bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proline-Rich Region in the Coxsackievirus 3A Protein Is Required for the Protein To Inhibit Endoplasmic Reticulum-to-Golgi Transport
Authors: Wessels Els , Duijsings Daniël , Notebaart Richard A. , Melchers Willem J. G. , van Kuppeveld Frank J. M. 
Published: March 2005

ABSTRACT

The ability of the 3A protein of coxsackievirus B (CVB) to inhibit protein secretion was investigated for this study. Here we show that the ectopic expression of CVB 3A blocked the transport of both the glycoprotein of vesicular stomatitis virus, a membrane-bound secretory marker, and the alpha-1 protease inhibitor, a luminal secretory protein, at a step between the endoplasmic reticulum (ER) and the Golgi complex. CVB 3A contains a conserved proline-rich region in its N terminus. The importance of this proline-rich region was investigated by introducing Pro-to-Ala substitutions. The mutation of Pro
19
completely abolished the ability of 3A to inhibit ER-to-Golgi transport. The mutation of Pro
14
, Pro
17
, or Pro
20
also impaired this ability, but to a lesser extent. The mutation of Pro
18
had no effect. We also investigated the possible importance of this proline-rich region for the function of 3A in viral RNA replication. To this end, we introduced the Pro-to-Ala mutations into an infectious cDNA clone of CVB3. The transfection of cells with in vitro-transcribed RNAs of these clones gave rise to mutant viruses that replicated with wild-type characteristics. We concluded that the proline-rich region in CVB 3A is required for its ability to inhibit ER-to-Golgi transport, but not for its function in viral RNA replication. The functional relevance of the proline-rich region is discussed in light of the proposed structural model of 3A.
Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease
Authors: Cunningham Colm , Wilcockson David C. , Boche Delphine , Perry V. Hugh 
Published: March 2005

ABSTRACTChronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrPScdeposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and α2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPScdeposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrPScis not a stimulus for splenic macrophages and that neither peripheral PrPScdeposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.
A Novel Assay Allows Genotyping of the Latent Reservoir for Human Immunodeficiency Virus Type 1 in the Resting CD4+T Cells of Viremic Patients
Authors: Monie Daphne , Simmons Rachel P. , Nettles Richard E. , Kieffer Tara L. , Zhou Yan , Zhang Haili , Karmon Sharon , Ingersoll Roxann , Chadwick Karen , Zhang Hao , Margolick Joseph B. , Quinn Thomas C. , Ray Stuart C. , Wind-Rotolo Megan , Miller Michael , Persaud Deborah , Siliciano Robert F. 
Published: March 2005

ABSTRACTA latent reservoir for human immunodeficiency virus type 1 (HIV-1) consisting of integrated provirus in resting memory CD4+T cells prevents viral eradication in patients on highly active antiretroviral therapy (HAART). It is difficult to analyze the nature and dynamics of this reservoir in untreated patients and in patients failing therapy, because it is obscured by an excess of unintegrated viral DNA that constitutes the majority of viral species in resting CD4+T cells from viremic patients. Therefore, we developed a novel culture assay that stimulates virus production from latent, integrated HIV-1 in resting CD4+T cells in the presence of antiretroviral drugs that prevent the replication of unintegrated virus. Following activation, resting CD4+T cells with integrated HIV-1 DNA produced virus particles for several days, with peak production at day 5. Using this assay, HIV-1polsequences from the resting CD4+T cells of viremic patients were found to be genetically distinct from contemporaneous plasma virus. Despite the predominance of a relatively homogeneous population of drug-resistant viruses in the plasma of patients failing HAART, resting CD4+T cells harbored a diverse array of wild-type and archival drug-resistant viruses that were less fit than plasma virus in the context of current therapy. These results provide the first direct evidence that resting CD4+T cells serve as a stable reservoir for HIV-1 even in the setting of high levels of viremia. The ability to analyze archival species in viremic patients may have clinical utility in detecting drug-resistant variants not present in the plasma.
In Vivo Evidence for Instability of Episomal Human Immunodeficiency Virus Type 1 cDNA
Authors: Sharkey Mark , Triques Karine , Kuritzkes Daniel R. , Stevenson Mario 
Published: March 2005

