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Sean C Edington, Andrea Gonzalez, Thomas R Middendorf, D Brent Halling, Richard W Aldrich, Carlos R Baiz
The Ca2+ -sensing protein calmodulin (CaM) is a popular model of biological ion binding since it is both experimentally tractable and essential to survival in all eukaryotic cells. CaM modulates hundreds of target proteins and is sensitive to complex patterns of Ca2+ exposure, indicating that it functions as a sophisticated dynamic transducer rather than a simple on/off switch. Many details of this transduction function are not well understood. Fourier transform infrared (FTIR) spectroscopy, ultrafast 2D infrared (2D IR) spectroscopy, and electronic structure calculations were used to probe interactions between bound metal ions (Ca2+ and several trivalent lanthanide ions) and the carboxylate groups in CaM's EF-hand ion-coordinating sites...
March 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shuai Zhang, Burkhard Militzer, Lorin X Benedict, François Soubiran, Philip A Sterne, Kevin P Driver
Carbon-hydrogen plasmas and hydrocarbon materials are of broad interest to laser shock experimentalists, high energy density physicists, and astrophysicists. Accurate equations of state (EOSs) of hydrocarbons are valuable for various studies from inertial confinement fusion to planetary science. By combining path integral Monte Carlo (PIMC) results at high temperatures and density functional theory molecular dynamics results at lower temperatures, we compute the EOSs for hydrocarbons from simulations performed at 1473 separate (ρ, T)-points distributed over a range of compositions...
March 14, 2018: Journal of Chemical Physics
Emily E Burns, Laura J Carter, Dana W Kolpin, Jane Thomas-Oates, Alistair B A Boxall
Many studies have quantified pharmaceuticals in the environment, few however, have incorporated detailed temporal and spatial variability due to associated costs in terms of time and materials. Here, we target 33 physico-chemically diverse pharmaceuticals in a spatiotemporal exposure study into the occurrence of pharmaceuticals in the wastewater system and the Rivers Ouse and Foss (two diverse river systems) in the city of York, UK. Removal rates in two of the WWTPs sampled (a conventional activated sludge (CAS) and trickling filter plant) ranged from not eliminated (carbamazepine) to >99% (paracetamol)...
March 3, 2018: Water Research
Michael A Taylor, Jong W Yu, Thomas L Howell, Stephen H Jones
Vibrio parahaemolyticus is the leading cause of seafood-borne human infections in the United States, and many of these illnesses are associated with consumption of raw molluscan shellfish. V. parahaemolyticus levels in shellfish vary temporally and spatially with environmental conditions in and around production areas. The objective of this study was to study the potential for reducing levels of V. parahaemolyticus in live oysters by relaying them during higher-risk warm weather to a site with elevated salinity and consistently low V...
March 15, 2018: Journal of Food Protection
Yan Zhang, Zhongyuan Huang, Letao Wang, Chunming Wang, Changde Zhang, Thomas E Wiese, Guangdi Wang, Kevin Eugene Riley, Zhe Wang
This work aims to face the challenge of monitoring small molecule drugs accurately and rapidly for point-of-care (POC) diagnosis in current clinical settings. Overdose of acetaminophen (AP), a commonly used OTC analgesic drug, has been determined to be a major cause of acute liver failure in the US and the UK. However, there is no rapid and accurate detection method available for this drug in the emergency room. The present study examined an AP sensing strategy that relies on a previously unexplored strong interaction between AP and the arginine (Arg) molecule...
March 15, 2018: Analytical Chemistry
J Kangara, Chingyun Cheng, S Pegahan, I Arakelyan, J E Thomas
We study the pairing of fermions in a one-dimensional lattice of tunable double-well potentials using radio-frequency spectroscopy. The spectra reveal the coexistence of two types of atom pairs with different symmetries. Our measurements are in excellent quantitative agreement with a theoretical model, obtained by extending the Green's function method of Orso et al. [Phys. Rev. Lett. 95, 060402 (2005)PRLTAO0031-900710.1103/PhysRevLett.95.060402] to a bichromatic 1D lattice with nonzero harmonic radial confinement...
