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https://www.readbyqxmd.com/read/28103472/microsatellite-expansion-diseases-repeat-toxicity-found-in-translation
#1
Fen-Biao Gao, Joel D Richter
Sellier et al. (2017) show that translation of expanded CGG repeats in fragile X-associated tremor/ataxia syndrome is initiated at an upstream ACG near-cognate start codon. The resulting polyglycine-containing protein, but not repeat RNA, is pathogenic by disrupting the nuclear lamina.
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28102901/risk-of-arrhythmic-death-in-ischemic-heart-disease-a-prospective-controlled-observer-blind-investigation-over-10-years
#2
Thomas Pezawas, André Diedrich, David Robertson, Robert Winker, Bernhard Richter, Li Wang, Herwig Schmidinger
BACKGROUND: Risk of arrhythmic death is considered highest in ischemic heart disease with severe left ventricular ejection fraction (LVEF) reduction. Non-invasive testing should improve decision-making of prophylactic defibrillator (ICD) implantation. METHODS AND RESULTS: We enrolled 120 patients with ischemic heart disease and LVEF <50% and 30 control subjects without ischemic heart disease and normal LVEF. An initial assessment, a second assessment after 3 years, and a final follow-up comprised of: pharmacological baroreflex testing (BRS), short-term spectral (low frequency (LF) to high frequency (HF) ratio) and long-term time domain analysis of heart rate variability (SDNN), exercise Microvolt T-wave alternans (MTWA) and others...
January 19, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28101667/impact-of-an-arbuscular-mycorrhizal-fungus-versus-a-mixed-microbial-inoculum-on-the-transcriptome-reprogramming-of-grapevine-roots
#3
Raffaella Balestrini, Alessandra Salvioli, Alessandra Dal Molin, Mara Novero, Giovanni Gabelli, Eleonora Paparelli, Fabio Marroni, Paola Bonfante
Grapevine, cultivated for both fruit and beverage production, represents one of the most economically important fruit crops worldwide. With the aim of better understanding how grape roots respond to beneficial microbes, a transcriptome sequencing experiment has been performed to evaluate the impact of a single arbuscular mycorrhizal (AM) fungal species (Funneliformis mosseae) versus a mixed inoculum containing a bacterial and fungal consortium, including different AM species, on Richter 110 rootstock. Results showed that the impact of a single AM fungus and of a complex microbial inoculum on the grapevine transcriptome differed...
December 27, 2016: Mycorrhiza
https://www.readbyqxmd.com/read/28101620/-home-based-telerehabilitation-after-stroke
#4
M Keidel, F Vauth, J Richter, B Hoffmann, H Soda, B Griewing, M Scibor
The use of modern information and telecommunication technologies enables telerehabilitation of neurological deficits in the domestic environment. The current state of studies on rehabilitative teletherapy for improvement of motor function and mobility deficits due to stroke is reviewed. Two neurolinguistic proof of concept studies investigating the efficacy of online interactive telespeech therapy are reported, which compared virtual screen to screen interactive telerehabilitation of aphasia after stroke and dysarthrophonia in Parkinson's disease to conventional face to face rehabilitation...
January 18, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28100454/gene-therapy-targeting-oligodendrocytes-provides-therapeutic-benefit-in-a-leukodystrophy-model
#5
Elena Georgiou, Kyriaki Sidiropoulou, Jan Richter, Christos Papaneophytou, Irene Sargiannidou, Alexia Kagiava, Georg von Jonquieres, Christina Christodoulou, Matthias Klugmann, Kleopas A Kleopa
Pelizaeus-Merzbacher-like disease or hypomyelinating leukodystrophy-2 is an autosomal recessively inherited leukodystrophy with childhood onset resulting from mutations in the gene encoding the gap junction protein connexin 47 (Cx47, encoded by GJC2). Cx47 is expressed specifically in oligodendrocytes and is crucial for gap junctional communication throughout the central nervous system. Previous studies confirmed that a cell autonomous loss-of-function mechanism underlies hypomyelinating leukodystrophy-2 and that transgenic oligodendrocyte-specific expression of another connexin, Cx32 (GJB1), can restore gap junctions in oligodendrocytes to achieve correction of the pathology in a disease model...
January 18, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28100182/electrocardiographic-assessments-and-cardiac-events-after-fingolimod-first-dose-a-comprehensive-monitoring-study
#6
Volker Limmroth, Tjalf Ziemssen, Michael Lang, Stephan Richter, Bert Wagner, Judith Haas, Stephan Schmidt, Kathrin Gerbershagen, Christoph Lassek, Luisa Klotz, Olaf Hoffmann, Christian Albert, Katrin Schuh, Monika Baier-Ebert, Guillaume Wendt, Heinke Schieb, Susanne Hoyer, Ralf Dechend, Wilhelm Haverkamp
BACKGROUND: First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring. METHODS: START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree AV blocks during treatment initiation...
January 18, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28100143/end-of-life-in-high-security-prisons-in-switzerland
#7
Irene Marti, Ueli Hostettler, Marina Richter
Similar to other institutions, the Swiss prison system faces a growing number of elderly prisoners, trends toward securitization, and, in consequence, more prisoners who will spend the end-of-life (EOL) period of time in prison. By law, prisoners should have the same access to care as the rest of the population. However, custody makes meeting the demands of medical and palliative care difficult. This article focuses on the organizational challenges related to EOL care. Based on ethnographic and documentary research, it examines the institutional logic of the prison and the competing "new" logic emerging with EOL care...
January 2017: Journal of Correctional Health Care
https://www.readbyqxmd.com/read/28100140/human-rights-and-dignity-behind-bars
#8
Tina Maschi, Marina Richter
Death and dying in prisons constitute a topic of growing importance across the globe. Based on the contributions made in this special issue, we reflect on current debates and outline recommendations for dialogue and practice. Scientific dialogue across the Atlantic, and across the globe, provides insights into different national carceral systems and their ways of dealing with end of life behind bars. At the same time, the comparison also helps to identify basic needs and practices that can work in various settings...
January 2017: Journal of Correctional Health Care
https://www.readbyqxmd.com/read/28098428/the-self-sufficient-p450-rhf-expressed-in-a-whole-cell-system-selectively-catalyses-the-5-hydroxylation-of-diclofenac
#9
Jan M Klenk, Bernd A Nebel, Joanne L Porter, Justyna K Kulig, Shaneela A Hussain, Sven M Richter, Michele Tavanti, Nicholas J Turner, Martin A Hayes, Bernhard Hauer, Sabine L Flitsch
P450 monooxygenases are able to catalyse the highly regio- and stereoselective oxidations of many organic molecules. However, the scale-up of such bio-oxidations remains challenging due to the often-low activity, level of expression and stability of P450 biocatalysts. Despite these challenges they are increasingly desirable as recombinant biocatalysts, particularly for the production of drug metabolites. Diclofenac is a widely used anti-inflammatory drug that is persistent in the environment along with the 4'- and 5-hydroxy metabolites...
January 18, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28098042/-joining-forces-for-quality-improvement-in-tuberculosis-control
#10
L Gil, M J T van de Ven, C Richter
The incidence of tuberculosis (TB) in the Netherlands is declining every year. We fear there may be a loss of knowledge and awareness of detecting TB in the new generation of medical specialists. As medical specialists a great challenge lies before us in maintaining the quality of TB control in the Netherlands. Collaboration between pulmonologist, infectious disease specialist, microbiologist and the public health services is a necessity. Here we describe how, in the region of Arnhem, we work closely with these medical specialists based on structural multidisciplinary meetings...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28096328/dynamic-pin-formed-auxin-efflux-carrier-phosphorylation-at-the-plasma-membrane-controls-auxin-efflux-dependent-growth
#11
Benjamin Weller, Melina Zourelidou, Lena Frank, Inês C R Barbosa, Astrid Fastner, Sandra Richter, Gerd Jürgens, Ulrich Z Hammes, Claus Schwechheimer
The directional distribution of the phytohormone auxin is essential for plant development. Directional auxin transport is mediated by the polarly distributed PIN-FORMED (PIN) auxin efflux carriers. We have previously shown that efficient PIN1-mediated auxin efflux requires activation through phosphorylation at the four serines S1-S4 in Arabidopsis thaliana The Brefeldin A (BFA)-sensitive D6 PROTEIN KINASE (D6PK) and the BFA-insensitive PINOID (PID) phosphorylate and activate PIN1 through phosphorylation at all four phosphosites...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#12
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28092368/molecular-insights-into-lipid-assisted-ca-2-regulation-of-the-trp-channel-polycystin-2
#13
Martin Wilkes, M Gregor Madej, Lydia Kreuter, Daniel Rhinow, Veronika Heinz, Silvia De Sanctis, Sabine Ruppel, Rebecca M Richter, Friederike Joos, Marina Grieben, Ashley C W Pike, Juha T Huiskonen, Elisabeth P Carpenter, Werner Kühlbrandt, Ralph Witzgall, Christine Ziegler
Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca(2+) signaling pathways. Malfunctioning Ca(2+) regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2SI), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2MI)...
January 16, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28092264/centriolar-sas-7-acts-upstream-of-spd-2-to-regulate-centriole-assembly-and-pericentriolar-material-formation
#14
Kenji Sugioka, Danielle R Hamill, Joshua B Lowry, Marie E McNeely, Molly Enrick, Alyssa C Richter, Lauren E Kiebler, James R Priess, Bruce Bowerman
The centriole/basal body is a eukaryotic organelle that plays essential roles in cell division and signaling. Among five known core centriole proteins, SPD-2/Cep192 is the first recruited to the site of daughter centriole formation and regulates the centriolar localization of the other components in C. elegans and in humans. However, the molecular basis for SPD-2 centriolar localization remains unknown. Here we describe a new centriole component, the coiled-coil protein SAS-7, as a regulator of centriole duplication, assembly and elongation...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28090681/excess-of-exercise-increases-the-risk-of-atrial-fibrillation
#15
REVIEW
A Müssigbrodt, A Weber, J Mandrola, Y van Belle, S Richter, M Döring, A Arya, P Sommer, A Bollmann, G Hindricks
An interesting and still not well-understood example for old medical wisdom "Sola dosis facit venenum" is the increased prevalence of atrial fibrillation (AF) in athletes. Numerous studies have shown a fourfold to eightfold increased risk of AF in athletes compared to the normal population. Analysis of the existing data suggests a dose-dependent effect of exercise. Moderate exercise seems to have a protective effect and decreases the risk of AF, whereas excessive exercise seems to increase the risk of AF. The described cases illustrate clinical manifestations within the spectrum of AF in elderly athletes, that is, exercise-induced AF, vagal AF, chronic AF, and atrial flutter...
January 16, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28090586/holliday-junction-trap-shows-how-cells-use-recombination-and-a-junction-guardian-role-of-recq-helicase
#16
Jun Xia, Li-Tzu Chen, Qian Mei, Chien-Hui Ma, Jennifer A Halliday, Hsin-Yu Lin, David Magnan, John P Pribis, Devon M Fitzgerald, Holly M Hamilton, Megan Richters, Ralf B Nehring, Xi Shen, Lei Li, David Bates, P J Hastings, Christophe Herman, Makkuni Jayaram, Susan M Rosenberg
DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28090293/relevance-of-angiopoietin-2-and-soluble-p-selectin-levels-in-patients-with-pulmonary-arterial-hypertension-receiving-combination-therapy-with-oral-treprostinil-a-freedom-c2-biomarker-substudy
#17
Manuel J Richter, Ralph Schermuly, Werner Seeger, Youlan Rao, Hossein A Ghofrani, Henning Gall
: Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin (sP-selectin) as biomarkers of disease severity and treatment response in pulmonary arterial hypertension (PAH), but additional data are required for validation. We evaluated these biomarkers using data from FREEDOM-C2, in which patients with PAH receiving stable monotherapy or combination therapy were randomized to receive additional treatment with oral treprostinil (up-titrated from 0.25 mg twice daily) or placebo for 16 weeks...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089729/urinary-biomarkers-in-women-with-refractory-urgency-urinary-incontinence-randomized-to-sacral-neuromodulation-versus-onabotulinumtoxina-compared-to-controls
#18
Holly E Richter, Pamela Moalli, Cindy L Amundsen, Anna P Malykhina, Dennis Wallace, Rebecca Rogers, Deborah Myers, Maria Paraiso, Michael Albo, Haolin Shi, Tracy Nolen, Susie Meikle, R Ann Word
PURPOSE: To measure urinary biomarker levels in women with refractory urgency urinary incontinence (UUI) and controls at baseline and 6 months post treatment from sacral neuromodulation (SNM) or intradetrusor injection onabotulinumtoxinA and to assess association of baseline biomarkers to post treatment UUI episodes (UUIE) and overactive bladder (OAB) symptom bother outcomes. MATERIALS AND METHODS: First morning urines were collected from consented trial participants and age-matched women without UUI...
January 13, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28089032/rule-of-three-for-esophageal-dilation-like-the-tortoise-versus-the-rabbit-low-and-slow-is-our-friend-and-our-patients-win
#19
EDITORIAL
Joel E Richter
No abstract text is available yet for this article.
February 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28088652/convergence-of-interoception-emotion-and-social-cognition-a-twofold-fmri-meta-analysis-and-lesion-approach
#20
Federico Adolfi, Blas Couto, Fabian Richter, Jean Decety, Jessica Lopez, Mariano Sigman, Facundo Manes, Agustín Ibáñez
Guided by indirect evidence, recent approaches propose a tripartite crosstalk among interoceptive signaling, emotional regulation, and low-level social cognition. Here we examined the neurocognitive convergence of such domains. First, we performed three meta-analyses of functional magnetic resonance imaging studies to identify which areas are consistently coactivated by these three systems. Multi-level Kernel Density Analysis (MKDA) revealed major overlaps in the right anterior insular and frontotemporal regions (viz...
December 29, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
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