ABSTRACT

Current regimens for the management of human immunodeficiency virus type 1 (HIV-1) infection suppress plasma viremia to below detectable levels for prolonged intervals. Nevertheless, there is a rapid resumption in plasma viremia if therapy is interrupted. Attempts to characterize the extent of viral replication under conditions of potent suppression and undetectable plasma viremia have been hampered by a lack of convenient assays that can distinguish latent from ongoing viral replication. Using episomal viral cDNA as a surrogate for ongoing replication, we previously presented evidence that viral replication persists in the majority of infected individuals with a sustained aviremic status. The labile nature of viral episomes and hence their validity as surrogate markers of ongoing replication in individuals with long-term-suppressed HIV-1 infection have been analyzed in short-term in vitro experiments with conflicting results. Since these in vitro experiments do not shed light on the long-term in vivo dynamics of episomal cDNA or recapitulate the natural targets of infection in vivo, we have analyzed the dynamics of episomal cDNA turnover in vivo by following the emergence of an M184V polymorphism in plasma viral RNA, in episomal cDNA, and in proviral DNA in patients on suboptimal therapies. We demonstrate that during acquisition of drug resistance, wild-type episomal cDNAs are replaced by M184V-harboring episomes. Importantly, a complete replacement of wild-type episomes with M184V-containing episomes occurred while proviruses remained wild type. This indicates that episomal cDNAs are turned over by degradation rather than through death or tissue redistribution of the infected cell itself. Therefore, evolution of episomal viral cDNAs is a valid surrogate of ongoing viral replication in HIV-1-infected individuals
.
Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses
Authors: Wu Xiaolin , Li Yuan , Crise Bruce , Burgess Shawn M. , Munroe David J. 
Published: March 2005

ABSTRACT
Integration into the host genome is one of the hallmarks of the retroviral life cycle and is catalyzed by virus-encoded integrases. While integrase has strict sequence requirements for the viral DNA ends, target site sequences have been shown to be very diverse. We carefully examined a large number of integration target site sequences from several retroviruses, including human immunodeficiency virus type 1, simian immunodeficiency virus, murine leukemia virus, and avian sarcoma-leukosis virus, and found that a statistical palindromic consensus, centered on the virus-specific duplicated target site sequence, was a common feature at integration target sites for these retroviruses.
Induction of Apoptosis by Rewiring the Signal Transduction of Epstein-Barr Virus Oncoprotein LMP1 toward Caspase Activation
Authors: Hatzivassiliou Eudoxia G. , Tsichritzis Theodore , Mosialos George 
Published: March 2005

ABSTRACT
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an oncoprotein which mimics activated tumor necrosis factor receptor family members. Here we demonstrate the principle that an inducible association of the LMP1 cytoplasmic carboxyl terminus with caspase-8 by a heterodimerizing agent causes apoptosis. This process depends on the catalytic activity of caspase-8 and the ability of LMP1 to oligomerize constitutively at the plasma membrane. Our data indicate that chemical inducers of the association of the LMP1 carboxyl terminus with caspase-8 can kill LMP1-expressing cells selectively. Such compounds could be used as chemotherapeutic agents for LMP1-associated malignancies.
Tissue-Resident Macrophages Are Productively Infected Ex Vivo by Primary X4 Isolates of Human Immunodeficiency Virus Type 1
Authors: Jayakumar Prerana , Berger Irina , Autschbach Frank , Weinstein Mark , Funke Benjamin , Verdin Eric , Goldsmith Mark A. , Keppler Oliver T. 
Published: March 2005

ABSTRACTInfection of macrophages has been implicated as a critical event in the transmission and persistence of human immunodeficiency virus type 1 (HIV-1). Here, we explore whether primary X4 HIV-1 isolates can productively infect tissue macrophages that have terminally differentiated in vivo. Using immunohistochemistry, HIV-1 RNA in situ hybridization, and confocal immunofluorescence microscopy, we demonstrate that macrophages residing in human tonsil blocks can be productively infected ex vivo by primary X4 HIV-1 isolates. This challenges the model in which macrophage tropism is a key determinant of the selective transmission of R5 HIV-1 strains. Infection of tissue macrophages by X4 HIV-1 may be highly relevant in vivo and contribute to key events in HIV-1 pathogenesis.
Ex Vivo Stimulation of B Cells Latently Infected with Gammaherpesvirus 68 Triggers Reactivation from Latency
Authors: Moser Janice M. , Upton Jason W. , Gray Kathleen S. , Speck Samuel H. 
Published: March 2005

