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Functional screen

Qian Chen, Chaoying Hu, Yanmei Liu, Rong Song, Wenjing Zhu, Hongxin Zhao, Antonio Nino, Fan Zhang, Yun Liu
BACKGROUND: Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, a cytokine essential for the formation, function and survival of osteoclasts. This study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of single-dose denosumab (60 and 120 mg) in healthy Chinese volunteers. METHODS: This randomized (3:3:2), single-blind, placebo-controlled study enrolled healthy Chinese volunteers to receive single subcutaneous injection of denosumab 60 mg, 120 mg, or placebo...
2018: PloS One
Leslie A Sadownik, Paul J Yong, Kelly B Smith
OBJECTIVES OF THE STUDY: To systematically evaluate the literature regarding vulvodynia treatment outcome measures. METHODS: A systematic literature search on OVID, PubMed, and PsycINFO databases was conducted from inception until May 2016. Studies were included/excluded based on prespecified criteria. Reported outcome measures were organized into 6 core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): pain; physical functioning, emotional functioning, participant ratings of global improvement and satisfaction with treatment, symptoms and adverse events, and participant disposition...
July 2018: Journal of Lower Genital Tract Disease
Elizabeth Stewart, Cathy Catroppa, Deepak Gill, Richard Webster, John Lawson, Anna Mandalis, Mark Sabaz, Belinda Barton, Suncica Lah
PURPOSE: This study aimed to examine Theory of Mind (ToM) and social competence in children and adolescents with genetic generalised epilepsy (GGE), and explore how they relate to neurocognitive and epilepsy variables. METHODS: Twenty-two children and adolescents with GGE (8-16 years old) and 22 typically developing controls completed two behavioural tasks (faux-pas, strange stories) assessing cognitive and affective ToM, and a battery of standardised neuropsychological tests...
June 18, 2018: Seizure: the Journal of the British Epilepsy Association
Kun Wang, Shuai Li, Yong Gao, Xiaobo Feng, Wei Liu, Rongjin Luo, Yu Song, JiTu, Yingle Liu, Cao Yang
OBJECTIVE: Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential component of the signaling complex that mediates osteoclastogenesis. As an adaptor protein of E3 ligase function, TRAF6 regulates NF-κB signaling via TAK1 and I-κB kinase (IKK) activation. Here, we investigated novel mechanisms by which TRAF6 signaling is regulated under receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. DESIGN: A yeast two-hybrid screen system identified cellular factors that interact with TRAF6...
June 19, 2018: Bone
Heather Allewelt, Mahsa Taskindoust, Jesse Troy, Kristin Page, Susan Wood, Suhag Parikh, Vinod K Prasad, Joanne Kurtzberg
Allogeneic hematopoietic stem cell transplantation (HSCT) can retard the progression of early infantile Krabbe disease (EIKD). Superior outcomes are achieved if HSCT is performed prior to the onset of symptoms, however little information is available about the long-term outcomes in surviving patients. We now describe functional outcomes in pre-symptomatic infants who underwent HSCT for EIKD at ≤2 months of life. Records of the 19 patients who underwent HSCT for EIKD at ≤2 months of age from 1996-2010 were reviewed...
June 19, 2018: Biology of Blood and Marrow Transplantation
Noor A Shaik, Zuhier A Awan, Prashant K Verma, Ramu Elango, Babajan Banaganapalli
The life-threatening group of irregular cardiac rhythmic disorders also known as Cardiac Arrhythmias (CA) are caused by mutations in highly conserved Calmodulin (CALM/CaM) genes. Herein, we present a multidimensional approach to diagnose changes in phenotypic, stability, and Ca2+ ion binding properties of CA-causing mutations. Mutation pathogenicity was determined by diverse computational machine learning approaches. We further modeled the mutations in 3D protein structure and analyzed residue level phenotype plasticity...
June 22, 2018: Journal of Cellular Biochemistry
Philippe Vuka Tsalu, Geun Wan Kim, Jong Wook Hong, Ji Won Ha
The most polarizable localized surface plasmon resonance (LSPR) longitudinal mode of anisotropic metallic nanoparticles, such as gold bipyramids (AuBPs), is of high prominence. This optical response has tremendous applications from spectroscopy to photonics and energy devices to sensing. In conventional LSPR-based sensing, broadening and asymmetry in peaks due to chemical and instrument noise hinder obtaining a precise insight on shift positions, accordingly limiting the effectiveness and impact of LSPR sensors...