February 23, 2018: Physical Review Letters
Dávid Szamosvári, Sina Rütschlin, Thomas Böttcher
Bacteria engage in numerous collaborative and competitive interactions, which are often mediated by small molecule metabolites. Bacterial competition involves for example the production of compounds that effectively kill or inhibit growth of their neighbours but also the secretion of siderophores that allow securing the essential and fiercely embattled resource of ferric iron. Yet, the enormous diversity of metabolites produced has remained puzzling in many cases. We here present examples of both types of competition from our recent work...
March 15, 2018: Organic & Biomolecular Chemistry
Thomas George Back, Kai N Sands, Tyler A Tuck
Selenium compounds play an important role in redox homeostasis in living organisms. One of their major functions is to suppress the harmful effects of hydrogen peroxide, hydroperoxides and downstream reactive oxygen species that lead to oxidative stress, which has in turn been implicated in many diseases and degenerative conditions. The glutathione peroxidase (GPx) family of selenoenzymes plays a key protective role by catalyzing the reduction of peroxides with glutathione. Considerable effort has been expended toward the discovery of small-molecule selenium compounds that mimic GPx...
March 14, 2018: Chemistry: a European Journal
Thomas Coquet, Michel Lefranc, Louis Chenin, Pascal Foulon, Éric Havet, Johann Peltier
In this anatomy report, we describe the first case of abducens nerve duplication limited to the sphenopetroclival venous gulf and the cavernous sinus. The objective point of division of the two duplicated roots was localized at the gulfar face of the dural porus, just distal to the unique cisternal trunk of the abducens nerve, as it pierced the petroclival dural mater. In the gulfar segment, both roots traveled through a variant of Dorello's canal called the "petrosphenoidal canal" and remained separated through the posterior half of the cavernous sinus...
March 15, 2018: Surgical and Radiologic Anatomy: SRA
Qianjin Li, Omar Awad Alsaidan, Yongjie Ma, Sungjin Kim, Junchen Liu, Thomas Albers, Kebin Liu, Zanna Beharry, Shaying Zhao, Fen Wang, Iryna Lebedyeva, Houjian Cai
Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling facilitates tumor initiation and progression. Although currently approved inhibitors of FGFR kinase have shown therapeutic benefit in clinical trials, over-expression or mutations of FGFRs eventually confer drug resistance and thereby abrogate the desired activity of kinase inhibitors in many cancer types. In this study, we report that loss of myristoylation of fibroblast growth factor receptor substrate 2 (FRS2α), a scaffold protein essential for FGFR signaling, inhibits FGF/FGFR-mediated oncogenic signaling and FGF10-induced tumorigenesis...
