bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic potential of nested PCR, galactomannan EIA, and Beta-D-glucan for invasive aspergillosis in pediatric patients
Authors: Badiee Parisa , Alborzi Abdolvahab , Karimi Mahammad , Pourabbas Bahman , Haddadi Pedram , Mardaneh Jalal , Moieni Mahsa 
Published: April 2012

Introduction: Limited specific data and investigations are available for invasive aspergillosis (IA) in pediatric patients. We evaluated the diagnostic potential of three noninvasive tests including the Platelia Aspergillus EIA kit for using galactomannan antigen, (1,3)-β-D-glucan Detection Reagent Kit, and nested-PCR for Aspergillus DNA in sera. We evaluated the diagnostic potential of three noninvasive tests including EIA for galactomannan antigen (Platelia Aspergillus), nested PCR assay for Aspergillus DNA and test for (1→3)-β-D-glucan (Glucatell assay Kit). Methodology: All pediatric patients treated at the hematology/oncology unit who were at increased risk of developing invasive aspergillosis were enrolled. Clinical samples were examined for Aspergillus infections by mycological methods. Serial blood samples were collected twice weekly and evaluated by noninvasive tests. Results: We analyzed 230 consecutive blood samples from 62 pediatric patients. The incidence rate of invasive aspergillosis in the patients was found to be 27.4%, and the etiologic agents were Aspergillus flavus, Aspergillus fumigatus, and Aspergillus spp. The sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results of galactomannan in patients with proven and probable IA were 90%, 92%, 81.8%, 96%, 11.25, and 0.1; for beta-D-glucan they were 50%, 46%, 26%, 70.6%, 0.9, 0.9; and for nested-PCR they were 80%, 96.2%, 88.9%, 92.6%, 21, and 0.2, respectively. Conclusions: The conventional methods are not able to detect IA, due to the lack of valid and proper sampling. Galactomannan and nested-PCR tests in serum, with enough accuracy and reliability, can serve as noninvasive methods for the detection of IA in pediatric patients. However, the beta-D-glucan test cannot serve as an efficient diagnostic tool in those with hematologic disorders.
Delayed Presentation of Traumatic Dislocation of a Visian Implantable Collamer Lens
Authors: Schmitz Joseph W. , McEwan Gavin C. , Hofmeister Elizabeth M. 
Published: April 2012

PURPOSE:
To report traumatic dislocation of a Visian Implantable Collamer Lens (ICL, STAAR Surgical Co) discovered on routine examination.

METHODS:
A 26-year-old man was found to have ICL subluxation into the anterior chamber with pupillary capture on routine screening examination. The patient reported being punched near the left eye 2 weeks earlier. He noted mild blurry vision, no pain, and uncorrected distance visual acuity (UDVA) was 20/30, which was decreased from his baseline of 20/20 in the affected eye.

RESULTS:

Surgical repositioning was performed under pupillary dilation without complication. Postoperatively, UDVA was 20/20
−2
. Persistent pigment on the ICL, slight pupillary margin peaking, and anterior chamber inflammation were noted.

CONCLUSIONS:
Traumatic ICL dislocation may occur with minimal signs and symptoms. Education of patients about the necessity for examination after ocular trauma and need to wear eye protection during activities at high risk of ocular trauma are important.
Recombinant Viral-Vectored Vaccines Expressing Plasmodium chabaudi AS Apical Membrane Antigen 1: Mechanisms of Vaccine-Induced Blood-Stage Protection
Authors: Biswas Sumi , Spencer Alexandra J. , Forbes Emily K. , Gilbert Sarah C. , Holder Anthony A. , Hill Adrian V. S. , Draper Simon J. 
Published: April 2012

