bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Perspectives on Akt Akt-ivation and Akt-ions
Authors: Matheny Ronald W. , Adamo Martin L.
Published: July 2009

The serine/threonine kinase Akt is an effector of PI3K-generated phosphatidylinositol ( 3 , 4 , 5 )-trisphosphate [PI( 3 , 4 , 5 )P3] and is a principle mediator of growth factor-induced signal transduction. Akt is activated through phosphorylation by specific kinases, and its activity is reduced directly by phosphorylation-site-specific phosphatases. In addition, Akt activity is effectively reduced by the action of phosphatases which dephosphorylate PI( 3 , 4 , 5 )P3, thereby reducing the levels of the essential lipid activators of PDK1 and Akt. The functions of Akt are pleiotropic and include regulation of cellular proliferation, differentiation, protein synthesis, and survival. Akt stimulates protein synthesis through actions on mTOR/p70S6K, and promotes survival by phosphorylating and inactivating pro-apoptotic molecules such as Ask1, Bad, Bax, and FoxO3a. Furthermore, loss of Akt decreases the intracellular ATP:AMP ratio, thus establishing a role for Akt in energy regulation. Three isoforms of Akt have been identified, and although redundant functions between isoforms exist, recent investigations have enumerated unique functions for each. Therefore, targeting specific Akt isozymes in a tissue- and context-specific fashion may lead to a greater understanding of Akt-mediated processes.
Biofouling Growth in Cold Estuarine Waters and Evaluation of Some Chitosan and Copper Anti-Fouling Paints
Authors: Pelletier Émilien , Bonnet Claudie , Lemarchand Karine
Published: July 2009

Ecological concerns about antifouling paints containing non-green tin and copper compounds have highlighted the need for environmentally friendly alternatives. We report here a field test conducted in estuarine waters over two months designed to evaluate the efficiency of a number of active natural and man-made chemical ingredients added into a silicon-polyurethane marine paint. Early steps of biofouling in cold seawater of the St. Lawrence Estuary (Canada) were observed. Analyses, including dry biomass, flow cytometry and spectrofluorimetry, demonstrated a short-term antibacterial action of chitosan-based paints although no significant anti-algal action was observed. Cuprous oxide paints were efficient against bacteria and algae invasion in the first two weeks, especially those with added organic biocides such as isothiazolone and copper pyrithione. However, the overall dry biomass and chlorophyll a content were similar for all chitosan- and copper-based paints after 63 days. Microscopic observations revealed variation in the highly diverse benthic diatom population including species Navicula, Melosira, Cocconeis, Nitshzcia, Fragilaria and Amphora. Results suggest no real long-term efficiency for tested antifouling paints and highlight a particular need for green antifouling ingredients that are active under northern estuarine conditions.
Variation of Cholinesterase-Based Biosensor Sensitivity to Inhibition by Organophosphate Due To Ionizing Radiation
Authors: Pohanka Miroslav , Koch Miroslav
Published: July 2009

A cholinesterase based biosensor was constructed in order to assess the effects of ionizing radiation on exposed AChE. Although the primary objective of the experiment was to investigate the effect of ionizing radiation on the activity of the biosensor, no changes in cholinesterase activity were observed. Current provided by oxidation of thiocholine previously created from acetylthiocholine by enzyme catalyzed reaction was in a range 395–455 nA. No significant influence of radiation on AChE activity was found, despite the current variation. However, a surprising phenomenon was observed when a model organophosphate paraoxon was assayed. Irradiated biosensors seem to be more susceptible to the inhibitory effects of paraoxon. Control biosensors provided a 94 ± 5 nA current after exposure to 1 ppm paraoxon. The biosensors irradiated by a 5 kGy radiation dose and exposed to paraoxon provided a current of 49 ± 6 nA. Irradiation by doses ranging from 5 mGy to 100 kGy were investigated and the mentioned effect was confirmed at doses above 50 Gy. After the first promising experiments, biosensors irradiated by 5 kGy were used for calibration on paraoxon and compared with the control biosensors. Limits of detection 2.5 and 3.8 ppb were achieved for irradiated and non-irradiated biosensors respectively. The overall impact of this effect is discussed.
DNA Sensors with Diamond as a Promising Alternative Transducer Material
Authors: Vermeeren Veronique , Wenmackers Sylvia , Wagner Patrick , Michiels Luc
Published: July 2009

Bio-electronics is a scientific field coupling the achievements in biology with electronics to obtain higher sensitivity, specificity and speed. Biosensors have played a pivotal role, and many have become established in the clinical and scientific world. They need to be sensitive, specific, fast and cheap. Electrochemical biosensors are most frequently cited in literature, often in the context of DNA sensing and mutation analysis. However, many popular electrochemical transduction materials, such as silicon, are susceptible to hydrolysis, leading to loss of bioreceptor molecules from the surface. Hence, increased attention has been shifted towards diamond, which surpasses silicon on many levels.
Karyological analysis of the five native Macaronesian Festuca (Gramineae) grasses supports a distinct diploid origin of two schizoendemic groups
Authors: Menezes de Sequeira Miguel , Díaz-Pérez Antonio , Santos-Guerra Arnoldo , Viruel Juan , Catalán Pilar
Published: July 2009

A karyological analysis has been conducted of all five native Macaronesian Festuca grasses belonging to fine-leaved F. subg. Festuca sect. Aulaxyper and broad-leaved F. subg. Drymanthele sect. Phaeochloa Loliinae lineages. Chromosomal analyses were made in 30 plants corresponding to 17 populations of the fineleaved F. agustinii, F. jubata, F. francoi and F. petraea and 2 populations of the broad-leaved F. donax. All counts except one tetraploid count were diploids, showing 2n = 14 chromosomes. Diploidy was confirmed for the robust F. donax, nested within a clade of relict ancestral fescues as reported in recent phylogenetic studies, and was also found in the more slender F. agustinii, F. jubata, F. francoi and F. petraea, which are basal to a recently evolved clade of polyploid red fescues. Karyotypes of the two groups are however distinct, with broad-leaved F. donax showing larger and more regular chromosomes and all four fine-leaved taxa showing smaller and more irregular submetacentric chromosomes. Our karyological data indicate that these two groups of diploid fescues correspond to distinct schizoendemics which apparently originated at different times after independent continental colonizations of Macaronesia.
On the presence of Cneorum (Cneoraceae) in Cuba: an example of biogeographic disjunction between the Mediterranean and the Caribbean?
Authors: Oviedo Ramona , Traveset Anna , Valido Alfredo , Brull Gabriel
Published: July 2009

The main goal of the study was to shed light on the enigmatic world distribution of the Cneoraceae family, frequently, and until very recently, used as an example of the connection between the Mediterranean and the Caribbean floras. Specifically, we wanted to document the presence/absence of an endemic taxon, first collected in 1861 by Charles Wright from Cuba (Cneorum trimerum). During the last five years, we have visited all the localities where this taxon was originally collected, at Sierra Maestra in eastern Cuba, and revised all available herbarium material. Moreover, we checked all botanical and historical references, and also interviewed local people, to whom we showed pictures of the Mediterranean Cneorum. The conclusions of our survey are the following: i) nowadays, there are no Cneorum plants growing in their type localities in Cuba; ii) all the collected material from Cuba and deposited in herbaria by Wright, and also others studied by Carlquist, correspond unequivocally to C. tricoccon. The material collected by Ekman in 1922, and identified as C. trimerum, is sterile, and cannot be identified with certainty, however we think it is unlikely to be C. tricoccon; iii) this plant was probably introduced during the mid 19th century from Southern France, although it never become naturalized. The presence of French colonist settlements in coffee plantations in those areas where Cneorum was collected, together with the fact that the plant has medicinal properties, lead us to suggest that the colonist themselves were those introducing the plant in Cuba. Lastly, iv) Schoepfia stenophylla (Olacaceae) has also been recently misidentified as Cneorum tricoccon due to the resemblance of their leaves. Schoepfia stenophylla is an endemic species currently threatened and for which there is an in situ conservation plan. Such confusion between these species has contributed to the maintenance and spreading of the mistakes through the long taxonomic history of the presence of Cneorum in Cuba. Hence, we conclude that Cneorum can no longer be used as an example of biogeographical disjunction between the floras of the Mediterranean and the Caribbean.
A revision of Passiflora sections Insignes and ×Inkea (Passifloraceae)
Authors: Møller Jørgensen Peter , Vásquez Roberto
Published: July 2009

