to benzylpenicilloic acid was analyzed using 100 mM sodium phosphate solution, pH 6.0, as a background electrolyte. In‐capillary assays employed an uncoated as well as a polyethylene oxide‐coated capillary, while the offline assays employing long end and short end injection were performed in an uncoated capillary. Using procaine hydrochloride or 4‐hydroxybenzoic acid as internal standard, the respective assays were validated with regard to linearity, LOD and LOQ, repeatability, precision, and accuracy. The assays were applied to the determination of the Michaelis‐Menten parameters Km and Vmax of Bacillus cereus penicillinase as well as New Delhi metallo‐β‐lactamase 1 and Verona integrin‐encoded metallo‐β‐lactamase 2. Furthermore, the inhibition of the enzymes by irreversible and competitive inhibitors was evaluated. Comparable data were obtained with all assays. The use of a simple substrate ensured broad applicability to the various types of β‐lactamases.
Flow resistance and hydraulic geometry in bedrock rivers with multiple roughness length scales
Authors: Ferguson Robert I. , Hardy Richard J. , Hodge Rebecca A. 
Published: May 2019

AbstractMany models of incision by bedrock rivers predict water depth and shear stress from discharge; conversely, palaeoflood discharge is sometimes reconstructed from flow depth markers in rock gorges. In both cases, assumptions are made about flow resistance. The depth–discharge relation in a bedrock river must depend on at least two roughness length scales (exposed rock and sediment cover) and possibly a third (sidewalls). A conceptually attractive way to model the depth–discharge relation in such situations is to partition the total shear stress and friction factor, but it is not obvious how to quantify the friction factor for rough walls in a way that can be used in incision process models. We show that a single flow resistance calculation using a spatially averaged roughness length scale closely approximates the partitioning of stress between sediment and rock, and between bed and walls, in idealized scenarios. Both approaches give closer fits to the measured depth–discharge relations in two small bedrock reaches than can be achieved using a fixed value of Manning's n or the Chézy friction factor. Sidewalls that are substantially rougher or smoother than the bed have a significant effect on the partitioning of shear stress between bed and sidewalls. More research is needed on how best to estimate roughness length scales from observable or measurable channel characteristics. © 2019 John Wiley & Sons, Ltd.
Building and Applying Quantitative Adverse Outcome Pathway Models for Chemical Hazard and Risk Assessment
Authors: Perkins Edward J. , Ashauer Roman , Burgoon Lyle , Conolly Rory , Landesmann Brigitte , Mackay Cameron , Murphy Cheryl A. , Pollesch Nathan , Wheeler James R. , Zupanic Anze , Scholz Stefan 
Published: May 2019

Abstract
An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway-based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Abstract
Quantitative adverse outcome pathway (AOP) model development.
Survival of Salmonids from an Experimental Commercial Fish Trap
Authors: Tuohy Adrian M , Skalski John R , Gayeski Nick J 
Published: May 2019

Abstract
Conventional harvest techniques used in mixed-stock commercial salmon fisheries frequently result in bycatch mortality, thereby impeding salmonid recovery and constraining fishing opportunities in the U.S. Pacific Northwest. To address the problem, a postrelease survival study was conducted in the Columbia River to evaluate the potential of an experimental salmon trap for stock-selective commercial harvest. A modified fish trap was constructed and operated in 2017, from August through September, with the goal of minimizing entanglement, air exposure, crowding, and handling of all captured fishes. Postrelease survival from the trap was estimated through a paired release–recapture study. Results demonstrate that the trap effectively targeted commercially viable quantities of hatchery-origin Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch while reducing bycatch mortality rates relative to conventional commercial fishing gears. During the study, 7,129 salmonids were captured. The postrelease survival effect over a 400-km migration ranged from 0.944 (SE¯ = 0.046) for steelhead O. mykiss to 0.995 (SE¯ = 0.078) for Chinook Salmon, supporting the potential application of traps for stock-selective commercial harvest.
Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice
Authors: Wang Chia‐Yu , Xiao Xia , Bayer Abraham , Xu Yang , Dev Som , Canali Susanna , Nair Anil V. , Masia Ricard , Babitt Jodie L. 
Published: May 2019

