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https://www.readbyqxmd.com/read/28647608/a-route-based-pathway-analysis-framework-integrating-mutation-information-and-gene-expression-data
#1
Yue Zhao, Tham H Hoang, Pujan Joshi, Seung-Hyun Hong, Charles Giardina, Dong-Guk Shin
We propose a new way of analyzing biological pathways in which the analysis combines both transcriptome data and mutation information and uses the outcome to identify "routes" of aberrant pathways potentially responsible for the etiology of disease. Each pathway route is encoded as a Bayesian Network which is initialized with a sequence of conditional probabilities which are designed to encode directionality of regulatory relationships encoded in the pathways, i.e. activation and inhibition relationships. First, we demonstrate the effectiveness of our model through simulation in which the model was able to easily separate Test samples from Control samples using fictitiously perturbed pathway routes...
June 21, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28647561/identification-of-a-novel-splicing-mutation-within-slc17a8-in-a-korean-family-with-hearing-loss-by-whole-exome-sequencing
#2
Nari Ryu, Seokwon Lee, Hong-Joon Park, Byeonghyeon Lee, Tae-Jun Kwon, Jinwoong Bok, Chan Ik Park, Kyu-Yup Lee, Jeong-In Baek, Un-Kyung Kim
Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of HL, and the clinical information about this family revealed that there are no other symptoms accompanied with HL...
June 21, 2017: Gene
https://www.readbyqxmd.com/read/28647489/a-high-throughput-assay-to-identify-substrate-selective-inhibitors-of-the-erk-protein-kinases
#3
Chad J Miller, Yagmur Muftuoglu, Benjamin E Turk
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylate a variety of substrates important for survival and proliferation, and their activity is frequently deregulated in tumors. ERK pathway inhibitors have shown clinical efficacy as anti-cancer drugs, but most patients eventually relapse due to reactivation of the pathway. One factor limiting the efficacy of current therapeutics is the difficulty in reaching clinically effective inhibition of the ERK pathway in the absence of on-target toxicities...
June 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28647488/autoreactivity-to-malondialdehyde-modifications-in-rheumatoid-arthritis-is-linked-to-disease-activity-and-synovial-pathogenesis
#4
Caroline Grönwall, Khaled Amara, Uta Hardt, Akilan Krishnamurthy, Johanna Steen, Marianne Engström, Meng Sun, A Jimmy Ytterberg, Roman A Zubarev, Dagmar Scheel-Toellner, Jeffrey D Greenberg, Lars Klareskog, Anca I Catrina, Vivianne Malmström, Gregg J Silverman
Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA antibodies are associated with inflammatory and autoimmune conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA)...
June 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28647475/advanced-cell-classifier-user-friendly-machine-learning-based-software-for-discovering-phenotypes-in-high-content-imaging-data
#5
Filippo Piccinini, Tamas Balassa, Abel Szkalisity, Csaba Molnar, Lassi Paavolainen, Kaisa Kujala, Krisztina Buzas, Marie Sarazova, Vilja Pietiainen, Ulrike Kutay, Kevin Smith, Peter Horvath
High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments...
June 16, 2017: Cell Systems
https://www.readbyqxmd.com/read/28647441/prevention-of-epilepsy-should-we-be-avoiding-clinical-trials
#6
REVIEW
Pavel Klein, Ivana Tyrlikova
Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon...
June 21, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28647387/practical-considerations-for-the-use-of-breast-mri-for-breast-cancer-evaluation-in-the-preoperative-setting
#7
Debra L Monticciolo
Preoperative contrast-enhanced (CE) breast magnetic resonance imaging (MRI) remains controversial in the newly diagnosed breast cancer patient. Additional lesions are frequently discovered in these patients with CE breast MRI. As staging and treatment planning evolve to include more information on tumor biology and aggression, so should our consideration of extent of disease. Directing CE breast MRI to those patients most likely to have additional disease may be beneficial. We sought to develop practical guidance for the use of preoperative CE breast MRI in the newly diagnosed breast cancer patient based on recent scientific data...
June 21, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28647372/delta-opioid-receptor-agonist-attenuates-lipopolysaccharide-induced-myocardial-injury-by-regulating-autophagy
#8
Pin Zhao, Jianke Kuai, Jinjian Gao, Li Sun, Yan Wang, Linong Yao
BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647196/smooth-muscle-cells-of-human-veins-show-an-increased-response-to-injury-at-valve-sites
#9
Shinsuke Kikuchi, Lihua Chen, Kevin Xiong, Yukihiro Saito, Nobuyoshi Azuma, Gale Tang, Michael Sobel, Thomas N Wight, Richard D Kenagy
OBJECTIVE: Venous valves are essential but are prone to injury, thrombosis, and fibrosis. We compared the behavior and gene expression of smooth muscle cells (SMCs) in the valve sinus vs nonvalve sites to elucidate biologic differences associated with vein valves. METHODS: Tissue explants of fresh human saphenous veins were prepared, and the migration of SMCs from explants of valve sinus vs nonvalve sinus areas was measured. Proliferation and death of SMCs were determined by staining for Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling...
June 21, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28646916/prc1-contributes-to-tumorigenesis-of-lung-adenocarcinoma-in-association-with-the-wnt-%C3%AE-catenin-signaling-pathway
#10
Ping Zhan, Bin Zhang, Guang-Min Xi, Ying Wu, Hong-Bing Liu, Ya-Fang Liu, Wu-Jian Xu, Qing-Qing Zhu, Feng Cai, Ze-Jun Zhou, Ying-Ying Miu, Xiao-Xia Wang, Jia-Jia Jin, Qian Li, Li-Ping Qian, Tang-Feng Lv, Yong Song
BACKGROUND: Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues...
June 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28646882/magnetic-foreign-body-ingestion-in-pediatric-patients-report-of-three-cases
#11
Jinbeom Cho, Kiyoung Sung, Dosang Lee
BACKGROUND: Although foreign bodies (FBs) typically pass spontaneously and uneventfully through the digestive tract, a subset of such bodies may become trapped, eventually leading to significant injury. In particular, the ingestion of magnetic materials can cause serious morbidity due to proximate attraction through the intestinal wall. CASE PRESENTATION: We recently treated three pediatric patients who had ingested several magnetic foreign materials. None of these patients exhibited any clinical symptoms or signs suggestive of surgical abdomen...
June 24, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28646846/molecular-epidemiology-of-human-respiratory-syncytial-virus-in-iranian-%C3%A2-60-years-old-hospitalized-patients-with-acute-respiratory-symptoms
#12
Yaser Arjeyni, Ebrahim Faghihloo, Katayoun Samimi Rad, Vahid Salimi, Mahmood Mahmoudi, Talat Mokhtari-Azad
BACKGROUND: Human respiratory syncytial virus (HRSV) is an important cause of acute respiratory infection (ARI) and mortality in ≥60 years old population around the world. The aim of this study was to determine the frequency and circulating genotypes of HRSV in Iranian patients ≥ 60 years old. METHODS: In this cross-sectional molecular epidemiology study, we examined the C-terminal located hypervariable domain of G glycoprotein of HRSV in throat swabs from Tehran, Hormozgan, Boushehr, West Azarbayjan, Ghom and Alborz provinces of Iran which were addressed to national influenza center between October 2013 and March 2015...
June 2017: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/28646761/regulation-on-the-aggregation-induced-emission-aie-of-dna-templated-silver-nanoclusters-by-bsa-and-its-hydrolysates
#13
Wei-Xian Wang, Yuqing Wu, Hong-Wei Li
The aggregation-induced emission (AIE) phenomenon of the metal nanoclusters (NCs) has been discovered quite recently, which is considered to be creative to improve the optical properties of NCs upon ligand aggregation. In the present study, we report an AIE system for double-stranded DNA-templated silver nanoclusters (AgNCs-dsDNA) by using bovine serum albumin (BSA) in solution, which induce a moderate emission enhancement of AgNCs (5-fold) and a blue-shift through a loosen interaction. In addition, significant luminescence enhancement (30-fold) is further stimulated by the addition of digestive enzyme to the system by altering the surface structure of the aggregated particles...
June 10, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28646326/transposable-elements-mediate-adaptive-debilitation-of-flagella-in-experimental-escherichia-coli-populations
#14
Gordon R Plague, Krystal S Boodram, Kevin M Dougherty, Sandar Bregg, Daniel P Gilbert, Hira Bakshi, Daniel Costa
Although insertion sequence (IS) elements are generally considered genomic parasites, they can mediate adaptive genetic changes in bacterial genomes. We discovered that among 12 laboratory-evolved Escherichia coli populations, three had experienced at least six different IS1-mediated deletions of flagellar genes. These deletions all involved the master flagellar regulator flhDC, and as such completely incapacitate motility. Two lines of evidence strongly suggest that these deletions were adaptive in our evolution experiment: (1) parallel evolution in three independent populations is highly unlikely just by chance, and (2) one of these deletion mutations swept to fixation within ~1000 generations, which is over two million times faster than expected if this deletion was instead selectively neutral and thus evolving by genetic drift...
June 23, 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/28646167/effectively-infinite-optical-path-length-created-using-a-simple-cubic-photonic-crystal-for-extreme-light-trapping
#15
Brian J Frey, Ping Kuang, Mei-Li Hsieh, Jian-Hua Jiang, Sajeev John, Shawn-Yu Lin
A 900 nm thick TiO2 simple cubic photonic crystal with lattice constant 450 nm was fabricated and used to experimentally validate a newly-discovered mechanism for extreme light-bending. Absorption enhancement was observed extending 1-2 orders of magnitude over that of a reference TiO2 film. Several enhancement peaks in the region from 600-950 nm were identified, which far exceed both the ergodic fundamental limit and the limit based on surface-gratings, with some peaks exceeding 100 times enhancement...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646083/does-depression-increase-the-risk-of-stroke-in-patients-with-rheumatoid-arthritis-a-population-based-cohort-study
#16
Tzung-Yi Tsai, Ming-Chi Lu, Hanoch Livneh, Shan-Yun Chiu, Ning-Sheng Lai, How-Ran Guo
OBJECTIVES: Comorbid depression is common and undertreated in patients with rheumatoid arthritis (RA). It remains uncertain whether comorbid depression provoked the risk of poor clinical outcome, stroke in particular, among patients with RA. This work aimed to determine if depression onset during the treatment process increases stroke risk for patients with RA as compared with those with (1) neither RA nor depression, (2) RA only and (3) depression only. DESIGN: A nationwide, population-based cohort study...
June 22, 2017: BMJ Open
https://www.readbyqxmd.com/read/28645898/dna-pk-facilitates-piggybac-transposition-by-promoting-paired-end-complex-formation
#17
Yan Jin, Yaohui Chen, Shimin Zhao, Kun-Liang Guan, Yuan Zhuang, Wenhao Zhou, Xiaohui Wu, Tian Xu
The involvement of host factors is critical to our understanding of underlying mechanisms of transposition and the applications of transposon-based technologies. Modified piggyBac (PB) is one of the most potent transposon systems in mammals. However, varying transposition efficiencies of PB among different cell lines have restricted its application. We discovered that the DNA-PK complex facilitates PB transposition by binding to PB transposase (PBase) and promoting paired-end complex formation. Mass spectrometry analysis and coimmunoprecipitation revealed physical interaction between PBase and the DNA-PK components Ku70, Ku80, and DNA-PKcs Overexpression or knockdown of DNA-PK components enhances or suppresses PB transposition in tissue culture cells, respectively...
June 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28645892/meis1-effects-on-motor-phenotypes-and-the-sensorimotor-system-in-mice
#18
Aaro V Salminen, Lillian Garrett, Barbara Schormair, Jan Rozman, Florian Giesert, Kristina M Niedermeier, Lore Becker, Birgit Rathkolb, Ildikó Rácz, Martin Klingenspor, Thomas Klopstock, Eckhard Wolf, Andreas Zimmer, Valérie Gailus-Durner, Miguel Torres, Helmut Fuchs, Martin Hrabě de Angelis, Wolfgang Wurst, Sabine M Hölter, Juliane Winkelmann
MEIS1 is a developmental transcription factor linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and with significant impact on the quality-of-life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the most potential system for modeling RLS in animals...
June 23, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#19
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28645611/activation-of-central-nesfatin-1-nucb2-after-intraperitoneally-administered-cisplatin-in-rats
#20
Yasuki Akiyama, Mitsuhiro Yoshimura, Kazuaki Nishimura, Haruki Nishimura, Satomi Sonoda, Hiromichi Ueno, Yasuhito Mitojima, Reiko Saito, Takashi Maruyama, Yuki Nonaka, Hirofumi Hashimoto, Yasuhito Uezono, Keiji Hirata, Yoichi Ueta
Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. Nesfatin-1/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central nesfatin-1/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (180-220 g)...
June 20, 2017: Biochemical and Biophysical Research Communications
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