bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis of Liver-Derived Cells Induced by Parvovirus B19 Nonstructural Protein
Authors: Poole Brian D. , Zhou Jing , Grote Amy , Schiffenbauer Adam , Naides Stanley J. 
Published: March 2006

ABSTRACT
Parvovirus B19 has been implicated in some cases of acute fulminant non-A, non-B, non-C, non-G liver failure. Our laboratory previously demonstrated that B19 infection of hepatocytes induces apoptosis and that the B19 viral nonstructural protein, NS1, may play a critical role. To study the involvement of NS1 in apoptosis of liver cells, we generated a fusion protein of NS1 with enhanced green fluorescent protein (eGFP) in a system allowing for inducible gene expression. Transfection of the liver-derived cell line HepG2 with the eGFP/NS1 vector allowed expression of the fusion protein, which was visualized by fluorescence microscopy and demonstrated by immunoblotting. The fusion protein localized to discrete domains in the nucleus. Transfection of HepG2 cells with the eGFP/NS1 vector led to apoptosis of 35% of transfected cells, a sevenfold increase over cells transfected with the parent eGFP expression vector. Mutation of the eGFP/NS1 vector to eliminate the nucleoside triphosphate-binding site of NS1 significantly decreased apoptosis, as did treatment of transfected cells with inhibitors of caspase 3 or 9. Neutralization of tumor necrosis factor alpha or Fas ligand had no effect on apoptosis. These results demonstrate that NS1 is sufficient to induce apoptosis in liver-derived cells and that it does so through the initiation of an intrinsic caspase pathway.
Formation of nsP3-Specific Protein Complexes during Sindbis Virus Replication
Authors: Frolova Elena , Gorchakov Rodion , Garmashova Natalia , Atasheva Svetlana , Vergara Leoncio A. , Frolov Ilya 
Published: March 2006

ABSTRACTAlphaviruses are arthropod-borne viruses (arboviruses) that include a number of important human and animal pathogens. Their replication proceeds in the cytoplasm of infected cells and does not directly depend on nuclei. Alphaviruses encode only four nonstructural proteins that are required for the replication of viral genome and transcription of the subgenomic RNA. However, the replicative enzyme complexes (RCs) appear to include cellular proteins and assemble on cellular organelles. We have developed a set of recombinant Sindbis (SIN) viruses with green fluorescent protein (GFP) insertions in one of the nonstructural proteins, nsP3, to further understand the RCs' genesis and structure. We studied the assembly of nsP3/GFP-containing protein complexes at different stages of infection and isolated a combination of cellular proteins that are associated with SIN nsP3. We demonstrated the following. (i) SIN nsP3 can tolerate the insertion of GFP into different fragments of the coding sequence; the designed recombinant viruses are viable, and their replication leads to the assembly of nsP3/GFP chimeric proteins into gradually developing, higher-order structures differently organized at early and late times postinfection. (ii) At late times postinfection, nsP3 is assembled into complexes of similar sizes, which appear to be bound to cytoskeleton filaments and can aggregate into larger structures. (iii) Protein complexes that are associated with nsP3/GFP contain a high concentration of cytoskeleton proteins, chaperones, elongation factor 1A, heterogeneous nuclear ribonucleoproteins, 14-3-3 proteins, and some of the ribosomal proteins. These proteins are proposed to be essential for SIN RC formation and/or functioning.
Baculovirus-Mediated Gene Delivery into Mammalian Cells Does Not Alter Their Transcriptional and Differentiating Potential but Is Accompanied by Early Viral Gene Expression
Authors: Kenoutis Christos , Efrose Rodica C. , Swevers Luc , Lavdas Alexandros A. , Gaitanou Maria , Matsas Rebecca , Iatrou Kostas 
Published: March 2006

ABSTRACT

Gene delivery to neural cells is central to the development of transplantation therapies for neurological diseases. In this study, we used a baculovirus derived from the domesticated silk moth,
Bombyx mori
, as vector for transducing a human cell line (HEK293) and primary cultures of rat Schwann cells. Under optimal conditions of infection with a recombinant baculovirus containing the reporter green fluorescent protein gene under mammalian promoter control, the infected cells express the transgene with high efficiency. Toxicity assays and transcriptome analyses suggest that baculovirus infection is not cytotoxic and does not induce differential transcriptional responses in HEK293 cells. Infected Schwann cells retain their characteristic morphological and molecular phenotype as determined by immunocytochemistry for the marker proteins S-100, glial fibrillary acidic protein, and p75 nerve growth factor receptor. Moreover, baculovirus-infected Schwann cells are capable of differentiating in vitro and express the P0 myelination marker. However, transcripts for several immediate-early viral genes also accumulate in readily detectable levels in the transduced cells. This transcriptional activity raises concerns regarding the long-term safety of baculovirus vectors for gene therapy applications. Potential approaches for overcoming the identified problem are discussed.
Cell Cycle Perturbations Induced by Infection with the Coronavirus Infectious Bronchitis Virus and Their Effect on Virus Replication
Authors: Dove Brian , Brooks Gavin , Bicknell Katrina , Wurm Torsten , Hiscox Julian A. 
Published: March 2006

ABSTRACT

In eukaryotic cells, cell growth and division occur in a stepwise, orderly fashion described by a process known as the cell cycle. The relationship between positive-strand RNA viruses and the cell cycle and the concomitant effects on virus replication are not clearly understood. We have shown that infection of asynchronously replicating and synchronized replicating cells with the avian coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus, resulted in the accumulation of infected cells in the G
2
/M phase of the cell cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology indicated that there was a down-regulation of cyclins D1 and D2 (G
1
regulatory cyclins) and that a proportion of virus-infected cells underwent aberrant cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division. We assessed the impact of the perturbations on the cell cycle for virus-infected cells and found that IBV-infected G
2
/M-phase-synchronized cells exhibited increased viral protein production when released from the block when compared to cells synchronized in the G
0
phase or asynchronously replicating cells. Our data suggested that IBV induces a G
2
/M phase arrest in infected cells to promote favorable conditions for viral replication.
Characterization of a Torovirus Main Proteinase
Authors: Smits Saskia L. , Snijder Eric J. , de Groot Raoul J. 
Published: March 2006

ABSTRACT

Viruses
of the order
Nidovirales
encode huge replicase polyproteins.
These are processed primarily by the chymotrypsin-like main proteinases
(M
pro
s). So far, M
pro
s have been studied only for
corona-, arteri-, and roniviruses. Here, we report the characterization
of the M
pro
of toroviruses, the fourth main Nidovirus
branch. Comparative sequence analysis of polyprotein 1a of equine
torovirus (EToV) strain Berne, identified a serine proteinase domain,
flanked by hydrophobic regions. Heterologous expression of this domain
resulted in autoprocessing at flanking cleavage sites. N-terminal
sequence analysis of cleavage products tentatively identified
FxxQ↓(S, A) as the substrate consensus sequence. EToV
M
pro
combines several traits of its closest relatives. It
has a predicted three-domain structure, with two catalyticβ
-barrel domains and an additional C-terminal domain of unknown
function. With respect to substrate specificity, the EToV
M
pro
resembles its coronavirus homologue in its preference
for P1-Gln, but its substrate-binding subsite, S1, more closely
resembles that of arteri- and ronivirus M
pro
s, which prefer
P1-Glu. Surprisingly, in contrast to the M
pro
s of corona-
and roniviruses, but like that of arterivirus, the torovirus
M
pro
uses serine instead of cysteine as its principal
nucleophile. Under the premise that the M
pro
s of corona- and
toroviruses are more closely related to each other than to those of
arteri- and roniviruses, the transition from serine- to cysteine-based
proteolytic catalysis (or vice versa) must have happened more than once
in the course of nidovirus evolution. In this respect, it is of
interest that a mutant EToV M
pro
with a
Ser
165
→Cys substitution retained partial enzymatic
activity.
Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein
Authors: Schornberg Kathryn , Matsuyama Shutoku , Kabsch Kirsten , Delos Sue , Bouton Amy , White Judith 
Published: March 2006

ABSTRACT
Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1 displays significantly enhanced infection and is largely resistant to the effects of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent endosomal/lysosomal function. These and other results support a model in which CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.
Hepatitis C Virus Protease Gene Diversity in Patients Coinfected with Human Immunodeficiency Virus
Authors: Winters Mark A. , Welles Seth L. , Holodniy Mark 
Published: March 2006

ABSTRACT

The clonal variability of the hepatitis C virus (HCV) protease gene in 24 individuals with HCV genotypes 1a, 1b, 2b, and 3a who were coinfected with the human immunodeficiency virus was evaluated. Within-genotype variability at the nucleotide and amino acid levels ranged from 6.5 to 8.6% and 2.2 to 3.8%, respectively. After adjustments were made for correlation of intrapatient clonal variation, mixed-model analysis indicated that nucleotide and amino acid variability among patients with different genotypes did not differ significantly. However, within individual patients, clonal variability differed by up to 5.3% and 5.8% at the nucleotide and amino acid levels, respectively, and genotype 1a had significantly greater nucleotide variability than other genotypes (
P
= 0.01). Significant variability exists within HCV protease gene variants at the patient level and could affect the effectiveness of HCV protease inhibitors.
Murine Cytomegalovirus Interference with Antigen Presentation Contributes to the Inability of CD8 T Cells To Control Virus in the Salivary Gland
Authors: Lu Xiuju , Pinto Amelia K. , Kelly Ann M. , Cho Kathy S. , Hill Ann B. 
Published: March 2006

ABSTRACT
Compared to other organs, murine cytomegalovirus (MCMV) replication in the salivary gland is uniquely resistant to CD8 T-cell control. The contribution of viral genes that interfere with antigen presentation (VIPRs) to this resistance was assessed using a mutant lacking MCMV's known VIPRs. Salivary gland titers of the VIPR-deficient virus were at least 10-fold lower than those of the wild type during the persistent phase of infection; the defect was reversed by depleting CD8 T cells. Thus, VIPRs contribute to CD8 T cells' inability to control virus in the salivary gland.
Torsion of the testicular appendix: importance of associated acute inflammation
Authors: Rakha E , Puls F , Saidul I , Furness P 
Published: March 2006

Background:Torsion of the testicular appendix is the commonest cause of acute scrotum in children. The histological picture of these cases is variable and many show a heavy acute inflammatory cell infiltrate, unlike the response to pure ischaemic necrosis in other organs. The clinical implications and consequences of this associated inflammation are not clear.Methods:A retrospective review of all cases presenting with torsion of the testicular appendix between 1987 and 2005 was carried out. In all, 79 cases were reviewed and the degree of acute inflammatory cell infiltrate and other morphological parameters were assessed and compared with the patients’ clinical, operative and postoperative findings. Stains for bacteria and fungi were examined.Results:A positive correlation was found between the severity of acute inflammatory cell infiltrates and the longer duration of symptoms and presence of clinical evidence of torsion of the testicular appendages. No other association was detected between the pattern or degree of acute inflammatory cell infiltrate and any other clinicopathological variable that may indicate pyogenic infection. No bacteria or fungal elements were identified. Marked lymphatic dilation may be the only histological finding to indicate the presence of early torsion in cases of scrotal pain secondary to torsion of the appendix testis.Conclusion:Heavy acute inflammatory cell infiltrates in the torted testicular appendix can be regarded as marker of progression of this condition. Investigation for infection is therefore not necessary in such cases.
SOME NON-PERTURBATIVE PATH INTEGRALS STUDIES IN STATISTICAL BURGER TURBULENCE: STRINGS AND STOCHASTIC INSTANTONS CONFIGURATIONS
Authors: BOTELHO LUIZ C. L. 
Published: March 2006

In this paper, we study Burger turbulence and the appearance of spatial coherent string dynamics structures for the statistical averaged vortex phase factor in a path integral framework. This result gives a strong mathematical method support to the unsolved long-standing Landau 1941's conjecture that in a turbulent field the flow vorticity should be confined to a limited region.Additionally, we present the exact instanton path-integral solubility — from a stochastic point of view — of a fluid flow bounded by a moving string (random) boundary together with a study of another exact path-integral solubility of a weakly stirred complete Navier–Stokes flow.
THOUGHTS ON NON-LOCALITY AND QUANTUM MECHANICS
Authors: UNRUH W. 
Published: March 2006

The debate about the non-locality of quantum mechanics is old, but still lively. Numerous people use non-locality as (bad) shorthand for quantum entanglement. But some have a long-standing commitment to the validity of this characterization. This paper examines two separate streams in this debate. The first is the arguments of Stapp, and especially his recent paper where he simplifies his contractual argument in the Hardy situation to argue for the non-locality of quantum mechanics. He has maintained his contention that an analysis of a Hardy-type correlation between two spatially separated observers proves that quantum mechanics itself is non-local, without any additional assumption of realism or hidden variables. In the second section, I try to carefully examine the Bell argument in the CHSH variant to see where the difference between the quantum and classical situations differ. Asher Peres was one of the great physicists of the late 20th century, especially for his intense concern with the fundamental nature of quantum mechanics. His courage in devoting his life to an area many considered "philosophical" (i.e. non-physical) paved the way for the rest of us to reveal our interests and confusions about this area. I am not sure that he would agree with everything in this paper, but I offer it as a tribute to him.
Views of College Students on Pit Bull "Ownership": New Providence, The Bahamas
Authors: Burrows Tyrone , Fielding William 
Published: March 2006