A failure of iron to appropriately regulate liver hepcidin production is central to the pathogenesis of hereditary hemochromatosis. SMAD1/5 transcription factors, activated by bone morphogenetic protein (BMP) signaling, are major regulators of hepcidin production in response to iron; however, the role of SMAD8 and the contribution of SMADs to hepcidin production by other systemic cues remain uncertain. Here, we generated hepatocyte Smad8 single (Smad8fl/fl;Alb‐Cre+
), Smad1/5/8 triple (Smad158;Alb‐Cre+
), and littermate Smad1/5 double (Smad15;Alb‐Cre+
) knockout mice to investigate the role of SMAD8 in hepcidin and iron homeostasis regulation and liver injury. We found that Smad8;Alb‐Cre+
mice exhibited no iron phenotype, whereas Smad158;Alb‐Cre+
mice had greater iron overload than Smad15;Alb‐Cre+
mice. In contrast to the sexual dimorphism reported for wild‐type mice and other hemochromatosis models, hepcidin deficiency and extrahepatic iron loading were similarly severe in Smad15;Alb‐Cre+
and Smad158;Alb‐Cre+
female compared with male mice. Moreover, epidermal growth factor (EGF) failed to suppress hepcidin in Smad15;Alb‐Cre+
hepatocytes. Conversely, hepcidin was still increased by lipopolysaccharide in Smad158;Alb‐Cre+
mice, although lower basal hepcidin resulted in lower maximal hepcidin. Finally, unlike most mouse hemochromatosis models, Smad158;Alb‐Cre+
developed liver injury and fibrosis at 8 weeks. Liver injury and fibrosis were prevented in Smad158;Alb‐Cre+
mice by a low‐iron diet and were minimal in iron‐loaded Cre–
mice. Conclusion: Hepatocyte Smad1/5/8 knockout mice are a model of hemochromatosis that encompasses liver injury and fibrosis seen in human disease. These mice reveal the redundant but critical role of SMAD8 in hepcidin and iron homeostasis regulation, establish a requirement for SMAD1/5/8 in hepcidin regulation by testosterone and EGF but not inflammation, and suggest a pathogenic role for both iron loading and SMAD1/5/8 deficiency in liver injury and fibrosis.
Case of acute respiratory distress syndrome in a patient with an extragonadal germ cell tumor without lung metastasis in which choriocarcinoma syndrome was suspected
Authors: Kobayashi Kota , Tsutsumi Sohgo , Noguchi Go , Umemoto Susumu , Osaka Kimito , Kisida Takeshi 
Published: May 2019

IntroductionChoriocarcinoma syndrome is caused by bleeding from metastatic germ cell tumors with choriocarcinoma components. Here, we report a case of acute respiratory distress syndrome, which arose after first‐line chemotherapy for an extragonadal germ cell tumor without lung metastasis.Case presentationA 41‐year‐old male visited our institution with chief complaints of back pain and weight loss. Computed tomography showed multiple lymph node metastases in the retroperitoneal cavity. There were no lung metastases. A lymph node biopsy resulted in a diagnosis of choriocarcinoma. Bleomycin etoposide cisplatin therapy was started as induction chemotherapy. On the first day, he was diagnosed with acute respiratory distress syndrome due to choriocarcinoma syndrome. We administered high‐dose hydrocortisone therapy for 3 days. The patient's respiratory status improved.ConclusionIn patients who are at high risk of developing choriocarcinoma syndrome, induction chemotherapy might lead to the development of acute respiratory distress syndrome due to the release of cytokines despite the absence of lung metastasis.
Measuring mortgage credit availability: A frontier estimation approach
Authors: Anenberg Elliot , Hizmo Aurel , Kung Edward , Molloy Raven 
Published: May 2019

SummaryWe construct a new measure of mortgage credit availability using a technique developed for production frontier estimation. The resulting “loan frontier” describes the maximum amount obtainable by a borrower of given characteristics. We estimate this frontier using mortgage originations data from 2001 to 2014. We find a substantial expansion of mortgage credit for all borrowers during the housing boom, not only for low‐score or low‐income borrowers. The subsequent contraction in credit was most pronounced for low‐score borrowers. Using variation in the frontier across metropolitan areas over time, we show that borrowing constraints played an important role in the recent housing cycle.
Neuroprotection by glucose‐6‐phosphate dehydrogenase and the pentose phosphate pathway
Authors: Tang Bor Luen 
Published: May 2019

