bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasion and Maintenance of Dengue Virus Type 2 and Type 4 in the Americas
Authors: Carrington Christine V. F. , Foster Jerome E. , Pybus Oliver G. , Bennett Shannon N. , Holmes Edward C.
Published: November 2005

Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic fever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic diversity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral diversity between outbreaks.
Antigen Expression Kinetics and Immune Responses of Mice Immunized with Noninfectious Simian-Human Immunodeficiency Virus DNA
Authors: Hegde Ramakrishna , Liu ZhenQian , Mackay Glenn , Smith Marilyn , Chebloune Yahia , Narayan Opendra , Singh Dinesh K.
Published: November 2005

In a previous report we demonstrated that three injections of an
rt
-deleted noninfectious genome of the simian-human immunodeficiency virus SHIV
KU2
induced protection against AIDS in macaques (D. K. Singh, Z. Liu, D. Sheffer, G. A. Mackay, M. Smith, S. Dhillon, R. Hegde, F. Jia, I. Adany, and O. Narayan, J. Virol 79:3419-3428, 2005). To make this DNA safer, we deleted two more genes, the integrase gene and
vif
, along with the 3′ long terminal repeat. We also replaced the
gag
,
pro
, and
nef
genes (SIVmac239 origin) with those of human immunodeficiency virus (HIV) type 1 strain SF2. The resultant construct, designated Δ4SHIV
KU2
DNA, was used in this study to evaluate gene expression and immunogenicity in BALB/c mice. DNA-transfected human embryonic kidney epithelial cells (HEK 293) produced all of the major viral proteins and released p24 in the supernatant for 12 days. Inoculation of the vaccine DNA into the gastrocnemius muscles resulted in intense mononuclear cell infiltration at the inoculated sites and the production of viral p24 in myocytes, in infiltrating mononuclear cells, and in cells in the spleen and draining lymph nodes between 3 and 10 days postinoculation. Expression of p24 in the muscle cells peaked at day 7 and became undetectable after day 12. The same 12-day period of expression of p24 was observed in mice that were given a second injection 4 weeks after the first. Evaluation of immune responses in BALB/c mice revealed that the DNA induced enzyme-linked immunospot and antigen-specific proliferative cell-mediated immunity responses. The responses were stronger in mice that were coinjected with a second plasmid expressing granulocyte-macrophage colony-stimulating factor. Since new waves of viral antigen production could be induced with each boosting injection of the vaccine DNA, this DNA could be a safe and efficient agent to induce long-term protection against HIV.
MysTR: an Endogenous Retrovirus Family in Mammals That Is Undergoing Recent Amplifications to Unprecedented Copy Numbers
Authors: Cantrell Michael A. , Ederer Martina M. , Erickson Issac K. , Swier Vicki J. , Baker Robert J. , Wichman Holly A.
Published: November 2005

A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in
Oryzomys palustris
, a species that has lost LINE-1 activity, versus
Sigmodon hispidus
, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed
gag
,
pro
, and
pol
coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in
S. hispidus
and the LINE-1 active outgroup species,
Peromyscus maniculatus
, by PCR of a
pro-pol
region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in
O. palustris
versus 1,000 in
S. hispidus
and 4,500 in the more distantly related
P.maniculatus
leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.
The Conserved Poxvirus L3 Virion Protein Is Required for Transcription of Vaccinia Virus Early Genes
Authors: Resch Wolfgang , Moss Bernard
Published: November 2005

We provide the initial characterization of the product of the vaccinia virus L3L open reading frame (VACWR090), which is conserved in all sequenced members of the poxvirus family. The predicted polypeptide contains no motifs or other features that provided a clue to the role of the L3 protein, and no functional information was available regarding a homolog discovered in
Plasmodium falciparum
. The L3 protein was expressed following viral DNA replication, a finding consistent with a putative late promoter sequence, and was packaged as a non-membrane protein in mature virus particles. A recombinant virus, in which the L3L gene was regulated by the
Escherichia coli lac
operator/repressor system, had a conditional lethal phenotype. The virus replicated in the presence of inducer, but in its absence, the yields of infectious virus were reduced by 99%. When cells were infected without inducer, however, no defect in gene expression or morphogenesis was noted. Virus particles lacking L3, which assembled in the absence of inducer, were indistinguishable from wild-type virions with regard to morphology, major structural proteins, and DNA content but were noninfectious. L3-deficient virions were able to bind and penetrate cells but produced extremely small amounts of viral early mRNA. A defect in transcription was demonstrated by in vitro studies with permeabilized virions, but soluble extracts of L3-deficient virions showed normal levels of template-dependent transcriptional activity, indicating that only transcription of the packaged genome is impaired.
A Mutation in the First Ligand-Binding Repeat of the Human Very-Low-Density Lipoprotein Receptor Results in High-Affinity Binding of the Single V1 Module to Human Rhinovirus 2
Authors: Nizet Stephane , Wruss Juergen , Landstetter Nathalie , Snyers Luc , Blaas Dieter
Published: November 2005

