Acquisition Of Tolerance Research Articles

Mechanisms of plant acquisition of cold tolerance

Mechanisms of plant acquisition of cold tolerance

Alleviation of Pathogen Susceptibility of Vigna sinensis L. seeds using lanthanum Nitrate

The main target of the present work was to investigate the effects of two different concentrations (1 and 5 ppm) of lanthanum nitrate on the susceptibility of V.sinensis seeds to pathogen infection during germination stage.The relatively low applied concentration of La-nitrate (1 ppm) led to rapid emergence of radicles, significant increase in percentage of germination and a significant decrease in percentage of infected seeds. Also,there was a significant increase in major growth attributes of the developed seedlings. The biochemical activities of Vigna sinensis L. responded well to the low concentration of La-nitrate and participated in acquisition of pathogen tolerance and in growth enhancement of the seedlings. Thus, in response to the relatively low applied concentration of La-nitrate a significant increase in total soluble sugars, amino acids, total nitrogen, antioxidant enzymes, phenolic compounds was obtained mean while the content of cytosolic calcium subjected to a significant decrease. On the other hand, application of a relatively high concentration of La-nitrate (5 ppm), via disturbing the biochemical activities had retarded seed germination, major defensive mechanism, hence increased susceptibility to pathogen infection and retarded seedling growth.

Chloroplast-to-Nucleus Signaling Regulates MicroRNA Biogenesis in Arabidopsis

As integral regulators in plant development and stress response, microRNAs (miRNAs) themselves need to be tightly regulated. Here, we show that tocopherols (vitamin E), lipid-soluble antioxidants synthesized from tyrosine in chloroplasts, positively regulate the biogenesis of miRNAs. Tocopherols are required for the accumulation of 3'-phosphoadenosine 5'-phosphate (PAP), a retrograde inhibitor of the nuclear exoribonucleases (XRN), which may protect primary miRNAs from being degraded and promote mature miRNA production. Such regulation is involved in heat-induced accumulation of miR398 and plant acquisition of heat tolerance. Our study reveals a chloroplast-to-nucleus signaling mechanism that favors miRNA biogenesis under heatand possibly other environmental perturbations.

A light-initiated chemiluminescent assay for rapid quantitation of allergen-specific IgG4 in clinical samples

BackgroundAn increase in allergen-specific IgG4 (sIgG4), which serves as a blocking antibody, is associated with acquisition of immune tolerance after immunotherapy. In this study, we developed a rapid, sensitive, and homogeneous immunoassay based on the light-initiated chemiluminescent assay (LICA) technology for quantifying allergen sIgG4 in serum samples. MethodsAllergen sIgG4 was measured in vitro by incubating the sample with biotinylated allergens and chemiluminescent beads coated with anti-human IgG4 antibody, followed by the addition of streptavidin-coated sensitizer beads. Multiple tests were performed to optimize the working conditions of the LICA and evaluate its performance. ResultsWe established the optimal concentration of biotinylated allergens (250 ng/mL), the optimal dilution range (1:8 for Gal d 1, Gal d 2 sIgG4 and 1:4 for Gal d 3, Gal d 4 sIgG4), and the optimal incubation time (20 min for Gal d 1, Gal d 2 sIgG4 and 40 min for Gal d 3, Gal d 4 sIgG4). The lower limit of quantification (LLOQ) was 0.261 ng/mL. The coefficient variation (CV) of the LICA was <10%. The assay was unaffected by general interfering substances at physiological concentrations.It exhibited excellent accuracy to detect allergen-sIgG4 in human serum. Additionally, we demonstrated that the levels of Gal d 1, Gal d 2, and Gal d 3-sIgG4 were significantly higher in the egg allergy group (p < .05), but no differences were found between the groups for Gal d 4-sIgG4. ConclusionsThe LICA demonstrated satisfactory performance and can be used for quantifying allergen sIgG4 in clinical practice.

Interplay between hydrogen sulfide and calcium/calmodulin enhances systemic acquired acclimation and antioxidative defense against nickel toxicity in zucchini

In this study 50 mg/l Ni stress reduced plant growth, induced oxidative stress, increased proline accumulation and H2S content in roots and leaves of zucchini. Indeed, Ni toxicity up-regulated calmodulin (CaM) gene expression in leaves. Root pretreatment with calcium and NaHS (as hydrogen sulfide donor) singly or in combination reduced SOD activity but enhanced activities of CAT, POD and lowered accumulation of proline and Ni element not only in root, but also in untreated leaves, suggesting a systemic mitigating effect of Ca2+/H2S pretreatment on Ni-evoked oxidative damage in both roots and leaves. Importantly, Ni-induced H2S accumulation was markedly strengthened by application of exogenous Ca2+ and this effect was weakened by addition of H2S scavenger, hypotaurine (HT), in roots and leaves, suggesting H2S acts downstream of Ca2+. On the other hand, root pretreatment with NaHS, amplified Ni-induced CaM gene expression in leaves and mediated antioxidant defense in both roots and leaves and addition of ethylene glycol tetra acetic acid (EGTA) as a Ca2+ chelator, verapamil (VPL) as a plasma membrane channel blocker, and trifluoperazine(TFP) as a calmodulin (CaM) antagonist, reversed these impacts. These results suggested that root pretreatment with H2S could induce systemic Ni tolerance not only in the site of application, but also in untreated distant parts in Ni-stressed zucchini seedlings and the acquisition of this Ni tolerance requires the entry of extracellular Ca2+ into cells across the plasma membrane and the mediation of intracellular CaM. Taken together, it seems that Ca2+/CaM complex functions both upstream and downstream of H2S and crosstalk of Ca2+ and H2S is essential for inducing systemic acquired acclimation in Ni-stressed zucchini seedlings.

Allergie à la noix de cajou : 36 tests de provocation orale pédiatriques à la noix de cajou avant le rAna o 3

IntroductionDespite the increased prevalence of allergy to anacardiaceae, oral food challenge tests (OFC) to cashews are more rarely carried out than peanut OFC. Despite a natural history of normal non-healing, this study shows that an allergy to cashews, even severe, can progress towards acquisition of spontaneous tolerance. Materials and methodsA retrospective, single-center study of 36 children who underwent cashew OFC at the pediatric hospitals of Nice CHU-Lenval. ResultsTwenty-five children reached the maximum cumulative dose of 4441mg, with 15 OFC being considered negative. 21 OFC were positive for a mean reactive cumulative dose of 2881mg of cashew, with 13 anaphylactic reactions. 6 of these still-allergic children received food immunotherapy and 15 children continued on a strict avoidance diet. DiscussionIn one-third of our patients, spontaneous tolerance was achieved. Only 15 children underwent the recently available IgE assay for rAna o 3, an allergenic component of cashews, considered a major predictor of reactivity and severity. The presence of IgE directed against Ana o 3 confirmed the predictive value of this test in our patients, although we could not derive a threshold value.

Cold Acclimation Favors Metabolic Stability in Drosophila suzukii.

The invasive fruit fly pest, Drosophila suzukii, is a chill susceptible species, yet it is capable of overwintering in rather cold climates, such as North America and North Europe, probably thanks to a high cold tolerance plasticity. Little is known about the mechanisms underlying cold tolerance acquisition in D. suzukii. In this study, we compared the effect of different forms of cold acclimation (at juvenile or at adult stage) on subsequent cold tolerance. Combining developmental and adult cold acclimation resulted in a particularly high expression of cold tolerance. As found in other species, we expected that cold-acclimated flies would accumulate cryoprotectants and would be able to maintain metabolic homeostasis following cold stress. We used quantitative target GC-MS profiling to explore metabolic changes in four different phenotypes: control, cold acclimated during development or at adult stage or during both phases. We also performed a time-series GC-MS analysis to monitor metabolic homeostasis status during stress and recovery. The different thermal treatments resulted in highly distinct metabolic phenotypes. Flies submitted to both developmental and adult acclimation were characterized by accumulation of cryoprotectants (carbohydrates and amino acids), although concentrations changes remained of low magnitude. After cold shock, non-acclimated chill-susceptible phenotype displayed a symptomatic loss of metabolic homeostasis, correlated with erratic changes in the amino acids pool. On the other hand, the most cold-tolerant phenotype was able to maintain metabolic homeostasis after cold stress. These results indicate that cold tolerance acquisition of D. suzukii depends on physiological strategies similar to other drosophilids: moderate changes in cryoprotective substances and metabolic robustness. In addition, the results add to the body of evidence supporting that mechanisms underlying the different forms of acclimation are distinct.

