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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212541/analysis-of-variability-in-high-throughput-screening-data-applications-to-melanoma-cell-lines-and-drug-responses
#2
Kuan-Fu Ding, Darren Finlay, Hongwei Yin, William P D Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar Sekulic, Patricia M LoRusso, Kristiina Vuori, Jeffrey M Trent, Nicholas J Schork
High-throughput screening (HTS) strategies and protocols have undergone significant development in the last decade. It is now possible to screen hundreds of thousands of compounds, each exploring multiple biological phenotypes and parameters, against various cell lines or model systems in a single setting. However, given the vast amount of data such studies generate, the fact that they use multiple reagents, and are often technician-intensive, questions have been raised about the variability, reliability and reproducibility of HTS results...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212410/a-high-throughput-genetic-screen-identifies-previously-uncharacterized-borrelia-burgdorferi-genes-important-for-resistance-against-reactive-oxygen-and-nitrogen-species
#3
Meghan E Ramsey, Jenny A Hyde, Diana N Medina-Perez, Tao Lin, Lihui Gao, Maureen E Lundt, Xin Li, Steven J Norris, Jon T Skare, Linden T Hu
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is exposed to reactive oxygen and nitrogen species (ROS and RNS) in both the tick vector and vertebrate reservoir hosts. B. burgdorferi contains a limited repertoire of canonical oxidative stress response genes, suggesting that novel gene functions may be important for protection of B. burgdorferi against ROS or RNS exposure. Here, we use transposon insertion sequencing (Tn-seq) to conduct an unbiased search for genes involved in resistance to nitric oxide, hydrogen peroxide, and tertiary-butyl hydroperoxide in vitro...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212378/sequencing-the-extrachromosomal-circular-mobilome-reveals-retrotransposon-activity-in-plants
#4
Sophie Lanciano, Marie-Christine Carpentier, Christel Llauro, Edouard Jobet, Dagmara Robakowska-Hyzorek, Eric Lasserre, Alain Ghesquière, Olivier Panaud, Marie Mirouze
Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA) forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28212328/differential-characteristics-based-iterative-multiuser-detection-for-wireless-sensor-networks
#5
Xiaoguang Chen, Xu Jiang, Zhilu Wu, Shufeng Zhuang
High throughput, low latency and reliable communication has always been a hot topic for wireless sensor networks (WSNs) in various applications. Multiuser detection is widely used to suppress the bad effect of multiple access interference in WSNs. In this paper, a novel multiuser detection method based on differential characteristics is proposed to suppress multiple access interference. The proposed iterative receive method consists of three stages. Firstly, a differential characteristics function is presented based on the optimal multiuser detection decision function; then on the basis of differential characteristics, a preliminary threshold detection is utilized to find the potential wrongly received bits; after that an error bit corrector is employed to correct the wrong bits...
February 16, 2017: Sensors
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#6
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28212287/big-data-analytics-for-genomic-medicine
#7
REVIEW
Karen Y He, Dongliang Ge, Max M He
Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients' genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212015/discovery-and-preclinical-characterization-of-3-4-4-chlorophenyl-7-fluoroquinoline-3-yl-sulfonyl-benzonitrile-a-novel-non-acetylenic-metabotropic-glutamate-receptor-5-mglur5-negative-allosteric-modulator-for-psychiatric-indications
#8
János Galambos, Attila Bielik, Mikhail Krasavin, Zoltán Orgován, György Domány, Katalin Nógrádi, Gábor Wágner, György T Balogh, Zoltán Béni, János Koti, Zoltán Szakács, Amrita Bobok, Sándor Kolok, Mónika L Miko-Bakk, Mónika Vastag, Katalin Sághy, Judit Laszy, Attila Sándor Halász, Ottilia Balázs, Krisztina Gál, István Greiner, Zsolt Szombathelyi, György M Keserű
Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as potential pharmacotherapy for a number of psychiatric diseases including anxiety and depression. Most of the mGluR5 NAM clinical candidates can be characterized by the central acetylenic moiety that connects the terminal pharmacophores. Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by optimization provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28211934/a-computational-assessment-of-the-electronic-thermoelectric-and-defect-properties-of-bournonite-cupbsbs3-and-related-substitutions
#9
Alireza Faghaninia, Guodong Yu, Umut Aydemir, Max Wood, Wei Chen, Gian-Marco Rignanese, G Jeffrey Snyder, Geoffroy Hautier, Anubhav Jain
Bournonite (CuPbSbS3) is an earth-abundant mineral with potential thermoelectric applications. This material has a complex crystal structure (space group Pmn21 #31) and has previously been measured to exhibit a very low thermal conductivity (κ < 1 W m(-1) K(-1) at T ≥ 300 K). In this study, we employ high-throughput density functional theory calculations to investigate how the properties of the bournonite crystal structure change with elemental substitutions. Specifically, we compute the stability and electronic properties of 320 structures generated via substitutions {Na-K-Cu-Ag}{Si-Ge-Sn-Pb}{N-P-As-Sb-Bi}{O-S-Se-Te} in the ABCD3 formula...