Minor group human rhinoviruses (HRVs) bind members of the low-density lipoprotein receptor family for cell entry. The ligand-binding domains of these membrane proteins are composed of various numbers of direct repeats of about 40 amino acids in length. Residues involved in binding of module 3 (V3) of the very-low-density lipoprotein receptor (VLDLR) to HRV2 have been identified by X-ray crystallography (N. Verdaguer, I. Fita, M. Reithmayer, R. Moser, and D. Blaas, Nat. Struct. Mol. Biol.
11:
429-434, 2004). Sequence comparisons of the eight repeats of VLDLR with respect to the residues implicated in the interaction between V3 and HRV2 suggested that (in addition to V3) V1, V2, V5, and V6 also fulfill the requirements for interacting with the virus. Using a highly sensitive binding assay employing phage display, we demonstrate that single modules V2, V3, and V5 indeed bind HRV2. However, V1 does not. A single mutation from threonine 17 to proline converted the nonbinding wild-type form of V1 into a very strong binder. We interpret the dramatic increase in affinity by the generation of a hydrophobic patch between virus and receptor; in the presence of threonine, the contact area might be disturbed. This demonstrates that the interaction between virus and its natural receptors can be strongly enhanced by mutation.
Interactions with Pocket Proteins Contribute to the Role of Human Papillomavirus Type 16 E7 in the Papillomavirus Life Cycle
Authors: Collins Asha S. , Nakahara Tomomi , Do Anh , Lambert Paul F.
Published: November 2005

Human papillomaviruses (HPVs), most commonly the HPV16 genotype, are the principle etiological determinant for cervical cancer, a common cancer worldwide resulting in over 200,000 deaths annually. The oncogenic properties of HPVs are attributable in part to the virally encoded protein E7, best known for its ability to bind to and induce the degradation of the retinoblastoma tumor suppressor, pRb, and related “pocket proteins” p107 and p130. Previously, we defined a role for E7 in the productive stage of the HPV16 life cycle, which takes place in stratified squamous epithelia. HPV perturbs the normal processes of cell growth and differentiation of stratified squamous epithelia. HPVs reprogram cells to support continued DNA synthesis and inhibit their differentiation in the suprabasal compartment of the epithelia, where cells normally have withdrawn from the cell cycle and initiated a well-defined pattern of terminal differentiation. These virus-induced perturbations, which contribute to the production of progeny HPVs, are dependent on E7. In this study, we define the mechanism of action by which E7 contributes to the productive stage of the HPV16 life cycle. We found that the ability of HPV16 to reprogram suprabasal cells to support DNA synthesis correlates with E7's ability to bind pocket proteins but not its ability to induce their degradation. In contrast, the ability of HPV16 to perturb differentiation correlated with both E7's binding to and degradation of pocket proteins. These data indicate that different hallmarks of the productive stage of the HPV16 life cycle rely upon different sets of requirements for E7.
Molecular Characterization of Adeno-Associated Viruses Infecting Children
Authors: Chen Chun-Liang , Jensen Ryan L. , Schnepp Bruce C. , Connell Mary J. , Shell Richard , Sferra Thomas J. , Bartlett Jeffrey S. , Clark K. Reed , Johnson Philip R.
Published: November 2005

Although adeno-associated virus (AAV) infection is common in humans, the biology of natural infection is poorly understood. Since it is likely that many primary AAV infections occur during childhood, we set out to characterize the frequency and complexity of circulating AAV isolates in fresh and archived frozen human pediatric tissues. Total cellular DNA was isolated from 175 tissue samples including freshly collected tonsils (
n
= 101) and archived frozen samples representing spleen (
n
= 21), lung (
n
= 16), muscle (
n
= 15), liver (
n
 = 19), and heart (
n
= 3). Samples were screened for the presence of AAV and adenovirus sequences by PCR using degenerate primers. AAV DNA was detected in 7 of 101 (7%) tonsil samples and two of 74 other tissues (one spleen and one lung). Adenovirus sequences were identified in 19 of 101 tonsils (19%), but not in any other tissues. Complete capsid gene sequences were recovered from all nine AAV-positive tissues. Sequence analyses showed that eight of the capsid sequences were AAV2-like (∼98% amino acid identity), while the single spleen isolate was intermediate between serotypes 2 and 3. Comparison to the available AAV2 crystal structure revealed that the majority of the amino acid substitutions mapped to surface-exposed hypervariable domains. To further characterize the AAV capsid structure in these samples, we used a novel linear rolling-circle amplification method to amplify episomal AAV DNA and isolate infectious molecular clones from several human tissues. Serotype 2-like viruses were generated from these DNA clones and interestingly, failed to bind to a heparin sulfate column. Inspection of the capsid sequence from these two clones (and the other six AAV2-like isolates) revealed that they lacked arginine residues at positions 585 and 588 of the capsid protein, which are thought to be essential for interaction with the heparin sulfate proteoglycan coreceptor. These data provide a framework with which to explore wild-type AAV persistence in vivo and provide additional tools to further define the biodistribution and form of AAV in human tissues.
Characterization of Adeno-Associated Virus Genomes Isolated from Human Tissues
Authors: Schnepp Bruce C. , Jensen Ryan L. , Chen Chun-Liang , Johnson Philip R. , Clark K. Reed
Published: November 2005

