bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cells with a CD4+CD25+Regulatory Phenotype Suppress In Vitro Proliferation of Virus-Specific CD8+T Cells during Chronic Hepatitis C Virus Infection
Authors: Boettler Tobias , Spangenberg Hans Christian , Neumann-Haefelin Christoph , Panther Elisabeth , Urbani Simonetta , Ferrari Carlo , Blum Hubert E. , von Weizsäcker Fritz , Thimme Robert 
Published: May 2005

ABSTRACTChronic hepatitis C virus (HCV) infection is associated with impaired proliferative, cytokine, and cytotoxic effector functions of HCV-specific CD8+T cells that probably contribute significantly to viral persistence. Here, we investigated the potential role of T cells with a CD4+CD25+regulatory phenotype in suppressing virus-specific CD8+T-cell proliferation during chronic HCV infection. In vitro depletion studies and coculture experiments revealed that peptide specific proliferation as well as gamma interferon production of HCV-specific CD8+T cells were inhibited by CD4+CD25+T cells. This inhibition was dose dependent, required direct cell-cell contact, and was independent of interleukin-10 and transforming growth factor beta. Interestingly, the T-cell-mediated suppression in chronically HCV-infected patients was not restricted to HCV-specific CD8+T cells but also to influenza virus-specific CD8+T cells. Importantly, CD4+CD25+T cells from persons recovered from HCV infection and from healthy blood donors exhibited significantly less suppressor activity. Thus, the inhibition of virus-specific CD8+T-cell proliferation was enhanced in chronically HCV-infected patients. This was associated with a higher frequency of circulating CD4+CD25+cells observed in this patient group. Taken together, our results suggest that chronic HCV infection leads to the expansion of CD4+CD25+T cells that are able to suppress CD8+T-cell responses to different viral antigens. Our results further suggest that CD4+CD25+T cells may contribute to viral persistence in chronically HCV-infected patients and may be a target for immunotherapy of chronic hepatitis C.
Involvement of the C-Terminal Disulfide-Bonded Loop of Murine Leukemia Virus SU Protein in a Postbinding Step Critical for Viral Entry
Authors: Burkhart Michael D. , D'Agostino Paul , Kayman Samuel C. , Pinter Abraham 
Published: May 2005

ABSTRACT
A role for the C-terminal domain (CTD) of murine leukemia virus (MuLV) Env protein in viral fusion was indicated by the potent inhibition of MuLV-induced fusion, but not receptor binding, by two rat monoclonal antibodies (MAbs) specific for epitopes in the CTD. Although these two MAbs, 35/56 and 83A25, have very different patterns of reactivity with viral isolates, determinants of both epitopes were mapped to the last C-terminal disulfide-bonded loop of SU (loop 10), and residues in this loop responsible for the different specificities of these MAbs were identified. Both MAbs reacted with a minor fraction of a truncated SU fragment terminating four residues after loop 10, indicating that while the deleted C-terminal residues were not part of these epitopes, they promoted their formation. Neither MAb recognized the loop 10 region expressed in isolated form, suggesting that these epitopes were not completely localized within loop 10 but required additional sequences located N terminal to the loop. Direct support for a role for loop 10 in fusion was provided by the demonstration that Env mutants containing an extra serine or threonine residue between the second and third positions of the loop were highly attenuated for infectivity and defective in fusion assays, despite wild-type levels of expression, processing, and receptor binding. Other mutations at positions 1 to 3 of loop 10 inhibited processing of the gPr80 precursor protein or led to increased shedding of SU, suggesting that loop 10 also affects Env folding and the stability of the interaction between SU and TM.
Inhibition of STAT 1 Phosphorylation by Human Parainfluenza Virus Type 3 C Protein
Authors: Malur Achut G. , Chattopadhyay Santanu , Maitra Ratan K. , Banerjee Amiya K. 
Published: May 2005

