bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1
Authors: Hong Gregory K. , Delecluse Henri-Jacques , Gruffat Henri , Morrison Thomas E. , Feng Wen-Hai , Sergeant Alain , Kenney Shannon C. 
Published: April 2004

ABSTRACTThe switch from the latent to the lytic form of Epstein-Barr virus (EBV) infection is mediated by expression of the viral immediate-early (IE) proteins, BZLF1 (Z) and BRLF1 (R). An EBV early protein, BRRF1 (Na), is encoded by the opposite strand of the BRLF1 intron, but the function of this nuclear protein in the viral life cycle is unknown. Here we demonstrate that Na enhances the R-mediated induction of lytic EBV infection in 293 cells latently infected with a recombinant EBV (R-KO) defective for the expression of both R and Na. Na also enhances R-induced lytic infections in a gastric carcinoma line (AGS) carrying the R-KO virus, although it has no effect in a Burkitt lymphoma line (BL-30) stably infected with the same mutant virus. We show that Na is a transcription factor that increases the ability of R to activate Z expression from the R-KO viral genome in 293 cells and that Na by itself activates the Z promoter (Zp) in EBV-negative cells. Na activation of Zp requires a CRE motif (ZII), and a consensus CRE motif is sufficient to transfer Na responsiveness to the heterologous E1b promoter. Furthermore, we show that Na enhances the transactivator function of a Gal4-c-Jun fusion protein but does not increase the transactivator function of other transcription factors (including ATF-1, ATF-2, and CREB) known to bind CRE motifs. Na expression in cells results in increased levels of a hyperphosphorylated form of c-Jun, suggesting a mechanism by which Na activates c-Jun. Our results indicate that Na is a transcription factor that activates the EBV Zp IE promoter through its effects on c-Jun and suggest that Na cooperates with BRLF1 to induce the lytic form of EBV infection in certain cell types.
Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion
Authors: Rodriguez Jason J. , Cruz Cristian D. , Horvath Curt M. 
Published: April 2004

ABSTRACT

The V proteins of Nipah virus and Hendra virus have been demonstrated to bind to cellular STAT1 and STAT2 proteins to form high-molecular-weight complexes that inhibit interferon (IFN)-induced antiviral transcription by preventing STAT nuclear accumulation. Analysis of the Nipah virus V protein has revealed a region between amino acids 174 and 192 that functions as a CRM1-dependent nuclear export signal (NES). This peptide is sufficient to complement an export-defective human immunodeficiency virus Rev protein, and deletion and substitution mutagenesis revealed that this peptide is necessary for both V protein shuttling and cytoplasmic retention of STAT1 and STAT2 proteins. However, the NES is not required for V-dependent IFN signaling inhibition. IFN signaling is blocked primarily by interaction between Nipah virus V residues 100 to 160 and STAT1 residues 509 to 712. Interaction with STAT2 requires a larger Nipah virus V segment between amino acids 100 and 300, but deletion of residues 230 to 237 greatly reduced STAT2 coprecipitation. Further, V protein interactions with cellular STAT1 is a prerequisite for STAT2 binding, and sequential immunoprecipitations demonstrate that V, STAT1, and STAT2 can form a tripartite complex. These findings characterize essential regions for
Henipavirus
V proteins that represent potential targets for therapeutic intervention.
Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses
Authors: Garbutt Michael , Liebscher Ryan , Wahl-Jensen Victoria , Jones Steven , Möller Peggy , Wagner Ralf , Volchkov Viktor , Klenk Hans-Dieter , Feldmann Heinz , Ströher Ute 
Published: April 2004

ABSTRACT
Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the foreign transmembrane glycoproteins in replacement of the VSV glycoprotein were slightly attenuated in growth. Biosynthesis and processing of the foreign glycoproteins were authentic, and the cell tropism was defined by the transmembrane glycoprotein. None of the rVSVs displayed pathogenic potential in animals. The rVSV expressing the Zaire Ebola virus transmembrane glycoprotein mediated protection in mice against a lethal Zaire Ebola virus challenge. Our data suggest that the recombinant VSV can be used to study the role of the viral glycoproteins in virus replication, immune response, and pathogenesis.
Regional Differences in Viral Growth and Central Nervous System Injury Correlate with Apoptosis
Authors: Richardson-Burns Sarah M. , Tyler Kenneth L. 
Published: April 2004

ABSTRACT
Infection of neonatal mice with reovirus T3 Dearing (T3D), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. T3D variant K (VarK) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to T3D and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. We wished to determine whether the restricted pattern of VarK-induced injury was due to a reduced capacity to replicate in or injure cortical, as opposed to hippocampal, tissue. We found that following i.c. inoculation, VarK grew to similar titers as T3D in the hippocampus but had significantly lower titers in the cortex. Both viruses grew to identical titers and infected the same percentage of cells in mouse primary hippocampal cultures (MHC). In mouse primary cortical cultures (MCC) both the number of infected cells and the viral yield per infected cell were significantly lower for VarK than T3D. VarK-induced apoptosis was limited to the hippocampus in vivo, and in vitro both viruses induced apoptosis equally in MHC but VarK induced significantly less apoptosis than T3D in MCC. Growth of T3D in MCC was reduced to levels comparable to those of VarK following treatment of MCC with caspase inhibitors. Conversely, induction of apoptosis in VarK-infected MCC with fatty acid synthase-activating antibody significantly enhanced viral yield. These results suggest that the decreased neurovirulence of VarK may be due to its failure to efficiently induce apoptosis in cortical neurons.
Moby-Dick and Compassion
Authors: Armstrong Philip 
Published: April 2004

AbstractBecause the notions of "anthropomorphism" and "sentimentality" often are used pejoratively to dismiss research in human-animal studies, there is much to be gained from ongoing and detailed analysis of the changing "structures of feeling" that shape representations and treatments of nonhuman animals. Literary criticism contributes to this project when it pays due attention to differences in historical and cultural contexts. As an example of this approach, a reading of the humanization of cetaceans in Herman Melville's Moby-Dick - and more broadly in nineteenth-century whaling discourse - demonstrates how radically human feelings for nonhuman species are affected by shifting material and ideological conditions.
NMR Studies of electrostatic fields around charged monosaccharides and related molecules
Authors: Glaser Robert , Novoselsky Artem , Shames Alexander , Likhtenshtein Gertz I. 
Published: April 2004

AbstractA new and simple technique has been developed to experimentally measure electrostatic fields around charged molecules in solution. Using a series of three charged or neutral [4‐hydroxy (or carboxy or amino)‐2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO)] spin probes, the apparent rate constants (k+, ko, and k‐) for a particular nucleus can be calculated as the slope of 1/T1 (i.e., the spin‐lattice relaxation rate) vs. increasing radical concentration. Protons residing within a particular charged region suffer a decrease in their apparent rate constants due to repulsive interactions when the nitroxide spin probe bears the same charge‐type as that of the local electrostatic environment. Accordingly, electrostatic forces of attraction increase the apparent rate constants for these same protons when the nitroxide spin probe bears the opposite charge to that present in the local electrostatic field. The apparent rate constants of the neutral nitroxide spin probe are an indication of the solvent accessibility to that particular site in the molecule being investigated. Ratios of these apparent relaxation rate constants (k+/k‐ > 1 or k‐/k+ > 1, etc.) thus provide a measurement of the sign and magnitude of the local electrostatic fields surrounding a particular proton in the target molecule. Three charged hexosamines [D‐glucosamine·HCl (4), D‐galactosamine·HCl (5), and D‐mannosamine·HCl (6)], a glucuronide metabolite of paracetamol [p‐acetamidophenyl‐ß‐D‐glucuronide sodium salt (7)], and a mononucleotide [thymidine‐3′‐phosphate sodium salt (8)], were investigated in this study. Positively charged environments around protons in the hexosamines are clearly seen by ko/k+ ratios greater than unity, while negatively charged surroundings about protons in the glucuronide and nucleotide are markedly evident from larger than unity k+/k‐ and ko/k‐ ratios. In the case of small charged target molecules such as 6–8, the electrostatic field seems to envelop the entire molecule. In general, a lack of statistically significant differences in the kattraction/krepulsion or kneutral/krepulsion ratios as a function of proton distance from the charged functionality was observed. This finding (with the possible exception of the methyl protons in 7) suggests that the present version of this method is not sensitive enough to map subtle differences in charged environments around small and conformationally flexible or dynamic target molecules.
Layer‐by‐layer deposition of J‐aggregates and polyelectrolytes for electroluminescence applications: A spectroscopic study
Authors: Kirstein Stefan , Bourbon Sebastien , Gao Mingyuan , De Rossi Umberto 
Published: April 2004

AbstractThe self‐assembly method of layer‐by‐layer deposition of oppositely charged polyelectrolytes is used to insert J‐aggregates of the dye tetrachloro‐diethyl‐disulfobutyl‐benzimido‐carbocyanine (TDBC) into thin polymeric films. The J‐aggregates are characterized by a narrow absorption‐ and fluorescence band with its maximum at 590 nm, which is red‐shifted with respect to the monomeric transition at 515 nm. The dyes are either coadsorbed with the polyelectrolytes poly(allylamine hydrochloride (PAH) and poly(styrene sulfonate) (PSS), or alternately deposited with the precursor of poly(phenylene vinylene) (pre‐PPV). The optical properties of the aggregates are not changed significantly by the deposition process. The pre‐PPV/TDBC films are heated under vacuum to convert the PPV to its conjugated form. The resulting films can be used for the fabrication of light‐emitting devices. The optical properties such as fluorescence and electroluminescence are dominated by the J‐aggregates. The excitation energy of PPV is transferred to the dye aggregates with an efficiency of 100%. The electroluminescence is not very stable and shows a very slow turn‐on time. However, the combination of self‐assembled PPV/TDBC layers with a spin‐coated film of PPV results in stable electroluminescence emission under ambient conditions. In this case, light is emitted from both species, the PPV and the J‐aggregates, whereas the ratio of the two intensities strongly depends on temperature.
Multi‐domain binding of cytochrome c peroxidase by cytochrome c: Thermodynamic vs. microscopic binding constants
Authors: Nocek Judith M. , Leesch Valerie W. , Zhou Jian S. , Jiang Min , Hoffman Brian M. 
Published: April 2004

AbstractWe have demonstrated that cytochrome c (Cc) binds to cytochrome c peroxidase (Cc P) with a 2:1 stoichiometry, and that: (i) Cc reacts at two distinct and non‐exclusive surface domains of Cc P; (ii) two molecules of Cc can bind simultaneously to Cc P; and (iii) the ternary complex is more reactive than the binary complex for the heme—heme reaction. The quenching studies, however, provide only stoichiometric (thermodynamic) parameters. They do not directly probe the microscopic properties of the individual domains, and thus do not apportion the reactivity due to 1:1 stoichiometry between the two types of binary complexes: one with Cc bound at the high‐affinity domain and one with Cc bound at a low‐affinity domain. We describe here a method for analyzing the stoichiometric parameters obtained from triplet quenching titrations to partition the quenching of ZnCc by Cc P into contributions from the binary and ternary complexes, and also to give limits on the partition of the quenching into contributions from the low‐ and high‐affinity binding domains. By applying this method to the experimental quenching titration data for the multi‐domain binding of Cc to Cc P, we were able to evaluate, for the first time, the functional relevance of the low‐affinity domain in the binary and ternary complexes at both low and high ionic strength. At low ionic strength, essentially no Cc binds at the low‐affinity domain in a binary complex. However, reactivity at this domain is significant and indeed can be dominant, in the ternary complex, which does form with measureable concentration. At higher, more physiologically‐relevant ionic strengths, very little ternary complex forms, but now the situation is changed, and there is significant reactivity from the 1:1 complex with Cc bound at the low‐affinity domain. In other words, there is substantial reactivity from Cc bound at the weakly binding domain over a wide range of ionic strengths, either in a binary or a ternary complex. Finally, we suggest that at high ionic strength, interactions between the two bound Cc are shielded such that it is easier to bind the second Cc molecule when one domain is occupied already.
Adhesion studies using contact mechanics
Authors: Ulman Abraham , Choi Gun‐Young , Shnidman Yitzhak , Zurawsky Walter 
Published: April 2004

AbstractWe report adhesion studies using the JKR contact mechanics method and poly(dimethylsiloxane) (PDMS) cross‐linked networks. When such networks are extracted, interdigitation of tethered chains into extraction zones at the network‐network interface results in a significant enhancement of adhesion. When these networks come into contact with a silicon oxide surface, an increase in adhesion hysteresis is observed in the order of increasing molecular weight between crosslinks, with a scaling factor of 1/2. Subjecting the system to maximum load for 30 min before unloading results in a scaling factor of 1/3, probably due to molecular weight dependent network relaxation rates. PDMS cross‐link networks form H‐bonds with surface Si–OH groups that result in significant and time‐dependent adhesion increase. Systematic studies of interfacial H‐bonding and its effect on adhesion have been carried out using self‐assembled monolayer (SAM) surfaces. An increase in adhesion strength was observed in the order of increasing acidity of surface OH protons [Au/S(CH2)11OH < Au/S(C6H4)2OH < Au/S(CH2)15COOH < Au/S(CH2)11PO(OH)2]. When surface OH concentration was controlled, the strength of adhesion was found to be proportional to the number of surface OH groups, with nonlinear relationship, probably due to the collective nature of H‐bonding between the PDMS chain and surface OH groups. Isotope effect studies confirmed the formation of interfacial H‐bonding.
Parametric MRI of Water Diffusion in Breast Cancer
Authors: Paran Yael , Adansky‐Boldin Swetlana A. , Margalit Raanan , Degani Hadassa 
Published: April 2004

AbstractDiffusion MRI studies revealed specific morphological and physiological properties of MCF7 tumors implanted in the mammary gland of immunodeficient mice. These tumors mimic the histological and pathophysiological properties of human breast cancer in patients. The experiments were conducted by (1) applying varying diffusion gradient strengths, Gd, from 0 to 20 G/cm and a short diffusion time (td = 16 ms) in order to minimize the effect of restriction and exchange of water between the intra‐ and extracellular compartments, and (2) applying a strong constant gradient and diffusion times up to 96 ms, revealing water restriction and exchange. The normalized signal intensity was plotted against the diffusion weighting factor b, taking into account interaction with the imaging gradients. The curves were analyzed by applying a bi‐exponential decay function assuming two exchanging water compartments, with fast and slow diffusion coefficients. The amplitudes and decay constants of the two exponents, a fast and a slow one, were related to the fraction and apparent diffusion coefficients of the extra‐ and intracellular water, respectively, considering contributions of restriction and exchange. During tumor progression the distribution of the diffusion parameters for the same experimental protocol varied and became less homogeneous. This was predominantly due to variations in the cellularity and increased necrosis. Upon treatment of the tumors with a new anti‐estrogenic drug, tamoxifen methiodide, the changes in the diffusion parameters indicated increased cell swelling. Hence, this cytostatic response to treatment was detected before actual cell death was apparent. The potential capacity of diffusion MRI is of high clinical relevance and may help improve the noninvasive diagnosis and followup of treatment of this devastating disease.
Suppression of sialylated by sulfated oligosaccharides in negative MALDI‐FTMS
Authors: An Hyun Joo , Lebrilla Carlito B. 
Published: April 2004

AbstractSialylated oligosaccharides are suppressed by sulfated oligosaccharides during matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. The sialylated oligosaccharide may be suppressed by as much as a factor of ten to twenty. This suppression factor is constant over a large concentration range. As both sialylated and sulfated (or anionic) oligosaccharides are found together in many biological systems, the suppression has important consequences in the analysis of these compounds. Methods for overcoming the effect of suppression without laborious separation are provided.
UV resonance Raman probe of heme‐bound imidazole established by 15N‐labeling of hemoglobin
Authors: Zhao Xiaojie , Chen Ruopian , Deng Qing , Mabrouk Patricia Ann , Spiro Thomas G. 
Published: April 2004

AbstractRecent studies of Cu, Zn superoxide dismutase, and of zinc‐finger peptides have established that histidine ligands can be detected in ultraviolet resonance Raman (UVRR) spectra, following NH/D exchange of the imidazole. UVRR spectroscopy therefore offers promise for monitoring histidine ligation in heme proteins. In this work, we characterize heme‐bound histidine UVRR bands for N‐acetyl‐microperoxidase‐8 (MP‐8) and microperoxidase‐11 (MP‐11), and also for hemoglobin (Hb). The Hb UVRR spectra are dominated by tyrosine and tryptophan contributions, but a band appears at 1340 cm−1 in D2O solution, which is assigned to a mode of Fe‐bound imidazole. This band shifted 24 cm−1 in protein which was labeled with 15N via expression of the Hb gene in E. coli grown on 15NH4+. In MP‐11, the position of this band is insensitive to ligation or oxidation state changes, but it is 2 cm−1 lower in deoxyHb than in the CO adduct. This shift may reflect mechanical forces on the proximal histidine in the T state, and/or changes in its H‐bonding.
Synthesis, structure, and thermal behavior of [Cu70Se35(PEt2Ph)24]
Authors: Eichhöfer Andreas , Beckmann Erich , Fenske Dieter , Herein Daniel , Krautscheid Harald , Schlögl Robert 
Published: April 2004

AbstractWe investigated the molecular and crystal structure as well as the thermal behavior of [Cu70Se35(PEt2Ph)24] using single‐crystal X‐ray diffraction, high‐resolution transmission electron microscopy (HRTEM), X‐ray powder diffractometry, and thermal gravimetric analysis (TGA). The use of a He‐cooled sample head in HRTEM makes possible for the first time the investigation of semiconductor cluster molecules under the extreme conditions of the experiment and, thus, comparison with the results of single‐crystal X‐ray diffraction. The lattice spacings and packing symmetry of the three‐dimensional cluster molecule superlattice found in HRTEM are in good agreement with the ones determined by X‐ray structure diffraction. The atomic ordering inside the cluster molecules, which resembles a hexagonal packing of the selenium atoms, could not be resolved in the HRTEM measurements, since upon irradiation with the electron beam the clusters start to move after a few seconds and the images go out of focus. This movement is possibly affected by cleavage processes of the phosphine ligands, as could be observed in thermal gravimetric analysis under comparably mild conditions. Powder diffraction measurements show that this cleavage of ligand molecules is accompanied by the formation of larger copper selenide cluster cores and ends up at high temperatures in the formation of bulk α‐Cu2Se.