Ascophyllum nodosum extract mitigates salinity stress in Arabidopsis thaliana by modulating the expression of miRNA involved in stress tolerance and nutrient acquisition.

Ascophyllum nodosum extract (ANE) contains bioactive compounds that improve the growth of Arabidopsis in experimentally-induced saline conditions; however, the molecular mechanisms through which ANE elicits tolerance to salinity remain largely unexplored. Micro RNAs (miRNAs) are key regulators of gene expression, playing crucial roles in plant growth, development, and stress tolerance. Next generation sequencing of miRNAs from leaves of control Arabidopsis and from plants subjected to three treatments (ANE, NaCl and ANE+NaCl) was used to identify ANE-responsive miRNA in the absence and presence of saline conditions. Differential gene expression analysis revealed that ANE had a strong effect on miRNAs expression in both conditions. In the presence of salinity, ANE tended to reduce the up-regulation or the down-regulation trend induced caused by NaCl in miRNAs such as ath-miR396a-5p, ath-miR399, ath-miR2111b and ath-miR827. To further uncover the effects of ANE, the expression of several target genes of a number of ANE-responsive miRNAs was analyzed by qPCR. NaCl, but not ANE, down-regulated miR396a-5p, which negatively regulated the expression of AtGRF7 leading to a higher expression of AtDREB2a and AtRD29 in the presence of ANE+NaCl, as compared to ANE alone. ANE+NaCl initially reduced and then enhanced the expression of ath-miR169g-5p, while the expression of the target genes AtNFYA1 and ATNFYA2, known to be involved in the salinity tolerance mechanism, was increased as compared to ANE or to NaCl treatments. ANE and ANE+NaCl modified the expression of ath-miR399, ath-miR827, ath-miR2111b, and their target genes AtUBC24, AtWAK2, AtSYG1 and At3g27150, suggesting a role of ANE in phosphate homeostasis. In vivo and in vitro experiments confirmed the improved growth of Arabidopsis in presence of ANE, in saline conditions and in phosphate-deprived medium, further substantiating the influence of ANE on a variety of essential physiological processes in Arabidopsis including salinity tolerance and phosphate uptake.

Functional characterization of galactinol synthase and raffinose synthase in desiccation tolerance acquisition in developing Arabidopsis seeds

Raffinose family oligosaccharides (RFOs) accumulate during seed development, and have been thought to be associated with the acquisition of desiccation tolerance (DT) by seeds. Here, comprehensive approaches were adopted to evaluate the changes of DT in developing Arabidopsis seeds of wild type, overexpression (OX-AtGS1/GS2/RS5), and mutant lines by manipulating the expression levels of the GALACTINOL SYNTHASE (GS) and RAFFINOSE SYNTHASE (RS) genes. Our results indicate that seeds of the double mutant (gs1, gs2) and rs5 delayed the timing of DT acquisition as compared to wild type. Subsequent detection confirmed that seeds from OX-AtGS1/GS2 plants with high levels of galactinol, raffinose, and stachyose, and OX-AtRS5 plants possess more raffinose and stachyose but less galactinol compared to wild type. These lines all showed greater germination percentage and shorter time to 50% germination after desiccation treatment at 11 and 15 days after flower (DAF). Further analysis revealed that the role of RFOs is time limited and mainly affects the middle stage (9–16 DAF) of seed development by enhancing seed viability and the ratio of GSH to GSSH in cells, but there is no significant difference in DT of mature seeds. In addition, RFOs could reduce damage to seeds caused by oxidative stress. We conclude that GALACTINOL SYNTHASE and RAFFINOSE SYNTHASE play important roles in DT acquisition during Arabidopsis seed development, and that galactinol and RFOs are crucial protective compounds in the response of seeds to desiccation stress.

Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome

BackgroundFew studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. ObjectiveWe have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. MethodsWe conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. ResultsSixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. ConclusionsIt is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.

Microbiota and Derived Parameters in Fecal Samples of Infants with Non-IgE Cow's Milk Protein Allergy under a Restricted Diet.

Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β1 levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases.

Anti‑osteopontin autoantibodies in various types of cancer.