March 14, 2018: Journal of Biological Chemistry
David Capper, David T W Jones, Martin Sill, Volker Hovestadt, Daniel Schrimpf, Dominik Sturm, Christian Koelsche, Felix Sahm, Lukas Chavez, David E Reuss, Annekathrin Kratz, Annika K Wefers, Kristin Huang, Kristian W Pajtler, Leonille Schweizer, Damian Stichel, Adriana Olar, Nils W Engel, Kerstin Lindenberg, Patrick N Harter, Anne K Braczynski, Karl H Plate, Hildegard Dohmen, Boyan K Garvalov, Roland Coras, Annett Hölsken, Ekkehard Hewer, Melanie Bewerunge-Hudler, Matthias Schick, Roger Fischer, Rudi Beschorner, Jens Schittenhelm, Ori Staszewski, Khalida Wani, Pascale Varlet, Melanie Pages, Petra Temming, Dietmar Lohmann, Florian Selt, Hendrik Witt, Till Milde, Olaf Witt, Eleonora Aronica, Felice Giangaspero, Elisabeth Rushing, Wolfram Scheurlen, Christoph Geisenberger, Fausto J Rodriguez, Albert Becker, Matthias Preusser, Christine Haberler, Rolf Bjerkvig, Jane Cryan, Michael Farrell, Martina Deckert, Jürgen Hench, Stephan Frank, Jonathan Serrano, Kasthuri Kannan, Aristotelis Tsirigos, Wolfgang Brück, Silvia Hofer, Stefanie Brehmer, Marcel Seiz-Rosenhagen, Daniel Hänggi, Volkmar Hans, Stephanie Rozsnoki, Jordan R Hansford, Patricia Kohlhof, Bjarne W Kristensen, Matt Lechner, Beatriz Lopes, Christian Mawrin, Ralf Ketter, Andreas Kulozik, Ziad Khatib, Frank Heppner, Arend Koch, Anne Jouvet, Catherine Keohane, Helmut Mühleisen, Wolf Mueller, Ute Pohl, Marco Prinz, Axel Benner, Marc Zapatka, Nicholas G Gottardo, Pablo Hernáiz Driever, Christof M Kramm, Hermann L Müller, Stefan Rutkowski, Katja von Hoff, Michael C Frühwald, Astrid Gnekow, Gudrun Fleischhack, Stephan Tippelt, Gabriele Calaminus, Camelia-Maria Monoranu, Arie Perry, Chris Jones, Thomas S Jacques, Bernhard Radlwimmer, Marco Gessi, Torsten Pietsch, Johannes Schramm, Gabriele Schackert, Manfred Westphal, Guido Reifenberger, Pieter Wesseling, Michael Weller, Vincent Peter Collins, Ingmar Blümcke, Martin Bendszus, Jürgen Debus, Annie Huang, Nada Jabado, Paul A Northcott, Werner Paulus, Amar Gajjar, Giles W Robinson, Michael D Taylor, Zane Jaunmuktane, Marina Ryzhova, Michael Platten, Andreas Unterberg, Wolfgang Wick, Matthias A Karajannis, Michel Mittelbronn, Till Acker, Christian Hartmann, Kenneth Aldape, Ulrich Schüller, Rolf Buslei, Peter Lichter, Marcel Kool, Christel Herold-Mende, David W Ellison, Martin Hasselblatt, Matija Snuderl, Sebastian Brandner, Andrey Korshunov, Andreas von Deimling, Stefan M Pfister
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting...
March 14, 2018: Nature
Dennis de Coninck, Thomas H Schmidt, Jan-Gero Schloetel, Thorsten Lang
Plasma membrane proteins organize into structures named compartments, microdomains, rafts, phases, crowds, or clusters. These structures are often smaller than 100 nm in diameter. Despite their importance in many cellular functions, little is known about their inner organization. For instance, how densely are molecules packed? Being aware of the protein compaction may contribute to our general understanding of why such structures exist and how they execute their functions. In this study, we have investigated plasma membrane crowds formed by the amyloid precursor protein (APP), a protein well known for its involvement in Alzheimer's disease...
March 13, 2018: Biophysical Journal
Gul H Dadlani, Thomas C Edwards, Steven Fishberger, Amos Epelman, Nicholas Erbrich
Electrocardiograms may be used to screen for cardiovascular disease (CVD) in children. Many forms of CVD that predispose to sudden cardiac death are associated with T-wave abnormalities in childhood. The T-wave is generated during ventricular repolarization. T-waves on an electrocardiogram typically undergo maturational changes throughout childhood and adolescence. A pediatric practitioner's ability to understand these changes is required to understand abnormal T-waves and recognize potentially life-threatening types of CVD...
March 1, 2018: Pediatric Annals
Randall J Harley, Joseph P Murdy, Zhirong Wang, Michael C Kelly, Tessa-Jonne F Ropp, SeHoon H Park, Patricia F Maness, Paul B Manis, Thomas M Coate
BACKGROUND: In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. NrCAM is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. RESULTS: Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells...
March 14, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Thomas Berk, Stephen D Silberstein
BACKGROUND: Lidocaine, an amide anesthetic, has been used in the treatment of a wide variety of pain disorders for over 75 years. In addition to pain control, lidocaine is an anti-arrhythmic agent and has anti-inflammatory properties. Lidocaine's unique properties, including nonlinear pharmacokinetics, have limited its modern-day use. OBJECTIVE: The purpose of this review is to offer a better understanding of the properties of this unique treatment, which we hope will allow more practitioners to offer this to their patients...
March 14, 2018: Headache
Mingming Pu, Lili Sheng, Sooyeon Song, Ting Gong, Thomas K Wood
Pseudomonas aeruginosa causes many biofilm infections, and the rugose small-colony variants (RSCVs) of this bacterium are important for infection. We found here that inactivation of PA2444, which we determined to be a serine hydroxymethyltransferase (SHMT), leads to the RSCV phenotype of P. aeruginosa PA14. In addition, loss of PA2444 increases biofilm formation by two orders of magnitude, increases exopolysaccharide by 45-fold, and abolishes swarming. The RSCV phenotype is related to higher cyclic diguanylate concentrations due to increased activity of the Wsp chemosensory system, including diguanylate cyclase WspR...
2018: Frontiers in Microbiology
Emily Aherne, Katie Beauchamp, Niamh Maher, Thomas Walsh, William Boyd, Maeve Eogan, Leo Lawler
A 32-year-old primiparous woman presented with severe abdominal pain at 21 weeks' gestation. Background history of laparoscopy for chronic pelvic pain and a spontaneous miscarriage was noted. On examination, she was peritonitic and tachycardic with low grade fever and anemia. MRI abdomen demonstrated a uterine rupture with a large cap of clotted blood overlying the uterine fundus with the appearance of a "shower cap" and large volume haemoperitoneum, the presumptive diagnosis was uterine rupture with placental extrusion...
May 2017: Ulster Medical Journal
Kirill A Vinnikov, Robert C Thomson, Thomas A Munroe
Members of the family Pleuronectidae are common representatives of the marine benthic fauna inhabiting northern regions of the Atlantic and Pacific oceans. The most recent comprehensive classification of the family, based entirely on morphological synapomorphies, recognized five subfamilies, 23 genera, and 61 extant species. However, several subsequent molecular studies have shown that many synapomorphic characters discovered in the morphological study might represent homoplasies, thereby questioning the reliance on these characters with the warning that they may provide misleading information for testing other morphology-based evolutionary hypotheses...
March 10, 2018: Molecular Phylogenetics and Evolution
Agnete B Madsen, Jonas R Knudsen, Carlos Henriquez-Olguin, Yeliz Angin, Kristien J Zaal, Lykke Sylow, Peter Schjerling, Evelyn Ralston, Thomas E Jensen
Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the β-actin isoform which, in many cell types, is the main actin isoform. However, it is not clear that β-actin plays such a role in mature skeletal muscle. Neither dependency of glucose transport on β-actin nor actin reorganization upon glucose transport have been tested in mature muscle. To investigate the role of β-actin in fully differentiated muscle, we have performed a detailed characterization of wildtype and muscle-specific β-actin knockout (KO) mice...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Christina Schneider, Sidney Becker, Hidenori Okamura, Antony Crisp, Tynchtyk Amatov, Michael Stadlmeier, Thomas Carell
The RNA world hypothesis assumes that life on earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G and U), but it contains in addition many chemically modified (non-canonical) bases. A yet open question is if these non-canonical bases were formed in parallel to the canonical bases (chemical origin), or whether they were created later, when life demanded higher functional diversity (biological origin)...
March 13, 2018: Angewandte Chemie
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