ABSTRACTMurine gammaherpesvirus 68 (γHV68) infection of mice results in the establishment of a chronic infection, which is largely maintained through latent infection of B lymphocytes. Acute virus replication is almost entirely cleared by 2 weeks postinfection. Spontaneous reactivation of γHV68 from latently infected splenocytes upon ex vivo culture can readily be detected at the early stages of infection (e.g., day 16). However, by 6 weeks postinfection, very little spontaneous reactivation is detected upon explant into tissue culture. Here we report that stimulation of latently infected splenic B cells harvested at late times postinfection with cross-linking surface immunoglobulin (Ig), in conjunction with anti-CD40 antibody treatment, triggers virus reactivation. As expected, this treatment resulted in B-cell activation, as assessed by upregulation of CD69 on B cells, and ultimately B-cell proliferation. Since anti-Ig/anti-CD40 stimulation resulted in splenic B-cell proliferation, we assessed whether this reactivation stimulus could overcome the previously characterized defect in virus reactivation of a v-cyclin null γHV68 mutant. This analysis demonstrated that anti-Ig/anti-CD40 stimulation could drive reactivation of the v-cyclin null mutant virus in latently infected splenocytes, but not to the levels observed with wild-type γHV68. Thus, there appears to be a role for the v-cyclin in B cells following anti-Ig/anti-CD40 stimulation independent of the induction of the cell cycle. Finally, to assess signals that are not mediated through the B-cell receptor, we demonstrate that addition of lipopolysaccharide to explanted splenocyte cultures also enhanced virus reactivation. These studies complement and extend previous analyses of Epstein-Barr virus and Kaposi's sarcoma-associated virus reactivation from latently infected cell lines by investigating reactivation of γHV68 from latently infected primary B cells recovered from infected hosts.
Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles
Authors: Gorny Miroslaw K. , Stamatatos Leonidas , Volsky Barbara , Revesz Kathy , Williams Constance , Wang Xiao-Hong , Cohen Sandra , Staudinger Robert , Zolla-Pazner Susan 
Published: March 2005

ABSTRACTThe selection of human monoclonal antibodies (MAbs) specific for human immunodeficiency virus (HIV) type 1 by binding assays may fail to identify Abs to quaternary epitopes on the intact virions. The HIV neutralization assay was used for the selection of human MAb 2909, which potently neutralizes SF162 and recognizes an epitope on the virus surface but not on soluble proteins. Three regions of gp120, the V2 and V3 loops and the CD4 binding domain, contribute to the epitope recognized by MAb 2909. The existence of such a unique MAb, which defines a complex epitope formed by a quaternary structure, suggests that there may be other new neutralizing HIV epitopes to target with vaccines.
Incidence of sports and recreation related injuries resulting in hospitalization in Wisconsin in 2000
Authors: Dempsey R L , Layde P M , Laud P W , Guse C E , Hargarten S W 
Published: April 2005

Objective:To describe the incidence and patterns of sports and recreation related injuries resulting in inpatient hospitalization in Wisconsin. Although much sports and recreation related injury research has focused on the emergency department setting, little is known about the scope or characteristics of more severe sports injuries resulting in hospitalization.Setting:The Wisconsin Bureau of Health Information (BHI) maintains hospital inpatient discharge data through a statewide mandatory reporting system. The database contains demographic and health information on all patients hospitalized in acute care non-federal hospitals in Wisconsin.Methods:The authors developed a classification scheme based on the International Classification of Diseases External cause of injury code (E code) to identify hospitalizations for sports and recreation related injuries from the BHI data files (2000). Due to the uncertainty within E codes in specifying sports and recreation related injuries, the authors used Bayesian analysis to model the incidence of these types of injuries.Results:There were 1714 (95% credible interval 1499 to 2022) sports and recreation-related injury hospitalizations in Wisconsin in 2000 (32.0 per 100 000 population). The most common mechanisms of injury were being struck by/against an object in sports (6.4 per 100 000 population) and pedal cycle riding (6.2 per 100 000). Ten to 19 year olds had the highest rate of sports and recreation related injury hospitalization (65.3 per 100 000 population), and males overall had a rate four times higher than females.Conclusions:Over 1700 sports and recreation related injuries occurred in Wisconsin in 2000 that were treated during an inpatient hospitalization. Sports and recreation activities result in a substantial number of serious, as well as minor injuries. Prevention efforts aimed at reducing injuries while continuing to promote participation in physical activity for all ages are critical.
CHARACTERISTIC ASPECTS OF CERAMIC COMPOUNDS CONTAINING YTTERBIUM
Authors: REDAC TEODOR-RADU 
Published: March 2005

This paper presents experimental data obtained by its author on superconductive ceramics of type 1-2-3, with ytterbium as the element of rare earth. Thermal, electric and magnetic analyses are presented. The aim of the paper is to put in evidence the effect of the substitution of Yb or Cu with Ga in the compound YbBa 2 Cu 3 O 7-δ, in order to compare these properties of this compound with other compounds from the same class having Y or Eu as rare earth ions.
COMPACT REPRESENTATIONS OF SEARCH IN COMPLEX DOMAINS
Authors: BEN-ASHER YOSI , FARCHI EITAN 
Published: April 2005

