bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Potent Anti-HIV Activity of CXCL12γ Correlates with Efficient CXCR4 Binding and Internalization
Authors: Altenburg Jeffrey D. , Jin Qingwen , Alkhatib Bashar , Alkhatib Ghalib 
Published: December 2009

ABSTRACT

We previously demonstrated that the naturally occurring splice variant stromal cell-derived factor 1γ/CXCL12γ is the most potent CXCL12 isoform in blocking X4 HIV-1, with weak chemotactic activity. A conserved BBXB domain (B for basic and X for any residue) located in the N terminus (
24
KHLK
27
) is found in all six isoforms of CXCL12. To determine whether the potent antiviral activity of CXCL12γ is due to the presence of the extra C-terminal BBXB domains, we mutated each domain individually as well as in combination. Although binding of CXCL12γ to heparan sulfate proteoglycan (HSPG) was 10-fold higher than that observed with CXCL12α, the results did not demonstrate a direct correlation between HSPG binding and the potent antiviral activity. CXCL12γ mutants lacking the conserved BBXB domain (designated γB1) showed increased binding to HSPG but reduced anti-HIV activity. In contrast, the mutants lacking the C-terminal second and/or third BBXB domain but retaining the conserved domain (designated B2, B3, and B23) showed decreased binding to HSPG but increased anti-HIV activity. The B2, B3, and B23 mutants were associated with enhanced CXCR4 binding, receptor internalization, and restored chemotaxis. Internalization of CXCR4 was more potent with CXCL12γ than with CXCL12α and was significantly reduced when the conserved BBXB domain was mutated. We concluded that the observed potent anti-HIV-1 activity of CXCL12γ is due to increased affinity for CXCR4 and to efficient receptor internalization.
Genomewide Association Analysis of Respiratory Syncytial Virus Infection in Mice
Authors: Stark James M. , Barmada M. Michael , Winterberg Abby V. , Majumber Nilanjana , Gibbons William J. , Stark Marilyn A. , Sartor Maureen A. , Medvedovic Mario , Kolls Jay , Bein Kiflai , Mailaparambil Beena , Krueger Marcus , Heinzmann Andrea , Leikauf George D. , Prows Daniel R. 
Published: December 2009

ABSTRACTRespiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants, with about half being infected in their first year of life. Yet only 2 to 3% of infants are hospitalized for RSV infection, suggesting that individual susceptibility contributes to disease severity. Previously, we determined that AKR/J (susceptible) mice developed high lung RSV titers and showed delayed weight recovery, whereas C57BL/6J (resistant) mice demonstrated low lung RSV titers and rapid weight recovery. In addition, we have reported that gene-targeted mice lacking the cystic fibrosis transmembrane conductance regulator (Cftr; ATP-binding cassette subfamily C, member 7) are susceptible to RSV infection. For this report, recombinant backcross and F2 progeny derived from C57BL/6J and AKR/J mice were infected with RSV, their lung titers were measured, and quantitative trait locus (QTL) analysis was performed. A major QTL, designatedRsvs1, was identified on proximal mouse chromosome 6 in both recombinant populations. Microarray analysis comparing lung transcripts of the parental strains during infection identified several candidate genes that mapped to theRsvs1interval, includingCftr. These findings add to our understanding of individual RSV susceptibility and strongly support a modifier role forCFTRin RSV infection, a significant cause of respiratory morbidity in infants with cystic fibrosis.
Comparative Immunogenicity of Subtype A Human Immunodeficiency Virus Type 1 Envelope Exhibiting Differential Exposure of Conserved Neutralization Epitopes
Authors: Blish Catherine A. , Sather D. Noah , Sellhorn George , Stamatatos Leonidas , Sun Yide , Srivastava Indresh , Barnett Susan W. , Cleveland Brad , Overbaugh Julie , Hu Shiu-lok 
Published: December 2009

