bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dissipation of excess pore pressures in contractive vibro-columns at small strains
Authors: Blewett J. , Woodward P. K. 
Published: November 2009

A laboratory investigation into the mechanisms contributing to the dissipation of excess pore pressures by vibro-replacement stone columns has been carried out. The paper examines the results of the laboratory programme by using a simplified version of the analytical approach proposed by Seed and Booker to describe the main mechanisms of pore pressure dissipation. Modifications to this analysis are proposed, in view of the laboratory results, to include aspects of liquefaction mitigation due to the rigidity of the columnar inclusion and the performance constraints caused by finite column permeability. Nous avons enqueêté en laboratoire sur les mécanismes contribuant à la dissipation des pressions de pores excessives au moyen de colonnes de pierre placées par vibration. Cette étude examine les résultats du programme mené en laboratoire en utilisant une version simplifiée de la méthode analytique proposée par Seed et Booker pour décrire les principaux mécanismes de dissipation de pression de pore. Au regard des résultats obtenus en laboratoire, nous proposons des modifications à cette analyse afin d'inclure les aspects de mitigation de la liquéfaction dus à la rigidité de l'inclusion colonnaire et aux contraintes de performance causées par la perméabilité finie des colonnes.
Increased Arterial Stiffness in HIV-Infected Children: Risk Factors and Antiretroviral Therapy
Authors: Charakida Marietta , Loukogeorgakis Stavros P , Okorie Michael I , Masi Stefano , Halcox Julian P , Deanfield John E , Klein Nigel J 
Published: November 2009

Background Recent evidence suggests that both the HIV virus and antiretroviral therapy (ART) are associated with premature atherosclerosis in adults. Increased arterial stiffness as assessed by pulse wave velocity (PWV) has been associated with adverse cardiovascular outcome in adults. The relationship between HIV infection and treatment and arterial stiffness has not been evaluated in children. Methods We studied 83 HIV-infected children with a mean ±sd age of 11.0 ±3.1 years and 59 controls aged 12.2 ±2.8 years. Among the HIV-infected children, 48 were receiving ART (23 including a protease inhibitor). Arterial stiffness was assessed non-invasively by carotid–radial PWV. Disease severity was defined according to the CDC classification. Results PWV was significantly increased in HIV-infected children compared with controls ( P<0.05). A significant association between age and PWV was noted in HIV-infected children but not in controls. HIV-infected children receiving ART had significantly increased total cholesterol levels and PWV compared with non-treated children ( P<0.001 and P<0.05, respectively). CDC stage was greater in ART-treated compared with non-treated HIV- infected children ( P<0.001). No differences in other cardiovascular risk factors were noted in the two groups. After multivariable analysis, ART, systolic blood pressure, disease severity and total cholesterol remained independent predictors of PWV. Conclusions HIV-infected children have increased arterial stiffness compared with healthy children. These changes were more pronounced with increasing age in HIV-infected children particularly in those who were receiving ART.
Systematic Review and Metaanalysis of Patient Self-Report versus Trained Assessor Joint Counts in Rheumatoid Arthritis
Authors: BARTON JENNIFER L. , CRISWELL LINDSEY A. , KAISER RACHEL , CHEN YEA-HUNG , SCHILLINGER DEAN 
Published: November 2009