Abstract
Apical membrane Ag 1 (AMA1) is one of the leading candidate Ags for inclusion in a subunit vaccine against blood-stage malaria. However, the efficacy of Ab-inducing recombinant AMA1 protein vaccines in phase IIa/b clinical trials remains disappointing. In this article, we describe the development of recombinant human adenovirus serotype 5 and modified vaccinia virus Ankara vectors encoding AMA1 from the Plasmodium chabaudi chabaudi strain AS. These vectors, when used in a heterologous prime-boost regimen in BALB/c mice, are capable of inducing strong transgene-specific humoral and cellular immune responses. We show that this vaccination regimen is protective against a nonlethal P. chabaudi chabaudi strain AS blood-stage challenge, resulting in reduced peak parasitemias. The role of vaccine-induced, AMA1-specific Abs and T cells in mediating the antiparasite effect was investigated by in vivo depletion of CD4+ T cells and adoptive-transfer studies into naive and immunodeficient mice. Depletion of CD4+ T cells led to a loss of vaccine-induced protection. Adoptive-transfer studies confirmed that efficacy is mediated by both CD4+ T cells and Abs functioning in the context of an intact immune system. Unlike previous studies, these results confirm that Ag-specific CD4+ T cells, induced by a clinically relevant vaccine-delivery platform, can make a significant contribution to vaccine blood-stage efficacy in the P. chabaudi model. Given that cell-mediated immunity may also contribute to parasite control in human malaria, these data support the clinical development of viral-vectored vaccines that induce both T cell and Abs against Plasmodium falciparum blood-stage malaria Ags like AMA1.
Genetic Variation at a Yin-Yang 1 Response Site Regulates the Transcription of Cyclin-Dependent Kinase Inhibitor p18INK4C Transcript in Lupus-Prone Mice
Authors: Potula Hari-Hara S. K. , Morel Laurence 
Published: April 2012

Abstract
We have previously shown that a novel −74 C-to-T mutation in the promoter of the cyclin-dependent kinase inhibitor p18Ink4c (p18) gene was associated with a reduced p18 expression in B cells from mice carrying the Sle2c1 lupus susceptibility locus. To determine the function of the −74 C/T single nucleotide polymorphism, we have characterized the proximal promoter of the mouse p18 gene. Functional analysis of the 5′ flanking region by sequential deletions revealed crucial elements between −300 and +1, confirming the in silico prediction that the −74 T allele created a novel Yin-Yang 1 (YY-1) binding site adjacent to an existing one common to both alleles. Moreover, we found that YY-1, E2F1, and Sp-1 can synergistically enhance the activity of the p18 promoter. Mutational inactivation revealed that YY-1 binding regulates the p18 activity in an allele-dependent fashion. EMSAs with splenic B cell extracts directly demonstrated that YY-1 binds to the p18 promoter with differences between the C and the T alleles. We also determined in vivo by chromatin immunoprecipitation that the T allele resulted in increased YY-1 and decreased Nrf-2 binding to the p18 promoter as compared with the C allele in B cells. Thus, YY-1 is a direct regulator of p18 gene expression in an allele-dependent fashion that is consistent with the lupus-associated T allele, inducing a lower p18 transcriptional activity by increasing YY-1 binding. These results establish the p18 −74 C/T mutation as the leading causal variant for the B1a cell expansion that characterizes the NZB and NZM2410 lupus-prone strains.
Mouse β-Defensin 14 (Defb14) Promotes Tumor Growth by Inducing Angiogenesis in a CCR6-Dependent Manner
Authors: Röhrl Johann , Huber Barbara , Koehl Gudrun E. , Geissler Edward K. , Hehlgans Thomas 
Published: April 2012

