CD28-negative cytolytic effector T cells frequently express NK receptors and are present at variable proportions in circulating lymphocytes from healthy donors and melanoma patients.

In humans, NK receptors are expressed by natural killer cells and some T cells, the latter of which are preferentially alphabetaTCR+ CD8+ cytolytic T lymphocytes (CTL). In this study we analyzed the expression of nine NK receptors (p58.1, p58.2, p70, p140, ILT2, NKRP1A, ZIN176, CD94 and CD94/NKG2A) in PBL from both healthy donors and melanoma patients. The percentages of NK receptor-positive T cells (NKT cells) varied strongly, and this variation was more important between individual patients than between individual healthy donors. In all the individuals, the NKT cells were preferentially CD28-, and a significant correlation was found between the percentage of CD28- T cells and the percentage of NK receptor+ T cells. Based on these data and the known activated phenotype of CD28- T cells, we propose that the CD28- CD8+ T cell pool represents or contains the currently active CTL population, and that the frequent expression of NK receptors reflects regulatory mechanisms modulating the extent of CTL effector function. Preliminary results indicate that some tumor antigen-specific T cells may indeed be CD28- and express NK receptors in vivo.

Low immunoglobulin levels in patients with cystic fibrosis: reduced inflammation or sign of common variable immunodeficiency syndrome?

Introduction: In children with cystic fibrosis (CF), low immunoglobulin (IgG) levels have been reported to be associated with significantly less severe lung disease. However, decreased IgG can be a sign for common variable immunodeficiency (CVID) and affect clinical outcome. The aim of this study was to analyze clinical and serological data of patients having low IgG levels in routine blood tests at annual assessment, particularly their antibody response to polysaccharide antigens. Method: Retrospective chart review of demographic data of CF patients followed at the pediatric CF clinic throughout 2009. Clinical parameters (genotype, pancreas sufficiency, FEV1), presence of Pseudomonas aeruginosa (PA) and number of exacerbations per year were correlated with immunoglobulin and vaccination antibodies levels (antibodies to pneumococcal serotypes 14, 19, 23, 1, 5 and 7F measured by enzyme-linked immune-sorbent assay). Results: 4 out of 60 patients (6.7%) had lower IgG-levels for age. Ages ranged from 1 year 8 months to 11 years, 2 boys, 2 girls. Three patients were delF508 homozygotes, one heterozygote composite delF508/G542X. All were pancreatic insufficient. FEV1 ranged from 74 to 108%. One patient never had colonization by PA, 2 had intermittent PA colonization and one was chronically infected. After conjugated vaccination all patients had protective antibodies against serotypes 14, 19, 23F. For serotypes not included in the vaccine, only one patient had protective titers for 1 out of 3 serotypes. None of the patients had received unconjugated pneumococcal vaccine. There was no significant clinical difference in FEV1, PA colonization or number of exacerbations according to IgG and vaccination antibody levels. Conclusion: Cystic Fibrosis patients with low immunoglobulin levels have normal antibody response to protein antigens. However, despite recurrent infections, there seems to be delayed or deficient antibody response to polysaccharide antigens. Prospective studies are needed to evaluate the development of polysaccharide antibody responses in CF-patients to monitor for CVID. With early detection of CF by newborn screening program, long term follow up could be started early in childhood.

Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans.

The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.

Melt/peridotite interaction in the Southern Lanzo peridotite: Field, textural and geochemical evidence

This paper presents field, petrographic-structural and geochemical data on spinet and plagioclase peridotites from the southern domain of the Lanzo ophiolitic peridotite massif (Western Alps). Spinet lherzolites, harzburgites and dunites crop out at Mt. Arpone and Mt. Musine. Field evidence indicates that pristine porphyroclastic spinet lherzolites are transformed to coarse granular spinet harzburgites, which are in turn overprinted by plagioclase peridotites, while strongly depleted spinet harzburgite and dunite bands and bodies replace the plagioclase peridotites. On the northern flank of Mt. Arpone, deformed, porphyroclastic (lithospheric) lherzolites, with diffuse pyroxenite banding, represent the oldest spinel-facies rocks. They show microstructures of a composite subsolidus evolution, suggesting provenance from deeper (asthenospheric) mantle levels and accretion to the lithosphere. These protoliths are locally transformed to coarse granular (reactive) spinet harzburgites and dunites, which show textures reminiscent of melt/rock reaction and geochemical characteristics suggesting that they are products of peridotite interaction with reactively percolating melts. Geochemical data and modelling suggest that <1-5% fractional melting of spinel-facies DMM produced the injected melts. Plagioclase peridotites are hybrid rocks resulting from pre-existing spinet peridotites and variable enrichment of plagioclase and micro-gabbroic material by percolating melts. The impregnating melts attained silica-saturation, as testified by widespread orthopyroxene replacement of olivine, during open system migration in the lithosphere. At Mt. Musine, coarse granular spinet harzburgite and dunite bodies replace the plagioclase peridotites. Most of these replacive, refractory peridotites have interstitial magmatic clinopyroxene with trace element compositions in equilibrium with MORB, while some Cpx have REE-depleted patterns suggesting transient geochemical features of the migrating MORB-type melts, acquired by interaction with the ambient plagioclase peridotite. These replacive spinet harzburgite and dunite bodies are interpreted as channels exploited for focused and reactive migration of silica-undersaturated melts with aggregate MORB compositions. Such melts were unrelated to the silica-saturated melts that refertilized the pre-existing plagioclase peridotites. Finally, MORB melt migration occurred along open fractures, now recorded as gabbroic dikes. Our data document the complexity of rock-types and mantle processes in the South Lanzo peridotite massif and describe a composite tectonic and magmatic scenario that is not consistent with the ``asthenospheric scenario'' proposed by previous authors. We envisage a ``transitional scenario'' in which extending subcontinental lithospheric mantle was strongly modified (both depleted and refertilized) by early melts with MORB-affinity formed by decompression partial melting of the upwelling asthenosphere, during pre-oceanic rifting and lithospheric thinning in the Ligurian Tethys realm. (C) 2006 Elsevier B.V. All rights reserved.

Effects of epitope modification on T cell receptor-ligand binding and antigen recognition by seven H-2Kd-restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative.

We tested for antigen recognition and T cell receptor (TCR)-ligand binding 12 peptide derivative variants on seven H-2Kd-restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd-peptide derivative complexes allowed direct assessment of TCR-ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR-ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was five-tenfold less efficient than TCR-ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR-ligand binding, and (d) one partial TCR agonist, which activated only Fas (C1)95), but not perforin/granzyme-mediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR-ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR-ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.

Influence of biocontrol strain Pseudomonas fluorescens CHA0 and its antibiotic overproducing derivative on the diversity of root colonizing pseudomonads

Non-target effects of biocontrol strains of Pseudomonas on the population of resident pseudomonads should be assessed prior to their large scale application in the environment. The rifampicin resistant bacterium P. fluorescens CHA0-Rif and its antibiotic overproducing derivative CHA0-Rif/pME3424 were introduced into soil microcosms and the population of resident pseudomonads colonizing cucumber roots was investigated after 10 and 52 days. Both CHA0-Rif and CHA0-Rif/pME3424 displaced a part of the resident pseudomonad population after 10 days. To investigate the population structure, utilization of 10 carbon sources and production of two exoenzymes was assessed for 5600 individual pseudomonad isolates and 1700 isolates were subjected to amplified ribosomal DNA restriction analysis of the spacer region (spacer-ARDRA). After 10 days, only the proportion of pseudomonads able to degrade -tryptophan was reduced in treatments inoculated with either biocontrol strain. In parallel the phenotypic diversity was reduced. These effects were only observed 10 days after inoculation, and they were similar for inoculation with CHA0-Rif and CHA0-Rif/pME3424. Changes in the population structure of resident pseudomonads on cucumber roots during plant growth were more pronounced than changes due to the inoculants. The inoculants did not affect the genotypic diversity detected with spacer-ARDRA, but the genotypic fingerprints corresponded only partially to the phenotypic profiles. Overall CHA0-Rif had a small and transient impact on the population of resident pseudomonads and the effect was essentially the same for the genetically engineered derivative CHA0-

Variable queen number in ant colonies: no impact on queen turnover, inbreeding, and population genetic differentiation in the ant Formica selysi.

Variation in queen number alters the genetic structure of social insect colonies, which in turn affects patterns of kin-selected conflict and cooperation. Theory suggests that shifts from single- to multiple-queen colonies are often associated with other changes in the breeding system, such as higher queen turnover, more local mating, and restricted dispersal. These changes may restrict gene flow between the two types of colonies and it has been suggested that this might ultimately lead to sympatric speciation. We performed a detailed microsatellite analysis of a large population of the ant Formica selysi, which revealed extensive variation in social structure, with 71 colonies headed by a single queen and 41 by multiple queens. This polymorphism in social structure appeared stable over time, since little change in the number of queens per colony was detected over a five-year period. Apart from queen number, single- and multiple-queen colonies had very similar breeding systems. Queen turnover was absent or very low in both types of colonies. Single- and multiple-queen colonies exhibited very small but significant levels of inbreeding, which indicates a slight deviation from random mating at a local scale and suggests that a small proportion of queens mate with related males. For both types of colonies, there was very little genetic structuring above the level of the nest, with no sign of isolation by distance. These similarities in the breeding systems were associated with a complete lack of genetic differentiation between single- and multiple-queen colonies, which provides no support for the hypothesis that change in queen number leads to restricted gene flow between social forms. Overall, this study suggests that the higher rates of queen turnover, local mating, and population structuring that are often associated with multiple-queen colonies do not appear when single- and multiple-queen colonies still coexist within the same population, but build up over time in populations consisting mostly of multiple-queen colonies.

Hydrogen and oxygen isotope behaviors during variable degrees of upper mantle melting: Example from the basaltic glasses from Macquarie Island

We present measurements of hydrogen and oxygen isotopes in MORB glasses from Macquarie Island (SW. Pacific Ocean) coupled with determination of bulk H2O content by two independent techniques: total dehydration and FTIR. The incompatible trace elements in these glasses vary by a factor of 12 to 17, with K2O varying from 0.1 to 1.7 wt.%; these ranges reflect a variable degree of closed-system mantle melting, estimated from 1 to 15%. Water concentrations determined by the two techniques match well, yielding a range from 0.25 to 1.49 wt.% which correlates positively with all of the measured incompatible trace elements, suggesting that water is un-degassed, and behaves conservatively during mantle melting. Also, the agreement between the FTIR-determined and extracted water contents gives us confidence that the measured isotopic values of hydrogen reflect that of the mantle. Comparison of the range of water content with that of other incompatible trace elements allows estimation of the water partition coefficient in lherzolite, 0.0208 (ranging from 0.017 to 0.023), and the water content in the source, 386 ppm (ranging from 370 to 440 ppm). We observe a fairly narrow range in delta D and delta O-18 values of -75.5 +/- 4.5 parts per thousand and 5.50 +/- 0 .05 parts per thousand respectively, that can be explained by partial melting of normal lherzolitic mantle. The measured delta D and delta O-18 values of Macquarie Island glasses that range from nepheline- to hypersthene-normative, and from MORB to EMORB in composition, are identical to those in average global MORB. The observed lack of variation of delta D and delta O-18 with 1 to 15% degree of mantle melting is consistent with a bulk melting model of delta D and delta O-18 fractionation, in which water is rapidly scavenged into the first partial melt. The narrow ranges of delta D and delta O-18 in normal mantle are mostly due to the buffering effect of clino- and orthopyroxenes in the residual assemblage; additionally, fast ``wet'' diffusion of oxygen and hydrogen isotopes through the melting regions may further smooth isotopic differences. (C) 2012 Elsevier B.V. All rights reserved.

T cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd-associated photoreactive peptide derivative.

To elucidate the structural basis of T cell recognition of hapten-modified antigenic peptides, we studied the interaction of the T1 T cell antigen receptor (TCR) with its ligand, the H-2Kd-bound Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI) containing photoreactive 4-azidobenzoic acid (ABA) on P. berghei circumsporozoite Lys259. The photoaffinity-labeled TCR residue(s) were mapped as Tyr48 and/or Tyr50 of complementary determining region 2beta (CDR2beta). Other TCR-ligand contacts were identified by mutational analysis. Molecular modeling, based on crystallographic coordinates of closely related TCR and major histocompatibility complex I molecules, indicated that ABA binds strongly and specifically in a cavity between CDR3alpha and CDR2beta. We conclude that TCR expressing selective Vbeta and CDR3alpha sequences form a binding domain between CDR3alpha and CDR2beta that can accommodate nonpeptidic moieties conjugated at the C-terminal portion of peptides binding to major histocompatibility complex (MHC) encoded proteins.

La fonction publique en Suisse : analyse géopolitique d'un fédéralisme à géométrie variable

Bien que présenté comme un modèle de stabilité, le fédéralisme est constamment remis en question. Le but de l'article est de présenter quelques-unes de ses caractéristiques lues à travers les effectifs de la fonction publique en Suisse. Pour ce faire, nous distinguerons quatre types d'employeurs : Confédération, cantons, communes et corporations de droit public, lesquels représentent 10,5 % du total des actifs en Suisse. Nous analyserons la densité administrative, la variation des emplois et le degré de décentralisation selon la culture, le territoire et la religion. Il ressort que la fonction publique intermédiaire, c'est-à-dire les cantons, joue le premier rôle avec ses 140'000 emplois en équivalents plein temps (EPT) sur un total de 328'000, en hausse de 10,3 % par rapport à 2001. Les communes comptent 38 % des agents publics (+3,6 % par rapport à 2001), loin devant la Confédération, 11 % du total (en perte de vitesse : -1,2 %) et les corporations de droit public, 9 % du total (+14,5 %). Le taux d'administration est plus élevé dans la partie francophone que dans la partie germanophone, ainsi que dans les centres économiques et les zones frontières. Les écarts entre les cantons peuvent varier du simple au triple. En fait, deux modèles politico-administratifs transparaissent : le premier « cantonaliste » et davantage étatiste dans la partie latine, l'autre « communaliste » et décentralisé, dominant dans la partie germanophone. Le quotient de décentralisation administrative montre de grandes différences entre l'est et l'ouest, qui s'estompent toutefois avec la modernisation des institutions et le repositionnement de la Suisse face à l'Europe.

Very high-resolution digital elevation models: are multi-scale-derived variables ecologically relevant?

1. Digital elevation models (DEMs) are often used in landscape ecology to retrieve elevation or first derivative terrain attributes such as slope or aspect in the context of species distribution modelling. However, DEM-derived variables are scale-dependent and, given the increasing availability of very high-resolution (VHR) DEMs, their ecological relevancemust be assessed for different spatial resolutions. 2. In a study area located in the Swiss Western Alps, we computed VHR DEMs-derived variables related to morphometry, hydrology and solar radiation. Based on an original spatial resolution of 0.5 m, we generated DEM-derived variables at 1, 2 and 4 mspatial resolutions, applying a Gaussian Pyramid. Their associations with local climatic factors, measured by sensors (direct and ambient air temperature, air humidity and soil moisture) as well as ecological indicators derived fromspecies composition, were assessed with multivariate generalized linearmodels (GLM) andmixed models (GLMM). 3. Specific VHR DEM-derived variables showed significant associations with climatic factors. In addition to slope, aspect and curvature, the underused wetness and ruggedness indices modelledmeasured ambient humidity and soilmoisture, respectively. Remarkably, spatial resolution of VHR DEM-derived variables had a significant influence on models' strength, with coefficients of determination decreasing with coarser resolutions or showing a local optimumwith a 2 mresolution, depending on the variable considered. 4. These results support the relevance of using multi-scale DEM variables to provide surrogates for important climatic variables such as humidity, moisture and temperature, offering suitable alternatives to direct measurements for evolutionary ecology studies at a local scale.