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Jeremy Lewis

Björn Over, Pär Matsson, Christian Tyrchan, Per Artursson, Bradley C Doak, Michael A Foley, Constanze Hilgendorf, Stephen E Johnston, Maurice D Lee, Richard J Lewis, Patrick McCarren, Giovanni Muncipinto, Ulf Norinder, Matthew W D Perry, Jeremy R Duvall, Jan Kihlberg
Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability...
October 17, 2016: Nature Chemical Biology
France Damseaux, Jeremy J Kiszka, Michael R Heithaus, George Scholl, Gauthier Eppe, Jean-Pierre Thomé, Jennifer Lewis, Wensi Hao, Michaël C Fontaine, Krishna Das
The bottlenose dolphin (Tursiops truncatus) is an upper trophic level predator and the most common cetacean species found in nearshore waters of southern Florida, including the Lower Florida Keys (LFK) and the Florida Coastal Everglades (FCE). The objective of this study was to assess contamination levels of total mercury (T-Hg) in skin and persistent organic pollutants (PCBs, PBDEs, DDXs, HCHs, HCB, Σ PCDD/Fs and Σ DL-PCBs) in blubber samples of bottlenose dolphins from LFK (n = 27) and FCE (n = 24)...
October 11, 2016: Environmental Pollution
Nobutaka Kato, Eamon Comer, Tomoyo Sakata-Kato, Arvind Sharma, Manmohan Sharma, Micah Maetani, Jessica Bastien, Nicolas M Brancucci, Joshua A Bittker, Victoria Corey, David Clarke, Emily R Derbyshire, Gillian Dornan, Sandra Duffy, Sean Eckley, Maurice A Itoe, Karin M J Koolen, Timothy A Lewis, Ping S Lui, Amanda K Lukens, Emily Lund, Sandra March, Elamaran Meibalan, Bennett C Meier, Jacob McPhail, Branko Mitasev, Eli L Moss, Morgane Sayes, Yvonne VanGessel, Mathias J Wawer, Takashi Yoshinaga, Anne-Marie Zeeman, Vicky M Avery, Sangeeta N Bhatia, John E Burke, Flaminia Catteruccia, Jon C Clardy, Paul A Clemons, Koen J Dechering, Jeremy R Duvall, Michael A Foley, Fabian Gusovsky, Clemens H M Kocken, Matthias Marti, Marshall L Morningstar, Benito Munoz, Daniel E Neafsey, Amit Sharma, Elizabeth A Winzeler, Dyann F Wirth, Christina A Scherer, Stuart L Schreiber
Antimalarial drugs have thus far been derived mainly from two sources - natural products and synthetic 'drug-like' compounds. We hypothesized that antimalarial agents with novel mechanisms of action might be discovered using a diverse collection of synthetic compounds having three-dimensional features reminiscent of natural products and underrepresented in typical screening collections. We identified such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase...
September 7, 2016: Nature
Andrew J Kennedy, Elizabeth J Rahn, Brynna S Paulukaitis, Katherine E Savell, Holly B Kordasiewicz, Jing Wang, John W Lewis, Jessica Posey, Sarah K Strange, Mikael C Guzman-Karlsson, Scott E Phillips, Kyle Decker, S Timothy Motley, Eric E Swayze, David J Ecker, Todd P Michael, Jeremy J Day, J David Sweatt
Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall...