Abstract
β-defensins are known for their antimicrobial activity and belong to the molecular barrier of the innate immune system against invading pathogens. In addition, it has been shown that some members of the β-defensin superfamily have the capacity to promote local innate inflammatory and systemic adaptive immune responses, mediated in part by the interaction with CCR6. We found that mouse β-defensin 14 (mBD14, Defb14), a newly identified member of the mouse β-defensin superfamily, is expressed in mouse fibrosarcoma tumor tissue. Tumor cells overexpressing mBD14 demonstrated enhanced solid tumor growth in syngeneic C57BL/6 mice concomitant with increased vascularization of these tumors. Furthermore, mBD14-overexpressing tumors demonstrated increased expression of proangiogenic MIP-2 (CXCL2) ex vivo. In contrast, vascular endothelial growth factor expression was not affected. Cellular analysis of tumor-infiltrating leukocytes revealed a significant increase of CCR6+ B220+ lymphocytes in solid tumors derived from mBD14-overexpressing tumor cells. Enhanced tumor growth of mBD14-overexpressing fibrosarcomas was abolished in CCR6-deficient mice, which was paralleled by decreased infiltration of CCR6+ B220+ lymphocytes, indicating the requirement of CCR6 expression on host cells. Previously, the interaction of activated, LTαβ+, lymphocytes with lymphotoxin β-receptor–expressing fibrosarcoma tumor cells has been identified as a new CXCL2-dependent proangiogenic pathway. Coexpression of a soluble lymphotoxin β-receptor:Ig fusion protein, an inhibitor of CXCL2-dependent angiogenesis, in mBD14-overexpressing fibrosarcoma tumor cells abolished enhanced solid tumor growth. Thus, we conclude that mBD14 expression by tumor-infiltrating host cells results in the chemoattraction of CCR6+ B220+ lymphocytes, which in turn initiates a proangiogenic pathway leading to enhanced angiogenesis and organized tumor tissue development.
Cutting Edge: Neuronal Recognition by CD8 T Cells Elicits Central Diabetes Insipidus
Authors: Scheikl Tanja , Pignolet Béatrice , Dalard Cécile , Desbois Sabine , Raison Danièle , Yamazaki Masanori , Saoudi Abdelhadi , Bauer Jan , Lassmann Hans , Hardin-Pouzet Hélène , Liblau Roland S. 
Published: April 2012

Abstract
An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction. This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus.
New Biomarkers with Relevance to Leprosy Diagnosis Applicable in Areas Hyperendemic for Leprosy
Authors: Geluk Annemieke , Bobosha Kidist , van der Ploeg-van Schip Jolien J. , Spencer John S. , Banu Sayera , V. S. B. Martins Marcia , Cho Sang-Nae , Franken Kees L. M. C. , Kim Hee Jin , Bekele Yonas , Uddin Mohammad K. M. , Abdul Hadi Sheikh , Aseffa Abraham , Pessolani Maria C. V. , Pereira Geraldo M. B. , Dockrell Hazel M. , Ottenhoff Tom H. M. 
Published: April 2012

Abstract
Leprosy is not eradicable with currently available diagnostics or interventions, as evidenced by its stable incidence. Early diagnosis of Mycobacterium leprae infection should therefore be emphasized in leprosy research. It remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease. To identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and endemic controls (EC) from high leprosy-prevalence areas (Bangladesh, Brazil, Ethiopia) and from South Korea, where leprosy is not endemic anymore. M. leprae-sonicate–induced IFN-γ was similar for all groups, excluding M. leprae/IFN-γ as a diagnostic readout. By contrast, ML2478 and ML0840 induced high IFN-γ concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-γ could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection and transmission, in different parts of Brazilian and Ethiopian cities. Notwithstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC in one leprosy-endemic area based on IFN-γ. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1β, and IL-1β in patients compared with EC, whereas IFN-inducible protein-10, like IFN-γ, differed between EC from areas with dissimilar leprosy prevalence. This study identifies M. leprae-unique Ags, particularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-γ or IFN-inducible protein-10, and also shows that MCP-1, MIP-1β, and IL-1β can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae.
The Relative Roles of Factor H Binding Protein, Neisserial Surface Protein A, and Lipooligosaccharide Sialylation in Regulation of the Alternative Pathway of Complement on Meningococci
Authors: Lewis Lisa A. , Carter Matthew , Ram Sanjay 
Published: April 2012

