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In the mouse, most mature olfactory sensory neurons (OSNs) express one allele of one gene from the repertoire of ~1100 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express a given OR coalesce into homogeneous glomeruli, which reside at conserved positions in the olfactory bulb. ORs are intimately involved in ensuring the expression of one OR per OSN and the coalescence of OSN axons into glomeruli. But the mechanisms whereby ORs accomplish these diverse functions remain poorly understood. An experimental approach that has been informative is to substitute an OR genetically with another GPCR that is normally not expressed in OSNs, in order to determine in which aspects this GPCR can serve as surrogate OR in mouse OSNs. Thus far only the β2-adrenergic receptor (β2AR, Ardb2) has been shown to be able to serve as surrogate OR in OSNs; the β2AR could substitute for the M71 OR in all aspects examined. Can other non-olfactory GPCRs function equally well as surrogate ORs in OSNs? Here, we have generated and characterized two novel gene-targeted mouse strains in which the mouse melanocortin 4 receptor (Mc4r) or the mouse dopamine receptor D1 (Drd1a) is coexpressed with tauGFP in OSNs that express the OR locus M71. These alleles and strains are abbreviated as Mc4r→M71-GFP and Drd1a→M71-GFP. We detected strong Mc4r or Drd1a immunoreactivity in axons and dendritic knobs and cilia of OSNs that express Mc4r or Drd1a from the M71 locus. These OSNs responded physiologically to cognate agonists for Mc4r (Ro27-3225) or Drd1a (SKF81297), and not to the M71 ligand acetophenone. Axons of OSNs expressing Mc4r→M71-GFP coalesced into glomeruli. Axons of OSNs expressing Drd1a→M71-GFP converged onto restricted areas of the olfactory bulb but did not coalesce into glomeruli. Thus, OR functions in OSNs can be substituted by Mc4r or Drd1a, but not as well as by β2AR. We attribute the weak performance of Drd1a as surrogate OR to poor OSN maturation.
The current knowledge of the scorpionfly genus Dicerapanorpa Zhong & Hua, 2013 is taxonomically reviewed. Two new species of Dicerapanorpa are described and illustrated, increasing the species number of this genus to 20. Dicerapanorpa bifurcata sp. nov. from the Minshan Mountains, Sichuan Province, is characterized by the absence of the paramere basal branch and the elongated mesal branch in males, and the medigynium having a short basal stalk in females. Dicerapanorpa zhengkuni sp. nov. from the Wuling and Miaoling Mountains, Guizhou Province, is distinguishable by the greatly elongated hypovalves, the very short basal branch of the paramere, and the dorsomedially curved lateral branch in males, and the rounded main plate of the medigynium in females. An updated key to species of Dicerapanorpa is presented.
Die Analyse früher Entwicklungsstadien von Säugetierembryonen und daraus gewonnener Stammzelllinien kann entscheidende Erkenntnisse im Bereich der Reproduktionsbiologie und der regenerativen Medizin hervorbringen. Dabei spielt die Maus, als geeignetes Modellsystem für die Übertragbarkeit auf den Menschen eine wichtige Rolle, in erster Linie weil die Blastozysten der Maus verglichen mit menschliche Blastozysten eine morphologische Ähnlichkeit aufweisen. Humane embryonale Stammzelllinien haben großes Potential für die Anwendung in der regenerativen Medizin und vergleichend dazu wurde Gen-Targeting in embryonalen Stammzellen verwendet, um tausende neuer Mausstämme zu generieren. Die Gewinnung embryonaler Stammzellen erfolgt im Blastozystenstadium, diese können dann nach Injektion in eine andere Blastozyste zur Entwicklung aller Gewebearten, einschließlich der Keimbahngewebe, beitragen (Martin, 1981; Evans and Kaufman 1981).
Ursache einer Fehlgeburt können vor allem Defekte in der Entwicklung des Trophoblasten und des primitive Entoderms (PrE) sein, dabei sind ca. 5 % der Paare betroffen die versuchen ein Kind zu bekommen (Stephenson and Kutteh, 2007). Eine Untersuchung dieser Zelllinien im Mausmodell könnte weitere Erkenntnisse für die Gründe einer Fehlentwicklung liefern. Trophoblasten Stammzelllinien können aus den Blastozysten der Maus und dem extraembryonalen Ektoderm von bereits implantieren Embryonen gewonnen werden (Tanaka et al., 1998). Diese Zelllinien geben Aufschluss über die Entwicklung des Trophoblasten, fördern die Entwicklung der Plazenta und sind gleichzeitig ein gutes Modellsystem um die Implantation des Embryos im Uterus näher zu untersuchen. Zellen des primitive Entoderms (PrE) beeinflussen das im Dottersack vorhandene extraembryonale Entoderm, welches dort als “frühe Plazenta” fungiert und für die Versorgung des Embryos mit Nährstoffen zuständig ist (Cross et al., 1994). Des Weiteren besitzt das Entoderm einen induktiven Einfluss auf die Bildung von anterioren Strukturen und die Bildung von Endothelzellen sowie Blutinseln (Byrd et al., 2002).
Extraembryonale Endodermstammzellen (XEN Zellen) können aus Blastozysten gewonnen und in embryonale Stammzellen (ES-Zellen) umgewandelt werden (Fujikura et al., 2002; Kunath et al., 2005). Es war jedoch nicht bekannt, ob XEN-Zellen auch aus Postimplantations-Embryonen gewonnen werden können. XEN-Zellen tragen in vivo zur Entwicklung des Darmendoderms bei (Kwon et al., 2008; Viotti et al., 2014) und könnten als alternative, selbsterneuernde Quelle für extraembryonale Endoderm-abgeleitete Zellen dienen, die zur Herstellung von Geweben für die regenerative Medizin verwendet werden könnten (Niakan et al., 2013).
In der Embryogenese der Maus zeigt sich an Tag E3.0 eine kompakte Morula die sich allmählich in das Trophektoderm (TE) differenziert, welches wiederum den Embryonalknoten (“innere Zellmasse”) umschließt (Johnson and Ziomek, 1981). Ein wichtiger Schritt im Rahmen der Entwicklung findet an Tag E3.5 statt, in diesem Zeitraum gehen aus dem Embryonalknoten der pluripotente Epiblast und das primitive Entoderm hervor. Im späten Blastozystenstadium an Tag E4.5 liegt das PrE als Zellschicht entlang der Oberfläche der Blastocoel-Höhle. Aus dem Epiblast entwickeln sich im weiteren Verlauf der Embryo, das Amnion und das extraembryonale Mesoderm des Dottersacks. Die Zellen des Trophektoderm führen zur Entwicklung der Plazenta. Das PrE differenziert sich im Zuge der Weiterentwicklung in das viszerale Entoderm (VE) und das parietale Entoderm (PE) des Dottersacks (Chazaud et al., 2006; Gardner and Rossant, 1979; Plusa et al., 2008). VE umgibt den Epiblast und extraembryonisches Ektoderm (ExE). PE-Zellen wandern entlang der inneren Oberfläche von TE und sezernieren zusammen mit Trophoblasten-Riesenzellen Basalmembranproteine, um die Reichert-Membran zu bilden (Hogan et al., 1980). Die Reichert-Membran besteht aus Basalmembranproteinen, einschließlich Kollagenen und Lamininen, die zwischen den parietalen Endoderm- und Trophoblastzellen liegen. Diese Membran wirkt als ein Filter, der dem Embryo den Zugang zu Nährstoffen ermöglicht, während er eine Barriere zu den Zellen der Mutter bildet (Gardner, 1983).
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Abs, Elisabeth ; Poorthuis, Rogier B. ; Apelblat, Daniella ; Muhammad, Karzan ; Pardi, M. Belen ; Enke, Leona ; Kushinsky, Dahlia ; Pu, De-Lin ; Eizinger, Max Ferdinand ; Conzelmann, Karl-Klaus ; Spiegel, Ivo ; Letzkus, Johannes J.
A wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha (PDGFRA) is thought to be essential for the derivation and maintenance of mouse XEN cell lines. Here, we have re-evaluated this requirement for PDGFRA. We derived multiple PDGFRA-deficient XEN cell lines from postimplantation and preimplantation embryos of a PDGFRA-GFP knockout strain. We also converted PDGFRA-deficient embryonic stem cell lines into XEN cell lines chemically by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of our 12 PDGFRA-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, PDGFRA is not essential for the derivation and maintenance of XEN cell lines.
Averdunk, Luisa ; Bernhagen, Jürgen ; Fehnle, Karl ; Surowy, Harald ; Lüdecke, Hermann-Josef ; Mucha, Sören ; Meybohm, Patrick ; Wieczorek, Dagmar ; Leng, Lin ; Marx, Gernot ; Leaf, David E. ; Zarbock, Alexander ; Zacharowski, Kai ; Bucala, Richard ; Stoppe, Christian
Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Adiwijaya, Bambang S. ; Herrmann, Eva ; Hare, Brian ; Kieffer, Tara ; Lin, Chao ; Kwong, Ann D. ; Garg, Varun ; Randle, John C. R. ; Sarrazin, Christoph ; Zeuzem, Stefan ; Caron, Paul R.
Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space. Fitness was represented in the absence of telaprevir by different variant production rate constants and in the presence of telaprevir by additional antiviral blockage by telaprevir. Model parameters, including rate constants for viral production, clearance, and effective telaprevir concentration, were estimated from 1) plasma HCV RNA levels of subjects before, during, and after dosing, 2) post-dosing prevalence of plasma variants from subjects, and 3) sensitivity of variants to telaprevir in the HCV replicon. The model provided a good fit to plasma HCV RNA levels observed both during and after telaprevir dosing, as well as to variant prevalence observed after telaprevir dosing. After an initial sharp decline in HCV RNA levels during dosing with telaprevir, HCV RNA levels increased in some subjects. The model predicted this increase to be caused by pre-existing variants with sufficient fitness to expand once available replication space increased due to rapid clearance of wild-type (WT) virus. The average replicative fitness estimates in the absence of telaprevir ranged from 1% to 68% of WT fitness. Compared to the relative fitness method, the in vivo estimates from the viral dynamic model corresponded more closely to in vitro replicon data, as well as to qualitative behaviors observed in both on-dosing and long-term post-dosing clinical data. The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
Benoit, Joshua B. ; Adelman, Zach N. ; Reinhardt, Klaus ; Dolan, Amanda ; Poelchau, Monica ; Jennings, Emily C. ; Szuter, Elise M. ; Hagan, Richard W. ; Gujar, Hemant ; Shukla, Jayendra Nath ; Zhu, Fang ; Mohan, Muthugounder ; Nelson, David R. ; Rosendale, Andrew J. ; Derst, Christian ; Resnik, Valentina ; Wernig, Sebastian ; Menegazzi, Pamela ; Wegener, Christian ; Peschel, Nicolai ; Hendershot, Jacob M. ; Blenau, Wolfgang ; Predel, Reinhard ; Johnston, Paul R. ; Ioannidis, Panagiotis ; Waterhouse, Robert M. ; Nauen, Ralf ; Schorn, Corinna ; Ott, Mark-Christoph ; Maiwald, Frank ; Johnston, J. Spencer ; Gondhalekar, Ameya D. ; Scharf, Michael E. ; Peterson, Brittany F. ; Raje, Kapil R. ; Hottel, Benjamin A. ; Armisén, David ; Crumière, Antonin Jean Johan ; Refki, Peter Nagui ; Santos, Maria Emilia ; Sghaier, Essia ; Viala, Séverine ; Khila, Abderrahman ; Ahn, Seung-Joon ; Childers, Christopher ; Lee, Chien-Yueh ; Lin, Han ; Hughes, Daniel S. T. ; Duncan, Elizabeth J. ; Murali, Shwetha C. ; Qu, Jiaxin ; Dugan, Shannon ; Lee, Sandra L. ; Chao, Hsu ; Dinh, Huyen ; Han, Yi ; Doddapaneni, Harshavardhan ; Worley, Kim C. ; Muzny, Donna Marie ; Wheeler, David ; Panfilio, Kristen A. ; Vargas Jentzsch, Iris M. ; Vargo, Edward L. ; Booth, Warren ; Friedrich, Markus ; Weirauch, Matthew T. ; Anderson, Michelle A. ; Jones, Jeffery W. ; Mittapalli, Omprakash ; Zhao, Chaoyang ; Zhou, Jing-Jiang ; Evans, Jay D. ; Attardo, Geoffrey M. ; Robertson, Hugh M. ; Zdobnov, Evgeny M. ; Ribeiro, José M. C. ; Gibbs, Richard A. ; Werren, John H. ; Palli, Subba Reddy ; Schal, Coby ; Richards, Stephen
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Periplasmic Sud protein encoded by the Wolinella succinogenes catalyses the transfer of bound polysulfide-sulfur to the active site of the membrane bound polysulfide reductase. The homodimeric protein consists of 131 residues per monomer, each with one cysteine residue in the active site. Polysulfide-sulfur is covalently bound to the catalytic Cys residues of the Sud protein. In order to understand the structure-function relationship of this protein, the features of its solution structure determined by heteronuclear multidimensional NMR techniques are reported here. The first step of structure determination leads to resonance assignments using 15N/13C/2H- and 15N/13C-labeled protein. The sequential backbone and side chain resonance assignments have been successfully completed. Structure calculations were carried out using the ARIA program package. The structure is based on 2688 NOE-derived distance restraints, 68 backbone hydrogen bond restraints derived from 34 slow-exchanging backbone amide protons and 334 torsion angle restraints obtained from the TALOS program as well as 158 residual dipolar coupling restraints for the refinement of relative vector orientations. The three-dimensional structure of the Sud protein was determined with an averaged rootmean- square deviation of 0.72 Å and 1.28 Å for the backbone and heavy atoms, respectively, excluding the terminal residues. Without the poorly defined segment between residues 90-94 the average r.m.s.d. value drops down to 0.6 Å and 1.14 Å. The ensemble refined with residual dipolar coupling (rdc) restraints shows good convergence. The r.m.s.d. value for the backbone heavy atoms, excluding residues 90- 94, drops down from 0.97 to 0.66 for the rdc-refined ensemble. The relative orientation of the two monomers in the protein structures refined with residual dipolar coupling restraints are also different from those without residual dipolar coupling restraints. The structure determination of the dimeric protein has been hampered by the high molecular mass (30 kDa), severe peak degeneracy, and by the small number of experimental intermonomer NOEs (relative orientation problem of two monomers). For the resonance assignments of aliphatic side chain, many resonances were ambiguously assigned because of severe overlap of signals. The Sud dimer protein contains 17 Lys, 14 Leu and one His tag for each monomer. It complicated the resonance assignments. The conventional 3D 15N-separated TOCSY HSQC experiment failed because of the large molecular weight which results in line broadening and hence made the resonance assignments of side chains more difficult. The determined structure contains a five-stranded parallel ß-sheet enclosing a hydrophobic core, a two-stranded anti-parallel ß-sheet and seven a-helices. The dimer structure is stabilized predominantly by hydrophobic residues. Sud catalyses the transfer of the polysulfide-sulfur to cyanide, similar to rhodanese encoded by Azotobacter vinelandii (Bordo et al., 2000). The two proteins are similar in the active site environment primarily owing to the main-chain conformation of the active-site loop with the cysteine residue and with respect to the surrounding positively charged residues. The active-site loop (residues 89-95) in the Sud protein appears to be flexible, reflected by few assigned proton resonances of residues 90-94 in the active site. Despite their similarity in function and their similar structure in active site, the amino acid sequences and the folds of the two proteins are remarkably different. The negatively charged polysulfide interacts with positively charged R46, R67, and R94 and hence may be stabilized in structure. The mutation of one of the three arginines that are also conserved in rhodanese from A. vinelandii leads to a loss of sulfur-transfer activity. The polysulfide chain extends from inside of Sud protein to outside, where Sud may form contacts with polysulfide reductase. These contacts provide the possible polysulfide-sulfur transfer from Sud protein to the active site of polysulfide reductase.
