bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Global Transcriptional Effects of the Human Papillomavirus E6 Protein in Cervical Carcinoma Cell Lines Are Mediated by the E6AP Ubiquitin Ligase
Authors: Kelley Melissa L. , Keiger Kerri E. , Lee Chan Jae , Huibregtse Jon M. 
Published: February 2005

ABSTRACT
The function of the human papillomavirus (HPV) E6 protein that is most clearly linked to carcinogenesis is the targeted degradation of p53, which is dependent on the E6AP ubiquitin ligase. Additional functions have been attributed to E6, including the stimulation of telomerase activity and the targeted degradation of other cellular proteins, but in most cases it is unclear whether these activities are also E6AP dependent. While E6 clearly influences the transcriptional program of HPV-positive cell lines through the inactivation of p53, it has been shown that at least a subset of its p53-independent functions are also reflected in the transcriptional program. For this study, we have determined the extent to which E6AP is involved in mediating the set of E6 functions that impact on the global transcriptional program of HPV-positive cell lines. The transcriptional profiles of ∼31,000 genes were characterized for three cell lines (HeLa, Caski, and SiHa cells) after small interfering RNA (siRNA)-mediated silencing of E6 or E6AP. We found that E6 and E6AP siRNAs elicited nearly identical alterations in the transcriptional profile of each cell line. Some of the expression alterations were apparent secondary effects of p53 stabilization, while the basis of most other changes was not reconcilable with previously proposed E6 functions. While expression changes of the TERT gene (telomerase catalytic subunit) were not revealed by the array, telomerase repeat amplification protocol assays showed that both E6 and E6AP knockouts resulted in a suppression of telomerase activity. Together, these results suggest that E6AP mediates a broad spectrum of E6 functions, including virtually all functions that impact on the transcriptional program of HPV-positive cell lines.
Enhanced Cellular Immunity in Macaques following a Novel Peptide Immunotherapy
Authors: Chea S. , Dale C. J. , De Rose R. , Ramshaw I. A. , Kent S. J. 
Published: February 2005

ABSTRACTAdvances in treating and preventing AIDS depend on understanding how human immunodeficiency virus (HIV) is eliminated in vivo and on the manipulation of effective immune responses to HIV. During the development of assays quantifying the elimination of fluorescent autologous cells coated with overlapping 15-mer simian immunodeficiency virus (SIV) or HIV-1 peptides, we made a remarkable observation: the reinfusion of macaque peripheral blood mononuclear cells, or even whole blood, pulsed with SIV and/or HIV peptides generated sharply enhanced SIV- and HIV-1-specific T-cell immunity. Strong, broad CD4+- and CD8+-T-cell responses could be enhanced simultaneously against peptide pools spanning 87% of all SIV- and HIV-1-expressed proteins—highly desirable characteristics of HIV-specific immunity. De novo hepatitis C virus-specific CD4+- and CD8+-T-cell responses were generated in macaques by the same method. This simple technique holds promise for the immunotherapy of HIV and other chronic viral infections.
The C-Terminal Half of TSG101 Blocks Rous Sarcoma Virus Budding and Sequesters Gag into Unique Nonendosomal Structures
Authors: Johnson Marc C. , Spidel Jared L. , Ako-Adjei Danso , Wills John W. , Vogt Volker M. 
Published: February 2005

ABSTRACT
Retroviral late domains (L domains) are short amino acid sequences in the Gag protein that facilitate the process of budding. L domains act by recruiting the ESCRT complexes, which normally function in the formation of multivesicular bodies. The PTAP late domain of human immunodeficiency virus (HIV) is believed to specifically recruit this machinery by binding the ESCRT protein TSG101. It was recently demonstrated that expression of a C-terminal fragment of TSG101 (TSG-3′) blocked the budding of both PTAP-dependent and PPPY-dependent retroviruses. We show here that TSG-3′ expression leads to the formation of large spherical entities that we call TICS (TSG-3′-induced cellular structures) in the cytoplasm. Rous sarcoma virus (RSV) and murine leukemia virus (MLV) Gag proteins are selectively recruited to these structures, but HIV type 1 Gag is completely excluded. Experiments with various HIV and RSV vector constructs as well as HIV and RSV chimeras suggest that recruitment to the TICS is late domain independent and does not involve recognition of any single amino acid sequence. TICS appear to have no limiting membrane and do not colocalize with markers for any membranous cellular compartment. Wild-type TSG101 is also recruited to TICS, but most other ESCRT proteins are excluded. These structures are similar in nature to aggresomes, colocalize with the aggresome marker GFP-250, and are highly enriched in ubiquitin but in other ways do not fully meet the description of aggresomes. We conclude that the block to retroviral budding by TSG-3′ may be the result of its sequestration of Gag, depletion of free TSG101, or depletion of free ubiquitin.
Functional Analysis of the Pseudorabies Virus UL51 Protein
Authors: Klupp Barbara G. , Granzow Harald , Klopfleisch Robert , Fuchs Walter , Kopp Martina , Lenk Matthias , Mettenleiter Thomas C. 
Published: February 2005