AbstractThis paper reports the finding of the first, known study of a Caribbean community's views on pit bulls. College students (375) provided their perceptions on a number of issues related to pit bull guardianship ("ownership"). Age, sex, and dog-owning status influenced some of their views. They saw pit bulls as being different from other dogs, but not all supported banning pit bulls. Some results reinforced the stereotypes associated with pit bull ownership: Most pit bull owners were under 19 years of age, and older respondents were more likely than younger ones to support a ban on pit bulls. Why different subgroups of respondents held their views would be a useful avenue for future research.
Unraveling the Methods of Childhood and Adolescent Cruelty to Nonhuman Animals
Authors: Tallichet Suzanne , Hensley Christopher , Singer Stephen 
Published: March 2006

AbstractStudies investigating the specific methods for committing nonhuman animal cruelty have only begun to expose the complexities of this particular form of violence. This study used a sample of 261 male inmates surveyed at both medium- and maximum-security prisons. The study examined the influence of demographic attributes (race, education, and residence while growing up). It also examined situational factors (was the abuse committed alone, did abuser try to conceal the act, was abuser upset by the abuse, what was the perpetrator's age at initial animal cruelty, how frequent was the animal abuse?) and specific methods of animal cruelty (shooting, drowning, hitting or kicking, choking, burning, sex). Regression analyses revealed that white inmates tended to shoot animals more frequently than did non-whites and were less likely to be upset or cover up their actions. Respondents who had sex with animals were more likely to have acted alone and to conceal their cruelty toward animals. However, we failed to find support for a potential link between childhood and adolescent animal cruelty methods and later violence against humans.
The Making of the "First Dog": President Warren G. Harding and Laddie Boy
Authors: Pycior Helena 
Published: March 2006

AbstractThis paper traces the history of the cultural icon of the "First Dog" of the United States back to the administration of President Warren G. Harding (1921-1923). It briefly explores technological and socio-cultural factors—including the early-twentieth-century cult of human and nonhuman celebrities—that laid a basis for the acceptance of Laddie Boy, Harding's Airedale terrier, as the third member of the First Family and a celebrity in his own right. Following Laddie Boy, First Dogs would greet and entertain visitors to the White House, pose for the press, make public appearances, and "talk." While recognizing that Laddie Boy's personality was essential to his success at the White House, the paper also documents the steps taken by President Harding, his wife Florence Kling Harding, and the American press to establish Laddie Boy as the First Dog of the land. The paper argues that the construction of the cultural icon of the First Dog was not simply a political ploy to humanize the President but more a calculated attempt by President Harding to further animal welfare.
The Under-representation of African American Employees in Animal Welfare Organizations in the United States
Authors: Brown Sue-Ellen 
Published: March 2006

AbstractThe purpose of this research was to document the alleged underrepresentation of African Americans employed in U.S. nonhuman animal welfare organizations. A telephone survey of 32 animal welfare organizations yielded responses from 13 with 1,584 employees. Almost all organizations were reluctant to respond. Of the 13 organizations responding, 62% (N = 8) had no African American employees. African Americans made up 4% (N = 63) of the total number of employees with only 0.8% (N = 12) at the top levels (officials, managers, and professionals). African Americans never made up more than 7% of the employees in their respective organization. This paper discusses a model of, and resources for, successful diversity building in nonprofit organizations.
Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25
Authors: Zhang Zhuo , Zhang Meili , Garmestani Kayhan , Talanov Vladimir S. , Plascjak Paul S. , Beck Barbara , Goldman Carolyn , Brechbiel Martin W. , Waldmann Thomas A. 
Published: March 2006

AbstractAdult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 (211At)–labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 μCi (0.444 MBq) 211At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 μg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human β-2 microglobulin (β2μ) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 μCi (0.444 MBq) of 211At-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody 211At-11F11–treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining 211At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL.
Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
Authors: Datta Abhik , Bellon Marcia , Sinha-Datta Uma , Bazarbachi Ali , Lepelletier Yves , Canioni Danielle , Waldmann Thomas A. , Hermine Olivier , Nicot Christophe 
Published: March 2006

AbstractThe antiviral thymidine analog azidothymidine (AZT) is used to treat several virus-associated human cancers. However, to date the mechanism of AZT action remains unclear and thus, reasons for treatment failure are unknown. Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of poor prognosis. Here, we report that enduring AZT treatment of T-cell leukemia virus I–infected cells, in vitro and in vivo in ATL patients, results in inhibition of telomerase activity, progressive telomere shortening, and increased p14ARF expression. In turn, this elicits stabilization and reactivation of the tumor suppressor p53-dependent transcription, increased expression of the cyclin-dependent kinase inhibitor p21Waf1, and accumulation of p27kip1, thereby inducing cellular senescence and tumor cell death. While ATL patients carrying a wild-type p53 enter remission following treatment with AZT, those with a mutated p53 did not respond, and patients' disease relapse was associated with the selection of a tumor clone carrying mutated inactive p53.