Background Although current molecular clock methods offer greater flexibility in modelling historical evolutionary events, calibration of the clock with dates from the fossil record is still problematic for many groups. Here we implement several new approaches in molecular dating to estimate evolutionary ages of Lacertidae, an Old World family of lizards with a poor fossil record and uncertain phylogeny. Four different models of rate variation are tested in a new program for Bayesian phylogenetic analysis called TreeTime, based on a combination of mitochondrial and nuclear gene sequences. We incorporate paleontological uncertainty into divergence estimates by expressing multiple calibration dates as a range of probabilistic distributions. We also test the reliability of our proposed calibrations by exploring effects of individual priors on posterior estimates. Results According to the most reliable model, as indicated by Bayes factor comparison, modern lacertids arose shortly after the K/T transition and entered Africa about 45 million years ago, with the majority of their African radiation occurring in the Eocene and Oligocene. Our findings indicate much earlier origins for these clades than previously reported, and we discuss our results in light of paleogeographic trends during the Cenozoic. Conclusions This study represents the first attempt to estimate evolutionary ages of a specific group of reptiles exhibiting uncertain phylogenetic relationships, molecular rate variation and a poor fossil record. Our results emphasize the sensitivity of molecular divergence dates to fossil calibrations, and support the use of combined molecular data sets and multiple, well-spaced dates from the fossil record as minimum node constraints. The bioinformatics program used here, TreeTime, is publicly available, and we recommend its use for molecular dating of taxa faced with similar challenges.
Hart, Thomas ; Nguyen, Ngoc Thien Thu ; Nowak, Nancy A. ; Zhang, Fuming ; Linhardt, Robert J. ; Diuk-Wasser, Maria A. ; Ram, Sanjay ; Kraiczy, Peter ; Lin, Yi-Pin
Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.
Ovseiko, Pavel V. ; Greenhalgh, Trisha ; Adam, Paula ; Grant, Jonathan ; Hinrichs-Krapels, Saba ; Graham, Kathryn E. ; Valentine, Pamela A. ; Sued, Omar ; Boukhris, Omar F. ; Al Olaqi, Nada M. ; Al Rahbi, Idrees S. ; Dowd, Anne-Maree ; Bice, Sara ; Heiden, Tamika L. ; Fischer, Michael D. ; Dopson, Sue ; Norton, Robyn ; Pollitt, Alexandra ; Wooding, Steven ; Balling, Gert V. ; Jakobsen, Ulla ; Kuhlmann, Ellen ; Klinge, Ineke ; Pololi, Linda H. ; Jagsi, Reshma ; Lawton Smith, Helen ; Etzkowitz, Henry ; Nielsen, Mathias W. ; Carrion, Carme ; Solans‐Domènech, Maite ; Vizcaino, Esther ; Naing, Lin ; Cheok, Quentin H. N. ; Eckelmann, Baerbel ; Simuyemba, Moses C. ; Msiska, Temwa ; Declich, Giovanna ; Edmunds, Laurel D. ; Kiparoglou, Vasiliki ; Buchan, Alison M. J. ; Williamson, Catherine ; Lord, Graham M. ; Channon, Keith M. ; Surender, Rebecca ; Buchan, Alastair M.
Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia and Europe – argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.
Bayessche Methoden zur Schätzung von Stammbäumen mit Verzweigungszeitpunkten aus molekularen Daten
(2009)
Ein großes Ziel der Evolutionsbiologie ist es, die Stammesgeschichte der Arten zu rekonstruieren. Historisch verwendeten Systematiker hierfür morphologische und anatomische Merkmale. Mit dem stetigen Zuwachs an verfügbaren Sequenzdaten werden heute verstärkt Methoden entwickelt und eingesetzt, welche die Rekonstruktion auf Basis von molekularen Daten ermöglichen. Im Fokus der aktuellen Forschung steht die Anwendung und Weiterentwicklung Bayesscher Methoden. Diese Methoden besitzen große Popularität, da sie in Verbindung mit Markov-Ketten-Monte-Carlo-Verfahren eingesetzt werden können, um einen Stammbaum zu vorgegebenen Spezies zu schätzen und dessen Variabilität zu bestimmen. Im Rahmen dieser Dissertation wurde die erweiterbare Software TreeTime entwickelt. TreeTime bietet Schnittstellen für die Einbindung von molekularen Evolutions- und Ratenänderungsmodellen und stellt neu entwickelte Methoden bereit, um Stammbäume mit Verzweigungszeitpunkten zu rekonstruieren. In TreeTime werden die molekularen Daten und die zeitlichen Informationen, wie z.B. Fossilfunde, in einem Bayes-Verfahren simultan berücksichtigt, um die Zeitpunkte der Artaufspaltungen genauer zu datieren. Für die Anwendung Bayesscher Methoden in der Rekonstruktion von Stammbäumen wird ein stochastisches Modell benötigt, das die Evolution der molekularen Sequenzen entlang den Kanten eines Stammbaums beschreibt. Der Mutationsprozess der Sequenzen wird durch ein molekulares Evolutionsmodell definiert. Die Verwendung der klassischen molekularen Evolutionsmodelle impliziert die Annahme einer konstanten Evolutionsgeschwindigkeit der Sequenzen im Stammbaum. Diese Annahme wird als Hypothese der molekularen Uhr bezeichnet und bildet die Grundlage zum Schätzen der Verzweigungszeiten des Stammbaums. Der Verzweigungszeitpunkt, an dem sich zwei Spezies im Stammbaum aufspalten, spiegelt sich in der Ähnlichkeit der zugehörigen molekularen Sequenzen. Je älter dieser Verzweigungszeitpunkt ist, desto größer ist die Anzahl der unterschiedlichen Positionen in den Sequenzen. Häufig ist jedoch die Annahme der molekularen Uhr verletzt, so dass in gewissen Teilbereichen eines Stammbaums eine erhöhte Evolutionsgeschwindigkeit nachweisbar ist. Falls die Verletzung konstanter Evolutionsgeschwindigkeiten nicht ausgeschlossen werden kann, sollten schwankende Mutationsraten in der Modellierung explizit berücksichtigt werden. Hierfür wurden verschiedene Ratenänderungsmodelle vorgeschlagen. Bisher sind nur wenige dieser Ratenänderungsmodelle in Softwarepaketen verfügbar und ihre Eigenschaften sind nicht ausreichend erforscht. Das Ziel dieser Arbeit ist die Entwicklung und Bereitstellung von Bayesschen Modellen und Methoden zum Schätzen von Stammbäumen mit Verzweigungszeitpunkten. Die Methoden sollten auch bei unterschiedlichen Evolutionsgeschwindigkeiten im Stammbaum anwendbar sein. Vorgestellt wird ein neues Ratenänderungsmodell, eine neue Möglichkeit der Angabe von flexiblen Beschränkungen für die Topologie des Stammbaums sowie die Nutzung dieser Beschränkungen für die zeitliche Kalibrierung. Das neue Raten Änderungsmodell sowie die topologischen und zeitlichen Beschränkungen werden in einen modularen Softwareentwurf eingebettet. Durch den erweiterbaren Entwurf können bestehende und zukünftige molekulare Evolutionsmodelle und Ratenänderungsmodelle in die Software eingebunden und verwendet werden. Die vorgestellten Modelle und Methoden werden gemäß dem Softwareentwurf in das neu entwickelte Programm TreeTime aufgenommen und effzient implementiert. Zusätzlich werden bereits vorhandene Modelle programmiert und eingebunden, die nicht in anderen Softwarepaketen verfügbar sind. Des Weiteren wird eine neue Methode entwickelt und angewendet, um die Passgenauigkeit eines Modells für die Apriori-Verteilung auf der Menge der Baumtopologien zu beurteilen. Diese Methode wird zur Auswahl geeigneter Modelle benutzt, indem eine Auswertung der beobachteten Baumtopologien der Datenbank TreeBASE durchgeführt wird. Anschließend wird die Software TreeTime in einer Simulationsstudie eingesetzt, um die Eigenschaften der implementierten Ratenänderungsmodelle zu vergleichen. Die Software wird für die Rekonstruktion des Stammbaums zu 38 Spezies aus der Familie der Eidechsen (Lacertidae) verwendet. Da die zugehörigen molekularen Daten von der Hypothese der molekularen Uhr abweichen, werden unterschiedliche Ratenänderungsmodelle bei der Rekonstruktion verwendet und abschließend bewertet. ........
Flamm, Steven ; Reddy, K. Rajender ; Zadeikis, Neddie ; Hassanein, Tarek ; Bacon, Bruce R. ; Maieron, Andreas ; Zeuzem, Stefan ; Bourliere, Marc ; Calleja, Jose L. ; Kosloski, Matthew P. ; Oberoi, Rajneet K. ; Lin, Chih-Wei ; Yu, Yao ; Lovell, Sandra ; Semizarov, Dimitri ; Mensa, Federico J.
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
Ariyawansa, Hiran A. ; Tsai, Ichen ; Wang, Jian-Yuan ; Withee, Patchareeya ; Tanjira, Medsaii ; Lin, Shiou-Ruei ; Suwannarach, Nakarin ; Kumla, Jaturong ; Elgorban, Abdallah M. ; Cheewangkoon, Ratchadawan
Camellia sinensis is one of the major crops grown in Taiwan and has been widely cultivated around the island. Tea leaves are prone to various fungal infections, and leaf spot is considered one of the major diseases in Taiwan tea fields. As part of a survey on fungal species causing leaf spots on tea leaves in Taiwan, 19 fungal strains morphologically similar to the genus Diaporthe were collected. ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α), tub2 (beta-tubulin), and cal (calmodulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. In total, six Diaporthe species, including one new species, Diaporthe hsinchuensis, were identified as linked with leaf spot of C. sinensis in Taiwan based on both phenotypic characters and phylogeny. These species were further characterized in terms of their pathogenicity, temperature, and pH requirements under laboratory conditions. Diaporthe tulliensis, D. passiflorae, and D. perseae were isolated from C. sinensis for the first time. Furthermore, pathogenicity tests revealed that, with wound inoculation, only D. hongkongensis was pathogenic on tea leaves. This investigation delivers the first assessment of Diaporthe taxa related to leaf spots on tea in Taiwan.
Hart, Thomas M. ; Dupuis, Alan P. II ; Tufts, Danielle M. ; Blom, Anna M. ; Starkey, Simon R. ; Rego, Ryan O. M. ; Ram, Sanjay ; Kraiczy, Peter ; Kramer, Laura D. ; Diuk-Wasser, Maria A. ; Kolokotronis, Sergios-Orestis ; Lin, Yi-Pin
Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Yu, Wei ; Ma, Xueyan ; Xu, Jinjin ; Heumüller, Andreas ; Fei, Zhaoliang ; Feng, Xue ; Wang, Xiaodong ; Liu, Kuo ; Li, Jinhui ; Cui, Guizhong ; Peng, Guangdun ; Ji, Hongbin ; Li, Jinsong ; Jing, Naihe ; Song, Hai ; Lin, Zhiqiang ; Zhao, Yun ; Wang, Zuoyun ; Zhou, Bin ; Zhang, Lei
Heart valve disease is a major clinical problem worldwide. Cardiac valve development and homeostasis need to be precisely controlled. Hippo signaling is essential for organ development and tissue homeostasis, while its role in valve formation and morphology maintenance remains unknown. VGLL4 is a transcription cofactor in vertebrates and we found it was mainly expressed in valve interstitial cells at the post-EMT stage and was maintained till the adult stage. Tissue specific knockout of VGLL4 in different cell lineages revealed that only loss of VGLL4 in endothelial cell lineage led to valve malformation with expanded expression of YAP targets. We further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained. These findings suggest that VGLL4 is important for valve development and manipulation of Hippo components would be a potential therapy for preventing the progression of congenital valve disease.
Seiro, Silvia ; Jiao, Lin ; Kirchner, Stefan ; Hartmann, Stefanie ; Friedemann, Sven ; Krellner, Cornelius ; Geibel, Christoph ; Si, Qimiao ; Steglich, Frank ; Wirth, Steffen
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
Efficient derivation of extraembryonic endoderm stem cell lines from mouse postimplantation embryos
(2016)
Various types of stem cell lines have been derived from preimplantation or postimplantation mouse embryos: embryonic stem cell lines, epiblast stem cell lines, and trophoblast stem cell lines. It is not known if extraembryonic endoderm stem (XEN) cell lines can be derived from postimplantation mouse embryos. Here, we report the derivation of 77 XEN cell lines from 85 postimplantation embryos at embryonic day E5.5 or E6.5, in parallel to the derivation of 41 XEN lines from 69 preimplantation embryos at the blastocyst stage. We attain a success rate of 100% of XEN cell line derivation with our E5.5 whole-embryo and E6.5 disaggregated-embryo methods. Immunofluorescence and NanoString gene expression analyses indicate that the XEN cell lines that we derived from postimplantation embryos (post-XEN) are very similar to the XEN cell lines that we derived from preimplantation embryos (pre-XEN) using a conventional method. After injection into blastocysts, post-XEN cells contribute to extraembryonic endoderm in chimeras at E6.5 and E7.5.
Marcinkiewicz, Ashley L. ; Lieknina, Ilva ; Kotelovica, Svetlana ; Yang, Xiuli ; Kraiczy, Peter ; Pal, Utpal ; Lin, Yi-Pin ; Tars, Kaspars
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Frantz, Laurent A. F. ; Haile, James ; Lin, Audrey T. ; Scheu, Amelie ; Geörg, Christina ; Benecke, Norbert ; Alexander, Michelle ; Linderholm, Anna ; Mullin, Victoria E. ; Daly, Kevin G. ; Battista, Vincent M. ; Price, Max ; Gron, Kurt J. ; Alexandri, Panoraia ; Arbogast, Rose-Marie ; Arbuckle, Benjamin ; Bălăşescu, Adrian ; Barnett, Ross ; Bartosiewicz, László ; Baryshnikov, Gennady ; Bonsall, Clive ; Borić, Dušan ; Boroneanţ, Adina ; Bulatović, Jelena ; Çakırlar, Canan ; Carretero, José-Miguel ; Chapman, John ; Church, Mike ; Crooijmans, Richard ; DeCupere, Bea ; Detry, Cleia ; Dimitrijević, Vesna ; Dumitraşcu, Valentin ; Du Plessis, Louis ; Edwards, Ceiridwen ; Erek, Cevdet Merih ; Erim Özdoğan, Aslı ; Ervynck, Anton ; Fulgione, Domenico ; Gligor, Mihai ; Götherström, Anders ; Gourichon, Lionel ; Groenen, Martien A. M. ; Helmer, Daniel ; Hongo, Hitomi ; Horwitz, Liora Kolska ; Irving-Pease, Evan K. ; Lebrasseur, Ophélie ; Lesur, Joséphine ; Malone, Caroline ; Manaserya, Ninna ; Marciniak, Arkadiusz ; Martlew, Holley ; Mashkour, Marjan ; Matthews, Roger ; Motuzaitė Matuzevičiūtė, Giedrė ; Maziar, Sepideh ; Meijaard, Erik ; McGovern, Tom ; Megens, Hendrik-Jan ; Miller, Rebecca ; Mohaseb, Azadeh Fatemeh ; Orschiedt, Jörg ; Orton, David ; Papathanasiou, Anastasia ; Parker Pearson, Michael ; Pinhasi, Ron ; Radmanović, Darko ; Ricaut, François-Xavier ; Richards, Mike ; Sabin, Richard ; Sarti, Lucia ; Schier, Wolfram ; Sheikhi, Shiva ; Stephan, Elisabeth ; Stewart, John R. ; Stoddart, Simon ; Tagliacozzo, Antonio ; Tasić, Nenad N. ; Trantalidou, Katerina ; Tresset, Anne ; Valdiosera, Cristina ; Hurk, Youri van den ; Poucke, Sophie van ; Vigne, Jean-Denis ; Yanevich, Alexander ; Zeeb-Lanz, Andrea ; Triantafyllidis, Alexandros ; Gilbert, M. Thomas P. ; Schibler, Jörg ; Rowley-Conwy, Peter ; Zeder, Melinda ; Peters, Joris ; Cucchi, Thomas ; Bradley, Daniel G. ; Dobney, Keith ; Burger, Joachim ; Evin, Allowen ; Girdland-Flink, Linus ; Larson, Greger
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Zhang, Chao ; Lin, Yuan ; Han, Zhihua ; Gao, Liang ; Guo, Ruipeng ; Shi, Qinglei ; Chen, Lei ; Chen, Chun
Background. Intervertebral disc degeneration (IDD) at the cervicothoracic junction of spine is clinically relevant, however, little attention had been paid. T2 mapping and magnetic transfer ratio (MTR) are useful magnetic resonance imaging (MRI) techniques to quantitatively evaluate IDD, revealing the biochemical changes within the intervertebral disc. To compare T2 mapping with MTR imaging regarding their accuracy to quantitatively diagnose intervertebral disc degeneration at the cervicothoracic junction, influences of anatomical level, gender, age, and Pfrrmann grade of T2 relaxation time values and MTR values were evaluated.
Methods. Sixty-seven patients with neck and upper back pain were included and examined with both T2 mapping andMTR imaging. Te Pfrrmann grade, T2 relaxation time values, and MTR value of each disc between C7 and T3 were measured. Diferences were investigated among diferent segmental levels, genders, age ranges, and Pfrrmann grades. Te diagnostic accuracy of both MRI techniques was compared using the receiver operating characteristic (ROC) curves.
Results. No signifcant diference was detected comparing T2 relaxation time values or MTR values among diferent anatomical levels, genders, and segmental levels. And we generally found that T2 relaxation time values decreased, while MTR value increased with increasing age. Importantly, we demonstrated the signifcant correlation between either T2 relaxation time values or MTR value and Pfrrmann grade.
Conclusion. We proved the better accuracy of T2 mapping over MTR imaging to quantitatively evaluate the intervertebral disc degeneration of the cervicothoracic junction.
Hofmann, Stefan G. ; Petrocchi, Nicola ; Steinberg, James ; Lin, Muyu ; Arimitsu, Kohki ; Kind, Shelley ; Mendes, Adriana ; Stangier, Ulrich
Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10), and one in Frankfurt, Germany (n = 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90), negative affect (d = 1.98 and 0.92), and positive affect (d = 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.
Background: While the efficacy of cognitive therapy (CT) has been well established for social anxiety disorder (SAD) in several randomized controlled trials, there are still large differences between trials with respect to effect sizes. The present study investigates the question of whether enhanced training and the use of behavioral experiments (BEs) increases the efficacy of traditional CT, based on verbal methods of cognitive restructuring. Methods/design: A mixed within/between conditions design will be applied, with therapists and patients being randomly allocated to one of two conditions: (1) training of CT plus BEs, (2) training of CT “as usual”. Sixty patients with the primary diagnosis of SAD will be recruited and treated in the outpatient clinic of the Department of Psychology, University of Frankfurt. To ensure adherence to therapist protocols, all therapists will be trained and supervised by the project coordinators. In addition, videotaped treatment sessions will be independently evaluated to guarantee both adherence to protocols and the quality of the intervention. Treatment effects will be assessed by independent SAD symptom ratings using the Liebowitz Social Anxiety Scale as the primary outcome measure and self-report measures as secondary outcome measures. Discussion: The present cognitive behavioral therapy (CBT) trial will be the first to clarify the contribution of BEs to the efficacy of CT in a randomized controlled design. Study results are relevant to clinical training and implementation of evidence-based treatments. Trial registration: German Clinical Trials Register International Clinical Trials Registry Platform (ICTRP) identifier: DRKS00014349. Trial status: recruiting.
The planthopper genus Arcofaciella Fennah, 1956 (Hemiptera: Fulgoromorpha: Delphacidae) is reviewed. Four species are recognized, of which A. obflexa Guo & Liang, 2005 and A. verrucosa Fennah, 1956 are redescribed, and one new species, A. indiana sp. nov., is described. Habitus photos for adults and illustrations of male genitalia (excluding A. penangensis (Muir, 1919)) are given. A key for identifying the species of Arcofaciella is also provided.
The planthopper genus Augilina Melichar, 1914, is recorded in China for the first time. Two new species of the genus Augilina, A. tetraina Chen & Gong sp. nov. and A. triaina Chen & Gong sp. nov., are described and illustrated from South China. The genus now has a total of four described species. New generic characteristics are proposed and photographs of the new species are provided. A checklist and a key to the species of Augilina are also included.
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14–Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14–Cys38 disulfide bond.
Three new species of the bamboo-feeding genus Bambusiphaga Huang & Ding, 1979, B. parvula sp. nov., B. angulosa sp. nov., and B. nigrigena sp. nov., are described and illustrated from China. A key to species of the genus is provided. Habitus photos for adults and illustrations of male genitalia are also given.
Ackermann, K. H. ; Adams, N. ; Adler, Clemens ; Ahammed, Zubayer ; Ahmad, Shakeel ; Allgower, Chris ; Amsbaugh, J. ; Anderson, Mike ; Anderssen, E. ; Arnesen, H. ; Arnold, L. ; Averichev, Georgy S. ; Baldwin, A. ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Beddo, M. ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Bennett, Samuel ; Bercovitz, J. ; Berger, Jens ; Betts, W. ; Bichsel, Hans ; Bieser, F. ; Bland, Leslie C. ; Bloomer, Matthew A. ; Blyth, Charles O. ; Boehm, J. ; Bonner, Billy E. ; Bonnet, D. ; Bossingham, R. ; Botlo, M. ; Boucham, Abdelkrim ; Bouillo, N. ; Bouvier, S. ; Bradley, K. ; Brady, Franklin Paul ; Braithwaite, E. S. ; Braithwaite, Wilfred J. ; Brandin, Andrei V. ; Brown, R. L. ; Brugalette, G. ; Byrd, C. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Cardenas, Andrés ; Carr, Lincoln D. ; Carroll, J. ; Castillo Castellanos, Javier Ernesto ; Caylor, B. ; Cebra, Daniel A. ; Chatopadhyay, S. ; Chen, M. L. ; Chen, W. ; Chen, Y. ; Chernenko, Sergey P. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Choi, B. ; Chrin, J. ; Christie, William ; Coffin, Jean Pierre ; Conin, L. ; Consiglio, C. ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; Danilov, V. I. ; Dayton, D. ; DeMello, M. ; Deng, W. S. ; Derevschikov, Anatoly A. ; Dialinas, M. ; Diaz, H. ; DeYoung, P. A. ; Didenko, Lidia ; Dimassimo, D. ; Dioguardi, J. ; Dominik, W. ; Drancourt, C. ; Draper, James E. ; Dunin, V. B. ; Dunlop, James C. ; Eckardt, Volker ; Edwards, W. R. ; Efimov, Leonid G. ; Eggert, T. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Etkin, A. ; Fachini, Patricia ; Feliciano, C. ; Ferenc, D. ; Ferguson, M. I. ; Fessler, H. ; Finch, Evan ; Fine, Valeri ; Fisyak, Yuri V. ; Flierl, Dominik Bernhard ; Flores, I. ; Foley, Kenneth John ; Fritz, D. ; Gagunashvili, N. ; Gans, J. ; Gaździcki, Marek ; Germain, Marie ; Geurts, Frank ; Ghazikhanian, Vahe ; Gojak, C. ; Grabski, J. ; Grachov, Oleg A. ; Grau, M. ; Greiner, D. ; Greiner, Leo Clifford ; Grigoriev, Vladislav A. ; Grosnick, David P. ; Gross, J. ; Guilloux, G. ; Gushin, E. ; Hall, J. ; Hallman, Timothy J. ; Hardtke, David H. ; Harper, G. ; Harris, John W. ; He, P. ; Heffner, M. ; Heppelmann, S. ; Herston, T. ; Hill, D. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, Gerald W. ; Horsley, M. ; Howe, Mark A. ; Huang, Huan Zhong ; Humanic, Thomas J. ; Hümmler, H. ; Hunt, W. ; Hunter, J. ; Igo, George J. ; Ishihara, A. ; Ivanshin, Yu. I. ; Jacobs, P. ; Jacobs, William W. ; Jacobson, S. ; Jared, R. ; Jensen, P. ; Johnson, I. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kaneta, Kaneta ; Kaplan, Morton ; Keane, Declan ; Kenney, V. P. ; Khodinov, A. ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Klyachko, A. ; Koehler, G. ; Konstantinov, A. S. ; Kormilitsyne, V. ; Kotchenda, L. ; Kotov, I. ; Kovalenko, A. D. ; Kramer, M. ; Kravtsov, Peter ; Krueger, Keith William ; Krupien, T. ; Kuczewski, P. ; Kuhn, Christian Claude ; Kunde, Gerd J. ; Kunz, Christopher Lee ; Kutuev, R. Kh. ; Kuznetsov, A. A. ; Lakehal-Ayat, L. ; Lamas-Valverde, Jose ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, S. ; Lansdell, Curtis Patrick Leon ; Lasiuk, Brian ; Laue, Frank ; Lebedev, Alexei ; LeCompte, T. ; Leonhardt, W. J. ; Leontiev, V. M. ; Leszczynski, P. ; LeVine, Micheal J. ; Li, Q. ; Li, Q. ; Li, Z. ; Liaw, C.-J. ; Lin, J. ; Lindenbaum, Sam J. ; Lindenstruth, Volker ; Lindstrom, P. J. ; Lisa, Michael A. ; Liu, H. ; Ljubicic, Tonko A. ; Llope, William Joseph ; LoCurto, G. ; Long, H. ; Longacre, Ronald S. ; Lopez-Noriega, M. ; Lopiano, D. ; Love, William A. ; Lutz, J. R. ; Lynn, David ; Madansky, L. ; Maier, R. ; Majka, Richard Daniel ; Maliszewski, A. ; Margetis, Spyridon ; Marks, K. ; Marstaller, R. ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; Matyushevski, E. A. ; McParland, C. ; McShane, Tom S. ; Meier, J. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Middlekamp, P. ; Mikhalin, N. ; Miller, B. ; Milosevich, Z. ; Minaev, Nikolai G. ; Minor, B. ; Mitchell, J. ; Mogavero, E. ; Moiseenko, V. A. ; Moltz, D. ; Moore, C. F. ; Morozov, V. ; Morse, R. ; de Moura, M. M. ; Munhoz, Marcelo Gameiro ; Mutchler, G. S. ; Nelson, John M. ; Nevski, P. ; Ngo, T. ; Nguyen, M. ; Nguyen, T. ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Noggle, T. ; Norman, B. ; Nurušev, Sandibek B. ; Nussbaum, T. ; Nystrand, Joakim Ingemar ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Ogilvie, C. A. ; Olchanski, K. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Ososkov, G. A. ; Ott, G. ; Padrazo, D. ; Paic, Guy ; Pandey, S. U. ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, Alexei I. ; Pawlak, Tomasz Jan ; Pentia, M. ; Perevotchikov, V. ; Peryt, Wiktor Stanislaw ; Petrov, V. A ; Pinganaud, W. ; Pirogov, S. ; Platner, E. ; Pluta, Jan Marian ; Polk, I. ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potrebenikova, E. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Puskar-Pasewicz, J. ; Rai, Gulshan ; Rasson, J. ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, J. ; Renfordt, Rainer Arno Ernst ; Retiere, Fabrice ; Ridiger, Alexey ; Riso, J. ; Ritter, Hans Georg ; Roberts, Jabus B. ; Röhrich, Dieter ; Rogachevski, O. V. ; Romero, Juan L. ; Roy, Christelle Sophie ; Russ, D. ; Rykov, Vladimir L. ; Sakrejda, Iwona ; Sanchez, R. ; Sandler, Z. ; Sandweiss, Jack H. ; Sappenfield, P. ; Saulys, A. C. ; Savin, Igor A. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Scheblien, J. ; Scheetz, R. ; Schlueter, R. ; Schmitz, Norbert ; Schroeder, Lee S. ; Schulz, M. ; Schüttauf, Andreas ; Sedlmeir, J. ; Seger, Janet Elizabeth ; Seliverstov, D. ; Seyboth, J. ; Seyboth, Peter ; Seymour, R. ; Shakaliev, E. I. ; Shestermanov, Konstantin E. ; Shi, Y. ; Šimanskij, Stepan S. ; Shuman, D. ; Shvetcov, V. S. ; Skoro, Goran P. ; Smirnov, N. ; Smykov, L. P. ; Snellings, Raimond ; Solberg, K. ; Sowinski, James ; Spinka, Harold. M. ; Srivastava, B. ; Stephenson, Edward J. ; Stock, Reinhard ; Stolpovsky, Alexander ; Stone, N. ; Stone, R. ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Stroebele, H. ; Struck, Christof ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Symons, Timothy James MacNeil ; Takahashi, Jun ; Tang, Aihong ; Tarchini, A. ; Tarzian, J. ; Thomas, James H. ; Tikhomirov, V. ; Toledo, Alejandro Szanto de ; Tonse, S. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tokarev, Mikhail V. ; Tonjes, Marguerite Belt ; Trofimov, V. ; Tsai, Oleg D. ; Turner, K. ; Ullrich, Thomas ; Underwood, David G. ; Vakula, I. ; Van Buren, Gene ; VanderMolen, A. M. ; Vanyashin, A. ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Vigdor, Steven E. ; Visser, G. ; Voloshin, Sergei ; Vu, C. ; Wang, F. ; Ward, H. ; Weerasundara, Dhammika D. ; Weidenbach, R. ; Wells, R. ; Wells, R. ; Wenaus, T. ; Westfall, Gary D. ; Whitfield, J. P. ; Whitten, Charles A. ; Wieman, Howard ; Willson, Robert ; Wilson, K. ; Wirth, Joana ; Wisdom, J. ; Wissink, Scott W. ; Witt, Richard ; Wolf, J. ; Wood, L. ; Xu, N. ; Xu, Z. ; Yakutin, A. E. ; Yamamoto, E. ; Yang, J. ; Yepes, Pablo P. ; Yokosawa, A. ; Yurevich, Vladimir Yurevich ; Zanevski, Y. V. ; Zhang, J. ; Zhang, W. M. ; Zhu, Jianhui ; Zimmerman, D. ; Zoulkarneev, R. ; Zubarev, A. N.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Two new species, Russula pseudopunicea C.L.Hou, G.Q.Cheng & H.Zhou sp. nov. and R. wulingshanensis C.L.Hou, G.Q.Cheng & H.Zhou sp. nov., from Yanshan mountains in North China are described herein based on morphological and phylogenetic analyses of nrITS, and nrLSU-rpb2-mtSSU gene regions. Morphologically, R. pseudopunicea sp. nov. is characterised by a reddish brown, light brown to brownish orange pileus with a greyish yellow margin, subglobose to broadly ellipsoid basidiospores with warts forming a partial reticulum and pleurocystidia turning grey to purplish red in sulfovanillin. Russula wulingshanensis sp. nov. is characterised by a purple pinkish pileus with a grey-white to grey-purple margin, subglobose to broadly ellipsoid basidiospores with isolated warts, and pileocystidia turning black in sulfovanillin. Phylogenetic and morphological analyses resolved the two species in Russula subg. Heterophyllidia. Russula pseudopunicea sp. nov. and R. wulingshanensis sp. nov. were placed in the lineages of subsect. Virescentinae and subsect. Griseinae, respectively.
Nguyen, Ngoc-Thach ; Röttgerding, Florian ; Devraj, Gayatri ; Lin, Yi-Pin ; Koenigs, Arno ; Kraiczy, Peter
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
Hansen, Anne-Louise Smidt ; Buchan, Gregory J. ; Rühl, Michael ; Mukai, Kojiro ; Salvatore, Sonia R. ; Ogawa, Emari ; Andersen, Sidsel ; Iversen, Marie B. ; Thielke, Anne L. ; Gunderstofte, Camilla ; Motwani, Mona ; Møller, Charlotte T. ; Jakobsen, Andreas S. ; Fitzgerald, Katherine A. ; Roos, Jessica ; Lin, Rongtuan ; Maier, Thorsten Jürgen ; Goldbach-Mansky, Raphaela ; Miner, Cathrine A. ; Qian, Wei ; Miner, Jonathan ; Rigby, Rachel ; Rehwinkel, Jan ; Jakobsen, Martin R. ; Arai, Hiroyuki ; Taguchi, Tomohiko ; Schopfer, Francisco J. ; Olagnier, David ; Holm, Christian K.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Wycisk, Agnes Isabella ; Lin, Jiacheng ; Loch, Sandra ; Hobohm, Kathleen ; Funke, Jessica ; Wieneke, Ralph ; Koch, Joachim ; Skach, William R. ; Mayerhofer, Peter Uli ; Tampé, Robert
Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.
Ma, Jialiang ; Xiao, Lin ; Zhang, Ke ; Jiao, Yukun ; Wang, Zhenzhen ; Li, Jinxiao ; Guo, Wenmu ; Gao, Pengpeng ; Qin, Shenjun ; Zhao, Cunliang
This paper provides new geochemical data focusing on valuable elements in the coal, parting, and floor samples in the No. 5 coal seam of the Taiyuan Formation from the Wujiawan mine, Datong coalfield, northern China. The minerals mainly consist of kaolinite, calcite, and pyrite, as well as trace amounts of quartz and illite. The No. 5 coal is enriched in Li, Ga, high field strength elements (HFSEs), and rare earth elements and yttrium (REY) when compared with world hard coals. Of particular interest is the high average concentration of Li (67.66 μg/g), which is around seven times higher than the value for world hard coals. Lithium, Ga, and HFSEs have strong inorganic affinities, whereas REY have organic affinities. The main carrier of Li, Ga, and HFSEs is aluminosilicate minerals, while REY appear to occur with organophosphorus. These HFSEs are enriched, both in the parting and in the adjacent coal samples. This suggests that these elements are likely to leach out during the diagenetic process. The distribution patterns of REY, along with the ratio of Al2O3/TiO2 and the figure of Zr/TiO2 vs. Nb/Y are suggestive of their derivation from felsic parent material. In the northern and eastern part of the Datong coalfield, there are several regions where the Li content is higher than the mineable grade, in particular in the northern Datong coalfield where there is a mine with an Li content of 294.6 μg/g. This is significantly higher than the mineable grade. Therefore, there is a potential for financially viable recovery of Li in these coals of the Datong coalfield.
Bauer, Michael ; Glenn, Tasha ; Achtyes, Eric D. ; Agaoglu, Esen ; Altınbaş, Kürşat ; Andreassen, Ole A. ; Angelopoulos, Elias ; Ardau, Raffaella ; Arrua Vares, Edgar ; Aydin, Memduha ; Ayhan, Yavuz ; Baethge, Christopher Jan ; Bauer, Rita ; Baune, Bernhard T. ; Balaban, Ceylan ; Becerra-Palars, Claudia ; Behere, Aniruddh P. ; Behere, Prakash B. ; Belete, Habte ; Belete, Tilahun ; Belizario, Gabriel Okawa ; Bellivier, Frank ; Belmaker, Robert H. ; Benedetti, Francesco ; Berk, Michael ; Bersudsky, Yuly ; Bicakci, Şule ; Birabwa-Oketcho, Harriet ; Bjella, Thomas D. ; Brady, Conan ; Cabrera, Jorge ; Cappucciati, Marco ; Castro, Angela Marianne Paredes ; Chen, Wei-Ling ; Cheung, Eric Y. Wo ; Chiesa, Silvia ; Crowe, Marie ; Cuomo, Alessandro ; Dallaspezia, Sara ; Del Zompo, Maria ; Desai, Pratikkumar ; Dodd, Seetal ; Donix, Markus ; Etain, Bruno ; Fagiolini, Andrea ; Fellendorf, Frederike Tabea ; Ferensztajn-Rochowiak, Ewa ; Fiedorowicz, Jess G. ; Fountoulakis, Kostas N. ; Frye, Mark A. ; Geoffroy, Pierre A. ; Gonzalez-Pinto, Ana ; Gottlieb, John F. ; Grof, Paul ; Haarman, Bartholomeus C. M. ; Harima, Hirohiko ; Hasse-Sousa, Mathias ; Henry, Chantal ; Høffding, Lone ; Houenou, Josselin ; Imbesi, Massimiliano ; Isometsä, Erkki T. ; Ivkovic, Maja ; Janno, Sven ; Johnsen, Simon ; Kapczinski, Flávio ; Karakatsoulis, Gregory N. ; Kardell, Mathias ; Kessing, Lars Vedel ; Kim, Seong Jae ; König, Barbara ; Kot, Timur L. ; Koval, Michael ; Kunz, Mauricio ; Lafer, Beny ; Landén, Mikael ; Larsen, Erik R. ; Lenger, Melanie ; Lewitzka, Ute ; Licht, Rasmus W. ; Lopez-Jaramillo, Carlos ; MacKenzie, Alan ; Madsen, Helle Østergaard ; Madsen, Simone Alberte Kongstad A. ; Mahadevan, Jayant ; Mahardika, Agustine ; Manchia, Mirko ; Marsh, Wendy ; Martinez-Cengotitabengoa, Monica ; Martiny, Klaus ; Mashima, Yuki ; McLoughlin, Declan M. ; Meesters, Ybe ; Melle, Ingrid ; Meza-Urzúa, Fátima ; Ming, Mok Yee ; Monteith, Scott ; Moorthy, Muthukumaran ; Morken, Gunnar ; Mosca, Enrica ; Mozzhegorov, Anton A. ; Munoz, Rodrigo ; Mythri, Starlin V. ; Nacef, Fethi ; Nadella, Ravi K. ; Nakanotani, Takako ; Nielsen, René Ernst ; O'Donovan, Claire ; Omrani, Adel ; Osher, Yamima ; Ouali, Uta ; Pantovic-Stefanovic, Maja ; Pariwatcharakul, Pornjira ; Petite, Joanne ; Pfennig, Andrea ; Pica Ruiz, Yolanda ; Pilhatsch, Maximilian ; Pinna, Marco ; Pompili, Maurizio ; Porter, Richard ; Quiroz, Danilo ; Rabelo-da-Ponte, Francisco Diego ; Ramesar, Raj ; Rasgon, Natalie ; Ratta-apha, Woraphat ; Ratzenhofer, Michaela ; Redahan, Maria ; Reddy, M. S. ; Reif, Andreas ; Reininghaus, Eva Z. ; Richards, Jenny Gringer ; Ritter, Philipp ; Rybakowski, Janusz K. ; Sathyaputri, Leela ; Scippa, Ângela M. ; Simhandl, Christian ; Severus, Emanuel ; Smith, Daniel ; Smith, José ; Stackhouse Jr., Paul W. ; Stein, Dan J. ; Stilwell, Kellen ; Strejilevich, Sergio ; Su, Kuan-Pin ; Subramaniam, Mythily ; Sulaiman, Ahmad Hatim ; Suominen, Kirsi ; Tanra, Andi J. ; Tatebayashi, Yoshitaka ; Teh, Wen Lin ; Tondo, Leonardo ; Torrent, Carla ; Tuinstra, Daniel ; Uchida, Takahito ; Vaaler, Arne E. ; Veeh, Julia ; Vieta, Eduard ; Viswanath, Biju ; Yoldi-Negrete, Maria ; Yalcinkaya, Oguz Kaan ; Young, Allan H. ; Zgueb, Yosra ; Whybrow, Peter C.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Schmidt, Frederik Lennart ; Sürth, Valerie ; Berg, Tim K. ; Lin, Yi-Pin ; Hovius, Joppe W. ; Kraiczy, Peter
Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.
Lin, Jiacheng ; Eggensperger, Sabine ; Hank, Susanne ; Wycisk, Agnes Isabella ; Wieneke, Ralph ; Mayerhofer, Peter Uli ; Tampé, Robert
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.
Lin, Michelle I. ; Fulton, David ; Babbitt, Roger ; Fleming, Ingrid ; Busse, Rudi ; Pritchard, Kirkwood A. ; Sessa, William C.
There is evidence that endothelial nitric-oxide synthase (eNOS) is regulated by reciprocal dephosphorylation of Thr497 and phosphorylation of Ser1179. To examine the interrelationship between these sites, cells were transfected with wild-type (WT), T497A, T497D, S1179D, and T497A/S1179D eNOS and activity, NO release and eNOS localization were assessed. Although eNOS T497A, S1179D and T497A/S1179D eNOS had greater enzymatic activity than did WT eNOS in lysates, basal production of NO from cells was markedly reduced in cells transfected with T497A and T497A/S1179D eNOS but augmented in cells transfected with S1179D eNOS. Stimulating cells with ATP or ionophore normalized the loss of function seen with T497A and T497A/S1179D eNOS to levels observed with WT and S1179D eNOS, respectively. Despite these functional differences, the localization of eNOS mutants were similar to WT. Because both T497A and T497A/S1179D eNOS exhibited higher enzyme activity but reduced production of NO, we examined whether these mutations were “uncoupling” NO synthesis. T497A and T497A/S1179D eNOS generated 2-3 times more superoxide anion than WT eNOS, and both basal and stimulated interactions of T497A/S1179D eNOS with hsp90 were reduced in co-immunoprecipitation experiments. Thus, the phosphorylation/dephosphorylation of Thr497 may be an intrinsic switch mechanism that determines whether eNOS generates NO versus superoxide in cells.
Adams, John ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Amonett, John ; Anderson, Bradley D. ; Arkhipkin, Dmitry A. ; Averichev, Georgy S. ; Badyal, S. K. ; Bai, Yu ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Berger, Jens ; Bezverkhny, B. I. ; Bharadwaj, Somnath ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhatia, V. S. ; Bichsel, Hans ; Bielčík, Jaroslav ; Bielčíková, Jana ; Billmeier, Anja ; Bland, Leslie C. ; Blyth, Charles O. ; Bonner, Billy E. ; Botje, Michiel ; Boucham, Abdelkrim ; Brandin, Andrei V. ; Bravar, Alessandro ; Bystersky, M. ; Cadman, Robert V. ; Cai, Xiang-Zhou ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Castillo Castellanos, Javier Ernesto ; Catu, Oana ; Cebra, Daniel A. ; Chajecki, Zbigniew ; Chaloupka, Petr ; Chattopadhyay, S. ; Chen, H. F. ; Chen, Y. ; Cheng, J. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Christie, William ; Coffin, Jean Pierre ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; Das, Debasish ; Das, Supriya ; Moura, M. M. de ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dietel, Thomas ; Dogra, Sunil Manohar ; Dong, W. J. ; Dong, X. ; Draper, James E. ; Du, F. ; Dubey, Anand Kumar ; Dunin, V. B. ; Dunlop, James C. ; Mazumdar, M. R. Dutta ; Eckardt, Volker ; Edwards, W. R. ; Efimov, Leonid G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Estienne, Magali Danielle ; Fachini, Patricia ; Faivre, Julien ; Fatemi, Renee H. ; Fedorišin, Jan ; Filimonov, Kirill ; Filip, Peter ; Finch, Evan ; Fine, Valeri ; Fisyak, Yuri V. ; Fomenko, K. ; Fu, J. ; Gagliardi, Carl A. ; Gaillard, L. ; Gans, Jonathan Edward ; Ganti, Murthy S. ; Gaudichet, L. ; Geurts, Frank ; Ghazikhanian, Vahe ; Ghosh, Premomoy ; Gonzalez, Johan Enmanuel ; Grachov, Oleg A. ; Grebenyuk, Oleksandr ; Grosnick, David P. ; Guertin, Steven M. ; Guo, Y. ; Gupta, Anik ; Gutierrez, Thomas Dominic ; Hallman, Timothy J. ; Hamed, Ahmed M. ; Hardtke, David H. ; Harris, John W. ; Heinz, Mark Thomas ; Henry, Thomas W. ; Hepplemann, S. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, Gerald W. ; Huang, Huan Zhong ; Huang, Shengli ; Hughes, Emlyn Willard ; Humanic, Thomas J. ; Igo, George J. ; Ishihara, A. ; Jacobs, Peter Martin ; Jacobs, William W. ; Janik, Michał ; Jiang, H. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kabana, Sonia ; Kang, K. ; Kaplan, Morton ; Keane, Declan ; Khodyrev, V. Yu. ; Kiryluk, Joanna ; Kisiel, Adam Ryszard ; Kislov, E. M. ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Koetke, Donald D. ; Kollegger, Thorsten ; Kopytine, M. ; Kotchenda, L. ; Kramer, M. ; Kravtsov, Peter ; Kravtsov, Vladimir I. ; Krueger, Keith William ; Kuhn, Christian Claude ; Kulikov, Anatoly I. ; Kumar, Ajay ; Kutuev, R. Kh. ; Kuznetsov, A. A. ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, Jens Sören ; Laue, Frank ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lehocka, S. ; LeVine, Micheal J. ; Li, C. ; Li, Q. ; Li, Y. ; Lin, G. ; Lindenbaum, Sam J. ; Lisa, Michael A. ; Liu, F. ; Liu, L. ; Liu, Q. J. ; Liu, Z. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Long, H. ; Langacre, R. S. ; Lopez-Noriega, M. ; Love, William A. ; Lu, Y. ; Ludlam, Thomas ; Lynn, David ; Ma, G. L. ; Ma, Jing-guo ; Ma, Yu-Gang ; Magestro, Daniel ; Mahajan, Sanjay ; Mahapatra, D. P. ; Majka, Richard Daniel ; Mangotra, Lalit K. ; Manweiler, Robert W. ; Margetis, Spyridon ; Markert, Christina ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; McClain, Christopher J. ; McShane, Tom S. ; Meissner, F. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Miller, M. L. ; Minaev, Nikolai G. ; Mironov, Camelia ; Mischke, André ; Mishra, D. K. ; Mitchell, J. ; Mohanty, Bedangadas ; Molnar, Levente ; Moore, C. F. ; Morozov, Dmitry A. ; Munhoz, Marcelo Gameiro ; Nandi, Basanta Kumar ; Nayak, S. K. ; Nayak, Tapan Kumar ; Nelson, John M. ; Netrakanti, Pawan Kumar ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Okorokov, Vitaly A. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Pal, Susanta Kumar ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A. I. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Perevoztchikov, V. ; Perkins, Chris ; Peryt, Wiktor Stanislaw ; Petrov, V. A. ; Phatak, S. C. ; Picha, R. ; Planinic, Mirko ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potekhin, Maxim ; Potrebenikova, E. ; Potukuchi, B. V. K. S. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Putschke, Jörn H. ; Rakness, Gregory L. ; Raniwala, Rashmi ; Raniwala, Sudhir ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, Jeffrey G. ; Renault, G. ; Retiere, Fabrice ; Ridiger, Alexey ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Rose, A. ; Roy, Christelle Sophie ; Ruan, Lijuan ; Sahoo, Raghunath ; Sakrejda, Iwona ; Salur, Sevil ; Sandweiss, Jack H. ; Sarsour, M. ; Savin, Igor A. ; Sazhin, P. S. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schmitz, Norbert ; Schweda, Kai ; Seger, Janet Elizabeth ; Seyboth, Peter ; Shahaliev, Ehtiram ; Shao, M. ; Shao, W. ; Sharma, M. ; Shen, W. Q. ; Shestermanov, Konstantin E. ; Shimanskiy, S. S. ; Sichtermann, Ernst P. ; Simon, F. ; Singaraju, Rama Narayana ; Skoro, Goran P. ; Smirnov, Nikolai ; Snellings, Raimond ; Sood, Gopika ; Sorensen, Paul Richard ; Sowinski, James ; Speltz, Jeff ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stadnik, A. ; Stanislaus, T. D. Shirvel ; Stock, Reinhard ; Stolpovsky, Alexander ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Šumbera, Michal ; Surrow, Bernd ; Symons, Timothy James MacNeil ; Toledo, Alejandro Szanto de ; Szarwas, Piotr ; Tai, An ; Takahashi, Jun ; Tang, Aihong ; Tarnowsky, Terence J. ; Thein, Dylan ; Thomas, James H. ; Timoshenko, Sergei ; Tokarev, Mikhail V. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tribble, Robert E. ; Tsai, Oleg D. ; Ulery, Jason Glyndwr ; Ullrich, Thomas ; Underwood, David G. ; Urkinbaev, Anarbay ; Van Buren, Gene ; Leeuwen, Marco van ; Molen, A. M. vander ; Varma, Raghava ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Vernet, Renaud ; Vigdor, Steven E. ; Viyogi, Yogendra P. ; Vokal, Stanislav ; Voloshin, Sergei ; Vznuzdaev, Marat ; Waggoner, William T. ; Wang, F. ; Wang, G. ; Wang, G. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Z. M. ; Ward, H. ; Watson, J. W. ; Webb, Jason C. ; Wells, R. ; Westfall, Gary D. ; Wetzler, Alexander Albert ; Whitten, Charles A. ; Wieman, Howard ; Wissink, Scott W. ; Witt, Richard ; Wood, J. ; Wu, J. ; Xu, N. ; Xu, Z. ; Xu, Z. Z. ; Yamamoto, E. ; Yepes, Pablo P. ; Yurevich, Vladimir Yurevich ; Zanevsky, Yuri V. ; Zhang, Haibin ; Zhang, W. M. ; Zhang, Z. P. ; Zoulkarneev, R. ; Zoulkarneeva, Youlia ; Zubarev, A. N. ; Braem, A. ; Davenport, M. ; De Cataldo, Giacinto ; Di Bari, Domenico ; Martinengo, Paolo ; Nappi, Eugenio ; Paic, Guy ; Posa, E. ; Puiz, F. ; Schyns, Emile
The results from the STAR Collaboration on directed flow (v1), elliptic flow (v2), and the fourth harmonic (v4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrt[sNN]=200GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a blast-wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v2, scaling with the number of constituent quarks and parton coalescence are discussed. For v4, scaling with v22 and quark coalescence are discussed.
This paper deals with the brachypterous Meconematini, including three new genera, Acosmetides gen. nov., Neocyrtopsides gen. nov. and Macrocosmetura gen. nov. Five new species are described: Acosmetides peltates gen. et sp. nov., Acosmetides dilobosa gen. et sp. nov., Acosmetides platycerca gen. et sp. nov., Neocyrtopsides bispina gen. et sp. nov. and Macrocosmetura truncata gen. et sp. nov. Two new combinations are proposed: Acosmetides trigentis (Wang, Bian & Shi, 2016) gen. et comb. nov. and Neocyrtopsides platycata (Shi & Zheng, 1994) gen. et comb. nov.
