bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Poverty Reduction in the EU: A Descriptive Analysis
Authors: Caminada Koen , Goudswaard Kees 
Published: July 2009

AbstractThe European Union coordinates and encourages Member State actions to combat poverty, and to reform their social protection systems on the basis of policy exchanges and mutual learning (‘best practices’). This paper analyses the effectiveness of welfare state policies and especially social transfers in EU‐countries in alleviating poverty. To indicate whether European economic integration may have had any impact on poverty reduction, we also include several non‐EU15 countries as a benchmark into our analysis. We analyze on a cross‐country basis the relationship between poverty rates and social effort, as measured by social expenditure ratios. We also correct these expenditure ratios for the impact of the tax system and for private social arrangements, using OECD methodology. Next, we compare poverty rates at the levels of market and disposable incomes; that is, before and after transfers, in order to analyze the effect of tax and transfer policies in reducing poverty, i.e., to determine the target efficiency of social transfers. We perform several tests with the most recent data. Our results are less clear cut than earlier findings. We still find a quite strong negative relationship between the level of social expenditure and poverty among OECD countries. However, for EU‐countries this relationship is weaker and there are substantial differences within the EU15. After correcting for the impact of taxes and for private social arrangements, the linkage between social effort and poverty levels becomes even weaker. Also, we do not find a strong relationship between levels of social spending and antipoverty effects of social transfers and taxes. At the program level, family programs and child support alleviate poverty to a large extent.
The Influence of Roles, Advocacy, and Adaptation to the Accounting Decision Environment
Authors: Pinsker Robert , Pennington Robin , Schafer Jennifer Kahle 
Published: July 2009

ABSTRACT: Decision makers often adapt strategies to specific task and context variables by balancing the need to make good decisions with the need to minimize cognitive effort. However, decision makers must have the requisite knowledge, based on training, to choose the most appropriate strategy. We extend the judgment and decision making literature by experimentally examining how training in specific professional roles (tax and audit) influences advocacy attitudes, and how the elements of the decision environment interact with these attitudes to influence accountants’ judgments.
Results indicate that attitudes are moderated by the requirements of the specific decision environment. Specifically, judgments of accounting professionals in a tax decision environment closely mirror their attitudes, whereas in an audit decision environment, this relationship is significantly weaker, indicative of a moderating effect of the decision environment. Supplemental analysis indicates that tax professionals are more likely than auditors to adapt to the professional requirements (advocacy or skepticism) of the task at hand.
TNF-α Preconditioning Protects Neurons via Neuron-Specific Up-Regulation of CREB-Binding Protein
Authors: Saha Ramendra N. , Ghosh Anamitra , Palencia Carlos A. , Fung Yiu K. , Dudek Serena M. , Pahan Kalipada 
Published: July 2009

Abstract
Despite being a proinflammatory cytokine, TNF-α preconditions neurons against various toxic insults. However, underlying molecular mechanisms are poorly understood. The present study identifies the importance of CREB-binding protein (CBP) in facilitating TNF-α-mediated preconditioning in neurons. Treatment of rat primary neurons with fibrillar amyloid β1–42 (Aβ) resulted in the loss of CBP protein. However, this loss was compensated by TNF-α preconditioning as the expression of neuronal CBP was up-regulated in response to TNF-α treatment. The induction of CBP by TNF-α was observed only in neurons, but not in astroglia and microglia, and it was contingent on the activation of transcription factor NF-κB. Interestingly, antisense knockdown of CBP abrogated the TNF-α-mediated preconditioning of neurons against Aβ and glutamate toxicity. Similarly in vivo, preadministration of TNF-α in mouse neocortex prevented Aβ-induced apoptosis and loss of choline acetyltransferase-positive cholinergic neurons. However, coadministration of cbp antisense, but not scrambled oligonucleotides, negated the protective effect of TNF-α against Aβ neurotoxicity. This study illustrates a novel biological role of TNF-α in increasing neuron-specific expression of CBP for preconditioning that may have therapeutic potential against neurodegenerative disorders.
IL-27 Regulates Homeostasis of the Intestinal CD4+ Effector T Cell Pool and Limits Intestinal Inflammation in a Murine Model of Colitis
Authors: Troy Amy E. , Zaph Colby , Du Yurong , Taylor Betsy C. , Guild Katherine J. , Hunter Christopher A. , Saris Christiaan J. M. , Artis David 
Published: July 2009

