bluuebunny/crossref_metadata_2025_split huggingface dataset:
FADD Deficiency Impairs Early Hematopoiesis in the Bone Marrow
Authors: Rosenberg Stephen , Zhang Haibing , Zhang Jianke 
Published: November 2010

Abstract
Signal transduction mediated by Fas-associated death domain protein (FADD) represents a paradigm of coregulation of apoptosis and cellular proliferation. During apoptotic signaling induced by death receptors including Fas, FADD is required for the recruitment and activation of caspase 8. In addition, a death receptor-independent function of FADD is essential for embryogenesis. In previous studies, FADD deficiency in embryonic stem cells resulted in a complete lack of B cells and dramatically reduced T cell numbers, as shown by Rag1−/− blastocyst complementation assays. However, T-specific FADD-deficient mice contained normal numbers of thymocytes and slightly reduced peripheral T cell numbers, whereas B cell-specific deletion of FADD led to increased peripheral B cell numbers. It remains undetermined what impact an FADD deficiency has on hematopoietic stem cells and progenitors. The current study analyzed the effect of simultaneous deletion of FADD in multiple cell types, including bone marrow cells, by using the IFN-inducible Mx1-cre transgene. The resulting FADD mutant mice did not develop lymphoproliferation diseases, unlike Fas-deficient mice. Instead, a time-dependent depletion of peripheral FADD-deficient lymphocytes was observed. In the bone marrow, a lack of FADD led to a dramatic decrease in the hematopoietic stem cells and progenitor-enriched population. Furthermore, FADD-deficient bone marrow cells were defective in their ability to generate lymphoid, myeloid, and erythroid cells. Thus, the results revealed a temporal requirement for FADD. Although dispensable during lymphopoiesis post lineage commitment, FADD plays a critical role in early hematopoietic stages in the bone marrow.
IL-9 Production by Regulatory T Cells Recruits Mast Cells That Are Essential for Regulatory T Cell-Induced Immune Suppression
Authors: Eller Kathrin , Wolf Dominik , Huber Julia M. , Metz Martin , Mayer Gert , McKenzie Andrew N. J. , Maurer Marcus , Rosenkranz Alexander R. , Wolf Anna M. 
Published: November 2010

Abstract
Both mast cells (MCs) and regulatory T cells (Tregs) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MCs and Tregs have been shown to play a protective role. Transfer of wild-type (wt) Tregs into wt recipients almost completely prevents development of NTS and leads to a profound increase of MCs in the renal draining lymph nodes (LNs). By contrast, transfer of wt Tregs into animals deficient in MCs, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a mAb in mice receiving Tregs abrogated protection from NTS. Moreover, transfer of IL-9–deficient Tregs also failed to protect from NTS. In the absence of Treg-derived IL-9, MCs fail to accumulate in the LNs, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Tregs. In summary, to our knowledge, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Tregs critically depend on IL-9–mediated attraction of MCs into kidney-draining LNs.
Remarkable Conservation of Distinct Nonclassical MHC Class I Lineages in Divergent Amphibian Species
Authors: Goyos Ana , Sowa Jessica , Ohta Yuko , Robert Jacques 
Published: November 2010

Abstract
Nonclassical MHC class Ib (class Ib) genes are heterogeneous genes encoding molecules that are structurally similar to classical MHC class Ia molecules but with limited tissue distribution and polymorphism. Mammalian class Ib genes have diverse and often uncharacterized functions, and because of their rapid rate of evolution, class Ib phylogeny is difficult to establish. We have conducted an extensive genomic, molecular, and phylogenetic characterization of class Ib genes in two Xenopodinae amphibian species of different genera that diverged from a common ancestor as long ago as primates and rodents (∼65 million years). In contrast with the unsteadiness of mammalian class Ib genes, our results reveal an unusual degree of conservation of most Xenopodinae class Ib gene lineages, including a novel monogenic lineage represented by the divergent Xenopus laevis XNC10 gene and its unequivocal Silurana (Xenopus) tropicalis orthologue, SNC10. The preferential expression of this gene lineage by thymocytes themselves from the onset of thymic organogenesis is consistent with a specialized role of class Ib in early T cell development and suggests such a function is conserved in all tetrapods.
5A, an Apolipoprotein A-I Mimetic Peptide, Attenuates the Induction of House Dust Mite-Induced Asthma
Authors: Yao Xianglan , Dai Cuilian , Fredriksson Karin , Dagur Pradeep K. , McCoy J. Philip , Qu Xuan , Yu Zu-Xi , Keeran Karen J. , Zywicke Gayle J. , Amar Marcelo J. A. , Remaley Alan T. , Levine Stewart J. 
Published: November 2010

AbstractNew treatment approaches are needed for patients with asthma. Apolipoprotein A-I (apoA-I), the major structural protein of high-density lipoproteins, mediates reverse cholesterol transport and has atheroprotective and anti-inflammatory effects. In this study, we hypothesized that an apoA-I mimetic peptide might be effective at inhibiting asthmatic airway inflammation. A 5A peptide, which is a synthetic, bihelical apoA-I mimetic, was administered to wild-type A/J mice via osmotic mini-pump prior to the induction of house dust mite (HDM)-induced asthma. HDM-challenged mice that received the 5A apoA-I mimetic peptide had significant reductions in the number of bronchoalveolar lavage fluid eosinophils, lymphocytes, and neutrophils, as well as in histopathological evidence of airway inflammation. The reduction in airway inflammation was mediated by a reduction in the expression of Th2- and Th17-type cytokines, as well as in chemokines that promote T cell and eosinophil chemotaxis, including CCL7, CCL17, CCL11, and CCL24. Furthermore, the 5A apoA-I mimetic peptide inhibited the alternative activation of pulmonary macrophages in the lungs of HDM-challenged mice. It also abrogated the development of airway hyperresponsiveness and reduced several key features of airway remodeling, including goblet cell hyperplasia and the expression of collagen genes (Col1a1 and Col3a1). Our results demonstrate that the 5A apoA-I mimetic peptide attenuates the development of airway inflammation and airway hyperresponsiveness in an experimental murine model of HDM-induced asthma. These data support the conclusion that strategies using apoA-I mimetic peptides, such as 5A, might be developed further as a possible new treatment approach for asthma.
CD8 Regulates T Regulatory Cell Production of IL-6 and Maintains Their Suppressive Phenotype in Allergic Lung Disease
Authors: Joetham Anthony , Okamoto Masakazu , Takeda Katsuyuki , Schedel Michaela , Ohnishi Hiroshi , Dakhama Azzeddine , Gelfand Erwin W. 
Published: November 2010

Abstract
Naturally occurring CD4+CD25+Foxp3+ T regulatory cells (nTregs) regulate lung allergic responses through production of IL-10 and TGF-β. nTregs from CD8−/− mice failed to suppress lung allergic responses and were characterized by reduced levels of Foxp3, IL-10, and TGF-β, and high levels of IL-6. Administration of anti–IL-6 or anti–IL-6R to wild-type recipients prior to transfer of CD8−/− nTregs restored suppression. nTregs from IL-6−/− mice were suppressive, but lost this capability if incubated with IL-6 prior to transfer. The importance of CD8 in regulating the production of IL-6 in nTregs was demonstrated by the loss of suppression and increases in IL-6 following transfer of nTregs from wild-type donors depleted of CD8+ cells. Transfer of nTregs from CD8−/− donors reconstituted with CD8+ T cells was suppressive, and accordingly, IL-6 levels were reduced. These data identify the critical role of CD8–T regulatory cell interactions in regulating the suppressive phenotype of nTregs through control of IL-6 production.
Murine FLT3 Ligand-Derived Dendritic Cell-Mediated Early Immune Responses Are Critical to Controlling Cell-Free Human T Cell Leukemia Virus Type 1 Infection
Authors: Rahman Saifur , Khan Zafar K. , Wigdahl Brian , Jennings Stephen R. , Tangy Frederic , Jain Pooja 
Published: November 2010

Abstract
Human T cell leukemia virus type 1 (HTLV-1) is associated with two immunologically distinct diseases: HTLV-1–associated myelopathy/tropical spastic paraparesis and adult T cell leukemia. We observed previously that depletion of dendritic cells (DCs) in CD11c-diphtheria toxin receptor transgenic mice followed by infection with cell-free virus led to greater proviral and Tax mRNA loads and diminished cellular immune response compared with mice infected with cell-associated virus. To understand the significance of these in vivo results and explore the host–pathogen interaction between DCs and cell-free HTLV-1, we used FLT3 ligand-cultured mouse bone marrow-derived DCs (FL-DCs) and chimeric HTLV-1. Phenotypically, the FL-DCs upregulated expression of surface markers (CD80, CD86, and MHC class II) on infection; however, the level of MHC class I remained unchanged. We performed kinetic studies to understand viral entry, proviral integration, and expression of the viral protein Tax. Multiplex cytokine profiling revealed production of an array of proinflammatory cytokines and type 1 IFN (IFN-α) by FL-DCs treated with virus. Virus-matured FL-DCs stimulated proliferation of autologous CD3+ T cells as shown by intracellular nuclear Ki67 staining and produced IFN-γ when cultured with infected FL-DCs. Gene expression studies using type 1 IFN-specific and DC-specific arrays revealed upregulation of IFN-stimulated genes, most cytokines, and transcription factors, but a distinct downregulation of many chemokines. Overall, these results highlight the critical early responses generated by FL-DCs on challenge with cell-free chimeric HTLV-1.
Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma
Authors: Li S. C. , Liebling M. S. , Haines K. A. , Weiss J. E. , Prann A. 
Published: November 2010

