bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Magnitude of the Virus-Specific Plasmablast Response and Disease Severity in Dengue Patients
Authors: Garcia-Bates Tatiana M. , Cordeiro Marli T. , Nascimento Eduardo J. M. , Smith Amanda P. , Soares de Melo Klécia M. , McBurney Sean P. , Evans Jared D. , Marques Ernesto T. A. , Barratt-Boyes Simon M. 
Published: December 2012

Abstract
Dengue is a globally expanding disease caused by infection with dengue virus (DENV) that ranges from febrile illness to acute disease with serious complications. Secondary infection predisposes individuals to more severe disease, and B lymphocytes may play a role in this phenomenon through production of Ab that enhance infection. To better define the acute B cell response during dengue, we analyzed peripheral B cells from an adult Brazilian hospital cohort with primary and secondary DENV infections of varying clinical severity. Circulating B cells in dengue patients were proliferating, activated, and apoptotic relative to individuals with other febrile illnesses. Severe secondary DENV infection was associated with extraordinary peak plasmablast frequencies between 4 and 7 d of illness, averaging 46% and reaching 87% of B cells, significantly greater than those seen in mild illness or primary infections. On average &gt;70% of IgG-secreting cells in individuals with severe secondary DENV infection were DENV specific. Plasmablasts produced Ab that cross-reacted with heterotypic DENV serotypes, but with a 3-fold greater reactivity to DENV-3, the infecting serotype. Plasmablast frequency did not correlate with acute serum-neutralizing Ab titers to any DENV serotype regardless of severity of disease. These findings indicate that massive expansion of DENV-specific and serotype cross-reactive plasmablasts occurs in acute secondary DENV infection of adults in Brazil, which is associated with increasing disease severity.
Blocking A2B Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation
Authors: Wei Wei , Du Changsheng , Lv Jie , Zhao Guixian , Li Zhenxin , Wu Zhiying , Haskó György , Xie Xin 
Published: December 2012

Abstract
Adenosine is a key endogenous signaling molecule that regulates immune responses. A2B adenosine receptor (AR) is a relatively low-affinity receptor for adenosine, and the activation of A2BAR is believed to require pathological level of adenosine that is associated with ischemia, inflammation, trauma, or other types of stress. The role of A2BAR in the pathogenesis of multiple sclerosis (MS) is still unclear. In this study, we discovered that A2BAR was upregulated both in the peripheral blood leukocytes of MS patients and the peripheral lymphoid tissues of experimental autoimmune encephalomyelitis (EAE) mice. A2BAR-specific antagonists, CVT-6883 and MRS-1754, alleviated the clinical symptoms of EAE and protected the CNS from immune damage. A2BAR-knockout mice also developed less severe EAE. Further study indicated that blocking or deleting A2BAR inhibited Th17 cell differentiation by blocking IL-6 production from APCs such as dendritic cells. In dendritic cells, A2BAR was also upregulated during the development of EAE. CVT-6883 and genetic deletion of A2BAR significantly reduced adenosine-mediated IL-6 production. The phospholipase Cβ–protein kinase C and p38 MAPK pathways were found to be involved in the A2BAR-mediated IL-6 production. Our findings not only revealed the pathological role of A2BAR in EAE, but also suggested that this receptor might be a new therapeutic target for the development of anti-MS drugs.
Effective Cooperation of Monoclonal Antibody and Peptide Vaccine for the Treatment of Mouse Melanoma
Authors: Ly Long V. , Sluijter Marjolein , van der Burg Sjoerd H. , Jager Martine J. , van Hall Thorbald 
Published: December 2012

Abstract
mAbs binding to tumor-associated surface Ags are therapeutically applied in a range of malignancies. Therapeutic vaccination only recently met with clinical success, and the first cancer vaccine received U.S. Food and Drug Administration approval last year. To improve current protocols, we combined peptide vaccines with mAb to the tyrosinase-related protein (TRP)-1 surface Ag for the treatment of B16F10 skin melanoma. Vaccine formulations with synthetic long peptides failed to elicit strong CD8 T cell responses to self-differentiation Ags gp100 and TRP-2, whereas altered peptide sequences recruited gp100-specific CD8 T cells from the endogenous repertoire with frequencies of 40%. However, these high frequencies were reached too late; large, progressively growing melanomas had already emerged. Addition of the TRP-1–directed mAb TA99 to the treatment protocol mediated eradication of s.c. lesions. The mode of action of the Ab did not depend on complement factor C3 and did not lead to improved Ag presentation and CD8 T cell immunity; rather, it recruited FcγR-bearing innate immune cells during early tumor control, thereby creating a window of time for the generation of protective cellular immunity. These data support the concept of combination therapy, in which passive transfer of mAbs is supplemented with cancer peptide vaccines. Moreover, we advocate that tumor Ag–specific T cell immunity directed against self-proteins can be exploited from the endogenous repertoire.
Early Growth Response Gene-2 Controls IL-17 Expression and Th17 Differentiation by Negatively Regulating Batf
Authors: Miao Tizong , Raymond Meera , Bhullar Punamdip , Ghaffari Emma , Symonds Alistair L. J. , Meier Ute C. , Giovannoni Gavin , Li Suling , Wang Ping 
Published: December 2012

Abstract
Early growth response gene (Egr)-2 is important for the maintenance of T cell homeostasis and controls the development of autoimmune disease. However, the underlying mechanisms are unknown. We have now discovered that Egr-2, which is induced by TGF-β and IL-6, negatively regulates the expression of IL-17, but not IL-2 or IFN-γ, in effector T cells. In the absence of Egr-2, CD4 T cells produce high levels of Th17 cytokines, which renders mice susceptible to experimental autoimmune encephalomyelitis induction. T cells lacking Egr-2 show increased propensity for Th17, but not Th1 or Th2, differentiation. Control of IL-17 expression and Th17 differentiation by Egr-2 is due to inhibition of Batf, a transcription factor that regulates IL-17 expression and Th17 differentiation. Egr-2 interacts with Batf in CD4 T cells and suppresses its interaction with DNA sequences derived from the IL-17 promoter, whereas the activation of STAT3 and expression of retinoic acid–related orphan receptor γt are unchanged in Th17 cells in the absence of Egr-2. Thus, Egr-2 plays an important role to intrinsically control Th17 differentiation. We also found that CD4 T cells from multiple sclerosis patients have reduced expression of Egr-2 and increased expression of IL-17 following stimulation with anti-CD3 in vitro. Collectively, our results demonstrate that Egr-2 is an intrinsic regulator that controls Th17 differentiation by inhibiting Batf activation, which may be important for the control of multiple sclerosis development.
Reduced Surface Expression of TLR4 by a V254I Point Mutation Accounts for the Low Lipopolysaccharide Responder Phenotype of BALB/c B Cells
Authors: Tsukamoto Hiroki , Fukudome Kenji , Takao Shoko , Tsuneyoshi Naoko , Ohta Shoichiro , Nagai Yoshinori , Ihara Hideyuki , Miyake Kensuke , Ikeda Yoshitaka , Kimoto Masao 
Published: December 2012

Abstract
LPS is recognized by TLR4 and radioprotective 105 kDa in B cells. Susceptibility to LPS in murine B cells is most closely linked to the locus containing the TLR4 gene. However, the molecular mechanism underlying genetic control of LPS sensitivity by this locus has not been fully elucidated. In this study, we revealed that C57BL/6 (B6) B cells respond to mAb-induced, TLR4-specific signals stronger than BALB/c (BALB) B cells, as assessed by proliferation and upregulation of CD69 and CD86. In contrast, BALB B cells were not hyporesponsive to agonistic anti–radioprotective 105 kDa mAb or the TLR9 agonist CpG. Although the level of TLR4 mRNA in BALB B cells was comparable with that in B6 B cells, surface TLR4 expression in BALB B cells was lower than that in B6 B cells. This lower surface expression of BALB TLR4 was also observed when HEK293 and Ba/F3 cells were transfected with a BALB TLR4 expression construct. We identified a V254I mutation as the responsible single nucleotide polymorphism for lower surface expression of BALB TLR4. Furthermore, cotransfection of myeloid differentiation factor-2 increased BALB TLR4 expression, although it was still lower than B6 TLR4 expression. In concordance with reduced expression, Ba/F3 cells transfected with BALB TLR4 and myeloid differentiation factor-2 were hyporesponsive compared with those with B6 TLR4, as assessed by LPS-induced NF-κB activation. In conclusion, we revealed that LPS sensitivity is genetically controlled by the level of surface TLR4 expression on B cells. A V254I mutation accounts for the LPS hyporesponsive phenotype of BALB B cells.
Cleavage of Anti-Apoptotic Bcl-2 Family Members after TCR Stimulation Contributes to the Decision between T Cell Activation and Apoptosis
Authors: Guerrero Alan D. , Welschhans Robert L. , Chen Min , Wang Jin 
Published: December 2012