ABSTRACT
Development of broadly cross-reactive neutralizing antibodies (NAbs) remains a major goal of HIV-1 vaccine development, but most candidate envelope immunogens have had limited ability to cross-neutralize heterologous strains. To evaluate the immunogenicity of subtype A variants of HIV-1, rabbits were immunized with pairs of closely related subtype A envelopes from the same individual. In each immunogen pair, one variant was readily neutralized by a variety of monoclonal antibodies and plasma antibodies, while the other was neutralization resistant, suggesting differences in the exposures of key epitopes. The breadth of the antibody response was evaluated against subtype A, B, C, and D variants of HIV-1. The specificity of the immunogen-derived neutralizing antibody response was also compared to that of the infected individuals from whom these variants were cloned. None of the immunogens produced broad neutralizing antibodies in immunized animals, and most of the neutralizing antibodies were directed to the variable loops, particularly the V3 loop. No detectable antibodies to either of the potentially exposed conserved epitopes, the membrane proximal external region, or the CD4 binding site were found with immunized rabbits. In contrast, relatively little of the neutralizing activity within the plasma samples of the infected individuals was directed to linear epitopes within the variable loops. These data indicate that immunogens designed to expose conserved regions did not enhance generation of broadly neutralizing antibodies in comparison with the immunogens that failed to expose those regions using this immunization approach.
Compartmentalization and Clonal Amplification of HIV-1 Variants in the Cerebrospinal Fluid during Primary Infection
Authors: Schnell Gretja , Price Richard W. , Swanstrom Ronald , Spudich Serena 
Published: December 2009

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is a severe neurological disease that affects a subset of HIV-1-infected individuals. Increased compartmentalization has been reported between blood and cerebrospinal fluid (CSF) HIV-1 populations in subjects with HAD, but it is still not known when compartmentalization arises during the course of infection. To assess HIV-1 genetic compartmentalization early during infection, we compared HIV-1 populations in the peripheral blood and CSF in 11 primary infection subjects, with analysis of longitudinal samples over the first 18 months for a subset of subjects. We used heteroduplex tracking assays targeting the variable regions ofenvand single-genome amplification and sequence analysis of the full-lengthenvgene to identify CSF-compartmentalized variants and to examine viral genotypes within the compartmentalized populations. For most subjects, HIV-1 populations were equilibrated between the blood and CSF compartments. However, compartmentalized HIV-1 populations were detected in the CSF of three primary infection subjects, and longitudinal analysis of one subject revealed that compartmentalization during primary HIV-1 infection was resolved. Clonal amplification of specific HIV-1 variants was identified in the CSF population of one primary infection subject. Our data show that compartmentalization can occur in the central nervous system (CNS) of subjects in primary HIV-1 infection in part through persistence of the putative transmitted parental variant or via viral genetic adaptation to the CNS environment. The presence of distinct HIV-1 populations in the CSF indicates that independent HIV-1 replication can occur in the CNS, even early after HIV-1 transmission.
Augmented Latent Membrane Protein 1 Expression from Epstein-Barr Virus Episomes with Minimal Terminal Repeats
Authors: Repic Allison M. , Shi Mingxia , Scott Rona S. , Sixbey John W. 
Published: December 2009

ABSTRACT
The major oncogene of the Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), can be expressed from either of two promoters, ED-L1 or L1-TR, producing mRNAs of 2.8 kb or 3.5 kb, respectively. L1-TR, active in nasopharyngeal carcinoma and Hodgkin's lymphoma, is located within the first of a highly variable reiteration of terminal repeat (TR) sequences that are joined by random recombination upon circularization of the linear genome at entry into cells. To determine whether the resultant TR number affects LMP1 promoter activity, we isolated single-cell clones bearing episomes of distinct TR numbers (6TR to 12TR) from epithelial cells newly infected with EBV. LMP1 mRNA levels correlated directly with the quantity of LMP1 protein expressed but varied inversely to TR number. Unexpectedly, the 3.5-kb transcript predominated only at lower TR reiterations. Diminished L1-TR activity in the context of a higher TR count was confirmed with a green fluorescent protein (GFP) reporter construct driven by L1-TR. Various levels of LMP1, expressed from virus isogenic in all but TR number, produced divergent morphological and growth phenotypes in each cell clone. Abundant LMP1 in 6TR cells yielded a relatively cytostatic state compared to the proliferative one produced by intermediate and smaller amounts in 8TR and 12TR clones. These findings suggest that the diversification of TR number, inherent in a round of EBV reactivation and reinfection, may itself be a component of the oncogenic process. The replicative burst preceding onset of many EBV-linked cancers may increase the likelihood that LMP1 levels compatible with clonal outgrowth are achieved in a subset of infected cells.
A GEOMETRIC PARAMETRIZATION OF THE CABIBBO–KOBAYASHI–MASKAWA MATRIX AND THE JARLSKOG INVARIANT
Authors: FUJII KAZUYUKI 
Published: December 2009