ABSTRACT

The P mRNA of the viruses belonging to the subfamily
Paramyxovirinae
possesses a unique property of giving rise to several accessory proteins by a process that involves the utilization of overlapping open reading frames (the C proteins) and by an “RNA-editing” mechanism (the V proteins). Although these proteins are considered accessory, numerous studies have highlighted the importance of these proteins in virus transcription and interferon signaling, including our previous observation on the role of human parainfluenza virus type 3 (HPIV 3) C protein in the transcription of viral genome (Malur et al., Virus Res.
99:
199-204, 2004). In this report, we have addressed its role in interferon signaling by generating a stable cell line, L-C6, by using the lentiviral expression system which expresses HPIV 3 C protein. The L-C6 cells were efficient in abrogating both alpha and gamma interferon-induced antiviral states and demonstrated a drastic reduction in the formation of gamma-activated factor complexes in the cell extracts. Western blot analysis subsequently revealed a defect in the phosphorylation of STAT 1 in these cells. Taken together, our results indicate that HPIV 3 C protein is capable of counteracting the interferon signaling pathway by specifically inhibiting the activation of STAT 1.
Complementation of Human Papillomavirus Type 16 E6 and E7 by Jagged1-Specific Notch1-Phosphatidylinositol 3-Kinase Signaling Involves Pleiotropic Oncogenic Functions Independent of CBF1;Su(H);Lag-1 Activation
Authors: Veeraraghavalu Karthikeyan , Subbaiah Vanitha K. , Srivastava Sweta , Chakrabarti Oishee , Syal Ruchi , Krishna Sudhir 
Published: May 2005

ABSTRACT
We have analyzed the induction and role of phosphatidylinositol 3-kinase (PI3K) by Notch signaling in human papillomavirus (HPV)-derived cancers. Jagged1, in contrast to Delta1, is preferentially upregulated in human cervical tumors. Jagged1 and not Delta1 expression sustained in vivo tumors by HPV16 oncogenes in HaCaT cells. Further, Jagged1 expression correlates with the rapid induction of PI3K-mediated epithelial-mesenchymal transition in both HaCaT cells and a human cervical tumor-derived cell line, suggestive of Delta1;Serrate/Jagged;Lag2 ligand-specific roles. Microarray analysis and dominant-negatives reveal that Notch-PI3K oncogenic functions can be independent of CBF1;Su(H);Lag-1 activation and instead relies on Deltex1, an alternative Notch effector.
Epstein-Barr Virus BZLF1 Protein Binds to Mitotic Chromosomes
Authors: Adamson Amy L. 
Published: May 2005

ABSTRACT
Epstein-Barr virus (EBV) is a human herpesvirus that causes infectious mononucleosis and is associated with several types of cancers, including nasopharyngeal carcinoma and Burkitt's lymphoma. An EBV protein that plays an integral role during lytic replication is the immediate-early protein BZLF1. Our laboratory has found that BZLF1 (Z) localizes to host chromosomes during mitosis. Two Z-interacting proteins are also found localized to mitotic chromosomes in the presence of Z. The association between Z and mitotic chromosomes may lead to the sequestering of Z-interacting proteins within the cell and potentially cause an alteration of chromosome compaction or chromatin structure.
Characterization of Nonstructural Protein Membrane Anchor Deletion Mutants Expressed in the Context of the Hepatitis C Virus Polyprotein
Authors: Gosert Rainer , Jendrsczok Wiebke , Berke Jan Martin , Brass Volker , Blum Hubert E. , Moradpour Darius 
Published: May 2005

ABSTRACT
Protein-protein interactions involved in formation of the membrane-associated hepatitis C virus (HCV) replication complex are poorly understood. Here, we investigated nonstructural proteins with deletions in their membrane anchor domains when expressed in the context of the entire HCV polyprotein. Interactions among cytosolic domains of HCV nonstructural proteins were found not to be sufficiently strong to rescue such mutants to the membrane. Thus, the membrane anchor domains of nonstructural proteins are essential for incorporation of these proteins into the HCV replication complex while interactions among the cytosolic domains appear to be relatively weak. This feature may provide the nonstructural proteins with a certain flexibility to perform their multiple functions during HCV replication.
Role of N-Linked Glycosylation of the Hendra Virus Fusion Protein
Authors: Carter James Richard , Pager Cara Theresia , Fowler Stephen Derrick , Dutch Rebecca Ellis 
Published: May 2005

ABSTRACT

The Hendra virus fusion (F) protein contains five potential sites for N-linked glycosylation in the ectodomain. Examination of F protein mutants with single asparagine-to-alanine mutations indicated that two sites in the F
2
subunit (N67 and N99) and two sites in the F
1
subunit (N414 and N464) normally undergo N-linked glycosylation. While N-linked modification at N414 is critical for protein folding and transport, F proteins lacking carbohydrates at N67, N99, or N464 remained fusogenically active. As N464 lies within heptad repeat B, these results contrast with those seen for several paramyxovirus F proteins.
G-Protein Signaling Triggered by R5 Human Immunodeficiency Virus Type 1 Increases Virus Replication Efficiency in Primary T Lymphocytes
Authors: Lin Yea-Lih , Mettling Clément , Portalès Pierre , Réant Brigitte , Clot Jacques , Corbeau Pierre 
Published: May 2005

ABSTRACTThe binding of R5 envelope to CCR5 during human immunodeficiency virus type 1 (HIV-1) entry provokes cell activation, which has so far been considered to have no effect on virus replication, since signaling-defective CCR5 molecules have been shown to function normally as HIV-1 coreceptors on transformed cells or mitogen-stimulated T lymphocytes. As the background state of activation of these cells might have biased the results, we performed experiments using the same approach but with nonactivated primary T lymphocytes. We now report that the single R126N mutation in the DRY motif, involved in G-protein coupling, results in a signaling-defective CCR5 coreceptor with a drastically impaired capacity to support HIV-1 infection.
The Frequency and Behavioral Outcomes of Goal Choices in the Self-management of Diabetes
Authors: Estabrooks Paul A. , Nelson Candace C. , Xu Stanley , King Diane , Bayliss Elizabeth A. , Gaglio Bridget , Nutting Paul A. , Glasgow Russell E. 
Published: May 2005

Purpose The purpose of this study was to determine the frequency and effectiveness of behavioral goal choices in the self-management of diabetes and to test goal-setting theory hypotheses that self-selection and behavioral specificity of goals are key to enhancing persistence. Methods Participants with type 2 diabetes in a randomized controlled trial (n = 422) completed baseline behavioral assessments using a clinic-based, interactive, self-management CD-ROM that allowed them to select a behavioral goal and receive mail and telephone support for the initial 6 months of the trial followed by additional behavioral assessments. Frequency of behavioral goal selection and 6-month behavioral data were collected. Results Approximately 49%, 27%, and 24% of the participants, respectively, set goals to increase physical activity (PA), reduce fat intake, or increase fruits and vegetables (F&V) consumed. At baseline, participants who selected PA, reduced fat consumption, or F&V were significantly, and respectively, less active, consumed more dietary fat, and ate fewer F&V regardless of demographic characteristics. Participants who selected a reduced-fat goal showed a significantly larger decrease than did those that selected PA or F&V goals. Participants who selected an F&V goal showed significant changes in F&V consumption. Participants who selected a PA goal demonstrated significant changes in days of moderate and vigorous physical activity. Conclusions When participants are provided with information on health behavior status and an option of behavioral goals for managing type 2 diabetes, they will select personally appropriate goals, resulting in significant behavioral changes over a 6-month period.
Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study
Authors: Downs Sara H , Brändli Otto , Zellweger Jean-Pierre , Schindler Christian , Künzli Nino , Gerbase Margaret W , Burdet Luc , Bettschart Robert , Zemp Elisabeth , Frey Martin , Keller Roland , Tschopp Jean-Marie , Leuenberger Philippe , Ackermann-Liebrich Ursula ,   the SAPALDIA team
Published: May 2005

AbstractBackgroundThe aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women.MethodsIn a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 – 60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years.ResultsIn both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002).ConclusionThere are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.
Exercise training improves aerobic endurance and musculoskeletal fitness in female cardiac transplant recipients
Authors: Haykowsky Mark , Riess Kenneth , Figgures Linda , Kim Daniel , Warburton Darren , Jones Lee , Tymchak Wayne 
Published: May 2005

Abstract

Aim
Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.

Methods
20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.

Results
At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).

Conclusion
Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients.
Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
Authors: Braissant Olivier , Henry Hugues , Villard Anne-Marie , Speer Oliver , Wallimann Theo , Bachmann Claude 
Published: May 2005

AbstractBackgroundCreatine (Cr) is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that lead to Cr deficiency, neurological symptoms in early infancy and severe neurodevelopmental delay. To investigate the involvement of Cr synthesis and uptake pathways during embryonic development, we determined the spatiotemporal expression of AGAT, GAMT and CT1 during the rat embryogenesis, at the mRNA and protein level.ResultsWe show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas. AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT. High levels of CT1 are found in epithelia.ConclusionOur results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development. This work provides new clues on how creatine can be provided to developing tissues, and suggests that Cr deficiencies might induce irreversible damages already in utero, particularly on the nervous system.
PAX6 mutations: genotype-phenotype correlations
Authors: Tzoulaki Ioanna , White Ian MS , Hanson Isabel M 
Published: May 2005

Abstract

Background
The PAX6 protein is a highly conserved transcriptional regulator that is important for normal ocular and neural development. In humans, heterozygous mutations of the PAX6 gene cause aniridia (absence of the iris) and related developmental eye diseases. PAX6 mutations are archived in the Human PAX6 Allelic Variant Database, which currently contains 309 records, 286 of which are mutations in patients with eye malformations.

Results
We examined the records in the Human PAX6 Allelic Variant Database and documented the frequency of different mutation types, the phenotypes associated with different mutation types, the contribution of CpG transitions to the PAX6 mutation spectrum, and the distribution of chain-terminating mutations in the open reading frame. Mutations that introduce a premature termination codon into the open reading frame are predominantly associated with aniridia; in contrast, non-aniridia phenotypes are typically associated with missense mutations. Four CpG dinucleotides in exons 8, 9, 10 and 11 are major mutation hotspots, and transitions at these CpG's account for over half of all nonsense mutations in the database. Truncating mutations are distributed throughout the PAX6 coding region, except for the last half of exon 12 and the coding part of exon 13, where they are completely absent. The absence of truncating mutations in the 3' part of the coding region is statistically significant and is consistent with the idea that nonsense-mediated decay acts on PAX6 mutant alleles.

Conclusion
The PAX6 Allelic Variant Database is a valuable resource for studying genotype-phenotype correlations. The consistent association of truncating mutations with the aniridia phenotype, and the distribution of truncating mutations in the PAX6 open reading frame, suggests that nonsense-mediated decay acts on PAX6 mutant alleles.
Use of SNPs to determine the breakpoints of complex deficiencies, facilitating gene mapping in Caenorhabditis elegans
Authors: Kadandale Pavan , Geldziler Brian , Hoffmann Melissa , Singson Andrew 
Published: May 2005

AbstractBackgroundGenetic deletions or deficiencies have been used for gene mapping and discovery in various organisms, ranging from the nematodeCaenorhabditis elegansall the way to humans. One problem with large deletions is the determination of the location of their breakpoints. This is exacerbated in the case of complex deficiencies that delete a region of the genome, while retaining some of the intervening sequence. Previous methods, using genetic complementation or cytology were hampered by low marker density and were consequently not very precise at positioning the breakpoints of complex deficiencies. The identification of increasing numbers of Single Nucleotide Polymorphisms (SNPs) has resulted in the use of these as genetic markers, and consequently in their utilization for defining the breakpoints of deletions using molecular biology methods.ResultsHere, we show that SNPs can be used to help position the breakpoints of a complex deficiency inC. elegans. The technique uses a combination of genetic crosses and molecular biology to generate robust and highly reproducible results with strong internal controls when trying to determine the breakpoints of deficiencies. The combined use of this technique and standard genetic mapping allowed us to rapidly narrow down the region of interest in our attempts to clone a gene.ConclusionUnlike previous methods used to locate deficiency breakpoints, our technique has the advantage of not being limited by the amount of starting material. It also incorporates internal controls to eliminate false positives and negatives. The technique can also easily be adapted for use in other organisms in which both genetic deficiencies and SNPs are available, thereby aiding gene discovery in these other models.
No role for quality scores in systematic reviews of diagnostic accuracy studies
Authors: Whiting Penny , Harbord Roger , Kleijnen Jos 
Published: May 2005

Abstract

Background
There is a lack of consensus regarding the use of quality scores in diagnostic systematic reviews. The objective of this study was to use different methods of weighting items included in a quality assessment tool for diagnostic accuracy studies (QUADAS) to produce an overall quality score, and to examine the effects of incorporating these into a systematic review.

Methods
We developed five schemes for weighting QUADAS to produce quality scores. We used three methods to investigate the effects of quality scores on test performance. We used a set of 28 studies that assessed the accuracy of ultrasound for the diagnosis of vesico-ureteral reflux in children.

Results
The different methods of weighting individual items from the same quality assessment tool produced different quality scores. The different scoring schemes ranked different studies in different orders; this was especially evident for the intermediate quality studies. Comparing the results of studies stratified as "high" and "low" quality based on quality scores resulted in different conclusions regarding the effects of quality on estimates of diagnostic accuracy depending on the method used to produce the quality score. A similar effect was observed when quality scores were included in meta-regression analysis as continuous variables, although the differences were less apparent.

Conclusion
Quality scores should not be incorporated into diagnostic systematic reviews. Incorporation of the results of the quality assessment into the systematic review should involve investigation of the association of individual quality items with estimates of diagnostic accuracy, rather than using a combined quality score.