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Functional screen

Jeffrey J Widrick, Matthew Alexander, Benjamin Sanchez, Devin Gibbs, Genri Kawahara, Alan Beggs, Louis Kunkel
Sapje zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that sapje mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic sapje larvae from their unaffected siblings and then studied trunk muscle contractility at 4-7 days post fertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparations were only 30-60% of normal...
October 7, 2016: Physiological Genomics
Alexander J Steiner, Nathalie Boulos, James Mirocha, Stephanie M Wright, Katherine L Collison, Waguih W IsHak
OBJECTIVES: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often have high comorbidity, consequently influencing patient-reported outcomes of depressive symptom severity, quality of life (QOL), and functioning. We hypothesized that the combined effects of concurrent PTSD and MDD would result in worse treatment outcomes, whereas individuals who achieved MDD remission would have better treatment outcomes. METHODS: We analyzed 2280 adult participants who received level 1 treatment (citalopram monotherapy) in the Sequenced Treatment Alternatives to Relieve Depression study, including 2158 participants with MDD without comorbid PTSD and 122 participants with MDD with comorbid PTSD (MDD + PTSD)...
October 18, 2016: Clinical Neuropharmacology
Panagiotis Kokotis, Martin Schmelz, Aikaterini E Papagianni, Thomas Zambelis, Nikos Karandreas
INTRODUCTION: In chronic inflammatory demyelinating polyradiculopathy (CIDP) the impairment of unmyelinated nerve fibers appears unexpected. The measurement of the electrically induced axon flare reflex is a clinical test to assess the peripheral C-nociceptor function. In this study we compared the flare area in patients suffering from chronic inflammatory demyelinating polyradiculopathy with healthy subjects. MATERIALS AND METHODS: We examined 18 patients fulfilling the criteria for CIDP (11 male, mean age 51...
October 18, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Shosuke Satake, Hidenori Arai
PURPOSE OF REVIEW: Many frailty screening instruments have been proposed due to the lack of consensus on a unified operational definition of frailty. This review reports on recent frailty screening tools in addition to revisiting the frailty concept. RECENT FINDINGS: Although there are two representative frailty models, both have issues that prevent them from being implemented in clinical settings despite their remarkable advantages. Due to their different characteristics, these models are thought to be complementary rather than substitutive...
October 18, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Li Zhou, Ji Wen, Zhao Huang, Edouard C Nice, Canhua Huang, Haiyuan Zhang, Qifu Li
Liver cancer is a major global health problem being the sixth most common cancer and the third cause of cancer-related death, with HCC representing more than 90% of primary liver cancers. Mounting evidence suggests that, compared with their normal counterparts, many types of cancer cell have increased levels of ROS. Therefore, cancer cells need to combat high levels of ROS, especially at early stages of tumour development. Recent studies have revealed that ROS-mediated regulation of redox-sensitive proteins (redox sensors) is involved in the pathogenesis and/or progression of many human diseases, including cancer...
October 20, 2016: Proteomics. Clinical Applications
Ido Sagi, Dieter Egli, Nissim Benvenisty
Haploid human pluripotent stem cells (PSCs) integrate haploidy and pluripotency, providing a novel system for functional genomics and developmental research in humans. We have recently derived haploid human embryonic stem cells (ESCs) by parthenogenesis and demonstrated their wide differentiation potential and applicability for genetic screening. Because haploid cells can spontaneously become diploid, their enrichment at an early passage is key for successful derivation. In this protocol, we describe two methodologies, namely metaphase spread analysis and cell sorting, for the identification of haploid human cells within parthenogenetic ESC lines...
November 2016: Nature Protocols
Omesh Goyal, Sandeep Singh Sidhu, Natasha Sehgal, Sandeep Puri
OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0...
September 2016: Journal of the Association of Physicians of India
Allison Ducharme-Smith, Ben Z Katz, Amy E Bobrowski, Carl L Backer, Elfriede Pahl
BKV infection and nephropathy complicate pediatric HTx, but the incidence and time course of the disease are unknown. We assessed the incidence of BKV infection and its association with kidney dysfunction in pediatric HTx recipients. A single center prospective study compared pediatric (<18 years) HTx recipients, with and without BKV infection, who received an allograft between September 2013 and December 2014. Screening of urine for BKV was performed prior to transplant, and at week 1, and at months 3, 6, 9, 12, and 15 months post-transplantation...
October 20, 2016: Pediatric Transplantation
F Creamer, A Balfour, S Nimmo, I Foo, J D Norrie, L J Williams, K C Fearon, H M Paterson
BACKGROUND: Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. METHODS: In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance...
October 20, 2016: British Journal of Surgery
Jingjing Li, Jin Gao, Lei Han, Yinjie Zhang, Wen Guan, Liang Zhou, Yan Yu, Wei Han
Identifying interactions between ligands and transmembrane receptors is crucial for understanding the endocrine system. However, the present approaches for this purpose are still not capable of high-throughput screening. In this report, a membrane-anchored ligand and receptor yeast two-hybrid (MALAR-Y2H) system was established. In the method, an extracellular ligand is linked with an intracellular split-ubiquitin reporter system via a chimeric transmembrane structure. Meanwhile, the prey proteins of transmembrane receptors are fused to the other half of the split-ubiquitin reporter system...