AbstractGlucose‐6‐phosphate dehydrogenase (G6PD), the rate limiting enzyme that channels glucose catabolism from glycolysis into the pentose phosphate pathway (PPP), is vital for the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in cells. NADPH is in turn a substrate for glutathione reductase, which reduces oxidized glutathione disulfide to sulfhydryl glutathione. Best known for inherited deficiencies underlying acute hemolytic anemia due to elevated oxidative stress by food or medication, G6PD, and PPP activation have been associated with neuroprotection. Recent works have now provided more definitive evidence for G6PD's protective role in ischemic brain injury and strengthened its links to neurodegeneration. In Drosophila models, improved proteostasis and lifespan extension result from an increased PPP flux due to G6PD induction, which is phenocopied by transgenic overexpression of G6PD in neurons. Moderate transgenic expression of G6PD was also shown to improve healthspan in mouse. Here, the deciphered and implicated roles of G6PD and PPP in protection against brain injury, neurodegenerative diseases, and in healthspan/lifespan extensions are discussed together with an important caveat, namely NADPH oxidase (NOX) activity and the oxidative stress generated by the latter. Activation of G6PD with selective inhibition of NOX activity could be a viable neuroprotective strategy for brain injury, disease, and aging.
Therapeutic effect of liraglutide on expression of CTGF and BMP‐7 in induced diabetic nephropathy
Authors: Ramzy Maggie M. , Abdalla Ahlam M. , Zenhom Nagwa M. , Okasha Ahmed M. , Abdelkafy Aya E. , Saleh Rabeh K. 
Published: May 2019

AbstractIntroductionDiabetic nephropathy (DN) is one of the critical complications of diabetes mellitus and the main cause of chronic renal dysfunction. The pathogenic mechanism causing the disease remains unclear and there is a lack of effective treatment methods so novel strategies are needed for DN management. The aim of this study, therefore, is to evaluate the effect of liraglutide as glucagon‐like peptide‐1 analogue and its underlying mechanisms on induced DN in ratsMaterials and MethodsSixty rats were divided into control group, diabetic group, and liraglutide‐treated group. At the end of experiment, renal CTGF and BMP‐7 messeger RNA expression were determined. Blood sugar, serum urea, and creatinine were measured. Also, histopathological changes were studied.ResultsLiraglutide can improve renal alterations associated with diabetes as it reduced CTGF expression and increased BMP‐7 expression. In the same time, it could improve histopathological changes and renal function tests.ConclusionThese findings influence the beneficial use of liraglutide for the management of DN in patients with diabetes mellitus.
Leukemia‐derived exosomes: Bringing oncogenic signals to blood cells
Authors: Sharifi Hossein , Shafiee Alimohammad , Molavi Ghader , Razi Ebrahim , Mousavi Nousin , Sarvizadeh Mostafa , Taghizadeh Mohsen 
Published: May 2019

AbstractLeukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano‐carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia‐derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.
HANR promotes lymphangiogenesis of hepatocellular carcinoma via secreting miR‐296 exosome and regulating EAG1/VEGFA signaling in HDLEC cells
Authors: Shi Yang , Yang Xiaohua , Xue Xiaofeng , Sun Ding , Cai Peng , Song Qingwei , Zhang Bin , Qin Lei 
Published: May 2019

AbstractThe long noncoding RNA HANR has been shown to be involved in the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC‐associated long noncoding RNA (HANR)–regulated HCC metastasis and lymphangiogenesis has not been elucidated. RT‐qPCR and Western blot methods were utilized to detect the gene expressions. Interaction of HANR with miR‐296 was predicted by a bioinformatic program and validated by a dual‐luciferase reporter assay. For the functional experiment, a transwell invasion assay was utilized to examine the invasion abilities of HepG2 and Huh‐7 cells. The lymphatic vessel formation assay was used to show the HCC‐associated lymphatic vessel formation ability of human dermal lymphatic endothelial cells (HDLEC). HANR was shown to directly bind to miR‐296, and miR‐296 downregulated HANR expression in HepG2 cells. Then, we observed that miR‐296 inhibitor transfection in shHANR HCC cells could promote lymphatic vessel formation and invasion of HDLEC cells compared with shHANR HCC cells. EAG1 or VEGFA overexpression in HDLEC cells rescued lymphatic vessel formation and invasion in HDLEC cells coincubated with the medium of HepG2 cells expressing shHANR or miR‐296 mimic. Ultimately, HANR knockdown and miR‐296 mimic led to a significant decrease in the EAG1 and VEGFA expression levels in HepG2 cells. Here, we reveal a novel molecular mechanism in which the HANR/miR‐296/EAG1/VEGF axis is responsible for the lymphangiogenesis of HCC cells. Our findings provide more insights into developing therapeutical or diagnostic methods by targeting HANR.
Identification and validation of key genes associated with non‐small‐cell lung cancer
Authors: Ma Qiang , Xu Yuan , Liao Hebin , Cai Yan , Xu Lei , Xiao Dan , Liu Chang , Pu Wenjie , Zhong Xiaowu , Guo Xiaolan 
Published: May 2019

AbstractNon‐small‐cell lung cancer (NSCLC) is one of the main causes of death induced by cancer globally. However, the molecular aberrations in NSCLC patients remain unclearly. In the present study, four messenger RNA microarray datasets (GSE18842, GSE40275, GSE43458, and GSE102287) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NSCLC tissues and adjacent lung tissues were obtained from GEO2R and the overlapping DEGs were identified. Moreover, functional and pathway enrichment were performed by Funrich, while the protein–protein interaction (PPI) network construction were obtained from STRING and hub genes were visualized and identified by Cytoscape software. Furthermore, validation, overall survival (OS) and tumor staging analysis of selected hub genes were performed by GEPIA. A total of 367 DEGs (95 upregulated and 272 downregulated) were obtained through gene integration analysis. The PPI network consisted of 94 nodes and 1036 edges in the upregulated DEGs and 272 nodes and 464 edges in the downregulated DEGs, respectively. The PPI network identified 46 upregulated and 27 downregulated hub genes among the DEGs, and six (such as CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M) of that have not been identified to be associated with NSCLC so far. Moreover, the expression differences of the mentioned hub genes were consistent with that in lung adenocarcinoma and lung squamous cell carcinoma in the TCGA database. Further analysis showed that all the six hub genes were associated with tumor staging except MYH11, while only the upregulated DEG CENPE was associated with the worse OS of patients with NSCLC. In conclusion, the current study showed that CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M might be the key genes contributed to tumorigenesis or tumor progression in NSCLC, further functional study is needed to explore the involved mechanisms.
Knockdown of periostin attenuates 5/6 nephrectomy‐induced intrarenal renin–angiotensin system activation, fibrosis, and inflammation in rats
Authors: Bian Xiaohui , Bai Yu , Su Xiaoxiao , Zhao Guifeng , Sun Guangping , Li Detian 
Published: May 2019

AbstractTo simulate clinical features in human chronic kidney disease (CKD), SD rats were subjected to 5/6 nephrectomy in this study. We found that periostin gene was upregulated in the remnant kidneys using Agilent gene microarrays, and further explored its role via in vivo and in vitro experiments. Intrarenal renin–angiotensin system (RAS) was activated in 5/6 nephrectomized rats and partly deactivated by injection of adenoviruses encoding short hairpin RNA against periostin (sh‐periostin). Renal fibrosis in nephrectomized rats and profibrotic transforming growth factor‐β‐induced epithelial–mesenchymal transition (EMT) and ERK1/2 activation in NRK‐52E cells were suppressed by sh‐periostin. Moreover, knockdown of periostin decreased the generation of Interleukin 6 (IL6) and tumor necrosis factor‐α (TNF‐α) and accelerated p62 degradation in the remnant kidneys. Both HK‐2 cells treated with recombinant periostin and NRK‐52E cells infected with adenoviruses expressing periostin produced more IL6 and TNF‐α than control cells and displayed impaired autophagy as evidenced by inhibition of LC3II to LC3I conversion, Beclin 1 expression, and p62 degradation. By treating cells with rapamycin, an inhibitor of mamalian target of rapamycin known to activate autophagy, we noted that periostin‐induced inflammation was inhibited. Additionally, HK‐2 cells transfected with periostin overexpression plasmid generated more CCL2 and CXCL10, two important chemotactic factors, than untransfected cells. Conditioned medium from HK‐2 cells overexpressing periostin augmented chemotaxis of THP‐1 macrophages. Collectively, our work demonstrates that knockdown of periostin attenuates 5/6 nephrectomy‐induced intrarenal RAS activation, fibrosis, and inflammation in rats. These findings advance our understanding of periostin's role in CKD induced by nephron loss.