Abstract
Neisseria meningitidis inhibits the alternative pathway (AP) of complement using diverse mechanisms, including expression of capsule (select serogroups), Neisserial surface protein A (NspA), factor H (fH) binding protein (fHbp), and lipooligosaccharide (LOS) sialylation. The contribution of the latter three molecules in AP regulation in encapsulated meningococci was studied using isogenic mutants. When LOS was unsialylated, deleting NspA alone from group A strain A2594 (low fHbp/high NspA) significantly increased AP-mediated C3 deposition. C3 deposition further increased ∼2-fold in a ΔfHbpΔNspA double mutant, indicating cooperative fHbp function. LOS sialylation of A2594 ΔfHbpΔNspA decreased the rate of C3 deposition, revealing AP inhibition by LOS sialic acid. Maximal C3 deposition on group B strain H44/76 (high fHbp/low NspA) occurred when all three molecules were absent; again, LOS sialylation attenuated the AP in the absence of both fHbp and NspA. When H44/76 LOS was unsialylated, both fHbp and NspA independently inhibited the AP. LOS sialylation enhanced binding of fH C-terminal domains 18–20 to C3 fragments deposited on bacteria. Interaction of meningococci with nonhuman complement is relevant for animal models and vaccine evaluation studies that use nonhuman complement. Consistent with their human-specific fH binding, neither fHbp nor NspA regulated the rat AP. However, LOS sialylation inhibited the rat AP and, as with human serum, enhanced binding of rat fH to surface-bound C3. These data highlight the cooperative roles of meningococcal NspA and fHbp in regulating the human AP and broaden the molecular basis for LOS sialylation in AP regulation on meningococci in more than one animal species.
Identification of a New Pathway for Th1 Cell Development Induced by Cooperative Stimulation with IL-4 and TGF-β
Authors: Tofukuji Soichi , Kuwahara Makoto , Suzuki Junpei , Ohara Osamu , Nakayama Toshinori , Yamashita Masakatsu 
Published: April 2012

Abstract
IL-4 plays an important role in the induction of Th2 and Th9 cells, as well as in the inhibition of Th1 cell generation. We show that a combination of IL-4 and TGF-β augments the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFN-γ is present. The T-box–containing transcription factor eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells and is involved in IFN-γ production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFN-γ gene loci. TGF-β is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6-signaling pathway. IFN-γ–producing CD103+ Th1 cells are detected in the intraepithelial lymphocytes of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. To our knowledge, these results represent the first molecular mechanism of IL-4/TGF-β–dependent augmentation of Th1 cell generation and raise the possibility that IL-4 and TGF-β simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions.
Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production
Authors: Ohtani Masashi , Hoshii Takayuki , Fujii Hideki , Koyasu Shigeo , Hirao Atsushi , Matsuda Satoshi 
Published: April 2012

Abstract
The mammalian target of rapamycin (mTOR) controls cell growth and survival through two distinct complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Although several reports have suggested the involvement of mTORC1 in development and function of dendritic cells (DCs), its physiological roles remain obscure. We therefore established mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as RaptorDC−/−). RaptorDC−/− mice exhibited cell expansion in specific subsets of DCs such as splenic CD8+ DCs and intestinal CD11c+CD11b+ DCs. We also found that impaired mTORC1 signal resulted in the suppression of IL-10 production along with enhanced CD86 expression in intestinal CD11c+CD11b+ DCs and that RaptorDC−/− mice were highly susceptible to dextran sodium sulfate-induced colitis. Our results uncover mTORC1-mediated anti-inflammatory programs in intestinal CD11c+CD11b+ DCs to limit the intestinal inflammation.
Differential Requirements for IRF-2 in Generation of CD1d-Independent T Cells Bearing NK Cell Receptors
Authors: Notake Tsuyoshi , Horisawa Shin , Sanjo Hideki , Miyagawa Shin-ichi , Hida Shigeaki , Taki Shinsuke 
Published: April 2012

Abstract
NK cell receptors (NKRs) such as NK1.1, NKG2D, and Ly49s are expressed on subsets of CD1d-independent memory phenotype CD8+ and CD4–CD8– T cells. However, the mechanism for the generation and functions of these NKR+ T cells remained elusive. In this study, we found that CD1d-independent Ly49+ T cells were reduced severely in the spleen, bone marrow, and liver, but not thymus, in mice doubly deficient for IFN regulatory factor-2 (IRF-2) and CD1d, in which the overall memory phenotype T cell population was contrastingly enlarged. Because a large fraction of Ly49+ T cells coexpressed NK1.1 or NKG2D, the reduction of Ly49+ T cells resulted indirectly in underrepresentation of NK1.1+ or NKG2D+ cells. Ly49+ T cell deficiency was observed in IRF-2−/− mice additionally lacking IFN-α/βR α-chain (IFNAR1) as severely as in IRF-2−/− mice, arguing against the involvement of the accelerated IFN-α/β signals due to IRF-2 deficiency. Rather, mice lacking IFN-α/βR alone also exhibited relatively milder Ly49+ T cell reduction, and IL-2 could expand Ly49+ T cells from IFNAR1−/−, but not from IRF-2−/−, spleen cells in vitro. These results together indicated that IRF-2 acted in Ly49+ T cell development in a manner distinct from that of IFN-α/β signals. The influence of IRF-2 deficiency on Ly49+ memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR+ T and memory phenotype T cells.
B Cell-Specific S1PR1 Deficiency Blocks Prion Dissemination between Secondary Lymphoid Organs
Authors: Mok Simon W. F. , Proia Richard L. , Brinkmann Volker , Mabbott Neil A. 
Published: April 2012

Abstract
Many prion diseases are peripherally acquired (e.g., orally or via lesions to skin or mucous membranes). After peripheral exposure, prions replicate first upon follicular dendritic cells (FDC) in the draining lymphoid tissue before infecting the brain. However, after replication upon FDC within the draining lymphoid tissue, prions are subsequently propagated to most nondraining secondary lymphoid organs (SLO), including the spleen, by a previously underdetermined mechanism. The germinal centers in which FDC are situated produce a population of B cells that can recirculate between SLO. Therefore, we reasoned that B cells were ideal candidates by which prion dissemination between SLO may occur. Sphingosine 1-phosphate receptor (S1PR)1 stimulation controls the egress of T and B cells from SLO. S1PR1 signaling blockade sequesters lymphocytes within SLO, resulting in lymphopenia in the blood and lymph. We show that, in mice treated with the S1PR modulator FTY720 or with S1PR1 deficiency restricted to B cells, the dissemination of prions from the draining lymph node to nondraining SLO is blocked. These data suggest that B cells interacting with and acquiring surface proteins from FDC and recirculating between SLO via the blood and lymph mediate the initial propagation of prions from the draining lymphoid tissue to peripheral tissues.
Extreme Version of Projectivity for Normed Modules Over Sequence Algebras
Authors: Helemskii A. Ya. 
Published: April 2012

AbstractWe define and study the so-called extreme version of the notion of a projective normed module. The relevant definition takes into account the exact value of the norm of the module in question, in contrast with the standard known definition that is formulated in terms of normtopology.After the discussion of the case where our normed algebra A is just C, we concentrate on the case of the next degree of complication, where A is a sequence algebra satisfying some natural conditions. The main results give a full characterization of extremely projective objects within the subcategory of the category of non-degenerate normed A-modules, consisting of the so-called homogeneous modules. We consider two cases, ‘non-complete’ and ‘complete’, and the respective answers turn out to be essentially different.In particular, all Banach non-degenerate homogeneous modules consisting of sequences are extremely projective within the category of Banach non-degenerate homogeneous modules. However, neither of them, provided it is infinite-dimensional, is extremely projective within the category of all normed non-degenerate homogeneous modules. On the other hand, submodules of these modules consisting of finite sequences are extremely projective within the latter category.
Quasimap Floer Cohomology for Varying Symplectic Quotients
Authors: Wilson Glen , Woodward Christopher T. 
Published: April 2012

AbstractWe show that quasimap Floer cohomology for varying symplectic quotients resolves several puzzles regarding displaceability of toric moment fibers. For example, we present a compact Hamiltonian torus action containing an open subset of non-displaceable orbits and a codimension four singular set, partly answering a question of McDuff, and we determine displaceability for most of the moment fibers of a symplectic ellipsoid.
Weak Sequential Completeness of 𝑲(X,Y)
Authors: Bu Qingying 
Published: April 2012

AbstractFor Banach spaces X and Y, we show that if X* and Y are weakly sequentially complete and every weakly compact operator from X to Y is compact, then the space of all compact operators from X to Y is weakly sequentially complete. The converse is also true if, in addition, either X* or Y has the bounded compact approximation property.