AbstractObjectiveTo evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U‐DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions.MethodsWe conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U‐DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences.ResultsWe studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U‐DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS.ConclusionThe U‐DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool.
Role of magnetic resonance imaging in the diagnosis and prognosis of rheumatoid arthritis
Authors: Suter Lisa G. , Fraenkel Liana , Braithwaite R. Scott 
Published: November 2010

AbstractObjectiveTo systematically evaluate the literature addressing the role of magnetic resonance imaging (MRI) in the diagnosis and prognosis of early undifferentiated inflammatory arthritis and rheumatoid arthritis (RA).MethodsWe performed a systematic literature review of the performance characteristics of MRI for diagnosing and prognosticating RA. We searched Ovid, supplementing this with manual searches of bibliographies, journals, meeting proceedings, and the ClinicalTrials.gov web site. To identify diagnostic studies, we included studies of any duration that prospectively examined whether MRI findings predicted RA diagnosis and reported adequate information to calculate sensitivity and specificity. To identify prognostic studies, we included prospective studies with at least a 12‐month followup period that measured both baseline MRI findings and clinical and/or radiographic outcomes.ResultsFor diagnostic studies (n = 11), sensitivity and specificity of MRI findings for RA diagnosis ranged from 20–100% and 0–100%, respectively, depending upon the criteria used. Diagnostic performance of MRI improved when lower‐quality studies or studies with longer disease duration were excluded. For prognostic studies (n = 17), MRI findings did not predict clinical remission, and the ability to predict radiographic progression varied significantly (range 18–100% for sensitivity and 5.9–97% for specificity). Restricting the analysis to specific MRI findings or earlier disease improved MRI prognostic performance. The only prognostic study reporting 100% of a priori quality criteria found MRI bone edema to be the strongest predictor of radiographic progression.ConclusionData evaluating MRI for the diagnosis and prognosis of early RA are currently inadequate to justify widespread use of this technology for these purposes, although MRI bone edema may be predictive of progression in certain RA populations.
Intentional and unintentional treatment nonadherence in patients with systemic lupus erythematosus
Authors: Daleboudt Gabriëlle M. N. , Broadbent Elizabeth , McQueen Fiona , Kaptein Ad A. 
Published: November 2010

AbstractObjectivePatients may be defined as nonadherent if they do not take their medications as prescribed by their physicians. Determinants of nonadherence may vary between and within patient groups. This study investigated the extent to which patients with systemic lupus erythematosus (SLE) show intentional and unintentional nonadherence, and the associations of nonadherence with psychological and medical parameters.MethodsThe study included 106 patients who were receiving at least one immunosuppressive agent to control their SLE. Level of self‐reported adherence and a measure of both intentional and unintentional nonadherence were obtained. Questionnaires were completed to assess associations between adherence and problems with cognitive functioning, beliefs about medicines, illness perceptions, emotional health, and disease characteristics.ResultsThe mean self‐reported adherence rate for the total patient group was 86.7%. At least occasional intentional nonadherence was reported by 46.2% of patients and 58.5% of patients were at least occasionally unintentionally nonadherent. Problems with cognitive functioning, concerns about adverse effects of medication, and younger age were the strongest predictors of (non)adherence. Patients who were emotionally affected by their SLE were more likely to report low adherence, but this was not a significant predictor after accounting for other variables. Disease characteristics showed no relationship to measures of adherence.ConclusionAlthough SLE patients reported high levels of adherence on average, they commonly reported intentional and unintentional nonadherence. Adherence was associated with both cognitions and emotions. Nonadherence may be reduced by targeting emotional and cognitive functioning and by fine tuning doctor–patient communication to address patients' individual concerns about their medications.
Natural history of radiographic hip osteoarthritis: A retrospective cohort study with 11–28 years of followup
Authors: Franklin Jonas , Ingvarsson Thorvaldur , Englund Martin , Ingimarsson Olafur , Robertsson Otto , Lohmander L. Stefan 
Published: November 2010

