bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnic variation of Fcγ receptor polymorphism in Sami and Norwegian populations
Authors: Torkildsen Øivind , Utsi Egil , Mellgren Svein Ivar , Harbo Hanne F. , Vedeler Christian A. , Myhr Kjell‐Morten 
Published: June 2005

SummaryReceptors for the Fc domain of IgG (FcγR) play a critical role in linking cellular and humoral immunity. The various FcγR genotypes may contribute to differences in infectious and immune‐related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune‐related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of FcγR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the FcγRIIA, FcγRIIIA and FcγRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian FcγRIIA, FcγRIIIA and FcγRIIIB genotypes differed significantly. The Samis had higher frequencies of the FcγRIIa‐H/H131, FcγRIIIa‐F/F158 and FcγRIIIb‐NA1/NA1 genotypes. The FcγR genotypes were non‐randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.
Lipoteichoic acid induces nuclear factor‐κB activation and nitric oxide synthase expression via phosphatidylinositol 3‐kinase, Akt, and p38 MAPK in RAW 264.7 macrophages
Authors: Kao Shang‐Jyh , Lei Hui‐Chieh , Kuo Chen‐Tzu , Chang Ming‐Shyan , Chen Bing‐Chang , Chang Yau‐Chong , Chiu Wen‐Ta , Lin Chien‐Huang 
Published: June 2005

SummaryWe previously demonstrated that lipoteichoic acid (LTA) might activate phosphatidylcholine‐phospholipase C (PC‐PLC) and phosphatidylinositol‐phospholipase C (PI‐PLC) to induce protein kinase C activation, which in turn initiates nuclear factor‐κB (NF‐κB) activation and finally induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release in RAW 264.7 macrophages. In this study, we further investigated the roles of tyrosine kinase, phosphatidylinositiol 3‐kinase (PI3K)/Akt, and p38 mitogen‐activated protein kinase (MAPK) in LTA‐induced iNOS expression and NO release in RAW 264.7 macrophages. Tyrosine kinase inhibitors (genistein and tyrphostin AG126), PI3K inhibitors (wortmannin and LY 294002), and a p38 MAPK inhibitor (SB 203580) attenuated LTA‐induced iNOS expression and NO release in concentration‐dependent manners. Treatment of RAW 264.7 macrophages with LTA caused time‐dependent activations of Akt and p38 MAPK. The LTA‐induced Akt activation was inhibited by wortmannin, LY 294002, genistein, and tyrphostin AG126. The LTA‐induced p38 MAPK activation was inhibited by genistein, tyrphostin AG126, wortmannin, LY 294002, and SB 203580. The LTA‐induced formation of an NF‐κB‐specific DNA–protein complex in the nucleus was inhibited by wortmannin, LY 294002, genistein, tyrphostin AG126, and SB 203580. Treatment of macrophages with LTA caused an increase in κB‐luciferase activity, and this effect was inhibited by tyrphostin AG126, wortmannin, LY 294002, the Akt dominant negative mutant (AktDN), and SB 203580. Based on those findings, we suggest that LTA might activate the PI3K/Akt pathway through tyrosine kinase to induce p38 MAPK activation, which in turn initiates NF‐κB activation, and ultimately induces iNOS expression and NO release in RAW 264.7 macrophages.
Multivalent recombinant proteins for probing functions of leucocyte surface proteins such as the CD200 receptor
Authors: Voulgaraki Despina , Mitnacht‐Kraus Rita , Letarte Michelle , Foster‐Cuevas Mildred , Brown Marion H. , Barclay A. Neil 
Published: June 2005

