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https://www.readbyqxmd.com/read/28107586/revealing-additional-stereocomplementary-pairs-of-old-yellow-enzymes-by-rational-transfer-of-engineered-residues
#1
Nathalie Nett, Sabine Duewel, Alexandra Annelis Richter, Sabrina Hoebenreich
Every year numerous protein engineering and directed evolution studies are published, increasing the knowledge which could be used by protein engineers. Here we test a protein engineering strategy that allows quick access to improved biocatalysts with very little screening effort. Conceptually it is assumed that engineered residues, previously identified by rational and random methods, induce similar improvements when transferred to family members. Applied to ene-reductases from the Old Yellow Enzyme family (OYE), the newly created variants were tested with three compounds revealing more stereocomplementary OYE pairs with potent turnover frequencies (up to 660 h-1) and excellent stereoselectivities (up to >99%)...
January 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28106529/a-joint-cross-border-investigation-of-a-cluster-of-multidrug-resistant-tuberculosis-in-austria-romania-and-germany-in-2014-using-classic-genotyping-and-whole-genome-sequencing-methods-lessons-learnt
#2
Lena Fiebig, Thomas A Kohl, Odette Popovici, Margarita Mühlenfeld, Alexander Indra, Daniela Homorodean, Domnica Chiotan, Elvira Richter, Sabine Rüsch-Gerdes, Beatrix Schmidgruber, Patrick Beckert, Barbara Hauer, Stefan Niemann, Franz Allerberger, Walter Haas
Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility...
January 12, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28106417/chaos-and-regularity-in-the-doubly-magic-nucleus-208-pb
#3
B Dietz, A Heusler, K H Maier, A Richter, B A Brown
High-resolution experiments have recently lead to a complete identification (energy, spin, and parity) of 151 nuclear levels up to an excitation energy of E_{x}=6.20  MeV in ^{208}Pb [Heusler et al., Phys. Rev. C 93, 054321 (2016)PRVCAN2469-998510.1103/PhysRevC.93.054321]. We present a thorough study of the fluctuation properties in the energy spectra of the unprecedented set of nuclear bound states. In a first approach, we group states with the same spin and parity into 14 subspectra, analyze standard statistical measures for short- and long-range correlations, i...
January 6, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28105277/design-and-synthesis-of-novel-meta-linked-phenylglycine-macrocyclic-fviia-inhibitors
#4
Jeremy M Richter, Daniel L Cheney, J Alex Bates, Anzhi Wei, Joseph M Luettgen, Alan R Rendina, Timothy M Harper, Rangaraj Narayanan, Pancras C Wong, Dietmar Seiffert, Ruth R Wexler, E Scott Priestley
Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28105163/selection-of-antitumor-displayed-peptides-for-the-specific-delivery-of-the-anticancer-drug-lactaptin
#5
Anna Andreevna Nemudraya, Elena Vladimirovna Kuligina, Alexandr Alexeevich Ilyichev, Alexandr Sergeevich Fomin, Grigory Alexandrovich Stepanov, Anna Valentinovna Savelyeva, Olga Alexandrovna Koval, Vladimir Alexandrovich Richter
It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cells in vitro and suppress the growth of HA-1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104812/antibody-secreting-plasma-cells-persist-for-decades-in-human-intestine
#6
Ole J B Landsverk, Omri Snir, Raquel Bartolomé Casado, Lisa Richter, Jeff E Mold, Pedro Réu, Rune Horneland, Vemund Paulsen, Sheraz Yaqub, Einar Martin Aandahl, Ole M Øyen, Hildur Sif Thorarensen, Mehran Salehpour, Göran Possnert, Jonas Frisén, Ludvig M Sollid, Espen S Baekkevold, Frode L Jahnsen
Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively...
January 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28104299/liquid-fiducial-marker-applicability-in-proton-therapy-of-locally-advanced-lung-cancer
#7
Jonas Scherman Rydhög, Rosalind Perrin, Rasmus Irming Jølck, Francis Gagnon-Moisan, Klaus Richter Larsen, Paul Clementsen, Steen Riisgaard de Blanck, Gitte Fredberg Persson, Damien Charles Weber, Tony Lomax, Thomas Lars Andresen, Per Munck Af Rosenschold
BACKGROUND AND PURPOSE: We investigated the clinical applicability of a novel liquid fiducial marker (LFM) for image-guided pencil beam scanned (PBS) proton therapy (PBSPT) of locally advanced lung cancer (LALC). MATERIALS AND METHODS: The relative proton stopping power (RSP) of the LFM was calculated and measured. Dose perturbations of the LFM and three solid markers, in a phantom, were measured. PBSPT treatment planning on computer tomography scans of five patients with LALC with the LFM implanted was performed with 1-3 fields...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28103472/microsatellite-expansion-diseases-repeat-toxicity-found-in-translation
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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