September 6, 2016: Cell Reports
Phyllissa Schmiedlin-Ren, Laura J Reingold, Christopher S Broxson, Ahren C Rittershaus, Josh S Brudi, Jeremy Adler, Scott R Owens, Ellen M Zimmermann
Anti-TNFα therapy decreases inflammation in Crohn's disease (CD). However, its ability to decrease fibrosis and alter the natural history of CD is not established. Anti-TNF-α prevents inflammation and fibrosis in the peptidoglycan-polysaccharide (PG-PS) model of CD. Here we studied anti-TNF-α in a treatment paradigm. PG-PS or human serum albumin (HSA; control) was injected into bowel wall of anesthetized Lewis rats at laparotomy. Mouse anti-mouse TNF-α or vehicle treatment was begun day (d)1, d7, or d14 postlaparotomy...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Yong-Jin Wu, Jason Guernon, Jianliang Shi, Lawrence Marcin, Mendi Higgins, Ramkumar Rajamani, Jodi Muckelbauer, Hal Lewis, ChiehYing Chang, Dan Camac, Jeremy H Toyn, Michael K Ahlijanian, Charles F Albright, John E Macor, Lorin A Thompson
Truncation of the S3 substituent of the biaryl aminothiazine 2, a potent BACE1 inhibitor, led to a low molecular weight aminothiazine 5 with moderate activity. Despite its moderate activity, compound 5 demonstrated significant brain Aβ reduction in rodents. The metabolic instability of 5 was overcome by the replacement of the 6-dimethylisoxazole, a metabolic soft spot, with a pyrimidine ring. Thus, truncation of the S3 substituent represents a viable approach to the discovery of orally bioavailable, brain-penetrant BACE1 inhibitors...
September 22, 2016: Journal of Medicinal Chemistry
Victoria Ryan, Hazel Brown, Catherine J Minns Lowe, Jeremy S Lewis
BACKGROUND: Frozen shoulder is a common yet poorly understood musculoskeletal condition, which for many, is associated with substantial and protracted morbidity. Understanding the pathology associated with this condition may help to improve management. To date this has not been presented in a systematic fashion. As such, the aim of this review was to summarise the pathological changes associated with this primary frozen shoulder. METHODS: HASH(0x4414930) DATABASES: Medline, Embase, CINAHL, AMED, BNI and the Cochrane Library, were searched from inception to 2nd May, 2014...
2016: BMC Musculoskeletal Disorders
Daniel G Beach, Sheila Crain, Nancy Lewis, Patricia LeBlanc, William R Hardstaff, Ruth A Perez, Sabrina D Giddings, Camilo F Martinez-Farina, Roumiana Stefanova, Ian W Burton, Jane Kilcoyne, Jeremy E Melanson, Michael A Quilliam, Pearse McCarron
Okadaic acid (OA) and its analogs dinophysistoxins-1 (DTX1) and -2 (DTX2) are lipophilic polyethers produced by marine dinoflagellates. These toxins accumulate in shellfish and cause diarrhetic shellfish poisoning (DSP) in humans. Regulatory testing of shellfish is essential to safeguard public health and for international trade. Certified reference materials (CRMs) play a key role in analytical monitoring programs. This paper presents an overview of the interdisciplinary work that went into the planning, production, and certification of calibration-solution CRMs for OA, DTX1, and DTX2...
September 2016: Journal of AOAC International
Julie A McMurry, Sebastian Köhler, Nicole L Washington, James P Balhoff, Charles Borromeo, Matthew Brush, Seth Carbon, Tom Conlin, Nathan Dunn, Mark Engelstad, Erin Foster, Jean-Philippe Gourdine, Julius O B Jacobsen, Daniel Keith, Bryan Laraway, Jeremy Nguyen Xuan, Kent Shefchek, Nicole A Vasilevsky, Zhou Yuan, Suzanna E Lewis, Harry Hochheiser, Tudor Groza, Damian Smedley, Peter N Robinson, Christopher J Mungall, Melissa A Haendel
The principles of genetics apply across the entire tree of life. At the cellular level we share biological mechanisms with species from which we diverged millions, even billions of years ago. We can exploit this common ancestry to learn about health and disease, by analyzing DNA and protein sequences, but also through the observable outcomes of genetic differences, i.e. phenotypes. To solve challenging disease problems we need to unify the heterogeneous data that relates genomics to disease traits. Without a big-picture view of phenotypic data, many questions in genetics are difficult or impossible to answer...
August 2016: Genetics
Matthew R Lewis, Jake T M Pearce, Konstantina Spagou, Martin Green, Anthony C Dona, Ada H Y Yuen, Mark David, David J Berry, Katie Chappell, Verena Horneffer-van der Sluis, Rachel Shaw, Simon Lovestone, Paul Elliott, John Shockcor, John C Lindon, Olivier Cloarec, Zoltan Takats, Elaine Holmes, Jeremy K Nicholson
To better understand the molecular mechanisms underpinning physiological variation in human populations, metabolic phenotyping approaches are increasingly being applied to studies involving hundreds and thousands of biofluid samples. Hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) has become a fundamental tool for this purpose. However, the seemingly inevitable need to analyze large studies in multiple analytical batches for UPLC-MS analysis poses a challenge to data quality which has been recognized in the field...