During the compilation of the Passifloraceae for the Catálogo de las Plantas Vasculares de Bolivia we found a new species belonging to Passiflora sect. Insignes, which we call Passiflora carrascoensis. We here present a taxonomic revision of the Passiflora sect. Insignes and ×Inkea and a brief outline of the history of the groups. The number of species in Passiflora sect. Insignes is now six, with four species endemic to Bolivia, one to Peru, and one widespread frequently cultivated species. Passiflora sect. ×Inkea consists of the hybrid Passiflora ×rosea. Four names are lectotypified.
Synopsis and lectotypification of Solanum (Solanaceae) species endemic in the West Indies
Authors: Knapp Sandra
Published: July 2009

The West Indies (Bahamas, Greater and Lesser Antilles) is an area of high species richness and more importantly, species-level endemism in many groups. Solanum (Solanaceae) is diverse in the region with 25 endemic species (S. bahamense is near-endemic, bringing number to 26). Nineteen of these taxa are single-island endemics, and some have not been re-collected since the early 20th century. A synopsis of the species endemic to the West Indies is presented, with full synonymy and distribution; a single representative specimen is cited for each. All accepted names and synonyms are lectotypified where necessary; many of these taxa were described from collections in Berlin (B) that are no longer extant. Lectotypes newly designated here are illustrated.
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

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

IL-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

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

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

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

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

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

Aspirin 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

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

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

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.
Genetically Detoxified Pertussis Toxin Induces Th1/Th17 Immune Response through MAPKs and IL-10-Dependent Mechanisms
Authors: Nasso Maria , Fedele Giorgio , Spensieri Fabiana , Palazzo Raffaella , Costantino Paolo , Rappuoli Rino , Ausiello Clara Maria
Published: July 2009

Genetically detoxified pertussis toxin (dPT) maintains the protein structure and the immunological properties, but not the enzymatic activity. In search of an adjuvant able to direct polarization of T cells to induce/potentiate protective immune response to a variety of infectious disease, we investigated the role played by dPT on human dendritic cell-driven Th polarization and analyzed the intracellular signaling events. To reach these aims, we used a highly purified dPT preparation devoid of contamination and monocyte-derived dendritic cells, a well-characterized model to study ex vivo the polarization of the immune responses. First, we analyzed dPT-induced monocyte-derived dendritic cell maturation, longevity, and cytokine production and, in a second step, we analyzed TLR4/2 engagement by dPT, the connected signaling events, and their relevance to the skewing of Th cell polarization. These approaches allowed us to clarify some of the mechanisms that are responsible for dPT-driven regulation of T cell polarization. We demonstrated that dPT acts utilizing TLR4/TLR2 engagement, being the signaling induced by the former stronger. dPT, through a crucial role played by MAPK and IL-10, favors the expansion of the Th1/Th17 immunity. Indirect evidences indicated that dPT-induced Th17 expansion is counterregulated by the PI3K pathway. For its properties and being already used in humans as vaccine Ag in pertussis, dPT may represents a valid candidate adjuvant to foster immune protective response in vaccines against infectious diseases where Th1/Th17 are mediating host immunity.
The p110δ Isoform of Phosphatidylinositol 3-Kinase Controls Susceptibility to Leishmania major by Regulating Expansion and Tissue Homing of Regulatory T Cells
Authors: Liu Dong , Zhang Tingting , Marshall Aaron J. , Okkenhaug Klaus , Vanhaesebroeck Bart , Uzonna Jude E.
Published: July 2009

Resistance to Leishmania major and most intracellular pathogens is usually associated with a strong T cell-mediated immunity, particularly a CD4+ Th1 response. Mice with an inactivating knock-in mutation in the p110δ isoform of PI3K (referred to as p110δD910A) show severely impaired T cell responses. Because a strong T cell response is thought to mediate resistance to intracellular pathogens, we examined the outcome of L. major infection in p110δD910A mice. Paradoxically, p110δD910A mice on “resistant” and “susceptible” genetic backgrounds showed more robust resistance manifested as significantly reduced lesion size and accelerated parasite clearance. This enhanced resistance was associated with dramatically diminished immune responses, including impaired cell proliferation and effector cytokine (IFN-γ and TNF) production. Interestingly, the ability of macrophages and dendritic cells from p110δD910A mice to produce NO and destroy Leishmania parasites was similar to those of wild-type mice. We show that the enhanced resistance of p110δD910A mice was due to impaired expansion and effector functions of regulatory T cells (Tregs). Adoptive transfer studies demonstrated that p110δD910A mice lost their increased resistance when given enriched Tregs from wild-type mice. We suggest on the basis of these and further observations that the lack of this enzyme prominently affects Treg expansion and homing to infection sites, and that in the absence of Tregs, weak Th1 responses are capable of containing parasites and prevent pathology. We also suggest that temporary pharmacological inhibition of this enzyme may be a very effective form of treatment against cutaneous leishmaniasis.
The Veterans Health Administration: A Preliminary Analysis of the Influence of The Independent Budget and Bureaucratic Performance on Funding Trends
Authors: Kidder Elizabeth
Published: July 2009

The Veterans Health Administration (VHA) is the largest integrated health system in the U.S. with 7.9 million U.S. veterans enrolled.  Both the number of veterans seeking VHA health services and the cost of delivering such services continue to rise as a result of myriad factors. Kidder examines VHA funding outcomes over the past 10 years in light of the participation of veterans' service organizations (VSOs) in committee hearings; the reliance of lawmakers upon The Independent Budget (IB); and the impact of new performance-based management initiatives on budget outcomes.  Her article highlights the political nature of the VHA budget and the influential role of VSOs in funding outcomes.
Vote Overreporting: The Statistical and Policy Implications
Authors: Jones Emily
Published: July 2009

Voting is a critical way for citizens to gain representation for their interests, as well as the most direct way that most citizens participate in the political process. Yet, many citizens fail to cast their vote on election day. America's comparatively low turnout rate has motivated reams of research on voting behaviors, but researchers are limited by data quality problems. In particular, vote overreporting, when systematic, can bias analysis of who votes and why, which hampers efforts to understand and increase turnout. Previous research using individual-level National Election Survey (NES) validated data found demographic and regional patterns of overreporting. Since the NES no longer validates voting, individual-level data is no longer available and region is the only remaining determinant of systematic vote overreporting that can be studied. This paper uses census data to examine regional variations in vote overreporting in the 2000 and 2004 Presidential elections. After reviewing the actual turnout rate and how it increased from 2000 to 2004, I use both conventional ways to measure overreporting and examine variation by region. My results using both methods fit with past research indicating that overreporting is slightly higher in the South, but only in 2000.
The Ethics of Dissent: Managing Guerrilla Government
Authors: Boyer Eric
Published: July 2009

No abstract available.
Countering Terrorism: Blurred Focus, Halting Steps
Authors: Gross Jennifer C.
Published: July 2009

No abstract available.
Incentives at the Eligibility Threshold: An Examination of Child Care Financial Assistance Policies
Authors: Derrick-Mills Teresa M.
Published: July 2009

For families with children, employment comes at a price. They must subtract from their wages the cost of someone else caring for their child. Their wage minus the costs of obtaining child care, transportation, and other expenses that may be generated by employment is generally referred to as the effective wage. The Child Care Development Fund (CCDF) child care subsidy voucher, the Earned Income Tax Credit (EITC), and the Child and Dependent Care Credit (CDCC) are all intended to increase the effective wage of parents to support them entering and staying in the workforce. This paper explores the trade-offs between employment and effective wage that parents must make through the lens of three hypothetical North Carolina families facing promotion, bonus, and employer relocation opportunities. Through their eyes we understand why it would be rational to turn down these opportunities due to the potential loss of thousands of dollars in benefits. These situations demonstrate the weaknesses of the current system, where the needs of employers and employees become increasingly opposed as families approach the income eligibility threshold and the portability threshold. This paper proposes a policy to better align the needs of employers and employees by restructuring the incentive system to phase out benefits gradually, guarantee help to anyone who is eligible, make support sensitive to regional changes in child care prices, and administer it through the tax system rather than local social services offices throughout the country. While this paper focuses on the child care benefit system, the framework used to explore the issues of reversed incentives at the eligibility threshold can be applied to any social policy with income eligibility requirements.
Caring Fathers: Addressing Domestic Violence and the Care Gap with Male Care Work
Authors: Cherrin Amanda
Published: July 2009

Traditional divisions of household labor have contributed to power dynamics and gender norms that exacerbate family violence and place the responsibility of care on women. As a result, American families today face separate but related problems in the care gap and the domestic violence epidemic. Using feminist economics as a theoretical framework, this paper examines policy responses to both the care gap and domestic violence that seek to address the common problem of unbalanced gender relations, with the shared solution of increased male care work. It specifically focuses on family and paternity leave programs and care work–oriented domestic violence prevention initiatives, arguing that male care work has the potential to help repair the damaged gender relations that contribute to the overlapping problems of the care gap and domestic violence through the creation and promotion of more respectful, egalitarian relationships.
Dulles Corridor Metrorail Project: A Cost-Benefit Analysis
Authors: Donnelly Lauren
Published: July 2009

This cost-benefit analysis studies several significant costs and benefits of the Dulles Corridor Metrorail Project. The two major costs of construction and operating expenses and the two major benefits of passenger benefits and car miles saved have been used to analyze the project over a 30-year period starting in 2009, to include four years of construction followed by 26 years of Metro operation. The project was determined to have a net cost of $1.78 billion. With the exception of the first four years, in which construction costs would be incurred but the other three costs and benefits would not yet be realized, the project creates annual benefits of $32 million or greater. Additionally, a break-even analysis was performed within the sensitivity analysis to determine the year in which net benefits would begin accruing on the project. This year was found to be 2063, or 54 years into the project (including four years of construction and 50 years of service). Any following years in which the Metrorail was still operating would create increasing net benefits.
Health Care Reform Now! A Prescription for Change
Authors: Kazan Matt
Published: July 2009

No abstract available.
Urban Regional Policy and Its Effects
Authors: McManmon Robert
Published: July 2009

No abstract available.
The Powers to Lead
Authors: Feroli Christine
Published: July 2009

No abstract available.
The impact of the Choice on Termination of Pregnancy Act of 1996 (Act 92 of 1996) on criminal abortions in the Mthatha area of South Africa
Authors: Meel Banwari L. , Kaswa Ram P.
Published: July 2009

Background: The Choice on Termination of Pregnancy Act of 1996 (Act 92 of 1996) allows abortions to be legally carried out in South Africa. It is not clear how many people are utilising this service. Mthatha is a poverty-stricken area with a high rate of illiteracy. The available infrastructure, such as roads, health facilities and communication, is poor.Method: This was a retrospective, descriptive study carried out at the Nelson Mandela Academic Hospital in Mthatha. The registered criminal abortion cases recorded between 1993 and 2006 were analysed.Results: There were 51 cases of criminal abortions recorded from 1993 to 2006. Of these, 32 were aborted in the first trimester of pregnancy and the rest were in the second trimester. No significant gender differences were observed among aborted babies. 10 of the foetuses were male and nine were female. The highest number (nine) of abortions was recorded in 1993 and in 2005. The highest number of criminal abortions (11) took place in May. Most cases (35) were concealed births and were discovered accidentally either by the public or the police.Conclusion: The Choice on Termination of Pregnancy Act of 1996 (Act 92 of 1996) had no impact on criminal abortions in the Mthatha area of South Africa.
Informal Ontology Design
Authors: Altheim Murray
Published: July 2009

Wiki software has historically provided little support for any form of organizational structure. Even given the assumption that the majority of wiki users have previous experience with file system-like hierarchies, most wiki systems keep things simple (as is the wiki way) and employ a flat page structure. As a wiki grows beyond a few dozen pages, some form of organization becomes increasingly necessary. This has typically been accomplished by adding “category links” to each page, essentially ad hoc terms from an unstructured and uncontrolled vocabulary. Because these terms are themselves often undefined it can be difficult to ascertain the reason why a given page belongs to a category. Even when this is done carefully, as the number of terms in the categorization grows a classification scheme for the terms themselves likewise becomes increasingly necessary.

This paper describes problems with existing wiki and “semantic wiki” categorization schemes and outlines an approach to information organization that avoids the pitfalls of computer-based ontologies by instead looking to library science for solutions. It describes the design and implementation of a wiki system permitting user-authored assertions, which are dynamically harvested to create a Topic Map graph mirroring the explicit structure of the wiki and providing it with an underlying classification system.
Hypertext Links and Relationships in XML Databases
Authors: Brüggemann-Klein Anne , Singer Lorenz
Published: July 2009

Hypertext links are, for semistructured data and narrative documents in XML databases, a fitting analogue to foreign-key references for structured data in relational databases. We encode hypertext links with XLink. For processing the links, we use the XLink processor HyQuery, an XQuery module which turns a native, XQuery-enabled XML database into a hyperdata system. This system is used in a lab course "XML Technology" and in the case study XTunes, a Web application that manages metadata and recordings of classical music.
Beyond the Semantic Web: the Semantic Space
Authors: Lévy Pierre
Published: July 2009

Today, the sharing of semantics remains a conundrum. Semantics can be shared within a universe of discourse, but individuals and communities cannot be relieved of the need to define their own universes of discourse. The emergence of collective intelligence is increasingly seen as necessary for human survival, but it is difficult for people who live in diverse universes of discourse to know when they are talking about the same things. Collective intelligence — the ability of a community to exhibit self-sustaining, rational behaviors — is inversely related to its participants' ability to understand each other.

Diverse minds can create, recognize, and think in terms of diverse sets of distinct concepts and relationships between them. A conceptual addressing system can map such sets into a shared abstract "semantic space" that is structured by an algebraically definable group of transformations. Information Economy Meta Language (IEML) is such a "semantic space addressing system"; it defines a very large space of semantic addresses. A small number of the points in that space — more than 2,500 of them — are now listed in an "IEML Dictionary", along with interpretations of each of them in several natural languages. A language for compactly specifying sets of locations in the space exists, and a parser that translates expressions in this language into XML is available. A programming language for discovering and asserting relationships between sets of semantics is being developed, along with a variety of related software tools.

The semantic space research program could provide a scientific (measurable, principled, experimentally repeatable) foundation on which technologies and professional disciplines can be created, including distributed collaborative semantic search engines, models and simulations of collective intelligences, tools and editorial practices for the automated production of multimedia documents, and many more.
But wait, there's more!
Authors: Sperberg-McQueen C. M.
Published: July 2009

XML has been widely adopted and forms part of the infrastructure of most modern information technology. We have a satisfyingly large collection of XML vocabularies and XML tools. Is it time to declare victory and go home yet? Or is there more to do?
Summary and Wrap-Up
Authors: Birnbaum David J.
Published: July 2009

There will be a lot of material presented at the Versioning Symposium: prepared presentations, questions and answers following those presentations, and mini-presentations from our Hyde Park Speaker's Corner. This wrap-up will summarize what we have heard, discussed, and learned in the Symposium. Since it will be composed on the fly, the presenter welcomes audience corrections on the points he inevitably will forget or misrepresent.
Axioms of Versioning
Authors: de Graauw Marc
Published: July 2009

The problems of language versioning can be better understood with the help of some formal axioms defining the relations among the extensions and semantics of languages. Such axioms allow us to specify what makes one language extensionally, syntactically, or semantically a subset, superset, or equivalent of another. The difference between syntactic and semantic compatibility makes clear how languages can grow in a forward-compatible way. The key to compatible versioning is to assign new semantics in the new version of a language for syntax that was already accepted in the prior version, but to which the prior version assigned no semantics.