Abstract
Engagement of the TCR induces activation-induced cell death (AICD) of T cells that have been previously stimulated. However, a portion of these T cells can survive and undergo further activation. The molecular mechanism that decides whether a T cell will live or die after TCR re-engagement is unclear. We found that cross-linking of TCR in preactivated primary mouse T cells led to the cleavage of anti-apoptotic Bcl-2 and Bcl-xL in dying cells. Cleavage-resistant Bcl-2 and Bcl-xL were more efficient than their wild-type counterparts in the inhibition of apoptosis in primary mouse T cells and in the H9 T cell line after TCR cross-linking. In contrast, the surviving T cells after TCR re-engagement displayed upregulation of Bcl-xL, and knockdown of Bcl-xL promoted AICD. This indicates that caspase-mediated cleavage of anti-apoptotic Bcl-2 or Bcl-xL facilitates AICD in T cells, whereas upregulation of Bcl-xL promotes T cell survival and allows further T cell activation. Our data suggest that cleavage of anti-apoptotic Bcl-2 and Bcl-xL contributes to the decision between T cell activation and apoptosis after TCR re-engagement.
Unraveling Graft-versus-Host Disease and Graft-versus-Leukemia Responses Using TCR Vβ Spectratype Analysis in a Murine Bone Marrow Transplantation Model
Authors: Fanning Stacey L. , Zilberberg Jenny , Stein Johann , Vazzana Kristin , Berger Stephanie A. , Korngold Robert , Friedman Thea M. 
Published: December 2012

Abstract
The optimum use of allogeneic blood and marrow transplantation (BMT) as a curative therapy for hematological malignancies lies in the successful separation of mature donor T cells that are host reactive and induce graft-versus-host disease (GVHD) from those that are tumor reactive and mediate graft-versus-leukemia (GVL) effects. To study whether this separation was possible in an MHC-matched murine BMT model (B10.BR→CBA) with a CBA-derived myeloid leukemia line, MMC6, we used TCR Vβ CDR3-size spectratype analysis to first show that the Vβ13 family was highly skewed in the B10.BR anti-MMC6 CD8+ T cell response but not in the alloresponse against recipient cells alone. Transplantation of CD8+Vβ13+ T cells at the dose equivalent of their constituency in 1 × 107 CD8+ T cells, a dose that had been shown to mediate lethal GVHD in recipient mice, induced a slight GVL response with no concomitant GVHD. Increasing doses of CD8+Vβ13+ T cells led to more significant GVL responses but also increased GVHD symptoms and associated mortality. Subsequent spectratype analysis of GVHD target tissues revealed involvement of gut-infiltrating CD8+Vβ13+ T cells accounting for the observed in vivo effects. When BMT recipients were given MMC6-presensitized CD8+Vβ13+ T cells, they displayed a significant GVL response with minimal GVHD. Spectratype analysis of tumor-presensitized, gut-infiltrating CD8+Vβ13+ T cells showed preferential usage of tumor-reactive CDR3-size lengths, and these cells expressed increased effector memory phenotype (CD44+CD62L−/lo). Thus, Vβ spectratyping can identify T cells involved in antihost and antitumor reactivity and tumor presensitization can aid in the separation of GVHD and GVL responses.
FcγRIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis
Authors: Sharp Phoebe E. H. , Martin-Ramirez Javier , Mangsbo Sara M. , Boross Peter , Pusey Charles D. , Touw Ivo P. , Cook H. Terence , Verbeek J. Sjef , Tarzi Ruth M. 
Published: December 2012

Abstract
FcγRIIb is the sole inhibitory FcR for IgG in humans and mice, where it is involved in the negative regulation of Ab production and cellular activation. FcγRIIb-deficient mice show exacerbated disease following the induction of nephrotoxic nephritis (NTN). In this study, we determined the cellular origin of the FcγRIIb-knockout phenotype by inducing NTN in mice with a deficiency of FcγRIIb on either B cells alone (FcγRIIBfl/fl/CD19Cre+) or myeloid cells (FcγRIIBfl/fl/CEBPαCre+). Deletion of FcγRIIb from B cells did not increase susceptibility to NTN, compared with wild-type (WT) mice, despite higher Ab titers in the FcγRIIBfl/fl/CD19Cre+ mice compared with the WT littermate controls. In contrast, mice lacking FcγRIIb on myeloid cells had exacerbated disease as measured by increased glomerular thrombosis, glomerular crescents, albuminuria, serum urea, and glomerular neutrophil infiltration when compared with WT littermate controls. The role for FcγRIIb expression on radioresistant intrinsic renal cells in the protection from NTN was then investigated using bone marrow chimeric mice. FcγRIIb−/− mice transplanted with FcγRIIb−/− bone marrow were more susceptible to NTN than WT mice transplanted with FcγRIIb−/− bone marrow, indicating that the presence of WT intrinsic renal cells protects from NTN. These results demonstrate that FcγRIIb on myeloid cells plays a major role in protection from NTN, and therefore, augmentation of FcγRIIb on these cells could be a therapeutic target in human Ab-mediated glomerulonephritis. Where there was a lack of FcγRIIb on circulating myeloid cells, expression of FcγRIIb on intrinsic renal cells provided an additional level of protection from Ab-mediated glomerulonephritis.
Tracking the evolution of the disaster management cycle: A general system theory approach
Authors: Coetzee Christo , Van Niekerk Dewald 
Published: December 2012

