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Organs chips

Pablo Huertas, Andrés Cruz-García
Homologous recombination is initiated by the so-called DNA end resection, the 5'-3' nucleolytic degradation of a single strand of the DNA at each side of the break. The presence of resected DNA is an obligatory step for homologous recombination. Moreover, the amount of resected DNA modulates the prevalence of different recombination pathways. In different model organisms, there are several published ways to visualize and measure with more or less detail the amount of DNA resected. In human cells, however, technical constraints hampered the study of resection at high resolution...
2018: Methods in Molecular Biology
Patrick van Eijk, Yumin Teng, Mark R Bennet, Katie E Evans, James R Powell, Richard M Webster, Simon H Reed
The genetic information contained within the DNA molecule is highly susceptible to chemical and physical insult, caused by both endogenous and exogenous sources that can generate in the order of thousands of lesions a day in each of our cells (Lindahl, Nature 362(6422):709-715, 1993). DNA damages interfere with DNA metabolic processes such as transcription and replication and can be potent inhibitors of cell division and gene expression. To combat these regular threats to genome stability, a host of DNA repair mechanisms have evolved...
2018: Methods in Molecular Biology
Zongdai Liu, Rui Chen, Yanjun Liu, Xinhai Zhang, Xiaowei Sun, Wenbin Huang, Dan Luo
Organic microcavity lasers based on liquid crystals have attracted substantial attention due to their easy processing, compact volume and excellent tunable properties. However, the threshold of traditional holographic polymer dispersed liquid crystals (H-PDLCs) laser doped with dye is usually as high as several tens of μJ/pulse, which hinders its broad applications. Herein, we demonstrate a low-threshold lasing from quasicrystal based on H-PDLCs. An conjugated polymer poly (2-methoxy-5-(2'-ethyl-hexyloxy)-p-phenylenevinylene (MEH-PPV) film is coated on the inner surface of glass substrate to dramatically reduce the lasing threshold, which is 20 times lower than that of dye-doped microcavity laser...
September 4, 2017: Optics Express
Heiner Zwickel, Stefan Wolf, Clemens Kieninger, Yasar Kutuvantavida, Matthias Lauermann, Timothy de Keulenaer, Arno Vyncke, Renato Vaernewyck, Jingdong Luo, Alex K-Y Jen, Wolfgang Freude, Johan Bauwelinck, Sebastian Randel, Christian Koos
High-speed interconnects in data-center and campus-area networks crucially rely on efficient and technically simple transmission techniques that use intensity modulation and direct detection (IM/DD) to bridge distances of up to a few kilometers. This requires electro-optic modulators that combine low operation voltages with large modulation bandwidth and that can be operated at high symbol rates using integrated drive circuits. Here we explore the potential of silicon-organic hybrid (SOH) Mach-Zehnder modulators (MZM) for generating high-speed IM/DD signals at line rates of up to 120 Gbit/s...
October 2, 2017: Optics Express
Han Wang, David J Cocovi-Solberg, Bin Hu, Manuel Miró
In this work, the concept of 3D printed microflow injection (3D-µFI) embodying a dedicated multi-functional 3D-printed stator onto a rotary microvalve along with a mesofluidic sample preparation platform is proposed for the first time. A transparent 3D-printed stereolithographic mesofluidic chip device accommodating polyaniline (PANI) decorated magnetic nanoparticles (32.5±3.8 mg) is harnessed to in-line sorptive microextraction as a front end to liquid chromatography with peak focusing. As a proof of concept application, the 3D-µFI assembly was resorted to matrix clean-up and automatic programmable-flow determination of organic emerging contaminants (4-hydroxybenzoate analogs and triclosan as antimicrobial model analytes) in human saliva and urine samples...
October 17, 2017: Analytical Chemistry
Samira Musah, Akiko Mammoto, Thomas C Ferrante, Sauveur S F Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, James C Weaver, George M Church, Donald E Ingber
An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes...
2017: Nature biomedical engineering
Samad Ahadian, Robert Civitarese, Dawn Bannerman, Mohammad Hossein Mohammadi, Rick Lu, Erika Wang, Locke Davenport-Huyer, Ben Lai, Boyang Zhang, Yimu Zhao, Serena Mandla, Anastasia Korolj, Milica Radisic
Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis...
October 16, 2017: Advanced Healthcare Materials
Shenqi Wang, On Sun Lau
In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions...
2018: Methods in Molecular Biology
Hui Gao, Chunyan Zhao
Chromatin immunoprecipitation (ChIP) has become the most effective and widely used tool to study the interactions between specific proteins or modified forms of proteins and a genomic DNA region. Combined with genome-wide profiling technologies, such as microarray hybridization (ChIP-on-chip) or massively parallel sequencing (ChIP-seq), ChIP could provide a genome-wide mapping of in vivo protein-DNA interactions in various organisms. Here, we describe a protocol of ChIP-on-chip that uses tiling microarray to obtain a genome-wide profiling of ChIPed DNA...
2018: Methods in Molecular Biology
Antonio Jordán-Pla, Neus Visa
Arguably one of the most valuable techniques to study chromatin organization, ChIP is the method of choice to map the contacts established between proteins and genomic DNA. Ever since its inception, more than 30 years ago, ChIP has been constantly evolving, improving, and expanding its capabilities and reach. Despite its widespread use by many laboratories across a wide variety of disciplines, ChIP assays can be sometimes challenging to design, and are often sensitive to variations in practical implementation...
2018: Methods in Molecular Biology
Neus Visa, Antonio Jordán-Pla
Protein-DNA interactions in vivo can be detected and quantified by chromatin immunoprecipitation (ChIP). ChIP has been instrumental for the advancement of epigenetics and has set the groundwork for the development of a number of ChIP-related techniques that have provided valuable information about the organization and function of genomes. Here, we provide an introduction to ChIP and discuss the applications of ChIP in different research areas. We also review some of the strategies that have been devised to improve ChIP performance...
2018: Methods in Molecular Biology
Brandon Praslicka, Jeremy S Harmson, Joohyun Kim, Vittobai Rashika Rangaraj, Aikseng Ooi, Chris R Gissendanner
Members of the NR4A subfamily of nuclear receptors make up a highly conserved, functionally diverse group of transcription factors implicated in a multitude of cellular processes such as proliferation, differentiation, apoptosis, metabolism and DNA repair. The gene nhr-6, which encodes the sole C. elegans NR4A nuclear receptor homolog, has a critical role in organogenesis and regulates the development of the spermatheca organ system. Our previous work revealed that nhr-6 is required for spermatheca cell divisions in late L3 and early L4 and spermatheca cell differentiation during the mid L4 stage...
2017: Nuclear Receptor Research
D Caballero, S Kaushik, V M Correlo, J M Oliveira, R L Reis, S C Kundu
Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease...
October 3, 2017: Biomaterials
Bryan A Hassell, Girija Goyal, Esak Lee, Alexandra Sontheimer-Phelps, Oren Levy, Christopher S Chen, Donald E Ingber
Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy observed in human patients in vivo. Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase...
October 10, 2017: Cell Reports
Rimantas Kodzius, Frank Schulze, Xinghua Gao, Marlon R Schneider
In the early days of pharmacy, the development of new drugs was frequently achieved by restless chemists who worked solitarily, day by day for years [...].
October 11, 2017: Genes
Yolanda Blanco, Ignacio Gallardo-Carreño, Marta Ruiz-Bermejo, Fernando Puente-Sánchez, Erika Cavalcante-Silva, Antonio Quesada, Olga Prieto-Ballesteros, Víctor Parro
The search for biomarkers of present or past life is one of the major challenges for in situ planetary exploration. Multiple constraints limit the performance and sensitivity of remote in situ instrumentation. In addition, the structure, chemical, and mineralogical composition of the sample may complicate the analysis and interpretation of the results. The aim of this work is to highlight the main constraints, performance, and complementarity of several techniques that have already been implemented or are planned to be implemented on Mars for detection of organic and molecular biomarkers on a best-case sample scenario...
October 10, 2017: Astrobiology
Marinke W van der Helm, Mathieu Odijk, Jean-Philippe Frimat, Andries D van der Meer, Jan C T Eijkel, Albert van den Berg, Loes I Segerink
Organs-on-chips, in vitro models involving the culture of (human) tissues inside microfluidic devices, are rapidly emerging and promise to provide useful research tools for studying human health and disease. To characterize the barrier function of cell layers cultured inside organ-on-chip devices, often transendothelial or transepithelial electrical resistance (TEER) is measured. To this end, electrodes are usually integrated into the chip by micromachining methods to provide more stable measurements than is achieved with manual insertion of electrodes into the inlets of the chip...
September 26, 2017: Journal of Visualized Experiments: JoVE
Juan Mucci, Santiago J Carmona, Romina Volcovich, Jaime Altcheh, Estefanía Bracamonte, Jorge D Marco, Morten Nielsen, Carlos A Buscaglia, Fernán Agüero
Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens...
October 9, 2017: PLoS Neglected Tropical Diseases
Lin Liu, Seokheun Choi
A microfluidic lab-on-a-chip system that generates its own power is essential for stand-alone, independent, self-sustainable point-of-care diagnostic devices to work in limited-resource and remote regions. Miniaturized biological solar cells (or micro-BSCs) can be the most suitable power source for those lab-on-a-chip applications because the technique resembles the earth's natural ecosystem - living organisms work in conjunction with non-living components of their environment to create a self-assembling and self-maintaining system...
October 9, 2017: Lab on a Chip
Elena Biselli, Elena Agliari, Adriano Barra, Francesca Romana Bertani, Annamaria Gerardino, Adele De Ninno, Arianna Mencattini, Davide Di Giuseppe, Fabrizio Mattei, Giovanna Schiavoni, Valeria Lucarini, Erika Vacchelli, Guido Kroemer, Corrado Di Natale, Eugenio Martinelli, Luca Businaro
In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from 'wild type' donors (with normal expression of FPR1)...
October 6, 2017: Scientific Reports
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