Objective.Patient self-report outcomes and physician-performed joint counts are important measures of disease activity and treatment response. This metaanalysis examines the degree of concordance in joint counts between trained assessors and patients with rheumatoid arthritis (RA).Methods.Studies eligible for inclusion met the following criteria: English language; compared patient with trained assessor joint counts; peer-reviewed; and RA diagnosis determined by board-certified or board-eligible specialist or met 1987 American College of Rheumatology criteria. We searched PubMed and Embase to identify articles between 1966 and January 1, 2008. We compared measures of correlation between patients and assessors for either tender/painful or swollen joint counts. We used metaanalysis methods to calculate summary correlation estimates.Results.We retrieved 462 articles and 18 were included. Self-report joint counts were obtained by a text and/or mannequin (picture) format. The summary estimates for the Pearson correlation coefficients for tender joint counts were 0.61 (0.47 lower, 0.75 upper) and for swollen joint counts 0.44 (0.15, 0.73). Summary results for the Spearman correlation coefficients were 0.60 (0.30, 0.90) for tender joint counts and 0.54 (0.35, 0.73) for swollen joint counts.Conclusion.A self-report tender joint count has moderate to marked correlation with those performed by a trained assessor. In contrast, swollen joint counts demonstrate lower levels of correlation. Future research should explore whether integrating self-report tender joint counts into routine care can improve efficiency and quality of care, while directly involving patients in assessment of RA disease activity.
Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection
Authors: Novais Fernanda O. , Santiago Rômulo C. , Báfica André , Khouri Ricardo , Afonso Lilian , Borges Valéria M. , Brodskyn Cláudia , Barral-Netto Manoel , Barral Aldina , de Oliveira Camila I. 
Published: November 2009

AbstractNeutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-α as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.
Cutting Edge: Normal Regional Lymph Node Enrichment of Antigen-Specific Regulatory T Cells with Autoimmune Disease-Suppressive Capacity
Authors: Wheeler Karen M. , Samy Eileen T. , Tung Kenneth S. K. 
Published: November 2009

AbstractNatural CD4+CD25+Foxp3+ regulatory T cells (Treg) effectively prevent autoimmune disease development, but their role in maintaining physiological tolerance against self-Ag of internal organs is not yet defined. In this study, we quantified disease-specific Treg (DS-Treg) as Treg that preferentially suppress one autoimmune disease over another in day 3 thymectomized recipients. A striking difference was found among individual lymph nodes (LN) of normal mice; Treg from draining LN were 15–50 times more efficient than those of nondraining LN at suppressing autoimmune diseases of ovary, prostate, and lacrimal glands. The difference disappeared upon auto-Ag ablation and returned upon auto-Ag re-expression. In contrast, the CD4+CD25− effector T cells from different individual LN induced multiorgan inflammation with comparable organ distribution. We propose that peripheral tolerance for internal organs relies on the control of autoreactive effector T cells by strategic enrichment of Ag-specific Treg in the regional LN.
IFN-γ Expressed by T Cells Regulates the Persistence of Antigen Presentation by Limiting the Survival of Dendritic Cells
Authors: Russell Marsha S. , Dudani Renu , Krishnan Lakshmi , Sad Subash 
Published: November 2009

AbstractAg presentation to T cells orchestrates the development of acquired immune response. Although it is considered that Ag presentation may persist at high levels during chronic infections, we have previously reported that in mice infected with bacillus Calmette-Guérin, Ag presentation gets drastically curtailed during the chronic stage of infection despite antigenic persistence. In this report we evaluated the mechanism of this curtailment. Ag presentation declined precipitously as the T cell response developed, and Ag presentation was not curtailed in mice that were deficient in CD8+ T cells or MHC class II, suggesting that T cells regulate Ag presentation. Curtailment of Ag presentation was reduced in IFN-γ-deficient mice, but not in mice with a deficiency/mutation in inducible NOS2, perforin, or Fas ligand. In hosts with no T cells (Rag1−/−), Ag presentation was not curtailed during the chronic stage of infection. However, adoptive transfer of wild-type, but not IFN-γ−/−, CD4+ and CD8+ T cells into Rag1-deficient hosts strongly curtailed Ag presentation. Increased persistence of Ag presentation in IFN-γ-deficient hosts correlated to increased survival of dendritic cells, but not of macrophages, and was not due to increased stimulatory capacity of IFN-γ-deficient dendritic cells. These results reveal a novel mechanism indicating how IFN-γ prevents the persistence of Ag presentation, thereby preventing memory T cells from going into exhaustion.
What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?
Authors: Belyakov Igor M. , Ahlers Jeffrey D. 
Published: November 2009

Abstract
The route of vaccination is important in influencing immune responses at the initial site of pathogen invasion where protection is most effective. Immune responses required for mucosal protection can differ vastly depending on the individual pathogen. For some mucosal pathogens, including acute self-limiting infections, high-titer neutralizing Abs that enter tissue parenchyma or transude into the mucosal lumen are sufficient for clearing cell-free virus. However, for pathogens causing chronic infections such as HIV, hepatitis C virus, herpes viruses, mycobacteria, and fungal and parasitic infections, a single arm of the immune response generated by systemic vaccination may be insufficient for protection. Induction of the mucosal innate and adaptive immune systems, including CD4+ T help, Th17, high avidity CD8+ CTL, and secretory IgA and IgG1 neutralizing Abs, at the site of pathogen entry may be required for effective protection against highly invasive pathogens that lead to chronic infection and may be generated predominantly by mucosal vaccination.
IL-23 Is Required for Protection against Systemic Infection withListeria monocytogenes
Authors: Meeks Karen D. , Sieve Amy N. , Kolls Jay K. , Ghilardi Nico , Berg Rance E. 
Published: November 2009

AbstractListeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while IFN-γ production is not altered by the lack of IL-23. LM induces the production of IL-17A from γδ T cells, but not CD4, CD8, or NK cells. Furthermore, a lack of efficient neutrophil recruitment to the liver is evident in both IL-23p19 KO and IL-17RA KO mice during LM infection. Immunocytochemical analysis of infected livers revealed that neutrophils were able to localize with LM in IL-23p19 KO and IL-17RA KO mice, indicating that IL-23 and IL-17RA do not regulate the precise localization of neutrophils with LM. The importance of IL-23-induced IL-17A was demonstrated by injecting IL-23p19 KO mice with recombinant IL-17A. These mice had reduced LM bacterial burdens compared with IL-23p19 KO mice that did not receive IL-17A. These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from γδ T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance.
Cutting Edge: Inhibitory Effects of CD4 and CD8 on T Cell Activation Induced by High-Affinity Noncognate Ligands
Authors: Chervin Adam S. , Stone Jennifer D. , Bowerman Natalie A. , Kranz David M. 
Published: November 2009

AbstractIt has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand cross-reactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD = 17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as “coreceptor inhibitors” to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
Matrix Metalloproteinase (MMP)-1 and MMP-3 Induce Macrophage MMP-9: Evidence for the Role of TNF-α and Cyclooxygenase-2
Authors: Steenport Michel , Khan K. M. Faisal , Du Baoheng , Barnhard Sarah E. , Dannenberg Andrew J. , Falcone Domenick J. 
Published: November 2009

AbstractMatrix metalloproteinase (MMP)-9 (gelatinase B) participates in a variety of diverse physiologic and pathologic processes. We recently characterized a cyclooxygenase-2 (COX-2)→PGE2→EP4 receptor axis that regulates macrophage MMP-9 expression. In the present studies, we determined whether MMPs, commonly found in inflamed and neoplastic tissues, regulate this prostanoid-EP receptor axis leading to enhanced MMP-9 expression. Results demonstrate that exposure of murine peritoneal macrophages and RAW264.7 macrophages to MMP-1 (collagenase-1) or MMP-3 (stromelysin-1) lead to a marked increase in COX-2 expression, PGE2 secretion, and subsequent induction of MMP-9 expression. Proteinase-induced MMP-9 expression was blocked in macrophages preincubated with the selective COX-2 inhibitor celecoxib or transfected with COX-2 small interfering RNA (siRNA). Likewise, proteinase-induced MMP-9 was blocked in macrophages preincubated with the EP4 antagonist ONO-AE3-208 or transfected with EP4 siRNA. Exposure of macrophages to MMP-1 and MMP-3 triggered the rapid release of TNF-α, which was blocked by MMP inhibitors. Furthermore, both COX-2 and MMP-9 expression were inhibited in macrophages preincubated with anti-TNF-α IgG or transfected with TNF-α siRNA. Thus, proteinase-induced MMP-9 expression by macrophages is dependent on the release of TNF-α, induction of COX-2 expression, and PGE2 engagement of EP4. The ability of MMP-1 and MMP-3 to regulate macrophage secretion of PGE2 and expression of MMP-9 defines a nexus between MMPs and prostanoids that is likely to play a role in the pathogenesis of chronic inflammatory diseases and cancer. These data also suggest that this nexus is targetable utilizing anti-TNF-α therapies and/or selective EP4 antagonists.
Duality of Enhancer Functioning Mode Revealed in a Reduced TCRβ Gene Enhancer Knockin Mouse Model
Authors: Bonnet Marie , Huang Fang , Benoukraf Touati , Cabaud Olivier , Verthuy Christophe , Boucher Anaelle , Jaeger Sébastien , Ferrier Pierre , Spicuglia Salvatore 
Published: November 2009