White, Helen ; Deprez, Liesbet ; Corbisier, Philippe ; Hall, Victoria ; Lin, Feng ; Mazoua, Stéphane ; Trapmann, Stefanie ; Aggerholm, Anni ; Andrikovics, Hajnalka ; Akiki, Susanna ; Barbany, Gisela ; Boeckx, Nancy ; Bench, Anthony ; Catherwood, Mark ; Cayuela, Jean-Michel ; Chudleigh, Sandra ; Clench, Tim ; Colomer, Dolors ; Daraio, Filomena ; Dulucq, Stephanie ; Farrugia, Joanna ; Fletcher, Linda ; Foroni, Letizia ; Ganderton, Ros ; Gerrard, Gareth ; Gineikienė, Eglė ; Hayette, Sandrine ; El Housni, Hakim ; Izzo, Barbara ; Jansson, Mattias ; Johnels, Petra ; Jurcek, Tomas ; Kairisto, Veli ; Kizilors, Aytug ; Kim, Dong-Wook ; Lange, Thoralf ; Lion, Thomas ; Polakova, Katerina Machova ; Martinelli, Giovanni ; McCarron, Sarah ; Merle, Pauline A. ; Milner, Ben ; Mitterbauer-Hohendanner, Gerlinde ; Nagar, Meital ; Nickless, Guillermina ; Nomdedéu, Josep F. ; Nymoen, Dag A. ; Leibundgut, Elisabeth Oppliger ; Ozbek, Ugur ; Pajič, Tadej ; Pfeifer, Heike ; Preudhomme, Claude ; Raudsepp, Kadri ; Romeo, Giuliana ; Sacha, Tomasz ; Talmaci, Rodica ; Touloumenidou, Tasoula ; Van der Velden, Vincent H. J. ; Waits, Paula ; Wang, Lihui ; Wilkinson, Elizabeth ; Wilson, Gill ; Wren, Dörte ; Zadro, Renata ; Ziermann, Janine ; Zoi, Katerina ; Müller, Martin C. ; Hochhaus, Andreas ; Schimmel, Heinz ; Cross, Nicholas C. P. ; Emons, Hendrik
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
Moustakim, Moses ; Clark, Peter G. K. ; Trulli, Laura ; Fuentes de Arriba, Angel L. ; Ehebauer, Matthias T. ; Chaikuad, Apirat ; Murphy, Emma J. ; Mendez-Johnson, Jacqui ; Daniels, Danette ; Hou, Chun-Feng D. ; Lin, Yu-Hui ; Walker, John R. ; Hui, Raymond ; Yang, Hongbing ; Dorrell, Lucy ; Rogers, Catherine M. ; Monteiro, Octovia ; Fedorov, Oleg ; Huber, Kilian ; Knapp, Stefan ; Heer, Jag ; Dixon, Darren ; Brennan, Paul E.
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Adams, John ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Amonett, John ; Anderson, Bryon D. ; Arkhipkin, Dmitry A. ; Averichev, Georgy S. ; Badyal, S. K. ; Bai, Yu ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Berger, Jens ; Bezverkhny, B. I. ; Bharadwa, S. ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhatia, V. S. ; Bichsel, Hans ; Billmeier, Anja ; Bland, Leslie C. ; Blyth, Charles O. ; Bonner, Billy E. ; Botje, Michiel ; Boucham, Abdelkrim ; Brandin, Andrei V. ; Bravar, Alessandro ; Bystersky, M. ; Cadman, R. V. ; Cai, X. Z. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Castillo Castellanos, Javier Ernesto ; Cebra, Daniel A. ; Chajecki, Zbigniew ; Chaloupka, Petr ; Chattopadhyay, S. ; Chen, H. F. ; Chen, Y. ; Cheng, J. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Christie, William ; Coffin, J. P. ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; Das, Debasish ; Das, S. ; Moura, M. M. de ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dietel, Thomas ; Dogra, Sunil Manohar ; Dong, W. J. ; Dong, X. ; Draper, James E. ; Du, F. ; Dubey, Anand Kumar ; Dunin, V. B. ; Dunlop, James C. ; Dutta Mazumdar, M. R. ; Eckardt, Volker ; Edwards, W. R. ; Efimov, L. G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Estienne, Magali Danielle ; Fachini, Patricia ; Faivre, Julien ; Fatemi, Renee H. ; Fedorišin, Jan ; Filimonov, Kirill ; Filip, Peter ; Finch, Evan ; Fine, Valeri ; Fisyak, Yuri V. ; Fomenko, K. ; Grebenyuk, Oleksandr ; Grosnick, David P. ; Guertin, Steven M. ; Guo, Y. ; Gupta, Anik ; Gutierrez, Thomas Dominic ; Hallman, Timothy J. ; Hamed, Ahmed M. ; Hardtke, David H. ; Harris, John W. ; Heinz, M. ; Henry, Thomas W. ; Hepplemann, S. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, G. W. ; Huang, H. Z. ; Huang, S. L. ; Hughes, Emlyn Willard ; Humanic, Thomas J. ; Igo, George J. ; Ishihara, A. ; Jacobs, Peter Martin ; Jacobs, W.W. ; Janik, Michał ; Jiang, H. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kabana, Sonia ; Kang, K. ; Kaplan, Morton ; Keane, Declan ; Khodyrev, V. Yu. ; Kiryluk, Joanna ; Kisiel, Adam Ryszard ; Kislov, E. M. ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Klyachko, A. ; Koetke, Donald D. ; Kollegger, Thorsten ; Kopytine, M. ; Kotchenda, L. ; Kramer, M. ; Kravtsov, Peter ; Kravtsov, Vladimir I. ; Krueger, Keith William ; Kuhn, Christian Claude ; Kulikov, Anatoly I. ; Kumar, Ajay ; Kutuev, R.Kh. ; Kuznetsov, A.A. ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, Jens Sören ; Laue, Frank ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lehocka, S. ; LeVine, Micheal J. ; Li, C. ; Li, Q. ; Li, Y. ; Lin, G. ; Lindenbaum, S. J. ; Lisa, Michael A. ; Liu, F. ; Liu, L. ; Liu, Q.J. ; Liu, Z. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Long, H. ; Longacre, Ronald S. ; López Noriega, M. ; Love, William A. ; Lu, Y. ; Ludlam, Thomas ; Lynn, David ; Ma, G. L. ; Ma, Jing-guo ; Ma, Y. G. ; Magestro, Daniel ; Mahajan, Sanjay ; Mahapatra, D. P. ; Majka, Richard Daniel ; Mangotra, Lalit K. ; Manweiler, Robert W. ; Margetis, Spyridon ; Markert, Christina ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; McClain, C. J. ; McShane, T. S. ; Meissner, F. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Miller, M. L. ; Minaev, Nikolai G. ; Mironov, Camelia ; Mischke, André ; Mishra, D. K. ; Mitchell, J. ; Mohanty, Bedangadas ; Molnar, Levente ; Moore, C. F. ; Morozov, D. A. ; Munhoz, Marcelo Gameiro ; Nandi, Basanta Kumar ; Nayak, S. K. ; Nayak, Tapan Kumar ; Nelson, John M. ; Netrakanti, Pawan Kumar ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Okorokov, Vitaly A. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Pal, Susanta Kumar ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A. I. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potekhin, Maxim ; Potrebenikova, E. ; Potukuchi, B. V. K. S. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Putschke, Jörn H. ; Rakness, Gregory L. ; Raniwala, Rashmi ; Raniwala, Sudhir ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, Jeffrey G. ; Renault, G. ; Retiere, Fabrice ; Ridiger, Alexey ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Rose, A. ; Roy, Christelle Sophie ; Ruan, Lijuan ; Sahoo, Raghunath ; Sakrejda, Iwona ; Salur, Sevil ; Sandweiss, Jack H. ; Savin, Igor A. ; Sazhin, P. S. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schmitz, Norbert ; Schweda, Kai ; Seger, Janet Elizabeth ; Seyboth, Peter ; Shahaliev, Ehtiram ; Shao, M. ; Shao, W. ; Sharma, M. ; Shen, W. Q. ; Shestermanov, Konstantin E. ; Shimanskiy, S. S. ; Sichtermann, E ; Simon, F. ; Singaraju, R. N. ; Skoro, Goran P. ; Smirnov, Nikolai ; Snellings, Raimond ; Sood, Gopika ; Sorensen, Paul Richard ; Sowinski, James ; Speltz, Jeff ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stadnik, A. ; Stadnik, A. ; Stanislaus, T. D. Shirvel ; Stock, Reinhard ; Stock, Reinhard ; Stolpovsky, Alexander ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Šumbera, Michal ; Surrow, Bernd ; Symons, T. J. M. ; Toledo, Alejandro Szanto de ; Szarwas, Piotr ; Tai, An ; Takahashi, Jun ; Tang, A. H. ; Tarnowsky, Terence J. ; Thein, Dylan ; Thomas, James H. ; Timoshenko, Sergei ; Tokarev, Mikhail V. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tribble, Robert E. ; Tsai, Oleg D. ; Ulery, Jason Glyndwr ; Ullrich, Thomas ; Underwood, David G. ; Urkinbaev, Anarbay ; Van Buren, Gene ; Ward, H. ; Watson, J. W. ; Webb, Jason C. ; Wells, R. ; Westfall, G. D. ; Wetzler, Alexander Albert ; Whitten, Charles A. ; Wieman, H. ; Wissink, Scott W. ; Witt, Richard ; Wood, J. ; Wu, J. ; Xu, N. ; Xu, Z. ; Xu, Z. Z. ; Yamamoto, E. ; Yepes, Pablo P. ; Yurevich, Vladimir I. ; Zanevsky, Yuri V. ; Zhang, Haitao ; Zhang, W. M. ; Zhang, Z. P. ; Zolnierczuk, Piotr Adam ; Zoulkarneev, R. ; Zoulkarneeva, Youlia ; Zubarev, A. N. ; Leeuwen, Marco van ; Vander Molen, A. M. ; Varma, Raghava ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Verne, R. ; Vigdor, Steven E. ; Viyogi, Yogendra P. ; Vokal, Stanislav ; Voloshin, S. A. ; Vznuzdaev, Marat ; Waggoner, William T. ; Wang, F. ; Wang, G. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Z. M.
We present a systematic analysis of two-pion interferometry in Au+Au collisions at sqrt[sNN]=200GeV using the STAR detector at Relativistic Heavy Ion Collider. We extract the Hanbury-Brown and Twiss radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianness of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast-wave parametrizations. The expansion of the source and its relation with the initial energy density distribution is studied.
