bluuebunny/crossref_metadata_2025 huggingface dataset:
Tachykinergic neurotransmission is enhanced in duodenum from dystrophic (mdx) mice
Authors: Zizzo Maria Grazia , Mulè Flavia , Serio Rosa
Published: March 2005

Duodenal longitudinal muscle of mdx mice, an animal model for Duchenne muscular dystrophy, showed a decrease in the electrically evoked nonadrenergic, noncholinergic (NANC) inhibitory responses associated with a reduction of the participation of nitric oxide (NO). In this study, we investigated whether the impairment of NO could also lead to alterations in the NANC excitatory transmission.

Nerve‐evoked responses consisted of an inhibitory phase followed, at the end of stimulation, by an excitatory response characterised by an increase in amplitude of the spontaneous contractions. In mdx mice, the amplitude of the nerve‐evoked contractions was significantly higher than in normals.

N‐nitro‐L‐arginine methyl ester (L‐NAME) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), an inhibitor of soluble guanylyl cyclase, increased the amplitude of the nerve‐evoked contractions only in normals, being ineffective in mdx mice. Apamin, a blocker of Ca2+‐dependent potassium channels, failed to affect the nerve‐evoked contractions.

In both models, substance P and neurokinin A produced concentration‐dependent contractions, reduced by tachykinin NK1 and NK2 receptor antagonists, respectively. Moreover, NK1 and NK2 receptor antagonists reduced the amplitude of the nerve‐evoked contractions.

Sodium nitroprusside (SNP) reduced the amplitude of nerve‐evoked contractions similarly in normal and mdx mice. ODQ, but not apamin, prevented the SNP‐induced effects. SNP did not affect the contractions induced by exogenous tachykinins.

The results suggest that NO can exert an inhibitory modulatory role on tachykinergic excitatory transmission via activation of guanylyl cyclase in mouse duodenum. In mdx mice, the impairment of NO function leads to an increase in the nerve‐evoked contractions.

British Journal of Pharmacology (2005) 145, 334–341. doi:10.1038/sj.bjp.0706171
Involvement of reactive oxygen species in cyclic stretch‐induced NF‐κB activation in human fibroblast cells
Authors: Amma Hideki , Naruse Keiji , Ishiguro Naoki , Sokabe Masahiro
Published: March 2005

Uniaxial cyclic stretch leads to an upregulation of cyclooxygenase (COX)‐2 through increases in the intracellular Ca2+ concentration via the stretch‐activated (SA) channel and following nuclear factor kappa B (NF‐κB) activation in human fibroblasts. However, the signaling mechanism as to how the elevated Ca2+ activates NF‐κB is unknown. In this study, we examined the involvement of reactive oxygen species (ROS) as an intermediate signal, which links the elevated Ca2+ with NF‐κB activation.

4‐Hydroxy‐2‐nonenal (HNE) was produced and modified IκB peaking at 2 min. The phosphorylation of IκB peaked at 8 min. HNE modification and IκB phosphorylation, NF‐κB translocation to the nucleus, and following COX‐2 production were inhibited by extracellular Ca2+ removal or Gd3+ application, as well as by the antioxidants. The stretch‐induced Ca2+ increase was inhibited by extracellular Ca2+ removal, or Gd3+ application.

IκB kinase (IKK) activity peaked at 4 min, which was inhibited by extracellular Ca2+ removal, Gd3+ or the antioxidants. IKK was also HNE‐modified and, similarly to IκB, peaked at 2 min. IKK under static conditions was activated by exogenously applied HNE at a relatively low dose (1 μM), while it was inhibited at higher concentrations, suggesting that HNE could be one of the candidate signals in the stretch‐induced NF‐κB activation.

The present study suggests that the NF‐κB activation by cyclic stretch is mediated by the following signal cascade: SA channel activation → intracellular Ca2+ increase → production of ROS → activation of IKK → phosphorylation of IκB → NF‐κB translocation to the nucleus.

British Journal of Pharmacology (2005) 145, 364–373. doi:10.1038/sj.bjp.0706182
Antagonism of ATP responses at P2X receptor subtypes by the pH indicator dye, Phenol red
Authors: King Brian F , Liu Min , Townsend‐Nicholson Andrea , Pfister Jürg , Padilla Fernando , Ford Anthony P , Gever Joel R , Oglesby Ian B , Schorge Stephanie , Burnstock Geoffrey
Published: March 2005

Many types of culture media contain a pH‐sensitive dye. One commonly occurring dye, Phenol red sodium (Na+) salt, was tested for blocking activity at rat P2X1−4 receptors (P2X1−4Rs) expressed in Xenopus oocytes.

Phenol red Na+‐salt antagonised adenosine 5′‐triphosphate (ATP) responses at P2X1R (IC50, 3 μM) and, at higher concentrations, also blocked P2X2R and P2X3R. Phenol red Na+‐salt, purified of lipophilic contaminants, blocked P2X1R and P2X3R by acting as an insurmountable antagonist.

Two lipophilic extracts of Phenol red antagonised ATP responses at P2XRs. Extract A was a potent antagonist at P2X1R (IC50, 1.4 μM), whereas extract B was a potent antagonist at P2X3R (IC50, 4.1 μM). A bisphenolic compound (RS151030) found in these extracts was a potent antagonist at P2X1R (IC50, 0.3 μM) and at P2X3R (IC50, 2.4 μM).

Phenolphthalein base was a potent irreversible antagonist at P2X1R (IC50, 1 μM), whereas Phenolphthalein K+‐salt was 25‐fold less potent here.

Phenolphthalein base was a reversible antagonist of ATP responses at rat P2X4R (IC50, 26 μM), whereas Phenolphthalein K+‐salt was inactive.

Dimethyl sulphoxide (DMSO), used to dissolve lipophilic extracts, showed pharmacological activity by itself at rat P2X1R and P2X4R.

Thus, Phenol red and related compounds are antagonists at rat P2X1R, but are also active at other rat P2XRs. Phenolphthalein base is a newly identified, low potency antagonist of ATP responses at P2X4R. Culture media containing these red dyes should be used cautiously in future pharmacological studies of P2XRs. Also, wherever possible, the solvent DMSO should be used with caution.

British Journal of Pharmacology (2005) 145, 313–322. doi:10.1038/sj.bjp.0706187
Expression of functional NK1 receptors in human alveolar macrophages: superoxide anion production, cytokine release and involvement of NF‐κB pathway
Authors: Bardelli Claudio , Gunella Gabriele , Varsaldi Federica , Balbo Pietro , Del Boca Elisa , Bernardone Ilaria Seren , Amoruso Angela , Brunelleschi Sandra
Published: March 2005

Substance P (SP) is deeply involved in lung pathophysiology and plays a key role in the modulation of inflammatory‐immune processes. We previously demonstrated that SP activates guinea‐pig alveolar macrophages (AMs) and human monocytes, but a careful examination of its effects on human AMs is still scarce.

This study was undertaken to establish the role of SP in human AM isolated from healthy smokers and non‐smokers, by evaluating the presence of tachykinin NK1 receptors (NK‐1R) and SP's ability to induce superoxide anion (O2−) production and cytokine release, as well as activation of the nuclear factor‐κB (NF‐κB) pathway.

By Western blot analysis and immunofluorescence, we demonstrate that authentic NK‐1R are present on human AMs, a three‐fold enhanced expression being observed in healthy smokers. These NK‐1R are functional, as SP and NK1 agonists dose‐dependently induce O2− production and cytokine release. In AMs from healthy smokers, SP evokes an enhanced respiratory burst and a significantly increased release of tumor necrosis factor‐α as compared to healthy non‐smokers, but has inconsistent effects on IL‐10 release. The NK1 selective antagonist CP 96,345 ((2S,3S)‐cis‐2‐diphenylmethyl‐N[(2‐methoxyphenyl)‐methyl]‐1‐azabicyclo‐octan‐3‐amine)) competitively antagonized SP‐induced effects.

SP activates the transcription factor NF‐κB, a three‐fold increased nuclear translocation being observed in AMs from healthy smokers. This effect is receptor‐mediated, as it is reproduced by the NK1 selective agonist [Sar9Met(O2)11]SP and reverted by CP 96,345.

These results clearly indicate that human AMs possess functional NK‐1R on their surface, which are upregulated in healthy smokers, providing new insights on the mechanisms involved in tobacco smoke toxicity.

British Journal of Pharmacology (2005) 145, 385–396. doi:10.1038/sj.bjp.0706198
Prostacyclin prevents nitric oxide‐induced megakaryocyte apoptosis
Authors: Gabriel Pozner Roberto , Negrotto Soledad , D'Atri Lina Paola , Lidia Kotler Mónica , Angela Lazzari María , Martin Gomez Ricardo , Schattner Mirta
Published: March 2005

We have previously demonstrated that nitric oxide (NO) triggers CD34+‐derived megakaryocyte apoptosis. We here show that prostacyclin (PGI2) inhibits PAPA/NO‐induced megakaryocyte death detected by fluorescent microscopy and flow cytometry.

The cAMP‐specific phosphodiesterase inhibitor, Ro 20‐1724, and the permeable analog dibutyryl‐cAMP also delayed apoptosis. PGI2 effect was fully prevented when adenylyl cyclase activity was suppressed by SQ 22536, and partially reversed by the permeable protein kinase A inhibitor PKI 14‐22 amide. ELISA showed that while both PGI2 and NO alone or synergistically raised cAMP, only NO was able to increase intracellular cGMP levels.

Treatment of megakaryocytes with PGI2 abolished both basal and NO‐raised cGMP levels. Addition of 8‐pCPT‐cGMP or activation of soluble guanylyl cyclase by BAY 41‐2272 induced cell death in a concentration‐dependent manner, and ODQ, an inhibitor of guanylyl cyclase, prevented both PAPA/NO‐ or BAY 41‐2272‐induced apoptosis. Specific cGMP phosphodiesterase inhibition by Zaprinast or suppression of adenylyl cyclase by SQ 22536 enhanced the PAPA/NO proapoptotic effect.

PGI2 completely inhibited NO‐mediated generation and the increased activity of the cleaved form of caspase‐3.

In conclusion, our results demonstrate that contrary to their well‐known direct and synergistic inhibitory effects on platelets, PGI2 and NO regulate opposite megakaryocyte survival responses through a delicate balance between intracellular cyclic nucleotide levels and caspase‐3 activity control.

British Journal of Pharmacology (2005) 145, 283–292. doi:10.1038/sj.bjp.0706200
Decreasing the infusion rate reduces the proarrhythmic risk of NS‐7: confirming the relevance of short‐term variability of repolarisation in predicting drug‐induced torsades de pointes
Authors: Detre Elke , Thomsen Morten B , Beekman Jet D , Petersen Karl‐Uwe , Vos Marc A
Published: March 2005

The rate of infusion has been suggested to be important for drug‐induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation‐prolonging effects and proarrhythmic properties of NS‐7, a neuroprotective drug in development, using two different infusion rates.

A fast (5 min intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg−1, n=4) of NS‐7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg−1, n=4) NS‐7. The similar dosing regimens were investigated in anaesthetised dogs with chronic, complete AV block (CAVB), an animal model of TdP (n=6).

No electrophysiological effects were seen after 0.3 mg kg−1 NS‐7. Fast infusion of 3.0 mg kg−1 caused prolongation of repolarisation, for example, heart rate corrected QT interval (QTc): in SR: 6±1%; in CAVB: 10±7%, which was accompanied by TdP in three of six CAVB dogs. No TdP were seen in SR dogs.

Slow infusion did not cause TdP in the same CAVB dogs, although NS‐7 caused repolarisation to prolong with a similar magnitude (QTc: 12±7%) as in the fast‐infusion experiment.

Short‐term variability (STV) is a novel parameter for the prediction of drug‐induced TdP analysing the beat‐to‐beat variability of repolarisation. STV was only increased after the fast infusion in CAVB dogs (2.6±0.3 versus 6.0±1.4 ms, P<0.05), while there was no increase (2.1±0.2 versus 2.5±1.0 ms) after the slow infusion of NS‐7.

Peak plasma concentrations attained were lower in slow (0.5±0.1 μg ml−1 after 50 min) than in fast‐infusion regimen (2.1±0.4 μg ml−1 after 5 min; P<0.05).

The results support the conclusion that limiting peak plasma concentration by decreasing the rate of infusion of NS‐7 reduces the proarrhythmic risk despite comparable prolongation in repolarisation parameters. The relevance of STV in predicting drug‐induced TdP was confirmed.

British Journal of Pharmacology (2005) 145, 397–404. doi:10.1038/sj.bjp.0706203
The economy of Australian rangelands — myth or mystery?
Authors: Fargher J. D. , Howard B. M. , Burnside D. G. , Andrew M. H.
Published: March 2005

Australian rangelands have been perceived as supporting mainly a pastoral economy for more than 150 years. This perception originated from colonial expansion in a frontier economy, with State and Commonwealth institutions established to support rangeland pastoralism. As Australia's economy shifts in focus towards sustainable development within a free and unprotected market, a new economic and social paradigm is needed for the rangelands. This is essential for strengthening regional economies in the rangelands that can survive in a globalised economy, preservation of environmental values in Australian rangelands, development of new land-use opportunities, as well as to facilitate a dignified change for those enterprises that are increasingly marginalised from the mainstream Australian and global economies. This paper explores the significance of rangelands in the Australian economy at national and regional scales, and the significance of grazing in the rangeland economy. It then considers how the grazing industry should be viewed within an alternative economic and social paradigm for rangelands in the 21st century – a paradigm that focuses on regional instead of sectoral economic opportunities and constraints.
Conservation and the maintenance of biodiversity in the rangelands
Authors: Woinarski J. C. Z. , Fisher A.
Published: March 2005

There has been substantial loss of biodiversity in the Australian rangelands, and evidence suggests that the attrition is continuing. We argue that rangeland users should be more aware of, and concerned about, this problem: that we are sullying an international asset; that we are undermining the basis of a major rangeland industry, tourism; that we are sabotaging the potential for the development of alternative rangeland uses (most notably sustainable use of native wildlife); that such losses provide evidence that we are poor managers; that such losses diminish our lives; that such losses indicate that at least some of our environments are operating at reduced functionality; and that such losses take away or reduce important and wide-ranging environmental services.
This loss is due to a complex array of factors, each affecting different components of biodiversity in different ways. Our responses are generally poorly coordinated across rangeland jurisdictions, and there is uncertainty about responsibilities across different land tenures. Given the diffuse but pervasive nature of the problem and the generally poorly coordinated and non-strategic current response, we suggest that biodiversity conservation needs to be far more clearly and systematically operationalised, that a clear goal for biodiversity conservation in the rangelands (maintenance of viable populations of all native species of plants and animals at appropriate spatial and temporal scales) needs to be developed, and that, from this, the community needs to set explicit targets relating to this goal, at continental, jurisdiction, regional and property scales. While we recognise that our existing knowledge base is imperfect, such limitation should not delay the implementation of these steps. We consider that there is sufficient management expertise to realise a rangeland biodiversity goal. However, there are two more serious impediments in achieving the goal: current lack of resources and of societal agreement.
Cattle grazing in a hummock grassland regenerating after fire: the short-term effects of cattle exclusion on vegetation in south-western Queensland
Authors: Letnic Mike
Published: March 2005

In the Simpson Desert of western Queensland fire is being used increasingly by pastoralists to manipulate hard spinifex (Triodia basedowii) pastures. In this study I investigated the short-term (20 month) effects of cattle grazing on hummock grasslands regenerating after fire in the Simpson Desert. Dung counts were used to determine if cattle grazed preferentially in areas regenerating after fire. Cattle exclosures and vegetation surveys were used to determine if grazing by cattle affected the structure and species composition of vegetation regenerating after fire.
Cattle grazed preferentially in areas regenerating after fire. Cattle grazing reduced the cover, height, vertical density and species richness of regrowth vegetation. Grazing reduced the cover of Ptilotus polystachyus and reduced the proportion of Eragrostis eriopodia individuals bearing flowers and seed. Grazing visibly disrupted microbiotic soil crusts. It is recommended, as a precaution until additional data is available, that areas regenerating after fire be rested from grazing during the first post-fire wet season. Resting during this period will assist the establishment of vegetation cover and provide opportunities for grasses to set seed.
Do the public gains from vegetation protection in north-western New South Wales exceed the landholders' loss of land value?
Authors: Sinden J. A.
Published: March 2005

Protection of native vegetation on farms provides many gains for the public as a whole, but may also lead to losses in property value for the landholders. At least 41% of Moree Plains Shire remains in native vegetation, most of which is grazed extensively and all of which must now be protected under recent laws. A benefit-cost analysis was combined with a risk simulation to estimate these gains and losses. The data collection stage of the analysis included a synthesis of the literature on the relationship between protection and land values. The analysis showed that protection of native vegetation leads to substantial public gains and to considerable losses in land value in this region. The public gains and the private losses are of the same magnitude, so there may be an economic case for protection. But the size of the landholders' losses demonstrates the need to better balance the gains and losses through policies to target protection and to redistribute the costs between the landholder and the community.
Application of genome-wide expression analysis to human health and disease
Authors: Cobb J. Perren , Mindrinos Michael N. , Miller-Graziano Carol , Calvano Steve E. , Baker Henry V. , Xiao Wenzhong , Laudanski Krzysztof , Brownstein Bernard H. , Elson Constance M. , Hayden Douglas L. , Herndon David N. , Lowry Stephen F. , Maier Ronald V. , Schoenfeld David A. , Moldawer Lyle L. , Davis Ronald W. , Tompkins Ronald G. ,   Inflammation and Host Response to Injury Large-Scale Collaborative Research Program§§
Published: March 2005

The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.
CD44 is a determinant of inflammatory bone loss
Authors: Hayer Silvia , Steiner Günter , Görtz Birgit , Reiter Erika , Tohidast-Akrad Makiyeh , Amling Michael , Hoffmann Oskar , Redlich Kurt , Zwerina Jochen , Skriner Karl , Hilberg Frank , Wagner Erwin F. , Smolen Josef S. , Schett Georg
Published: March 2005

Chronic inflammation is a major trigger of local and systemic bone loss. Disintegration of cell–matrix interaction is a prerequisite for the invasion of inflammatory tissue into bone. CD44 is a type I transmembrane glycoprotein that connects a variety of extracellular matrix proteins to the cell surface. Tumor necrosis factor (TNF) is a major inducer of chronic inflammation and its overexpression leads to chronic inflammatory arthritis. By generating CD44−/− human TNF-transgenic (hTNFtg) mice, we show that destruction of joints and progressive crippling is far more severe in hTNFtg mice lacking CD44, which also develop severe generalized osteopenia. Mutant mice exhibit an increased bone resorption due to enhanced number, size, and resorptive capacity of osteoclasts, whereas bone formation and osteoblast differentiation are not affected. Responsiveness of CD44-deficient osteoclasts toward TNF is enhanced and associated with increased activation of the p38 mitogen-activated protein kinase. These data identify CD44 as a critical inhibitor of TNF-driven joint destruction and inflammatory bone loss.
Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA
Authors: Leslie Alasdair , Kavanagh Daniel , Honeyborne Isobella , Pfafferott Katja , Edwards Charles , Pillay Tilly , Hilton Louise , Thobakgale Christina , Ramduth Danni , Draenert Rika , Le Gall Sylvie , Luzzi Graz , Edwards Anne , Brander Christian , Sewell Andrew K. , Moore Sarah , Mullins James , Moore Corey , Mallal Simon , Bhardwaj Nina , Yusim Karina , Phillips Rodney , Klenerman Paul , Korber Bette , Kiepiela Photini , Walker Bruce , Goulder Philip
Published: March 2005

Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of “negatively associated” or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development.
Platelet activation leads to activation and propagation of the complement system
Authors: del Conde Ian , Crúz Miguel A. , Zhang Hui , López José A. , Afshar-Kharghan Vahid
Published: March 2005

Inflammation and thrombosis are two responses that are linked through a number of mechanisms, one of them being the complement system. Various proteins of the complement system interact specifically with platelets, which, in turn, activates them and promotes thrombosis. In this paper, we show that the converse is also true: activated platelets can activate the complement system. As assessed by flow cytometry and immunoblotting, C3 deposition increased on the platelet surface upon cell activation with different agonists. Activation of the complement system proceeded to its final stages, which was marked by the increased generation of the anaphylotoxin C3a and the C5b-9 complex. We identified P-selectin as a C3b-binding protein, and confirmed by surface plasmon resonance binding that these two proteins interact specifically with a dissociation constant of 1 μM. Using heterologous cells expressing P-selectin, we found that P-selectin alone is sufficient to activate the complement system, marked by increases in C3b deposition, C3a generation, and C5b-9 formation. In summary, we have found that platelets are capable of activating the complement system, and have identified P-selectin as a receptor for C3b capable of initiating complement activation. These findings point out an additional mechanism by which inflammation may localize to sites of vascular injury and thrombosis.
Granulocyte/macrophage colony-stimulating factor and accessory cells modulate radioprotection by purified hematopoietic cells
Authors: Katsumoto Tamiko R. , Duda Jennifer , Kim Andrew , Wardak Zabihullah , Dranoff Glenn , Clapp D. Wade , Shannon Kevin
Published: March 2005

Granulocyte/macrophage colony-stimulating factor (GM-CSF) promotes the survival, proliferation, and differentiation of myeloid lineage cells and regulates chemotaxis and adhesion. However, mice in which the genes encoding GM-CSF (Gmcsf) or the β common subunit of the GM-CSF receptor (βc) are inactivated display normal steady-state hematopoiesis. Here, we show that host GM-CSF signaling strongly modulates the ability of donor hematopoietic cells to radioprotect lethally irradiated mice. Although bone marrow mononuclear cells efficiently rescue Gmcsf mutant recipients, fetal liver cells and Sca1+ lin−/dim marrow cells are markedly impaired. This defect is partially attributable to accessory cells that are more prevalent in bone marrow. In contrast, Gmcsf-deficient hematopoietic stem cells demonstrate normal proliferative potentials. Short-term survival is also impaired in irradiated βc mutant recipients transplanted with fetal liver or bone marrow. These data demonstrate a nonredundant function of GM-CSF in radioprotection by donor hematopoietic cells that may prove relevant in clinical transplantation.
A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice
Authors: Yoshitomi Hiroyuki , Sakaguchi Noriko , Kobayashi Katsuya , Brown Gordon D. , Tagami Tomoyuki , Sakihama Toshiko , Hirota Keiji , Tanaka Satoshi , Nomura Takashi , Miki Ichiro , Gordon Siamon , Akira Shizuo , Nakamura Takashi , Sakaguchi Shimon
Published: March 2005

A combination of genetic and environmental factors can cause autoimmune disease in animals. SKG mice, which are genetically prone to develop autoimmune arthritis, fail to develop the disease under a microbially clean condition, despite active thymic production of arthritogenic autoimmune T cells and their persistence in the periphery. However, in the clean environment, a single intraperitoneal injection of zymosan, a crude fungal β-glucan, or purified β-glucans such as curdlan and laminarin can trigger severe chronic arthritis in SKG mice, but only transient arthritis in normal mice. Blockade of Dectin-1, a major β-glucan receptor, can prevent SKG arthritis triggered by β-glucans, which strongly activate dendritic cells in vitro in a Dectin-1–dependent but Toll-like receptor-independent manner. Furthermore, antibiotic treatment against fungi can prevent SKG arthritis in an arthritis-prone microbial environment. Multiple injections of polyinosinic-polycytidylic acid double-stranded RNA also elicit mild arthritis in SKG mice. Thus, specific microbes, including fungi and viruses, may evoke autoimmune arthritis such as rheumatoid arthritis by stimulating innate immunity in individuals who harbor potentially arthritogenic autoimmune T cells as a result of genetic anomalies or variations.
Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen
Authors: Haynes Laura , Eaton Sheri M. , Burns Eve M. , Randall Troy D. , Swain Susan L.
Published: March 2005

Using a T cell receptor transgenic (TCR Tg) mouse model, we have shown that TCR Tg CD4 cells from aged mice retain a naive phenotype, but exhibit reduced proliferation and IL-2 production in response to the antigen compared with cells from young mice. We hypothesize that age-related decreases in T cell function may be partly related to the age of the T cells. Because thymic output is decreased with age, peripheral T cells in older individuals are likely to be older than those in younger individuals. To investigate this possibility, we have manipulated the age of CD4 T cells in the periphery of young and aged mice. The production of new T cells was induced by depleting peripheral CD4 T cells or by creating bone marrow chimeras. In both young and aged individuals where we induced the production of new T cells, these newly generated cells exhibited robust responses to antigen ex vivo and in vivo, exhibiting good expansion, IL-2 production, and cognate helper function. Our results suggest that age-related defects in response to antigenic stimulation, in part, are caused by the age of the CD4 T cells.
A mutation in the Icsbp1 gene causes susceptibility to infection and a chronic myeloid leukemia–like syndrome in BXH-2 mice
Authors: Turcotte Karine , Gauthier Susan , Tuite Ashleigh , Mullick Alaka , Malo Danielle , Gros Philippe
Published: March 2005

BXH-2 mice develop a fatal myeloid leukemia by a two-step mutagenic process. First, a BXH-2–specific recessive mutation causes a myeloproliferative syndrome. Second, retroviral insertions alter oncogenes or tumor suppressors, resulting in clonal expansion of leukemic cells. We have identified a recessive locus on chromosome 8 (Myls) that is responsible for myeloproliferation in BXH-2. This Myls interval has been narrowed down to 2 Mb and found to contain several positional candidates, including the interferon consensus sequence–binding protein 1 gene (Icsbp, also known as interferon regulatory factor 8 [IRF8]). We show that BXH-2 mice carry a mutation (915 C to T) resulting in an arginine-to-cysteine substitution at position 294 within the predicted IRF association domain of the protein. Although expression of Icsbp1 mRNA transcripts is normal in BXH-2 splenocytes, these cells are unable to produce interleukin 12 and interferon-γ in response to activating stimuli, confirming that R294C behaves as a loss-of-function mutation. Myeloproliferation in BXH-2 mice is concomitant to increased susceptibility to Mycobacterium bovis (BCG) despite the presence of resistance alleles at the Nramp1 locus. These results suggest a two-step model for chronic myeloid leukemia in BXH-2, in which inactivation of Icsbp1 predisposes to myeloproliferation and immunodeficiency. This event is required for retroviral replication, and subsequent insertional mutagenesis that causes leukemia in BXH-2 mice.
In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma
Authors: van Rijt Leonie S. , Jung Steffen , KleinJan Alex , Vos Nanda , Willart Monique , Duez Catherine , Hoogsteden Henk C. , Lambrecht Bart N.
Published: March 2005

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell–mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4+ T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c+ DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c+ cells, endogenous or adoptively transferred CD4+ Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c+ DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.
Signaling for NKT cell development
Authors: Borowski Christine , Bendelac Albert
Published: March 2005

New studies demonstrate a critical role for the adaptor protein SAP (SLAM-associated protein) during NKT cell development. By connecting homotypic SLAM family receptor interactions with the FynT Src kinase, SAP may integrate a set of long-standing yet seemingly disparate observations characterizing NKT cell development. In fact, SAP-dependent signaling may underlie the development of multiple unconventional T cell lineages whose thymic selection relies on homotypic interactions between hematopoietic cells.
T cell aging
Authors: Nikolich-Žugich Janko
Published: March 2005

The immune system exhibits profound age-related changes, collectively termed immunosenescence. The most visible of these is the decline in protective immunity, which results from a complex interaction of primary immune defects and compensatory homeostatic mechanisms. The sum of these changes is a dysregulation of many processes that normally ensure optimal immune function. Recent advances suggest that old mice can produce fully functional new T cells, opening both intriguing inquiry avenues and raising critical questions to be pursued.
Identifying genes that regulate bone remodeling as potential therapeutic targets
Authors: Krane Stephen M.
Published: March 2005

Bone remodeling, a coupled process involving bone resorption and formation, is initiated by mechanical signals and is controlled by local and systemic factors that regulate osteoblast and osteoclast differentiation and function. An excess of resorption over formation leads to the bone loss and increased propensity to fracture that is characteristic of osteoporosis. A newly described inhibitor of osteoblast differentiation, Ciz, interferes with bone morphogenic protein signaling. As a consequence, Ciz-deficient mice develop increased bone mass.
Large-scale behaviour of packet-switched networks: theoretical analysis framework
Authors: Stepanenko Alexander S , Constantinou Costas C , Arvanitis Theodoros N
Published: March 2005

We present a possible way to study large-size packet-switched networks capable of accounting for interactions between adjacent queues. The interaction between queues arises, because of the influence of the routing protocol on each switching decision, and the stochastic nature of packet lengths and inter-arrival times.Both the methodology and the analysis tools are adaptations of methods of statistical mechanics. The justification for their use lies in recent experimental evidence indicating that aggregate, core-network IP traffic, exhibits quasi-Markovian properties when the network is heavily loaded.In this paper, we present a general methodology and introduce approximations that greatly simplify the analysis. These approximations, are owing to the quasi-Markovian nature of the traffic and the large size of the network.
Effects on weed and invertebrate abundance and diversity of herbicide management in genetically modified herbicide-tolerant winter-sown oilseed rape
Authors: Bohan David A , Boffey Caroline W.H , Brooks David R , Clark Suzanne J , Dewar Alan M , Firbank Les G , Haughton Alison J , Hawes Cathy , Heard Matthew S , May Mike J , Osborne Juliet L , Perry Joe N , Rothery Peter , Roy David B , Scott Rod J , Squire Geoff R , Woiwod Ian P , Champion Gillian T
Published: March 2005

We evaluated the effects of the herbicide management associated with genetically modified herbicide-tolerant (GMHT) winter oilseed rape (WOSR) on weed and invertebrate abundance and diversity by testing the null hypothesis that there is no difference between the effects of herbicide management of GMHT WOSR and that of comparable conventional varieties. For total weeds there were few treatment differences between GMHT and conventional cropping, but large and opposite treatment effects were observed for dicots and monocots. In the GMHT treatment, there were fewer dicots and more monocots than in conventional crops. At harvest, dicot biomass and seed rain in the GMHT treatment were one-third of that in the conventional, while monocot biomass was threefold greater and monocot seed rain almost fivefold greater in the GMHT treatment than in the conventional. These differential effects persisted into the following two years of the rotation. Bees and butterflies that forage and select for dicot weeds were less abundant in GMHT WOSR management in July. Year totals for Collembola were greater under GMHT management. There were few other treatment effects on invertebrates, despite the marked effects of herbicide management on the weeds.
Developing indicators for European birds
Authors: Gregory Richard D , van Strien Arco , Vorisek Petr , Gmelig Meyling Adriaan W , Noble David G , Foppen Ruud P.B , Gibbons David W
Published: March 2005

The global pledge to deliver ‘a significant reduction in the current rate of biodiversity loss by 2010’ is echoed in a number of regional and national level targets. There is broad consensus, however, that in the absence of conservation action, biodiversity will continue to be lost at a rate unprecedented in the recent era. Remarkably, we lack a basic system to measure progress towards these targets and, in particular, we lack standard measures of biodiversity and procedures to construct and assess summary statistics. Here, we develop a simple classification of biodiversity indicators to assist their development and clarify purpose. We use European birds, as example taxa, to show how robust indicators can be constructed and how they can be interpreted. We have developed statistical methods to calculate supranational, multi-species indices using population data from national annual breeding bird surveys in Europe. Skilled volunteers using standardized field methods undertake data collection where methods and survey designs differ slightly across countries. Survey plots tend to be widely distributed at a national level, covering many bird species and habitats with reasonable representation. National species' indices are calculated using log-linear regression, which allows for plot turnover. Supranational species' indices are constructed by combining the national species' indices weighted by national population sizes of each species. Supranational, multi-species indicators are calculated by averaging the resulting indices. We show that common farmland birds in Europe have declined steeply over the last two decades, whereas woodland birds have not. Evidence elsewhere shows that the main driver of farmland bird declines is increased agricultural intensification. We argue that the farmland bird indicator is a useful surrogate for trends in other elements of biodiversity in this habitat.
Volatile corrosion inhibitors: a review
Authors: Bastidas D.M. , Cano E. , Mora E.M.
Published: March 2005

Purpose

To provide a selective bibliography for graduate students and new faculty members with sources which can help them develop their academic career.

Design/methodology/approach

A range of published (1951‐2004) works, which aim to discuss the main parameters of the volatile corrosion inhibition process. The sources are sorted into sections: transport of the volatile corrosion inhibitor (VCI) to the metallic surface, vapour pressure of a VCI, dependence of vapour pressure upon temperature, effect of pH on VCI behaviour, formation and destruction of adsorbed films, and volatile corrosion inhibitor monitors (VCIM).

Findings

Provides information about each source, indicating what can be found there and how the information can help. Recognises the lack of real training of many academics before they are expected to take on teaching/researching duties and finds some texts which help.

Research limitations/implications

It is not an exhaustive list and apart from several UK and US books all the rest are EU and US publications which perhaps limits its usefulness elsewhere.

Practical implications

A very useful list of the most common compounds used as VCIs is reported.

Originality/value

This paper fulfils an identified information/resources need and offers practical help to an individual starting out on and academic career and to professional with some experience on corrosion inhibition.
Corrosion protection aspects of electrochemically prepared polyfurfural film on low carbon steel
Authors: Grosser F.N. , Gonçalves R.S.
Published: March 2005

Purpose

This paper describes new experimental evidence of the electropolymerization of furfural on non‐noble metals such as low‐carbon steel. The organic compound (2‐furancarboxaldehyde) was selected because it is easily obtained from biomass and other sources. These results confirm the possibility of synthesizing a polymeric film, with good adherence and stability that provides a new protective barrier against corrosion to this kind of metal.

Design/methodology/approach

Electrochemical methods such as chronoamperometry, chronopotentiometry and cyclic voltammetry (CV) were used to synthesize and characterize the polymer formed on the electrode surface. Some electrochemical impedance experiments were conducted in order to confirm the electrochemical behavior modification of the electrode, due to the presence of the organic film on the surface.

Findings

The polymer film could be grown galvanostatically, potentiostatically or, during CV. The corrosion protection afforded by polyfurfural (PFy) that had been formed on a low‐carbon steel surface was confirmed by the CV, EIS and polarization curves.

Research limitations/implications

The possible synthesis of a new polymeric structure on a non‐noble metal is interesting from a practical point of view. However, more experiments are necessary in order to test other organic solvents and other non‐noble metals such as zinc, aluminium, copper, etc.

Practical implications

The corrosion protection afforded by PFy that had been formed on a low‐carbon steel surface was confirmed by the CV, EIS and polarization curves. Anodic current values associated with metal oxidation decreased when the metal surface was covered with the organic film.

Originality/value

This is the first paper that deals with the electropolymerization of furfural on this type of metal. It was not found in the literature evidences that this polymer was synthesized before.
Studies of plasma spray coatings on a Fe‐base superalloy, their structure and high temperature oxidation behaviour
Authors: Singh Harpreet , Puri D. , Prakash S.
Published: March 2005

Purpose

Plasma spray coating technologies are capable of depositing a wide range of compositions without significantly heating the substrate. The objective is to characterise plasma sprayed metallic coatings on a Fe‐based superalloy.

Design/methodology/approach

NiCrAlY, Ni‐20Cr, Ni3Al and Stellite‐6 metallic coatings were deposited on a Fe‐based superalloy (32Ni‐21Cr‐0.3Al‐0.3Ti‐1.5Mn‐1.0Si‐0.1C‐Bal Fe) by the shrouded plasma spray process. The coatings were characterised in relation to coating thickness, porosity, microhardness and microstructure. The high temperature oxidation behaviour of the coatings was investigated in brief. The techniques used in the present investigation include metallography, XRD and SEM/EDAX.

Findings

All the coatings exhibited a lamellar structure with distinctive boundaries along with the presence of some porosity and oxide inclusions. The microhardness of the coatings was observed to vary with the distance from the coating‐substrate interface. The St‐6 coating had the maximum microhardness, whereas the lowest hardness was exhibited by the Ni3Al coating. The phases revealed by XRD of the coatings confirmed the formation of solid solutions, whereas EDAX analysis of the as‐sprayed coatings confirmed the presence of basic elements of the coating powders. So far as high temperature oxidation behaviour is concerned, all of the coatings followed the parabolic rate law and resulted in the formation of protective oxide scales on the substrate superalloy.

Originality/value

The plasma spray process provides the possibility of developing coatings of Ni3Al as well as commercial available NiCrAlY, Ni‐20Cr and St‐6 powders on Fe‐based superalloy Superfer 800H
The effect of some phthalimide derivatives on the corrosion behaviour of copper in nitric acid
Authors: Fouda A.S. , Abd El‐Aal A. , Kandil A.B.
Published: March 2005

Purpose

To show the effect of organic compounds containing O and N atoms on the corrosion inhibition of Cu in HNO3 and; the effect of some donating substituent groups on the corrosion inhibition.

Design/methodology/approach

A range of published papers (1956‐1995), which aim to discuss the effect of organic compounds on the corrosion inhibition process. Two methods were used to determine the rate of corrosion, these methods were weight loss and polarisation. The effect of temperature and concentration were studied. The thermodynamic parameters for the process were computed and discussed.

Findings

Provides information about weight loss and polarisation methods and how to prepare the Cu samples before and after tests. This will provide many academics relevant information before teaching or researching duties.

Research limitation/implications

The paper may be using withdrawing substituting groups in addition to donating groups, this will improve the discussion, also the paper does not use the technique of impedance spectroscopy for comparison.

Practical implications

To use Cu alloy for comparison and to use other compounds with larger molecular weights.

Originality value

The use of some phthalimide derivatives as corrosion inhibitors for Cu in HNO3, provide more information on Cu corrosion for academic researchers and provide practical help for starting researchers.
Robert Fairthorne and the empirical power laws
Authors: Rousseau Ronald
Published: March 2005

Purpose

Aims to review Fairthorne's classic article “Empirical hyperbolic distributions (Bradford‐Zipf‐Mandelbrot) for bibliometric description and prediction” (Journal of Documentation, Vol. 25, pp. 319‐343, 1969), as part of a series marking the Journal of Documentation's 60th anniversary.

Design/methodology/approach

Analysis of article content, qualitative evaluation of its subsequent impact, citation analysis, and diffusion analysis.

Findings

The content, further developments and influence on the field of informetrics of this landmark paper are explained.

Originality/value

A review is given of the contents of Fairthorne's original article and its influence on the field of informetrics. Its transdisciplinary reception is measured through a diffusion analysis.