We introduce a new zero-sum matrix game for modeling search in structured domains. In this game, one player tries to find a "bug" while the other tries to hide it. Both players exploit the structure of the "search" domain. Intuitively, this search game is a mathematical generalization of the well known binary search. The generalization is from searching over totally ordered sets to searching over more complex search domains such as trees, partial orders and general set systems. As there must be one row for every search strategy, and there are exponentially many ways to search even in very simple search domains, the game's matrix has exponential size ("space"). In this work we present two ways to reduce the space required to compute the Nash value (in pure strategies) of this game: • First we show that a Nash equilibrium in pure strategies can be computed by using a backward induction on the matrices of each "part" or sub structure of the search domain. This can significantly reduce the space required to represent the game. • Next, we show when general search domains can be represented as DAGs (Directed Acycliqe Graphs). As a result, the Nash equilibrium can be directly computed using the DAG. Consequently the space needed to compute the desired search strategy is reduced to O(n2) where n is the size of the search domain.
REDUCING FUZZY ALGEBRA TO CLASSICAL ALGEBRA
Authors: WEINBERGER ARTHUR 
Published: April 2005

This paper presents three main ideas. They are the Metatheorem, the lattice embedding for sets, and the lattice embedding for algebras. The Metatheorem allows you to convert existing theorems about classical subsets into corresponding theorem about fuzzy subsets. The concept of a fuzzyfiable operation on a powerset is defined. The main result states that any implication or identity which can be stated using fuzzyfiable operations is true about fuzzy subsets if and only if it is true about classical subsets. The lattice embedding theorem for sets shows that for any set X, there is a set Y such that the lattice of fuzzy subsets of X is isomorphic to a sublattice of the classical subsets of Y. In fact it is further proved that if X is infinite, then we can choose Y = X and get the surprising result that the lattice of fuzzy subsets of X is isomorphic to a sublattice of the classical subsets of X itself. The idea is illustrated with an example explicitly showing how the lattice of fuzzy subsets of the closed unit interval 𝕀 = [0,1] embeds into the lattice of classical subsets of 𝕀. The lattice embedding theorem for algebras shows that under certain circumstances the lattice of fuzzy subalgebras of an algebra A embeds into the lattice of classical subalgebras of a closely related algebra A′. The following sample use of this embeding theorem is given. It is a well known fact that the lattice of normal subgroups of a group is a modular lattice. The embeding theorem is used here to conclude that lattice of fuzzy normal subgroups of a group is a modular lattice too.
Early Dynamics of Hepatitis C Virus in the Circulation of Chimpanzees with Experimental Infection
Authors: Tanaka Junko , Katayama Keiko , Kumagai Junko , Komiya Yutaka , Yugi Hisao , Kishimoto Shinya , Mizui Masaaki , Tomoguri Tetsushi , Miyakawa Yuzo , Yoshizawa Hiroshi 
Published: April 2005

Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 10<sup>2</sup> copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.3–8.6 h and log time (time required to grow 10-fold) at 31.3– 42.9 h. The exact doubling time of HCV determined in them would help plan an efficient strategy for screening out blood donors in the window period of infection between the exposure and the development of antibody to HCV in serum.
El Niño: Catastrophe or Opportunity
Authors: Goddard Lisa , Dilley Maxx 
Published: March 2005

AbstractEl Niño–Southern Oscillation (ENSO) phenomenon, a periodic warming of sea surface temperatures in the eastern and central equatorial Pacific, generates a significant proportion of short-term climate variations globally, second only to the seasonal cycle. Global economic losses of tens of billions of dollars are attributed to extremes of ENSO (i.e., El Niño and La Niña), suggesting that these events disproportionately trigger socioeconomic disasters on the global scale. Since global El Niño/La Niña–associated climate impacts were first documented in the 1980s, the prevailing assumption has been that more severe and widespread climate anomalies, and, therefore, greater climate-related socioeconomic losses, should be expected during ENSO extremes. Contrary to expectations, climate anomalies associated with such losses are not greater overall during ENSO extremes than during neutral periods. However, during El Niño and La Niña events climate forecasts are shown to be more accurate. Stronger ENSO events lead to greater predictability of the climate and, potentially, the socioeconomic outcomes. Thus, the prudent use of climate forecasts could mitigate adverse impacts and lead instead to increased beneficial impacts, which could transform years of ENSO extremes into the least costly to life and property.
Variability of Upper Pacific Ocean Overturning in a Coupled Climate Model
Authors: Merryfield William J. , Boer George J. 
Published: March 2005

Abstract
Variability of subtropical cell (STC) overturning in the upper Pacific Ocean is examined in a coupled climate model in light of large observed changes in STC transport. In a 1000-yr control run, modeled STC variations are smaller than observed, but correlate in a similar way with low-frequency ENSO-like variability. In model runs that include anthropogenically forced climate change, STC pycnocline transports decrease progressively under the influence of global warming, attaining reductions of 8% by 2000 and 46% by 2100. Although the former reduction is insufficient to fully account for the apparent observed decline in STC transport over recent decades, it does suggest that global warming may have contributed to the observed changes. Analysis of coupled model results shows that STC transports play a significant role in modulating tropical Pacific Ocean heat content, and that such changes are dominated by anomalous currents advecting mean temperature, rather than by advection of temperature anomalies by mean currents.