bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus-Encoded Protein Kinase and Its Interaction with K-bZIP
Authors: Izumiya Yoshihiro , Izumiya Chie , Van Geelen Albert , Wang Don-Hong , Lam Kit S. , Luciw Paul A. , Kung Hsing-Jien 
Published: November 2006

ABSTRACT
The oncogenic herpesvirus, Kaposi's sarcoma-associated herpesvirus, also identified as human herpesvirus 8, contains genes producing proteins that control transcription and influence cell signaling. Open reading frame 36 (ORF36) of this virus encodes a serine/threonine protein kinase, which is designated the viral protein kinase (vPK). Our recent efforts to elucidate the role of vPK in the viral life cycle have focused on identifying viral protein substrates and determining the effects of vPK-mediated phosphorylation on specific steps in viral replication. The vPK gene was transcribed into 4.2-kb and 3.6-kb mRNAs during the early and late phases of viral reactivation. vPK is colocalized with viral DNA replication/transcription compartments as marked by a polymerase processivity factor, and K-bZIP, a protein known to bind the viral DNA replication origin (Ori-Lyt) and to regulate viral transcription. The vPK physically associated with and strongly phosphorylated K-bZIP at threonine 111, a site also recognized by the cyclin-dependent kinase Cdk2. Both K-bZIP and vPK were corecruited to viral promoters targeted by K-bZIP as well as to the Ori-Lyt region. Phosphorylation of K-bZIP by vPK had a negative impact on K-bZIP transcription repression activity. The extent of posttranslational modification of K-bZIP by sumoylation, a process that influences its repression function, was decreased by vPK phosphorylation at threonine 111. Our data thus identify a new role of vPK as a modulator of viral transcription.
Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovirus Glycoprotein B, Phosphoprotein 65-2, and Viral Interleukin-10 in Rhesus Macaques
Authors: Yue Yujuan , Kaur Amitinder , Eberhardt Meghan K. , Kassis Nadine , Zhou Shan Shan , Tarantal Alice F. , Barry Peter A. 
Published: November 2006

ABSTRACT

Rhesus cytomegalovirus (RhCMV) infection of macaques exhibits strong similarities to human CMV (HCMV) persistence and pathogenesis. The immunogenicity of DNA vaccines encoding three RhCMV proteins (a truncated version of glycoprotein B lacking the transmembrane region and endodomain [gBΔTM], phosphoprotein 65-2 [pp65-2], and viral interleukin-10 [vIL-10]) was evaluated in rhesus macaques. Two groups of monkeys (four per group) were genetically immunized four times with a mixture of either pp65-2 and gBΔTM or pp65-2, vIL-10, and gBΔTM. The vaccinees developed anti-gB and anti-pp65-2 antibodies in addition to pp65-2 cellular responses after the second booster immunization, with rapid responses observed with subsequent DNA injections. Weak vIL-10 immune responses were detected in two of the four immunized animals. Neutralizing antibodies were detected in seven monkeys, although titers were weak compared to those observed in naturally infected animals. The immunized monkeys and naïve controls were challenged intravenously with 10
5
PFU of RhCMV. Anamnestic binding and neutralizing antibody responses were observed 1 week postchallenge in the vaccinees. DNA vaccination-induced immune responses significantly decreased peak viral loads in the immunized animals compared to those in the controls. No difference in peak viral loads was observed between the pp65-2/gBΔTM DNA- and pp65-2/vIL-10/gBΔTM-vaccinated groups. Antibody responses to nonvaccine antigens were lower postchallenge in both vaccine groups than in the controls, suggesting long-term control of RhCMV protein expression. These data demonstrated that DNA vaccines targeting the RhCMV homologues of HCMV gB and pp65 altered the course of acute and persistent RhCMV infection in a primate host.
Retinoic Acid-Inducible Gene I Mediates Early Antiviral Response and Toll-Like Receptor 3 Expression in Respiratory Syncytial Virus-Infected Airway Epithelial Cells
Authors: Liu Ping , Jamaluddin Mohammad , Li Kui , Garofalo Roberto P. , Casola Antonella , Brasier Allan R. 
Published: November 2006