Infection with wild-type adeno-associated virus (AAV) is common in humans, but very little is known about the in vivo biology of AAV. On a molecular level, it has been shown in cultured cells that AAV integrates in a site-specific manner on human chromosome 19, but this has never been demonstrated directly in infected human tissues. To that end, we tested 175 tissue samples for the presence of AAV DNA, and when present, examined the specific form of the viral DNA. AAV was detected in 7 of 101 tonsil-adenoid samples and in 2 of 74 other tissue samples (spleen and lung). In these nine samples, we were unable to detect AAV integration in the AAVS1 locus using a sensitive PCR assay designed to amplify specific viral-cellular DNA junctions. Additionally, we used a second complementary assay, linear amplification-mediated-PCR (LAM-PCR) to widen our search for integration events. Analysis of individual LAM-PCR products revealed that the AAV genomes were arranged predominantly in a head-to-tail array, with deletions and extensive rearrangements in the inverted terminal repeat sequences. A single AAV-cellular junction was identified from a tonsil sample and it mapped to a highly repetitive satellite DNA element on chromosome 1. Given these data, we entertained the possibility that instead of integrated forms, AAV genomes were present as extrachromosomal forms. We used a novel amplification assay (linear rolling-circle amplification) to show that the majority of wild-type AAV DNA existed as circular double-stranded episomes in our tissues. Thus, following naturally acquired infection, AAV DNA can persist mainly as circular episomes in human tissues. These findings are consistent with the circular episomal forms of recombinant AAV vectors that have been isolated and characterized from in vivo transduced tissues.
Effect of Cell Cycle Arrest on the Activity of Nucleoside Analogues against Human Immunodeficiency Virus Type 1
Authors: Wurtzer Sebastien , Compain Séverine , Benech Henri , Hance Allan J. , Clavel François
Published: November 2005

Human immunodeficiency virus (HIV) reverse transcription can be notably affected by cellular activation, differentiation, and division. We hypothesized that changes in the cell cycle could also affect HIV susceptibility to nucleoside analogues, which compete with natural nucleotides for incorporation into viral DNA and inhibit viral replication through premature termination of reverse transcription. Proliferating HeLa-derived indicator cells were arrested in the S/G
2
phase with etoposide, a topoisomerase II inhibitor, or in the G
1
/S phase with aphidicolin, a polymerase α inhibitor. Cell cycle arrest by both agents induced a remarkable decrease in HIV susceptibility to zidovudine (AZT). This decrease was seen both with a single-cycle infectivity assay and with a viral DNA quantitation assay, indicating that the effect of cell cycle arrest was exerted at the reverse transcription stage. The increase in the 50% inhibitory concentration (IC
50
) seen with arrested cells was strongest for AZT (23-fold) and stavudine (21-fold) but more modest for other drugs (lamivudine, 11-fold; dideoxyinosine, 7-fold; and nevirapine, 3-fold). In drug-resistant reverse transcriptase mutants, the increase in AZT IC
50
(relative to that in dividing cells) was most prominent with a Q151M mutant and was comparable to the wild type in other drug-resistant mutants. Quantitation of intracellular pools of dTTP and AZT 5′-triphosphate (AZTTP) showed that etoposide treatment induced a significant increase in intracellular dTTP and consequently a decrease in AZTTP/dTTP ratios, suggesting that the decrease in viral susceptibility to AZT was caused by reduced incorporation of the analogue into nascent viral DNA. These results emphasize the importance of cellular proliferation and deoxynucleoside triphosphate metabolism in HIV susceptibility to nucleoside analogues and underscore the need to study the activities of drugs of this class with natural target cells under physiological conditions of activation and proliferation.
Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8+T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia
Authors: van Lint Allison L. , Kleinert Lauren , Clarke Sally R. M. , Stock Angus , Heath William R. , Carbone Francis R.
Published: November 2005

CD8+T-cell persistence can be seen in ganglia harboring latent herpes simplex virus (HSV) infection. While there is some evidence that these cells suppress virus reactivation, this view remains controversial. Given that maintenance of latency by CD8+T cells would necessitate ongoing exposure to antigen within this site, we sought evidence for such chronic stimulation. Initial experiments showed infiltration by activated but not naïve CD8+T cells into ganglia harboring latent HSV infection. While such infiltration was independent of T-cell specificity, once recruited, only virus-specific T cells expressed high levels of preformed granzyme B, a marker of ongoing activation. Moreover, bone marrow replacement chimeras showed that these elevated granzyme levels were totally dependent on presentation by parenchymal cells within the ganglia. Overall, this study argues that activated CD8+T cells are nonspecifically recruited into latently infected ganglia, and in this site they are exposed to ongoing antigen stimulation, most likely by infected neuronal cells.
Specific Recognition and Cleavage of the Plus-Strand Primer by Reverse Transcriptase
Authors: Atwood-Moore Angela , Ejebe Kenechi , Levin Henry L.
Published: November 2005

Reverse transcriptases (RTs) of retroviruses and long terminal repeat (LTR)-retrotransposons possess DNA polymerase and RNase H activities. During reverse transcription these activities are necessary for the programmed sequence of events that include template switching and primer processing. Integrase then inserts the completed cDNA into the genome of the host cell. The RT of the LTR-retrotransposon Tf1 was subjected to random mutagenesis, and the resulting transposons were screened with genetic assays to test which mutations reduced reverse transcription and which inhibited integration. We identified a cluster of mutations in the RNase H domain of RT that were surprising because they blocked integration without reducing cDNA levels. The results of immunoblots demonstrated that these mutations did not reduce levels of RT or integrase. DNA blots showed that the mutations did not lower the amounts of full-length cDNA. The sequences of the 3′ ends of the cDNA revealed that mutations within the cluster in RNase H specifically reduced the removal of the polypurine tract (PPT) primer from the ends of the cDNA. These results indicate that primer removal is not a necessary component of reverse transcription. The residues mutated in Tf1 RNase H are conserved in human immunodeficiency virus type 1 and make direct contact with DNA opposite the PPT. Thus, our results identify a conserved element in RT that contacts the PPT and is specifically required for PPT removal.
CD8+and CD20+Lymphocytes Cooperate To Control Acute Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys: Modulation by Major Histocompatibility Complex Genotype
Authors: Mao Hanwen , Lafont Bernard A. P. , Igarashi Tatsuhiko , Nishimura Yoshiaki , Brown Charlie , Hirsch Vanessa , Buckler-White Alicia , Sadjadpour Reza , Martin Malcolm A.
Published: November 2005

We have previously described two isogenic molecularly cloned simian immunodeficiency virus/human immunodeficiency virus chimeric viruses (SHIVs) that differ from one another by 9 amino acids and direct distinct clinical outcomes in inoculated rhesus monkeys. SHIVDH12R-Clone 7, like other highly pathogenic CXCR4-tropic SHIVs, induces rapid and complete depletions of CD4+T lymphocytes and immunodeficiency in infected animals. In contrast, macaques inoculated with SHIVDH12R-Clone 8experience only partial and transient losses of CD4+T cells, show prompt control of their viremia, and remain healthy for periods of time extending for up to 4 years. The contributions of CD8+and CD20+lymphocytes in suppressing the replication of the attenuated SHIVDH12R-Clone 8and maintaining a prolonged asymptomatic clinical course was assessed by treating animals with monoclonal antibodies that deplete each lymphocyte subset at the time of virus inoculation. The absence of either CD8+or CD20+cells during the SHIVDH12R-Clone 8acute infection resulted in the rapid, complete, and irreversible loss of CD4+T cells; sustained high levels of postpeak plasma viremia; and symptomatic disease in Mamu-A*01-negative Indian rhesus monkeys. In Mamu-A*01-positive animals, however, the aggressive, highly pathogenic phenotype was observed only in macaques depleted of CD8+cells; SHIVDH12R-Clone 8was effectively controlled in Mamu-A*01-positive monkeys in the absence of B lymphocytes. Taken together, these results indicate that both CD8+and CD20+B cells contribute to the control of primate lentiviral infection in Mamu-A*01-negative macaques. Furthermore, the major histocompatibility complex genotype of an infected animal, as exemplified by the Mamu-A*01 allele in this study, has the additional capacity to shift the balance of the composite immune response.
A Hydrophobic Domain in the Large Envelope Protein Is Essential for Fusion of Duck Hepatitis B Virus at the Late Endosome
Authors: Chojnacki J. , Anderson D. A. , Grgacic E. V. L.
Published: November 2005

The duck hepatitis B virus (DHBV) envelope is comprised of two transmembrane (TM) proteins, the large (L) and the small (S), that assemble into virions and subviral particles. Secondary-structure predictions indicate that L and S have three α-helical, membrane-spanning domains, with TM1 predicted to act as the fusion peptide following endocytosis of DHBV into the hepatocyte. We used bafilomycin A1 during infection of primary duck hepatocytes to show that DHBV must be trafficked from the early to the late endosome for fusion to occur. Alanine substitution mutations in TM1 of L and S, which lowered TM1 hydrophobicity, were used to examine the role of TM1 in infectivity. The high hydrophobicity of the TM1 domain of L, but not of S, was shown to be essential for virus infection at a step downstream of receptor binding and virus internalization. Using wild-type and mutant synthetic peptides, we demonstrate that the hydrophobicity of this domain is required for the aggregation and the lipid mixing of phospholipid vesicles, supporting the role of TM1 as the fusion peptide. While lipid mixing occurred at pH 7, the kinetics of insertion of the fusion peptide was increased at pH 5, consistent with the location of DHBV in the late-endosome compartment and previous studies of the nonessential role of low pH for infectivity. Exchange of the TM1 of DHBV with that of hepatitis B virus yielded functional, infectious DHBV particles, suggesting that TM1 of all of the hepadnaviruses act similarly in the fusion mechanism.
Common Ancestry of Herpesviruses and Tailed DNA Bacteriophages
Authors: Baker Matthew L. , Jiang Wen , Rixon Frazer J. , Chiu Wah
Published: November 2005

Comparative analysis of capsid protein structures in the eukaryote-infecting herpesviruses (
Herpesviridae
) and the prokaryote-infecting tailed DNA bacteriophages (
Caudovirales
) revealed a characteristic fold that is restricted to these two virus lineages and is indicative of common ancestry. This fold not only serves as a major architectural element in capsid stability but also enables the conformational flexibility observed during viral assembly and maturation. On the basis of this and other emerging relationships, it seems increasingly likely that the very diverse collection of extant viruses may have arisen from a relatively small number of primordial progenitors.
Breaking an Absolute Species Barrier: Transgenic Mice Expressing the Mink PrP Gene Are Susceptible to Transmissible Mink Encephalopathy
Authors: Windl O. , Buchholz M. , Neubauer A. , Schulz-Schaeffer W. , Groschup M. , Walter S. , Arendt S. , Neumann M. , Voss A. K. , Kretzschmar H. A.
Published: November 2005

