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Gregory J Kato, Frédéric B Piel, Clarice D Reid, Marilyn H Gaston, Kwaku Ohene-Frempong, Lakshmanan Krishnamurti, Wally R Smith, Julie A Panepinto, David J Weatherall, Fernando F Costa, Elliott P Vichinsky
Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system...
March 15, 2018: Nature Reviews. Disease Primers
Thomas K F Foo, Evangelos Laskaris, Mark Vermilyea, Minfeng Xu, Paul Thompson, Gene Conte, Christopher Van Epps, Christopher Immer, Seung-Kyun Lee, Ek T Tan, Dominic Graziani, Jean-Baptise Mathieu, Christopher J Hardy, John F Schenck, Eric Fiveland, Wolfgang Stautner, Justin Ricci, Joseph Piel, Keith Park, Yihe Hua, Ye Bai, Alex Kagan, David Stanley, Paul T Weavers, Erin Gray, Yunhong Shu, Matthew A Frick, Norbert G Campeau, Joshua Trzasko, John Huston, Matt A Bernstein
PURPOSE: To build and evaluate a small-footprint, lightweight, high-performance 3T MRI scanner for advanced brain imaging with image quality that is equal to or better than conventional whole-body clinical 3T MRI scanners, while achieving substantial reductions in installation costs. METHODS: A conduction-cooled magnet was developed that uses less than 12 liters of liquid helium in a gas-charged sealed system, and standard NbTi wire, and weighs approximately 2000 kg...
March 13, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Pablo J Sáez, Lucie Barbier, Rafaele Attia, Hawa-Racine Thiam, Matthieu Piel, Pablo Vargas
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21...
2018: Methods in Molecular Biology
Camille Pouchieu, Chantal Raherison, Clément Piel, Lucile Migault, Camille Carles, Pascale Fabbro-Perray, Hugues Loiseau, Jean-Sébastien Guillamo, Pierre Lebailly, Isabelle Baldi
Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004-2010. Participants' histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview...
March 2, 2018: Journal of Neuro-oncology
Drew T Wagner, Zhicheng Zhang, Roy A Meoded, Alexis J Cepeda, Joern Piel, Adrian T Keatinge-Clay
trans-Acyltransferase assembly lines possess enzymatic domains often not observed in their better characterized cis-acyltransferase counterparts. Within this repertoire of largely unexplored biosynthetic machinery is a class of enzyme called the pyran synthase that catalyzes the formation of five- and six-membered cyclic ethers from diverse polyketide chains. The 1.55 Å-resolution crystal structure of a pyran synthase domain excised from the ninth module of the sorangicin assembly line highlights the similarity of this enzyme to the ubiquitous dehydratase domain and provides insight into the mechanism of ring formation...
February 26, 2018: ACS Chemical Biology
Kirsten Yakoub, Sascha Jung, Christian Sattler, Helen Damerow, Judith Weber, Annika Kretzschmann, Aylin S Cankaya, Markus Piel, Frank Rösch, Anne S Haugaard, Bente Frølund, Tanja Schirmeister, Hartmut Lüddens
Delta selective compounds 1 and 2 (DS1, compound 22; DS2, compound 16) were introduced as functionally selective modulators of δ-containing GABA receptors type A (GABAAR). In our hands [ 3 H]EBOB binding experiments with recombinant GABA A R using compound 22, showed no proof of δ-selectivity, though a minimally higher preference with respect to potency for α4β3δ and α6β2/3δ receptors. In order to delineate the structural determinant for δ-preference, we synthesized 25 derivatives of DS1 and DS2, and investigated their structure-activity relationship (SAR)...
February 16, 2018: Journal of Medicinal Chemistry
Brandon I Morinaka, Edgars Lakis, Marjan Verest, Maximilian J Helf, Thibault Scalvenzi, Anna L Vagstad, James Sims, Shinichi Sunagawa, Muriel Gugger, Jörn Piel
Current textbook knowledge holds that the structural scope of ribosomal biosynthesis is based exclusively on α-amino acid backbone topology. Here we report the genome-guided discovery of bacterial pathways that posttranslationally create β-amino acid-containing products. The transformation is widespread in bacteria and is catalyzed by an enzyme belonging to a previously uncharacterized radical S -adenosylmethionine family. We show that the β-amino acids result from an unusual protein splicing process involving backbone carbon-carbon bond cleavage and net excision of tyramine...