ABSTRACT
Respiratory syncytial virus (RSV) is one of the most common viral pathogens causing severe lower respiratory tract infections in infants and young children. Infected host cells detect and respond to RNA viruses using different mechanisms in a cell-type-specific manner, including retinoic acid-inducible gene I (RIG-I)-dependent and Toll-like receptor (TLR)-dependent pathways. Because the relative contributions of these two pathways in the recognition of RSV infection are unknown, we examined their roles in this study. We found that RIG-I helicase binds RSV transcripts within 12 h of infection. Short interfering RNA (siRNA)-mediated RIG-I “knockdown” significantly inhibited early nuclear factor-κB (NF-κB) and interferon response factor 3 (IRF3) activation 9 h postinfection (p.i.). Consistent with this finding, RSV-induced beta interferon (IFN-β), interferon-inducible protein 10 (IP-10), chemokine ligand 5 (CCL-5), and IFN-stimulated gene 15 (ISG15) expression levels were decreased in RIG-I-silenced cells during the early phase of infection but not at later times (18 h p.i.). In contrast, siRNA-mediated TLR3 knockdown did not affect RSV-induced NF-κB binding but did inhibit IFN-β, IP-10, CCL-5, and ISG15 expression at late times of infection. Further studies revealed that TLR3 knockdown significantly reduced NF-κB/RelA transcription by its ability to block the activating phosphorylation of NF-κB/RelA at serine residue 276. We further found that TLR3 induction following RSV infection was regulated by RIG-I-dependent IFN-β secreted from infected airway epithelial cells and was mediated by both IFN response-stimulated element (ISRE) and signal transducer and activator of transcription (STAT) sites in its proximal promoter. Together these findings indicate distinct temporal roles of RIG-I and TLR3 in mediating RSV-induced innate immune responses, which are coupled to distinct pathways controlling NF-κB activation.
The Old World and New World Alphaviruses Use Different Virus-Specific Proteins for Induction of Transcriptional Shutoff
Authors: Garmashova Natalia , Gorchakov Rodion , Volkova Eugenia , Paessler Slobodan , Frolova Elena , Frolov Ilya 
Published: November 2006

ABSTRACT
Alphaviruses
are widely distributed throughout the world. During the last few
thousand years, the New World viruses, including Venezuelan equine
encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV),
evolved separately from those of the Old World, i.e., Sindbis virus
(SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our
study indicate that both groups have developed the same characteristic:
their replication efficiently interferes with cellular transcription
and the cell response to virus replication. Transcriptional shutoff
caused by at least two of the Old World alphaviruses, SINV and SFV,
which belong to different serological complexes, depends on nsP2, but
not on the capsid protein, functioning. Our data suggest that the New
World alphaviruses VEEV and EEEV developed an alternative mechanism of
transcription inhibition that is mainly determined by their capsid
protein, but not by the nsP2. The ability of the VEEV capsid to inhibit
cellular transcription appears to be controlled by the amino-terminal
fragment of the protein, but not by its protease activity or by the
positively charged RNA-binding domain. These data provide new insights
into alphavirus evolution and present a plausible explanation for the
particular recombination events that led to the formation of western
equine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors.
The recombination allowed WEEV to acquire capsid protein functioning in
transcription inhibition from EEEV-like virus. Identification of the
new functions in the New World alphavirus-derived capsids opens an
opportunity for developing new, safer alphavirus-based gene expression
systems and designing new types of attenuated vaccine strains of VEEV
and
EEEV.
Vaccinia Virus A6L Encodes a Virion Core Protein Required for Formation of Mature Virion
Authors: Meng Xiangzhi , Embry Addie , Sochia Debbi , Xiang Yan 
Published: November 2006

ABSTRACT
Vaccinia virus A6L is a previously uncharacterized gene that is conserved in all sequenced vertebrate poxviruses. Here, we constructed a recombinant vaccinia virus encoding A6 with an epitope tag and showed that A6 was expressed in infected cells after viral DNA replication and packaged in the core of the mature virion. Furthermore, we showed that A6 was essential for vaccinia virus replication by performing clustered charge-to-alanine mutagenesis on A6, which resulted in two vaccinia virus mutants (vA6L-mut1 and vA6L-mut2) that displayed a temperature-sensitive phenotype. At 31°C, both mutants replicated efficiently; however, at 40°C, vA6L-mut1 grew to a low titer, while vA6L-mut2 failed to replicate. The A6 protein expressed by vA6L-mut2 exhibited temperature-dependent instability. At the nonpermissive temperature, vA6L-mut2 was normal at viral gene expression and viral factory formation, but it was defective for proteolytic processing of the precursors of several major virion proteins, a defect that is characteristic of a block in virion morphogenesis. Electron microscopy further showed that the morphogenesis of vA6L-mut2 was arrested before the formation of immature virion with nucleoid and mature virion. Taken together, our data show that A6 is a virion core protein that plays an essential role in virion morphogenesis.
Verification phase as a useful tool in the determination of the maximal oxygen uptake of distance runners
Authors: Midgley Adrian W. , McNaughton Lars R. , Carroll Sean 
Published: November 2006

