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Dennis Walczyk, Markus Gößringer, Walter Rossmanith, Timofei S Zatsepin, Tatiana S Oretskaya, Roland K Hartmann
Ribonuclease P (RNase P) is the enzyme that endonucleolytically removes 5'-precursor sequences from tRNA transcripts in all domains of life. RNase P activities are either ribonucleoprotein (RNP) or protein-only (PRORP) enzymes, raising the question about the mechanistic strategies utilized by these architecturally different enzyme classes to catalyze the same type of reaction. Here we analyzed the kinetics and cleavage-site selection by PRORP3 from Arabidopsis thaliana (AtPRORP3) using precursor tRNAs (pre-tRNAs) with individual modifications at the canonical cleavage site, either Rp- or Sp-phosphorothioate, or 2'-deoxy, 2'-fluoro, 2'-amino or 2'-O-methyl substitutions...
October 18, 2016: Journal of Molecular Biology
Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
Jie Yang, Markus Guehr, Xiaozhe Shen, Renkai Li, Theodore Vecchione, Ryan Coffee, Jeff Corbett, Alan Fry, Nick Hartmann, Carsten Hast, Kareem Hegazy, Keith Jobe, Igor Makasyuk, Joseph Robinson, Matthew S Robinson, Sharon Vetter, Stephen Weathersby, Charles Yoneda, Xijie Wang, Martin Centurion
Observing the motion of the nuclear wave packets during a molecular reaction, in both space and time, is crucial for understanding and controlling the outcome of photoinduced chemical reactions. We have imaged the motion of a vibrational wave packet in isolated iodine molecules using ultrafast electron diffraction with relativistic electrons. The time-varying interatomic distance was measured with a precision 0.07 Å and temporal resolution of 230 fs full width at half maximum. The method is not only sensitive to the position but also the shape of the nuclear wave packet...
October 7, 2016: Physical Review Letters
Laura Whitton, Donna Cosgrove, Christopher Clarkson, Denise Harold, Kimberley Kendall, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, James Walters, Annette Hartmann, Betina Konte, Dan Rujescu, Michael Gill, Aiden Corvin, Stephen Rea, Gary Donohoe, Derek W Morris
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Olga Besharova, Verena M Suchanek, Raimo Hartmann, Knut Drescher, Victor Sourjik
Many bacteria primarily exist in nature as structured multicellular communities, so called biofilms. Biofilm formation is a highly regulated process that includes the transition from the motile planktonic to sessile biofilm lifestyle. Cellular differentiation within a biofilm is a commonly accepted concept but it remains largely unclear when, where and how exactly such differentiation arises. Here we used fluorescent transcriptional reporters to quantitatively analyze spatio-temporal expression patterns of several groups of genes during the formation of submerged Escherichia coli biofilms in an open static system...
2016: Frontiers in Microbiology
Julia Smedbråten, Geir Mjøen, Anders Hartmann, Anders Åsberg, Halvor Rollag, Tom Eirik Mollnes, Leiv Sandvik, Morten W Fagerland, Steffen Thiel, Solbjørg Sagedal
BACKGROUND: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient's native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation. METHODS: Two mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000-2001...
October 18, 2016: BMC Nephrology
Maxime Cailleret, Steven Jansen, Elisabeth M R Robert, Lucía Desoto, Tuomas Aakala, Joseph A Antos, Barbara Beikircher, Christof Bigler, Harald Bugmann, Marco Caccianiga, Vojtěch Čada, J Julio Camarero, Paolo Cherubini, Hervé Cochard, Marie R Coyea, Katarina Čufar, Adrian J Das, Hendrik Davi, Sylvain Delzon, Michael Dorman, Guillermo Gea-Izquierdo, Sten Gillner, Laurel J Haavik, Henrik Hartmann, Ana-Maria Hereş, Kevin R Hultine, Pavel Janda, Jeffrey M Kane, Vyacheslav I Kharuk, Thomas Kitzberger, Tamir Klein, Koen Kramer, Frederic Lens, Tom Levanic, Juan Carlos Linares Calderon, Francisco Lloret, Raquel Lobo-Do-Vale, Fabio Lombardi, Rosana López Rodríguez, Harri Mäkinen, Stefan Mayr, Ilona Mészáros, Juha M Metsaranta, Francesco Minunno, Walter Oberhuber, Andreas Papadopoulos, Mikko Peltoniemi, Any Mary Petritan, Brigitte Rohner, Gabriel Sangüesa-Barreda, Dimitrios Sarris, Jeremy M Smith, Amanda B Stan, Frank Sterck, Dejan B Stojanović, Maria Laura Suarez, Miroslav Svoboda, Roberto Tognetti, José M Torres-Ruiz, Volodymyr Trotsiuk, Ricardo Villalba, Floor Vodde, Alana R Westwood, Peter H Wyckoff, Nikolay Zafirov, Jordi Martínez-Vilalta
Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2,970 dead and 4,224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca...