February 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28211907/identification-of-extracellular-segments-by-mass-spectrometry-improves-topology-prediction-of-transmembrane-proteins
#10
Tamás Langó, Gergely Róna, Éva Hunyadi-Gulyás, Lilla Turiák, Julia Varga, László Dobson, György Várady, László Drahos, Beáta G Vértessy, Katalin F Medzihradszky, Gergely Szakács, Gábor E Tusnády
Transmembrane proteins play crucial role in signaling, ion transport, nutrient uptake, as well as in maintaining the dynamic equilibrium between the internal and external environment of cells. Despite their important biological functions and abundance, less than 2% of all determined structures are transmembrane proteins. Given the persisting technical difficulties associated with high resolution structure determination of transmembrane proteins, additional methods, including computational and experimental techniques remain vital in promoting our understanding of their topologies, 3D structures, functions and interactions...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211892/high-throughput-in-situ-cell-electroporation-microsystem-for-parallel-delivery-of-single-guide-rnas-into-mammalian-cells
#11
Shengtai Bian, Yicen Zhou, Yawei Hu, Jing Cheng, Xiaofang Chen, Youchun Xu, Peng Liu
Arrayed genetic screens mediated by the CRISPR/Cas9 technology with single guide RNA (sgRNA) libraries demand a high-throughput platform capable of transfecting diverse cell types at a high efficiency in a genome-wide scale for detection and analysis of sophisticated cellular phenotypes. Here we developed a high-throughput in situ cell electroporation (HiCEP) microsystem which leveraged the superhydrophobic feature of the microwell array to achieve individually controlled conditions in each microwell and coupled an interdigital electrode array chip with the microwells in a modular-based scheme for highly efficient delivery of exogenous molecules into cells...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211844/a-tool-named-iris-for-versatile-high-throughput-phenotyping-in-microorganisms
#12
George Kritikos, Manuel Banzhaf, Lucia Herrera-Dominguez, Alexandra Koumoutsi, Morgane Wartel, Matylda Zietek, Athanasios Typas
Advances in our ability to systematically introduce and track controlled genetic variance in microorganisms have, in the past decade, fuelled high-throughput reverse genetics approaches. When coupled to quantitative readouts, such approaches are extremely powerful at elucidating gene function and providing insights into the underlying pathways and the overall cellular network organization. Yet, until now, all efforts to quantify microbial macroscopic phenotypes have been restricted to monitoring growth in a small number of model microorganisms...
February 17, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28211757/mice-and-the-a-bomb-irradiation-systems-for-realistic-exposure-scenarios
#13
Guy Garty, Yanping Xu, Carl Elliston, Stephen A Marino, Gerhard Randers-Pehrson, David J Brenner
Validation of biodosimetry assays is normally performed with acute exposures to uniform external photon fields. Realistically, exposure to a radiological dispersal device or reactor leak will include exposure to low dose rates and likely exposure to ingested radionuclides. An improvised nuclear device will likely include a significant neutron component in addition to a mixture of high- and low-dose-rate photons and ingested radionuclides. We present here several novel irradiation systems developed at the Center for High Throughput Minimally Invasive Radiation Biodosimetry to provide more realistic exposures for testing of novel biodosimetric assays...
February 17, 2017: Radiation Research
https://www.readbyqxmd.com/read/28211678/high-throughput-screening-of-sulfated-proteins-by-using-a-genome-wide-proteome-microarray-and-protein-tyrosine-sulfation-system
#14
Bo-Yu Huang, Po-Chung Chen, Bo-Han Chen, Chen-Chu Wang, Hsuan-Fu Liu, Yi-Zao Chen, Chien-Sheng Chen, Yuh-Shyong Yang
Protein tyrosine sulfation (PTS) is a widespread posttranslational modification that induces intercellular and extracellular responses by regulating protein-protein interactions and enzymes activities. Although PTS affects numerous physiological and pathological processes, only a small fraction of the total predicted sulfated proteins has been identified to date. Here, we localized the potential sulfation sites of Escherichia coli proteins on a proteome microarray by using a 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase-coupled tyrosylprotein sulfotransferase (TPST) catalysis system that involves in situ PAPS generation and TPST catalysis...
February 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28211495/characterization-of-biocarbon-source-recovery-and-microbial-community-shifts-from-waste-activated-sludge-by-conditioning-with-cornstover-assessment-of-cellulosic-compositions
#15
Kaili Wen, Aijuan Zhou, Jiaguang Zhang, Zhihong Liu, Guoying Wang, Wenzong Liu, Aijie Wang, Xiuping Yue
Most studies on the production of volatile fatty acids (VFAs) from waste activated sludge (WAS) digestion have focused on operating conditions, pretreatments and characteristic adjustments. Conditioning by extra carbon sources (ECS), normally added in a solid form, has been reported to be an efficient approach. However, this has caused considerable waste of monomeric sugars in the hydrolysate. In this study, the effects of two added forms (pretreated straw (S) and hydrolyzed liquid (L)) of cornstover (CS) on WAS acidification were investigated...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211071/accurate-robust-and-reliable-calculations-of-poisson-boltzmann-binding-energies
#16
Duc D Nguyen, Bao Wang, Guo-Wei Wei
Poisson-Boltzmann (PB) model is one of the most popular implicit solvent models in biophysical modeling and computation. The ability of providing accurate and reliable PB estimation of electrostatic solvation free energy, ΔGel, and binding free energy, ΔΔGel, is important to computational biophysics and biochemistry. In this work, we investigate the grid dependence of our PB solver (MIBPB) with solvent excluded surfaces for estimating both electrostatic solvation free energies and electrostatic binding free energies...
February 16, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#17
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28210733/super-high-energy-density-single-bonded-trigonal-nitrogen-allotrope-a-chemical-twin-of-the-cubic-gauche-form-of-nitrogen
#18
Sergey V Bondarchuk, Boris F Minaev
A new ambient-pressure metastable single-bonded 3D nitrogen allotrope (TrigN) of trigonal symmetry (space group R3[combining macron]) was calculated using density functional theory (DFT). A comprehensive characterization of this material, comprising thermodynamic, elastic, and spectral (vibrational, UV-vis absorption, and nuclear magnetic resonance) properties, was performed. Using high-throughput band structure calculation, the TrigN phase was characterized as an insulator with an indirect band gap of 2.977 eV...
February 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28210245/pcr-inhibition-of-a-quantitative-pcr-for-detection-of-mycobacterium-avium-subspecies-paratuberculosis-dna-in-feces-diagnostic-implications-and-potential-solutions
#19
Kamal R Acharya, Navneet K Dhand, Richard J Whittington, Karren M Plain
Molecular tests such as polymerase chain reaction (PCR) are increasingly being applied for the diagnosis of Johne's disease, a chronic intestinal infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Feces, as the primary test sample, presents challenges in terms of effective DNA isolation, with potential for PCR inhibition and ultimately for reduced analytical and diagnostic sensitivity. However, limited evidence is available regarding the magnitude and diagnostic implications of PCR inhibition for the detection of MAP in feces...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28209627/characterization-of-a-blood-spot-creatine-kinase-skeletal-muscle-isoform-immunoassay-for-high-throughput-newborn-screening-of-duchenne-muscular-dystrophy
#20
Stuart J Moat, Teemu Korpimäki, Petra Furu, Harri Hakala, Hanna Polari, Liisa Meriö, Pauliina Mäkinen, Ian Weeks
BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive, lethal X-linked neuromuscular disorder with an average worldwide incidence of 1:5000. Blood spot creatine kinase (CK) enzyme assays previously used in newborn screening programs for DMD are nonspecific because measured CK enzyme activity is attributable to 3 isoenzyme forms of CK (CK-MM, CK-MB, and CK-BB) and it is the CK-MM isoform that is found predominantly in skeletal muscle. CK-MM is increased in boys with DMD owing to muscle damage...
February 16, 2017: Clinical Chemistry
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