February 16, 2018: Science
Sara Roldan Ramons, Guido Ehrenfried Pieles, Mei Sun, Cameron Slorach, Wei Hui, Mark K Friedberg
BACKGROUND: Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis and apoptosis which are attenuated by endothelin-1 (ET1) receptor blockade (ERB). Little is known about the time-course of remodelling and whether early versus late ERB confers improved outcome. MATERIALS AND METHODS: PAB was performed in 5-groups of rabbits: Shams, 3W (3-weeksPAB), 6W (6-weeksPAB), 6WERB1 (6-weeksPAB+ERB from day-1) and 6WERB21 (6-weeksPAB+ERB from day-21)...
February 15, 2018: Journal of Applied Physiology
Tetsushi Mori, Jackson K B Cahn, Micheal C Wilson, Roy A Meoded, Vincent Wiebach, Ana Flávia Canovas Martinez, Eric J N Helfrich, Andreas Albersmeier, Daniel Wibberg, Steven Dätwyler, Ray Keren, Adi Lavy, Christian Rückert, Micha Ilan, Jörn Kalinowski, Shigeki Matsunaga, Haruko Takeyama, Jörn Piel
Marine sponges are prolific sources of unique bioactive natural products. The sponge Theonella swinhoei is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism " Candidatus Entotheonella factor," produces almost all of these compounds. To obtain further insights into the chemistry of "Entotheonella," we investigated another phylotype, " Candidatus Entotheonella serta," present in the T...
February 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
T Mann, K Zilles, H Dikow, A Hellfritsch, M Cremer, M Piel, F Rösch, A Hawlitschka, O Schmitt, A Wree
Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α 1, α 2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography...
February 5, 2018: Neuroscience
Juan Pablo Castanedo-Cazares, Diana Hernández-Blanco, Juan Diego García-Cortés, Liliana Medina-Aguilar, Bertha Torres-Álvarez
Antecedentes: La mezcla de melanina, hemoglobina y carotenos definen el color cutáneo. La pigmentación constitutiva está determinada genéticamente, la facultativa se induce cuando la piel se expone al ambiente. El objetivo fue cuantificar ambas pigmentaciones en una muestra de población mexicana, y analizar su relación con el género, edad y fototipo. Métodos: Se evaluaron 259 personas durante un periodo invernal. La colorimetría cutánea se obtuvo mediante espectrometría de reflectancia difusa utilizando las coordenadas de la Comisión Internacional de Iluminación...
2018: Gaceta Médica de México
Aaron Webster Puri, Emily Mevers, Timothy R Ramadhar, Daniel Petras, Darren Liu, Joern Piel, Pieter C Dorrestein, Peter Greenberg, Mary E Lidstrom, Jon Clardy
Methane-oxidizing bacteria, aerobes that utilize methane as their sole carbon and energy source, are increasingly studied for their environmentally significant ability to remove methane from the atmosphere. Their genomes indicate that they also have a robust and unusual secondary metabolism. Bioinformatic analysis of the Methylobacter tundripaludum genome identified biosynthetic gene clusters for several intriguing metabolites, and this report discloses the structural and genetic characterization of tundrenone, one of these metabolites...
January 23, 2018: Journal of the American Chemical Society
Jennifer L Piel, Rejoice Opara
A recent Washington State case revisits the obligation of mental health clinicians to protect third parties from the violent acts of their patients. Although the case of Volk v DeMeerleer raises multiple legal, ethical, and policy issues, this article will focus on a potential ethical conflict between the case law and professional guidelines, namely the American Medical Association's Code of Medical Ethics.