June 22, 2018: Nanoscale
Run-Ze Li, Xing-Xing Fan, Dan-Feng Shi, Guo-Yuan Zhu, Yu-Wei Wang, Lian-Xiang Luo, Hu-Dan Pan, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
OBJECTIVE: Lung cancer is the number one cancer in terms of both mortality and incidence. Cancer cells differ from normal cells in that they can reprogram their metabolism to support a rapid proliferation rate and alter oxidative phosphorylation processes toward lactic acid fermentation, even under aerobic conditions. Therefore we aimed to identify new compounds that might act as Pyruvate kinase M2 isoform (PKM2) activators and to investigate their anti-cancer efficacy in non-small cell lung cancer (NSCLC) cells...
June 21, 2018: Chemical Biology & Drug Design
Iman Beheshti, Norihide Maikusa, Hiroshi Matsuda
INTRODUCTION: We present the Brain-Age Score (BAS) as a magnetic resonance imaging (MRI)-based index for Alzheimer's disease (AD). We developed a fully automated framework for estimating the BAS in healthy controls (HCs) and individuals with mild cognitive impairment (MCI) or AD, using MRI scans. METHODS: We trained the proposed framework using 385 HCs from the IXI and OASIS datasets and evaluated 146 HCs, 102 stable-MCI (sMCI), 112 progressive-MCI (pMCI), and 147 AD patients from the J-ADNI dataset...
June 22, 2018: Brain and Behavior
Giacomo Tondo, Fabiola De Marchi, Emanuela Terazzi, Paolo Prandi, Marta Sacchetti, Cristoforo Comi, Roberto Cantello
BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) may be associated with worsening of cognitive performance. We studied patients with Alzheimer's disease (AD) with and without COPD, and we analyzed, in a retrospective way, clinical and neuropsychological variables to verify if COPD plays a pejorative role on cognitive or functional autonomy in patients with dementia. METHODS: We enrolled 23 adult patients (AD-COPD) with probable AD and COPD and 23 with AD only (AD-only); they were matched for sex, age, educational level, and Mini Mental State Examination (MMSE) at the disease onset...
June 21, 2018: Neurological Sciences
Benjamin D Diplock, Kaitlin M C McGarragle, Willem A Mueller, Sana Haddad, Rachel Ehrlich, Dong-Hyun A Yoon, Xingshan Cao, Yaseen Al-Allaq, Paul Karanicolas, Margaret I Fitch, Jeff Myers, Alex J Mitchell, Janet W M Ellis
PURPOSE: We aimed to assess the impact of implementing Edmonton Symptom Assessment System (ESAS) screening on health-related quality of life (HRQoL) and patient satisfaction with care (PSC) in ambulatory oncology patients. ESAS is now a standard of care in Ontario cancer centers, with the goal of improving symptom management in cancer patients, yet few studies examine impact of ESAS on patient outcomes. METHODS: We compared ambulatory oncology patients who were not screened prior to ESAS site implementation (2011-2012), to a similar group who were screened using ESAS after site implementation (2012-2013), to examine between-group differences in patient HRQoL, PSC outcomes, and supportive care needs (Supportive Care Service Survey)...
June 21, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Yi-Kai Su, Laura B Willis, Lars Rehmann, David Smith, Thomas W Jeffries
This study employed cell recycling, batch adaptation, cell mating and high throughput screening to select adapted Spathaspora passalidarum strains with improved fermentative ability.The most promising candidate, YK208-E11 (E11) showed a 3-fold increase in specific fermentation rate compared to the parental strain and an ethanol yield greater than 0.45 g/g substrate while co-utilizing cellobiose, glucose, and xylose. Further characterization showed that strain E11 also makes 40% less biomass compared to the parental strain when cultivated in rich media under aerobic conditions...
June 21, 2018: FEMS Yeast Research
Qing Zhou, Kyu Joon Lee, Yasuhiro Kurasawa, Huiqing Hu, Tai An, Ziyin Li
Faithful chromosome segregation depends on correct spindle microtubule-kinetochore attachment and requires certain spindle-associated proteins (SAPs) involved in regulating spindle dynamics and chromosome segregation. Little is known about the spindle-associated proteome in the early divergent Trypanosoma brucei and its roles in chromosome segregation. Here we report the identification of a cohort of divergent SAPs through localization-based screening and proximity-dependent biotin identification. We identified seven new SAPs and seventeen new nucleolar proteins that associate with the spindle, and demonstrated that the kinetochore protein KKIP4 also associates with the spindle...
June 21, 2018: Nucleic Acids Research
Shane P Duggan, Catherine Garry, Fiona M Behan, Sinead Phipps, Hiromi Kudo, Murat Kirca, Abdul Zaheer, Sarah McGarrigle, John V Reynolds, Robert Goldin, Steve E Kalloger, David F Schaeffer, Aideen Long, Jessica Strid, Dermot Kelleher
Background & Aims: Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barrett's esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation. Methods: This study used a druggable genome small interfering RNA (siRNA) screening library of 6022 siRNAs in conjunction with bioinformatics platforms, genomic studies of EAC tissues, somatic variation data of EAC from The Cancer Genome Atlas data of EAC, and pathologic and functional studies to define novel EAC-associated, and targetable, immune factors...