October 19, 2016: Global Change Biology
Stephan Brauckmann, Katharina Effenberger-Neidnicht, Herbert de Groot, Michael Nagel, Christian Mayer, Jürgen Peters, Matthias Hartmann
While hemolysis in patients with sepsis is associated with increased mortality its mechanisms are unknown and Toll-like receptor (TLR)-4 mediated effects, complement-mediated hemolysis, or direct cell membrane effects are all conceivable mechanisms. In this study, we tested the hypotheses that toxic lipopolysaccharide (LPS) as well as non-toxic RS-LPS evokes hemolysis (1) by direct membrane effects, and (2) independent of the complement system and TLR-4 activation. We found, that incubation with LPS resulted in a marked time and concentration dependent increase of free hemoglobin concentration and LDH activity in whole blood and washed red cells...
October 19, 2016: Scientific Reports
Matthias Hartmann, Jochen Laubrock, Martin H Fischer
In the domain of language research, the simultaneous presentation of a visual scene and its auditory description (i.e., the visual world paradigm) has been used to reveal the timing of mental mechanisms. Here we apply this rationale to the domain of numerical cognition in order to explore the differences between fast and slow arithmetic performance, and to further study the role of spatial-numerical associations during mental arithmetic. We presented 30 healthy adults simultaneously with visual displays containing four numbers and with auditory addition and subtraction problems...
October 19, 2016: Quarterly Journal of Experimental Psychology: QJEP
Elizabeth S Barrie, Katherine Hartmann, Sung-Ha Lee, John T Frater, Michal Seweryn, Danxin Wang, Wolfgang Sadee
Functionally related genes often cluster into a genome region under coordinated regulation, forming a local regulome. To understand regulation of the CHRNA5/CHRNA3/CHRNB4 nicotinic receptor gene cluster, we integrate large-scale RNA expression data (brain and peripheral) from GTEx (Genotype Tissue Expression), clinical associations (GRASP) and linkage disequilibrium data (1,000 Genomes) to find candidate SNPs representing independent regulatory variants. CHRNA3, CHRNA5, CHRNB4 mRNAs, and a well-expressed CHRNA5 antisense RNA (RP11-650L12...
October 19, 2016: Human Mutation
Stefanie Memmer, Sandra Weil, Steffen Beyer, Tobias Zöller, Eike Peters, Jessica Hartmann, Alexander Steinle, Joachim Koch
The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3ζ signaling remain unsolved. Here, we show that the stalk domain (K129EHPQLGAGTVLLLR143) of NKp30 is very sensitve to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3ζ for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting and/or ligand induced receptor signaling...
October 17, 2016: Journal of Biological Chemistry
Abhik Bhattacharya, Bhavana B Rao, Ioannis E Koutroubakis, Benjamin Click, Eric J Vargas, Miguel Regueiro, Marc Schwartz, Jason M Swoger, Dmitriy Babichenko, Douglas Hartmann, Claudia R Rivers, Arthur Barrie, Jana G Hashash, Michael A Dunn, David G Binion
BACKGROUND: Patients with Crohn's disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled "silent CD" and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. METHODS: Observational study of patients with CD prospectively followed in a tertiary referral natural history registry...
