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https://www.readbyqxmd.com/read/28103025/identification-of-the-first-selective-activin-receptor-like-kinase-1-inhibitor-a-reversible-version-of-l-783277
#1
Hanna Cho, Sandip Sengupta, Sean Sh Jeon, Wooyoung Hur, Hwan Geun Choi, Hong Seog Seo, Byung Joo Lee, Jeong Hun Kim, Minhwan Chung, Noo Li Jeon, Nam Doo Kim, Taebo Sim
We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102869/design-considerations-to-minimize-the-impact-of-drug-absorption-in-polymer-based-organ-on-a-chip-platforms
#2
V S Shirure, S C George
Biocompatible polymers, such as polydimethylsiloxane (PDMS), are the materials of choice for creating organ-on-a-chip microfluidic platforms. Desirable qualities include ease of fabrication, optical clarity, and hydrophobicity, the latter of which facilitates oxygen transport to encased cells. An emerging and important application of organ-on-a-chip technology is drug discovery; however, a potential issue for polymer-based microfluidic devices has been highlighted by recent studies with PDMS, which have demonstrated absorption (and thus loss) of hydrophobic drugs into PDMS under certain experimental conditions...
January 19, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28092941/21st-century-cell-culture-for-21st-century-toxicology
#3
David Pamies, Thomas Hartung
There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092692/smile-seq-identifies-binding-motifs-of-single-and-dimeric-transcription-factors
#4
Alina Isakova, Romain Groux, Michael Imbeault, Pernille Rainer, Daniel Alpern, Riccardo Dainese, Giovanna Ambrosini, Didier Trono, Philipp Bucher, Bart Deplancke
Resolving the DNA-binding specificities of transcription factors (TFs) is of critical value for understanding gene regulation. Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes...
January 16, 2017: Nature Methods
https://www.readbyqxmd.com/read/28092380/chromatin-immunoprecipitation-in-microfluidic-droplets-towards-fast-and-cheap-analyses
#5
Bruno Teste, Jerome Champ, Arturo Londono-Vallejo, Stéphanie Descroix, Laurent Malaquin, Jean-Louis Viovy, Irena Draskovic, Guillaume Mottet
Genetic organization is governed by the interaction of DNA with histone proteins, and differential modifications of these proteins is a fundamental mechanism of gene regulation. Histone modifications are primarily studied through chromatin immunoprecipitation (ChIP) assays, however conventional ChIP procedures are time consuming, laborious and require a large number of cells. Here we report for the first time the development of ChIP in droplets based on a microfluidic platform combining nanoliter droplets, magnetic beads (MB) and magnetic tweezers (MT)...
January 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28090668/studies-of-anticancer-drug-cytotoxicity-based-on-long-term-hepg2-spheroid-culture-in-a-microfluidic-system
#6
Agnieszka Zuchowska, Karina Kwapiszewska, Michal Chudy, Artur Dybko, Zbigniew Brzozka
Cell-on-a-chip systems have become promising devices to study the effectiveness of new anticancer drugs recently. Several microdevices for liver cancer culture and evaluation of the drug cytotoxicity have been reported. However, there are still no proven reports about high-throughput and simple methods for the evaluation of drug cytotoxicity on liver cancer cells. The paper presents the results of the effects of the anticancer drug (5-fluorouracil, 5-FU) on the HepG2 spheroids as a model of liver cancer. The experiments were based on the long-term 3D spheroid culture in the microfluidic system and monitoring of the effect of 5-FU at two selected concentrations (0...
January 16, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28090219/integrated-microfluidic-aptasensor-for-mass-spectrometric-detection-of-vasopressin-in-human-plasma-ultrafiltrate
#7
J Yang, J Zhu, R Pei, J A Oliver, D W Landry, M N Stojanovic, Q Lin
We present a microfluidic aptamer-based biosensor for detection of low-molecular-weight biomarkers in patient samples. Using a microfluidic device that integrates aptamer-based specific analyte extraction, isocratic elution, and detection by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, we demonstrate rapid, sensitive and label-free detection of arginine vasopressin (AVP) in human plasma ultrafiltrate. AVP molecules in complex matrices are specifically captured by an aptamer that is immobilized on microbeads via affinity binding in a microchamber...
July 14, 2016: Analytical Methods: Advancing Methods and Applications
https://www.readbyqxmd.com/read/28089275/microfluidic-membrane-suppressor-module-design-and-evaluation-for-capillary-ion-chromatography
#8
Sam Wouters, Cees Bruggink, Yury Agroskin, Christopher Pohl, Sebastiaan Eeltink
A microfluidic ion-suppression module for use in ion-exchange chromatography has been developed and evaluated. The device consists of an ion-exchange membrane clamped between two polymer chips featuring a 200×100μm (width×depth) eluent channel (l=60mm), and a 300×150μm regenerant channel (60mm), respectively. The suppression efficacy using a Nafion membrane was compared with that of a styrene-sulfonate grafted fluorinated ethylene propylene (FEP) membrane. The latter was found to outperform Nafion in terms of lowest attainable background signal (suppression efficacy) and dynamic suppression range...
December 29, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28088752/microfluidic-approaches-for-isolation-detection-and-characterization-of-extracellular-vesicles-current-status-and-future-directions
#9
REVIEW
Shima Gholizadeh, Mohamed Shehata Draz, Maryam Zarghooni, Amir Sanati-Nezhad, Saeid Ghavami, Hadi Shafiee, Mohsen Akbari
Extracellular vesicles (EVs) are cell-derived vesicles present in body fluids that play an essential role in various cellular processes, such as intercellular communication, inflammation, cellular homeostasis, survival, transport, and regeneration. Their isolation and analysis from body fluids have a great clinical potential to provide information on a variety of disease states such as cancer, cardiovascular complications and inflammatory disorders. Despite increasing scientific and clinical interest in this field, there are still no standardized procedures available for the purification, detection, and characterization of EVs...
December 30, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088281/flow-injection-microfluidic-device-with-on-line-fluorescent-derivatization-for-the-determination-of-cr-iii-and-cr-vi-in-water-samples-after-solid-phase-extraction
#10
Guilong Peng, Qiang He, Ying Lu, Jing Huang, Jin-Ming Lin
In this paper, a rapid and simple method using magnetic multi-walled carbon nanotubes (MWCNTS), as a solid-phase extraction (SPE) sorbent, was successfully developed for extraction and preconcentration trace amounts of Cr(III) in water samples. The synthesized magnetic-MWCNTs nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A rhodamine derivative (R1) was synthesized and characterized as a highly selective and sensitive fluorescent derivatizing agent for Cr(III)...
February 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28074962/crossed-flow-microfluidics-for-high-throughput-screening-of-bioactive-chemical-cell-interactions
#11
Ziqiu Tong, Angela Ivask, Keying Guo, Scott McCormick, Enzo Lombi, Craig Priest, Nicolas H Voelcker
This paper describes the use of crossed laminar flow microfluidics for the selective capture of multiple cell types on-chip aiming for high throughput screening of various cell treatment compounds. Parallel laminar streams containing different cell types were perfused and captured on a cell adhesion protein-functionalized reaction area. Thereafter, parallel streams containing cell treatment solutions were delivered orthogonally over the captured cells. Multiple cell types and a range of cell treatment conditions could therefore be assessed in a single experiment...
January 11, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28074384/microfluidic-gut-liver-chip-for-reproducing-the-first-pass-metabolism
#12
Aerim Choe, Sang Keun Ha, Inwook Choi, Nakwon Choi, Jong Hwan Sung
After oral intake of drugs, drugs go through the first pass metabolism in the gut and the liver, which greatly affects the final outcome of the drugs' efficacy and side effects. The first pass metabolism is a complex process involving the gut and the liver tissue, with transport and reaction occurring simultaneously at various locations, which makes it difficult to be reproduced in vitro with conventional cell culture systems. In an effort to tackle this challenge, here we have developed a microfluidic gut-liver chip that can reproduce the dynamics of the first pass metabolism...
March 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28073898/two-stage-isothermal-enzymatic-amplification-for-concurrent-multiplex-molecular-detection
#13
Jinzhao Song, Changchun Liu, Michael G Mauk, Shelley C Rankin, James B Lok, Robert M Greenberg, Haim H Bau
BACKGROUND: The wide array of pathogens responsible for infectious diseases makes it difficult to identify causative pathogens with single-plex tests. Although multiplex PCR detects multiple targets, it is restricted to centralized laboratories, which delays test results or makes multiplexing unavailable, depriving healthcare providers of critical, real-time information. METHODS: To address the need for point-of-care (POC) highly multiplexed tests, we propose the 2-stage, nested-like, rapid (<40 min) isothermal amplification assay, dubbed rapid amplification (RAMP)...
January 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28073029/multiplexed-efficient-on-chip-sample-preparation-and-sensitive-amplification-free-detection-of-ebola-virus
#14
K Du, H Cai, M Park, T A Wall, M A Stott, K J Alfson, A Griffiths, R Carrion, J L Patterson, A R Hawkins, H Schmidt, R A Mathies
An automated microfluidic sample preparation multiplexer (SPM) has been developed and evaluated for Ebola virus detection. Metered air bubbles controlled by microvalves are used to improve bead-solution mixing thereby enhancing the hybridization of the target Ebola virus RNA with capture probes bound to the beads. The method uses thermally stable 4-formyl benzamide functionalized (4FB) magnetic beads rather than streptavidin coated beads with a high density of capture probes to improve the target capture efficiency...
January 3, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28067427/on-controlling-the-flow-behavior-driven-by-induction-electrohydrodynamics-in-microfluidic-channels
#15
Yanbo Li, Yukun Ren, Weiyu Liu, Xiaoming Chen, Ye Tao, Hongyuan Jiang
In this study, we develop a nondimensional physical model to demonstrate fluid flow at the micrometer dimension driven by traveling-wave induction electrohydrodynamics (EHD) through direct numerical simulation. In order to realize an enhancement in the pump flow rate as well as a flexible adjustment of anisotropy of flow behavior generated by induction EHD in microchannels, while not adding the risk of causing dielectric breakdown of working solution and material for insulation, a pair of synchronized traveling-wave voltage signals are imposed on double-sided electrode arrays that are mounted on the top and bottom insulating substrate, respectively...
January 9, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28067319/c-elegans-on-a-chip-for-in-situ-and-in-vivo-ag-nanoparticles-uptake-and-toxicity-assay
#16
Jin Ho Kim, Seung Hwan Lee, Yun Jeong Cha, Sung Jin Hong, Sang Kug Chung, Tai Hyun Park, Shin Sik Choi
Nanomaterials are extensively used in consumer products and medical applications, but little is known about their environmental and biological toxicities. Moreover, the toxicity analysis requires sophisticated instruments and labor-intensive experiments. Here we report a microfluidic chip incorporated with the nematode Caenorhabditis elegans that rapidly displays the changes in body growth and gene expression specifically responsive to the silver nanoparticles (AgNPs). C. elegans were cultured in microfluidic chambers in the presence or absence of AgNPs and were consequently transferred to wedge-shaped channels, which immobilized the animals, allowing the evaluation of parameters such as length, moving distance, and fluorescence from the reporter gene...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062831/glioblastoma-on-a-microfluidic-chip-generating-pseudopalisades-and-enhancing-aggressiveness-through-blood-vessel-obstruction-events
#17
Jose M Ayuso, Rosa Monge, Alicia Martínez-González, María Virumbrales-Muñoz, Guillermo A Llamazares, Javier Berganzo, Aurelio Hernández-Laín, Jorge Santolaria, Manuel Doblaré, Christopher Hubert, Jeremy N Rich, Pilar Sánchez-Gómez, Víctor M Pérez-García, Ignacio Ochoa, Luis J Fernández
BACKGROUND: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudopalisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells. These "waves" of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM's spread and invasion, the recreation of these structures in vitro has remained challenging...
January 6, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28061811/the-nature-and-nurture-of-cell-heterogeneity-accounting-for-macrophage-gene-environment-interactions-with-single-cell-rna-seq
#18
Quin F Wills, Esther Mellado-Gomez, Rory Nolan, Damien Warner, Eshita Sharma, John Broxholme, Benjamin Wright, Helen Lockstone, William James, Mark Lynch, Michael Gonzales, Jay West, Anne Leyrat, Sergi Padilla-Parra, Sarah Filippi, Chris Holmes, Michael D Moore, Rory Bowden
BACKGROUND: Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome's limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic 'snapshots' of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic ('nature') and environmental ('nurture') modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages...
January 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28059451/logic-digital-fluidic-in-miniaturized-functional-devices-perspective-to-the-next-generation-of-microfluidic-lab-on-chips
#19
Qiongdi Zhang, Ming Zhang, Lyas Deghlaf, Jeanne Bataille, Jean Gamby, Anne-Marie Haghiri-Gosnet, Antoine Pallandre
Microfluidics has emerged following the quest for scale reduction inherent to micro and nanotechnologies. By definition, microfluidics manipulates fluids in small channels with dimensions of tens to hundreds of micrometers. Recently, microfluidics has been greatly developed and its influence extends not only the domains of chemical synthesis, bioanalysis and medical researches but also optics and information technology. In this review article, we will shortly discuss an enlightening analogy between electrons transport in electronics and fluids transport in microfluidic channels...
January 6, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28059147/an-on-chip-imaging-droplet-sorting-system-a-real-time-shape-recognition-method-to-screen-target-cells-in-droplets-with-single-cell-resolution
#20
Mathias Girault, Hyonchol Kim, Hisayuki Arakawa, Kenji Matsuura, Masao Odaka, Akihiro Hattori, Hideyuki Terazono, Kenji Yasuda
A microfluidic on-chip imaging cell sorter has several advantages over conventional cell sorting methods, especially to identify cells with complex morphologies such as clusters. One of the remaining problems is how to efficiently discriminate targets at the species level without labelling. Hence, we developed a label-free microfluidic droplet-sorting system based on image recognition of cells in droplets. To test the applicability of this method, a mixture of two plankton species with different morphologies (Dunaliella tertiolecta and Phaeodactylum tricornutum) were successfully identified and discriminated at a rate of 10 Hz...
January 6, 2017: Scientific Reports
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