Exploring the MHC-peptide matrix of central tolerance in the human thymus

Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.

Growth response to climate and drought change along an aridity gradient in the southernmost Pinus nigra relict forests

Tree populations at the rear edge of species distribution are sensitive to climate stress and drought. However, growth responses of these tree populations to those stressors may vary along climatic gradients. To analyze growth responses to climate and drought using dendrochronology in rear-edge Pinus nigra populations located along an aridity gradient. Tree-ring width chronologies were built for the twentieth century and related to monthly climatic variables, a drought index (Standardized Precipitation-Evapotranspiration Index), and two atmospheric circulation patterns (North Atlantic and Western Mediterranean Oscillations). Growth was enhanced by wet and cold previous autumns and warm late winters before tree-ring formation. The influence of the previous year conditions on growth increased during the past century. Growth was significantly related to North Atlantic and Western Mediterranean Oscillations in two out of five sites. The strongest responses of growth to the drought index were observed in the most xeric sites. Dry conditions before tree-ring formation constrain growth in rear-edge P. nigra populations. The comparisons of climate-growth responses along aridity gradients allow characterizing the sensitivity of relict stands to climate warming.

Identification and expression of different dehydrin subclasses involved in the drought response of Trifolium repens

Reverse transcribed RNAs coding for YnKn, YnSKn, SKn, and KS dehydrin types in drought-stressed white clover (Trifolium repens) were identified and characterized. The nucleotide analyses revealed the complex nature of dehydrin-coding sequences, often featured with alternative start and stop codons within the open reading frames, which could be a prerequisite for high variability among the transcripts originating from a single gene. For some dehydrin sequences, the existence of natural antisense transcripts was predicted. The differential distribution of dehydrin homologues in roots and leaves from a single white clover stolon under normal and drought conditions was evaluated by semi-quantitative RT-PCR and immunoblots with antibodies against the conserved K-, Y- and S-segments. The data suggest that different dehydrin classes have distinct roles in the drought stress response and vegetative development, demonstrating some specific characteristic features. Substantial levels of YSK-type proteins with different molecular weights were immunodetected in the non-stressed developing leaves. The acidic SK2 and KS dehydrin transcripts exhibited some developmental gradient in leaves. A strong increase of YK transcripts was documented in the fully expanded leaves and roots of drought-stressed individuals. The immunodetected drought-induced signals imply that Y- and K-segment containing dehydrins could be the major inducible Late Embryogenesis Abundant class 2 proteins (LEA 2) that accumulate predominantly under drought.

The contribution of intra- and interspecific tolerance variability to biodiversity changes along toxicity gradients

The worldwide distribution of toxicants is an important yet understudied driver of biodiversity, and the mechanisms relating toxicity to diversity have not been adequately explored. Here, we present a community model integrating demography, dispersal and toxicant-induced effects on reproduction driven by intraspecific and interspecific variability in toxicity tolerance. We compare model predictions to 458 species abundance distribu- tions (SADs) observed along concentration gradients of toxicants to show that the best predictions occur when intraspecific variability is five and ten times higher than interspecific variability. At high concentrations, lower settings of intraspecific variability resulted in predictions of community extinction that were not supported by the observed SADs. Subtle but significant species losses at low concentrations were predicted only when intraspecific variability dominated over interspecific variability. Our results propose intraspecific variability as a key driver for biodiversity sustenance in ecosystems challenged by environmental change.

Role of diuretics, blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

OBJECTIVE To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. DESIGN Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. SETTING NAVIGATOR trial. PARTICIPANTS Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. MAIN OUTCOME MEASURES Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. RESULTS During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). CONCLUSIONS Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.

Increasing intercultural competence and tolerance in multicultural schools: A Training Program and its effectiveness

This study reports the implementation of a Training of Intercultural Competence and Tolerance (TICT) for upper-secondary school students and the empirical evaluation of its effectiveness. The TICT program was developed to counteract increasing interethnic conflicts in the North Caucasus Federal District of Russia. It is based on the theoretical and empirical framework of social psychology and cross-cultural psychology. The training effectiveness was assessed by conducting pre- and post-surveys among the training participants. The results indicate that TICT contributes to the development of a positive ethnic identity and the formation of a civic identity among the participating youth. It also increases their optimism regarding the future of interethnic relations in Russia and the subjective level of intercultural competence of majority group youth towards minority cultures. Thus, the evaluation of the training effectiveness of the TICT has shown that the aims of the training have been achieved to a large extent and that the Training of Intercultural Competence and Tolerance can be effectively used to prevent interethnic conflicts and promote interethnic relations in multicultural schools. Suggestions for the practical implementation of the TICT as well as for future research on the training's effectiveness are discussed.

BVDV: a pestivirus inducing tolerance of the innate immune response

Animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) retain a strain-specific B- and T-cell immunotolerance. Pestiviral RNA triggers interferon (IFN) synthesis, and the viral RNase E(rns) inhibits IFN expression induced by extracellular viral RNA. In addition, N(pro) promotes the degradation of the transcription factor IRF-3, which effectively blocks IFN expression in BVDV-infected cells. As not all the potential target cells are infected in PI animals, these are 'chimeric' with respect to BVDV. This suggests that N(pro) and E(rns) are non-redundant IFN antagonists that act in infected and non-infected cells, respectively. Moreover, E(rns) may take a paradoxical function, both as virulence as well as "attenuation" factor: The former by preventing the activation of the innate and, consequently, of the adaptive immune system, the latter by minimizing the detrimental effects of systemic IFN production. Thus, BVDV maintains "self-tolerance" by avoiding the induction of IFN while itself being largely resistant to it without, however, interfering with the IFN action against unrelated viruses ('nonself'). This unique extension of 'self' to a virus suggests that the host's own RNases may have evolved as a guard against inadvertent activation of the innate immune system by host RNA, thus establishing a state of "innate tolerance".

Contrasting vulnerability and resilience to drought-induced decline of densely planted vs. natural rear-edge Pinus nigra forests

The southernmost European natural and planted pine forests are among the most vulnerable areas to warming-induced drought decline. Both drought stress and management factors (e.g., stand origin or reduced thinning) may induce decline by reducing the water available to trees but their relative importances have not been properly assessed. The role of stand origin - densely planted vs. naturally regenerated stands - as a decline driver can be assessed by comparing the growth and vigor responses to drought of similar natural vs. planted stands. Here, we compare these responses in natural and planted Black pine (Pinus nigra) stands located in southern Spain. We analyze how environmental factors - climatic (temperature and precipitation anomalies) and site conditions - and biotic factors - stand structure (age, tree size, density) and defoliation by the pine processionary moth - drive radial growth and crown condition at stand and tree levels. We also assess the climatic trends in the study area over the last 60 years. We use dendrochronology, linear mixed-effects models of basal area increment and structural equation models to determine how natural and planted stands respond to drought and current competition intensity. We observed that a temperature rise and a decrease in precipitation during the growing period led to increasing drought stress during the late 20th century. Trees from planted stands experienced stronger growth reductions and displayed more severe crown defoliation after severe droughts than those from natural stands. High stand density negatively drove growth and enhanced crown dieback, particularly in planted stands. Also pine processionary moth defoliation was more severe in the growth of natural than in planted stands but affected tree crown condition similarly in both stand types. In response to drought, sharp growth reduction and widespread defoliation of planted Mediterranean pine stands indicate that they are more vulnerable and less resilient to drought stress than natural stands. To mitigate forest decline of planted stands in xeric areas such as the Mediterranean Basin, less dense and more diverse stands should be created through selective thinning or by selecting species or provenances that are more drought tolerant. (C) 2013 Elsevier B.V. All rights reserved.

Impacts of drought stress on water relations and carbon assimilation in grassland species at different altitudes

Grassland is an important ecosystem type which is not only used agriculturally, but also covers sites which cannot be used for other purposes, e.g. in very steep locations or above timberlines. Prolonged summer droughts in the mid-term future, as are predicted for Central Europe, are expected to have a major impact on such ecosystems. To address this topic, rainfall exclusion via shelters was performed on three grassland sites at different altitudes (393, 982 and 1978 m above sea level) in Switzerland. Diurnal drought treatment effects were studied at each study site on a completely sunny day towards the end of an 8–10 week shelter period. Ecophysiological parameters including gas exchange (An, gs and intrinsic WUE) and chlorophyll a fluorescence (Fv/Fm, ΦPSII and NPQ) were considered for several species. The lowland and the Alpine field site were more strongly affected by soil drought than the pre-Alpine site. At all sites, grasses showed different patterns of reductions in stomatal conductance under soil drought compared to legumes and forbs. In addition, grasses were significantly more affected by reductions in assimilation rates at all sites. Time courses of reductions in assimilation rates relative to controls differed between species at the Alpine site, as some species showed reduced assimilation rates at this site in the early morning. Thus, similar rainfall exclusion treatments can trigger different reactions in various species at different sites, which might not become obvious during mere midday measurements. Overall, results suggest strong impacts of prolonged summer drought on grassland net photosynthesis especially at the Alpine site and, within sites, for grasses

Modeling tree water deficit from microclimate: an approach to quantifying drought stress

Tree water deficit estimated by measuring water-related changes in stem radius (DeltaW) was compared with tree water deficit estimated from the output of a simple, physiologically reasonable model (DeltaW(E)), with soil water potential (Psi(soil)) and atmospheric vapor pressure deficit (VPD) as inputs. Values of DeltaW were determined by monitoring stem radius changes with dendrometers and detrending the results for growth, We followed changes in DeltaW and DeltaW(E) in Pinus sylvestris L. and Quercus pubescens Willd. over 2 years at a dry site (2001-2002; Salgesch, Wallis) and in Picea abies (L.) Karst. for 1 year at a wet site (1998; Davos, Graubuenden) in the Swiss Alps. The seasonal courses of DeltaW in deciduous species and in conifers at the same site were similar and could be largely explained by variation in DeltaW(E). This finding strongly suggests that DeltaW, despite the known species-specific differences in stomatal response to microclimate, is mainly explained by a combination of atmospheric and soil conditions. Consequently, we concluded that trees are unable to maintain any particular DeltaW. Either Psi(soil) or VPD alone provided poorer estimates of AWthan a model incorporating both factors. As a first approximation of DeltaW(E), Psi(soil) can be weighted so that the negative mean Psi(soil) reaches 65 to 75% of the positive mean daytime VPD over a season (Q. pubescens: similar to65%, P abies: similar to70%, P sylvestris: similar to75%). The differences in DeltaW among species can be partially explained by a different weighting of Psi(soil) against VPD. The DeltaW of P. sylvestris was more dependent on Psi(soil) than that of Q. pubescens, but less than that of P. abies, and was less dependent on VPD than that of P. abies and Q. pubescens. The model worked well for P. abies at the wet site and for Q. pubescens and P. sylvestris at the dry site, and may be useful for estimating water deficit in other tree species.

Resistance of a lowland rain forest to increasing drought intensity in Sabah, Borneo

Occasional strong droughts are an important feature of the climatic environment of tropical rain forest in much of Borneo. This paper compares the response of a lowland dipterocarp forest at Danum, Sabah, in a period of low (LDI) and a period of high (HDI) drought intensity (1986-96, 9.98 y;1996-99, 2.62 y). Mean annual drought intensity was two-fold higher in the HDI than LDI period (1997 v. 976 mm), and each period had one moderately strong main drought (viz. 1992, 1998). Mortality of `all' trees greater than or equal to 10 cm gbh (girth at breast height) and stem growth rates of `small' trees 10less than or equal to50 cm gbh were measured in sixteen 0.16-ha subplots (half on ridge, half on lower slope sites) within two 4-ha plots. These 10-50-cm trees were composed largely of true understorey species. A new procedure was developed to correct for the effect of differences in length of census interval when comparing tree mortality rates. Mortality rates of small trees declined slightly but not significantly between the LDI and HDI periods (1.53 to 1.48% y(-1)): mortality of all trees showed a similar pattern. Relative growth rates declined significantly by 23% from LDI to HDI periods (11.1 to 8.6 mm m(-1) y(-1)): for absolute growth rates the decrease was 28% (2.45 to 1.77 mm y(-1)). Neither mortality nor growth rates were significantly influenced by topography. For small trees, across subplots, absolute growth rate was positively correlated in the LDI period, but negatively correlated in the HDI period, with mortality rate. There was no consistent pattern in the responses among the 19 most abundant species (n greater than or equal to 50 trees) which included a proposed drought-tolerant guild. In terms of tree survival, the forest at Danum was resistant to increasing drought intensity, but showed decreased stem growth attributable to increasing water stress.

Drought avoidance and the effect of local topography on trees in the understorey of Bornean lowland rain forest

The water relations of two tree species in the Euphorbiaceae were compared to test in part a hypothesis that the forest understorey plays an integral role in drought response. At Danum, Sabah, the relatively common species Dimorphocalyx muricatus is associated with ridges whilst another species, Mallotus wrayi, occurs widely both on ridges and lower slopes. Sets of subplots within two 4 -ha permanent plots in this lowland dipterocarp rain forest, were positioned on ridges and lower slopes. Soil water potentials were recorded in 1995-1997, and leaf water potentials were measured on six occasions. Soil water potentials on the ridges (-0.047 MPa) were significantly lower than on the lower slopes (-0.012 MPa), but during the driest period in May 1997 they fell to similarly low levels on both sites (-0.53 MPa). A weighted 40-day accumulated rainfall index was developed to model the soil water potentials. At dry times, D. muricatus (ridge) had significantly higher pre-dawn (-0.21 v. -0.57 MPa) and mid-day (-0.59 v. -1.77 MPa) leaf water potentials than M. wrayi (mean of ridge and lower slope). Leaf osmotic potentials of M. wrayi on the ridges were lower (-1.63 MPa) than on lower slopes (-1.09 MPa), with those for D. muricatus being intermediate (-1.29 MPa): both species adjusted osmotically between wet and dry times. D. muricatus trees were more deeply rooted than M. wrayi trees (97 v. 70 cm). M. wrayi trees had greater lateral root cross-sectional areas than D. muricatus trees although a greater proportion of this sectional area for D. muricatus was further down the soil profile. D. muricatus appeared to maintain relatively high water potentials during dry periods because of its access to deeper water supplies and thus it largely avoided drought effects, but M. wrayi seemed to be more affected yet tolerant of drought and was more plastic in its response. The interaction between water availability and topography determines these species' distributions and provides insights into how rain forests can withstand occasional strong droughts.

Effect of combined drought and heat stress on heat shock proteins in wheat varieties

Introduction: The re sponse of crop plants ex posed on drought or heat shock is related to de crease in the synthesis of normal proteins, accompanied by increased translation of heat shock proteins (HSPs). Though drought and heat stress have been studied individually, little is known about their combined effect on plants. Methods: The wheat (Triticum aestivum L.) varieties (Katya-tolerant, Sadovo or Mladka-susceptible) were potted in soil. Eight-day-old plants were ex posed to with drawing water for seven days. Heat shock was realized in growth chamber at 40 °C for 6h. A combination of drought and heat shock was per formed by subjecting drought-stressed plants to heat shock treatment. Expression of HSPs in the first leaf of wheat varieties was analyzed by SDS electrophoresis and immunoblotting. Polyclonal antibodies against HSP20, HSP60, HSP110 and mononclonal antibodies against HSP70 were used to distinguish the mentioned HSPs. Results: The leaf relative water content (RWC), which indicated the level of plant dehydration decreased significantly (34 %) under drought stressed conditions The electrolyte leakage of ions (EL), representing the level of the cell membrane stability in creased mark edly (68 %), especially under combination of drought and heat. Maximum EL was ob served in drought susceptible varieties Sadovo and Mladka. Drought and heat shock combination in the wheat plants resulted in the induction of specific HSPs. Conclusions: Our results demonstrate that the response of the wheat plants to a combination of drought and heat stress is different from the response of plants to each of these stresses applied separately. Induction of synergetic effect on HSP expression in case of combination between drought and heat was discussed in the case of two contrasting wheat varieties.