bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Activated” STAT Proteins: A Paradoxical Consequence of Inhibited JAK-STAT Signaling in Cytomegalovirus-Infected Cells
Authors: Trilling Mirko , Le Vu Thuy Khanh , Rashidi-Alavijeh Jassin , Katschinski Benjamin , Scheller Jürgen , Rose-John Stefan , Androsiac Gabriela Elena , Jonjić Stipan , Poli Valeria , Pfeffer Klaus , Hengel Hartmut 
Published: December 2013

Abstract
We have previously characterized mouse CMV (MCMV)–encoded immune-evasive IFN signaling inhibition and identified the viral protein pM27 as inducer of proteasomal degradation of STAT2. Extending our analysis to STAT1 and STAT3, we found that MCMV infection neither destabilizes STAT1 protein nor prevents STAT1 tyrosine Y701 phosphorylation, nuclear translocation, or the capability to bind γ-activated sequence DNA-enhancer elements. Unexpectedly, the analysis of STAT3 revealed an induction of STAT3 Y705 phosphorylation by MCMV. In parallel, we found decreasing STAT3 protein amounts upon MCMV infection, although STAT3 expression normally is positive autoregulative. STAT3 phosphorylation depended on the duration of MCMV infection, the infectious dose, and MCMV gene expression but was independent of IFNAR1, IL-10, IL-6, and JAK2. Although STAT3 phosphorylation did not require MCMV immediate early 1, pM27, and late gene expression, it was restricted to MCMV-infected cells and not transmitted to bystander cells. Despite intact STAT1 Y701 phosphorylation, IFN-γ–induced target gene transcription (e.g., IRF1 and suppressor of cytokine signaling [SOCS] 1) was strongly impaired. Likewise, the induction of STAT3 target genes (e.g., SOCS3) by IL-6 was also abolished, indicating that MCMV antagonizes STAT1 and STAT3 despite the occurrence of tyrosine phosphorylation. Consistent with the lack of SOCS1 induction, STAT1 phosphorylation was prolonged upon IFN-γ treatment. We conclude that the inhibition of canonical STAT1 and STAT3 target gene expression abrogates their intrinsic negative feedback loops, leading to accumulation of phospho–tyrosine-STAT3 and prolonged STAT1 phosphorylation. These findings challenge the generalization of tyrosine-phosphorylated STATs necessarily being transcriptional active and document antagonistic effects of MCMV on STAT1/3-dependent target gene expression.
The p53 Transcription Factor Modulates Microglia Behavior through MicroRNA-Dependent Regulation of c-Maf
Authors: Su Wei , Hopkins Stephanie , Nesser Nicole K. , Sopher Bryce , Silvestroni Aurelio , Ammanuel Simon , Jayadev Suman , Möller Thomas , Weinstein Jonathan , Garden Gwenn A. 
Published: December 2013

Abstract
Neuroinflammation occurs in acute and chronic CNS injury, including stroke, traumatic brain injury, and neurodegenerative diseases. Microglia are specialized resident myeloid cells that mediate CNS innate immune responses. Disease-relevant stimuli, such as reactive oxygen species (ROS), can influence microglia activation. Previously, we observed that p53, a ROS-responsive transcription factor, modulates microglia behaviors in vitro and in vivo, promoting proinflammatory functions and suppressing downregulation of the inflammatory response and tissue repair. In this article we describe a novel mechanism by which p53 modulates the functional differentiation of microglia both in vitro and in vivo. Adult microglia from p53-deficient mice have increased expression of the anti-inflammatory transcription factor c-Maf. To determine how p53 negatively regulates c-Maf, we examined the impact of p53 on known c-Maf regulators. MiR-155 is a microRNA that targets c-Maf. We observed that cytokine-induced expression of miR-155 was suppressed in p53-deficient microglia. Furthermore, Twist2, a transcriptional activator of c-Maf, is increased in p53-deficient microglia. We identified recognition sites in the 3′ untranslated region of Twist2 mRNA that are predicted to interact with two p53-dependent microRNAs: miR-34a and miR-145. In this article, we demonstrate that miR-34a and -145 are regulated by p53 and negatively regulate Twist2 and c-Maf expression in microglia and the RAW macrophage cell line. Taken together, these findings support the hypothesis that p53 activation induced by local ROS or accumulated DNA damage influences microglia functions and that one specific molecular target of p53 in microglia is c-Maf.
Soluble gC1qR Is an Autocrine Signal That Induces B1R Expression on Endothelial Cells
Authors: Ghebrehiwet Berhane , Ji Yan , Valentino Alisa , Pednekar Lina , Ramadass Mahalakshmi , Habiel David , Kew Richard R. , Hosszu Kinga H. , Galanakis Dennis K. , Kishore Uday , Peerschke Ellinor I. B. 
Published: December 2013

Abstract
Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein–coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174–180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37°C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174–180 and 154–162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R.
Modulation of the seasonal footprinting mechanism by the boreal spring Arctic Oscillation
Authors: Chen Shangfeng , Chen Wen , Yu Bin , Graf Hans‐F. 
Published: December 2013

AbstractPrevious studies suggest that wintertime North Pacific Oscillation (NPO) is able to force an El Niño event during the following winter via the seasonal footprinting mechanism (SFM). In this study, we present evidence that springtime Arctic Oscillation (AO) has a significant modulation effect on the connection between the NPO and El Niño. When the spring AO is positive, a positive wintertime NPO can result in significant El Niño‐like warming anomalies via the SFM. However, when the spring AO is negative, the connection of the NPO and the El Niño is not robust at all. Thus, the phase of spring AO should be taken into account when using NPO as a predictor for El Niño. Further analysis reveals that the mechanism of the AO modulation may be through changing the underlying SST footprinting over the subtropical northeastern Pacific.
Crustal‐scale seismic profiles across the Manila subduction zone: The transition from intraoceanic subduction to incipient collision
Authors: Eakin Daniel H. , McIntosh Kirk D. , Van Avendonk H. J. A. , Lavier Luc , Lester Ryan , Liu Char‐Shine , Lee Chao‐Shing 
Published: December 2013

AbstractWe use offshore multichannel seismic (MCS) reflection and wide‐angle seismic data sets to model the velocity structure of the incipient arc‐continent collision along two trench perpendicular transects in the Bashi Strait between Taiwan and Luzon. This area represents a transition from a tectonic regime dominated by subduction of oceanic crust of the South China Sea, west of the Philippines, to one dominated by subduction and eventual collision of rifted Chinese continental crust with the Luzon volcanic arc culminating in the Taiwan orogeny. The new seismic velocity models show evidence for extended to hyperextended continental crust, ~10–15 km thick, subducting along the Manila trench at 20.5°N along transect T1, as well as evidence indicating that this thinned continental crust is being structurally underplated to the accretionary prism at 21.5°N along transect T2, but not along T1 to the south. Coincident MCS reflection imaging shows highly stretched and faulted crust west of the trench along both transects and what appears to be a midcrustal detachment along transect T2, a potential zone of weakness that may be exploited by accretionary processes during subduction. An additional seismic reflection transect south of T1 shows subduction of normal ocean crust at the Manila trench.
Impacts of background field removal on CMIP5 projected changes in Pacific winter cyclone activity
Authors: Chang Edmund K. M. 
Published: December 2013

AbstractCyclones are responsible for much of the high impact weather in the extratropics, thus how they will change under global warming is of great concern. Several studies have used the multimodel climate simulations conducted under Phase 5 of the Coupled Model Intercomparison Project (CMIP5) to examine such changes. One study suggested that the frequency of strong cyclones is projected to decrease over the North Pacific, while another concluded that this frequency will increase. A single tracking algorithm has been used to derive cyclone statistics from 23 CMIP5 simulations using two different definitions of cyclones: cyclones as minima in total sea level pressure (SLP) or cyclones as minima in SLP perturbations about a large scale, low‐frequency background. When cyclones are defined by total SLP, the frequency of deep cyclones over the Pacific is projected to increase, while if cyclones are defined as perturbations, this frequency is projected to decrease. These differences are shown to be due to a projected deepening of the climatological mean Aleutian low. In view of these results, it is important to critically assess how cyclones should be defined. Preliminary results suggest that among CMIP5 simulations, over the Pacific, both the projected changes in the frequency of high wind events and mean available potential energy are better correlated with the projected changes in the frequency of cyclones defined as perturbations. It is concluded that more research should be done to quantify and understand the impacts of the different definitions of cyclones.
Dominant‐negative effects of KCNQ2 mutations are associated with epileptic encephalopathy
Authors: Orhan Gökce , Bock Merle , Schepers Dorien , Ilina Elena I. , Reichel Stephanie Nadine , Löffler Heidi , Jezutkovic Nicole , Weckhuysen Sarah , Mandelstam Simone , Suls Arvid , Danker Timm , Guenther Elke , Scheffer Ingrid E. , De Jonghe Peter , Lerche Holger , Maljevic Snezana 
Published: December 2013

ObjectiveMutations in KCNQ2 and KCNQ3, encoding the voltage‐gated potassium channels KV7.2 and KV7.3, are known to cause benign familial neonatal seizures mainly by haploinsufficiency. Here, we set out to determine the disease mechanism of 7 de novo missense KCNQ2 mutations that were recently described in patients with a severe epileptic encephalopathy including pharmacoresistant seizures and pronounced intellectual disability.MethodsMutations were inserted into the KCNQ2 cDNA. Potassium currents were recorded using 2‐microelectrode voltage clamping, and surface expression was analyzed by a biotinylation assay in cRNA‐injected Xenopus laevis oocytes.ResultsWe observed a clear loss of function for all mutations. Strikingly, 5 of 7 mutations exhibited a drastic dominant‐negative effect on wild‐type KV7.2 or KV7.3 subunits, either by globally reducing current amplitudes (3 pore mutations) or by a depolarizing shift of the activation curve (2 voltage sensor mutations) decreasing potassium currents at the subthreshold level at which these channels are known to critically influence neuronal firing. One mutation significantly reduced surface expression. Application of retigabine, a recently marketed KV7 channel opener, partially reversed these effects for the majority of analyzed mutations.InterpretationThe development of severe epilepsy and cognitive decline in children carrying 5 of the 7 studied KCNQ2 mutations can be related to a dominant‐negative reduction of the resulting potassium current at subthreshold membrane potentials. Other factors such as genetic modifiers have to be postulated for the remaining 2 mutations. Retigabine or similar drugs may be used as a personalized therapy for this severe disease. Ann Neurol 2014;75:382–394
Study of nanoscale structural changes in isolated bamboo constituents using multiscale instrumental analyses
Authors: Nishida Masakazu , Tanaka Tomoko , Miki Tsunehisa , Shigematsu Ichinori , Kanayama Kozo , Kanematsu Wataru 
Published: December 2013

ABSTRACTTo reveal morphological changes in bamboo constituents induced by delignification and hemicelluloses removal processes, changes in chemical composition and dynamics were examined at molecular‐ to nano‐scales, using scanning electron microscopy images, attenuated total reflection infrared spectra, solid state nuclear magnetic resonance spectra, and relaxation time analysis at multiple hierarchical levels. Boiling removed spherical particles from the parenchymal cells of bamboo, leaving the cells containing water that had infiltrated into the nanostructure composed of carbohydrates and lignin. Treatment of the boiled bamboo with NaClO2 solution removed most of lignin, leaving hemicellulose chains that made the parenchymal cells stretch. In contrast, treatment of the boiled bamboo with NaOH solution removed both hemicellulose and lignin, with the result that parenchymal cells shrank in the cross‐section direction. Furthermore, treatment of the delignified bamboo with NaOH solution demolished the parenchymal cells due to complete removal of hemicellulose and lignin. A nanostructural model proposed on the basis of molecular‐ to nano‐scale analyses was consistent with the changes of vascular bundles and parenchymal cells. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40243.
Enantioselective disposition of clenbuterol in rats
Authors: Hirosawa Iori , Ishikawa Mai , Ogino Mio , Ito Hiroshi , Hirao Takuya , Yamada Harumi , Asahi Mariko , Kotaki Hajime , Sai Yoshimichi , Miyamoto Ken‐ichi 
Published: December 2013

ABSTRACTClenbuterol is a long‐acting β2‐adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (‐)‐R‐enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC‐MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1 ml volumes of plasma were precisely quantified at concentrations as low as 0.25 ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2 mg/kg) in rats were significantly different. The distribution volume of (‐)‐R‐clenbuterol (9.17 l/kg) was significantly higher than that of (+)‐S‐clenbuterol (4.14 l/kg). The total body clearance of (‐)‐R‐clenbuterol (13.5 ml/min/kg) was significantly higher than that of the (+)‐S‐enantiomer (11.5 ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (‐)‐R‐ and (+)‐S‐enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (‐)‐R‐clenbuterol was higher than that of the (+)‐S‐enantiomer. The fractions of free (non‐protein‐bound) (‐)‐R‐ and (+)‐S‐clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding. Copyright © 2013 John Wiley & Sons, Ltd.
A Description–Experience Gap in Social Interactions: Information about Interdependence and Its Effects on Cooperation
Authors: Martin Jolie M. , Gonzalez Cleotilde , Juvina Ion , Lebiere Christian 
Published: December 2013

ABSTRACTIn social interactions, decision makers are often unaware of their interdependence with others, precluding the realization of shared long‐term benefits. In an experiment, pairs of participants played an Iterated Prisoner's Dilemma under various conditions involving differing levels of interdependence information. Each pair was assigned to one of four conditions: “No‐Info” players saw their own actions and outcomes, but were not told that they interacted with another person; “Min‐Info” players knew they interacted with another person but still without seeing the other's actions or outcomes; “Mid‐Info” players discovered the other's actions and outcomes as they were revealed over time; and “Max‐Info” players were also shown a complete payoff matrix mapping actions to outcomes from the outset and throughout the game. With higher levels of interdependence information, we found increased individual cooperation and mutual cooperation, driven by increased reciprocating cooperation (in response to a counterpart's cooperation). Furthermore, joint performance and satisfaction were higher for pairs with more information. We discuss how awareness of interdependence may encourage cooperative behavior in real‐world interactions. Copyright © 2013 John Wiley & Sons, Ltd.
Suspension and optical properties of the crystalline lens in the eyes of basal vertebrates
Authors: Kröger Ronald H.H. , Gustafsson Ola S.E. , Tuminaite Inga 
Published: December 2013

AbstractWe have investigated the apparatus suspending the crystalline lens in the eyes of basal vertebrates. Data are presented for Holocephali (Chondrichthyes) and the actinopterygians Polypteriformes, Polyodontidae (Acipenseriformes), Lepisosteiformes, Amiiformes, and one teleost species, the banded archerfish (Toxotes jaculatrix). We also studied the optical properties of the lens in Polypteriformes, Lepisosteiformes, and the archerfish. Together with previously published results, our findings show that there are three basic types of lens suspension in vertebrates. These are i) a rotationally symmetric suspension (Petromyzontida, lampreys; Ceratodontiformes, lungfishes; Tetrapoda), ii) a suspension with a dorso‐ventral axis of symmetry and a ventral papilla (all Chondrichthyes and Acipenseriformes), and iii) an asymmetric suspension with a ventral muscle and a varying number of ligaments (all Actinopterygii except for Acipenseriformes). Large eyes with presumably high spatial resolution have evolved in all groups. Multifocal lenses creating well‐focused color images are also present in all groups studied. Stable and exact positioning of the lens, in many cases in combination with accommodative changes in lens position or shape, is achieved by all three types of lens suspension. It is somewhat surprising that lens suspensions are strikingly similar in Chondrichthyes and Acipenseriformes (Actinopterygii), while the suspension apparatus in Polypteriformes, usually being regarded as an actinopterygian group more basal than Acipenseriformes, are considerably more teleostean‐like. This study completes a series of investigations on lens suspensions in nontetrapod vertebrates, covering all major groups except for the rare and highly derived coelacanths. J. Morphol. 275:613–622, 2014. © 2013 Wiley Periodicals, Inc.
Mass spectrometry analysis of nitrotyrosine‐containing proteins
Authors: Zhan Xianquan , Wang Xiaowei , Desiderio Dominic M. 
Published: December 2013

AbstractOxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a protein is a chemically stable oxidative modification, and a marker of oxidative injuries. Mass spectrometry (MS) is a key technique to identify nitrotyrosine‐containing proteins and nitrotyrosine sites in endogenous and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine‐containing proteins occur with extreme low‐abundance to severely challenge the use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A preferential enrichment of nitroproteins and/or nitropeptides is necessary before MS analysis. Current enrichment methods include immuno‐affinity techniques, chemical derivation of the nitro group plus target isolations, followed with tandem mass spectrometry analysis. This article reviews the MS techniques and pertinent before‐MS enrichment techniques for the identification of nitrotyrosine‐containing proteins. This article reviews future trends in the field of nitroproteomics, including quantitative nitroproteomics, systems biological networks of nitroproteins, and structural biology study of tyrosine nitration to completely clarify the biological functions of tyrosine nitration. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 34: 423–448, 2015.
Multivariate age‐dependent imperfect repair
Authors: Sheu Shey‐Huei , Griffith William S. 
Published: December 2013

AbstractIn this article we consider models of systems whose components have dependent life lengths with specific multivariate distributions. Upon failure, components are repaired. Two types of repair are distinguished. After perfect repair, a unit has the same life distribution as a new item. After imperfect repair, a unit has the life distribution of an item which is of the same age but has never failed. We study a model in which the mechanism for determining the nature of the repair is age dependent.
Testing guaranteed exponentiality
Authors: Shanmugam Ramalingam 
Published: December 2013

AbstractAmong distributions that are used in survival analysis, of interest to us here is the Guaranteed exponential (for details about the distribution, see Gross and Clark 7). In this article, we present a new approach to testing guaranteed exponentiality. Using engineering data on the number of load cycles until a crack appears in the titanium and steel sheet in aircraft, medical data on the number of weeks tumor patients survived, data on modulus of rupture, a measurement on the breaking strength of lumber, and original I.Q. data on 112 children attending kindergarten classes in San Jose and San Mateo Counties, CA, we illustrate our method. The first two data sets are known to follow exponential distribution, while the last data set is known to follow normal distribution. Our method confirms these and nonexponentiality for the third data set. A discussion on the merits and disadvantages of our approach is included. Based on simulation, a comparison is made between the power of our test and EDF test statisticA2. Our test has excellent power for many nonexponential alternatives.