SummaryCD200 (OX2) is a membrane glycoprotein that interacts with a structurally related receptor (CD200R) involved in the regulation of macrophage function. The interaction is of low affinity (KD ∼ 1 μm) but can be detected using CD200 displayed in a multivalent form on beads or with dimeric fusion proteins consisting of the extracellular region of CD200 and immunoglobulin Fc regions. We prepared putative pentamers and trimers of mouse CD200 with sequences from cartilage oligomeric matrix protein (COMP) and surfactant protein D (SP‐D), respectively. The COMP protein gave high‐avidity binding and was a valuable tool for showing the interaction whilst the SP‐D protein gave weak binding. In vivo experiments showed that an agonistic CD200R monoclonal antibody caused some amelioration in a model of experimental autoimmune encephalomyelitis but the COMP protein was cleared rapidly and had minimal effect. Pentameric constructs also allowed detection of the rat CD48/CD2 interaction, which is of much lower affinity (KD ∼ 70 μm). These reagents may have an advantage over Fc‐bearing hybrid molecules for probing cell surface proteins without side‐effects due to the Fc regions. The CD200‐COMP gave strong signals in protein microarrays, suggesting that such reagents may be valuable in high throughput detection of weak interactions.
Inhibition of immunoglobulin E synthesis through FcγRII (CD32) by a mechanism independent of B‐cell receptor co‐cross‐linking
Authors: Horejs‐Hoeck Jutta , Hren Andrea , Mudde Geert C. , Woisetschläger Maximilian 
Published: June 2005

SummaryThe inhibitory effect on antibody production by immune complexes has been shown to depend on co‐ligation of the B‐cell antigen receptor (BCR) with the low‐affinity receptor for immunoglobulin G (IgG) (FcγRIIb, CD32). Here we report that immunoglobulin E (IgE) synthesis, induced in a BCR‐independent manner by interleukin‐4 (IL‐4) and anti‐CD40 antibody, was inhibited by CD32 ligation. The observed effect was specific for CD32 as, first, antibodies directed against other B‐cell surface structures had no inhibitory effect, and, second, treatment with anti‐CD32 of cells that had been in culture for 2 days was ineffective owing to the down‐regulation of CD32 expression. IgE inhibition was also observed in cells stimulated by IL‐4/CD40 F(ab′)2 or IL‐4 plus soluble CD40 ligand, demonstrating that co‐cross‐linking of CD32 and CD40 was not necessary to induce inhibition. Mechanistic studies into the IgE class switch process demonstrated that IL‐4/anti‐CD40‐induced IgE germline gene transcription and B‐cell proliferation were not affected by CD32 ligation. The data demonstrate that the negative regulatory role of the CD32 molecule is not restricted to BCR‐induced B‐cell activation, but is also functional on other B‐cell activation pathways mediated by CD40 and IL‐4.
Maintenance of long‐term tumour‐specific T‐cell memory by residual dormant tumour cells
Authors: Mahnke Yolanda D. , Schwendemann Jochen , Beckhove Philipp , Schirrmacher Volker 
Published: June 2005

SummaryLacZ (Gal)‐reactive immune cells were transferred into athymic nu/nu mice inoculated with Gal‐expressing syngeneic tumour cells (ESbL‐Gal) in order to study tumour‐protective T‐cell memory. This transfer prevented tumour outgrowth in recipients and resulted in the persistence of a high frequency of Gal‐specific CD8+ T cells in the bone marrow and spleen. In contrast, such Ag‐specific memory CD8+ T cells were not detectable by peptide–major histocompatibility complex (MHC) multimer staining in animals that had not previously received an antigenic challenge. Even though CD44hi memory T cells from the bone marrow showed a significantly higher turnover rate, as judged by bromodeoxyuridine (BrdU) incorporation, than respective cells from spleen or lymph nodes, as well as in comparison to CD44lo naïve T cells, these findings suggest that tumour‐associated antigen (TAA) from residual dormant tumour cells are implicated in maintaining high frequencies of long‐term surviving Gal‐specific memory CD8+ T cells. Memory T cells could be recruited to the peritoneal cavity by tumour vaccination of immunoprotected nu/nu mice and exhibited ex vivo antitumour reactivity. Long‐term immune memory and tumour protection could be maintained over four successive transfers between tumour‐inoculated recipients, which involved periodic antigenic restimulation in vivo prior to reisolating the cells for adoptive transfer. Using a cell line (ESbL‐Gal‐BM) that was established from dormant tumour cells isolated from the bone marrow of immunoprotected animals, it could be demonstrated that the tumour cells had up‐regulated the expression of MHC class I molecules and down‐regulated the expression of several adhesion molecules during the in vivo passage. Our results suggest that the bone marrow microenvironment has special features that are of importance for the maintenance of tumour dormancy and immunological T‐cell memory, and that a low level of persisting antigen favours the maintenance of Ag‐specific memory T cells over irrelevant memory T cells.
Circulating anti‐retinal antibodies as immune markers in age‐related macular degeneration
Authors: Patel Nishal , Ohbayashi Masahara , Nugent Alex K. , Ramchand Kanchan , Toda Masako , Chau Kai‐Yin , Bunce Catey , Webster Andrew , Bird Alan C. , Ono Santa Jeremy , Chong Victor 
Published: June 2005

SummaryAge‐related macular maculopathy (ARM) and age‐related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age‐matched controls to detect circulating anti‐retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age‐matched control subjects (n = 39). The sera were analysed for anti‐retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93·75%) and CNV (82·27%) were found to have a significantly (P = 0·02) higher titre of autoantibodies to the retina in comparison with controls (8·69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0·0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti‐retinal immunoglobulins to retinal antigens. As anti‐retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD.
Expression of regulator of G protein signalling proteins in natural killer cells, and their modulation by Ly49A and Ly49D
Authors: Kveberg Lise , Ryan James C. , Rolstad Bent , Inngjerdingen Marit 
Published: June 2005

SummaryThe small GTPase accelerators regulator of G protein signalling (RGS) proteins are important regulators of proximal signalling from G protein coupled receptors. Although natural killer (NK) cells express a number of G‐protein coupled receptors, expression of RGS proteins has not been investigated. We analysed the expression of RGS proteins in rat NK cells, and detected mRNA for RGS1, RGS2, RGS5, RGS8, RGS16, and RGS18. Interestingly, when we included a panel of different leucocyte subsets, we found that RGS8 was selectively expressed by NK cells. NK cells are under control of both activating and inhibitory receptors and, utilizing a xenogeneic system where the mouse activating Ly49D or inhibitory Ly49A receptors were transfected into the rat RNK‐16 cell line, the potential regulation of RGS proteins by single NK cell receptors was studied. We found that ligation of Ly49D led to a rapid and transient increase in message for RGS2, while Ly49A ligation up‐regulated RGS2, RGS16, and RGS18 mRNA. Both receptors also induced a prolonged increase in RGS2 endogenous protein levels. These findings suggest that RGS proteins may be influenced by or involved in NK cell receptor events, suggesting a crosstalk between G‐protein coupled receptors and NK cell receptors.
Integrin CD11a cytoplasmic tail interacts with the CD45 membrane‐proximal protein tyrosine phosphatase domain 1
Authors: Geng Xin , Tang Ren‐Hong , Law S. K. Alex , Tan Suet‐Mien 
Published: June 2005

SummaryLeucocyte adhesion receptor integrin CD11aCD18 and the transmembrane receptor‐like protein tyrosine phosphatase (RPTP) CD45 mediate immune synapse formation and signalling during antigen presentation. Previous cocapping studies on human naïve T cells demonstrate an interaction between CD11aCD18 and CD45. CD45 cross‐linking also has an effect on the ligand‐binding activity of CD11aCD18. However, the mode of interaction between CD11aCD18 and CD45 remains unclear. Herein, yeast two‐hybrid analysis identified a partial CD45 cytoplasmic tail interacting with that of CD11a. The CD45 cytoplasmic tail comprises a membrane proximal (Mp) region, protein tyrosine phosphatase domain 1 (D1), spacer, D2, and carboxyl terminus. CD45 Mp‐D1 was found to be the main interacting region for the CD11a cytoplasmic tail. In contrast, the full‐length CD45 cytoplasmic tail interacted weakly with that of CD11a. It has been reported that CD45 Mp‐D1 but not the full‐length cytoplasmic tail forms a homodimer whose enzymatic activity is inhibited. Our in vitro binding and enzymatic assays showed that the homodimeric CD45 cytoplasmic tail interacts with that of CD11a. The biological function of CD45 dimerization and its association with CD11a remains to be investigated.
Supplementation of CXCL12 (CXCL12) induces homing of CD11c+ dendritic cells to the spleen and enhances control of Plasmodium berghei malaria in BALB/c mice
Authors: Garnica Margoth Ramos , De Moraes Luciana Vieira , Rizzo Luiz Vicente , De Andrade Heitor Franco 
Published: June 2005

SummaryIn malaria, parasitaemia is controlled in the spleen, a multicomponent organ that undergoes changes in its cellular constituents to control the parasite. During this process, dendritic cells (DCs) orchestrate the positioning of effector cells in a timely manner for optimal parasite clearance. We have recently demonstrated that CXCL12 [stromal cell‐derived factor‐1 (CXCL12)] supplementation partially restores the ability to control parasitaemia in Plasmodium berghei‐infected mice. In the present study, we investigated the nature of the DCs involved by flow cytometry and immunohistochemistry of CD11c+ cells. Flow cytometry of bone marrow cells showed that infection with P. berghei did not alter the proportion of CD11c+ cells present in this haematopoietic compartment, while CXCL12 supplementation of naïve uninfected mice induced only minor increases in the population of CD11c+ cells. In the spleen, P. berghei infection alone resulted in an increase in CD11c+ cells as compared with naïve animals. Exogenously administered CXCL12 in the absence of infection resulted in a significant expansion of the splenic CD11c+ population, and this effect was even more pronounced in infected and supplemented mice. Immunohistochemistry revealed that CD11c+ cells infiltrated the perivascular areas and marginal zone of the spleen in infected animals treated with CXCL12, suggesting that this chemokine induces homing of CD11c+ dendritic cells to the splenic compartment. Our results show that small amounts of CXCL12 supplementation are effective in recruiting DCs to the spleens of both uninfected and infected mice, suggesting the participation of CXCL12 and CD11c+ cells in the establishment of an adequate environment in the spleen for malaria control.
A model of ruddy duck Oxyura jamaicensis eradication for the UK
Authors: SMITH G. C. , HENDERSON I. S. , ROBERTSON P. A. 
Published: June 2005

Summary

Non‐native species are the second most important threat to global biodiversity after habitat loss. The North American ruddy duck Oxyura jamaicensis established a feral population in the UK more than 40 years ago, and it is now threatening the endangered white‐headed duck Oxyura leucocephala through hybridization. We utilized a simple generic model, which includes uncertainty in parameter estimates and can be used for any invasive species, to assess the time frame for successful control.
A simple spreadsheet‐based model was produced to provide the UK government with an assessment of whether sufficient ruddy ducks could be culled to allow the UK population to be reduced to fewer than 175 individuals (> 97% population reduction) within 10 years.
Data on changes in numbers of ruddy duck at the main UK wintering sites were collected during a regional control trial, and a stochastic Monte Carlo simulation model was constructed to project the UK population under a variety of control strategies. Three variables were included in the model: cull rate per person (i.e. by how much each control officer could reduce the national population per year), number of control officers, and changes in the ruddy duck population growth rate as the population was reduced.
Parameter estimation was kept to a minimum by using historical annual population growth rates as a basis for future growth rates. The historical data show a reduction in both the mean growth rate and in its variability when the population is in excess of 2000 birds. Density‐dependent and density‐independent models were produced. These all gave similar times to reach the target population, with some difference in the variance estimates between models.
Simulations were run with a maximum annual population reduction of between 0·50 and 0·80, and between 12 and 20 control officers. A total of 8000 simulations was performed for each of the 63 different scenarios for each of the models.
The mean time to reduce the UK ruddy duck population by 97% was predicted to be between 3 and 5 years, with 14 or 15 control officers reducing the population by between 65% and 70% per year. There was an 80% certainty that the population could be reduced to this level by 16 control officers within 4–6 years if annual reductions of more than 60% were achieved.
Synthesis and applications. The novel spreadsheet model presented here can easily be applied to a range of eradication schemes where limited data are available on population size and culling efficacy. This would allow funding bodies to have a greater degree of certainty about the cost and outcome of a trial eradication programme.
Nitrogen saturation in UK moorlands: the critical role of bryophytes and lichens in determining retention of atmospheric N deposition
Authors: CURTIS C. J. , EMMETT B. A. , GRANT H. , KERNAN M. , REYNOLDS B. , SHILLAND E. 
Published: June 2005

Summary

Anthropogenic nitrogen (N) deposition may have several impacts on upland moorland ecosystems, including changes in vegetation composition, eutrophication and surface water acidification through nitrate leaching, but few studies linking N deposition to key biogeochemical processes have been published.
A stable isotope tracer (15N) was used to determine the fate of inorganic N inputs to four moorland catchments across gradients of N deposition and leaching, through 2‐weekly additions to experimental plots on major soil types over 1 year.
An apparent decline in total 15N recovery from soils and vegetation as the proportion of leached N deposition increased was not significant at the P = 0·05 level, but a significant relationship was found for recovery in mosses and lichens.
Vegetation retained 31–68% of 15N inputs, and 15N recovery increased significantly (P = 0·01) with biomass for all compartments except woody shrubs. Mosses and lichens showed far greater 15N recovery per unit biomass than grasses or ericaceous shrubs. There was no significant variation in the proportion of 15N recovered in higher plants across the N deposition gradient (24–29%). In contrast, the proportion recovered in mosses and lichens declined from 44% to 2% as deposition increased, mirroring a decline in their biomass and showing a highly significant inverse relationship (P = 0·01) with nitrate leaching.
The proportion of 15N recovered in litter plus surface soils (33–39%) was remarkably constant across the deposition gradient for a variety of soil types. However, significantly declining recovery per unit biomass in litter (P < 0·05) suggested progressive N saturation of this sink and increasing importance of retention in underlying surface soils as deposition increased.
Synthesis and applications. Past studies have demonstrated a decline in mosses and lichens in response to increasing N deposition, but we show here for the first time that reduced N retention might result together with increased nitrate leaching into surface waters. The conservation of bryophyte and lichen flora on moorlands is therefore critical to prevent excessive nitrate leaching and associated surface water acidification and eutrophication. Ensuring management practices such as grazing or burning are at an intensity that does not further degrade the bryophyte and lichen communities may help minimize the impact of N deposition on freshwaters, but the only effective means to reduce the risk of N leaching is a reduction in N emissions.
Differences in invasibility of two contrasting habitats and invasiveness of two mugwort Artemisia vulgaris populations
Authors: BARNEY JACOB N. , DI TOMMASO ANTONIO , WESTON LESLIE A. 
Published: June 2005

Summary

Establishment success of non‐native invasive species is often attributable either to habitat invasibility or inherent species traits. In this study we explored the interplay between these two factors in the establishment, expansion and plasticity in growth of the clonally reproducing invasive weed mugwort Artemisia vulgaris in two contrasting habitats, as well as the potential management practice of monthly mowing.
We investigated resource allocation patterns and spatial distribution of ramets originating from two naturalized populations over a 3‐year period. Ramets from these morphologically distinct populations were transplanted into each of two contrasting habitats to determine the invasive potential of these populations and the relative resistance of each habitat to invasion.
Total ramet production, average ramet height and spatial distribution patterns differed significantly between the two populations, but the degree of variation in the response was habitat dependent. There were no interpopulation differences in total biomass production. Plastic responses in resource allocation patterns, spatial distribution of ramets and relative growth rates were observed, demonstrating differences in invasive potential between the two mugwort populations.
The two habitats differed in invasibility. This could have been the result of differences in community structure, competition for available resources, disturbance and/or invader traits. In addition, monthly defoliation (mowing) reduced mugwort ramet production by as much as 90% and as little as 10%.
Synthesis and applications. This study demonstrates that variation exists in habitat invasibility, and that intraspecific variation in growth patterns occurs in mugwort. The interaction between habitat traits and species characteristics was found to be important when determining invasion success. We also demonstrated that monthly mowing following the introduction of mugwort can substantially decrease the rate of spread of this clonal species, which may provide an effective management opportunity both for this species and for other clonal invaders.