AbstractIL-27 limits CD4+ TH17 cell development in vitro and during inflammatory responses in the CNS. However, whether IL-27-IL-27R interactions regulate the homeostasis or function of CD4+ T cell populations in the intestine is unknown. To test this, we examined CD4+ T cell populations in the intestine of wild-type and IL-27R−/− mice. Naive IL-27R−/− mice exhibited a selective decrease in the frequency of IFN-γ producing CD4+ TH1 cells and an increase in the frequency of TH17 cells in gut-associated lymphoid tissues. Associated with elevated expression of IL-17A, IL-27R−/− mice exhibited earlier onset and significantly increased severity of clinical disease compared with wild-type controls in a murine model of intestinal inflammation. Rag−/−/IL-27R−/− mice were also more susceptible than Rag−/− mice to development of dextran sodium sulfate-induced intestinal inflammation, indicating an additional role for IL-27-IL-27R in the regulation of innate immune cell function. Consistent with this, IL-27 inhibited proinflammatory cytokine production by activated neutrophils. Collectively, these data identify a role for IL-27-IL-27R interaction in controlling the homeostasis of the intestinal T cell pool and in limiting intestinal inflammation through regulation of innate and adaptive immune cell function.
Microarray Analysis of Lymphatic Tissue Reveals Stage-Specific, Gene Expression Signatures in HIV-1 Infection
Authors: Li Qingsheng , Smith Anthony J. , Schacker Timothy W. , Carlis John V. , Duan Lijie , Reilly Cavan S. , Haase Ashley T. 
Published: July 2009

Abstract
Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. Although each of the three stages has well-known clinical, virologic, and immunologic characteristics, much less is known of the molecular mechanisms underlying each stage. In this study, we report lymphatic tissue microarray analyses, revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that although there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g., RIG-1, MDA-5, TLR7 and TLR8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the proapoptotic Fas-Fas ligand pathway. Yet, quite strikingly, the expression of nearly all acute stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. This transition from acute to asymptomatic stage is tied to increased expression of a diverse array of immunosuppressive genes (e.g., CLEC12B, ILT4, galectin-3, CD160, BCMA, FGL2, LAG3, GPNMB). In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific gene expression signatures identify potential molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
TREM-1 Activation Alters the Dynamics of Pulmonary IRAK-M Expression In Vivo and Improves Host Defense during Pneumococcal Pneumonia
Authors: Lagler Heimo , Sharif Omar , Haslinger Isabella , Matt Ulrich , Stich Karin , Furtner Tanja , Doninger Bianca , Schmid Katharina , Gattringer Rainer , de Vos Alex F. , Knapp Sylvia 
Published: July 2009

Abstract
Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of TLR-mediated inflammation during bacterial infections. Thus far, TREM-1 is primarily associated with unwanted signs of overwhelming inflammation, rendering it an attractive target for conditions such as sepsis. Respiratory tract infections are the leading cause of sepsis, but the biological role of TREM-1 therein is poorly understood. To determine the function of TREM-1 in pneumococcal pneumonia, we first established TREM-1 up-regulation in infected lungs and human plasma together with augmented alveolar macrophage responsiveness toward Streptococcus pneumoniae. Mice treated with an agonistic TREM-1 Ab and infected with S. pneumoniae exhibited an enhanced early induction of the inflammatory response that was indirectly associated with lower levels of negative regulators of TLR signaling in lung tissue in vivo. Later in infection, TREM-1 engagement altered S. pneumoniae-induced IRAK-M (IL-1R-associated kinase-M) kinetics so as to promote the resolution of pneumonia and remarkably led to an accelerated elimination of bacteria and consequently improved survival. These data show that TREM-1 exerts a protective role in the innate immune response to a common bacterial infection and suggest that caution should be exerted in modulating TREM-1 activity during certain clinically relevant bacterial infections.
JAK3 Inhibition Significantly Attenuates Psoriasiform Skin Inflammation in CD18 Mutant PL/J Mice
Authors: Chang Betty Y. , Zhao Feifei , He Xiaodong , Ren Hong , Braselmann Sylvia , Taylor Vanessa , Wicks Joan , Payan Donald G. , Grossbard Elliott B. , Pine Polly R. , Bullard Daniel C. 
Published: July 2009

Abstract
JAK3, a member of the Janus kinase family, is predominantly expressed in hemopoietic cells and binds specifically to the common γ chain of a subfamily of cytokine receptors that includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Previous studies suggest that this tyrosine kinase plays key roles in mediating T cell functions, and inhibition of JAK3 has been shown to prevent graft rejection and decrease the severity of arthritis in rodent models. However, the functions of JAK3 in the development of skin immune responses and diseases such as psoriasis have not been determined. CD18 mutant PL/J mice develop spontaneous T cell-dependent psoriasiform skin disease with several similarities to human psoriasis. In this study, we treated mice with established skin disease with R348, a small molecule inhibitor of JAK3, and observed a marked attenuation of skin lesions following 6 wk of treatment. Histological analyses revealed major reductions of both epidermal and dermal lesion severity scores in R348-treated CD18-deficient PL/J mice compared with vehicle controls, which was associated with decreased CD4+ T cell infiltration. In addition, systemic levels of IL-17, IL-22, IL-23, and TNF-α were significantly lower in mice receiving the compound, and T cells isolated from R348-treated mice also showed reduced phosphorylation of Stat5 after stimulation with IL-2. These findings suggest that small-molecule inhibitors of JAK3 may be useful in the treatment of inflammatory skin diseases such as psoriasis and strongly implicate JAK signaling events as important in the pathogenesis of this disease.
Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis
Authors: Lai Wen-Qi , Irwan Anastasia Windy , Goh Hong Heng , Melendez Alirio J. , McInnes Iain B. , Leung Bernard P. 
Published: July 2009

Abstract
Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate (S1P). S1P plays a critical role in angiogenesis, inflammation, and various pathologic conditions. To date, two mammalian isoenzymes, SphK1 and SphK2, have been identified. Although both SphK1 and SphK2 share overall homology and produce the common product, S1P, it has been proposed they display different unique and separate functions. In this study, we examined the role of SphK1 and SphK2 in a murine collagen-induced arthritis model by down-regulating each isoenzyme via specific small interfering RNA (siRNA). Prophylactic i.p. administration of SphK1 siRNA significantly reduced the incidence, disease severity, and articular inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA also down-regulated serum levels of S1P, IL-6, TNF-α, IFN-γ, and IgG2a anti-collagen Ab. Ex vivo analysis demonstrated significant suppression of collagen-specific proinflammatory/Th1 cytokine (IL-6, TNF-α, IFN-γ) release in SphK siRNA-treated mice. Interestingly, mice received with SphK2 siRNA develop more aggressive disease; higher serum levels of IL-6, TNF-α, and IFN-γ; and proinflammatory cytokine production to collagen in vitro when compared with control siRNA recipients. Together, these results demonstrate the distinct immunomodulatory roles of SphK1 and SphK2 in the development of inflammatory arthritis by regulating the release of proinflammatory cytokines and T cell responses. These findings raise the possibility that drugs which specifically target SphK1 activity may play a beneficial role in the treatment of inflammatory arthritis.
Site-Specific Production of IL-6 in the Central Nervous System Retargets and Enhances the Inflammatory Response in Experimental Autoimmune Encephalomyelitis
Authors: Quintana Albert , Müller Marcus , Frausto Ricardo F. , Ramos Raquel , Getts Daniel R. , Sanz Elisenda , Hofer Markus J. , Krauthausen Marius , King Nicholas J. C. , Hidalgo Juan , Campbell Iain L. 
Published: July 2009

Abstract
IL-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. To establish the role of site-specific production of IL-6 in autoimmunity, we examined myelin oligodendrocyte glycoprotein immunization-induced EAE in transgenic mice (GFAP-IL6) with IL-6 production restricted to the cerebellum. Myelin oligodendrocyte glycoprotein-immunized (Mi-) GFAP-IL6 mice developed severe ataxia but no physical signs of spinal cord involvement, which was in sharp contrast to Mi-wild type (WT) animals that developed classical EAE with ascending paralysis. Immune pathology and demyelination were nearly absent from the spinal cord, but significantly increased in the cerebellum of Mi-GFAP-IL6 mice. Tissue damage in the cerebellum in the Mi-GFAP-IL6 mice was accompanied by increased total numbers of infiltrating leukocytes and increased proportions of both neutrophils and B-cells. With the exception of IL-17 mRNA, which was elevated in both control immunized and Mi-GFAP-IL6 cerebellum, the level of other cytokine and chemokine mRNAs were comparable with Mi-WT cerebellum whereas significantly higher levels of IFN-γ and TNF-α mRNA were found in Mi-WT spinal cord. Thus, site-specific production of IL-6 in the cerebellum redirects trafficking away from the normally preferred antigenic site the spinal cord and acts as a leukocyte “sink” that markedly enhances the inflammatory cell accumulation and disease. The mechanisms underlying this process likely include the induction of specific chemokines, activation of microglia, and activation and loss of integrity of the blood-brain barrier present in the cerebellum of the GFAP-IL6 mice before the induction of EAE.
Effects of Low-Dose Aspirin on Acute Inflammatory Responses in Humans
Authors: Morris Thea , Stables Melanie , Hobbs Adrian , de Souza Patricia , Colville-Nash Paul , Warner Tim , Newson Justine , Bellingan Geoffrey , Gilroy Derek W. 
Published: July 2009

AbstractAspirin is a unique nonsteroidal anti-inflammatory drug; at high doses (aspirinhigh, 1g), it is anti-inflammatory stemming from the inhibition of cyclooxygenase and proinflammatory signaling pathways including NF-κB, but is cardioprotective at lower doses (aspirinlow, 75 mg). The latter arises from the inhibition of thromboxane (Tx) B2, a prothrombotic eicosanoid also implicated in polymorphonuclear leukocyte trafficking. As a result, aspirinlow is widely used as a primary and secondary preventative against vascular disease. Despite this and its ability to synthesize proresolution 15-epi-lipoxin A4 it is not known whether aspirinlow is anti-inflammatory in humans. To address this, we generated skin blisters by topically applying cantharidin on the forearm of healthy male volunteers, causing an acute inflammatory response including dermal edema formation and leukocyte trafficking. Although not affecting blister fluid volume, aspirinlow (75 mg, oral, once daily/10 days) reduced polymorphonuclear leukocyte and macrophage accumulation independent of NF-κB-regulated gene expression and inhibition of conventional prostanoids. However, aspirinlow triggered 15-epi-lipoxin A4 synthesis and up-regulated its receptor (FPRL1, ALX). From complimentary in vitro experiments, we propose that 15-epi-lipoxin A4 exerts its protective effects by triggering antiadhesive NO, thereby dampening leukocyte/endothelial cell interaction and subsequent extravascular leukocyte migration. Since similar findings were obtained from murine zymosan-induced peritonitis, we suggest that aspirinlow possesses the ability to inhibit mammalian innate immune-mediated responses. This highlights 15-epi-lipoxin A4 as a novel anti-inflammatory working through a defined receptor and suggests that mimicking its mode of action represents a new approach to treating inflammation-driven diseases.
Selective Expansion of the Monocytic Lineage Directed by Bacterial Infection
Authors: Serbina Natalya V. , Hohl Tobias M. , Cherny Mathew , Pamer Eric G. 
Published: July 2009

Abstract
CCR2-mediated recruitment of Ly6Chigh monocytes is essential for defense against a range of microbial pathogens. Although our understanding of monocyte trafficking to inflammatory sites is increasing, how innate immune inflammation influences monocyte development and maturation during microbial infection remains undefined. Herein, we demonstrate that infection with the intracellular bacterial pathogen Listeria monocytogenes specifically and selectively promotes monopoiesis. Systemic infection with virulent L. monocytogenes induces marked proliferation of bone marrow monocyte precursors and results in depletion of myeloid progenitors. Proliferation of monocyte precursors correlates with the intensity of systemic infection and is unaffected by the density of monocytes in the bone marrow. Although MyD88/Trif-mediated signaling is not required for early emigration of the mature monocyte population from the bone marrow, replenishment of monocyte populations depends on MyD88/Trif. Our studies demonstrate that TLR-mediated signals play an essential role in the maintenance of monocyte homeostasis during systemic bacterial infection.
MicroRNA-146a Feedback Inhibits RIG-I-Dependent Type I IFN Production in Macrophages by Targeting TRAF6, IRAK1, and IRAK2
Authors: Hou Jin , Wang Pin , Lin Li , Liu Xingguang , Ma Feng , An Huazhang , Wang Zhugang , Cao Xuetao 
Published: July 2009

Abstract
Upon recognition of viral components by pattern recognition receptors, including TLRs and retinoic acid-inducible gene I (RIG-I)- like helicases, cells are activated to produce type I IFN and proinflammatory cytokines. These pathways are tightly regulated by host to prevent inappropriate cellular response, but viruses can down-regulate these pathways for their survival. Recently, identification of negative regulators for cytoplasmic RNA-mediated antiviral signaling, especially the RIG-I pathway, attract much attention. However, there is no report about negative regulation of RIG-I antiviral pathway by microRNAs (miRNA) to date. We found that vesicular stomatitis virus (VSV) infection up-regulated miR-146a expression in mouse macrophages in TLR-myeloid differentiation factor 88-independent but RIG-I-NF-κB-dependent manner. In turn, miR-146a negatively regulated VSV-triggered type I IFN production, thus promoting VSV replication in macrophages. In addition to two known miR-146a targets, TRAF6 and IRAK1, we proved that IRAK2 was another target of miR-146a, which also participated in VSV-induced type I IFN production. Furthermore, IRAK1 and IRAK2 participated in VSV-induced type I IFN production by associating with Fas-associated death domain protein, an important adaptor in RIG-I signaling, in a VSV infection-inducible manner. Therefore, we demonstrate that miR-146a, up-regulated during viral infection, is a negative regulator of the RIG-I-dependent antiviral pathway by targeting TRAF6, IRAK1, and IRAK2.
Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H1 Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions
Authors: Shahriar Masum , Mizuguchi Hiroyuki , Maeyama Kazutaka , Kitamura Yoshiaki , Orimoto Naoki , Horio Shuhei , Umehara Hayato , Hattori Masashi , Takeda Noriaki , Fukui Hiroyuki 
Published: July 2009

Abstract
Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H1 receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively.