bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hijacking Components of the Cellular Secretory Pathway for Replication of Poliovirus RNA
Authors: Belov George A. , Altan-Bonnet Nihal , Kovtunovych Gennadiy , Jackson Catherine L. , Lippincott-Schwartz Jennifer , Ehrenfeld Ellie 
Published: December 2006

ABSTRACT
Infection of cells with poliovirus induces a massive intracellular membrane reorganization to form vesicle-like structures where viral RNA replication occurs. The mechanism of membrane remodeling remains unknown, although some observations have implicated components of the cellular secretory and/or autophagy pathways. Recently, we showed that some members of the Arf family of small GTPases, which control secretory trafficking, became membrane-bound after the synthesis of poliovirus proteins in vitro and associated with newly formed membranous RNA replication complexes in infected cells. The recruitment of Arfs to specific target membranes is mediated by a group of guanine nucleotide exchange factors (GEFs) that recycle Arf from its inactive, GDP-bound state to an active GTP-bound form. Here we show that two different viral proteins independently recruit different Arf GEFs (GBF1 and BIG1/2) to the new structures that support virus replication. Intracellular Arf-GTP levels increase ∼4-fold during poliovirus infection. The requirement for these GEFs explains the sensitivity of virus growth to brefeldin A, which can be rescued by the overexpression of GBF1. The recruitment of Arf to membranes via specific GEFs by poliovirus proteins provides an important clue toward identifying cellular pathways utilized by the virus to form its membranous replication complex.
Compensatory Mutations in E1, p7, NS2, and NS3 Enhance Yields of Cell Culture-Infectious Intergenotypic Chimeric Hepatitis C Virus
Authors: Yi MinKyung , Ma Yinghong , Yates Jeremy , Lemon Stanley M. 
Published: December 2006

ABSTRACT
There is little understanding of mechanisms underlying the assembly and release of infectious hepatitis C virus (HCV) from cultured cells. Cells transfected with synthetic genomic RNA from a unique genotype 2a virus (JFH1) produce high titers of virus, while virus yields are much lower with a prototype genotype 1a RNA containing multiple cell culture-adaptive mutations (H77S). To characterize the basis for this difference in infectious particle production, we constructed chimeric genomes encoding the structural proteins of H77S within the background of JFH1. RNAs encoding polyproteins fused at the NS2/NS3 junction (“H-NS2/NS3-J”) and at a site of natural, intergenotypic recombination within NS2 [“H-(NS2)-J”] produced infectious virus. In contrast, no virus was produced by a chimera fused at the p7-NS2 junction. Chimera H-NS2/NS3-J virus (vH-NS2/NS3-J) recovered from transfected cultures contained compensatory mutations in E1 and NS3 that were essential for the production of infectious virus, while yields of infectious vH-(NS2)-J were enhanced by mutations within p7 and NS2. These compensatory mutations were chimera specific and did not enhance viral RNA replication or polyprotein processing; thus, they likely compensate for incompatibilities between proteins of different genotypes at sites of interactions essential for virus assembly and/or release. Mutations in p7 and NS2 acted additively and increased the specific infectivity of vH-(NS2)-J particles, while having less impact on the numbers of particles released. We conclude that interactions between NS2 and E1 and p7 as well as between NS2 and NS3 are essential for virus assembly and/or release and that each of these viral proteins plays an important role in this process.
Replicase Genes of Murine Coronavirus Strains A59 and JHM Are Interchangeable: Differences in Pathogenesis Map to the 3′ One-Third of the Genome
Authors: Navas-Martin Sonia , Brom Maarten , Chua Ming-Ming , Watson Richard , Qiu Zhaozhu , Weiss Susan R. 
Published: December 2006

ABSTRACT
The important roles of the spike protein and other structural proteins in murine coronavirus (MHV) pathogenesis have been demonstrated; however, the role of the replicase gene remains unexplored. We assessed the influence of the replicase genes of the highly neurovirulent MHV-JHM strain and the hepatotropic and mildly neurovirulent A59 strain in acute infection of the mouse. Analysis of chimeric A59/JHM recombinant viruses indicates that the replicase genes are interchangeable and that it is the 3′ end of the genome, encoding the structural proteins, rather than the replicase gene, that determines the pathogenic properties of these chimeras.
Increased Neutralization Sensitivity of Recently Emerged CXCR4-Using Human Immunodeficiency Virus Type 1 Strains Compared to Coexisting CCR5-Using Variants from the Same Patient
Authors: Bunnik Evelien M. , Quakkelaar Esther D. , van Nuenen Ad C. , Boeser-Nunnink Brigitte , Schuitemaker Hanneke 
Published: December 2006

