bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Latent Membrane Protein 2A Activates β-Catenin Signaling in Epithelial Cells
Authors: Morrison J. A. , Klingelhutz A. J. , Raab-Traub N. 
Published: October 2003

ABSTRACT
The Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) functions to maintain latency in EBV-infected B lymphocytes. Although LMP2A is nonessential for the immortalization of B lymphocytes by EBV, its expression in B lymphocytes prevents viral reactivation by blocking B-cell receptor activation and signaling. LMP2A also provides an antiapoptotic signal in transgenic mice that express LMP2A in B lymphocytes. LMP2A activates phosphatidylinositol 3-kinase (PI3K) and the serine/threonine kinase Akt in lymphocytes and epithelial cells. Here we show that EBV LMP2A activates the PI3K and β-catenin signaling pathways in telomerase-immortalized human foreskin keratinocytes (HFK). LMP2A activated Akt in a PI3K-dependent manner, and the downstream Akt targets glycogen synthase kinase 3β (GSK3β) and the Forkhead transcription factor FKHR were phosphorylated and inactivated in LMP2A-expressing HFK cells. GSK3β is a negative regulator of the Wnt signaling pathway, and inactivation of GSK3β by LMP2A signaling led to stabilization of β-catenin, the central oncoprotein of Wnt signaling. In LMP2A-expressing cells, β-catenin accumulated in the cytoplasm and translocated into the nucleus via a two-step mechanism. The cytoplasmic accumulation of β-catenin downstream of LMP2A was independent of PI3K signaling, whereas its nuclear translocation was dependent on PI3K signaling. In the nucleus, β-catenin activated a reporter responsive to T-cell factor, and this activation was augmented by LMP2A coexpression. The Wnt pathway is inappropriately activated in 90% of colon cancers and is dysregulated in several other cancers, and these data suggest that activation of this pathway by LMP2A may contribute to the generation of EBV-associated cancers.
Presence of Host ICAM-1 in Human Immunodeficiency Virus Type 1 Virions Increases Productive Infection of CD4
+
T Lymphocytes by Favoring Cytosolic Delivery of Viral Material
Authors: Tardif Mélanie R. , Tremblay Michel J. 
Published: October 2003

ABSTRACT

Although there is now convincing evidence that the infectivity of human immunodeficiency virus type 1 (HIV-1) is increased by incorporation of host intercellular adhesion molecule 1 (ICAM-1) in budding virions, the exact mechanism(s) through which ICAM-1 can so significantly affect HIV-1 biology remains obscure. To address this question, we focused our attention on the most proximal events in the virus life cycle. We made comparative analyses to estimate attachment and internalization of isogenic HIV-1 particles either lacking or bearing host-derived ICAM-1. Using attachment-and-entry assays and confocal fluorescence microscopy, we found that virus binding and uptake were both markedly enhanced by insertion of ICAM-1 within the virus envelope when PM1 lymphoid cells and primary human cells (i.e., peripheral blood lymphocytes and purified CD4
+
T cells) were used as targets. Moreover, ICAM-1-bearing virions entered cells with faster uptake kinetics than viruses devoid of ICAM-1. Experiments conducted with fully competent viruses further confirmed the positive effect of virion-anchored host ICAM-1 on HIV-1 replication. Interestingly, subcellular-fractionation assays revealed that ICAM-1 incorporation modifies the HIV-1 entry route by increasing the level of viral material released in the cytosol, a process of internalization known to be mediated mainly by pH-independent membrane fusion and to result in productive infection. A virion-based fusion assay confirmed that the acquisition of ICAM-1 increases the efficiency of productive HIV-1 entry in primary CD4
+
T lymphocytes. These observations provide new insights into how interactions other than those with gp120 and CD4-coreceptor complex can modulate the process of productive HIV-1 infection in CD4
+
T lymphocytes, a cell target highly relevant to HIV-1 pathogenesis.
Analysis of Herpes Simplex Virus ICP0 Promoter Function in Sensory Neurons during Acute Infection, Establishment of Latency, and Reactivation In Vivo
Authors: Thompson R. L. , Shieh May T. , Sawtell N. M. 
Published: October 2003

ABSTRACT

We have begun an analysis of the functional architecture of the ICP0 promoter in neurons in vivo with the ultimate goal of determining how this gene is regulated during reactivation in vivo. Promoter/reporter mutants in which the
Escherichia coli
beta-galactosidase (β-Gal) gene was driven by various permutations of the ICP0 promoter were employed to permit the analysis of promoter function without the added complications that would arise due to inappropriate regulation of ICP0 protein levels. A whole-ganglion immunohistochemical staining procedure (N. M. Sawtell, J. Virol.
77:
4127-4138, 2003) was used for direct comparisons of the expression of the promoter/reporter gene to expression of the native protein in the same cell. In this way, the expression of the putative wild-type promoter could be validated and results for mutant promoters could be compared to expression of the native gene. We found that a DNA fragment from bp −562 through the methionine start codon of the ICP0 gene contained all sequences required for properly regulated ICP0 expression in diverse cell types (including sensory neurons of the trigeminal ganglia [TG]) in vitro and in vivo, as indicated by colocalization of ICP0 and β-Gal. Truncation of the ICP0 promoter to bp −145 or −129 resulted in the loss of immediate-early (α) kinetics. The truncated promoters expressed high levels of the reporter gene with leaky late (γ1) kinetics in vitro and in some cell types in vivo. Unexpectedly, the truncated promoters did not express in TG neurons. Thus, TAATGARAT or other sequences upstream of bp −145 in the ICP0 promoter are required for basal expression of ICP0 in neurons but are not required for basal expression in other cells in vivo. There was a >95% concordance between reporter and native protein expression detected with the 562-bp promoter in neurons during the acute stage. However, this was not the case during reactivation from latency in vivo, as nearly twice as many neurons contained detectable β-Gal as contained detectable ICP0. This same 562-bp promoter/reporter cassette, when placed in the context of a latency-associated transcript (LAT) null mutant, resulted in >95% concordance of expression of β-Gal and ICP0 during reactivation in vivo. These last results strongly suggest that there is a posttranscriptional constraint on the expression of ICP0 protein during reactivation from latency and that this constraint is mediated by LAT.
Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1
env
Genes Derived from Brain and Blood of Patients with AIDS
Authors: Ohagen Asa , Devitt Amy , Kunstman Kevin J. , Gorry Paul R. , Rose Patrick P. , Korber Bette , Taylor Joann , Levy Robert , Murphy Robert L. , Wolinsky Steven M. , Gabuzda Dana 
Published: October 2003

ABSTRACT

The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that in lymphoid tissues, indicating tissue-specific compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins (Envs) from uncultured brain tissues have been biologically well characterized. In this study, we analyzed 37 full-length
env
genes from uncultured brain biopsy and blood samples from four patients with AIDS. Phylogenetic analysis of intrapatient sequence sets showed distinct clustering of brain relative to blood
env
sequences. However, no brain-specific signature sequence was identified. Furthermore, there was no significant difference in the number or positions of N-linked glycosylation sites between brain and blood
env
sequences. The patterns of coreceptor usage were heterogeneous, with no clear distinction between brain and blood
env
clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia. Recognition of epitopes by the 2F5, T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among
env
clones, reflecting genetic and conformational heterogeneity. Envs from two patients contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab strains and well-characterized primary isolates. These results suggest that HIV-1 Envs in brain cannot be distinguished from those in blood on the basis of coreceptor usage or the number or positions of N-glycosylation sites, indicating that other properties underlie neurotropism. The study also demonstrates characteristics of primary HIV-1 Envs from uncultured tissues and implies that Env variants that are glycosylated more extensively than lab strains and well-characterized primary isolates should be considered during development of vaccines and neutralizing antibodies.
A Lymphatic Mechanism of Rotavirus Extraintestinal Spread in the Neonatal Mouse
Authors: Mossel Eric C. , Ramig Robert F. 
Published: October 2003

ABSTRACT

We used the neonatal mouse model of rotavirus infection and virus strains SA11-clone 4 (SA11-Cl4) and Rhesus rotavirus (RRV) to examine the mechanism of the extraintestinal spread of viruses following oral inoculation. The spread-competent viruses, RRV and reassortant R7, demonstrated a temporal progression from the intestine, to the terminal ileum, to the mesenteric lymph nodes (MLN), and to the peripheral tissues. SA11-Cl4 was not found outside the intestine. Reassortant virus S7, which was unable to reach the liver in previous studies (E. C. Mossel and R. F. Ramig, J. Virol. 76:6502-6509, 2002), was recovered from 60% of the MLN, suggesting that there are multiple determinants for the spread of virus from the intestine to the MLN. Phenotypic segregation analysis identified RRV genome segment 6 (VP6) as a secondary determinant of the spread of virus to the MLN (
P
= 0.02) in reassortant viruses containing segment 7 from the spread-incompetent parent. These data suggest that in the orally infected neonatal mouse, the extraintestinal spread of rotavirus occurs via a lymphatic pathway, and the spread phenotype is primarily determined by NSP3 and can be modified by VP6.
Relative Age of Proviral Porcine Endogenous Retrovirus Sequences in
Sus scrofa
Based on the Molecular Clock Hypothesis
Authors: Tönjes Ralf R. , Niebert Marcus 
Published: October 2003

ABSTRACT

Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation. PERV classes A, B, and C harbor different envelope proteins. Two different types of long terminal repeat (LTR) structures exist, of which both are present only in PERV-A. One type of LTR contains a distinct repeat structure in U3, while the other is repeatless, conferring a lower level of transcriptional activity. Since the different LTR structures are distributed unequally among the proviruses and, apparently, PERV is the only virus harboring two different LTR structures, we were interested in determining which LTR is the ancestor. Replication-competent viruses can still be found today, suggesting an evolutionary recent origin. Our studies revealed that the age of PERV is at most 7.6 × 10
6
years, whereas the repeatless LTR type evolved approximately 3.4 × 10
6
years ago, being the phylogenetically younger structure. The age determined for PERV correlates with the time of separation between pigs (Suidae,
Sus scrofa
) and their closest relatives, American-born peccaries (Tayassuidae,
Pecari tajacu
), 7.4 × 10
6
years ago.
Requirement of Varicella-Zoster Virus Immediate-Early 4 Protein for Viral Replication
Authors: Sato Bunji , Sommer Marvin , Ito Hideki , Arvin Ann M. 
Published: October 2003

ABSTRACT
Varicella-zoster virus (VZV) is an alphaherpesvirus that causes two diseases, chickenpox and zoster. VZV open reading frame 4 (ORF4) encodes the immediate-early 4 (IE4) protein, which is conserved among alphaherpesvirus and has transactivation activity in transient transfections. To determine whether the ORF4 gene product is essential for viral replication, we used VZV cosmids to remove ORF4 from the VZV genome. Deleting ORF4 was incompatible with recovery of infectious virus, whereas transfections done by using repaired cosmids with ORF4 inserted at a nonnative site yielded virus. To analyze the functional domain of IE4, we introduced a mutation altering the C-terminal amino acids, KYFKC (K443S), which was designed to disrupt the dimerization of IE4 protein. Transfections with these mutant cosmids yielded no virus, indicating that this KYFKC motif was essential for IE4 function.
Maritime Security in a Multilateral Context: IMO Activities to Enhance Maritime Security
Authors: Hesse Hartmut 
Published: October 2003

AbstractIMO has, as an integral part of its mandate, the duty to make travel and transport by sea as safe as possible. In the wake of the tragic events of 11 September 2001 in the United States of America, the 22nd Session of the Assembly of the International Maritime Organization (IMO), which met at the Organization's London headquarters in November 2001, adopted Resolution A.924(22) on the "Review of Measures and Procedures to Prevent Acts of Terrorism which Threaten the Security of Passengers and Crews and the Safety of Ships". Since then a number of meetings of the Maritime Safety Committee (MSC) and its Working Group on maritime security were held and new maritime security regulations were developed. These mandatory provisions are detailed in the new Chapter XI-2 of the SOLAS Convention and the new International Ship and Port Facility Security (ISPS) Code, which was subsequently adopted by a Diplomatic Conference on Maritime Security, held at the IMO headquarters in London from 9-13 December 2002, for formal entry into force on 1 July 2004 (if deemed accepted on 1 January 2004). In addition, a Memorandum of Understanding (MoU) has been signed between the World Customs Organization (WCO) and the IMO in July 2001 to ensure closer co-operation. In addition to the work that the International Labour Organization (ILO) is undertaking regarding the development of a new seafarers' Identity Document, further co-operation is also anticipated in a Joint ILO/IMO Working Group to develop a comprehensive regulatory framework for the security of all port areas.
Container and Port Security: A Bilateral Perspective
Authors: Roach Ashley 
Published: October 2003

AbstractAs a follow-up to the terrorist attack of 11 September 2001 and due to the threat that such attacks may be reiterated in different forms, the United States has taken several measures with the view to forestall terrorist attacks from the sea. The measures include the Container Security Initiative and measures to enhance port security. This presentation describes the content of such measures and the reaction of states and international organisations thereto. The question is raised whether such measures may be taken unilaterally or rather through international force.
Protection of Foreign Ships against Piracy and Terrorism at Sea: Legal Aspects
Authors: Jesus H.E. Joséluis 
Published: October 2003

AbstractThis presentation gives a factual assessment of the phenomenon of piracy and other forms of terrorism at sea as well as a legal analysis of the respective international provisions to suppress such forms of violence. The points of difference between the international rules against piracy and terrorism are noted and the author calls for a more coherent approach and a more intensified cooperation in that respect. Otherwise, he argues, the freedom of navigation will be jeopardised.
The Protection of Navigation in Case of Armed Conflict
Authors: von Heinegg Wolff Heintschel 
Published: October 2003

AbstractThis presentation gives a reassessment of the rules on naval warfare on the background of the fact that most armed conflicts in the post-World War II period have been internal or mixed armed conflicts. In this context the questions concerning the applicability of the traditional rules on naval warfare and the potential area for naval warfare are raised. The paper deals predominantly with the protection of navigation of neutrals.
Post September 11 Security Challenges to the Legal Regime of the Maritime Carriage of Nuclear and Radioactive Materials
Authors: Suarez A. Suzette 
Published: October 2003

AbstractRadioactive material which is transported over sea has, so far, not resulted in any pollution of the sea. This paper reviews the legal regime of the maritime carriage of nuclear and radioactive materials and assesses its sufficiency in general and in the context of the risks of nuclear terrorism. It is noted that the respective provisions have been elaborated under the auspices of two different international organisations, namely IMO and IAEA, and that their reaction to possible nuclear threats is slow.
Islamic Law, Practice, and Legal Doctrine: Exempting the Poor from the Jizya Under the Ayyubids (1171-1250)
Authors: Alshech Eli 
Published: October 2003

AbstractMost Sunnī scholars unequivocally exempt poor dhimmīs (mostly Christians and Jews under Muslim rule) from the duty to pay the Qur ān-imposed poll tax. Shāfi ī scholars, however, hold two conflicting opinions, one that exempts the poor and another that does not. This article examines the reality of destitute Jews living in Egypt and Syria under the Ayyubid regime in order to determine which of the two conflicting Shāfi ī rulings was applied in practice. Drawing on Geniza documents and literary sources, I argue that in the Ayyubid period no exemptions were offered to the poor whatsoever. This taxation policy, in my view, may reflect not an arbitrary choice made by local Ayyubid tax officials, but a conscious decision made by the Ayyubid rulers and the leading contemporary Shāfi ī scholars. The Ayyubids most likely appealed to the Shāfi ī religious authorities, pressing them to adopt the more stringent opinion, which would allow authorities to refrain from exempting the poor.
A Post-qur'ānic Religion Between Apostasy and Public Order: Egyptian Muftis and Courts on the Legal Status of the Bahā'ī Faith
Authors: Pink Johanna 
Published: October 2003

AbstractThe more than 100-year presence of Bahā'īs in Egypt has caused a number of legal problems for Muslim jurists and Egyptian courts. Both have dealt with the status of Bahā'īs in personal status, criminal and administrative law. In this essay, I describe the solutions put forward by muftis and courts for novel problems generated by the presence of a post-Qur ānic religious minority in Egypt, and I analyze the interaction between shari a and state jurisdiction. Special attention is given to methods of dealing with issues that have no precedent in classical Islamic law, like the status of Bahā īs of non-Muslim descent and the consequences of apostasy for matters of administrative law or employment in public service.
Elite workers and the colony-level pattern of labor division in the yellowjacket wasp, Vespula germanica
Authors: Nordheim Erik , Hurd Christine , Jeanne Robert 
Published: October 2003

AbstractMeasurements of carbohydrate foraging behavior of Vespula germanica yellowjackets show that the distribution of the number of foragers over the number of trips is highly skewed with a few foragers making a disproportionate number of trips. We tested several empirical models based on different biological assumptions to see which model best described the distribution. For all periods of observation, the data are well fitted by a straight line on a log-log plot. This fit indicates that the distribution of labor is non-increasing monotonic; i.e. continually decreasing, and follows a power law. Stochasticity and self-organization are two possible explanations for the power law distribution. As an alternative approach, cluster analysis of various foraging characteristics of individual foragers clearly separated foragers into two groups and is consistent with a bimodal model for the division of foraging labor. Based on these cluster results, we operationally defined workers as either 'elite' or 'non-elite'. We found that elite foragers are not more likely than non-elites to be task specialists. The data show that workers develop into elites but do not support the hypothesis of self-reinforcement as the mechanism.
Substitution of silk stabilimenta for egg sacs by Allocyclosa bifurca (Araneae: Araneidae) suggests that silk stabilimenta function as camouflage devices
Authors: Eberhard William 
Published: October 2003

AbstractThe matching form and orientation of egg sacs and spiders, the match between egg sac color and that of the spider, ontogenetic changes in spider coloration that occur when egg sacs begin to be produced, differences in the positions of the spiders' legs during the day and at night, and coordinated changes in spider and egg sac colors in different populations all indicated that the egg sac and detritus stabilimenta near the hub function as camouflage in Allocyclosa bifurca. Silk stabilimentum construction was induced by experimental removal of egg sac stabilimenta, and was inhibited by addition of egg sacs. This implies that silk stabilimenta also function as camouflage devices.
Social and spatial aspects of male subgrouping in a community of wild chimpanzees
Authors: Mitani John , Amsler Sylvia 
Published: October 2003

AbstractStrong social bonds typically develop between dyadic pairs of male chimpanzees. These bonds are manifest in several contexts, including association, grooming, and proximity. Here we demonstrate that social bonds exist at a higher level of organization among males living in an extremely large community at Ngogo, Kibale National Park, Uganda. An analysis of over 2,500 hours of observation of 35 individuals revealed two distinct subgroups of male chimpanzees. Males that composed each subgroup can be identified on the basis of their tendency to associate in temporary parties. Matrix permutation tests indicated that subgroup members tended to maintain spatial proximity to each other and participate together in territorial boundary patrols. Subgroups formed along the lines of age and rank; members of a small subgroup were younger and lower ranking than individuals in a larger subgroup. Despite this social clustering of males, community integrity remained intact with low levels of aggression between individuals of different subgroups. After controlling for the effect of association, significantly more aggression occurred within compared to between subgroups. In addition, males of the different subgroups displayed significant overlap in their use of the community territory and thus showed no tendency to divide spatially. We compare our findings with those from other animal species and chimpanzee populations and discuss them in the context of the unusual demography of the Ngogo community.
Influence of advertisement calls on reproductive success in the male midwife toad Alytes obstetricans
Authors: Le Jacques Dominique , Lodé Thierry 
Published: October 2003

AbstractConsidering the advertisement call in anuran as a sexually selected trait, we investigated the effects of male call parameters on reproductive success in midwife toad Alytes obstetricans. The pattern of advertisement call was studied in 81 males. The mean fundamental frequency varied among males. Fundamental frequency, call duration and male size correlated with the male mating success. From the stepwise regression analysis, the low call frequency was found to influence significantly the number of carried eggs and the hatching success. The fact that a single male may fertilise the eggs of several females and a single female may mate with several males constitutes an original sexual system. Large males obtained more matings and showed a higher hatching success. Female choice for dominant frequency may be regarded as a related-fitness trait being correlated with male size. Anyway, the male size and the female choice for low calls result in a same evolutionary trend favouring a best fitness.