Abstract
The TCRβ gene enhancer (Eβ) commands TCRβ gene expression through the lifespan of T lymphocytes. Genetic and molecular studies have implied that in early thymocytes, Eβ directs chromatin opening over the Dβ-Jβ-Cβ domains and triggers initial Dβ-Jβ recombination. In mature T cells, Eβ is required for expression of the assembled TCRβ gene. Whether these separate activities rely on distinct Eβ regulatory sequences and involve differing modes of activation is unclear. Using gene targeting in mouse embryonic stem cells, we replaced Eβ by a conserved core fragment (Eβ169). We found that Eβ169-carrying alleles were capable of sustaining β gene expression and the development of mature T cells in homozygous knockin mice. Surprisingly, these procedures and underlying molecular transactions were affected to a wide range of degrees depending on the developmental stage. Early thymocytes barely achieved Dβ-Jβ germline transcription and recombination. In contrast, T cells displayed substantial though heterogeneous levels of VDJ-rearranged TCRβ gene expression. Our results have implications regarding enhancer function in cells of the adaptive immune system and, potentially, TCRβ gene recombination and allelic exclusion.
Viruses within theFlaviviridaeDecrease CD4 Expression and Inhibit HIV Replication in Human CD4+ Cells
Authors: Xiang Jinhua , McLinden James H. , Rydze Robert A. , Chang Qing , Kaufman Thomas M. , Klinzman Donna , Stapleton Jack T. 
Published: November 2009

AbstractViral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. Two flaviviruses are associated with a reduction in HIV replication or improved survival in HIV-infected people (dengue virus (DV) and GB virus type C (GBV-C)). GBV-C infection and expression of the GBV-C nonstructural protein 5A (NS5A) and the DV NS5 protein in CD4+ T cells inhibit HIV replication in vitro. To determine whether the inhibitory effect on HIV replication is conserved among other flaviviruses and to characterize mechanism(s) of HIV inhibition, the NS5 proteins of GBV-C, DV, hepatitis C virus, West Nile virus, and yellow fever virus (YFV; vaccine strain 17D) were expressed in CD4+ T cells. All NS5 proteins inhibited HIV replication. This correlated with decreased steady-state CD4 mRNA levels and reduced cell surface CD4 protein expression. Infection of CD4+ T cells and macrophages with YFV (17D vaccine strain) also inhibited HIV replication and decreased CD4 gene expression. In contrast, mumps virus was not inhibited by the expression of flavivirus NS5 protein or by YFV infection, and mumps infection did not alter CD4 mRNA or protein levels. In summary, CD4 gene expression is decreased by all human flavivirus NS5 proteins studied. CD4 regulation by flaviviruses may interfere with innate and adaptive immunity and contribute to in vitro HIV replication inhibition. Characterization of the mechanisms by which flaviviruses regulate CD4 expression may lead to novel therapeutic strategies for HIV and immunological diseases.
Activated CD8+ T-Effector/Memory Cells Eliminate CD4+ CD25+ Foxp3+ T-Suppressor Cells from Tumors via FasL Mediated Apoptosis
Authors: Kilinc Mehmet O. , Rowswell-Turner Rachael B. , Gu Tao , Virtuoso Lauren P. , Egilmez Nejat K. 
Published: November 2009