This study investigated the utility of a verification phase for increasing confidence that a “true” maximal oxygen uptake had been elicited in 16 male distance runners (mean age (±SD), 38.7 (± 7.5 y)) during an incremental treadmill running test continued to volitional exhaustion. After the incremental test subjects performed a 10 min recovery walk and a verification phase performed to volitional exhaustion at a running speed 0.5 km·h–1 higher than that attained during the last completed stage of the incremental phase. Verification criteria were a verification phase peak oxygen uptake ≤ 2% higher than the incremental phase value and peak heart rate values within 2 beats·min–1 of each other. Of the 32 tests, 26 satisfied the oxygen uptake verification criterion and 23 satisfied the heart rate verification criterion. Peak heart rate was lower (p = 0.001) during the verification phase than during the incremental phase, suggesting that the verification protocol was inadequate in eliciting maximal values in some runners. This was further supported by the fact that 7 tests exhibited peak oxygen uptake values over 100 mL·min–1 (≥ 3%) lower than the peak values attained in the incremental phase. Further research is required to improve the verification procedure before its utility can be confirmed.
Influence de la phase du cycle menstruel sur les réponses en catécholamines à l’exercice de sprint chez la femme
Authors: Botcazou Maïtel , Gratas-Delamarche Arlette , Allain Stéphanie , Jacob Christophe , Bentué-Ferrer Danièle , Delamarche Paul , Zouhal Hassane 
Published: November 2006

The aim of the present study was to verify the menstrual cycle phase influence on catecholamine concentrations (adrenaline (A) and noradrenaline (NA)), peak power (Ppic), and peak lactatemia (Lapic) in response to a 6 s sprint exercise on a cycle ergometer in eight untrained women (19.1 ± 0.9 years, 167.7 ± 5.4 cm, 59.5 ± 4.7 kg). All women realize the 6 s sprint test in the morning, within the same menstrual cycle, in the follicular (PF) and the luteal phase (PL). Plasma catecholamine concentrations were determined at rest (A0 and NA0), immediately at the end of the sprint exercise (AEX and NAEX), and after 5 min of recovery (A5 and NA5). Ppic and Lapic were not significantly affected by the menstrual cycle phase. Catecholamine concentrations measured at rest, in response to the 6 s sprint test and after 5 min of recovery were not significantly different in PF and PL. Significant relationships were observed between AEX and Lapic (r = 0.53, p < 0.01) and between AEX and Ppic (r = 0.70, p < 0.01). In conclusion, this study demonstrated that the menstrual cycle phase did not alter performance, lactatemia, and sympatho-adrenergic responses to a short sprint exercise in untrained women.
Relationship between right ventricular wave speed and elastance in dogs
Authors: Sun Yichun , Wang Jiun-Jr , Belenkie Israel , Tyberg John V. 
Published: November 2006

Wave speed (c) must be known to separate forward- and backward-going waves during wave-intensity analysis, which measures the energy transported by the waves in the circulation. c is related to elastance; the present study was performed to measure right ventricular (RV) c during the cardiac cycle and to compare c with RV elastance. In 7 dogs, we measured right atrial, pulmonary arterial, pericardial and 2 RV pressures, and pulmonary arterial flow. A pulse generator was connected to the RV apex, and c was measured by determining the transit time between the 2 high-fidelity RV pressure transducers; the distance was measured roentgenographically. Eight sonomicrometry crystals were implanted in the RV endocardium to calculate RV volume and, thereby, elastance. RV c ranged from ~1 m/s during diastole to ~4 m/s during systole. Log–log plots of c vs. elastance were linear. These slopes represent the power relationships between c and elastance and ranged from 0.30 to 0.56; for the combined data, it was 0.31. Given knowledge of c, forward- and backward-going waves can be identified and their energy quantitated. In the canine RV, c is approximately proportional to 1/3 the power of elastance: log c = 0.31·log E – 2.05.
Roger Sperry: pioneer of neuronal specificity
Authors: Grafstein Bernice 
Published: November 2006

This essay looks at the historical significance of two APS classic papers that are freely available online:Sperry RW.Optic nerve regeneration with return of vision in anurans. J Neurophysiol 7: 57–69, 1944 ( http://jn.physiology.org/cgi/reprint/7/1/57 ).Sperry RW.Restoration of vision after crossing of optic nerves and after contralateral transplantation of eye. J Neurophysiol 8: 15–28, 1945 ( http://jn.physiology.org/cgi/reprint/8/1/15 ).
A Novel SV40 TAg Transgenic Model of Asbestos-Induced Mesothelioma: Malignant Transformation Is Dose Dependent
Authors: Robinson Cleo , van Bruggen Ivonne , Segal Amanda , Dunham Melissa , Sherwood Amanda , Koentgen Frank , Robinson Bruce W.S. , Lake Richard A. 
Published: November 2006

Abstract
Although it has been clear for &gt;40 years that mesothelioma can be caused by asbestos, not all patients with this disease have a history of asbestos exposure. Other factors, including non-asbestos fibers and ionizing radiation, are known to cause malignant transformation of mesothelial cells. In addition, it is likely that genetics will play some role in susceptibility. Recently, it has been suggested that SV40 viral oncogenes could contribute to the carcinogenicity of asbestos. To better understand the role of SV40, we used the mesothelin promoter to construct MexTAg mice that express SV40 large T antigen (TAg) in the mesothelial compartment. We generated four MexTAg lines that carry high, intermediate, and low copy numbers of the transgene. All of these mice show a relatively low level of spontaneous tumor development. High-copy, 299h mice rapidly developed mesotheliomas when exposed to asbestos, and these tumors were faster growing and more invasive than those developing in wild-type and single-copy (266s) mice. In addition, we found a direct relationship between transgene copy number and survival after exposure to asbestos. A single copy of TAg was sufficient to immortalize mesothelial cells in vitro, but these cells did not show evidence of malignant transformation. In contrast, cell lines developed from mesothelial cells of animals carrying multiple copies of TAg were growth factor independent and could be cloned at limiting dilution in soft agar. These data provide the first in vivo demonstration of co-carcinogenicity between SV40 and asbestos. (Cancer Res 2006; 66(22): 10786-94)
Enhanced Antitumor Response by Divergent Modulation of Natural Killer and Natural Killer T Cells in the Liver
Authors: Subleski Jeff J. , Hall Veronica L. , Back Timothy C. , Ortaldo John R. , Wiltrout Robert H. 
Published: November 2006

AbstractThe use of interleukin-18 (IL-18) together with IL-12 induced high levels of IFN-γ in tumor-bearing mice and regression of liver tumors that was abolished in IFN-γ(−/−) mice. Natural killer (NK) and NKT cells were the major producers of IFN-γ in the livers of mice treated with IL-18 and/or IL-12. Liver NK cells were significantly increased by treatment with IL-18/IL-12, whereas the degree of liver NKT cell TCR detection was diminished by this treatment. Reduction of NK cells with anti-asGM1 decreased the antitumor activity of IL-18/IL-12 therapy and revealed NK cells to be an important component for tumor regression in the liver. In contrast, the antitumor effects of both IL-18 and IL-12 were further increased in CD1d(−/−) mice, which lack NKT cells. Our data, therefore, show that the antitumor activity induced in mice by IL-18/IL-12 is NK and IFN-γ dependent and is able to overcome an endogenous immunosuppressive effect of NKT cells in the liver microenvironment. These results suggest that immunotherapeutic approaches that enhance NK cell function while eliminating or altering NKT cells could be effective in the treatment of cancer in the liver. (Cancer Res 2006; 66(22): 11005-12)
DNA Repair and Cell Cycle Control Genes and the Risk of Young-Onset Lung Cancer
Authors: Landi Stefano , Gemignani Federica , Canzian Federico , Gaborieau Valérie , Barale Roberto , Landi Debora , Szeszenia-Dabrowska Neonilia , Zaridze David , Lissowska Jolanta , Rudnai Peter , Fabianova Eleonora , Mates Dana , Foretova Lenka , Janout Vladimir , Bencko Vladimir , Gioia-Patricola Lydie , Hall Janet , Boffetta Paolo , Hung Rayjean J. , Brennan Paul 
Published: November 2006