Adamczyk, Leszek ; Adkins, J. Kevin ; Agakishiev, Geydar ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Ajitanand, N.N. ; Alekseev, Igor G. ; Anderson, Derek M. ; Aoyama, Ryo ; Aparin, Alexey ; Arkhipkin, Dmitry A. ; Aschenauer, Elke Caroline ; Ashraf, Muhammad Usman ; Attri, Anjali ; Averichev, Georgy S. ; Bai, Xiaozhi ; Bairathi, Vipul ; Behera, Arabinda ; Bellwied, Rene ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhattarai, P. ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bland, Leslie C. ; Bordyuzhin, Igor G. ; Bouchet, Jonathan ; Brandenburg, James D. ; Brandin, Andrei V. ; Brown, D. ; Bunzarov, Ivan ; Butterworth, Joseph ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Campbell, J.M. ; Cebra, Daniel A. ; Chakaberia, Irakli ; Chaloupka, Petr ; Chang, Z. ; Chankova-Bunzarova, N. ; Chatterjee, A. ; Chattopadhyay, S. ; Chen, X. ; Chen, J.H. ; Chen, X. ; Cheng, J. ; Cherney, Michael Gerard ; Christie, William ; Contin, Giacomo ; Crawford, Henry J. ; Das, Supriya ; De Silva, L.C. ; Debbe, R.R. ; Dedovič, Tatiana G. ; Deng, J. ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dilks, Christopher ; Dong, X. ; Drachenberg, James Lucus ; Draper, James E. ; Dunkelberger, Lloyd Edward ; Dunlop, James C. ; Efimov, Leonid G. ; Elsey, Nicholas ; Engelage, Jon M. ; Eppley, Geary Wareham ; Esha, Roli ; Esumi, ShinIchi ; Evdokimov, Olga Y. ; Ewigleben, Justin ; Eyser, Kjeld Oleg ; Fatemi, Renee H. ; Fazio, Salvatore ; Federič, Pavol ; Federicova, P. ; Fedorišin, Jan ; Feng, Z. ; Filip, Peter ; Finch, Evan ; Fisyak, Yuri V. ; Flores, C.E. ; Fulek, Łukasz ; Gagliardi, Carl A. ; Garand, David ; Geurts, Frank ; Gibson, Adam ; Girard, M. ; Grosnick, David P. ; Gunarathne, D.S. ; Guo, Y. ; Gupta, Anik ; Gupta, S. ; Guryn, Włodzimierz ; Hamad, Ayman ; Hamed, Ahmed M. ; Harlenderova, Alena ; Harris, John W. ; He, L. ; Heppelmann, Steven Francis ; Heppelmann, Steven Francis ; Hirsch, Andrew S. ; Hoffmann, Gerald W. ; Horvat, S. ; Huang, T. ; Huang, B. ; Huang, X. ; Huang, H.Z. ; Humanic, Thomas J. ; Huo, P. ; Igo, George J. ; Jacobs, William W. ; Jentsch, Alexander ; Jia, J. ; Jiang, K. ; Jowzaee, S. ; Judd, Eleanor G. ; Kabana, Sonia ; Kalinkin, Dmitry ; Kang, K. ; Kauder, Kolja ; Ke, Hongwei ; Keane, Declan ; Kechechyan, Armen ; Khan, Z. ; Kikoła, Daniel P. ; Kisel, Ivan ; Kisiel, Adam Ryszard ; Kočenda, L. M. ; Kocmanek, M. ; Kollegger, Thorsten ; Kosarzewski, Leszek Krzysztof ; Kraishan, A.F. ; Kravtsov, Peter ; Krueger, Keith William ; Kulathunga, Nalinda ; Kumar, Lokesh ; Kvapil, Jakub ; Kwasizur, Joseph H. ; Lacey, Roy Alphanso ; Landgraf, Jeffery M. ; Landry, K.D. ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lee, J.H. ; Li, Xiaomei ; Li, C. ; Li, W. ; Li, Y. ; Lidrych, J. ; Lin, T. ; Lisa, Michael A. ; Liu, H. ; Liu, P. ; Liu, Y. ; Liu, F. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Lomnitz, Michael ; Longacre, Ronald S. ; Luo, S. ; Luo, X. ; Ma, G.L. ; Ma, L. ; Ma, Yu-Gang ; Ma, R. ; Magdy Abdelwahab Abdelrahman, Niseem ; Majka, Richard Daniel ; Mallick, Dukhishyam ; Margetis, Spyridon ; Markert, Christina ; Matis, Howard S. ; Meehan, Kathryn ; Mei, Jincheng ; Miller, Z.W. ; Minaev, Nikolai G. ; Mioduszewski, Saskia ; Mishra, Debadeepti ; Mizuno, S. ; Mohanty, Bedangadas ; Mondal, Mriganka Mouli ; Morozov, Dmitry A. ; Mustafa, M.K. ; Nasim, Md. ; Nayak, Tapan Kumar ; Nelson, John M. ; Nie, Maowu ; Nigmatkulov, Grigory A. ; Niida, Takafumi ; Nogach, Larisa V. ; Nonaka, Toshihiro ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Oh, Kunsu ; Okorokov, Vitaly A. ; Olvitt, D. ; Page, Brian S. ; Pak, Robert ; Pandit, Y. ; Panebratsev, Yuri ; Pawlik, Bogdan ; Pei, Hua ; Perkins, Chris ; Pile, P. ; Pluta, Jan Marian ; Poniatowska, K. ; Porter, Jeffrey Brent ; Posik, Matthew ; Poskanzer, Arthur M. ; Pruthi, Navneet Kumar ; Przybycien, Mariusz ; Putschke, Jörn H. ; Qiu, H. ; Quintero, Amilkar ; Ramachandran, Suvarna ; Ray, Robert L. ; Reed, Rosi Jan ; Rehbein, M.J. ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Roth, J.D. ; Ruan, Lijuan ; Rusnak, Jan ; Rusnakova, Olga ; Sahoo, Nihar Ranjan ; Sahu, Pradip Kumar ; Salur, Sevil ; Sandweiss, Jack H. ; Saur, M. ; Schambach, Joachim ; Schmah, Alexander ; Schmidke, William B. ; Schmitz, Norbert ; Schweid, Benjamin R. ; Seger, Janet Elizabeth ; Sergeeva, Maria ; Seyboth, Peter ; Shah, N. ; Shahaliev, Ehtiram ; Shanmuganathan, Prashanth V. ; Shao, M. ; Sharma, A. ; Sharma, M.K. ; Shen, W.Q. ; Shi, Z. ; Shi, S.S. ; Shou, Q.Y. ; Sichtermann, Ernst P. ; Sikora, Rafał ; Šimko, Miroslav ; Singha, Subhash ; Skoby, M.J. ; Smirnov, Nikolai ; Smirnov, Dmitri V. ; Solyst, William ; Song, L. ; Sorensen, Paul Richard ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stanislaus, T. D. Shirvel ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Sugiura, Tetsuro ; Šumbera, Michal ; Summa, Branden ; Sun, Y. ; Sun, X.M. ; Sun, X. ; Surrow, Bernd ; Svirida, Dmitry N. ; Tang, Aihong ; Tang, Zebo ; Taranenko, Arkadiy ; Tarnowsky, Terence J. ; Tawfik, Abdel Nasser ; Thäder, Jochen ; Thomas, James H. ; Timmins, Anthony Robert ; Tlusty, David ; Todoroki, Takahito ; Tokarev, Mikhail V. ; Trentalange, Stephen ; Tribble, Robert E. ; Tribedy, Prithwish ; Tripathy, Srikanta Kumar ; Trzeciak, Barbara Antonina ; Tsai, Oleg D. ; Ullrich, Thomas ; Underwood, David G. ; Upsal, Isaac ; Van Buren, Gene ; Nieuwenhuizen, Gerrit J. van ; Vasiliev, Alexander Nikolaevich ; Videbæk, Flemming ; Vokal, Stanislav ; Voloshin, Sergei ; Vossen, A. ; Wang, G. ; Wang, Y. ; Wang, F. ; Wang, Y. ; Webb, Jason C. ; Webb, Grant ; Wen, L. ; Westfall, Gary D. ; Wieman, Howard ; Wissink, Scott W. ; Witt, Richard ; Wu, Y. ; Xiao, Z.G. ; Xie, W. ; Xie, Guannan ; Xu, J. ; Xu, N. ; Xu, Q.H. ; Xu, Y.F. ; Xu, Z. ; Yang, Y. ; Yang, Q. ; Yang, C. ; Yang, S. ; Ye, Z. ; Ye, Z. ; Yi, L. ; Yip, K. ; Yoo, In-Kwon ; Yu, N. ; Zbroszczyk, Hanna Paulina ; Zha, W. ; Zhang, Zuman ; Zhang, X.P. ; Zhang, J.B. ; Zhang, S. ; Zhang, J. ; Zhang, Y. ; Zhang, J. ; Zhang, S. ; Zhao, J. ; Zhong, C. ; Zhou, L. ; Zhou, C. ; Zhu, X. ; Zhu, Z. ; Zyzak, Maksym
We present three-particle mixed-harmonic correlations 〈cos(mφa + nφb − (m + n)φc )〉 for harmonics m, n = 1 − 3 for charged particles in √sN N = 200 GeV Au+Au collisions at RHIC. These measurements provide information on the three-dimensional structure of the initial collision zone and are important for constraining models of a subsequent low-viscosity quark–gluon plasma expansion phase. We investigate correlations between the first, second and third harmonics predicted as a consequence of fluctuations in the initial state. The dependence of the correlations on the pseudorapidity separation between particles show hints of a breaking of longitudinal invariance. We compare our results to a number of state-of-the art hydrodynamic calculations with different initial states and temperature dependent viscosities. These measurements provide important steps towards constraining the temperature dependent viscosity and longitudinal structure of the initial state at RHIC.
Adamczyk, Leszek ; Adams, Joseph R. ; Adkins, J. Kevin ; Agakishiev, Geydar ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Ajitanand, N.N. ; Alekseev, Igor G. ; Anderson, Derek M. ; Aoyama, Ryo ; Aparin, Alexey ; Arkhipkin, Dmitry A. ; Aschenauer, Elke Caroline ; Ashraf, Muhammad Usman ; Attri, Anjali ; Averichev, Georgy S. ; Bai, Xiaozhi ; Bairathi, Vipul ; Barish, Kenneth ; Behera, Arabinda ; Bellwied, Rene ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhattarai, P. ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bland, Leslie C. ; Bordyuzhin, Igor G. ; Bouchet, Jonathan ; Brandenburg, James D. ; Brandin, Andrei V. ; Brown, D. ; Bunzarov, Ivan ; Butterworth, Joseph ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Campbell, J.M. ; Cebra, Daniel A. ; Chakaberia, Irakli ; Chaloupka, Petr ; Chang, Z. ; Chankova-Bunzarova, N. ; Chatterjee, A. ; Chattopadhyay, S. ; Chen, J.H. ; Chen, X. ; Chen, X. ; Cheng, J. ; Cherney, Michael Gerard ; Christie, William ; Contin, Giacomo ; Crawford, Henry J. ; Das, Supriya ; De Silva, L.C. ; Debbe, R.R. ; Dedovič, Tatiana G. ; Deng, J. ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dilks, Christopher ; Dong, X. ; Drachenberg, James Lucus ; Draper, James E. ; Dunkelberger, Lloyd Edward ; Dunlop, James C. ; Efimov, Leonid G. ; Elsey, Nicholas ; Engelage, Jon M. ; Eppley, Geary Wareham ; Esha, Roli ; Esumi, ShinIchi ; Evdokimov, Olga Y. ; Ewigleben, Justin ; Eyser, Kjeld Oleg ; Fatemi, Renee H. ; Fazio, Salvatore ; Federič, Pavol ; Federicova, P. ; Fedorišin, Jan ; Feng, Z. ; Filip, Peter ; Finch, Evan ; Fisyak, Yuri V. ; Flores, C.E. ; Fujita, J. ; Fulek, Łukasz ; Gagliardi, Carl A. ; Garand, David ; Geurts, Frank ; Gibson, Adam ; Girard, M. ; Grosnick, David P. ; Gunarathne, D.S. ; Guo, Y. ; Gupta, S. ; Gupta, Anik ; Guryn, Włodzimierz ; Hamad, Ayman ; Hamed, Ahmed M. ; Harlenderova, Alena ; Harris, John W. ; He, L. ; Heppelmann, Steven Francis ; Heppelmann, Steven Francis ; Hirsch, Andrew S. ; Hoffmann, Gerald W. ; Horvat, S. ; Huang, X. ; Huang, H.Z. ; Huang, T. ; Huang, B. ; Humanic, Thomas J. ; Huo, P. ; Igo, George J. ; Jacobs, William W. ; Jentsch, Alexander ; Jia, J. ; Jiang, K. ; Jowzaee, S. ; Judd, Eleanor G. ; Kabana, Sonia ; Kalinkin, Dmitry ; Kang, K. ; Kapukchyan, David ; Kauder, Kolja ; Ke, Hongwei ; Keane, Declan ; Kechechyan, Armen ; Khan, Z. ; Kikoła, Daniel P. ; Kim, C. ; Kisel, Ivan ; Kisiel, Adam Ryszard ; Kočenda, L. M. ; Kocmanek, M. ; Kollegger, Thorsten ; Kosarzewski, Leszek Krzysztof ; Kraishan, A.F. ; Krauth, L. ; Kravtsov, Peter ; Krueger, Keith William ; Kulathunga, Nalinda ; Kumar, Lokesh ; Kvapil, Jakub ; Kwasizur, Joseph H. ; Lacey, Roy Alphanso ; Landgraf, Jeffery M. ; Landry, K.D. ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lee, J.H. ; Li, C. ; Li, W. ; Li, Y. ; Li, Xiaomei ; Lidrych, J. ; Lin, T. ; Lisa, Michael A. ; Liu, P. ; Liu, F. ; Liu, H. ; Liu, Y. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Lomnitz, Michael ; Longacre, Ronald S. ; Luo, X. ; Luo, S. ; Ma, G.L. ; Ma, L. ; Ma, Yu-Gang ; Ma, R. ; Magdy Abdelwahab Abdelrahman, Niseem ; Majka, Richard Daniel ; Mallick, Dukhishyam ; Margetis, Spyridon ; Markert, Christina ; Matis, Howard S. ; Meehan, Kathryn ; Mei, Jincheng ; Miller, Z.W. ; Minaev, Nikolai G. ; Mioduszewski, Saskia ; Mishra, Debadeepti ; Mizuno, S. ; Mohanty, Bedangadas ; Mondal, Mriganka Mouli ; Morozov, Dmitry A. ; Mustafa, M.K. ; Nasim, Md. ; Nayak, Tapan Kumar ; Nelson, John M. ; Nie, Maowu ; Nigmatkulov, Grigory A. ; Niida, Takafumi ; Nogach, Larisa V. ; Nonaka, Toshihiro ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Oh, Kunsu ; Okorokov, Vitaly A. ; Olvitt, D. ; Page, Brian S. ; Pak, Robert ; Pandit, Y. ; Panebratsev, Yuri ; Pawlik, Bogdan ; Pei, Hua ; Perkins, Chris ; Pile, P. ; Pluta, Jan Marian ; Poniatowska, K. ; Porter, Jeffrey Brent ; Posik, Matthew ; Pruthi, Navneet Kumar ; Przybycien, Mariusz ; Putschke, Jörn H. ; Qiu, H. ; Quintero, Amilkar ; Ramachandran, Suvarna ; Ray, Robert L. ; Reed, Rosi Jan ; Rehbein, M.J. ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Roth, J.D. ; Ruan, Lijuan ; Rusnak, Jan ; Rusnakova, Olga ; Sahoo, Nihar Ranjan ; Sahu, Pradip Kumar ; Salur, Sevil ; Sandweiss, Jack H. ; Sarkar, Amal ; Saur, M. ; Schambach, Joachim ; Schmah, Alexander ; Schmidke, William B. ; Schmitz, Norbert ; Schweid, Benjamin R. ; Seger, Janet Elizabeth ; Sergeeva, Maria ; Seto, Richard ; Seyboth, Peter ; Shah, N. ; Shahaliev, Ehtiram ; Shanmuganathan, Prashanth V. ; Shao, M. ; Sharma, M.K. ; Sharma, A. ; Shen, W.Q. ; Shi, Z. ; Shi, S.S. ; Shou, Q.Y. ; Sichtermann, Ernst P. ; Sikora, Rafał ; Šimko, Miroslav ; Singha, Subhash ; Skoby, M.J. ; Smirnov, Dmitri V. ; Smirnov, Nikolai ; Solyst, William ; Song, L. ; Sorensen, Paul Richard ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stanislaus, T. D. Shirvel ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Sugiura, Tetsuro ; Šumbera, Michal ; Summa, Branden ; Sun, X.M. ; Sun, Y. ; Sun, X. ; Surrow, Bernd ; Svirida, Dmitry N. ; Tang, Aihong ; Tang, Zebo ; Taranenko, Arkadiy ; Tarnowsky, Terence J. ; Tawfik, Abdel Nasser ; Thäder, Jochen ; Thomas, James H. ; Timmins, Anthony Robert ; Tlusty, David ; Todoroki, Takahito ; Tokarev, Mikhail V. ; Trentalange, Stephen ; Tribble, Robert E. ; Tribedy, Prithwish ; Tripathy, Srikanta Kumar ; Trzeciak, Barbara Antonina ; Tsai, Oleg D. ; Ullrich, Thomas ; Underwood, David G. ; Upsal, Isaac ; Van Buren, Gene ; Nieuwenhuizen, Gerrit J. van ; Vasiliev, Alexander Nikolaevich ; Videbæk, Flemming ; Vokal, Stanislav ; Voloshin, Sergei ; Vossen, A. ; Wang, F. ; Wang, Y. ; Wang, G. ; Wang, Y. ; Webb, Jason C. ; Webb, Grant ; Wen, L. ; Westfall, Gary D. ; Wieman, Howard ; Wissink, Scott W. ; Witt, Richard ; Wu, Y. ; Xiao, Z.G. ; Xie, Guannan ; Xie, W. ; Xu, Z. ; Xu, N. ; Xu, Y.F. ; Xu, Q.H. ; Xu, J. ; Yang, Q. ; Yang, C. ; Yang, S. ; Yang, Y. ; Ye, Z. ; Ye, Z. ; Yi, L. ; Yip, K. ; Yoo, In-Kwon ; Yu, N. ; Zbroszczyk, Hanna Paulina ; Zha, W. ; Zhang, X.P. ; Zhang, S. ; Zhang, J.B. ; Zhang, J. ; Zhang, Zuman ; Zhang, S. ; Zhang, J. ; Zhang, Y. ; Zhao, J. ; Zhong, C. ; Zhou, L. ; Zhou, C. ; Zhu, Z. ; Zhu, X. ; Zyzak, Maksym
Fluctuations of conserved quantities such as baryon number, charge, and strangeness are sensitive to the correlation length of the hot and dense matter created in relativistic heavy-ion collisions and can be used to search for the QCD critical point. We report the first measurements of the moments of net-kaon multiplicity distributions in Au+Au collisions at √sNN = 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV. The collision centrality and energy dependence of the mean (M), variance (σ 2), skewness (S), and kurtosis (κ) for net-kaon multiplicity distributions as well as the ratio σ 2/M and the products Sσ and κσ 2 are presented. Comparisons are made with Poisson and negative binomial baseline calculations as well as with UrQMD, a transport model (UrQMD) that does not include effects from the QCD critical point. Within current uncertainties, the net-kaon cumulant ratios appear to be monotonic as a function of collision energy.
Adam, Jaroslav ; Adamczyk, Leszek ; Adams, Joseph R. ; Adkins, J. Kevin ; Agakishiev, Geydar ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Ajitanand, N.N. ; Alekseev, Igor G. ; Anderson, Derek M. ; Aoyama, Ryo ; Aparin, Alexey ; Arkhipkin, Dmitry A. ; Aschenauer, Elke Caroline ; Ashraf, Muhammad Usman ; Atetalla, Fareha ; Attri, Anjali ; Averichev, Georgy S. ; Bai, Xiaozhi ; Bairathi, Vipul ; Barish, Kenneth ; Bassill, Aaron J. ; Behera, Arabinda ; Bellwied, Rene ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bland, Leslie C. ; Bordyuzhin, Igor G. ; Brandenburg, James D. ; Brandin, Andrei V. ; Brown, D. ; Bryslawskyj, Jason ; Bunzarov, Ivan ; Butterworth, Joseph ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Campbell, J.M. ; Cebra, Daniel A. ; Chakaberia, Irakli ; Chaloupka, Petr ; Chang, F.-H. ; Chang, Z. ; Chankova-Bunzarova, N. ; Chatterjee, A. ; Chattopadhyay, S. ; Chen, J.H. ; Chen, X. ; Chen, X. ; Cheng, J. ; Cherney, Michael Gerard ; Christie, William ; Contin, Giacomo ; Crawford, Henry J. ; Das, Supriya ; Dedovič, Tatiana G. ; Deppner, Ingo Martin ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dilks, Christopher ; Dong, X. ; Drachenberg, James Lucus ; Dunlop, James C. ; Efimov, Leonid G. ; Elsey, Nicholas ; Engelage, Jon M. ; Eppley, Geary Wareham ; Esha, Roli ; Esumi, ShinIchi ; Evdokimov, Olga Y. ; Ewigleben, Justin ; Eyser, Kjeld Oleg ; Fatemi, Renee H. ; Fazio, Salvatore ; Federič, Pavol ; Federicova, P. ; Fedorišin, Jan ; Filip, Peter ; Finch, Evan ; Fisyak, Yuri V. ; Flores, C.E. ; Fulek, Łukasz ; Gagliardi, Carl A. ; Galatyuk, Tetyana ; Geurts, Frank ; Gibson, Adam ; Grosnick, David P. ; Gunarathne, D.S. ; Guo, Y. ; Gupta, Anik ; Guryn, Włodzimierz ; Hamad, Ayman ; Hamed, Ahmed M. ; Harlenderova, Alena ; Harris, John W. ; He, L. ; Heppelmann, Steven Francis ; Heppelmann, Steven Francis ; Herrmann, Norbert ; Hirsch, Andrew S. ; Holub, Lukáš ; Horvat, S. ; Huang, X. ; Huang, B. ; Huang, Shengli ; Huang, H.Z. ; Huang, T. ; Humanic, Thomas J. ; Huo, P. ; Igo, George J. ; Jacobs, William W. ; Jentsch, Alexander ; Jia, J. ; Jiang, K. ; Jowzaee, S. ; Judd, Eleanor G. ; Kabana, Sonia ; Kalinkin, Dmitry ; Kang, K. ; Kapukchyan, David ; Kauder, Kolja ; Ke, Hongwei ; Keane, Declan ; Kechechyan, Armen ; Kikoła, Daniel P. ; Kim, C. ; Kinghorn, Todd Adler ; Kisel, Ivan ; Kisiel, Adam Ryszard ; Kočenda, L. M. ; Kosarzewski, Leszek Krzysztof ; Kraishan, A.F. ; Kramárik, Lukáš ; Krauth, L. ; Kravtsov, Peter ; Krueger, Keith William ; Kulathunga, Nalinda ; Kumar, Shyam ; Kumar, Lokesh ; Kvapil, Jakub ; Kwasizur, Joseph H. ; Lacey, Roy Alphanso ; Landgraf, Jeffery M. ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lee, J.H. ; Li, Xiaomei ; Li, C. ; Li, W. ; Li, Y. ; Liang, Y. ; Lidrych, J. ; Lin, T. ; Lipiec, Andrzej ; Lisa, Michael A. ; Liu, F. ; Liu, P. ; Liu, H. ; Liu, Y. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Lomnitz, Michael ; Longacre, Ronald S. ; Luo, X. ; Luo, S. ; Ma, G.L. ; Ma, Yu-Gang ; Ma, L. ; Ma, R. ; Magdy Abdelwahab Abdelrahman, Niseem ; Majka, Richard Daniel ; Mallick, Dukhishyam ; Margetis, Spyridon ; Markert, Christina ; Matis, Howard S. ; Matonoha, Oliver ; Mayes, D. ; Mazer, Joel Anthony ; Meehan, Kathryn ; Mei, Jincheng ; Minaev, Nikolai G. ; Mioduszewski, Saskia ; Mishra, Debadeepti ; Mohanty, Bedangadas ; Mondal, Mriganka Mouli ; Mooney, Isaac A. ; Morozov, Dmitry A. ; Nasim, Md. ; Negrete, J.D. ; Nelson, John M. ; Nemes, Daniel B. ; Nie, Maowu ; Nigmatkulov, Grigory A. ; Niida, Takafumi ; Nogach, Larisa V. ; Nonaka, Toshihiro ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Oh, Kunsu ; Oh, Saehanseul ; Okorokov, Vitaly A. ; Olvitt, D. ; Page, Brian S. ; Pak, Robert ; Panebratsev, Yuri ; Pawlik, Bogdan ; Pei, Hua ; Perkins, Chris ; Pluta, Jan Marian ; Porter, Jeffrey Brent ; Posik, Matthew ; Pruthi, Navneet Kumar ; Przybycien, Mariusz ; Putschke, Jörn H. ; Quintero, Amilkar ; Radhakrishnan, Sooraj Krishnan ; Ramachandran, Suvarna ; Ray, Robert L. ; Reed, Rosi Jan ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Ruan, Lijuan ; Rusnak, Jan ; Rusnakova, Olga ; Sahoo, Nihar Ranjan ; Sahu, Pradip Kumar ; Salur, Sevil ; Sandweiss, Jack H. ; Schambach, Joachim ; Schmah, Alexander ; Schmidke, William B. ; Schmitz, Norbert ; Schweid, Benjamin R. ; Seck, Florian ; Seger, Janet Elizabeth ; Sergeeva, Maria ; Seto, Richard ; Seyboth, Peter ; Shah, N. ; Shahaliev, Ehtiram ; Shanmuganathan, Prashanth V. ; Shao, M. ; Shen, W.Q. ; Shen, F. ; Shi, S.S. ; Shou, Q.Y. ; Sichtermann, Ernst P. ; Siejka, Sebastian ; Sikora, Rafał ; Šimko, Miroslav ; Singha, Subhash ; Smirnov, Nikolai ; Smirnov, Dmitri V. ; Solyst, William ; Sorensen, Paul Richard ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stanislaus, T. D. Shirvel ; Stewart, David J. ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Suaide, Alexandre Alarcon do Passo ; Sugiura, Tetsuro ; Šumbera, Michal ; Summa, Branden ; Sun, Y. ; Sun, X. ; Sun, X.M. ; Surrow, Bernd ; Svirida, Dmitry N. ; Szymański, Paweł ; Tang, Zebo ; Tang, Aihong ; Taranenko, Arkadiy ; Tarnowsky, Terence J. ; Thomas, James H. ; Timmins, Anthony Robert ; Tlusty, David ; Todoroki, Takahito ; Tokarev, Mikhail V. ; Tomkiel, Catherine A. ; Trentalange, Stephen ; Tribble, Robert E. ; Tribedy, Prithwish ; Tripathy, Srikanta Kumar ; Tsai, Oleg D. ; Tu, B. ; Ullrich, Thomas ; Underwood, David G. ; Upsal, Isaac ; Van Buren, Gene ; Vanek, Jan ; Vasiliev, Alexander Nikolaevich ; Vassiliev, Iouri ; Videbæk, Flemming ; Vokal, Stanislav ; Voloshin, Sergei ; Vossen, A. ; Wang, G. ; Wang, Y. ; Wang, F. ; Wang, Y. ; Webb, Jason C. ; Wen, L. ; Westfall, Gary D. ; Wieman, Howard ; Wissink, Scott W. ; Witt, Richard ; Wu, Y. ; Xiao, Z.G. ; Xie, Guannan ; Xie, W. ; Xu, Q.H. ; Xu, Z. ; Xu, J. ; Xu, Y.F. ; Xu, N. ; Yang, S. ; Yang, C. ; Yang, Q. ; Yang, Y. ; Ye, Z. ; Ye, Z. ; Yi, L. ; Yip, K. ; Yoo, In-Kwon ; Yu, N. ; Zbroszczyk, Hanna Paulina ; Zha, W. ; Zhang, Zuman ; Zhang, L. ; Zhang, Y. ; Zhang, X.P. ; Zhang, J. ; Zhang, S. ; Zhang, S. ; Zhang, J. ; Zhao, J. ; Zhong, C. ; Zhou, C. ; Zhou, L. ; Zhu, Z. ; Zhu, X. ; Zyzak, Maksym
New measurements of directed flow for charged hadrons, characterized by the Fourier coefficient v1, are presented for transverse momenta pT, and centrality intervals in Au+Au collisions recorded by the STAR experiment for the center-of-mass energy range √sN N = 7.7–200 GeV. The measurements underscore the importance of momentum conservation, and the characteristic dependencies on √sN N , centrality and pT are consistent with the expectations of geometric fluctuations generated in the initial stages of the collision, acting in concert with a hydrodynamic-like expansion. The centrality and pT dependencies of veven 1 , as well as an observed similarity between its excitation function and that for v3, could serve as constraints for initial-state models. The veven 1 excitation function could also provide an important supplement to the flow measurements employed for precision extraction of the temperature dependence of the specific shear viscosity.
A collection of 1149 otoliths of the Ypresian and Ypresian–Lutetian transition (early Eocene) from 18 sites across five states in the eastern and southern regions of the USA was analyzed. In total, 33 otolith-based taxa are documented, of which 27 are identified at the species level. Nine of these are introduced as new species: “Conger” biaculeatus sp. nov., Bauzaia gibbosa sp. nov., Ampheristus brevicaudatus sp. nov., Symmetrosulcus virginicus sp. nov., Neobythites longesulcatus sp. nov., “Neobythites” pamunkeyensis sp. nov., “Neobythites” stringeri sp. nov., Waitakia dorsogibbosa sp. nov., and “Haemulon” ypresiensis sp. nov. The assemblages are distinct when compared to their younger Eocene counterparts in America. This distinction is primarily characterized by the high proportion of the newly introduced species or exclusive Ypresian species. Additionally, we highlight the presence of 10 amphi-Atlantic species originally described in European deposits. Significantly, the composition of the otolith collection supports the interpretation of a shallow-water environment for the sampled sites during the Ypresian. This ecological setting appears to persist into the subsequent middle and late Eocene within the same geographic region.
Four new species of the genus Catonidia Uhler, 1896, C. triangula sp. nov., C. saccata sp. nov., C. trilobata sp. nov. and C. uncinata sp. nov. from China (Fujian, Guizhou, Yunnan and Hainan provinces), are described and illustrated, giving the genus 14 species in total. A checklist and key to all known species of Catonidia are provided, as well as a map of their geographic distributions.