October 20, 2016: Scientific Reports
Joshua Bloom, Shan Sun, Yousef Al-Abed
Macrophage migration inhibitory factor (MIF) has emerged as a promising drug target in diseases including sepsis, rheumatoid arthritis, and cancer. MIF has multiple properties that favor development of specific, targeted therapies: it is expressed broadly among human cells, has noted roles in diverse inflammatory and oncological processes, and has intrinsic enzymatic activity amenable to high-throughput screening. Despite these advantages, anti-MIF therapy remains well behind other cytokine-targeted therapeutics, with no small molecules in the pipeline for clinical development and anti-MIF antibodies only recently beginning clinical trials...
October 20, 2016: Expert Opinion on Therapeutic Targets
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
Hasan Emre Koçak, Ayşe Şermin Filiz Acıpayam, Harun Acıpayam, Bilgen Çakıl Erdoğan, Wesam M E Alakhras, Mehmet Nurettin Kıral, Mehmet Keskin, Fatma Tülin Kayhan
OBJECTIVE: The aim of our study is to investigate whether systemic microvascular function affects the development and prognosis of sudden idiopathic hearing loss (SHL). TYPE OF STUDY: A prospective case-control study. MATERIALS-METHOD: 50 patients diagnosed with SHL at our hospital between September 2015 and May 2016 were included as the SHL group, and 50 healthy volunteers who came to the hospital for medical screening were included in the control group...
October 19, 2016: Clinical Otolaryngology
Thomas McCaffrey, Michela Guglieri, Alexander P Murphy, Katherine Md Bushby, Anna Johnson, John P Bourke
Introduction The significance of abnormal cardiac measures in asymptomatic females who harbor dystrophin gene mutations is controversial. Methods Echo-measures of ventricular function were compared with published norms in a cross-sectional study of 130 (age 39 ± 15.7 years) 'carriers' of Duchenne or Becker muscular dystrophy (DBMD). Correlations between cardiomyopathy (CM) and mutation, CK levels, age, and muscle symptoms were investigated. Results Depending on definition, CM prevalence was 3-33%. Ejection fraction (Simpson) was < 55% in 9 (13%) and < 40% in 2 (2...
October 19, 2016: Muscle & Nerve
Sieglinde Bayer, Matthias Wirth
The protein sequences of class I HDACs in mice and humans are 96-99 % identical. These highly conserved proteins have crucial roles in biological processes, such as proliferation and development, which is reflected in the lethality that occurs in conventional whole body knockout mice. Therefore, conditional knockouts are inevitable to investigate the functions of class I HDACs in mice. Here, we describe the generation of conditional class I Hdac knockout mice, using Hdac1 as an example. We explain a relatively quick procedure to generate the necessary target vectors by recombination-mediated genetic engineering and gateway techniques...
2017: Methods in Molecular Biology
Noriyasu Chika, Minoru Fukuchi, Okihide Suzuki, Tetsuya Ito, Azusa Yamamoto, Toru Ishiguro, Youichi Kumagai, Keiichiro Ishibashi, Erito Mochiki, Hideyuki Ishida
The loss of mismatch repair(MMR)function as a result of MLH1 promoter methylation is closely correlated with high frequency microsatellite instability, and tumors with such characteristics are resistant to anticancer drugs such as 5-FU. We examined the incidence and characteristics of deficient MMR(dMMR)in elderly gastric cancer patients by performing a comprehensive immunohistochemical screening. The study was conducted in 199 patients diagnosed with gastric cancer, aged 75 years or older, who underwent a gastrectomy between April 2005 and January 2014...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
Yiqin Jiang, Elise Pitmon, Jack Berry, Fred W Wolf, Zach McKenzie, Tim J Lebestky
Sleep is an essential behavioral state of rest that is regulated by homeostatic drives to ensure a balance of sleep and activity, as well as independent arousal mechanisms in the central brain. Dopamine has been identified as a critical regulator of both sleep behavior and arousal. Here we present results of a genetic screen that selectively restored the Dopamine Receptor (DopR/DopR1/dumb) to specific neuroanatomical regions of the adult Drosophila brain to assess requirements for DopR in sleep behavior. We have identified subsets of the mushroom body that utilize DopR in daytime sleep regulation...
October 19, 2016: G3: Genes—Genomes—Genetics
Y H Shi, J H Zhao, J L Song, Y J Li, K Liang
Objective: To explore the clinical and perfusion weighted imaging (PWI) characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in order to improve the early diagnosis rate. Methods: Clinical and imaging data of 46 patients with final diagnosis of MELAS treated in Henan Province People's Hospital from January 2012 to June 2016 were collected. Results: Patients presented with symptoms of epilepsy, hemiplegia, language disorders, and decreased visual acuity and so on...
October 11, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jeroen Aerts, Annelies Laeremans, Laurens Minerva, Kurt Boonen, Budamgunta Harshavardhan, Rudi D'hooge, Dirk Valkenborg, Geert Baggerman, Lutgarde Arckens
The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task...
October 17, 2016: Biochimica et Biophysica Acta
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