September 20, 2016: Analytical Chemistry
Elizabeth C Townsend, Mark A Murakami, Alexandra Christodoulou, Amanda L Christie, Johannes Köster, Tiffany A DeSouza, Elizabeth A Morgan, Scott P Kallgren, Huiyun Liu, Shuo-Chieh Wu, Olivia Plana, Joan Montero, Kristen E Stevenson, Prakash Rao, Raga Vadhi, Michael Andreeff, Philippe Armand, Karen K Ballen, Patrizia Barzaghi-Rinaudo, Sarah Cahill, Rachael A Clark, Vesselina G Cooke, Matthew S Davids, Daniel J DeAngelo, David M Dorfman, Hilary Eaton, Benjamin L Ebert, Julia Etchin, Brant Firestone, David C Fisher, Arnold S Freedman, Ilene A Galinsky, Hui Gao, Jacqueline S Garcia, Francine Garnache-Ottou, Timothy A Graubert, Alejandro Gutierrez, Ensar Halilovic, Marian H Harris, Zachary T Herbert, Steven M Horwitz, Giorgio Inghirami, Andrew M Intlekofer, Moriko Ito, Shai Izraeli, Eric D Jacobsen, Caron A Jacobson, Sébastien Jeay, Irmela Jeremias, Michelle A Kelliher, Raphael Koch, Marina Konopleva, Nadja Kopp, Steven M Kornblau, Andrew L Kung, Thomas S Kupper, Nicole R LeBoeuf, Ann S LaCasce, Emma Lees, Loretta S Li, A Thomas Look, Masato Murakami, Markus Muschen, Donna Neuberg, Samuel Y Ng, Oreofe O Odejide, Stuart H Orkin, Rachel R Paquette, Andrew E Place, Justine E Roderick, Jeremy A Ryan, Stephen E Sallan, Brent Shoji, Lewis B Silverman, Robert J Soiffer, David P Steensma, Kimberly Stegmaier, Richard M Stone, Jerome Tamburini, Aaron R Thorner, Paul van Hummelen, Martha Wadleigh, Marion Wiesmann, Andrew P Weng, Jens U Wuerthner, David A Williams, Bruce M Wollison, Andrew A Lane, Anthony Letai, Monica M Bertagnolli, Jerome Ritz, Myles Brown, Henry Long, Jon C Aster, Margaret A Shipp, James D Griffin, David M Weinstock
No abstract text is available yet for this article.
July 11, 2016: Cancer Cell
Eva Barrett, Mary O'Keeffe, Kieran O'Sullivan, Jeremy Lewis, Karen McCreesh
INTRODUCTION: Excessive thoracic kyphosis is considered a predisposing factor for shoulder pain, though there is uncertainty about the nature of the relationship between shoulder pain and thoracic spine posture. The aim of this systematic review was to investigate the relationship between thoracic kyphosis and shoulder pain, shoulder range of motion (ROM) and function. METHODS: Two reviewers independently searched eight electronic databases and identified relevant studies by applying eligibility criteria...
July 21, 2016: Manual Therapy
Laure Saint-Aubert, Jérémie Pariente, Herve Dumas, Pierre Payoux, Jean-Philippe Brandel, Michèle Puel, Anne Vital, Eric Guedj, Suzanne Lesage, Katell Peoc'h, Christine Brefel Courbon, Fabienne Ory Magne
BACKGROUND: Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease. CASE PRESENTATION: We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations...
2016: BMC Neurology
Rachel Chester, Christina Jerosch-Herold, Jeremy Lewis, Lee Shepstone
BACKGROUND/AIM: Shoulder pain is a major musculoskeletal problem. We aimed to identify which baseline patient and clinical characteristics are associated with a better outcome, 6 weeks and 6 months after starting a course of physiotherapy for shoulder pain. METHODS: 1030 patients aged ≥18 years referred to physiotherapy for the management of musculoskeletal shoulder pain were recruited and provided baseline data. 840 (82%) provided outcome data at 6 weeks and 811 (79%) at 6 months...