Abstract
Tumor-resident CD8+ T cells display a quiescent effector/memory phenotype that is maintained in part by infiltrating CD4+ CD25+ Foxp3+ T-suppressor cells. Intratumoral delivery of IL-12, in contrast, can restore cytotoxic function to tumor-associated CD8+ T cells and induce the apoptotic death of T-suppressor cells. Depletion of CD8+ T cells from tumors before IL-12 treatment resulted in the abrogation of treatment-mediated T-suppressor cell apoptosis revealing a link between CD8+ T cell activation and T-suppressor elimination. Furthermore, IL-12 failed to induce T-suppressor cell loss in IFN-γ- or FasL-deficient mice demonstrating a requirement for IFN-γ and FasL in this process. Adoptive transfer of wild-type CD8+ T cells to FasL-knockout mice restored posttherapy T-suppressor cell elimination from tumors establishing that expression of FasL on CD8+ T cells was sufficient to promote T-suppressor cell death. IL-12 failed to induce FasL on T-effectors in IFN-γ-knockout mice demonstrating a requirement for IFN-γ in FasL up-regulation. Adoptive transfer of wild-type CD8+ T cells induced T-suppressor cell death in IFN-γ-knockout mice confirming that autocrine IFN-γ was sufficient for CD8+ T cell FasL expression. These findings reveal a mechanism by which cytotoxic T cells can abrogate regulatory cell activity.
The Tpl2 Mutation Sluggish Impairs Type I IFN Production and Increases Susceptibility to Group B Streptococcal Disease
Authors: Xiao Nengming , Eidenschenk Celine , Krebs Philippe , Brandl Katharina , Blasius Amanda L. , Xia Yu , Khovananth Kevin , Smart Nora G. , Beutler Bruce 
Published: November 2009

Abstract
Sluggish was identified in a population of third generation mice descended from N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes exhibited impaired TNF-α production in response to all TLR ligands tested and displayed impaired type I IFN production in response to TLR7 and TLR9 stimulations. The phenotype was confined to a critical region on mouse chromosome 18 and then ascribed to a T to A transversion in the acceptor splice site of intron 4 at position 13346 of the Map3k8 gene, resulting in defective splicing. The Map3k8Sluggish mutation does not result in susceptibility to viral infections, but Sluggish mice displayed high susceptibility to group B streptococcus infection, with impaired TNF-α and type I IFN production in infected macrophages. Our data demonstrate that the encoded protein kinase Tpl2 plays an essential role in cell signaling in the immune response to certain pathogens.
Distinct Antiviral Roles for Human 2′,5′-Oligoadenylate Synthetase Family Members against Dengue Virus Infection
Authors: Lin Ren-Jye , Yu Han-Pang , Chang Bi-Lan , Tang Wei-Chun , Liao Ching-Len , Lin Yi-Ling 
Published: November 2009

Abstract
The 2′,5′-oligoadenylate synthetase (OAS) and its downstream effector RNase L play important roles in host defense against virus infection. Oas1b, one of the eight Oas1 genes in the mouse genome, has been identified as a murine flavivirus-resistance gene. Four genes, OAS1, OAS2, OAS3, and OAS-like (OASL), have been identified in the human OAS gene family, and 10 isoforms, including OAS1 (p42, p44, p46, p48, and p52), OAS2 (p69 and p71), OAS3 (p100), and OASL (p30 and p59) can be generated by alternative splicing. In this study, we determined the role of the human OAS/RNase L pathway in host defense against dengue virus (DEN) infection and assessed the antiviral potential of each isoform in the human OAS family. DEN replication was reduced by overexpression and enhanced by knockdown of RNase L expression, indicating a protective role for RNase L against DEN replication in human cells. The human OAS1 p42, OAS1 p46, and OAS3 p100, but not the other OAS isoforms, blocked DEN replication via an RNase L-dependent mechanism. Furthermore, the anti-DEN activities of these three OAS isoforms correlated with their ability to trigger RNase L activation in DEN-infected cells. Thus, OAS1 p42/p46 and OAS3 p100 are likely to contribute to host defense against DEN infection and play a role in determining the outcomes of DEN disease severity.