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Hyun-Ji Park, Eun Je Jeon, Jung Seung Lee, Sang Hyeon Hong, Ann-Na Cho, Joan Lee, Jae-Su Moon, Kyeong-Eun Jung, Jong-Won Oh, Haeshin Lee, Seung-Woo Cho
Small interfering RNA (siRNA) delivery can provide an effective therapy for treating viral diseases by silencing genes involved in viral replication. In this study, a liver-targeting formulation of lipidoid nanoparticle for delivery of siRNA that targets protein kinase C-related kinase 2 (PRK2) to inhibit hepatitis C virus (HCV) replication is reported. The most effective, minimally cytotoxic lipidoid for siRNA delivery to hepatic cells is identified from a small library of alkyl epoxide-polyamine conjugates...
October 24, 2016: Advanced Healthcare Materials
Anne S Bie, Paula Fernandez-Guerra, Rune I D Birkler, Shahar Nisemblat, Dita Pelnena, Xinping Lu, Joshua L Deignan, Hane Lee, Naghmeh Dorrani, Thomas J Corydon, Johan Palmfeldt, Liga Bivina, Abdussalam Azem, Kristin Herman, Peter Bross
We here report molecular investigations of a missense mutation in the HSPE1 gene encoding the HSP10 subunit of the HSP60/ HSP10 chaperonin complex that assists protein folding in the mitochondrial matrix. The mutation was identified in an infant who came to clinical attention due to infantile spasms at 3 months of age. Clinical exome sequencing revealed heterozygosity for a HSPE1 NM_002157.2:c.217C>T de novo mutation causing replacement of leucine with phenylalanine at position 73 of the HSP10 protein. This variation has never been observed in public exome sequencing databases or the literature...
2016: Frontiers in Molecular Biosciences
Sharon A Gutman, Kristin A Gregory, Megan M Sadlier-Brown, Marcy A Schlissel, Allison M Schubert, Lee Ann Westover, Richard C Miller
Although sleep intervention is within the domain of occupational therapy, few studies exist supporting practice. Effectiveness of three sleep interventions was compared: Dreampad Pillow®, iRest® meditation, and sleep hygiene. Twenty-nine participants were randomly assigned to the Dreampad Pillow® (n = 10), iRest® meditation (n = 9), and sleep hygiene (n = 10) groups. In Phase 1, all participants used a 7-day sleep hygiene regimen to reduce poor sleep habits. In Phase 2 (14 days), 10 participants used the Dreampad Pillow® and sleep hygiene, nine used the iRest meditation and sleep hygiene, and 10 continued sleep hygiene only...
October 18, 2016: OTJR: Occupation, Participation and Health
Peri E Bolton, Lee Ann Rollins, James Brazill-Boast, Kang-Wook Kim, Terry Burke, Simon C Griffith
In socially monogamous species, individuals can use extra-pair paternity and offspring sex allocation as adaptive strategies to ameliorate costs of genetic incompatibility with their partner. Previous studies on domesticated Gouldian finches (Erythrura gouldiae) demonstrated a genetic incompatibility between head colour morphs, the effects of which are more severe in female offspring. Domesticated females use differential sex allocation, and extra-pair paternity with males of compatible head colour, to reduce fitness costs associated with incompatibility in mixed-morph pairings...
October 18, 2016: Journal of Evolutionary Biology
Anna Ngo, Ann Koay, Christian Pecquet, Carmen C Diaconu, Yasmine Ould-Amer, Qiwei Huang, Congbao Kang, Anders Poulsen, May Ann Lee, David Jenkins, Andrew Shiau, Stefan N Constantinescu, Meng Ling Choo
BACKGROUND: Rather than a Janus Kinase 2 inhibitor (ruxolitinib), a specific thrombopoietin receptor (TpoR) inhibitor would be more specific for the treatment of myeloproliferative neoplasms due to TpoR mutations. OBJECTIVE: A cell-based phenotypic approach to identify specific TpoR inhibitors was implemented and a library of 505,483 small molecules was screened for inhibitory effects on cells transformed by TpoR mutants. RESULTS: Among the identified hits are two analogs of 3-(4-piperidinyl) indole...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Ho Shin Kim, Mannkyu Hong, Jihyae Ann, Suyoung Yoon, Cong-Truong Nguyen, Su-Chan Lee, Ho-Young Lee, Young-Ger Suh, Ji Hae Seo, Hoon Choi, Jun Yong Kim, Kyu-Won Kim, Joohwan Kim, Young-Myeong Kim, So-Jung Park, Hyun-Ju Park, Jeewoo Lee
Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80...
September 30, 2016: Bioorganic & Medicinal Chemistry
Peter T Campbell, Christina C Newton, Neal D Freedman, Jill Koshiol, Michael C Alavanja, Laura E Beane Freeman, Julie E Buring, Andrew T Chan, Dawn Q Chong, Mridul Datta, Mia M Gaudet, J Michael Gaziano, Edward L Giovannucci, Barry I Graubard, Albert R Hollenbeck, Lindsey King, I-Min Lee, Martha S Linet, Julie R Palmer, Jessica L Petrick, Jenny N Poynter, Mark P Purdue, Kim Robien, Lynn Rosenberg, Vikrant V Sahasrabuddhe, Catherine Schairer, Howard D Sesso, Alice J Sigurdson, Victoria L Stevens, Jean Wactawski-Wende, Anne Zeleniuch-Jacquotte, Andrew G Renehan, Katherine A McGlynn
Incidence rates for liver cancer have increased 3-fold since the mid-1970s in the United States in parallel with increasing trends for obesity and type II diabetes mellitus. We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and type II diabetes mellitus with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated HRs and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and type II diabetes mellitus)...
October 15, 2016: Cancer Research
Daniel A Thomas, Matthew M Coggon, Hanna Lignell, Katherine Ann Schilling, Xuan Zhang, Rebecca H Schwantes, Richard C Flagan, John H Seinfeld, Jesse Lee Beauchamp
The complexation of iron (III) with oxalic acid in aqueous solution yields a strongly absorbing chromophore that undergoes efficient photodissociation to give iron (II) and the carbon dioxide anion radical. Importantly, iron (III) oxalate complexes absorb near-UV radiation (λ > 350 nm), providing a potentially powerful source of oxidants in aqueous tropospheric chemistry. Although this photochemical system has been studied extensively, the mechanistic details associated with its role in the oxidation of dissolved organic matter within aqueous aerosol remain largely unknown...
October 12, 2016: Environmental Science & Technology
Eun Bong Lee, Nikki Daskalakis, Christine Xu, Anne Paccaly, Barry Miller, Roy Fleischmann, Inga Bodrug, Alan Kivitz
INTRODUCTION: Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction...
October 8, 2016: Clinical Pharmacokinetics
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Cheng-Chih Chung, Ting-I Lee, Wen-Chin Tsai, Shih-Ann Chen, Yi-Jen Chen
Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0...
October 4, 2016: Oncotarget
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
Michael Costanzo, Benjamin VanderSluis, Elizabeth N Koch, Anastasia Baryshnikova, Carles Pons, Guihong Tan, Wen Wang, Matej Usaj, Julia Hanchard, Susan D Lee, Vicent Pelechano, Erin B Styles, Maximilian Billmann, Jolanda van Leeuwen, Nydia van Dyk, Zhen-Yuan Lin, Elena Kuzmin, Justin Nelson, Jeff S Piotrowski, Tharan Srikumar, Sondra Bahr, Yiqun Chen, Raamesh Deshpande, Christoph F Kurat, Sheena C Li, Zhijian Li, Mojca Mattiazzi Usaj, Hiroki Okada, Natasha Pascoe, Bryan-Joseph San Luis, Sara Sharifpoor, Emira Shuteriqi, Scott W Simpkins, Jamie Snider, Harsha Garadi Suresh, Yizhao Tan, Hongwei Zhu, Noel Malod-Dognin, Vuk Janjic, Natasa Przulj, Olga G Troyanskaya, Igor Stagljar, Tian Xia, Yoshikazu Ohya, Anne-Claude Gingras, Brian Raught, Michael Boutros, Lars M Steinmetz, Claire L Moore, Adam P Rosebrock, Amy A Caudy, Chad L Myers, Brenda Andrews, Charles Boone
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments...
September 23, 2016: Science
Amy E Blain, Sema Mandal, Henry Wu, Jessica R MacNeil, Lee H Harrison, Monica M Farley, Ruth Lynfield, Lisa Miller, Megin Nichols, Sue Petit, Arthur Reingold, William Schaffner, Ann Thomas, Shelley M Zansky, Raydel Anderson, Brian H Harcourt, Leonard W Mayer, Thomas A Clark, Amanda C Cohn
In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines.
September 2016: Open Forum Infectious Diseases
Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, John-Anker Zwart, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie
No abstract text is available yet for this article.
September 28, 2016: Nature Genetics
Charles A Odonkor, Lee Ann Sprankle, Solomon Rojhani, Teresa Tang, Ada Yao, Erik H Hoyer
No abstract text is available yet for this article.
September 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
Celia Kun-Rodrigues, Owen A Ross, Tatiana Orme, Claire Shepherd, Laura Parkkinen, Lee Darwent, Dena Hernandez, Olaf Ansorge, Lorraine N Clark, Lawrence S Honig, Karen Marder, Afina Lemstra, Philippe Scheltens, Wiesje van der Flier, Eva Louwersheimer, Henne Holstege, Ekaterina Rogaeva, Peter St George-Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Walter Maetzler, Daniela Berg, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, John Q Trojanowski, Geidy E Serrano, Thomas G Beach, Jordi Clarimon, Alberto Lleó, Estrella Morenas-Rodríguez, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Monica Diez, Pau Pastor, Pentti J Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F Boeve, Ronald C Petersen, Tanis J Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J Cairns, John C Morris, David J Stone, Stuart Pickering-Brown, David Mann, Dennis W Dickson, Glenda M Halliday, Andrew Singleton, Rita Guerreiro, Jose Bras
C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB...
September 2, 2016: Neurobiology of Aging
Eunsohl Lee, Jingcheng Wang, Kenji Yumoto, Younghun Jung, Frank C Cackowski, Ann M Decker, Yan Li, Renny T Franceschi, Kenneth J Pienta, Russell S Taichman
Cancer metastasis is a multistep process associated with the induction of an epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Although significant progress has been made in understanding the molecular mechanisms regulating EMT and the CSC phenotype, little is known of how these processes are regulated by epigenetics. Here we demonstrate that reduced expression of DNA methyltransferase 1 (DNMT1) plays an important role in the induction of EMT and the CSC phenotype by prostate cancer (PCa) cells, with enhanced tumorigenesis and metastasis...
September 2016: Neoplasia: An International Journal for Oncology Research
Ann Fiegen Durbin, Chen Wang, Joseph Marcotrigiano, Lee Gehrke
UNLABELLED: Invading pathogen nucleic acids are recognized and bound by cytoplasmic (retinoic acid-inducible gene I [RIG-I]-like) and membrane-bound (Toll-like) pattern recognition receptors to activate innate immune signaling. Modified nucleotides, when present in RNA molecules, diminish the magnitude of these signaling responses. However, mechanisms explaining the blunted signaling have not been elucidated. In this study, we used several independent biological assays, including inhibition of virus replication, RIG-I:RNA binding assays, and limited trypsin digestion of RIG-I:RNA complexes, to begin to understand how RNAs containing modified nucleotides avoid or suppress innate immune signaling...
2016: MBio
David A Hess, Katherine M Strelau, Anju Karki, Mei Jiang, Ana C Azevedo-Pouly, Ann-Hwee Lee, Tye G Deering, Chinh Q Hoang, Raymond J MacDonald, Stephen F Konieczny
Transcriptional networks that govern secretory cell specialization, including instructing cells to develop a unique cytoarchitecture, amass extensive protein synthesis machinery, and be embodied to respond to endoplasmic reticulum (ER) stress, remain largely uncharacterized. In this study, we discovered that the secretory cell transcription factor MIST1 (Bhlha15), previously shown to be essential for cytoskeletal organization and secretory activity, also functions as a potent ER stress-inducible transcriptional regulator...
September 19, 2016: Molecular and Cellular Biology
Maya Ghoussaini, Juliet D French, Kyriaki Michailidou, Silje Nord, Jonathan Beesley, Sander Canisus, Kristine M Hillman, Susanne Kaufmann, Haran Sivakumaran, Mahdi Moradi Marjaneh, Jason S Lee, Joe Dennis, Manjeet K Bolla, Qin Wang, Ed Dicks, Roger L Milne, John L Hopper, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Kenneth Muir, Artitaya Lophatananon, Peter A Fasching, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Elinor J Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérèse Truong, Stig E Bojesen, Henrik Flyger, Javier Benitez, Anna González-Neira, M Rosario Alonso, Guillermo Pita, Susan L Neuhausen, Hoda Anton-Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Daniel C Tessier, Daniel Vincent, Heli Nevanlinna, Sofia Khan, Keitaro Matsuo, Hidemi Ito, Thilo Dörk, Natalia V Bogdanova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Anna H Wu, David Van Den Berg, Diether Lambrechts, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Monica Barile, Fergus J Couch, Emily Hallberg, Graham G Giles, Christopher A Haiman, Loic Le Marchand, Mark S Goldberg, Soo H Teo, Cheng Har Yip, Anne-Lise Borresen-Dale, Wei Zheng, Qiuyin Cai, Robert Winqvist, Katri Pylkäs, Irene L Andrulis, Peter Devilee, Rob A E M Tollenaar, Montserrat García-Closas, Jonine Figueroa, Per Hall, Kamila Czene, Judith S Brand, Hatef Darabi, Mikael Eriksson, Maartje J Hooning, Linetta B Koppert, Jingmei Li, Xiao-Ou Shu, Ying Zheng, Angela Cox, Simon S Cross, Mitul Shah, Valerie Rhenius, Ji-Yeob Choi, Daehee Kang, Mikael Hartman, Kee Seng Chia, Maria Kabisch, Diana Torres, Craig Luccarini, Don M Conroy, Anna Jakubowska, Jan Lubinski, Suleeporn Sangrajrang, Paul Brennan, Curtis Olswold, Susan Slager, Chen-Yang Shen, Ming-Feng Hou, Anthony Swerdlow, Minouk J Schoemaker, Jacques Simard, Paul D P Pharoah, Vessela Kristensen, Georgia Chenevix-Trench, Douglas F Easton, Alison M Dunning, Stacey L Edwards
Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1...
October 6, 2016: American Journal of Human Genetics
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