2018: Cellular and Molecular Gastroenterology and Hepatology
Helin Feng, Heather Tillman, Gang Wu, Andrew M Davidoff, Jun Yang
Osteosarcoma (OS) cell lines are widely used in understanding the biological functions of cancer, identification and validation of therapeutic targets, as well as in vitro or in vivo preclinical drug screening. Here we report there is a frequent loss-of-function of polycomb repressive complex 2 (PRC2) in OS cell lines but it is rare in tumor samples based on genomic sequencing data, western blotting and immunohistochemistry analysis of H3K27me3. U2OS and 143B cell lines have a complete loss of function of PRC2 and several others have partial loss...
June 5, 2018: Oncotarget
Jingya Sun, Xin Wang, Boyun Tang, Hongchun Liu, Minmin Zhang, Yueqin Wang, Fangfang Ping, Jian Ding, Aijun Shen, Meiyu Geng
Over the past decade, therapies targeting the VEGF/VEGFR and mTOR pathways have served as the standard of care for the clinical management of renal cell carcinoma (RCC) patients. Albeit promising, these targeted drugs have attained only modest clinical benefits with limited prolonged progression-free survival. Therefore, alternative reasonable and applicable therapeutic approaches should be introduced to improve the clinical outcome of RCC patients. Methods: FDA approved kinase inhibitors were screened to evaluate their abilities to suppress the proliferation of RCC cells...
2018: Theranostics
Shira Dishon, Adi Schumacher, Joseph Fanous, Alaa Talhami, Ibrahim Kassis, Dimitrios Karussis, Chaim Gilon, Amnon Hoffman, Gabriel Nussbaum
MyD88 is a cytoplasmic adaptor protein that plays a central role in signaling downstream of the TLRs and the IL1R superfamily. We previously demonstrated that MyD88 plays a critical role in EAE, the murine model of multiple sclerosis, and showed that the MyD88 BB-loop decoy peptide RDVLPGT ameliorates EAE. We now designed and screened a library of backbone cyclized peptides based on the linear BB loop peptide, to identify a metabolically stable inhibitor of MyD88 that retains the binding properties of the linear peptide...
June 21, 2018: Scientific Reports
Miroslav P Ivanov, Rene Ladurner, Ina Poser, Rebecca Beveridge, Evelyn Rampler, Otto Hudecz, Maria Novatchkova, Jean-Karim Hériché, Gordana Wutz, Petra van der Lelij, Emanuel Kreidl, James Ra Hutchins, Heinz Axelsson-Ekker, Jan Ellenberg, Anthony A Hyman, Karl Mechtler, Jan-Michael Peters
Chromosome segregation depends on sister chromatid cohesion which is established by cohesin during DNA replication. Cohesive cohesin complexes become acetylated to prevent their precocious release by WAPL before cells have reached mitosis. To obtain insight into how DNA replication, cohesion establishment and cohesin acetylation are coordinated, we analysed the interaction partners of 55 human proteins implicated in these processes by mass spectrometry. This proteomic screen revealed that on chromatin the cohesin acetyltransferase ESCO2 associates with the MCM2-7 subcomplex of the replicative Cdc45-MCM-GINS helicase...
June 21, 2018: EMBO Journal
Jeremy S Morris, Ryan A Groves, Jillian M Hagel, Peter J Facchini
Phenylalkylamines, such as the plant compounds ephedrine and pseudoephedrine and the animal neurotransmitters dopamine and adrenaline, compose a large class of natural and synthetic molecules with important physiological functions and pharmaceutically valuable bioactivities. The final steps of ephedrine and pseudoephedrine biosynthesis in members of the plant genus Ephedra involve N -methylation of norephedrine and norpseudoephedrine, respectively. Here, using a plant transcriptome screen, we report the isolation and characterization of an N -methyltransferase (NMT) from Ephedra sinica able to catalyze the formation of (pseudo)ephedrine and other naturally occurring phenylalkylamines, including N -methylcathinone and N -methyl(pseudo)ephedrine...
June 21, 2018: Journal of Biological Chemistry
Saro H Armenian, Derek Rinderknecht, Kaylene Au, Lanie Lindenfeld, George Mills, Aida Siyahian, Claudia Herrera, Karla Wilson, Kalyanasundaram Venkataraman, Kristen Mascarenhas, Peyman Tavallali, Marianne Razavi, Niema Pahlevan, Jon Detterich, Smita Bhatia, Morteza Gharib
Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference)...
June 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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