Transmissible mink encephalopathy (TME) is a rare disease of the North American mink, which has never been successfully transmitted to laboratory mice. We generated transgenic mice expressing the mink prion protein (PrP) and inoculated them with TME or the mouse-adapted scrapie strain 79A. TME infected mink PrP-transgenic mice on a murine PrP knockout background. The absolute species barrier between the infectious agent of TME and mice was therefore broken. Following TME and 79A infection of mice carrying both mink and murine PrP
C
, only proteinase-resistant PrP homologous to the incoming agent was detectable. The presence of the murine PrP
C
prolonged the incubation time of TME substantially.
Activation of p21-Activated Kinase 2 by Human Immunodeficiency Virus Type 1 Nef Induces Merlin Phosphorylation
Authors: Wei Bangdong L. , Arora Vivek K. , Raney Alexa , Kuo Lillian S. , Xiao Guang-Hui , O'Neill Eduardo , Testa Joseph R. , Foster John L. , Garcia J. Victor
Published: November 2005

The accessory human immunodeficiency virus type 1 (HIV-1) protein Nef activates the autophosphorylation activity of p21-activated kinase 2 (PAK2). Merlin, a cellular substrate of PAK2, is homologous to the ezrin-radixin-moesin family and plays a critical role in Rac signaling. To assess the possible impact on host cell metabolism of Nef-induced PAK2 activation, we investigated the phosphorylation of merlin in Nef expressing cells. Here we report that Nef induces merlin phosphorylation in multiple cell lines independently of protein kinase A. This intracellular phosphorylation of merlin directly correlates with in vitro assay of the autophosphorylation activity of Nef-activated PAK2. Importantly, merlin phosphorylation induced by Nef was also observed in human primary T cells. The finding that Nef induces phosphorylation of the key signaling molecule merlin suggests several possible roles for PAK2 activation in HIV pathogenesis.
Human Metapneumovirus Induces a Profile of Lung Cytokines Distinct from That of Respiratory Syncytial Virus
Authors: Guerrero-Plata Antonieta , Casola Antonella , Garofalo Roberto P.
Published: November 2005

Lung cytokine and chemokine production by BALB/c mice infected with human metapneumovirus (hMPV) was compared to respiratory syncytial virus (RSV)-infected mice. hMPV infection induced lower levels of the inflammatory cytokines interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha but was a more potent inducer of granulocyte-macrophage colony-stimulating factor and triggered a more sustained production of the CXC chemokine KC compared to RSV. hMPV was a stronger inducer of both alpha interferon (IFN-α) and IFN-γ responses than RSV. In regard to immunomodulatory cytokines, hMPV failed to induce detectable IL-10 or IL-12p70 but was a potent inducer of IL-12 p40 subunit. The implications for hMPV pathogenesis are discussed.
Evolution of Cyclophilin A and
TRIMCyp
Retrotransposition in New World Primates
Authors: Ribeiro Ieda P. , Menezes Albert N. , Moreira Miguel A. M. , Bonvicino Cibele R. , Seuánez Héctor N. , Soares Marcelo A.
Published: November 2005

Host cell factors modulate retroviral infections. Among those, cyclophilin A (CypA) promotes virus infectivity by facilitating virus uncoating or capsid unfolding or by preventing retroviral capsid interaction with cellular restriction factors. In
Aotus
species, a retrotransposed copy of
CypA
inserted into the tripartite motif 5 (
TRIM5
) gene encodes a fusion protein which may block human immunodeficiency virus type 1 by targeting the incoming virus to ubiquitin-ligated degradation or by interfering with normal uncoating of the incoming particle, rendering those monkeys resistant to infection. In this study, we have extensively analyzed representative specimens from all New World primate genera and shown that the retrotransposed
CypA
copy is only present in
Aotus
. We have shown that this inserted copy diverged from its original counterpart and that this occurred prior to
Aotus
radiation, although no positive selection was observed. Finally, our data underscores the need for a precise taxonomic identification of primate species used as models for retroviral infections and novel antiviral approaches.
TWISTORS, YANG-MILLS AMPLITUDES AND LANDAU LEVELS
Authors: NAIR V. P.
Published: November 2005

We give a short discussion/review of the recent developments expressing the perturbative scattering amplitudes in Yang-Mills theory, specifically for the [Formula: see text] theory, in terms of holomorphic curves in a supersymmetric twistor space. Holomorphic curves, which are maps of CP1 to the supertwistor space, can also be interpreted as the lowest Landau level wave functions; this point of view is also briefly explained.
INCOMPRESSIBLE FLUIDS
Authors: RAJEEV S. G.
Published: November 2005

We propose a model for random forces in a turbulent incompressible fluid by balancing the energy gain from fluctuations against dissipation by viscosity. This leads to a more singular covariance distribution for the random forces than is ordinarily allowed. We then propose regularization of the fluid system by matrix models. A formula for entropy of a two dimensional fluid is derived and then a vorticity profile of a hurricane that maximizes entropy. A regularization of three dimensional incompressible fluid flow using quantum groups is also proposed.
ISOBAR RESCATTERING MODEL AND LIGHT SCALAR MESONS
Authors: SCHECHTER J.
Published: November 2005

We use a toy model to discuss the problem of parameterizing the possible contribution of a light scalar meson, sigma, to the final state interactions in the non leptonic decays of heavy mesons.
BYPASSING THE AXIAL ANOMALIES
Authors: KEKEZ DALIBOR , KLABUČAR DUBRAVKO , SCADRON M. D.
Published: November 2005

Many meson processes are related to the UA(1) axial anomaly, present in the Feynman graphs where fermion loops connect axial vertices with vector vertices. However, the coupling of pseudoscalar mesons to quarks does not have to be formulated via axial vertices. The pseudoscalar coupling is also possible, and this approach is especially natural on the level of the quark substructure of hadrons. In this paper we point out the advantages of calculating these processes using (instead of the anomalous graphs) the Feynman graphs where axial vertices are replaced by pseudoscalar vertices. We elaborate especially the case of the processes related to the Abelian axial anomaly of QED, but we speculate that it seems possible that effects of the non-Abelian axial anomaly of QCD can be accounted for in an analogous way.
A RUNAWAY DIRECTION IN BRANE-GAS MODULI SPACE
Authors: BERNDSEN A.
Published: November 2005

Brane Gas Cosmology (BGC) is an M-theory motivated attempt to reconcile aspects of standard cosmology based on Einstein's theory of general relativity. The background in this framework is described by dilaton gravity, which introduces various moduli fields for the shape and size of the extra dimensions and the dilaton. Following previous successes in this field, we dimensionally reduce a gas of strings and branes to the d + 1-dimensional Einstein frame with the hopes of understanding late-time BGC. This procedure generates an effective potential for the moduli fields, which we analyze in the hopes of stabilizing all fields; however, with the inclusion of strings and branes alone we find one direction remains free to roll away.
BOUNDS ON THE COUPLING CONSTANTS OF THE MAJORON TO TWO NEUTRINOS IN EXTRA DIMENSIONS FROM Z → νν(J) DECAY
Authors: MOUSSA SHERIF , NASRI SALAH , SANNINO FRANCESCO , SCHECHTER JOSEPH
Published: November 2005

We give an overview for the bounds of Majoron-neutrino coupling constants from supernova and accelerators. Using the accurate known value for the invisible partial width for Z boson we obtained constraints on the coupling of the Majoron to two neutrinos, for singlet Majoron model, in case of 3+1 dimensions as well as in extra dimensions, where we assumed the singlet Majoron can propagate in higher dimensions. We found that the predicted coupling constants are far below these upper bounds if a natural see-saw is adopted. Also, the expected increase in Z partial width due to many Kaluza-Klein excitations has been suppressed due to the decrease of the coupling constants.
BPS AND DUALITY IN SUPERSYMMETRIC QUANTUM MECHANICS
Authors: SPECTOR DONALD
Published: November 2005

This paper explores the consequences of superalgebras with central charges in the context of non-relativistic quantum mechanics. We find the emergence of target space duality structures in these theories. We also demonstrate that shape invariance is understood most naturally in the context of such centrally extended superalgebras, with their exact solvability a consequence of a BPS structure.
DENDRITIC FLUORENE OLIGOMERS FOR NONLINEAR ABSORPTION IN THE VISIBLE RANGE
Authors: BARSU CYRIL , ANDRAUD CHANTAL , AMARI NADIA , SPAGNOLI SYLVIE , BALDECK PATRICE L.
Published: November 2005

We report here the nonlinear absorption properties of dendritic molecules of oligofluorenes. Measurements were performed in chloroform between 450 and 650 nm for nanosecond time duration pulses. The nonlinear absorption is attributed to a three-photon absorption process involving first a two-photon absorption (TPA) step followed by an excited state absorption (ESA) process. The corresponding three-photon absorption coefficient α3 presents at resonance high values (α3 > 10000 cm 3/ GW 2 for 2G1 the first dendrimer generation bearing a bifluorene at a concentration of 50 g/L). These values are strongly enhanced with respect to those obtained in the same conditions for analog linear oligofluorenes.
SYNTHESIS AND CHARACTERIZATION OF EFFICIENT TWO-PHOTON ABSORPTION CHROMOPHORES WITH INCREASED DIMENSIONALITY
Authors: LINCKER FREDERIC , MASSON PATRICK , NICOUD JEAN-FRANCOIS , DIDIER PASCAL , GUIDONI LUCA , BIGOT JEAN-YVES
Published: November 2005

New organic "donor–donor" bis-stilbenyl conjugated chromophores arranged in increasing dimensionality (1D to 3D) have been synthesized in high yields by multiple Heck coupling. The central core is based on a biphenyl, triphenylenyl or spiro-bifluorenyl group when the donor part at each extremity is based on a 3,4,5-tridodecyloxyphenyl group that ensures a high solubility in organic solvents and favors the catalytic coupling reactions. Femtosecond two-photon absorption measurements in solution have evidenced improved two-photon absorption cross-sections (≅ 10-19 cm 4/ GW ) that depend on the arrangement of the chromophores.
DIRECT NANO-PATTERNING METHODS USING NONLINEAR ABSORPTION IN PHOTOPOLYMERIZATION INDUCED BY A FEMTOSECOND LASER
Authors: PARK SANG HU , LIM TAE WOO , YANG DONG-YOL , YI SHIN WOOK , KONG HONG JIN , LEE KWANG-SUP
Published: November 2005

Investigation into the methods of direct fabrication for submicron-detailed patterns without the use of any photomask was carried out using two-photon polymerization (TPP). Some patterns can be fabricated easily in the range of several micrometers by solidifying inside a photopolymerizable resin by a scanning process using a volume-pixel (voxel) matrix that is transformed from a bitmap figure file. The voxels are generated consecutively to merge into adjoining voxels in the process of fabricating a pattern. The resolution of a fabricated pattern can be obtained under the diffraction limit of a laser beam due to the nonlinear absorption phenomenon. In this paper, a top-down reverse building technique was introduced to fabricate a polymeric pattern on a metal layer. Also, a contour offset algorithm (COA) and a beam expanding method have been attempted to make precise patterns and to enlarge the working area. Through this work, several patterns for various applications on nano- and microtechnology were fabricated on a glass plate and a thin metal layer to demonstrate the usefulness of the developed algorithm.
NEW TRIMETHYLAMMONIUM DERIVATIVES TOWARD SECOND-ORDER NONLINEAR OPTICS
Authors: GLAVCHEVA ZORNITZA , UMEZAWA HIROHITO , OKADA SHUJI , NAKANISHI HACHIRO
Published: November 2005

In order to find new ionic compounds with good characteristics for second harmonic generation (SHG), the relationship between first hyperpolarizabilities (β) and the position of the cationic center with respect to the benzene ring was investigated. The β values of a series of trimethylammonium cations: X–C 6 H 4–( CH 2)n N +( CH 3)3, where X = H , CH 3, OCH 3, NH 2, and N ( CH 3)2; n = 0–2, were calculated by using the MOPAC PM3 method. Relatively large calculated β values were obtained when X = N ( CH 3)2 and X = NH 2. Series of [4-(dimethylamino)phenyl]trimethylammonium ( X = N ( CH 3)2; n = 0) and [2-(4-aminophenyl)ethyl]trimethylammonium ( X = NH 2; n = 2) derivatives were synthesized. Among them, seven SHG-active complexes were found and four crystal structures were determined.
TOWARDS THERMALLY STABLE, HIGHLY ELECTRO-OPTICALLY ACTIVE ORGANIC POLYMERS: DESIGN AND SYNTHESIS OF CROSSLINKABLE POLYIMIDES CONTAINING ZWITTERIONIC NONLINEAR OPTICAL CHROMOPHORES
Authors: SONG NAIHENG , MEN LIQIU , GAO JIAN PING , YU GUOMIN , BEAUDIN ANDREW M. R. , WANG ZHI YUAN
Published: November 2005

A series of nonlinear optical (NLO) polymers were synthesized by grafting a zwitterionic chromophore onto host acid-containing polyimides with different glass transition temperatures and chain mobility. All the NLO polymers showed good solubility, thermal stability and good film-forming ability. The poling and electro-optic (EO) studies revealed a strong dependence of EO coefficients on the polymer chain mobility or the glass transition temperatures. A new thermally crosslinkable group was introduced into the NLO polymers, in order to achieve high temporal stability of the poled NLO polymers.
ROTATIONAL PROPERTIES OF MICRO-SLABS DRIVEN BY LINEARLY-POLARIZED LIGHT
Authors: LIN CHIH-LANG , WANG IRÈNE , PIERRE MARC , COLOMBIER ISABELLE , ANDRAUD CHANTAL , BALDECK PATRICE L.
Published: November 2005

We study the rotational motion of objects trapped in a focused laser beam (optical tweezers). Micrometer-sized flat slabs are fabricated using two-photon photopolymerization. These objects, trapped by linearly-polarized light, tend to align parallel to the polarization plane. This alignment effect is attributed to the polarization anisotropy resulting from the object shape and we present a simple electromagnetic approach to estimate the resulting optical torque. Micro-rotors of different sizes are studied experimentally. We characterize the behavior of micro-objects when the light polarization is rotated at constant speed. Our theoretical approach gives a good prediction of how the size of micro-objects affects their rotation efficiency.
FABRICATION OF LOW-LOSS WAVEGUIDES USING ORGANIC-INORGANIC HYBRID MATERIALS
Authors: YOON KEUN BYOUNG , BAE BYEONG-SOO , POPALL MICHAEL
Published: November 2005

The fabrication of single and multimode waveguides and optical characteristics were investigated. The singlemode waveguide was fabricated by a laser direct writing technique and a multimode waveguide was produced by means of a direct UV patterning technique using organic-inorganic hybrid materials. The fabrication of waveguide channels with these techniques are of interest for simple processes. The resulting single and multimode waveguides exhibited a near rectangular shape and low optical loss. The average propagation losses of these waveguides were 0.07 dB/cm (at 850 nm) and 0.3 dB/cm (at 1310 nm), respectively.
POLYMER-BASED OPTICAL PRINTED CIRCUIT BOARD (O-PCB) AS A POTENTIAL PLATFORM FOR VLSI MICROPHOTONIC INTEGRATION
Authors: LEE EL-HANG , LEE SEUNG-GOL , O BEOM HOAN , PARK SE-GEUN
Published: November 2005

We introduce the concept of optical printed circuit board (O-PCB) and discuss the issues regarding the miniaturization, interconnection, and integration of polymer-based photonic devices with a view to using it as a potential platform for VLSI microphotonic integration. We present new approaches to miniaturize and integrate some examples of microphotonic devices and examine the considerations regarding the design, fabrication, and characterization for miniaturization and integration for O-PCB application. Devices that we have used for our study include mode conversion adaptors, micro-ring resonator devices, multimode interference devices, arrayed waveguide gratings. Scaling rules are also discussed.
INFRARED PHOTOREFRACTIVE COMPOSITES BASED ON POLYIMIDE AND J-AGGREGATES OF CYANINE DYE
Authors: VANNIKOV A. V. , GRISHINA A. D. , PERESHIVKO L. YA. , KRIVENKO T. V. , SAVELYEV V. V. , RYCHWALSKI R. W.
Published: November 2005

Photorefractive composites sensitive to 1064 nm on a base of an aromatic polyimide containing J-aggregates of a thiacarbocyanine dye are presented. The molecules of the dye form the nanocrystalline J-aggregates that are responsible for photoelectric sensitivity at 1064 nm and nonlinear third-order optical properties. The net gain coefficient 266 cm-1 and the response time 0.09 s were achieved at an external electric field of about 15 V/μm.
HIGHLY FE-DOPED InGaAs/InP SATURABLE ABSORBER MODE-LOCKING OF AN ERBIUM FIBER LASER
Authors: LECOURT J.-B. , ORTAÇ B. , GUÉZO M. , LABBÉ C. , FOLLIOT H. , LOUALICHE S. , HIDEUR A. , MARTEL G.
Published: November 2005

Erbium-doped unidirectional fiber ring laser has been passively mode-locked with a novel ultra-fast semiconductor saturable absorber used in transmission. The structure is based on InGaAs/InP multiple quantum wells grown on an InP substrate. Different structures with recovery time down to picosecond have been tested. Relaxation time reduction have been obtained by iron doping. With such structures, detrimental regimes such as Q-switch and Q-switch/ModeLock regimes have been avoided. Solitonic and slightly stretched-pulse dispersion regimes have been tested. The laser delivers for both, completely self-starting picosecond pulses of 8 mW maximum average output power at a repetition rate around 25 MHz.
Modulation of α7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells
Authors: Chao Jun-Tzu , Martinez-Lemus Luis A. , Kaufman Stephen J. , Meininger Gerald A. , Ramos Kenneth S. , Wilson Emily
Published: November 2005

We showed previously that the expression of α7-integrin in aortic vascular smooth muscle cells (VSMC) is enhanced in a rat model of atherosclerosis. In the present study, we investigated the effects of platelet-derived growth factor (PDGF) on α7-integrin expression and VSMC adhesion and migration. Expression of the α7-integrin gene was determined by real-time RT-PCR, whereas protein levels were determined by fluorescence-activated cell sorting analysis. PDGF increased α7 cell surface protein expression (12 and 24 h: 3.3 ± 0.8- and 3.6 ± 0.4-fold, P < 0.05 vs. control) and mRNA levels (24 h: 3.1-fold, P < 0.05 vs. control) in a time-dependent manner. Actinomycin D and cycloheximide attenuated PDGF-induced increases in α7-integrin, indicating the involvement of de novo mRNA and protein synthesis. Treatment with the MAPK inhibitors PD-98059, SP-600125, and SB-203580 attenuated PDGF-induced increases in mRNA. In contrast, PD-98059 and SP-600125, but not SB-203580, attenuated PDGF-induced increases in cell surface protein levels. PDGF-treated VSMC adhered to laminin more efficiently (42 ± 6% increase, P < 0.01), and this increase was partially inhibited by anti-α7-integrin function-blocking antibody. However, PDGF did not alter migration on laminin, and there was no effect of the anti-α7-integrin function-blocking antibody on basal or PDGF-stimulated migration. Immunofluorescence imaging revealed an increase in α7-integrin distribution along the stress fibers. Together, these observations indicate that PDGF enhances α7-integrin expression in VSMC and promotes α7-integrin-mediated adhesion to laminin.
Norepinephrine activates store-operated Ca2+entry coupled to large-conductance Ca2+-activated K+channels in rat pinealocytes
Authors: Lee So-Young , Choi Bo-Hwa , Hur Eun-Mi , Lee Jong-Hee , Lee Sung-Jin , Lee Chin Ok , Kim Kyong-Tai
Published: November 2005

Norepinephrine (NE) is one of the major neurotransmitters that determine melatonin production in the pineal gland. Although a substantial amount of Ca2+influx is triggered by NE, the Ca2+entry pathway and its physiological relevance have not been elucidated adequately. Herein we report that the Ca2+influx triggered by NE significantly regulates the protein level of serotonin N-acetyltransferase, or arylalkylamine N-acetyltransferase (AANAT), a critical enzyme in melatonin production, and is responsible for maintaining the Ca2+response after repetitive stimulation. Ca2+entry evoked by NE was dependent on PLC activation. NE evoked a substantial amount of Ca2+entry even after cells were treated with 1-oleoyl-2-acetyl- sn-glycerol (OAG), an analog of diacylglycerol. To the contrary, further OAG treatment after cells had been exposed to OAG did not evoke additional Ca2+entry. Moreover, NE failed to induce further Ca2+entry after the development of Ca2+entry induced by thapsigargin (Tg), suggesting that the pathway of Ca2+entry induced by NE might be identical to that of Tg. Interestingly, Ca2+entry evoked by NE or Tg induced membrane hyperpolarization that was reversed by iberiotoxin (IBTX), a specific inhibitor of large-conductance Ca2+-activated K+(BK) channels. Moreover, IBTX-sensitive BK current was observed during application of NE, suggesting that activation of the BK channels was responsible for the hyperpolarization. Furthermore, the activation of BK channels triggered by NE contributed to regulation of the protein level of AANAT. Collectively, these results suggest that NE triggers Ca2+entry coupled to BK channels and that NE-induced Ca2+entry is important in the regulation of AANAT.