ABSTRACT
CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-using (R5) variants relatively late in the natural course of infection in 50% of HIV-1 subtype B-infected individuals and subsequently coexist with R5 HIV-1 variants. This relatively late appearance of X4 HIV-1 variants is poorly understood. Here we tested the neutralization sensitivity for soluble CD4 (sCD4) and the broadly neutralizing antibodies IgG1b12, 2F5, 4E10, and 2G12 of multiple coexisting clonal R5 and (R5)X4 (combined term for monotropic X4 and dualtropic R5X4 viruses) HIV-1 variants that were obtained at two time points after the first appearance of X4 variants in five participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Recently emerged (R5)X4 viruses were significantly more sensitive to neutralization by the CD4-binding-site-directed agents sCD4 and IgG1b12 than their coexisting R5 viruses. This difference was less pronounced at the later time point. Early (R5)X4 variants from two out of four patients were also highly sensitive to neutralization by autologous serum (50% inhibition at serum dilutions of >200). Late (R5)X4 viruses from these two patients were neutralized at lower serum dilutions, which suggested escape of X4 variants from humoral immunity. Autologous neutralization of coexisting R5 and (R5)X4 variants was not observed in the other patients. In conclusion, the increased neutralization sensitivity of HIV-1 variants during the transition from CCR5 usage to CXCR4 usage may imply an inhibitory role for humoral immunity in HIV-1 phenotype evolution in some patients, thus potentially contributing to the late emergence of X4 variants.
Lethal Infection of K18-
hACE2
Mice Infected with Severe Acute Respiratory Syndrome Coronavirus
Authors: McCray Paul B. , Pewe Lecia , Wohlford-Lenane Christine , Hickey Melissa , Manzel Lori , Shi Lei , Netland Jason , Jia Hong Peng , Halabi Carmen , Sigmund Curt D. , Meyerholz David K. , Kirby Patricia , Look Dwight C. , Perlman Stanley 
Published: December 2006

ABSTRACT
The
severe acute respiratory syndrome (SARS), caused by a novel coronavirus
(SARS-CoV), resulted in substantial morbidity, mortality, and economic
losses during the 2003 epidemic. While SARS-CoV infection has not
recurred to a significant extent since 2003, it still remains a
potential threat. Understanding of SARS and development of therapeutic
approaches have been hampered by the absence of an animal model that
mimics the human disease and is reproducible. Here we show that
transgenic mice that express the SARS-CoV receptor (human
angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia
develop a rapidly lethal infection after intranasal inoculation with a
human strain of the virus. Infection begins in airway epithelia, with
subsequent alveolar involvement and extrapulmonary virus spread to the
brain. Infection results in macrophage and lymphocyte infiltration in
the lungs and upregulation of proinflammatory cytokines and chemokines
in both the lung and the brain. This model of lethal infection with
SARS-CoV should be useful for studies of pathogenesis and for the
development of antiviral
therapies.
Expression of Viral MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma
Authors: Kim Do Nyun , Chae Hiun-Suk , Oh Sang Taek , Kang Jin-Hyoung , Park Cho Hyun , Park Won Sang , Takada Kenzo , Lee Jae Myun , Lee Won-Keun , Lee Suk Kyeong 
Published: December 2006

ABSTRACT
Epstein-Barr virus (EBV) is associated with about 6 to 16% of gastric carcinoma cases worldwide. Expression of the EBV microRNAs (miRNAs) was observed in B cells and nasopharyngeal carcinoma cells infected with EBV. However, it is not clear if the EBV miRNAs are expressed in EBV-associated gastric carcinomas (EBVaGCs). We found that BART miRNAs but not BHRF1 miRNAs were expressed in EBV-infected gastric carcinoma cell lines and the tumor tissues from patients as well as the animal model. The expression of viral miRNAs in EBVaGCs suggests that these EBV miRNAs may play important roles in the tumorigenesis of EBVaGCs.
Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia
Authors: Picard Stephane , Titier Karine , Etienne Gabriel , Teilhet Emmanuelle , Ducint Dominique , Bernard Marie-Agnes , Lassalle Regis , Marit Gerald , Reiffers Josy , Begaud Bernard , Moore Nicholas , Molimard Mathieu , Mahon Francois-Xavier 
Published: December 2006

Abstract
Using high-performance liquid chromatography–tandem mass spectrometry, we assessed trough imatinib plasma levels in 68 patients with chronic myeloid leukemia (CML) who responded or not to standard-dose imatinib, after at least 12 months' treatment. Mean trough imatinib plasma levels were significantly higher in the group with complete cytogenetic response (56 patients) than in the group without (12 patients; P = .03) and higher in the group with major molecular response (MMR) than in the group without (34 patients [1452 ± 649 ng/mL] versus 34 patients [869 ± 427 ng/mL]; P < .001). Regarding trough imatinib plasma levels and their discrimination potential for MMR, the area under receiver operating characteristic curve was 0.775, with best sensitivity (77%) and specificity (71%) at a plasma threshold of 1002 ng/mL. Therefore, monitoring of imatinib plasma levels could be very useful for the management of patients with CML or should at least be checked in the case of treatment failure or suboptimal response.
Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia
Authors: dos Santos Nuno R. , Rickman David S. , de Reynies Aurélien , Cormier Françoise , Williame Maryvonne , Blanchard Camille , Stern Marc-Henri , Ghysdael Jacques 
Published: December 2006

Abstract
The TEL-JAK2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. TEL-JAK2 transgenic expression in the mouse lymphoid lineage results in fatal and rapid T-cell leukemia/lymphoma. In the present report we show that T-cell leukemic cells from EμSRα-TEL-JAK2 transgenic mice present an aberrant CD8+ differentiation phenotype, as determined by the expression of stage-specific cell surface markers and lineage-specific genes. TEL-JAK2 transforms immature CD4−CD8− double-negative thymocytes, as demonstrated by the development of T-cell leukemia with full penetrance in a Rag2-deficient genetic background. This disease is similar to the bona fide TEL-JAK2 disease as assessed by phenotypic and gene profiling analyses. Pre-TCR signaling synergizes with TEL-JAK2 to transform immature thymocytes and initiate leukemogenesis as shown by (1) the delayed leukemia onset in Rag2-, CD3ϵ- and pTα-deficient mice, (2) the occurrence of recurrent chromosomal alterations in pre-TCR–deficient leukemia, and (3) the correction of delayed leukemia onset in Rag2-deficient TEL-JAK2 mice by an H-Y TCRαβ transgene that mimics pre-TCR signaling. Although not affecting leukemia incidence and mouse survival, TCRαβ expression was shown to facilitate leukemic cell expansion in secondary lymphoid organs.
Conservation of noncoding microsatellites in plants: implication for gene regulation
Authors: Zhang Lida , Zuo Kaijing , Zhang Fei , Cao Youfang , Wang Jiang , Zhang Yidong , Sun Xiaofen , Tang Kexuan 
Published: December 2006

Abstract

Background
Microsatellites are extremely common in plant genomes, and in particular, they are significantly enriched in the 5' noncoding regions. Although some 5' noncoding microsatellites involved in gene regulation have been described, the general properties of microsatellites as regulatory elements are still unknown. To address the question of microsatellites associated with regulatory elements, we have analyzed the conserved noncoding microsatellite sequences (CNMSs) in the 5' noncoding regions by inter- and intragenomic phylogenetic footprinting in the Arabidopsis and Brassica genomes.

Results
We identified 247 Arabidopsis-Brassica orthologous and 122 Arabidopsis paralogous CNMSs, representing 491 CT/GA and CTT/GAA repeats, which accounted for 10.6% of these types located in the 500-bp regions upstream of coding sequences in the Arabidopsis genome. Among these identified CNMSs, 18 microsatellites show high conservation in the regulatory regions of both orthologous and paralogous genes, and some of them also appear in the corresponding positions of more distant homologs in Arabidopsis, as well as in other plants. A computational scan of CNMSs for known cis-regulatory elements showed that light responsive elements were clustered in the region of CT/GA repeats, as well as salicylic acid responsive elements in the (CTT)n/(GAA)n sequences. Patterns of gene expression revealed that 70–80% of CNMS (CTT)n/(GAA)n associated genes were regulated by salicylic acid, which was consistent with the prediction of regulatory elements in silico.

Conclusion
Our analyses showed that some noncoding microsatellites were conserved in plants and appeared to be ancient. These CNMSs served as regulatory elements involved in light and salicylic acid responses. Our findings might have implications in the common features of the over-represented microsatellites for gene regulation in plant-specific pathways.
Amygdala size in amyotrophic lateral sclerosis without dementia: an in vivostudy using MRI volumetry
Authors: Pinkhardt Elmar H , van Elst Ludger Tebartz , Ludolph Albert C , Kassubek Jan 
Published: December 2006

AbstractBackgroundEvidence for extra-motor involvement in non-demented patients with amyotrophic lateral sclerosis (ALS) has been provided by multiple studies, in particular neuropathological studies have demonstrated neuronal loss in the amygdala. The aim of this study was to investigate possible alterations of amygdala volumesin vivo.MethodsTwenty-two moderately disabled patients with definite ALS without cognitive or behavioural deficits and 22 age-matched healthy controls were included. Amygdala and total brain volumes were measured by region-of-interest-based volumetry in 3-D MRI.ResultsA trend was observed with reduced amygdala size in the ALS group, since mean absolute and brain size-corrected amygdala volumes were 6.9% and 7.6% lower in the patient group compared to those in normal controls (P = 0.086 and P = 0.110), respectively.ConclusionVolumetrically identifiable alterations of the amygdala can be mappedin vivoand may be associated with psychopathological findings in later stages of ALS.
The use of a pre-operative scoring system for the prediction of phacoemulsification case difficulty and the selection of appropriate cases to be performed by trainees
Authors: Osborne Stuart A , Severn Phillip , Bunce Catey V , Fraser Scott G 
Published: December 2006

Abstract

Background
To establish whether a previously validated scoring system (Habib) for the prediction of risk or likelihood of posterior capsule rupture during phacoemulsification surgery could be used to: 1. Predict the difficulty of a phacoemulsification case, and 2. Select appropriate phacoemulsification cases for trainees.