Officials and scholars have used the disaster management cycle for the past 30 years to explain and manage impacts. Although very little understanding and agreement exist in terms of where the concept originated it is the purpose of this article to address the origins of the disaster management cycle. To achieve this, general system theory concepts of isomorphisms, equifinality, open systems and feedback arrangements were applied to linear disaster phase research (which emerged in the 1920s) and disaster management cycles. This was done in order to determine whether they are related concepts with procedures such as emergency, relief, recovery and rehabilitation.
Integrating Rapid Pathogen Identification and Antimicrobial Stewardship Significantly Decreases Hospital Costs
Authors: Perez Katherine K. , Olsen Randall J. , Musick William L. , Cernoch Patricia L. , Davis James R. , Land Geoffrey A. , Peterson Leif E. , Musser James M. 
Published: December 2012

Context.—Early diagnosis of gram-negative bloodstream infections, prompt identification of the infecting organism, and appropriate antibiotic therapy improve patient care outcomes and decrease health care expenditures. In an era of increasing antimicrobial resistance, methods to acquire and rapidly translate critical results into timely therapies for gram-negative bloodstream infections are needed.
Objective.—To determine whether mass spectrometry technology coupled with antimicrobial stewardship provides a substantially improved alternative to conventional laboratory methods.
Design.—An evidence-based intervention that integrated matrix-assisted laser desorption and ionization time-of-flight mass spectrometry, rapid antimicrobial susceptibility testing, and near–real-time antimicrobial stewardship practices was implemented. Outcomes in patients hospitalized prior to initiation of the study intervention were compared to those in patients treated after implementation. Differences in length of hospitalization and hospital costs were assessed in survivors.
Results.—The mean hospital length of stay in the preintervention group survivors (n = 100) was 11.9 versus 9.3 days in the intervention group (n = 101; P = .01). After multivariate analysis, factors independently associated with decreased length of hospitalization included the intervention (hazard ratio, 1.38; 95% confidence interval, 1.01–1.88) and active therapy at 48 hours (hazard ratio, 2.9; confidence interval, 1.15–7.33). Mean hospital costs per patient were $45 709 in the preintervention group and $26 162 in the intervention group (P = .009).
Conclusions.—Integration of rapid identification and susceptibility techniques with antimicrobial stewardship significantly improved time to optimal therapy, and it decreased hospital length of stay and total costs. This innovative strategy has ramifications for other areas of patient care.
Prebiotic approach alleviates hepatic steatosis: Implication of fatty acid oxidative and cholesterol synthesis pathways
Authors: Pachikian Barbara D. , Essaghir Ahmed , Demoulin Jean‐Baptiste , Catry Emilie , Neyrinck Audrey M. , Dewulf Evelyne M. , Sohet Florence M. , Portois Laurence , Clerbaux Laure‐Alix , Carpentier Yvon A. , Possemiers Sam , Bommer Guido T. , Cani Patrice D. , Delzenne Nathalie M. 
Published: December 2012

ScopeRecent data suggest that gut microbiota contributes to the regulation of host lipid metabolism. We report how fermentable dietary fructo‐oligosaccharides (FOS) control hepatic steatosis induced by n‐3 PUFA depletion, which leads to hepatic alterations similar to those observed in non‐alcoholic fatty liver disease patients.Methods and resultsC57Bl/6J mice fed an n‐3 PUFA‐depleted diet for 3 months were supplemented with FOS during the last 10 days of treatment. FOS‐treated mice exhibited higher caecal Bifidobacterium spp. and lower Roseburia spp. content. Microarray analysis of hepatic mRNA revealed that FOS supplementation reduced hepatic triglyceride accumulation through a proliferator‐activated receptor α‐stimulation of fatty acid oxidation and lessened cholesterol accumulation by inhibiting sterol regulatory element binding protein 2‐dependent cholesterol synthesis. Cultured precision‐cut liver slices confirmed the inhibition of fatty acid oxidation. FOS effects were related to a decreased hepatic micro‐RNA33 expression and to an increased colonic glucagon‐like peptide 1 production.ConclusionsThe changes in gut microbiota composition by n‐3 PUFA‐depletion and prebiotics modulate hepatic steatosis by changing gene expression in the liver, a phenomenon that could implicate micro‐RNA and gut‐derived hormones. Our data underline the advantage of targeting the gut microbiota by colonic nutrients in the management of liver disease.
Synthesis and Surface Active Properties of 1,1,1,1‐Tetra‐(2‐oxypropyl Sulfonate‐3‐alkylether‐propoxy)neopentanes
Authors: Zhou Ming , Zhong Xiang , Zhao Jinzhou , Wang Xu 
Published: December 2012

AbstractTetrameric sulfonate surfactants 1,1,1,1‐tetra‐(2‐oxypropyl sulfonate‐3‐alkylether‐propoxy)neopentanes were prepared with raw materials containing epichlorohydrin, pentaerythritol, long‐chain alcohols, 1,3‐propane sultone and sodium hydroxide by esterification, a ring opening reaction, and a sulfonation reaction. The chemical structures of the prepared compounds were confirmed by FTIR, 1H‐NMR and element analysis. With the increasing length of the carbon chain, the values of their CMC initially decreased. The longer the alkyl chain, the higher the melting point. The Krafft point of all these tetrameric sulfonate surfactants was below 0 °C and they had excellent water solubility. These compounds were superior in surface active properties to general sulfonate surfactants SDS. The efficiency of adsorption at the water/air interface (pC20) of these surfactants was very high. Their foaming properties, their wetting ability of a felt chip, and their lime‐soap dispersing ability was investigated.
TrFAST: A Tool to Predict Signaling Pathway-Specific Transcription Factor Binding Sites
Authors: Seemab Umair , Ain Qurrat ul , Nawaz Muhammad Sulaman , Saeed Zafar , Rashid Sajid 
Published: December 2012

Abstract
Recent advances in the development of high-throughput tools have significantly revolutionized our understanding of molecular mechanisms underlying normal and dysfunctional biological processes. Here we present a novel computational tool, transcription factor search and analysis tool (TrFAST), which was developed for the in silico analysis of transcription factor binding sites (TFBSs) of signaling pathway-specific TFs. TrFAST facilitates searching as well as comparative analysis of regulatory motifs through an exact pattern matching algorithm followed by the graphical representation of matched binding sites in multiple sequences up to 50 kb in length. TrFAST is proficient in reducing the number of comparisons by the exact pattern matching strategy. In contrast to the pre-existing tools that find TFBS in a single sequence, TrFAST seeks out the desired pattern in multiple sequences simultaneously. It counts the GC content within the given multiple sequence data set and assembles the combinational details of consensus sequence(s) located at these regions, thereby generating a visual display based on the abundance of unique pattern. Comparative regulatory region analysis of multiple orthologous sequences simultaneously enhances the features of TrFAST and provides a significant insight into study of conservation of non-coding cis-regulatory elements. TrFAST is freely available at http://www.fi-pk.com/trfast.html.
Musket: a multistage k-mer spectrum-based error corrector for Illumina sequence data
Authors: Liu Yongchao , Schröder Jan , Schmidt Bertil 
Published: December 2012

Abstract
Motivation: The imperfect sequence data produced by next-generation sequencing technologies have motivated the development of a number of short-read error correctors in recent years. The majority of methods focus on the correction of substitution errors, which are the dominant error source in data produced by Illumina sequencing technology. Existing tools either score high in terms of recall or precision but not consistently high in terms of both measures.
Results: In this article, we present Musket, an efficient multistage k-mer-based corrector for Illumina short-read data. We use the k-mer spectrum approach and introduce three correction techniques in a multistage workflow: two-sided conservative correction, one-sided aggressive correction and voting-based refinement. Our performance evaluation results, in terms of correction quality and de novo genome assembly measures, reveal that Musket is consistently one of the top performing correctors. In addition, Musket is multi-threaded using a master–slave model and demonstrates superior parallel scalability compared with all other evaluated correctors as well as a highly competitive overall execution time.
Availability: Musket is available at http://musket.sourceforge.net.
Contact: liuy@uni-mainz.de or bertil.schmidt@uni-mainz.de
Supplementary information: Supplementary data are available at Bioinformatics online.