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1.
Elena Vargas-Accarino Carlos Herrera-Montvez Santiago Ramn y Cajal Trond Aasen 《International journal of molecular sciences》2021,22(9)
There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis. 相似文献
2.
Belcher Calvin H. Zheng Baolong MacDonald Benjamin E. Langlois Eric D. Lehman Benjamin Pearce Charles Delaney Robert Apelian Diran Lavernia Enrique J. Monson Todd C. 《Journal of Materials Science》2022,57(9):5518-5532
Journal of Materials Science - For transformers and inductors to meet the world’s growing demand for electrical power, more efficient soft magnetic materials with high saturation magnetic... 相似文献
3.
Lopez Daniel Andres Sanchez Chagas Luciana Gomes Batista Aline Domingues Guaita Maria Gabriella Detone Amorin Luís Henrique Cardozo da Silva Paulo Rogério Catarini Yamanishi Gustavo Zaia Dimas Augusto Morozin de Santana Henrique Urbano Alexandre 《Journal of Materials Science: Materials in Electronics》2021,32(13):17462-17472
Journal of Materials Science: Materials in Electronics - The increasing demand for lithium-ion batteries has stimulated the investigation of new compounds in order to reduce the costs and the... 相似文献
4.
Santiago Enrique Sanchez Daniel R. Whiten Dr. Georg Meisl Dr. Francesco Simone Ruggeri Eric Hidari Prof. David Klenerman 《Chembiochem : a European journal of chemical biology》2021,22(19):2867-2871
The aggregation of α-synuclein into small soluble aggregates and then fibrils is important in the development and spreading of aggregates through the brain in Parkinson's disease. Fibrillar aggregates can grow by monomer addition and then break into fragments that could spread into neighboring cells. The rate constants for fibril elongation and fragmentation have been measured but it is not known how large an aggregate needs to be before fibril formation is thermodynamically favorable. This critical size is an important parameter controlling at what stage in an aggregation reaction fibrils can form and replicate. We determined this value to be approximately 70 monomers using super-resolution and atomic force microscopy imaging of individual α-synuclein aggregates formed in solution over long time periods. This represents the minimum size for a stable α-synuclein fibril and we hypothesis the formation of aggregates of this size in a cell represents a tipping point at which rapid replication occurs. 相似文献
5.
Christian Grin-Ferr Júlia Companys-Alemany Júlia Jarn-Ferrer Sandra Codony Celia Gonzlez-Castillo Daniel Ortuo-Sahagún Lluïsa Vilageliu Daniel Grinberg Santiago Vzquez Merc Palls 《International journal of molecular sciences》2021,22(7)
Niemann–Pick type C (NPC) disease is a rare autosomal recessive inherited childhood neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids, involving the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 12-diols, exerts beneficial effects in modulating inflammation and autophagy, critical features of the NPC disease. This study aims to evaluate the effects of UB-EV-52, an sEH inhibitor (sEHi), in an NPC mouse model (Npc) by administering it for 4 weeks (5 mg/kg/day). Behavioral and cognitive tests (open-field test (OF)), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that the treatment produced an improvement in short- and long-term memory as well as in spatial memory. Furthermore, UB-EV-52 treatment increased body weight and lifespan by 25% and reduced gene expression of the inflammatory markers (i.e., Il-1β and Mcp1) and enhanced oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. As for autophagic markers, surprisingly, we found significantly reduced levels of LC3B-II/LC3B-I ratio and significantly reduced brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in treated Npc mice group compared to untreated ones in hippocampal tissue. Lipid profile analysis showed a significant reduction of lipid storage in the liver and some slight changes in homogenated brain tissue in the treated NPC mice compared to the untreated groups. Therefore, our results suggest that pharmacological inhibition of sEH ameliorates most of the characteristic features of NPC mice, demonstrating that sEH can be considered a potential therapeutic target for this disease. 相似文献
6.
Scientometrics - The purpose of this study is to ascertain the suitability of GS’s url-based method as a valid approximation of universities’ academic output measures, taking into... 相似文献
7.