Abstract
Exposure to tobacco smoke and to mutagenic xenobiotics can cause various types of DNA damage in lung cells, which, if not corrected by DNA repair systems, may lead to deregulation of the cell cycle and, ultimately, to cancer. Genetic variation could thus be an important factor in determining susceptibility to tobacco-induced lung cancer with genetic susceptibility playing a larger role in young-onset cases compared with that in the general population. We have therefore studied 102 single-nucleotide polymorphisms (SNP) in 34 key DNA repair and cell cycle control genes in 299 lung cancer cases diagnosed before the age of 50 years and 317 controls from six countries of Central and Eastern Europe. We have found no association of lung cancer risk with polymorphisms in genes related to cell cycle control, single-strand/double-strand break repair, or base excision repair. Significant associations (P &lt; 0.05) were found with polymorphisms in genes involved in DNA damage sensing (ATM) and, interestingly, in four genes encoding proteins involved in mismatch repair (LIG1, LIG3, MLH1, and MSH6). The strongest associations were observed with heterozygote carriers of LIG1 −7C&gt;T [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.13-2.64] and homozygote carriers of LIG3 rs1052536 (OR, 2.05; 95% CI, 1.25-3.38). Consideration of the relatively large number of markers assessed diminishes the significance of these findings; thus, these SNPs should be considered promising candidates for further investigation in other independent populations. (Cancer Res 2006; 66(22): 11062-9)
Biological Properties of IDN5174, a New Synthetic Camptothecin with the Open Lactone Ring
Authors: Beretta Giovanni L. , Petrangolini Giovanna , De Cesare Michelandrea , Pratesi Graziella , Perego Paola , Tinelli Stella , Tortoreto Monica , Zucchetti Massimo , Frapolli Roberta , Bello Ezia , Manzotti Carla , Fontana Gabriele , Bombardelli Ezio , Battaglia Arturo , Samorì Cristian , Zunino Franco 
Published: November 2006

Abstract
A series of water-soluble camptothecins obtained by linking a spermidine moiety to the 21-position of the open form through an amidic bond have been tested for their biochemical and biological activities. Growth inhibition assay on the human non–small cell lung cancer carcinoma NCI-H460 cell line revealed that the camptothecin analogues were less potent than topotecan and SN38 after 1 hour of treatment. The potency increased after 72 hours of exposure, being similar to that of reference camptothecins. The analysis of topoisomerase I–mediated DNA cleavage using the purified enzyme indicated that the novel camptothecin analogues retained ability to poison topoisomerase I and displayed the same cleavage pattern of SN38. Persistence of the DNA cleavage was comparable with that of SN38. Stabilization of the cleavable complex was not the result of hydrolysis of the N-C bond between polyamine and the drug because no free camptothecin was recovered at the end of DNA cleavage in presence of IDN5174, the analogue selected for detailed studies. IDN5174 exhibited an antitumor activity comparable with that of topotecan and irinotecan against NCI-H460 tumor xenograft. The pharmacokinetics in mice showed a favorable disposition in tumor tissue with low amount of camptothecin detectable in plasma and tumor (around 5-10%), thus supporting the efficacy of intact IDN5174. In conclusion, we found that IDN5174 maintained the biological and antitumor properties, in spite of lack of the closed E ring. The available results support the interpretation that the polyamine linked at the 21-position may allow a favorable drug interaction in the ternary complex. (Cancer Res 2006; 66(22): 10976-82)
Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation
Authors: Lim Ji-Hong , Park Jong-Wan , Chun Yang-Sook 
Published: November 2006

Abstract
Arrest defective 1 (ARD1), an acetyltransferase, is essential for the yeast life cycle. Although its human homologue (hARD1) has been identified, its biological functions in human cells remain unclear. In the present study, we examined the biological function of hARD1. In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G1 arrest. Cyclin D1 was also found to be down-regulated in these growth-arrested cells, and the ectopic expression of cyclin D1 rescued cell growth. hARD1 knockdown repressed the promoter activity of the cyclin D1 gene, which inhibited the transcription of cyclin D1. Moreover, hARD1 knockdown reduced the binding of β-catenin/TCF4 transcription factor to cyclin D1 promoter and repressed its transcriptional activity. Inversely, hARD1 expression increased the transcriptional activity of β-catenin. Both endogenous and ectopically expressed hARD1 was coimmunoprecipitated with β-catenin. hARD1 knockdown did not affect β-catenin expression or degradation but noticeably reduced acetylated β-catenin. The β-catenin binding and acetylation by hARD1 were observed in vitro. Therefore, it is suggested that hARD1 participates in proliferation of lung cancer cells via the activation of β-catenin. (Cancer Res 2006; 66(22): 10677-82)
Interlayer adsorption of macrocyclic compounds (crown-ethers and cryptands) in 2:1 phyllosilicates: I. Isotherms and kinetics
Authors: Casal B. , Ruiz-Hitzky E. 
Published: November 2006

AbstractThe intercalation process of crown-ethers and cryptands into Ba2+- and Na+-montmorillonites leads to H-type adsorption isotherms according to the Giles et al. classification. The experimental monolayer capacity shows that 1:1 or 2:1 macrocyclic ligand/interlayer cation complexes can be produced. Kinetic experiments at different temperatures indicate that the intercalation is diffusion-controlled. The activation energies deduced from Arrhenius plots are 25–38 kJ mol−1.