ABSTRACT
Homologs of the UL51 protein of herpes simplex virus have been identified in all herpesvirus subfamilies, but until now, no function has been assigned to any of them. To investigate function of the UL51 gene product of the alphaherpesvirus pseudorabies virus (PrV), we isolated and analyzed a mutant lacking the major part of the open reading frame, PrV-ΔUL51F, and a rescuant. One-step growth analysis of PrV-ΔUL51F revealed only slightly reduced titers, but plaque size was notably diminished and reached only approximately 30% the plaque size of wild-type PrV. Ultrastructurally, intracytoplasmic capsids were found in large numbers either without envelope or in different stages of envelopment, indicating that secondary envelopment in the cytoplasm was less efficient. However, neuroinvasion in the mouse trigeminal pathway after intranasal infection was only slightly delayed. A PrV UL11 mutant also showed a defect in secondary envelopment (M. Kopp, H. Granzow, W. Fuchs, B. G. Klupp, E. Mundt, A. Karger, and T. C. Mettenleiter, J. Virol. 77:5339-5351, 2003). Since both proteins are part of the viral tegument and are predicted to be membrane associated, they may serve similar, possibly redundant functions during viral morphogenesis. Therefore, we also isolated a mutant simultaneously lacking UL51 and UL11. This mutant exhibited further reduced plaque size compared to the single-deletion mutants, but viral titers were comparable to those for the UL11 mutant. In electron microscopic analyses, the observed defect in secondary envelopment was similar to that found in the UL11 single-deletion mutant. In conclusion, both conserved tegument proteins, either singly or in combination, are involved in virion morphogenesis in the cytoplasm but are not essential for viral replication in vitro and in vivo.
Pairs of Vp1 Cysteine Residues Essential for Simian Virus 40 Infection
Authors: Li Peggy P. , Nakanishi Akira , Fontanes Vanessa , Kasamatsu Harumi 
Published: February 2005

ABSTRACT

Transient disulfide bonding occurs during the intracellular folding and pentamerization of simian virus 40 (SV40) major capsid protein Vp1 (P. P. Li, A. Nakanishi, S. W. Clark, and H. Kasamatsu, Proc. Natl. Acad. Sci. USA
99:
1353-1358, 2002). We investigated the requirement for Vp1 cysteine pairs during SV40 infection. Our analysis identified three Vp1 double-cysteine mutant combinations that abolished viability as assayed by plaque formation. Mutating the Cys49-Cys87 pair or the Cys87-Cys254 pair led to ineffective nuclear localization and diminished accumulation of the mutant Vp1s, and the defect extended in a dominant-negative manner to the wild-type minor capsid proteins Vp2/3 and an affinity-tagged recombinant Vp1 expressed in the same cells. Mutating the Cys87-Cys207 pair preserved the nuclear localization and normal accumulation of the capsid proteins but diminished the production of virus-like particles. Our results are consistent with a role for Cys49, Cys87, and Cys254 in the folding and cytoplasmic-nuclear trafficking of Vp1 and with a role for Cys87 and Cys207 in the assembly of infectious particles. These findings suggest that transient disulfide bond formation between certain Vp1 cysteine residues functions at two stages of SV40 infection: during Vp1 folding and oligomerization in the cytoplasm and during virion assembly in the nucleus.
Human Cytomegalovirus Immediate-Early 2 Gene Expression Blocks Virus-Induced Beta Interferon Production
Authors: Taylor R. Travis , Bresnahan Wade A. 
Published: February 2005

ABSTRACT
The effect of human cytomegalovirus (HCMV) gene expression on beta interferon (IFN-β) expression was examined. We demonstrate that the HCMV immediate-early 2 (IE2) gene product IE86 can effectively block the induction of IFN-β during HCMV infection. IE86 also efficiently blocked the induction of IFN-β following Sendai virus infection, demonstrating that IE86's ability to block induction of IFN-β is not limited to HCMV infection, identifying IE2 as an IFN-β antagonist.
Relation between foot arch index and ankle strength in elite gymnasts: a preliminary study
Authors: Aydog S T , Özçakar L , Tetik O , Demirel H A , Hasçelik Z , Doral M N 
Published: February 2005

Background:Gymnasts usually start intensive training from early childhood. The impact of such strenuous training on the musculoskeletal system is not clear.Objectives:To evaluate the relation between muscle strength of the ankle joint and foot structure in gymnasts.Methods:The study population comprised 20 high level male gymnasts and 17 non-athletic healthy male controls. Arch indices were measured using a podoscope. Ankle plantar/dorsiflexion and eversion/inversion strengths were measured using a Biodex 3 dynamometer within the protocol of concentric/concentric five repetitions at 30°/s velocity.Results:The mean arch index of the right and left foot of the gymnasts and the controls were respectively: 31.4 (29.1), 34.01 (34.65); 60.01 (30.3), 63.75 (32.27). Both the arch indices and the ankle dorsiflexion strengths were lower in the gymnasts. Although no correlation was found between strength and arch index in the control group, a significant correlation was observed between eversion strengths and arch indices of the gymnasts (r =  0.41, p  =  0.02).Conclusions:Whether or not the findings indicate sport specific adaptation or less training of the ankle dorsiflexors, prospective data are required to elucidate the tendency for pes cavus in gymnasts, for whom stabilisation of the foot is a priority.
Does changing the configuration of a motor racing circuit make it safer?
Authors: Leonard L , Lim A , Chesser T J S , Norton S A , Nolan J P 
Published: February 2005

Objectives:To assess the pattern of injuries presenting to a racing circuit medical centre in two three-year periods before and after two chicanes were built into the track.Methods:Medical centre records were used to identify all patients assessed during the two time periods. Those referred to hospital were categorised by injury severity into three groups.Results:The proportions of those attending the medical centre that were referred and admitted to hospital were the same in both periods (12–13% and 3% respectively). During the two study periods, the risk of a severe injury for a car driver decreased from 0.1% to 0.03% (p<0.05). For a motorcyclist, similar values were 0% and 0.2% (not significant).Conclusions:Chicanes have improved the safety of the racing circuit for car drivers, reducing the risk of injury.
Effect of sporting activity on absenteeism in a working population
Authors: van den Heuvel S G , Boshuizen H C , Hildebrandt V H , Blatter B M , Ariëns G A , Bongers P M 
Published: February 2005

Objectives:To determine the effects of sporting activity on absenteeism in a working population.Methods:Data were used from a prospective cohort study in a working population with a follow up period of 3 years and were collected with yearly questionnaires or collected from company records. Complete data on absenteeism, sporting activity, and potential confounders were collected for 1228 workers. ANOVA was used to test differences in frequency and duration of absenteeism, correlations were computed to measure the association between number of sporting years (divided by age) and frequency and duration of absenteeism, and survival analysis, according to the Cox proportional hazards model, was used to test differences in relative risk at absenteeism and recovery. All analyses were adjusted for age, gender, smoking, and alcohol consumption, and were stratified for employees with sedentary and with more active jobs.Results:ANOVA showed a statistically significant higher mean duration of absenteeism among employees not practicing sports, of approximately 20 days over a period of 4 years. The survival analysis showed an increased relative risk at absenteeism (relative risk (RR) 1.09; confidence interval (CI) 1.01 to 1.18) and a decreased relative risk at recovery (RR 0.90; CI 0.85 to 0.95) for employees not practicing sports. The effect of sporting activity is larger in employees with sedentary work. No associations were found between number of sporting years and absenteeism.Conclusion:Employees practicing sports take sick leave significantly less often than their colleagues not practicing sports, while their periods of sick leave are shorter, especially when their work is sedentary.
EVOLUTION OF RELATIVE SYNONYMOUS CODON USAGE IN HUMAN IMMUNODEFICIENCY VIRUS TYPE-1
Authors: MEINTJES PETER L. , RODRIGO ALLEN G. 
Published: February 2005

Mutation in Human Immunodeficiency Virus type-1 (HIV-1) is extremely rapid, a consequence of a low-fidelity viral reverse transcription process. The envelope gene has been shown to accumulate substitutions at a rate of approximately 1% per year and can frequently spend a long time in the host (approximately 10 years). The relative synonymous codon usage (RSCU) in HIV-1 is known to be different from that of the human host. However, by reengineering the protein coding sequences of HIV-1 to reflect the RSCU patterns observed in humans, a large increase in protein expression is observed. It is reasonable to suggest that within a host there may be a selective drive for change in the RSCU of HIV-1 towards human RSCU.To test this hypothesis we analyzed HIV-1 partial envelope sequences from eight patients sampled serially in time. For each sequence, an RSCU table was constructed. Sequences were labelled as "early" or "late" depending on whether they were sampled before or after the mid-point of the study. Using the RSCU values as descriptor variables, a Principal Components Analysis (PCA) was performed. The first three components clearly discriminated between early and late sequences. We also constructed pooled groupwise RSCU tables for early and late sequences. The viral RSCU values of each of the groups were correlated with human RSCU. If there is selection for host-adaptation in RSCU, we expect that "late" viral RSCUs would tend to be more highly correlated with human RSCU than "early" viral RSCUs. In fact, tests of significance suggest that this is the case. However, closer examination of the data revealed that the apparent trend towards human RSCU can be attributed to the homogenization of the codon usage by mutation pressure rather than host adaptation.
Study on the Si(111) √3×√3-Ag Surface Structure by X-Ray Diffraction
Authors: Takahashi Toshio , Nakatani Shinichiro , Okamoto Naoko , Ishikawa Tetsuya , Kikuta Seishi 
Published: February 2005

The surface structure of Si(111) √3×√3-Ag has been analyzed from the X-ray intensity versus energy curves measured both for the integral- and fractional-order spots. A modified trimer model with three Ag atoms in the √3×√3 unit cell is proposed, in which triangles made of Ag atoms are chained in a honeycomb arrangement. The distances between the nearest neighbor Ag atoms are about twice the van der Waals radius. The height of the Ag layer measured from the ideal first Si layer is 2.9±0.1 A. The center of each triangle coincides with the position of the honeycomb protrusion observed by scanning tunneling microscopy.
A classification system for cross-reactive material-negative factor XI deficiency
Authors: Kravtsov Dmitri V. , Monahan Paul E. , Gailani David 
Published: February 2005

AbstractThe bleeding disorder associated with factor XI (fXI) deficiency is typically inherited as an autosomal recessive trait. However, some fXI mutations may be associated with dominant disease transmission. FXI is a homodimer, a feature that could allow certain mutations to exert a dominant-negative effect on wild-type fXI secretion through heterodimer formation. We describe 2 novel fXI mutations (Ser225Phe and Cys398Tyr) that form intracellular dimers, are secreted poorly, and exhibit dominant-negative effects on wild-type fXI secretion in cotransfection experiments. Available data now suggest that mutations associated with crossreactive material-negative fXI deficiency fall into 1 of 3 mechanistic categories: (1) mutations that reduce or prevent polypeptide synthesis, (2) polypeptides that fail to form intracellular dimers and are retained in cells as monomers, and (3) polypeptides that form dimers that are not secreted. The latter category likely accounts for many cases of dominant disease transmission. (Blood. 2005;105: 4671-4673)
Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow
Authors: Pelayo Rosana , Hirose Jun , Huang Jiaxue , Garrett Karla P. , Delogu Alessio , Busslinger Meinrad , Kincade Paul W. 
Published: February 2005

AbstractPlasmacytoid dendritic cells (pDCs) competent to make type I interferon were rigorously defined as a Ly-6C+ and CD11cLo subset of the B220+CD19- CD43+CD24Lo bone marrow (BM) Fraction A. Otherwise similar Ly6C- cells expressed the natural killer (NK) markers DX5 and NK1.1. pDCs represented a stable, discrete, and long-lived population. Stem cells and early lymphoid progenitors (ELPs), but not prolymphocytes, were effective precursors of pDCs, and their differentiation was blocked by ligation of Notch receptors. Furthermore, pDCs were present in the BM of RAG1-/-, CD127/IL-7Ra-/-, and Pax5-/- mice. pDCs in RAG1/GFP knock-in mice could be subdivided, and immunoglobulin DH-JH rearrangements, as well as transcripts for the B-lineage–related genes Pax5, mb1/CD79a, ebf, and Bcl11a, were identified only in the green fluorescent protein–positive (GFP+) pDC1 subset. All pDCs expressed terminal deoxynucleotidyl transferase (TdT), the ETS transcription factor Spi-B, the nuclear factor-κB transcription factor RelB, toll-like receptor 9 (TLR9), and interferon consensus sequence binding protein (ICSBP)/interferon regulatory factor 8 (IRF-8) transcripts; lacked CD16 and granulocyte colony-stimulating factor receptor (G-CSFR); and were uniformly interleukin-7 receptor α (IL-7Rα-) AA4.1Lo, CD27-, Flk-2Lo, c-Kit-, DX-5-, and CD11b-, while CD4 and CD8α were variable. GFP+ pDC1 subset was less potent than GFP- pDC2s in T allostimulation and production of tumor necrosis factor α (TNFα), interferon α (IFNα), and interleukin-6 (IL-6), while only pDC2s made IFNγ and IL-12 p70. Thus, 2 functionally specialized subsets of pDCs arise in bone marrow from progenitors that diverge from B, T, and NK lineages at an early stage.
From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential
Authors: Re Daniel , Thomas Roman K. , Behringer Karolin , Diehl Volker 
Published: February 2005

AbstractReclassification of Hodgkin disease as Hodgkin lymphoma (HL) represents a milestone in the lymphoma field, awarding recent insights in the molecular biology of Hodgkin and Reed-Sternberg (H-RS) cells and their environment. This review summarizes antiapoptotic and proproliferative pathways involved in the pathogenesis of this disease with the ultimate goal of translating laboratory knowledge into clinical decision making. The focus is on potential targets and novel drugs, which are discussed in the context of the complex biology of HL. Considering that HL patients are more likely to die from acute and late treatment-related toxicities than from HL itself, the introduction of targeted, biologically based therapies for HL patients with palliative and eventually curative intention might be justified. (Blood. 2005;105:4553-4560)
Accumulation of an intron-retained mRNA for granulocyte macrophage-colony stimulating factor receptor common β chain in neutrophils of myelodysplastic syndromes
Authors: Shikama Yayoi , Shichishima Tsutomu , Matsuoka Isao , Jubinsky Paul T , Sieff Colin A , Maruyama Yukio 
Published: February 2005

AbstractWe recently identified a reduction in the neutrophil surface expression of common β chain (βc) of the receptor for granulocyte macrophage-colony stimulating factor (GM-CSF) in the patients with myelodysplastic syndromes (MDS). To determine the etiology of the impaired βc expression, βc mRNA from neutrophilic granulocytes of MDS patients and healthy controls was analyzed by a combination of direct reverse transcriptiase-polymerase chain reaction-based single-strand conformational polymorphism and sequencing. Nine different βc transcripts were detected, but none was specific for MDS. However, one of the transcripts (βc79) containing a 79-base intron insertion between exons V and VI was significantly increased in MDS. This 27-kd isoform consisted of the βc N-terminal 182 amino acids followed by a new 84-amino-acid sequence. βc79 was overexpressed in all MDS subtypes. No genomic mutations were detected within the intron or at the intron/exon boundaries. The isoform is predominantly located in the cytoplasm by Western blot analysis and was unable to generate high-affinity binding sites or transduce a signal for proliferation when coexpressed with the receptor for human GM-CSF α chain. Our study suggests that the accumulation of the abnormal βc transcripts with intron V retention results in the reduction in cell-surface expression of βc observed in MDS.