AbstractObjectiveTo evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture.MethodsWe studied a cohort of individuals who had colon radiography from 1980–1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture.ResultsA total of 2,953 hips were studied (57% women). The cumulative incidence of THR was 2.5% and the cumulative incidence of hip fracture was 2.6%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9% and the hazard ratio (HR) for THR was 13.2 (95% confidence interval [95% CI] 8.1–21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95% CI 7.9–21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95% CI 0.15–1.5), for intracapsular fractures was 0.29 (95% CI 0.04–2.1), and for extracapsular fractures was 0.67 (95% CI 0.16–2.8).ConclusionThe risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11–28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.
Pushing the Functionality of Diamond Nanoparticles to New Horizons: Orthogonally Functionalized Nanodiamond Using Click Chemistry
Authors: Meinhardt Thomas , Lang Daniel , Dill Holger , Krueger Anke 
Published: November 2010

AbstractClick chemistry is one of the most versatile means for the efficient grafting of larger units such as fluorescence labels or biomolecules onto the surface of nanoparticles. Here, a first study on the applicability of different strategies for the copper‐catalyzed azide–alkyne coupling of diamond nanoparticles and organic moieties is reported. Both thermally annealed nanodiamond and mechanically pretreated diamond nanoparticles of different origin can be modified with moieties carrying either azide or alkyne groups. Several organic units have been efficiently “clicked” onto these particles. The method is then applied for the bifunctional surface modification of nanodiamond leading to a material exhibiting carboxylic and alkyne groups at the same time. These can be addressed by orthogonal coupling linkers. A model material carrying two distinct fluorescent dyes is produced this way and shows the characteristic luminescence of both dyes. The findings open the way for the application of nanodiamond as multifunctional labels, drug delivery vehicles, and targeting agents in biomedical applications.
A Small Molecule Non‐fullerene Electron Acceptor for Organic Solar Cells
Authors: Schwenn Paul E. , Gui Ke , Nardes Alexandre M. , Krueger Karsten B. , Lee Kwan H. , Mutkins Karyn , Rubinstein‐Dunlop Halina , Shaw Paul E. , Kopidakis Nikos , Burn Paul L. , Meredith Paul 
Published: November 2010

AbstractOrganic bulk heterojunction photovoltaic devices predominantly use the fullerene derivatives [C60]PCBM and [C70]PCBM as the electron accepting component. This report presents a new organic electron accepting small molecule 2‐[{7‐(9,9‐di‐n‐propyl‐9H‐fluoren‐2‐yl)benzo[c][1,2,5]thiadiazol‐4‐yl}methylene]malononitrile (K12) for organic solar cell applications. It can be processed by evaporation under vacuum or by solution processing to give amorphous thin films and can be annealed at a modest temperature to give films with much greater order and enhanced charge transport properties. The molecule can efficiently quench the photoluminescence of the donor polymer poly(3‐n‐hexylthiophene‐2,5‐diyl) (P3HT) and time resolved microwave conductivity measurements show that mobile charges are generated indicating that a truly charge separated state is formed. The power conversion efficiencies of the photovoltaic devices are found to depend strongly on the acceptor packing. Optimized K12:P3HT bulk heterojunction devices have efficiencies of 0.73±0.01% under AM1.5G simulated sunlight. The efficiencies of the devices are limited by the level of crystallinity and nanoscale morphology that was achievable in the blend with P3HT.
The evolution of the meningeal vascular system in the human genus: From brain shape to thermoregulation
Authors: Bruner Emiliano , Mantini Simone , Musso Fabio , De La Cuétara José Manuel , Ripani Maurizio , Sherkat Shahram 
Published: November 2010

AbstractObjectives:The imprints of the middle meningeal vessels make it possible to analyze vascularization in fossil specimens. The association between changes in the cortical anatomy and vascular organization raises questions about the actual physiological meaning of these features, most of all when dealing with the origin of the modern human brain. Metabolism and thermoregulation may be relevant factors in influencing morphological adaptations between brain and vessels. This study is aimed at investigating the relationships between endocranial morphology and endocranial vessels in modern humans and to analyze the pattern of heat dissipation through the endocranial surface in fossil specimens.Methods:Through angiotomography, it is possible to make an anatomical reconstruction of the meningeal and cerebral vessels, providing information on the morphology of the endocranial vascular system. At the same time, digital modeling can be performed to investigate the relationships between the endocranial geometry and physical properties such as heat dissipation patterns in extinct hominids.Results:The middle meningeal network is largely independent from the cerebral vascular system. Furthermore, in adults, the medium and upper tracts of the middle meningeal artery shows scarce or absent blood flow. Parietal bossing in modern humans involves relative cooling of the cortical surface at the supramarginal gyrus.Conclusions:The evidence does not support a thermoregulatory role for the meningeal vascular network, at least in adult normal blood flow conditions. On the other hand, biomechanical protective functions (hydraulic skeleton for shock adsorption) cannot be ruled out. Am. J. Hum. Biol., 2011. © 2010 Wiley‐Liss, Inc.