bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential mechanisms for anisotropy in ice-penetrating radar data
Authors: Drews R. , Eisen O. , Steinhage D. , Weikusat I. , Kipfstuhl S. , Wilhelms F. 
Published: May 2012

AbstractRadar data (center frequency 150 MHz) collected on the Antarctic plateau near the EPICA deep-drilling site in Dronning Maud Land vary systematically in backscattered power, depending on the azimuth antenna orientation. Backscatter extrema are aligned with the principal directions of surface strain rates and change with depth. In the upper 900m, backscatter is strongest when the antenna polarization is aligned in the direction of maximal compression, while below 900 m the maxima shift by 90° pointing towards the lateral flow dilatation. We investigate the backscatter from elongated air bubbles and a vertically varying crystal-orientation fabric (COF) using different scattering models in combination with ice-core data. We hypothesize that short-scale variations in COF are the primary mechanism for the observed anisotropy, and the 900 m boundary between the two regimes is caused by ice with varying impurity content. Observations of this kind allow the deduction of COF variations with depth and are potentially also suited to map the transition between Holocene and glacial ice.
Theoretical Ab initio and Density Functional Study of the Hydrogen Bonding Nature Between the Pyridine-nitrogenic Base Pairs
Authors: Al-anber M. J. 
Published: May 2012

The pyridine interact with two nitrogenic bases (adenine and uracil) so that they may cause a significant point mutation. The results of theoretical ab initio study on the hydrogen bonding energies of pyridine with the adenine and uracil are reported. The geometries of the local minima for all suggested cases were optimized with Restricted Hartree-Fock RHF/cc-pVDZ and then density functional B3LYP/cc-pVDZ. The geometrical parameters, relative stability, interaction energies and nature of hydrogen bonding energy are reported. Also, focus on the range of the hydrogen bonding energy and the flexibility of the rotation angle in the P:A¹ base pair have been investigated. Additionally, the influence of the hydrogen bonding energy with the dihedral angle between the two planes of the adenine and the pyridine in the P:A¹ pair are studied. The pyridine with the adenine and uracil may be classified as multi-point mutation. In general, enzymes may have three mechanisms to recorrect the errors in the DNA and the RNA. Keywords: Ab initio; Density funtional theory; Mutating; Pyridine ; DNA. © 2012 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v4i2.8721 J. Sci. Res. 4 (2), 419-425 (2012)
Nanoencapsulation of Nisin and Ethylenediaminetetraacetic Acid in Niosomes and Their Antibacterial Activity
Authors: Kopermsub P. , Mayen V. , Warin C. 
Published: May 2012

Ethylenediaminetetraacetic acid or EDTA was used complementarily with nisin to give a synergistic antibacterial effect against Gram positive and negative bacteria. Nisin and EDTA were encapsulated in nonionic surfactant vesicles or niosomes. Sorbitan monooleate and polyethylene glycol were precursors in preparation of niosomes. Size reduction of niosomes was conducted via extrusion through polycarbonate membrane with pore size of 200 nm. Diameters of prepared blank niosomes and nisin-EDTA-encapsulated niosomes were approximately 130 nm and 270 nm, respectively. Bilayer structure of niosomes was observed from negative staining-transmission electron microscopic images. Long-termed investigation of antimicrobial activity of nisin-EDTA-encapsulated niosomes and free nisin/EDTA were conducted against Staphylococcus aureus and Escherichia coli. Bacterial counts denoted a slow release of nisin-EDTA-encapsulated niosomes overtime whilst free nisin/EDTA gave a sudden bactericidal activity. Due to that free nisin/EDTA was immediately exploited at the beginning, bacterial counts then tended towards higher during the latter time of antimicrobial activity test. Keywords: antibacterial; EDTA; Escherichia coli; niosomes; nisin; Staphylococcus aureus. © 2012 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v4i2.9407 J. Sci. Res. 4 (2), 457-465 (2012)
Association of Partner Status and Disposition With Rehospitalization in Heart Failure Patients
Authors: Howie-Esquivel Jill , Spicer Joan Gygax 
Published: May 2012

Background
Sociodemographic variables that are predictors of rehospitalization for heart failure may better inform hospital discharge strategies.

Objectives
(1) To determine whether sociodemographic variables are predictors of hospital readmission, (2) to determine whether sociodemographic or laboratory variables differ by age group as predictors of readmission, and (3) to compare whether patients’ discharge disposition differs by age group in predicting readmission.

Methods
Retrospective chart review of hospitalized patients with heart failure admitted in 2007.

Results
Mean age was 68 (SD, 17) years for the 809 patients, with slightly more than one-third (n = 311, 38%) reporting a legal partner. Fewer than half (n = 359, 44%) were white. Almost one-third (n = 261, 32%) were rehospitalized within 90 days. Multivariable analysis revealed that patients younger than 65 years old and not partnered were at 1.8 times greater risk for being readmitted 90 days after discharge (P = .02; 95% CI, 0.33–0.92). Patients who were 65 years and older and not partnered were at 2.2 times greater risk for readmission (P = .01; 95% CI, 0.25–0.85) after creatinine level and discharge disposition were controlled for. For older patients discharged to home or to home with home services, the risk of readmission was 2.6 times greater than that for patients discharged to a skilled nursing facility (P = .02; 95% CI, 1.20–5.56).

Conclusions
The absence of a partner was predictive of readmission in all patients. Older patients with heart failure who were discharged to a skilled nursing facility had lower readmission rates. The effect of partner and disposition status may suggest a proxy for social support. Strategies to provide social support during discharge planning may have an effect on hospital readmission rates.
The Size of the Plasmacytoid Dendritic Cell Compartment Is a Multigenic Trait Dominated by a Locus on Mouse Chromosome 7
Authors: Pelletier Adam-Nicolas , Guimont-Desrochers Fanny , Ashton Michelle P. , Brodnicki Thomas C. , Lesage Sylvie 
Published: May 2012

Abstract
Plasmacytoid dendritic cells (pDC) compose one of the many distinct dendritic cell subsets. The primary function of pDC is to potently produce type 1 IFNs upon stimulation, which is highly relevant in antiviral responses. Consequently, the ability to manipulate the size of the pDC compartment in vivo may increase the capacity to clear viral infections. In an attempt to identify genetic loci affecting the size of the pDC compartment, defined by both the proportion and absolute number of pDC, we undertook an unbiased genetic approach. Linkage analysis using inbred mouse strains identified a locus on chromosome 7 (Pdcc1) significantly linked to both the proportion and the absolute number of pDC in the spleen. Moreover, loci on either chromosome 11 (Pdcc2) or 9 (Pdcc3) modified the effect of Pdcc1 on chromosome 7 for the proportion and absolute number of pDC, respectively. Further analysis using mice congenic for chromosome 7 confirmed Pdcc1, demonstrating that variation within this genetic interval can regulate the size of the pDC compartment. Finally, mixed bone marrow chimera experiments showed that both the proportion and the absolute number of pDC are regulated by cell-intrinsic hematopoietic factors. Our findings highlight the multigenic regulation of the size of the pDC compartment and will facilitate the identification of genes linked to this trait.
TRPV1 Deletion Enhances Local Inflammation and Accelerates the Onset of Systemic Inflammatory Response Syndrome
Authors: Fernandes Elizabeth S. , Liang Lihuan , Smillie Sarah-Jane , Kaiser Frank , Purcell Robert , Rivett Damian W. , Alam Saydul , Howat Sarah , Collins Helen , Thompson Stephen J. , Keeble Julie E. , Riffo-Vasquez Yanira , Bruce Kenneth D. , Brain Susan D. 
Published: May 2012

Abstract
The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK1-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.
Essential Role of IL-4 and IL-4Rα Interaction in Adaptive Immunity of Zebrafish: Insight into the Origin of Th2-like Regulatory Mechanism in Ancient Vertebrates
Authors: Zhu Lv-yun , Pan Ping-ping , Fang Wei , Shao Jian-zhong , Xiang Li-xin 
Published: May 2012

Abstract
The roles of IL-4 and IL-4Rα in Th2-mediated immunity have been well characterized in humans and other mammals. In contrast, few reports have been documented in ancient vertebrates. Several putative IL-4– and IL-4Rα–like molecules were identified recently from a few fish species, providing preliminary insight into the occurrence of Th2-type immunity in teleosts. However, functional determination still is required to address this hypothesis. To this end, these two molecules were characterized functionally in zebrafish (Danio rerio). Besides the identification of a full-length IL-4Rα molecule and an isoform lacking most of the cytoplasmic region as predicted previously, two novel alternatively spliced soluble variants with the extracellular domain only also were identified. Zebrafish IL-4Rα (DrIL-4Rα) shared overall conserved structural features of the IL-4Rα family. Immunofluorescence staining showed that DrIL-4Rα distributed on B cells. In vitro binding assays demonstrated that zebrafish IL-4 (DrIL-4) can bind specifically to DrIL-4Rα. In vivo administration of DrIL-4 significantly upregulated B cell proliferation and Ab production. These DrIL-4–elicited immune responses were downregulated by the administration of zebrafish soluble IL-4Rα or by DrIL-4Rα blockade using anti–DrIL-4Rα Abs. In addition, Th2-related cytokines or transcription factors were upregulated by DrIL-4. The DrIL-4–DrIL-4Rα interaction promoted CD40 expression on B cells and enhanced the CD154–CD40 costimulatory response, both of which are crucial for the initiation of Th2-type immunity. To our knowledge, this is the first report showing that a possible Th2-mediated regulatory mechanism may have appeared before the divergence of teleosts and mammals. These results add greater insight into the evolutionary history of adaptive immunity.
Altered Ig Hypermutation Pattern and Frequency in Complementary Mouse Models of DNA Polymerase ζ Activity
Authors: Daly Janssen , Bebenek Katarzyna , Watt Danielle L. , Richter Kathleen , Jiang Chuancang , Zhao Ming-Lang , Ray Madhumita , McGregor W. Glenn , Kunkel Thomas A. , Diaz Marilyn 
Published: May 2012

Abstract
To test the hypothesis that DNA polymerase ζ participates in Ig hypermutation, we generated two mouse models of Pol ζ function: a B cell-specific conditional knockout and a knock-in strain with a Pol ζ mutagenesis-enhancing mutation. Pol ζ-deficient B cells had a reduction in mutation frequency at Ig loci in the spleen and in Peyer’s patches, whereas knock-in mice with a mutagenic Pol ζ displayed a marked increase in mutation frequency in Peyer’s patches, revealing a pattern that was similar to mutations in yeast strains with a homologous mutation in the gene encoding the catalytic subunit of Pol ζ. Combined, these data are best explained by a direct role for DNA polymerase ζ in Ig hypermutation.
IL-10+CTLA-4+ Th2 Inhibitory Cells Form in a Foxp3-Independent, IL-2–Dependent Manner from Th2 Effectors during Chronic Inflammation
Authors: Altin John A. , Goodnow Chris C. , Cook Matthew C. 
Published: May 2012

Abstract
Activated Th cells influence other T cells via positive feedback circuits that expand and polarize particular types of response, but little is known about how they may also initiate negative feedback against immunopathological reactions. In this study, we demonstrate the emergence, during chronic inflammation, of GATA-3+ Th2 inhibitory (Th2i) cells that express high levels of inhibitory proteins including IL-10, CTLA-4, and granzyme B, but do so independently of Foxp3. Whereas other Th2 effectors promote proliferation and IL-4 production by naive T cells, Th2i cells suppress proliferation and IL-4 production. We show that Th2i cells develop directly from Th2 effectors, in a manner that can be promoted by effector cytokines including IL-2, IL-10, and IL-21 ex vivo and that requires T cell activation through CD28, Card11, and IL-2 in vivo. Formation of Th2i cells may act as an inbuilt activation-induced feedback inhibition mechanism against excessive or chronic Th2 responses.
Dectin-1 Stimulation Induces Suppressor of Cytokine Signaling 1, Thereby Modulating TLR Signaling and T Cell Responses
Authors: Eberle Mariel E. , Dalpke Alexander H. 
Published: May 2012

Abstract
Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be induced by the non-TLR pattern recognition receptor Dectin-1 in murine bone marrow-derived dendritic cells and macrophages (BMMs). The C-type lectin Dectin-1 binds to yeasts and signals either in an autonomous manner or can be triggered in combination with TLRs. In our study, SOCS1 was expressed independently of any TLR engagement as a direct target gene of the Dectin-1 ligand Zymosan. Induction of SOCS1 was mediated by a novel pathway encompassing the tyrosine kinases Src and Syk that activated the downstream kinase proline-rich tyrosine kinase 2. Proline-rich tyrosine kinase 2, in turn, caused activation of the MAPK ERK, thereby triggering SOCS1 induction. SOCS1 did not modulate Dectin-1 signaling but affected TLR signaling, leading to decreased and abbreviated NF-κB activation in BMMs triggered by TLR9. Furthermore, IL-12 and IL-10 secretion were inhibited by SOCS1. We additionally observed that IL-17–producing Th cells were clearly increased by SOCS1 in BMMs. Our results show that SOCS1 is expressed via a new, NF-κB–independent pathway in Dectin-1–triggered murine BMMs and influences TLR cross talk and T cell priming.
Cyr61 Induces IL-6 Production by Fibroblast-like Synoviocytes Promoting Th17 Differentiation in Rheumatoid Arthritis
Authors: Lin Jinpiao , Zhou Zhou , Huo Rongfen , Xiao Lianbo , Ouyang Guilin , Wang Li , Sun Yue , Shen Baihua , Li Dangsheng , Li Ningli 
Published: May 2012

Abstract
Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17–dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvβ5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4+ T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.
Wnt5a Induces a Tolerogenic Phenotype of Macrophages in Sepsis and Breast Cancer Patients
Authors: Bergenfelz Caroline , Medrek Catharina , Ekström Elin , Jirström Karin , Janols Helena , Wullt Marlene , Bredberg Anders , Leandersson Karin 
Published: May 2012

Abstract
A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, Gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163+ anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy.
Defining GM-CSF– and Macrophage-CSF–Dependent Macrophage Responses by In Vitro Models
Authors: Lacey Derek C. , Achuthan Adrian , Fleetwood Andrew J. , Dinh Hang , Roiniotis John , Scholz Glen M. , Chang Melody W. , Beckman Sandra K. , Cook Andrew D. , Hamilton John A. 
Published: May 2012

Abstract
GM-CSF and M-CSF (CSF-1) induce different phenotypic changes in macrophage lineage populations. The nature, extent, and generality of these differences were assessed by comparing the responses to these CSFs, either alone or in combination, in various human and murine macrophage lineage populations. The differences between the respective global gene expression profiles of macrophages, derived from human monocytes by GM-CSF or M-CSF, were compared with the differences between the respective profiles for macrophages, derived from murine bone marrow cells by each CSF. Only 17% of genes regulated differently by these CSFs were common across the species. Whether a particular change in relative gene expression is by direct action of a CSF can be confounded by endogenous mediators, such as type I IFN, IL-10, and activin A. Time-dependent differences in cytokine gene expression were noted in human monocytes treated with the CSFs; in this system, GM-CSF induced a more dramatic expression of IFN-regulated factor 4 (IRF4) than of IRF5, whereas M-CSF induced IRF5 but not IRF4. In the presence of both CSFs, some evidence of “competition” at the level of gene expression was observed. Care needs to be exercised when drawing definitive conclusions from a particular in vitro system about the roles of GM-CSF and M-CSF in macrophage lineage biology.
CD40 Stimulates a “Feed-Forward” NF-κB–Driven Molecular Pathway That Regulates IFN-β Expression in Carcinoma Cells
Authors: Moschonas Aristides , Ioannou Marina , Eliopoulos Aristides G. 
Published: May 2012

Abstract
IFN-β and the CD40L (CD154) share important roles in the antiviral and antitumor immune responses. In this study, we show that CD40 receptor occupancy results in IFN-β upregulation through an unconventional “feed-forward” mechanism, which is orchestrated by canonical NF-κB and involves the sequential de novo synthesis of IFN regulatory factor (IRF)1 and Viperin (RSAD2), an IRF1 target. RelA (p65) NF-κB, IRF1, and Viperin-dependent IRF7 binding to the IFN-β promoter largely controls its activity. However, full activation of IFN-β also requires the parallel engagement of noncanonical NF-κB2 signaling leading to p52 recruitment to the IFN-β promoter. These data define a novel link between CD40 signaling and IFN-β expression and provide a telling example of how signal propagation can be exploited to ensure efficient regulation of gene expression.
NLRC4 Inflammasome-Mediated Production of IL-1β Modulates Mucosal Immunity in the Lung against Gram-Negative Bacterial Infection
Authors: Cai Shanshan , Batra Sanjay , Wakamatsu Nobuko , Pacher Pal , Jeyaseelan Samithamby 
Published: May 2012

Abstract
Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a nonflagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the flagellin-deficient fliC strain of P. aeruginosa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary P. aeruginosa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all P. aeruginosa studies, IL-1β production was attenuated in NLRC4−/− mice; however, the role of IL-1β in NLRC4-mediated innate immunity in the lungs against a nonflagellated bacterium was not explored. In this article, we report that NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. NLRC4 is essential for K. pneumoniae-induced production of IL-1β, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs. NLRC4 signaling in hematopoietic cells contributes to K. pneumoniae-induced lung inflammation. Furthermore, exogenous IL-1β, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation, and cytokine/chemokine expression in the lungs of NLRC4−/− mice following infectious challenge. Furthermore, IL-1R1−/− mice displayed a decrease in neutrophilic inflammation in the lungs postinfection. Taken together, these findings provide novel insights into the role of NLRC4 in host defense against K. pneumoniae infection.