bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants That Specify the Integration Pattern of Retrotransposon Tf1 in the
fbp1
Promoter of
Schizosaccharomyces pombe
Authors: Majumdar Anasuya , Chatterjee Atreyi Ghatak , Ripmaster Tracy L. , Levin Henry L. 
Published: October 2010

ABSTRACT

Long terminal repeat (LTR) retrotransposons are closely related to retroviruses and, as such, are important models for the study of viral integration and target site selection. The transposon Tf1 of
Schizosaccharomyces pombe
integrates with a strong preference for the promoters of polymerase II (Pol II)-transcribed genes. Previous work
in vivo
with plasmid-based targets revealed that the patterns of insertion were promoter specific and highly reproducible. To determine which features of promoters are recognized by Tf1, we studied integration in a promoter that has been characterized. The promoter of
fbp1
has two upstream activating sequences, UAS1 and UAS2. We found that integration was targeted to two windows, one 180 nucleotides (nt) upstream and the other 30 to 40 nt downstream of UAS1. A series of deletions in the promoter showed that the integration activities of these two regions functioned autonomously. Integration assays of UAS2 and of a synthetic promoter demonstrated that strong promoter activity alone was not sufficient to direct integration. The factors that modulate the transcription activities of UAS1 and UAS2 include the activators Atf1p, Pcr1p, and Rst2p as well as the repressors Tup11p, Tup12p, and Pka1p. Strains lacking each of these proteins revealed that Atf1p alone mediated the sites of integration. These data indicate that Atf1p plays a direct and specific role in targeting integration in the promoter of
fbp1
.
Structure-Based Analysis of the Interaction between the Simian Virus 40 T-Antigen Origin Binding Domain and Single-Stranded DNA
Authors: Meinke Gretchen , Phelan Paul J. , Fradet-Turcotte Amélie , Bohm Andrew , Archambault Jacques , Bullock Peter A. 
Published: October 2010

ABSTRACT

The origin-binding domain (OBD) of simian virus 40 (SV40) large T-antigen (T-Ag) is essential for many of T-Ag's interactions with DNA. Nevertheless, many important issues related to DNA binding, for example, how single-stranded DNA (ssDNA) transits along the T-Ag OBD, have yet to be established. Therefore, X-ray crystallography was used to determine the costructure of the T-Ag OBD bound to DNA substrates such as the single-stranded region of a forked oligonucleotide. A second structure of the T-Ag OBD crystallized in the presence of poly(dT)
12
is also reported. To test the conclusions derived from these structures, residues identified as being involved in binding to ssDNA by crystallography or by an earlier nuclear magnetic resonance study were mutated, and their binding to DNA was characterized via fluorescence anisotropy. In addition, these mutations were introduced into full-length T-Ag, and these mutants were tested for their ability to support replication. When considered in terms of additional homology-based sequence alignments, our studies refine our understanding of how the T-Ag OBDs encoded by the polyomavirus family interact with ssDNA, a critical step during the initiation of DNA replication.
Translational Control of the Abundance of Cytoplasmic Poly(A) Binding Protein in Human Cytomegalovirus-Infected Cells
Authors: Perez Cesar , McKinney Caleb , Chulunbaatar Uyanga , Mohr Ian 
Published: October 2010

ABSTRACT
Irrespective of their effects on ongoing host protein synthesis, productive replication of the representative alphaherpesvirus herpes simplex virus type 1, the representative gammaherpesvirus Kaposi's sarcoma herpesvirus, and the representative betaherpesvirus human cytomegalovirus [HCMV] stimulates the assembly of the multisubunit, cap-binding translation factor eIF4F. However, only HCMV replication is associated with an increased abundance of eIF4F core components (eIF4E, eIF4G, eIF4A) and the eIF4F-associated factor poly(A) binding protein (PABP). Here, we demonstrate that the increase in translation factor concentration was readily detected in an asynchronous population of HCMV-infected primary human fibroblasts, abolished by prior UV inactivation of virus, and genetically dependent upon viral immediate-early genes. Strikingly, while increased mRNA steady-state levels accompanied the rise in eIF4E and eIF4G protein levels, the overall abundance of PABP mRNA, together with the half-life of the polypeptide it encodes, remained relatively unchanged by HCMV infection. Instead, HCMV-induced PABP accumulation resulted from new protein synthesis and was sensitive to the mTORC1-selective inhibitor rapamycin, which interferes with phosphorylation of the mTORC1 substrate p70 S6K and the translational repressor 4E-BP1. While virus-induced PABP accumulation did not require p70 S6K, it was inhibited by the expression of a dominant-acting 4E-BP1 variant unable to be inactivated by mTORC1. Finally, unlike the situation in alpha- or gammaherpesvirus-infected cells, where PABP is redistributed to nuclei, PABP accumulated in the cytoplasm of HCMV-infected cells. Thus, cytoplasmic PABP accumulation is translationally controlled in HCMV-infected cells via a mechanism requiring mTORC1-mediated inhibition of the cellular 4E-BP1 translational repressor.
Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus
Authors: Sheahan Timothy , Whitmore Alan , Long Kristin , Ferris Martin , Rockx Barry , Funkhouser William , Donaldson Eric , Gralinski Lisa , Collier Martha , Heise Mark , Davis Nancy , Johnston Robert , Baric Ralph S. 
Published: October 2010

ABSTRACT

Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP
3014
) or wild-type VEE glycoproteins (VRP
3000
) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP
3000
-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP
3014
-based vaccines were not. The superior protection for the aged observed with VRP
3000
-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP
3000
vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP
3014
platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.
Persistent Friend Virus Replication and Disease inApobec3-Deficient Mice Expressing Functional B-Cell-Activating Factor Receptor
Authors: Santiago Mario L. , Smith Diana S. , Barrett Bradley S. , Montano Mauricio , Benitez Robert L. , Pelanda Roberta , Hasenkrug Kim J. , Greene Warner C. 
Published: October 2010

ABSTRACTRfv3is an autosomal dominant gene that influences the recovery of resistant mice from Friend retrovirus (FV) infection by limiting viremia and promoting a more potent neutralizing antibody response. We previously reported thatRfv3is encoded byApobec3, an innate retrovirus restriction factor. However, it was recently suggested that theRfv3 susceptible phenotype of high viremia at 28 days postinfection (dpi) was more dominantly controlled by the B-cell-activating factor receptor (BAFF-R), a gene that is linked to but located outside the genetically mapped region containingRfv3. Although one prototypicalRfv3susceptible mouse strain, A/WySn, indeed contains a dysfunctional BAFF-R, two otherRfv3susceptible strains, BALB/c and A.BY, express functional BAFF-R genes, determined on the basis of genotyping and B-cell immunophenotyping. Furthermore, transcomplementation studies in (C57BL/6 [B6] × BALB/c)F1and (B6 × A.BY)F1mice revealed that the B6Apobec3gene significantly influences recovery from FV viremia, cellular infection, and disease at 28 dpi. Finally, theRfv3phenotypes of prototypic B6, A.BY, A/WySn, and BALB/c mouse strains correlate with reportedApobec3mRNA expression levels. Overall, these findings argue against the generality ofBAFF-Rpolymorphisms as a dominant mechanism to explain theRfv3recovery phenotype and further strengthen the evidence thatApobec3encodesRfv3.
B7-Mediated Costimulation of CD4 T Cells Constrains Cytomegalovirus Persistence
Authors: Arens Ramon , Loewendorf Andrea , Her Min J. , Schneider-Ohrum Kirsten , Shellam Geoffrey R. , Janssen Edith , Ware Carl F. , Schoenberger Stephen P. , Benedict Chris A. 
Published: October 2010

ABSTRACT
Cytomegalovirus (CMV) utilizes multiple strategies to modulate immunity and promote lifelong, persistent/latent infection, including suppressing T cell activation pathways. Here we examined the role of B7 costimulatory ligands in establishing immune détente from both the host and virus perspectives. Mice lacking both B7.1 and B7.2 showed reduced early expansion of CMV-specific CD4 T cells, consequently allowing for enhanced levels of persistent virus replication. In turn, a CMV mutant lacking expression of the m138 and m147.5 gene products, which restrict B7.1 and B7.2 expression in infected antigen-presenting cells, induced a more robust CD4 T cell response and showed decreased persistence. Together, these data reveal a requirement for B7-mediated signaling in regulating the CMV-specific CD4 T cell response and establishing host-virus equilibrium.
The B Cell Response Is Redundant and Highly Focused on V1V2 during Early Subtype C Infection in a Zambian Seroconverter
Authors: Lynch Rebecca M. , Rong Rong , Boliar Saikat , Sethi Anurag , Li Bing , Mulenga Joseph , Allen Susan , Robinson James E. , Gnanakaran S. , Derdeyn Cynthia A. 
Published: October 2010

ABSTRACT

High-titer autologous neutralizing antibody responses have been demonstrated during early subtype C human immunodeficiency virus type 1 (HIV-1) infection. However, characterization of this response against autologous virus at the monoclonal antibody (MAb) level has only recently begun to be elucidated. Here we describe five monoclonal antibodies derived from a subtype C-infected seroconverter and their neutralizing activities against pseudoviruses that carry envelope glycoproteins from 48 days (0 month), 2 months, and 8 months after the estimated time of infection. Sequence analysis indicated that the MAbs arose from three distinct B cell clones, and their pattern of neutralization compared to that in patient plasma suggested that they circulated between 2 and 8 months after infection. Neutralization by MAbs representative of each B cell clone was mapped to two residues: position 134 in V1 and position 189 in V2. Mutational analysis revealed cooperative effects between glycans and residues at these two positions, arguing that they contribute to a single epitope. Analysis of the cognate gp120 sequence through homology modeling places this potential epitope near the interface between the V1 and V2 loops. Additionally, the escape mutation R189S in V2, which conferred resistance against all three MAbs, had no detrimental effect on virus replication
in vitro
. Taken together, our data demonstrate that independent B cells repeatedly targeted a single structure in V1V2 during early infection. Despite this assault, a single amino acid change was sufficient to confer complete escape with minimal impact on replication fitness.
A controlled evaluation of the WHO Safe Communities model approach to injury prevention: increasing child restraint use in motor vehicles
Authors: Istre Gregory R , Stowe Martha , McCoy Mary A , Moore Billy J , Culica Dan , Womack Katie N , Anderson Ron J 
Published: October 2010

ObjectiveTo measure the effect of the WHO Safe Communities model approach to increasing child restraint use in motor vehicles.DesignPre- and post-intervention observations of restraint use in motor vehicles in several sites in the target area, and in a comparison area community.SettingCommunity; southeast Dallas, Texas, 2003–2005.InterventionsA multifaceted approach to increasing use of child safety seats, booster seats and seat belts that included efforts in schools, day care centres, neighbourhoods and a local public clinic, along with child safety seat classes and a low-cost distribution programme.Main outcome measuresPrevalence of restraint use among children 0–8 years old riding in motor vehicles.ResultsIn the target area, the adjusted child restraint use increased by 23.9 percentage points versus 11.8 in the comparison area (difference 12.1; 95% CI 9.9 to 14.3), and adjusted driver seat belt use increased by 16.3 percentage points in the target area versus 4.9 in the comparison area (difference 11.4; 95% CI 11.0 to 11.7). Multivariable multilevel analysis showed that the increase in the target area was significantly greater than in the comparison area for child restraint use (OR 1.6; 95% CI 1.2 to 2.2), as well as for driver seat belt use and proportion of children riding in the back seat.ConclusionsThe Safe Communities approach was successful in promoting the use of child restraints in motor vehicles through a multifaceted intervention that included efforts in various community settings, instructional classes and child safety seat distribution.
The expression of EMP1 is downregulated in oral squamous cell carcinoma and possibly associated with tumour metastasis
Authors: Zhang Jun , Cao Wei , Xu Qin , Chen Wan-tao 
Published: October 2010

AimsTo investigate the expression of EMP1 in oral squamous cell carcinoma (OSCC) tissues and its correlation with available clinical parameters of patients with OSCC.MethodsThe mRNA levels of EMP1 were measured in 18 paired OSCC and corresponding adjacent normal tissues using RT-PCR. Another 45 pairs of OSCC samples were selected to detect the mRNA level of EMP1 using quantitative RT-PCR (qRT-PCR). The protein levels of EMP1 were also evaluated in 60 cases of patients with OSCC using immunohistochemical staining. The correlation between EMP1 expression and clinical parameters was analysed with non-parametric analysis.ResultsThe results of RT-PCR and qRT-PCR showed that, compared with the paired normal tissues, the mRNA levels of EMP1 were significantly decreased in OSCC. The immunohistochemical results indicated that the EMP1 protein was also downregulated in OSCC (p=0.031). Decreased expression of EMP1 was significantly correlated with clinical stage (p=0.002) and lymph node metastasis (p=0.044) of patients with OSCC. Meanwhile, there was a significant difference between OSCCs at early and advanced stages (p=0.003), and between OSCCs with lymph node metastasis and no lymph node metastasis (p=0.045), respectively.ConclusionsThe results suggest that EMP1 may be a tumour suppressor and associated with lymph node metastasis in OSCC.
FastTrack
Authors: Flanagan Cormac , Freund Stephen N. 
Published: October 2010

Multithreaded programs are notoriously prone to race conditions. Prior work developed precise dynamic race detectors that never report false alarms. However, these checkers employ expensive data structures, such as vector clocks (VCs), that result in significant performance overhead.
This paper exploits the insight that the full generality of VCs is not necessary in most cases. That is, we can replace VCs with an adaptive lightweight representation that, for almost all operations of the target program, requires constant space and supports constant-time operations. Experimental results show that the resulting race detection algorithm is over twice as fast as prior precise race detectors, with no loss of precision.
Two New Iterative Methods for a Countable Family of Nonexpansive Mappings in Hilbert Spaces
Authors: Wang Shuang , Hu Changsong 
Published: October 2010

AbstractWe consider two new iterative methods for a countable family of nonexpansive mappings in Hilbert spaces. We proved that the proposed algorithms strongly converge to a common fixed point of a countable family of nonexpansive mappings which solves the corresponding variational inequality. Our results improve and extend the corresponding ones announced by many others.
p38 Kinase Is Crucial for Osteopontin-Induced Furin Expression That Supports Cervical Cancer Progression
Authors: Kumar Vinit , Behera Reeti , Lohite Kirti , Karnik Swapnil , Kundu Gopal C 
Published: October 2010

Abstract
p38 kinases activated by growth factors, hormones, and environmental stresses exert diverse functions in regulating normal and malignant cell pathophysiology. Enhanced levels of activated p38 isoforms have been linked with poor prognosis in breast cancer, although the mechanistic basis for this association is poorly understood. In this study, we report that p38 activation in cervical cancer cells is driven by osteopontin (OPN), an extracellular matrix–associated cytokine that drives invasive progression. OPN regulates CD44-mediated p38 phosphorylation that induces NF-κB activation and NF-κB–dependent expression of furin, an extracellular protease implicated in human papilloma virus (HPV) processing that enhances cervical cancer cell motility. OPN induces CD44-mediated MKK3/6 phosphorylation which in turn phosphorylates p38 in these cells. OPN-induced furin expression and cell motility was impeded by blockades to MKK3/6, p38α/β or NF-κB signaling. In a mouse xenograft model of human cervical cancer, tumor growth was enhanced by OPN overexpression and blocked by short hairpin RNA (shRNA)–mediated OPN silencing. Furin overexpression similarly augmented tumor growth in the model, whereas blocking MKK3/6, p38, or furin reduced OPN-induced cervical tumor growth. Analysis of clinical specimens revealed that enhanced expression of OPN, phosphorylated NF-κB, p65, and furin correlated with cervical cancer progression, further strengthening the in vitro and in vivo results. In summary, our findings offer a proof of concept for targeting OPN and its downstream p38 signaling as a novel therapeutic strategy to manage cervical cancer. Cancer Res; 70(24); 10381–91. ©2010 AACR.
RGS-GAIP–Interacting Protein Controls Breast Cancer Progression
Authors: Wang Ling , Lau Julie S. , Patra Chitta Ranjan , Cao Ying , Bhattacharya Santanu , Dutta Shamit , Nandy Debashis , Wang Enfeng , Rupasinghe Chamila N. , Vohra Pawan , Spaller Mark R. , Mukhopadhyay Debabrata 
Published: October 2010

Abstract
Although the importance of RGS-GAIP–interacting protein (GIPC) in the biology of malignant cells is well known, the molecular mechanism of GIPC in the inhibition of tumor progression has not been identified. This study focused on elucidating the molecular role of GIPC in breast cancer progression. By using a human breast tumor specimen, an in vivo mouse model, and breast cancer cell lines, we showed for the first time that GIPC is involved in breast cancer progression through regulation of breast cancer cell proliferation, survival, and invasion. Furthermore, we found that the Akt/Mdm2/p53 axis, insulin-like growth factor-1 receptor, matrix metalloproteinase-9, and Cdc42 were downstream of GIPC signaling in breast cancer cells. Moreover, we showed that wild-type p53 reduced GIPC-induced breast cancer cell survival, whereas mutant p53 inhibited GIPC-induced cell invasion. Finally, we demonstrated that an N-myristoylated GIPC peptide (CR1023, N-myristoyl-PSQSSSEA) capable of blocking the PDZ domain of GIPC successfully inhibited MDA-MB-231 cell proliferation, survival, and further in vivo tumor growth. Taken together, these findings demonstrate the importance of GIPC in breast tumor progression, which has a potentially significant impact on the development of therapies against many common cancers expressing GIPC, including breast and renal cancer. Mol Cancer Res; 8(12); 1591–600. ©2010 AACR.
Body mass index, nutrient intakes, health behaviours and nutrition knowledge: A quantile regression application in Taiwan
Authors: Chen Shih-Neng , Tseng Jauling 
Published: October 2010

Objective: To assess various marginal effects of nutrient intakes, health behaviours and nutrition knowledge on the entire distribution of body mass index (BMI) across individuals. Design: Quantitative and distributional study. Setting: Taiwan Methods: This study applies Becker’s (1965) model of health production to construct an individual’s BMI determining function. Quantile regression method is used to analyse the entire distribution of BMI across a nationwide survey sample in Taiwan. Endogeneity associated with choice variables of nutrient intakes, health behaviours and nutrition knowledge in determining BMI is corrected using a two-stage least-squares method. Results: Empirical results indicate that energy, oleic acid and cholesterol increase BMI, while fibre, calcium and sodium reveal a reverse effect. For overweight and obese females, protein lowers BMI. For underweight and slightly to severely obese males, vitamin C reduces BMI. Jogging lowers BMI, but drinking raises non-obese individuals’ BMI. For males whose BMI is in the ideal weight to slightly overweight ranges, nutrition knowledge reduces BMI, but this effect is insignificant for females. Conclusions: Several important conclusions can be drawn. (1) Having a BMI which is too high or too low is a risk factor to health. (2) Quantile regression is a useful empirical method to evaluate crucial factors determining the entire distribution (high, medium and low) of BMI. (3) The econometric problem of endogeneity in regressors has to be considered and corrected when using a quantile regression approach. (4) BMI-relevant health education and policy can be evaluated and derived using quantile regression effects of an individual’s choices of nutrient intakes, health behaviours and nutrition knowledge.
Regulation of steady-state neutrophil homeostasis by macrophages
Authors: Gordy Claire , Pua Heather , Sempowski Gregory D. , He You-Wen 
Published: October 2010

AbstractThe timely clearance of apoptotic neutrophils from inflammation sites is an important function of macrophages; however, the role of macrophages in maintaining neutrophil homeostasis under steady-state conditions is less well understood. By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal macrophages. These mice develop severe neutrophilia, splenomegaly, extramedullary hematopoiesis, decreased body weight, and increased production of granulocyte colony-stimulating factor (G-CSF) and IL-1β, but not IL-17. c-FLIPf/f LysM-Cre mice exhibit delayed clearance of circulating neutrophils, suggesting that failure of macrophages to efficiently clear apoptotic neutrophils causes production of cytokines that drive excess granulopoiesis. Further, blocking G-CSF but not IL-1R signaling in vivo rescues this neutrophilia, suggesting that a G-CSF–dependent, IL-1β–independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells.