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https://www.readbyqxmd.com/read/29750799/population-specific-genetic-modification-of-huntington-s-disease-in-venezuela
#1
Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E MacDonald, James F Gusella, Jong-Min Lee
Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers...
May 11, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29734490/designed-to-react-terminal-copper-nitrenes-and-their-application-in-catalytic-c-h-aminations
#2
Sonja Herres-Pawlis, Julian Moegling, Alexander Hoffmann, Fabian Thomas, Nicole Orth, Patricia Liebhäuser, Ulrich Herber, Robert Rampmaier, Ivana Ivanovic-Burmazovic, Gerhard Fink, Julia Stanek
Heteroscorpionate ligands of the bis(pyrazolyl)methane family have been applied in the stabilisation of terminal copper tosyl nitrenes. These species are highly active intermediates in the copper catalysed direct C-H amination and nitrene transfer. Novel perfluoroalkyl-pyrazolyl and pyridinyl containing ligands have been synthesised, designed for the coordination to a reactive copper nitrene centre. Four distinct copper tosyl nitrenes have been prepared at low temperatures by the reaction with SO2tBuPhINTs and copper(I) acetonitrile complexes...
May 7, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29728409/subchondral-drilling-for-articular-cartilage-repair-a-systematic-review-of-translational-research
#3
Liang Gao, Lars K H Goebel, Patrick Orth, Magali Cucchiarini, Henning Madry
Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed...
May 3, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29702381/nonenzymatic-electrochemical-sensor-based-on-imidazole-functionalized-graphene-oxide-for-progesterone-detection
#4
Ava Gevaerd, Sirlon F Blaskievicz, Aldo J G Zarbin, Elisa S Orth, Márcio F Bergamini, Luiz H Marcolino-Junior
The modification of electrode surfaces has been the target of study for many researchers in order to improve the analytical performance of electrochemical sensors. Herein, the use of an imidazole-functionalized graphene oxide (GO-IMZ) as an artificial enzymatic active site for voltammetric determination of progesterone (P4) is described for the first time. The morphology and electrochemical performance of electrode modified with GO-IMZ were characterized by scanning electron microscopy and cyclic voltammetry, respectively...
April 21, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29682858/natural-biological-variation-of-white-matter-microstructure-is-accentuated-in-huntington-s-disease
#5
Sarah Gregory, Helen Crawford, Kiran Seunarine, Blair Leavitt, Alexandra Durr, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Geraint Rees, Douglas Langbehn, Michael Orth
Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification...
April 22, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29677517/gpr68-senses-flow-and-is-essential-for-vascular-physiology
#6
Jie Xu, Jayanti Mathur, Emilie Vessières, Scott Hammack, Keiko Nonomura, Julie Favre, Linda Grimaud, Matt Petrus, Allain Francisco, Jingyuan Li, Van Lee, Fu-Li Xiang, James K Mainquist, Stuart M Cahalan, Anthony P Orth, John R Walker, Shang Ma, Viktor Lukacs, Laura Bordone, Michael Bandell, Bryan Laffitte, Yan Xu, Shu Chien, Daniel Henrion, Ardem Patapoutian
Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29643182/my-winding-trail-while-fulfilling-my-love-for-science-and-family
#7
Kim Orth
My winding path toward a career in science was awkward, like an adolescent finding an identity. It did not follow a classic course; it had many interruptions, complications, and challenges. It also involved a bit of luck and extremely supportive colleagues, mentors, and family, including my husband, children, and in-laws. I was inspired to tell my story here because I met a young woman interviewing in 2018 for graduate school who is growing up with the same complicated family expectations, social challenges, love for science, and desire to be a scientist as I had four decades ago...
April 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29642445/effect-of-gypsum-on-the-early-hydration-of-cubic-and-na-doped-orthorhombic-tricalcium-aluminate
#8
Ana Paula Kirchheim, Erich D Rodríguez, Rupert J Myers, Luciano A Gobbo, Paulo J M Monteiro, Denise C C Dal Molin, Rui B de Souza, Maria Alba Cincotto
The tricalcium aluminate (C₃A) and sulfate content in cement influence the hydration chemistry, setting time and rheology of cement paste, mortar and concrete. Here, in situ experiments are performed to better understand the effect of gypsum on the early hydration of cubic (cub-)C₃A and Na-doped orthorhombic (orth-)C₃A. The isothermal calorimetry data show that the solid-phase assemblage produced by the hydration of C₃A is greatly modified as a function of its crystal structure type and gypsum content, the latter of which induces non-linear changes in the heat release rate...
April 7, 2018: Materials
https://www.readbyqxmd.com/read/29624598/high-costs-of-infection-alphavirus-infection-reduces-digestive-function-and-bone-and-feather-growth-in-nestling-house-sparrows-passer-domesticus
#9
Carol A Fassbinder-Orth, Tess L Killpack, Dylan S Goto, Ellecia L Rainwater, Valerie I Shearn-Bochsler
Increasingly, ecoimmunology studies aim to use relevant pathogen exposure to examine the impacts of infection on physiological processes in wild animals. Alphaviruses are arthropod-borne, single-stranded RNA (ssRNA) viruses ("arboviruses") responsible for millions of cases of human illnesses each year. Buggy Creek virus (BCRV) is a unique alphavirus that is transmitted by a cimicid insect, the swallow bug, and is amplified in two avian species: the house sparrow (Passer domesticus) and the cliff swallow (Petrochelidon pyrrhonota)...
2018: PloS One
https://www.readbyqxmd.com/read/29555695/natural-transformation-of-vibrio-parahaemolyticus-a-rapid-method-to-create-genetic-deletions
#10
Suneeta Chimalapati, Marcela de Souza Santos, Kelly Servage, Nicole J De Nisco, Ankur B Dalia, Kim Orth
The Gram-negative bacterium Vibrio parahaemolyticus is an opportunistic human pathogen and the leading cause of seafood borne acute gastroenteritis worldwide. Recently, this bacterium was implicated as the etiologic agent of a severe shrimp disease with consequent devastating outcomes to shrimp farming. In both cases, acquisition of genetic material via horizontal transfer provided V. parahaemolyticus with new virulence tools to cause disease. Dissecting the molecular mechanisms of V. parahaemolyticus pathogenesis often requires manipulating its genome...
March 19, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29529833/extended-depth-of-field-imaging-through-multicore-optical-fibers
#11
Antony Orth, Martin Ploschner, Ivan S Maksymov, Brant C Gibson
Compact microendoscopes use multicore optical fibers (MOFs) to visualize hard-to-reach regions of the body. These devices typically have a large numerical aperture (NA) and are fixed-focus, leading to blurry images from a shallow depth of field with little focus control. In this work, we demonstrate a method to digitally adjust the collection aperture and therefore extend the depth of field of lensless MOF imaging probes. We show that the depth of field can be more than doubled for certain spatial frequencies, and observe a resolution enhancement of up to 78% at a distance of 50μm from the MOF facet...
March 5, 2018: Optics Express
https://www.readbyqxmd.com/read/29507225/long-term-nutrient-reductions-lead-to-the-unprecedented-recovery-of-a-temperate-coastal-region
#12
Jonathan S Lefcheck, Robert J Orth, William C Dennison, David J Wilcox, Rebecca R Murphy, Jennifer Keisman, Cassie Gurbisz, Michael Hannam, J Brooke Landry, Kenneth A Moore, Christopher J Patrick, Jeremy Testa, Donald E Weller, Richard A Batiuk
Humans strongly impact the dynamics of coastal systems, yet surprisingly few studies mechanistically link management of anthropogenic stressors and successful restoration of nearshore habitats over large spatial and temporal scales. Such examples are sorely needed to ensure the success of ecosystem restoration efforts worldwide. Here, we unite 30 consecutive years of watershed modeling, biogeochemical data, and comprehensive aerial surveys of Chesapeake Bay, United States to quantify the cascading effects of anthropogenic impacts on submersed aquatic vegetation (SAV), an ecologically and economically valuable habitat...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29505615/circulating-mirnas-isomirs-and-small-rna-clusters-in-human-plasma-and-breast-milk
#13
Mercedes Rubio, Mariona Bustamante, Carles Hernandez-Ferrer, Dietmar Fernandez-Orth, Lorena Pantano, Yaris Sarria, Maria Piqué-Borras, Kilian Vellve, Silvia Agramunt, Ramon Carreras, Xavier Estivill, Juan R Gonzalez, Alfredo Mayor
Circulating small RNAs, including miRNAs but also isomiRs and other RNA species, have the potential to be used as non-invasive biomarkers for communicable and non-communicable diseases. This study aims to characterize and compare small RNA profiles in human biofluids. For this purpose, RNA was extracted from plasma and breast milk samples from 15 healthy postpartum mothers. Small RNA libraries were prepared with the NEBNext® small RNA library preparation kit and sequenced in an Illumina HiSeq2000 platform...
2018: PloS One
https://www.readbyqxmd.com/read/29495149/-current-status-of-job-burnout-in-in-service-sailors-from-13-provinces-and-cities-in-china
#14
L C Shi, J J Dai, H R Wang, J L Wang, L Q Miao, L R Yang
Objective: To investigate the current status of job burnout in in-service sailors, and to provide a basis for the development of intervention measures for job burnout in sailors. Methods: From September 2015 to May 2016, stratified cluster random sampling was used to select 6 172 in-service sailors from 13 provinces and cities as research subjects. General demographic data including age, education background, and household registration and occupational characteristics such as job position, navigating zone, and nature of employment were collected...
December 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29491749/impact-of-early-versus-late-diuretic-exposure-on-metabolic-bone-disease-and-growth-in-premature-neonates
#15
Lucas E Orth, Keliana L O'Mara
OBJECTIVES: This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. METHODS: This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay...
January 2018: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29459650/a-dual-mode-mobile-phone-microscope-using-the-onboard-camera-flash-and-ambient-light
#16
A Orth, E R Wilson, J G Thompson, B C Gibson
Mobile phone microscopes are a natural platform for point-of-care imaging, but current solutions require an externally powered illumination source, thereby adding bulk and cost. We present a mobile phone microscope that uses the internal flash or sunlight as the illumination source, thereby reducing complexity whilst maintaining functionality and performance. The microscope is capable of both brightfield and darkfield imaging modes, enabling microscopic visualisation of samples ranging from plant to mammalian cells...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29424392/reproductive-biology-of-varronia-curassavica-jacq-boraginaceae
#17
Marcia P Hoeltgebaum, Tiago Montagna, Ana Paula Lando, Catarina Puttkammer, Afonso Inácio Orth, Miguel P Guerra, Maurício S Dos Reis
Varronia curassavica, a subshrubby medicinal species associated with restinga in the Atlantic Forest, has been exploited by local people and the pharmaceutical industry. Indeed, restingas have experienced a continuous process of degradation, and thus, with species and ecosystem both at risk, efforts to support conservation actions are required. The present study aimed to evaluate aspects of V. curassavica reproductive biology. To accomplish this, morphological characterization was performed by monitoring flowering events...
January 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29416716/robust-diagnosis-of-ewing-sarcoma-by-immunohistochemical-detection-of-super-enhancer-driven-ewsr1-ets-targets
#18
Michaela C Baldauf, Martin F Orth, Marlene Dallmayer, Aruna Marchetto, Julia S Gerke, Rebeca Alba Rubio, Merve M Kiran, Julian Musa, Maximilian M L Knott, Shunya Ohmura, Jing Li, Nusret Akpolat, Ayse N Akatli, Özlem Özen, Uta Dirksen, Wolfgang Hartmann, Enrique de Alava, Daniel Baumhoer, Giuseppina Sannino, Thomas Kirchner, Thomas G P Grünewald
Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4- , BCOR-CCNB3- , EWSR1-NFATc2- , and EWSR1-ETS -translocated sarcomas are distinct entities, and revealed that ATP1A1 , BCL11B , and GLG1 constitute specific markers for Ewing sarcoma...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414767/fic-mediated-deampylation-is-not-dependent-on-homodimerization-and-rescues-toxic-ampylation-in-flies
#19
Amanda K Casey, Andrew T Moehlman, Junmei Zhang, Kelly A Servage, Helmut Krämer, Kim Orth
No abstract text is available yet for this article.
February 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29409277/the-current-standard-of-foot-and-ankle-fellowship-in-the-uk
#20
R Brown, P Akimau, J Hsuan, T Williams
BACKGROUND: The aim of this study was to evaluate the current standards of Fellowship training in Foot and Ankle Surgery Fellowship in the UK. METHODS: Thirteen UK post-FRCS (Tr&Orth) or equivalent Fellows completed a questionnaire detailing their outpatient, surgical, teaching and research experience, along with documenting their supervision and terms of employment. RESULTS: A Fellow attended a mean of 2.5 (0.5-4) clinics and 3.84 (2-7) theatre sessions per week...
June 10, 2017: Foot and Ankle Surgery: Official Journal of the European Society of Foot and Ankle Surgeons
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