In this paper we give a geometric parametrization to the Cabibbo–Kobayashi–Maskawa (CKM) mixing matrix and the Jarlskog invariant, which is based on two flag manifolds SU(3)/U(1)2. To treat a fourth generation of quarks on CP violation we generalize the parametrization to one based on two flag manifolds SU(4)/U(1)3.
An Improvement in Forecasting Rapid Intensification of Typhoon Sinlaku (2008) Using Clear-Sky Full Spatial Resolution Advanced IR Soundings
Authors: Liu Hui , Li Jun 
Published: December 2009

Abstract
Hyperspectral infrared (IR) sounders, such as the Atmospheric Infrared Sounder (AIRS) and the Infrared Atmospheric Sounding Interferometer (IASI), provide unprecedented global atmospheric temperature and moisture soundings with high vertical resolution and accuracy. In this paper, the authors investigate whether advanced IR soundings of water vapor and temperature observations can improve the analysis of a tropical cyclone vortex and the forecast of rapid intensification of a tropical cyclone. Both the IR water vapor and temperature soundings significantly improve the typhoon vortex in the analysis and the forecast of the rapid intensification of Typhoon Sinlaku (2008). The typhoon track forecast is also substantially improved when the full spatial resolution AIRS soundings are assimilated. This study demonstrates the potential important application of high spatial and hyperspectral IR soundings in forecasting tropical cyclones.
Exploration of Climate Data Using Interactive Visualization*
Authors: Ladstädter Florian , Steiner Andrea K. , Lackner Bettina C. , Pirscher Barbara , Kirchengast Gottfried , Kehrer Johannes , Hauser Helwig , Muigg Philipp , Doleisch Helmut 
Published: December 2009

AbstractIn atmospheric and climate research, the increasing amount of data available from climate models and observations provides new challenges for data analysis. The authors present interactive visual exploration as an innovative approach to handle large datasets. Visual exploration does not require any previous knowledge about the data, as is usually the case with classical statistics. It facilitates iterative and interactive browsing of the parameter space to quickly understand the data characteristics, to identify deficiencies, to easily focus on interesting features, and to come up with new hypotheses about the data. These properties extend the common statistical treatment of data, and provide a fundamentally different approach. The authors demonstrate the potential of this technology by exploring atmospheric climate data from different sources including reanalysis datasets, climate models, and radio occultation satellite data. Results are compared to those from classical statistics, revealing the complementary advantages of visual exploration. Combining both the analytical precision of classical statistics and the holistic power of interactive visual exploration, the usual workflow of studying climate data can be enhanced.
Social Support to Empower Parents (STEP)
Authors: Sullivan-Bolyai Susan , Bova Carol , Leung Katherine , Trudeau Allison , Lee Mary , Gruppuso Philip 
Published: December 2009

Purpose The purpose of this study was to test the efficacy of a social support intervention with parents of children <13 years old newly diagnosed with type 1 diabetes mellitus (T1DM). Methods For this randomized, controlled clinical trial, 10 parent mentors of children diagnosed with T1DM ≥1 year and 60 parent participants were recruited from 2 pediatric diabetes centers. Mentors were trained to provide social support (home visits and phone calls) for 12 months to families in the experimental arm (32 mothers). Control group parents (28 mothers) received the phone number of an experienced parent (not trained to give social support) to call as needed. Findings Mothers in the experimental and control arms differed at baseline only in birth order of the child with T1DM. The 2 groups did not differ significantly at 3, 6, or 12 months in parent concern, confidence, worry, impact on the family, or perceived social support. Mothers in the experimental arm identified the parent mentor as someone they would seek for advice and issues regarding growth and development, sleep, eating habits, and identification of community agencies. Parent mentors consistently referred mothers to health care providers for advice on medications and treatments but helped them incorporate this advice into day-to-day management. Conclusion Mothers in the experimental arm valued the mentors’ help in adjusting to the diagnosis, but this value was not measured by the study instruments. Focus group research is under way to clarify the concept of parent mentor social support and to develop a social support measurement tool.
A novel Rag2−/−γc−/−-xenograft model of human CLL
Authors: Bertilaccio Maria Teresa Sabrina , Scielzo Cristina , Simonetti Giorgia , Ponzoni Maurilio , Apollonio Benedetta , Fazi Claudia , Scarfò Lydia , Rocchi Martina , Muzio Marta , Caligaris-Cappio Federico , Ghia Paolo 
Published: December 2009