July 21, 2016: British Journal of Sports Medicine
Germaine Wong, Natalie Staplin, Jonathan Emberson, Colin Baigent, Robin Turner, John Chalmers, Sophia Zoungas, Carol Pollock, Bruce Cooper, David Harris, Jie Jin Wang, Paul Mitchell, Richard Prince, Wai Hon Lim, Joshua Lewis, Jeremy Chapman, Jonathan Craig
BACKGROUND: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease but the relevance of reduced kidney function to cancer risk is uncertain. METHODS: Individual patient data were collected from six studies (32,057 participants); including one population-based cohort and five randomized controlled trials. Participants were grouped into one of five CKD categories (estimated glomerular filtration rate [eGFR] ≥75 mL/min/1.73 m(2); eGFR ≥60 to <75 mL/min/1...
2016: BMC Cancer
Robert C Bourge, Aaron B Waxman, Mardi Gomberg-Maitland, Shelley M Shapiro, James H Tarver, Dianne L Zwicke, Jeremy P Feldman, Murali M Chakinala, Robert P Frantz, Fernando Torres, Jeffrey Cerkvenik, Marty Morris, Melissa Thalin, Leigh Peterson, Lewis J Rubin
BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system...
July 2016: Chest
Robert C Green, Katrina A B Goddard, Gail P Jarvik, Laura M Amendola, Paul S Appelbaum, Jonathan S Berg, Barbara A Bernhardt, Leslie G Biesecker, Sawona Biswas, Carrie L Blout, Kevin M Bowling, Kyle B Brothers, Wylie Burke, Charlisse F Caga-Anan, Arul M Chinnaiyan, Wendy K Chung, Ellen W Clayton, Gregory M Cooper, Kelly East, James P Evans, Stephanie M Fullerton, Levi A Garraway, Jeremy R Garrett, Stacy W Gray, Gail E Henderson, Lucia A Hindorff, Ingrid A Holm, Michelle Huckaby Lewis, Carolyn M Hutter, Pasi A Janne, Steven Joffe, David Kaufman, Bartha M Knoppers, Barbara A Koenig, Ian D Krantz, Teri A Manolio, Laurence McCullough, Jean McEwen, Amy McGuire, Donna Muzny, Richard M Myers, Deborah A Nickerson, Jeffrey Ou, Donald W Parsons, Gloria M Petersen, Sharon E Plon, Heidi L Rehm, J Scott Roberts, Dan Robinson, Joseph S Salama, Sarah Scollon, Richard R Sharp, Brian Shirts, Nancy B Spinner, Holly K Tabor, Peter Tarczy-Hornoch, David L Veenstra, Nikhil Wagle, Karen Weck, Benjamin S Wilfond, Kirk Wilhelmsen, Susan M Wolf, Julia Wynn, Joon-Ho Yu
No abstract text is available yet for this article.
July 7, 2016: American Journal of Human Genetics
Shea Palmer, Fiona Cramp, Emma Clark, Rachel Lewis, Sara Brookes, William Hollingworth, Nicky Welton, Howard Thom, Rohini Terry, Katharine A Rimes, Jeremy Horwood
BACKGROUND: Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness. OBJECTIVES: To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT...
June 2016: Health Technology Assessment: HTA
Crystal S Lewis, Luisa Torres, Jeremy T Miyauchi, Cyrus Rastegar, Jonathan M Patete, Jacqueline M Smith, Stanislaus S Wong, Stella E Tsirka
Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm...
May 1, 2016: Toxicology Research
Jérémie Topin, Mickaël Lelimousin, Julie Arnaud, Aymeric Audfray, Serge Pérez, Annabelle Varrot, Anne Imberty
Histo-blood group epitopes are fucosylated branched oligosaccharides with well-defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group antigens by bacterial and fungal lectins. The Lewis x trisaccharide adopts a rigid closed conformation in solution, while crystallography and molecular dynamics reveal several higher energy open conformations when bound to the Ralstonia solanacearum lectin, which is in agreement with thermodynamic and kinetic measurements...
July 15, 2016: ACS Chemical Biology
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