January 1, 2018: AMA Journal of Ethics
J H Piel, T A Lett, C Wackerhagen, M M Plichta, S Mohnke, O Grimm, N Romanczuk-Seiferth, F Degenhardt, H Tost, S Witt, M Nöthen, M Rietschel, A Heinz, A Meyer-Lindenberg, H Walter, S Erk
Major depressive disorder (MDD) is characterized by low mood for at least two weeks. Impaired emotion regulation has been suggested to be the consequence of dysfunctional serotonergic regulation of limbic and prefrontal regions, especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The impact of genetic variation on brain function can be investigated with intermediate phenotypes. A suggested intermediate phenotype of MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other serotonergic genes have been associated with amygdala and prefrontal function during emotion recognition...
March 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Laura Laencina, Violaine Dubois, Vincent Le Moigne, Albertus Viljoen, Laleh Majlessi, Justin Pritchard, Audrey Bernut, Laura Piel, Anne-Laure Roux, Jean-Louis Gaillard, Bérengère Lombard, Damarys Loew, Eric J Rubin, Roland Brosch, Laurent Kremer, Jean-Louis Herrmann, Fabienne Girard-Misguich
Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for a wide spectrum of clinical manifestations ranging from pulmonary to skin and soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms of amoebae and macrophages, an ability that has not been observed in other RGM. M. abscessus can up-regulate several virulence factors during transient infection of amoebae, thereby becoming more virulent in subsequent respiratory infections in mice...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
Fabrice Dalier, Galina V Dubacheva, Marie Coniel, Drazen Zanchi, Anouk Galtayries, Matthieu Piel, Emmanuelle Marie, Christophe Tribet
Dynamic guidance of living cells is achieved by fine tuning and spatiotemporal modulation on artificial polymer layers enabling reversible peptide display. Adjustment of surface composition and interactions is obtained by coadsorption of mixed poly(lysine) derivatives, grafted with either repellent PEG, RGD adhesion peptides, or T-responsive poly(N-isopropylacrylamide) strands. Deposition of mixed adlayers provides a straightforward mean to optimize complex substrates, which is here implemented to achieve 1) thermal control of ligand accessibility and 2) adjustment of relative adhesiveness between adjacent micropatterns, while preserving cell attachment during thermal cycles...
January 9, 2018: ACS Applied Materials & Interfaces
Fiona A Stewart, Alexander K Piel, Lydia Luncz, Joanna Osborn, Yingying Li, Beatrice H Hahn, Michael Haslam
Most of our knowledge of wild chimpanzee behaviour stems from fewer than 10 long-term field sites. This bias limits studies to a potentially unrepresentative set of communities known to show great behavioural diversity on small geographic scales. Here, we introduce a new genetic approach to bridge the gap between behavioural material evidence in unhabituated chimpanzees and genetic advances in the field of primatology. The use of DNA analyses has revolutionised archaeological and primatological fields, whereby extraction of DNA from non-invasively collected samples allows researchers to reconstruct behaviour without ever directly observing individuals...
2018: PloS One
L Migault, C Piel, C Carles, F Delva, A Lacourt, E Cardis, C Zaros, R de Seze, I Baldi, G Bouvier
OBJECTIVES: To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF EMF) and the risk of moderate prematurity and small for gestational age within the Elfe cohort. METHODS: The Elfe study included 18,329 infants born at 33weeks of gestation or more in France in 2011 and was designed to follow the children until 20years of age. Gestational age and anthropometric data at birth were collected in medical records and small for gestational age was defined according to a French customized growth standard...
December 20, 2017: Environment International
Holly Felix, Brett Rowland, Christopher R Long, Marie-Rachelle Narcisse, Michelle Piel, Peter A Goulden, Pearl A McElfish
Marshallese experience high rates of type 2 diabetes. Proper management of diabetes requires multiple self-care behaviors, yet little is known about Marshallese's diabetes-related self-care behaviors. Survey data from 111 Marshallese adults with diabetes were used to examine relationships between self-care behaviors and socio-demographic characteristics. The most common self-care behavior was attending annual doctor visits, while the least common was maintaining a normal weight. Age group, education level, and having a regular doctor were significantly associated with engaging in self-care behaviors...
December 14, 2017: Journal of Immigrant and Minority Health
Stephanie Tran, Peter-Joseph DeGiovanni, Brandon Piel, Prakash Rai
Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity...
December 11, 2017: Clinical and Translational Medicine
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