Abstract
Easily reproducible animal models that allow for study of the biology of chronic lymphocytic leukemia (CLL) and to test new therapeutic agents have been very difficult to establish. We have developed a novel transplantable xenograft murine model of CLL by engrafting the CLL cell line MEC1 into Rag2−/−γc−/− mice. These mice lack B, T, and natural killer (NK) cells, and, in contrast to nude mice that retain NK cells, appear to be optimal recipient for MEC1 cells, which were successfully transplanted through either subcutaneous or intravenous routes. The result is a novel in vivo model that has systemic involvement, develops very rapidly, allows the measurement of tumor burden, and has 100% engraftment efficiency. This model closely resembles aggressive human CLL and could be very useful for evaluating both the biologic basis of CLL growth and dissemination as well as the efficacy of new therapeutic agents.
Individual-level socioeconomic status is associated with worse asthma morbidity in patients with asthma
Authors: Bacon Simon L , Bouchard Anne , Loucks Eric B , Lavoie Kim L 
Published: December 2009

Abstract

Background
Low socioeconomic status (SES) has been linked to higher morbidity in patients with chronic diseases, but may be particularly relevant to asthma, as asthmatics of lower SES may have higher exposures to indoor (e.g., cockroaches, tobacco smoke) and outdoor (e.g., urban pollution) allergens, thus increasing risk for exacerbations.

Methods
This study assessed associations between adult SES (measured according to educational level) and asthma morbidity, including asthma control; asthma-related emergency health service use; asthma self-efficacy, and asthma-related quality of life, in a Canadian cohort of 781 adult asthmatics. All patients underwent a sociodemographic and medical history interview and pulmonary function testing on the day of their asthma clinic visit, and completed a battery of questionnaires (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Asthma Self-Efficacy Scale). General Linear Models assessed associations between SES and each morbidity measure.

Results
Lower SES was associated with worse asthma control (F = 11.63, p < .001), greater emergency health service use (F = 5.09, p = .024), and worse asthma self-efficacy (F = 12.04, p < .01), independent of covariates. Logistic regression analyses revealed that patients with <12 years of education were 55% more likely to report an asthma-related emergency health service visit in the last year (OR = 1.55, 95%CI = 1.05-2.27). Lower SES was not related to worse asthma-related quality of life.

Conclusions
Results suggest that lower SES (measured according to education level), is associated with several indices of worse asthma morbidity, particularly worse asthma control, in adult asthmatics independent of disease severity. Results are consistent with previous studies linking lower SES to worse asthma in children, and add asthma to the list of chronic diseases affected by individual-level SES.
Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout
Authors: Sokolova Niina , Vendelin Marko , Birkedal Rikke 
Published: December 2009

Abstract

Background
Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss), which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20°C in the absence and presence of creatine.

Results
Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria.

Conclusions
The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that trout heart lacks mitochondrial creatine kinase tightly coupled to respiration. This argues against diffusion restriction by the outer mitochondrial membrane. These results from rainbow trout cardiomyocytes resemble those from other low-performance hearts such as neonatal rat and rabbit hearts. Thus, it seems that metabolic regulation is related to cardiac performance, and it is likely that rainbow trout can be used as a model animal for further studies of the localization and role of diffusion restrictions in low-performance hearts.
Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer
Authors: Itadani Hiraku , Oshima Hiroko , Oshima Masanobu , Kotani Hidehito 
Published: December 2009

AbstractBackgroundGastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models.ResultsGlobal expression profiling initially found gastric tumors fromCOX-2/mPGES-1(C2mE)-related transgenic mice (K19-C2mE,K19-Wnt1/C2mE, andK19-Nog/C2mE) resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2pathway in mice (K19-Wnt1/C2mEmice) further reproduce features of human gastric intestinal-type tumors.ConclusionWe demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especiallyK19-Wnt1/C2mEmice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers.