bluuebunny/crossref_metadata_2025_split huggingface dataset:
African Home Associations in Britain: Between Political Belonging and Moral Conviviality
Authors: Mercer Claire , Page Ben 
Published: July 2010

AbstractThis paper argues that significant analytical and political possibilities for thinking about the African diaspora in Britain are opened up by shifting the analytical lens from ethnicity to place. Drawing on recent research with Cameroonian and Tanzanian home associations in Britain we suggest that the concept of a ‘progressive politics of place’, which distinguishes between ‘political belonging’ and ‘moral conviviality’, can help us to explore the morality of convivial relations in the African diaspora. We highlight the ways in which home associations provide space for debate about what is an intrinsically good way to live together in the diaspora. However, if moral conviviality is about debating the right and wrong ways of living together in a place, then we need to think explicitly about the places inhabited by the diaspora. The paper addresses the ways in which home associations provide a space not only for debate among members, but also a forum for debating how to live in Britain.
The life span of short-lived plasma cells is partly determined by a block on activation of apoptotic caspases acting in combination with endoplasmic reticulum stress
Authors: Auner Holger W. , Beham-Schmid Christine , Dillon Niall , Sabbattini Pierangela 
Published: July 2010

AbstractApoptosis of short-lived plasma cells after a few days of intense immunoglobulin secretion is critical for maintaining a controlled humoral immune response. The mechanisms that regulate this process are poorly understood. Here we report that the key apoptotic caspases, caspase-3 and caspase-9, become resistant to activation by apoptotic stimuli when B cells differentiate into short-lived plasma cells. As a consequence, apoptosis of most short-lived plasma cells in vitro and in vivo is effector caspase-independent. We also show that a triaspartic acid repeat that normally prevents activation of caspase-3 becomes stabilized in short-lived plasma cells and myeloma cell lines. The block on caspase activation occurs before the accumulation of intracellular immunoglobulins and a progressive rise in secretory stress in the endoplasmic reticulum (ER). Plasma cells show increased susceptibility to ER stress–induced apoptosis and activate the ER-associated caspase-12, which is required specifically for nuclear apoptotic events. In nonlymphoid cells that cannot activate effector caspases, programmed cell death is delayed in response to ER stress. These observations suggest that the block on activation of key apoptotic caspases has evolved in short-lived plasma cells to prolong survival under conditions of ER stress resulting from high-level immunoglobulin secretion.
Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma
Authors: Görgün Güllü , Calabrese Elisabetta , Soydan Ender , Hideshima Teru , Perrone Giulia , Bandi Madhavi , Cirstea Diana , Santo Loredana , Hu Yiguo , Tai Yu-Tzu , Nahar Sabikun , Mimura Naoya , Fabre Claire , Raje Noopur , Munshi Nikhil , Richardson Paul , Anderson Kenneth C. 
Published: July 2010

AbstractThe bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferonγ, and IL-6 regulator suppressor of cytokine signaling (SOCS)1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1 expression in effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression. SOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing–MM cells than unmodified MM cells. These data therefore demonstrate that modulation of SOCS1 may enhance immune response and efficacy of IMiDs in MM.
Regional ventilation distribution in the first 6 months of life
Authors: Pham T.M.T. , Yuill M. , Dakin C. , Schibler A. 
Published: July 2010

Electrical impedance tomography (EIT) has been used to study regional ventilation distribution in neonatal and paediatric lung disease; however, little information has been obtained in healthy newborns and infants.Data on regional ventilation distribution and regional filling characteristics were obtained using EIT in the neonatal period, at 3 and 6 months of age, in spontaneously breathing infants during non-rapid eye movement sleep. Regional ventilation distribution was described using regional end-expiratory and end-inspiratory impedance amplitudes, and geometric centre of ventilation. Regional filling characteristics were described with the phase lag or lead of the regional impedance change in comparison to global impedance change.32 infants were measured in the supine position. Regional impedance amplitudes increased with age but regional ventilation distribution remained unchanged in all infants at any age, with the dependent (posterior) lung always better ventilated. Regional filling characteristics showed that the dependent lung filled during inspiration before the nondependent lung during all follow-up measurements.Regional ventilation distribution and regional filling characteristics remained unchanged over the first 6 months of life, and the results obtained on regional ventilation distribution are very similar to those in adult subjects.
Host defence duringKlebsiellapneumonia relies on haematopoietic-expressed Toll-like receptors 4 and 2
Authors: Wieland C.W. , van Lieshout M.H.P. , Hoogendijk A.J. , van der Poll T. 
Published: July 2010

In this study, the relative roles of Toll-like receptor (TLR)2 and TLR4 were investigated independently and together. Moreover, we studied the role of haematopoietic compartment in anti-Klebsiellahost defence.We infected TLR2 and TLR4 single-, and TLR2×4 double knockout (KO) animals with different doses ofKlebsiella pneumoniae. In addition, bone marrow chimeric mice were created and infected.TLR4 played a more prominent role in antibacterial defence than TLR2, considering that only TLR4 KO mice demonstrated enhanced bacterial growth in lungs and spleen 24 h after infection with 3×103colony-forming units ofKlebsiellacompared with wild-type (WT) mice. In late-stage infection or after exposure to a higher infectious dose, bacterial counts in lungs of TLR2 KO animals were elevated compared with WT mice and TLR2×4 KO animals were more susceptible to infection than TLR4 KO mice. TLR signalling in cells of haematopoietic origin is of primary importance in host defence againstK. pneumoniae.These data suggest that: 1) TLR4 drives the antibacterial host response after induction of pneumonia with relatively lowKlebsielladoses; 2) TLR2 becomes involved at a later phase of the infection and/or upon exposure to higher bacterial burdens; and 3) haematopoietic TLR2 and TLR4 are important for an adequate host response duringKlebsiellapneumonia.
Lymphatic and blood microvasculature organisation in pulmonary sarcoid granulomas
Authors: Kambouchner M. , Pirici D. , Uhl J-F. , Mogoanta L. , Valeyre D. , Bernaudin J-F. 
Published: July 2010

Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions.Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context.Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce.Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.
Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis
Authors: Pfaff E-M. , Becker S. , Günther A. , Königshoff M. 
Published: July 2010

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with unknown pathogenesis. The WNT/β-catenin pathway has recently been reported to be operative in epithelial cells in IPF. Dickkopf (DKK) proteins are known to regulate WNT signallingviainteraction with Kremen (KRM) receptors, yet their expression and role in the adult lung and in IPF has not been addressed.We analysed the expression, localisation and function of DKK and KRM proteins in IPF lungs using Western blotting, quantitative RT-PCR, immunohistochemistry, ELISA and functionalin vitrostudies.Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localised in basal bronchial epithelial cells. Furthermore, prominent expression of all proteins was observed in hyperplastic alveolar epithelial cells in IPF. Quantitative measurement of DKK1 revealed enhanced protein expression in the bronchoalveolar lumen of IPF patients. Finally, functional studies using human bronchial and alveolar epithelial cell lines demonstrated that WNT-induced epithelial cell proliferation is regulated by DKK1 in a dose-dependent fashion.In summary, DKK proteins are expressed in the lung epithelium in IPF. DKK proteins influence epithelial cell proliferation and may, therefore, be suitable therapeutic targets for IPF.
Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1β synthesis by human neutrophils
Authors: Langereis J.D. , Oudijk E-J.D. , Schweizer R.C. , Lammers J-W.J. , Koenderman L. , Ulfman L.H. 
Published: July 2010

Chronic obstructive pulmonary disease (COPD) is characterised by neutrophilic inflammation in the airways and these neutrophils contribute to the production of inflammatory mediators. Dampening the production of proinflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do soviainhibition of nuclear factor-κB. However, this pathway is important for the control of pro- and anti-inflammatory genes.We studied the effects of dexamethasone on production and secretion of pro-inflammatory interleukin (IL)-1β and anti-inflammatory secreted IL-1 receptor antagonist (sIL-1Ra) by human neutrophils activated with tumor necrosis factor (TNF)-α.In vitro, TNF-α-stimulated neutrophils produced significant amounts of IL-1β and sIL-1Ra; this production was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1β, which changed the IL-1β:sIL-1Ra ratio significantly. This altered ratio resulted in a more pro-inflammatory condition, as visualised by increased intercellular adhesion molecule-1 expression on human endothelial cells.In vivo, moderate-to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sIL-Ra levels compared with mild-to-moderate patients not on glucocorticosteroid treatment.In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1β:sIL-1Ra cytokine balance in neutrophilsin vitro, which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammationin vivo.
Legionella pneumophila-induced IκBζ-dependent expression of interleukin-6 in lung epithelium
Authors: Lorenz J. , Zahlten J. , Pollok I. , Lippmann J. , Scharf S. , N'Guessan P.D. , Opitz B. , Flieger A. , Suttorp N. , Hippenstiel S. , Schmeck B. 
Published: July 2010

Severe community- and hospital-acquired pneumonia is caused byLegionella pneumophila. Lung airway and alveolar epithelial cells comprise an important sentinel system in airborne infections. Although interleukin (IL)-6 is known as a central regulator of the immune response in pneumonia, its regulation in the lung is widely unknown.Herein, we demonstrate that differentL. pneumophilastrains induce delayed expression of IL-6 in comparison with IL-8 by human lung epithelial cells. IL-6 expression depended, at early time points, on flagellin recognition by Toll-like receptor (TLR)5, activity of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)1 and p38 mitogen-activated protein (MAP) kinase, and, at later time points, on the type-IV secretion system. In the same manner, but more rapidly, the recently described transcription factor IκBζ was induced byLegionellainfection and, binding to the nuclear factor (NF)-κB subunit p50 - recruited to theil6promoter together with CCAAT-enhancer-binding protein β and phosphorylated activator protein-1 subunit cJun. Similarly, histone modifications and NF-κB subunit p65/RelA appeared at theiκbζand subsequently at theil6gene promoter, thereby initiating gene expression. Gene silencing of IκBζ reducedLegionella-related IL-6 expression by 41%.Overall, these data indicate a sequence of flagellin/TLR5- and type IV-dependent IκBζ expression, recruitment of IκBζ/p50 to theil6promoter, chromatin remodelling and subsequent IL-6 transcription inL. pneumophila-infected lung epithelial cells.
A comparison of internal validation techniques for multifactor dimensionality reduction
Authors: Winham Stacey J , Slater Andrew J , Motsinger-Reif Alison A 
Published: July 2010

Abstract

Background
It is hypothesized that common, complex diseases may be due to complex interactions between genetic and environmental factors, which are difficult to detect in high-dimensional data using traditional statistical approaches. Multifactor Dimensionality Reduction (MDR) is the most commonly used data-mining method to detect epistatic interactions. In all data-mining methods, it is important to consider internal validation procedures to obtain prediction estimates to prevent model over-fitting and reduce potential false positive findings. Currently, MDR utilizes cross-validation for internal validation. In this study, we incorporate the use of a three-way split (3WS) of the data in combination with a post-hoc pruning procedure as an alternative to cross-validation for internal model validation to reduce computation time without impairing performance. We compare the power to detect true disease causing loci using MDR with both 5- and 10-fold cross-validation to MDR with 3WS for a range of single-locus and epistatic disease models. Additionally, we analyze a dataset in HIV immunogenetics to demonstrate the results of the two strategies on real data.

Results
MDR with 3WS is computationally approximately five times faster than 5-fold cross-validation. The power to find the exact true disease loci without detecting false positive loci is higher with 5-fold cross-validation than with 3WS before pruning. However, the power to find the true disease causing loci in addition to false positive loci is equivalent to the 3WS. With the incorporation of a pruning procedure after the 3WS, the power of the 3WS approach to detect only the exact disease loci is equivalent to that of MDR with cross-validation. In the real data application, the cross-validation and 3WS analyses indicate the same two-locus model.

Conclusions
Our results reveal that the performance of the two internal validation methods is equivalent with the use of pruning procedures. The specific pruning procedure should be chosen understanding the trade-off between identifying all relevant genetic effects but including false positives and missing important genetic factors. This implies 3WS may be a powerful and computationally efficient approach to screen for epistatic effects, and could be used to identify candidate interactions in large-scale genetic studies.
Roles of the Anterior Cingulate Cortex and Medial Thalamus in Short-Term and Long-Term Aversive Information Processing
Authors: Chai Sin-Chee , Kung Jen-Chuang , Shyu Bai-Chuang 
Published: July 2010

Background: The anterior cingulate cortex (ACC) and medial thalamus (MT) are two of the main components of the medial pain pathway that subserve the affective aspect of pain. The hypothesis of the present study was that the ACC is involved in short-term aversive information processing and that the MT is critical for encoding unconditioned nociceptive information. The roles of these two components in short-term and long-term aversive information processing was investigated using a step-through inhibitory avoidance task. Results: Behavioral training began 1 week after surgery, in which radiofrequency lesions of the ACC or MT were performed. The retention tests were conducted 30 s (short-term) or 24 h (long-term) after training. Pretraining radiofrequency lesions of the ACC impaired performance in the 30 s, but not 24 h, retention test. Microinfusions of lidocaine into the ACC immediately after training impaired performance in the retention test conducted 10 min later. Pretraining radiofrequency lesions of the MT impaired performance in both the 30 s and 24 h retention tests. However, posttraining, but not pretest, microinfusions of lidocaine into the MT impaired performance in the 24 h retention test. Conclusions: These results suggest that the ACC may play an important role in short-term, but not long-term, nociceptive information processing. In contrast, the MT may be important for the consolidation of nociceptive information storage.
The biomechanical analysis of three plating fixation systems for periprosthetic femoral fracture near the tip of a total hip arthroplasty
Authors: Lever James P. , Zdero Rad , Nousiainen Markku T. , Waddell James P. , Schemitsch Emil H. 
Published: July 2010

AbstractBackgroundA variety of techniques are available for fixation of femoral shaft fractures following total hip arthroplasty. The optimal surgical repair method still remains a point of controversy in the literature. However, few studies have quantified the performance of such repair constructs. This study biomechanically examined 3 different screw-plate and cable-plate systems for fixation of periprosthetic femoral fractures near the tip of a total hip arthroplasty.MethodsTwelve pairs of human cadaveric femurs were utilized. Each left femur was prepared for the cemented insertion of the femoral component of a total hip implant. Femoral fractures were created in the femurs and subsequently repaired with Construct A (Zimmer Cable Ready System), Construct B (AO Cable-Plate System), or Construct C (Dall-Miles Cable Grip System). Right femora served as matched intact controls. Axial, torsional, and four-point bending tests were performed to obtain stiffness values.ResultsAll repair systems showed 3.08 to 5.33 times greater axial stiffness over intact control specimens. Four-point normalized bending (0.69 to 0.85) and normalized torsional (0.55 to 0.69) stiffnesses were lower than intact controls for most comparisons. Screw-plates provided either greater or equal stiffness compared to cable-plates in almost all cases. There were no statistical differences between plating systems A, B, or C when compared to each other (p > 0.05).ConclusionsScrew-plate systems provide more optimal mechanical stability than cable-plate systems for periprosthetic femur fractures near the tip of a total hip arthroplasty.
Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality
Authors: Marchlik Erica , Thakker Paresh , Carlson Thaddeus , Jiang Zhaozhao , Ryan Mark , Marusic Suzana , Goutagny Nadege , Kuang Wen , Askew G Roger , Roberts Victoria , Benoit Stephen , Zhou Tianhui , Ling Vincent , Pfeifer Richard , Stedman Nancy , Fitzgerald Katherine A , Lin Lih-Ling , Hall J Perry 
Published: July 2010

Abstract
Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues, altered circulating immune cell compartments, and increased susceptibility to LPS-induced lethality.
TBK1 is critical for immunity against microbial pathogens that activate TLR4- and TLR3-dependent signaling pathways. To address the role of TBK1 in inflammation, mice were generated that harbor two copies of a mutant Tbk1 allele. This Tbk1Δ allele encodes a truncated Tbk1Δ protein that is catalytically inactive and expressed at very low levels. Upon LPS stimulation, macrophages from Tbk1Δ/Δ mice produce normal levels of proinflammatory cytokines (e.g., TNF-α), but IFN-β and RANTES expression and IRF3 DNA-binding activity are ablated. Three-month-old Tbk1Δ/Δ mice exhibit mononuclear and granulomatous cell infiltrates in multiple organs and inflammatory cell infiltrates in their skin, and they harbor a 2-fold greater amount of circulating monocytes than their Tbk1+/+ and Tbk1+/Δ littermates. Skin from 2-week-old Tbk1Δ/Δ mice is characterized by reactive changes, including hyperkeratosis, hyperplasia, necrosis, inflammatory cell infiltrates, and edema. In response to LPS challenge, 3-month-old Tbk1Δ/Δ mice die more quickly and in greater numbers than their Tbk1+/+ and Tbk1+/Δ counterparts. This lethality is accompanied by an overproduction of several proinflammatory cytokines in the serum of Tbk1Δ/Δ mice, including TNF-α, GM-CSF, IL-6, and KC. This overproduction of serum cytokines in Tbk1Δ/Δ mice following LPS challenge and their increased susceptibility to LPS-induced lethality may result from the reactions of their larger circulating monocyte compartment and their greater numbers of extravasated immune cells.
Immune regulation by peripheral suppressor T cells induced upon homotypic T cell/T cell interactions
Authors: Thümmler Katja , Leipe Jan , Ramming Andreas , Schulze-Koops Hendrik , Skapenko Alla 
Published: July 2010

Abstract
Activated effector T cells induce the generation of suppressor T cells from bystander memory T cells via interactions involving LFA-1 and its receptors.
We have shown previously that homotypic interaction of resting memory CD4 T cells with activated T cells induces the production of cytokines with immunoregulatory potential (IL-10, IL-4) from the former. Here, we analyzed the effector functions of these T cells stimulated by homotypic T cell interaction. T cells induced upon homotypic T cell interaction expressed CD25 and reduced levels of CD127 and produced TGF-β. Functionally, homotypic T cell interaction-induced T cells were anergic and inhibited the proliferation of CD25-negative T cells as potently as naturally occurring CD25-positive Tregs in vitro. They also prevented clonotypic expansion of OVA TCR tg T cells in BALB/c mice upon antigenic challenge in vivo. The generation of suppressor T cells by homotypic T cell contact is anchored and tuned through interactions of LFA-1 and its ligands ICAM-1, ICAM-2, and ICAM-3. Together, the data suggest a negative-feedback mechanism of specific immunity involving bystander-activated memory T cells.