bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon Regulatory Factor 7 Contributes to the Control ofLeishmania donovaniin the Mouse Liver
Authors: Beattie Lynette , Phillips Rebecca , Brown Najmeeyah , Owens Benjamin M. J. , Chauhan Neal , Dalton Jane E. , Kaye Paul M. 
Published: December 2010

ABSTRACTOptimal hepatic resistance toLeishmania donovaniin mice requires the coordinated effort of a variety of leukocyte populations that together induce activation of local macrophages to a leishmanicidal state. Although nitric oxide and reactive oxygen intermediates are potent leishmanicidal effector molecules operating in the acquired phase of immunity, there have long been suggestions that other mechanisms of leishmanicidal activity exist. We recently discovered thatIrf-7regulates a novel innate leishmanicidal response in resident splenic macrophages that line the marginal zone. Here, we tested whether this mechanism also operates in Kupffer cells, the resident macrophage population of the liver and the major target for hepatic infection byL. donovani. Comparing the Kupffer cell responsesin situin B6 and B6.Irf-7−/−mice, we found no evidence thatIrf-7affected amastigote uptake or early survival. However, we did find thatIrf-7-deficient mice had impaired acquired resistance to hepaticL. donovaniinfection. This phenotype was attributable to a reduction in the capacity of hepatic CD4+T cells, NK cells, and NKT cells to produce gamma interferon (IFN-γ) and also to defective induction of NOS2 in infected Kupffer cells. Our data therefore add interferon regulatory factor 7 (IRF-7) to the growing list of interferon regulatory factors that have effects on downstream events in the acquired cellular immune response to nonviral pathogens.
Distinct CCR2+Gr1+Cells Control Growth of theYersinia pestisΔyopMMutant in Liver and Spleen during Systemic Plague
Authors: Ye Zhan , Uittenbogaard Annette M. , Cohen Donald A. , Kaplan Alan M. , Ambati Jayakrishna , Straley Susan C. 
Published: December 2010

ABSTRACTWe are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacteriumYersinia pestis. In this study, we pursued previous findings that Gr1+cells are required to selectively limit growth of ΔyopM Y. pestisand that CD11b+cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parentY. pestis. When PMNs were ablated from mice, ΔyopM Y. pestisgrew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestisin both organs. In spleen, the Gr1+cells differentially recruited by parent and ΔyopM Y. pestisinfections were CCR2+Gr1+CD11b+CD11cLo-IntMAC3+iNOS+(inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopMmutant was relieved by the parentY. pestisstrain in a coinfection assay in which the parent strain could affect the fate of the mutant intrans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestisto show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.
Characterization of Diverse Subvariants of the Meningococcal Factor H (fH) Binding Protein for Their Ability To Bind fH, To Mediate Serum Resistance, and To Induce Bactericidal Antibodies
Authors: Seib Kate L. , Brunelli Brunella , Brogioni Barbara , Palumbo Emmanuelle , Bambini Stefania , Muzzi Alessandro , DiMarcello Federica , Marchi Sara , van der Ende Arie , Aricó Beatrice , Savino Silvana , Scarselli Maria , Comanducci Maurizio , Rappuoli Rino , Giuliani Marzia M. , Pizza Mariagrazia 
Published: December 2010

ABSTRACTNeisseria meningitidisis a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbpstrain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.
Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation
Authors: Kurtis Jonathan D. , Higashi Ashley , Wu Hai-Wei , Gundogan Fusun , McDonald Emily A. , Sharma Surrendra , PondTor Sunthorn , Jarilla Blanca , Sagliba Marriane Joy , Gonzal Analisa , Olveda Remigio , Acosta Luz , Friedman Jennifer F. 
Published: December 2010

ABSTRACTSchistosomes infect ∼40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial inSchistosoma mansonidid not detect this association. We conducted an observational study among 99 pregnant women living in an area ofSchistosoma japonicumendemicity in the Philippines. We enrolled women at 32 weeks gestation and measuredS. japonicumand geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (allP< 0.05). After adjusting for confounders, placental IL-1β, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (bothP< 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.
The Tetraspanin CD82 Is Specifically Recruited to Fungal and Bacterial Phagosomes prior to Acidification
Authors: Artavanis-Tsakonas Katerina , Kasperkovitz Pia V. , Papa Eliseo , Cardenas Michael L. , Khan Nida S. , Van der Veen Annemarthe G. , Ploegh Hidde L. , Vyas Jatin M. 
Published: December 2010

ABSTRACTCD82 is a member of the tetraspanin superfamily, whose physiological role is best described in the context of cancer metastasis. However, CD82 also associates with components of the class II major histocompatibility complex (MHC) antigen presentation pathway, including class II MHC molecules and the peptide-loading machinery, as well as CD63, another tetraspanin, suggesting a role for CD82 in antigen presentation. Here, we observe the dynamic rearrangement of CD82 after pathogen uptake by imaging CD82-mRFP1 expressed in primary living dendritic cells. CD82 showed rapid and specific recruitment toCryptococcus neoformans-containing phagosomes compared to polystyrene-containing phagosomes, similar to CD63. CD82 was also actively recruited to phagosomes containing other pathogenic fungi, includingCandida albicansandAspergillus fumigatus. Recruitment of CD82 to fungal phagosomes occurred independently of Toll-like receptor (TLR) signaling. Recruitment was not limited to fungi, as bacterial organisms, includingEscherichia coliandStaphylococcus aureus, also induced CD82 recruitment to the phagosome. CD82 intersected the endocytic pathway used by lipopolysaccharide (LPS), implicating CD82 in trafficking of small, pathogen-associated molecules. Despite its partial overlap with lysosomal compartments, CD82 recruitment toC. neoformans-containing phagosomes occurred independently of phagosome acidification. Kinetic analysis of fluorescence imaging revealed that CD82 and class II MHC simultaneously appear in the phagosome, indicating that the two proteins may be associated. Together, these data show that the CD82 tetraspanin is specifically recruited to pathogen-containing phagosomes prior to fusion with lysosomes.
Cholera Toxin Impairs the Differentiation of Monocytes into Dendritic Cells, Inducing Professional Antigen-Presenting Myeloid Cells
Authors: Veglia Filippo , Sciaraffia Ester , Riccomi Antonella , Pinto Dora , Negri Donatella R. M. , De Magistris Maria Teresa , Vendetti Silvia 
Published: December 2010

ABSTRACTCholera toxin (CT) is a potent adjuvant for mucosal vaccination; however, its mechanism of action has not been clarified completely. It is well established that peripheral monocytes differentiate into dendritic cells (DCs) bothin vitroandin vivoand that monocytes are thein vivoprecursors of mucosal CD103−proinflammatory DCs. In this study, we asked whether CT had any effects on the differentiation of monocytes into DCs. We found that CT-treated monocytes, in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), failed to differentiate into classical DCs (CD14lowCD1ahigh) and acquired a macrophage-like phenotype (CD14highCD1alow). Cells differentiated in the presence of CT expressed high levels of major histocompatibility complex class I (MHC-I) and MHC-II and CD80 and CD86 costimulatory molecules and produced larger amounts of IL-1β, IL-6, and IL-10 but smaller amounts of tumor necrosis factor alpha (TNF-α) and IL-12 than did monocytes differentiated into DCs in the absence of CT. The enzymatic activity of CT was found to be important for the skewing of monocytes toward a macrophage-like phenotype (Ma-DCs) with enhanced antigen-presenting functions. Indeed, treatment of monocytes with scalar doses of forskolin (FSK), an activator of adenylate cyclase, induced them to differentiate in a dose-dependent manner into a population with phenotype and functions similar to those found after CT treatment. Monocytes differentiated in the presence of CT induced the differentiation of naïve T lymphocytes toward a Th2 phenotype. Interestingly, we found that CT interferes with the differentiation of monocytes into DCsin vivoand promotes the induction of activated antigen-presenting cells (APCs) following systemic immunization.
Spinal injury in car crashes: crash factors and the effects of occupant age
Authors: Bilston Lynne E , Clarke Elizabeth C , Brown Julie 
Published: December 2010

ObjectiveMotor vehicle crashes are the leading cause of serious spinal injury in most developed nations. However, since these injuries are rare, systematic analyses of the crash factors that are predictive of spinal injury have rarely been performed. This study aimed to use a population-reference crash sample to identify crash factors associated with moderate to severe spinal injury, and how these vary with occupant age.MethodsThe US National Automotive Sampling System Crashworthiness Data System (NASS) data for 1993–2007 were analysed using logistic regression to identify crash factors associated with Abbreviated Injury Scale (AIS)2+ spinal injury among restrained vehicle passengers.ResultsRisk of moderate or severe spinal injury (AIS2+) was associated with higher severity crashes (OR=3.5 (95% CI 2.6 to 4.6)), intrusion into an occupant's seating position (OR=2.7 (95% CI 1.9 to 3.7)), striking a fixed object rather than another car (OR=1.7 (95% CI 1.3 to 2.1)), and use of a shoulder-only belt (OR=2.7 (95% CI 1.5 to 4.8)). Older occupants (65 years or older) were at higher risk of spinal injury than younger adults in frontal, side and rollover crashes. Children under 16 were at a lower risk of spinal injury than adults in all crash types except frontal crashes.ConclusionsWhile the risk of serious spinal injury in motor vehicle crashes is low, these injuries are more common in crashes of higher severity or into fixed objects, and in the presence of intrusion. There are elevated risks of spinal injury for older occupants compared with younger adults, which may reflect changes in biomechanical tolerances with age. Children appear to be at lower risk of serious spinal injury than adults except in frontal crashes.
ON THE ALGEBRAIC HOLONOMY OF STABLE PRINCIPAL BUNDLES
Authors: BISWAS INDRANIL 
Published: December 2010

Let EGbe a stable principal G–bundle over a compact connected Kähler manifold, where G is a connected reductive linear algebraic group defined over ℂ. Let H ⊂ G be a complex reductive subgroup which is not necessarily connected, and let EH⊂ EGbe a holomorphic reduction of structure group to H. We prove that EHis preserved by the Einstein–Hermitian connection on EG. Using this we show that if EHis a minimal reductive reduction (which means that there is no complex reductive proper subgroup of H to which EHadmits a holomorphic reduction of structure group), then EHis unique in the following sense: For any other minimal reduction of structure group (H′, EH′) of EGto some reductive subgroup H′, there is some element g ∈ G such that H′ = g-1Hg and EH′= EHg. As an application, we show the following:Let M be a simply connected, irreducible smooth complex projective variety of dimension n such that the Picard number of M is one. If the canonical line bundle KMis ample, then the algebraic holonomy of the holomorphic tangent bundle T1, 0M is GL (n, ℂ). If [Formula: see text] is ample, the rank of the Picard group of M is one, the biholomorphic automorphism group of M is finite, and M admits a Kähler–Einstein metric, then the algebraic holonomy of T1, 0M is GL (n, ℂ).These answer some questions posed in V. Balaji and J. Kollár, Publ. Res. Inst. Math. Sci.44 (2008) 183–211.
The use of NEXTMap Britain for geological surveying in the Vale of York
Authors: Hall M. , Cooper A. H. , Ford J. , Price S. , Burke H. 
Published: December 2010

Abstract
The NEXTMap Britain digital elevation model (DEM) has opened many new opportunities that considerably help and enhance the way we undertake our geological mapping of bedrock, structure, and superficial and artificial deposits. The dataset has been successfully integrated into the digital and conventional mapping workflows of the Vale of York mapping team.
A variety of visualization and analysis techniques have been applied throughout the mapping process. These techniques include an initial appraisal of NEXTMap with a comparison to existing geological mapping to define the field mapping strategy and site-specific manipulation using Tablet PCs.
NEXTMap interpretation has made an important contribution to the understanding of the extensive glacial and proglacial deposits found in the Vale of York; such as sand bodies resting on lake deposits, and identifying details within morainic and alluvial complexes. For bedrock mapping, NEXTMap has been used to identify landform features that relate to the underlying geology, such as breaks in slope, the extent of escarpments, hillcrests and dip slopes, to provide an overview of the landscape and to save time in mapping out features in the field. Techniques have also been developed to automatically generate these landform features.
The dataset has also been used to identify areas where landsliding has occurred, for the accurate mapping of artificial ground and as a key surface for three-dimensional (3D) geological modelling.
Clustering lines in high-dimensional space
Authors: Gao Jie , Langberg Michael , Schulman Leonard J. 
Published: December 2010

A set of
k
balls
B
1
, …,
B

k

in a Euclidean space is said to cover a collection of lines if every line intersects some ball. We consider the
k
-
center problem for lines
in high-dimensional space: Given a set of
n
lines

l

= {
l
1
,…,
l

n

in R
d
, find
k
balls of minimum radius which cover
l
. We present a 2-approximation algorithm for the cases
k
= 2, 3 of this problem, having running time quasi-linear in the number of lines and the dimension of the ambient space.

Our result for 3-clustering is strongly based on a new result in discrete geometry that may be of independent interest: a Helly-type theorem for collections of axis-parallel “crosses” in the plane. The family of crosses does not have finite Helly number in the usual sense. Our Helly theorem is of a new type: it depends on ε-contracting the sets.
In statistical practice, data is often incompletely specified; we consider lines as the most elementary case of incompletely specified data points. Clustering of data is a key primitive in nonparametric statistics. Our results provide a way of performing this primitive on incomplete data, as well as imputing the missing values.
Relation between Fixed Point and Asymptotical Center of Nonexpansive Maps
Authors: Haddadi MohammadReza , Mazaheri Hamid , Ghasemi MohammadHusseinLabbaf 
Published: December 2010

AbstractWe introduce the concept of asymptotic center of maps and consider relation between asymptotic center and fixed point of nonexpansive maps in a Banach space.
Behavioral/Lifestyle and Immunologic Factors Associated with HPV Infection among Women Older Than 45 Years
Authors: González Paula , Hildesheim Allan , Rodríguez Ana Cecilia , Schiffman Mark , Porras Carolina , Wacholder Sholom , Piñeres Alfonso García , Pinto Ligia A. , Burk Robert D. , Herrero Rolando 
Published: December 2010

AbstractBackground: Cervical human papilloma virus (HPV) detection increases after menopause, but its determinants need clarification.Methods: In a case–control study nested within a 10,049 women cohort, we evaluated women 45 to 75 years old who acquired HPV infection and were HPV positive 5 to 6 years after enrollment (N = 252), and HPV-negative women as matched controls (N = 265). Detailed sexual behavior and cellular immune response were investigated. Odds ratios (OR) and attributable fractions were estimated.Results: Women with 2+ lifetime partners had 1.7-fold (95% CI = 1.1–2.7) higher risk than monogamous women, with similar findings if their partners had other partners. Women with 2+ partners after last HPV-negative result had the highest risk (OR = 3.9; 95% CI = 1.2–12.4 compared with 0–1 partners). Weaker immune response to HPV-16 virus-like particles increased risk (OR = 1.7; 95% CI = 1.1–2.7 comparing lowest to highest tertile). Among women with no sexual activity in the period before HPV appearance, reduced immune response to phytohemagglutinin was the only determinant (OR = 2.9; 95% CI = 0.94–8.8). Twenty-one percent of infections were explained by recent sexual behavior, 21% by past sexual behavior, and 12% by reduced immune response.Conclusions: New infections among older women may result from sexual activity of women and/or their partners or reappearance of past (latent) infections possibly related to weakened immune response.Impact: HPV infections among older women are associated with current and past sexual exposures and possibly with immune senescence. The risk of cancer from these infections is likely to be low but could not be fully evaluated in the context of this study. Cancer Epidemiol Biomarkers Prev; 19(12); 3044–54. ©2010 AACR.
Urine Menthol as a Biomarker of Mentholated Cigarette Smoking
Authors: Benowitz Neal L. , Dains Katherine M. , Dempsey Delia , Havel Christopher , Wilson Margaret , Jacob Peyton 
Published: December 2010

AbstractObjectives: Menthol cigarettes are smoked by 27% of U.S. smokers, and there are concerns that menthol might enhance toxicity of cigarette smoking by increasing systemic absorption of smoke toxins. We measured urine menthol concentrations in relation to biomarkers of exposure to nicotine and tobacco carcinogens.Methods: Concentrations of menthol glucuronide (using a novel analytical method), nicotine plus metabolites (nicotine equivalents, NE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and polycyclic aromatic hydrocarbon (PAH) metabolites were measured in the urine of 60 menthol and 67 regular cigarette smokers.Results: Urine menthol was measurable in 82% of menthol and 54% in regular cigarette smokers. Among menthol smokers, urine menthol was highly correlated with NE, NNAL, and PAHs. In a multiple regression model NE but not menthol was significantly associated with NNAL and PAHs.Conclusions: Urine menthol concentration is a novel biomarker of exposure in menthol cigarette smokers, and is highly correlated with exposure to nicotine and carcinogens. Menthol is not independently associated with carcinogen exposure when nicotine intake is considered. Cancer Epidemiol Biomarkers Prev; 19(12); 3013–9. ©2010 AACR.