Methods
The study sample was consecutive phacoemulsification cases undertaken by senior surgeons at a single ophthalmic unit over a three-week period (170 cases). Each case was scored using a potential difficulty scoring system. Immediately post-operatively, each case was given two scores by the operating surgeon (who was masked with regard to the potential complication score). The first score indicated the perceived difficulty of the case, and the second score, the degree of experience that they thought a trainee would require in order to have performed the same case without complication.

Results
Using Cuzick's non-parametric test for trend, there was evidence for a trend of increasing perceived difficulty with increasing potential difficulty score (p = 0.05), and of increasing experience required with increasing potential difficulty score (p < 0.001)

Conclusion
The authors advocate that Habib's potential difficulty scoring system can be used to inform the surgeon of the likely difficulty of a phacoemulsification case and to aid selection of appropriate cases for trainees prior to surgery.
Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes
Authors: Ros Axel , Carlsson Per , Rahmqvist Mikael , Bäckman Karin , Nilsson Erik 
Published: December 2006

AbstractBackgroundLaparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial.MethodsCharacteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy.ResultsDuring the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older – and had more complications from gallstone disease, higher co-morbidity, and higher ASA – score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy.ConclusionNon-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials.
Illness-related behaviour and utilization of oral health services among adult city-dwellers in Burkina Faso: evidence from a household survey
Authors: Varenne Benoît , Petersen Poul Erik , Fournet Florence , Msellati Philippe , Gary Jean , Ouattara Seydou , Harang Maud , Salem Gérard 
Published: December 2006

Abstract
Background
In sub-Saharan Africa, the availability and accessibility of oral health services are seriously constrained and the provision of essential oral care is limited. Reports from the region show a very low utilization of oral health care services, and visits to dental-care facilities are mostly undertaken for symptomatic reasons. The objectives of the present study were to describe the prevalence of oral symptoms among adults in Ouagadougou, capital city of Burkina Faso and the use of oral health services and self-medication in response to these symptoms and to measure the associations between predisposing, enabling and needs factors and decisions to seek oral health care.

Methods
The conceptual design of the study was derived from both the Andersen-Newman model of health care utilization and the conceptual framework of the WHO International Collaborative Study of Oral Health Outcomes. Data were obtained by two-stage stratified sampling through four areas representative of different stages of urbanization of Ouagadougou. The final study population comprised 3030 adults aged 15 years or over and the response rate was 65%.

Results
Overall, 28% of the respondents had experienced an oral health problem during the past 12 months; a high proportion (62%) reported pain or acute discomfort affecting daily life. In response to symptoms, only 28% used oral health facilities, 48% used self-medication and 24% sought no treatment at all. Multivariate analyses revealed that several socio-economic and socio-cultural factors such as religious affiliation, material living conditions and participation in a social network were significantly associated with the use of oral health care services by adults who had experienced oral health problems during the previous year.

Conclusion
The proportion of people who have obtained oral health care is alarmingly low in Ouagadougou and self-medication appears to be an important alternative source of care for adult city-dwellers. Decision-makers in sub-Saharan countries must seek to ensure that access to essential oral health care is improved.
Proteomic alteration in gastic adenocarcinomas from Japanese patients
Authors: Yoshihara Takahiro , Kadota Yoshito , Yoshimura Yoshiyuki , Tatano Yutaka , Takeuchi Naohiro , Okitsu Hiroshi , Umemoto Atsushi , Yamauchi Takashi , Itoh Kohji 
Published: December 2006

Abstract

Background
Gastric adenocarcinomas comprise one of the common types of cancers in Asian countries including Japan. Comprehensive protein profiling of paired surgical specimens of primary gastric adenocarcinomas and nontumor mucosae derived from Japanese patients was carried out by means of two-dimensional gel electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as putative clinical biomarkers and molecular targets for chemotherapy.

Results
Relatively common alterations in protein expression were revealed in the tumor tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG-1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II, glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa stomach-specific protein with putative tumor suppressor activity, were detected. RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression in tumor tissues.

Conclusion
A possible pathological role for down-regulation of FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific decreases in gene and protein expression of FOV in patients may be utilized as clinical biomarkers for effective diagnosis and assessment of gastric cancer.