Pedro Freire Filgueiras Joo Teixeira Oliveira de Menezes Juan Elias Perez Ipia Enrique Mariano Castrodeza 《Fatigue & Fracture of Engineering Materials & Structures》2019,42(2):572-582
Recently released, BS 8571:2014 standard offers an alternative for the experimental determination of fracture toughness and resistance curves of metallic materials from SE(T) specimens. Similar in stress conditions and constraint to cracked tubes, specimens in SE(T) geometry should yield less conservative toughness values than conventional high‐constraint specimens, such as SE(B) geometry. However, the convention to determine the J‐integral fracture toughness proposed in the new BS standard is different from ASTM standards. In this work, SE(T) and SE(B) specimens of similar dimensions of a tough high‐strength seamless pipe steel were tested following the BS 8571:2014 and ASTM E1820‐16 standards, respectively. Because of the different standardized definitions, SE(T) specimens yield lower fracture toughness than SE(B) specimens, which could lead to more conservative results in structural integrity analysis. This investigation also suggests the introduction of the blunting line concept in the BS 8571:2014 standard in order to minimize this problem. 相似文献
8.
Miguel Pallares Davide Fascione Gianluca Iannotta Alessandro Laner Alessandro Leanti Enrico Pellegrini Jenny Spagnolatti Santiago Trujillo Anna Zauli Andrea Martiradonna 《世界建筑导报》2018,(5)
正Piuarch建筑师事务所负责设计了2015年米兰世博会埃内尔(意大利国家电力公司)展馆及卡里塔斯展馆。为了将客户想表达的含义与价值观更好地传达给观众,Piuarch选择了一种特殊的建筑语言来体现两个展馆的特点。埃内尔展馆沿东西大街而建,占地900平方米。设计体现出智能电网这一概念,传达出以智能科技优化世博会整体用电的理念。 相似文献
9.
David A. Serje Enrique E. Niebles Sheila K. Lascano 《Journal of Failure Analysis and Prevention》2018,18(5):1053-1061
This article details the analysis of two conducting shafts operating on blowers of a tunnel dryer. A deductive analysis was applied looking toward a successful recognition of root cause(s), where based on knowledge of background, and failure characteristics, multiple hypothesis are exposed that are further confirmed or rejected according to different tests, material analysis or maintenance history. In both shafts, failure arises from inadequate repairing. In order to confirm this, the failure analysis methodology included the following steps: technical review, visual inspection, fractography, penetrating inks, metallography, optic microscopy and stress analysis. Evidence obtained through these techniques indicates a fatigue failure induced by inadequate repairing procedures; therefore, main recommendation is to take the necessary precautions in order to guarantee minimal alterations on shaft geometry or material microstructure. 相似文献
10.
Mostafa Dellahi Hattab Maker Guillermo Botella Enrique Alameda-Hernandez Azeddine Mouhsen 《International Journal of Circuit Theory and Applications》2020,48(6):887-905
The three-phase four-wire shunt active power filter (SAPF) was developed to suppress the harmonic currents generated by nonlinear loads, and for the compensation of unbalanced nonlinear load currents, reactive power, and the harmonic neutral current. In this work, we consider instantaneous reactive power theory (PQ theory) for reference current identification based on the following two algorithms: the classic low-pass filter (LPF) and the second-order generalized integrator (SOGI) filter. Furthermore, since an important process in SAPF control is the regulation of the DC bus voltage at the capacitor, a new controller based on the Lyapunov function is also proposed. A complete simulation of the resultant active filtering system confirms its validity, which uses the SOGI filter to extract the reference currents from the distorted line currents, compared with the traditional PQ theory based on LPF. In addition, the simulation performed also demonstrates the superiority of the proposed approach, for DC bus voltage control based on the Lyapunov function, compared with the traditional proportional-integral (PI) controller. Both novel approaches contribute towards an improvement in the overall performance of the system, which consists of a small rise and settling time, a very low or nonexistent overshoot, and the minimization of the total harmonic distortion (THD). 相似文献