November 2016: Inflammatory Bowel Diseases
William Peacock
Dear Editor I read with great interest the manuscript titled "A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults" by Shan R, et al, published in the January issue of the Journal. (1) I do have some questions. The key to marker discovery studies is a precise and accurate description of how the population was identified, including controls. I have significant concerns about the control population in the manuscript. In the presentation the characteristics of the control group are unclear, described only as "not patients in the ED" and with the same exclusion criteria of the other cohorts...
October 18, 2016: Journal of Neurotrauma
Andreas Hartmann
In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation...
2016: F1000Research
Nadine Lilla, Jasmin Hartmann, Stefan Koehler, Ralf-Ingo Ernestus, Thomas Westermaier
A lack of nitric oxide (NO) may be a possible factor in the pathogenesis of an acute decrease of cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether early therapy with an NO-donor can improve CBF and offer neuroprotection after experimental SAH in rats. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated with 1.5μg/kg/min of intravenous sodium nitroprusside (SNP) or vehicle (n=10) starting 15min after induction of SAH until 180min thereafter...
September 20, 2016: Journal of the Neurological Sciences
Michael Feichtinger, Elisabeth Wallner, Beda Hartmann, Angelika Reiner, Thomas Philipp
OBJECTIVE: To assess the cytogenetic and embryoscopic characteristics of primary and secondary recurrent pregnancy loss. DESIGN: Clinical prospective descriptive study. SETTING: Tertiary care center. PATIENT(S): Nine hundred and eighty-four women affected by first-trimester pregnancy loss; 145 patients with recurrent pregnancy loss (RPL) and 839 patients with nonrecurrent pregnancy loss as controls. INTERVENTION(S): Transcervical embryoscopic examination of the embryo before uterine evacuation, and cytogenetic analysis of the chorionic villi by standard G-banding cytogenetic techniques...
October 12, 2016: Fertility and Sterility
Jörg T Regula, Peter Lundh von Leithner, Richard Foxton, Veluchamy A Barathi, Chui Ming Gemmy Cheung, Sai Bo Bo Tun, Yeo Sia Wey, Daiju Iwata, Miroslav Dostalek, Jörg Moelleken, Kay G Stubenrauch, Everson Nogoceke, Gabriella Widmer, Pamela Strassburger, Michael J Koss, Christian Klein, David T Shima, Guido Hartmann
Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A...
October 14, 2016: EMBO Molecular Medicine
Heidi Hirsch, Isabell Hensen, Karsten Wesche, Daniel Renison, Catherina Wypior, Matthias Hartmann, Henrik von Wehrden
Introduced plants often face new environmental conditions in their non-native ranges. To become invasive, they need to overcome several biotic and abiotic filters that may trigger adaptive changes in life-history traits, like post-germination processes. Such early life cycle traits may play a crucial role in the colonization and establishment success of invasive plants. As a previous study revealed that seeds of non-native populations of the woody Siberian elm, Ulmus pumila germinated faster than those of native populations, we expected growth performance of seedlings to mirror this finding...
October 13, 2016: AoB Plants
Tom Hartmann, An-Chiang Chu, Martin Middendorf, Matthias Bernt
The tandem duplication random loss operation (TDRL) is an important genome rearrangement operation in metazoan mitochondrial genomes. A TDRL consists of a duplication of a contiguous set of genes in tandem followed by a random loss of one copy of each duplicated gene. This paper presents an analysis of the combinatorics of TDRLs on circular genomes, e.g., the mitochondrial genome. In particular, results on TDRLs for circular genomes and their linear representatives are established. Moreover, the distance between gene orders with respect to linear TDRLs and circular TDRLs is studied...
September 26, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
M Rosenberg, Gabor J Kalman, P Hartmann, Z Donkó
In a two-dimensional (2D) dusty plasma composed of superparamagnetic, charged dust grains and immersed in an external magnetic field B, the grains interact via both Yukawa and magnetic dipole-dipole potentials. Because the grains' magnetic dipole moments are induced by B, the dipole moments all lie along B. When B is tilted with respect to the normal to the dust layer, the interaction between the grains becomes anisotropic. In our previous paper [Hartmann et al., Phys. Rev. E 89, 043102 (2014)PLEEE81539-375510...
September 2016: Physical Review. E
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