The aberrant processing of biomolecules by cancer cells may give rise to autoimmune phenomena. The metastasis gene osteopontin is alternatively spliced only in transformed cells, and the variants promote tumor progression. They may also serve as tumor‑associated antigens, and their neutralization by autoantibodies could favorably affect prognosis. A competitive solid‑phase ELISA format was applied to determine reactivity toward recombinant osteopontin in human serum or plasma samples. Approximately 35% of thyroid cancer patients and 15% of other cancer patients were found to harbor autoantibodies directed to osteopontin variants, averaging 21% of patients across all cancers studied. The reactivity of the autoantibodies was consistent with the differential appearance of splice variants in individual malignancies. In thyroid cancer, autoantibodies were found to be more frequently associated with a milder form of the disease. The junctions of osteopontin splice variants produced by cancers represent tumor‑associated neo‑epitopes. Whereas the uniqueness of their sequences renders the acquisition of tolerance during immune maturation improbable, their immunogenicity is predicted to be low. The rare occurrence of antibodies to either osteopontin‑b or osteopontin‑c suggests that the breaking of tolerance to full‑length osteopontin is more prevalent in tumor autoimmunity than a reaction to a poorly immunogenic neo‑epitope.

Plant lyophilisate carrying S-HBsAg as an oral booster vaccine against HBV

A formulation of a defined antigen dosage together with an appropriate and convenient immunisation regime are the main problems of a plant-derived oral vaccine against HBV. Both factors have to be mutually adjusted to ensure efficacious vaccination and to minimise the risk of oral tolerance acquisition. As based on previous research, solely oral immunisation appears to be of limited effectiveness, but a combined immunisation scheme via injection priming and oral boosting can be proposed. Thus, the previously optimised plant lyophilisate with accumulated S-HBsAg was orally administered in a series of mouse immunisation trials. The impact of various S-HBsAg oral dosages and concentrations on the induction of an active immune response was studied. Immunisation via i.m. priming followed by double oral boosting in 6-week intervals was comparably efficient as standard i.m. vaccination. Among the tested dosages, 2× 5 or 200 ng triggered effective and exclusively systemic responses. Mucosal adjuvants CTB or quillaja bark saponins as well as alhydrogel either had no or a negative effect on immune response, which indicates that a low-dosed plant lyophilisate as an oral booster vaccine may not require exogenous adjuvants. Additionally, a positive effect of S-HBsAg encapsulation in lyophilised cells on immune response stimulation was confirmed by comparison with the antigen released in the plant extract. The low-dosed plant lyophilisate with concentrated S-HBsAg was proven as an effective and convenient oral booster vaccine. Results of immunisation via a mixed injection-oral route provide the foundation for research on further standardisation of a plant-derived oral vaccine against HBV and details of immune response together with effects for health condition.

Antigen Uptake by Langerhans Cells Is Required for the Induction of Regulatory T Cells and the Acquisition of Tolerance During Epicutaneous Immunotherapy in OVA-Sensitized Mice.

The skin is a major immunologic organ that may induce protection, sensitization or tolerance. Epicutaneous immunotherapy (EPIT) has been proposed as an attractive strategy to actively treat food allergy and has been shown to induce tolerance in sensitized mice through the induction of Foxp3+ regulatory T cells (Tregs), especially CD62L+ Tregs. Among immune cells in the skin, dendritic cells are key players in antigen-specific immune activation or regulation. The role of different populations of skin DCs in tolerance induction remains to be elucidated. Using OVA-sensitized BALB/c mice, we demonstrated that the application of a patch containing OVA-A647 to the skin resulted in allergen uptake by Langerhans cells (LCs) and CD11b+ dermal cDC2 and subsequent migration into skin draining lymph nodes. These 2 populations induced Foxp3 expression in CD4+ cells in vitro. Only LCs induced LAP+ cells and CD62L+ Tregs. Using Langerin-eGFP-DTR mice, we analyzed the role of LCs in the mechanisms of tolerance induction by EPIT in vivo. Following complete depletion of LCs, a dramatic decrease in the number of OVA+ DCs and OVA+ CD11b+ dermal cDC2 was observed in skin draining lymph nodes 48 h after epicutaneous application. Likewise, 2 weeks of EPIT in non-depleted mice induced Foxp3+ Tregs, especially CD62L+, and LAP+ Tregs in skin draining lymph nodes and spleen, whereas no induction of Tregs was observed in LC-depleted mice. Following 8 weeks of treatment, EPIT-treated mice showed significant protection against anaphylaxis accompanied by a significant increase of Foxp3+ Tregs, especially CD62L+ Tregs, which was not seen in the absence of LCs. In summary, although both LCs and CD11b+ dermal cDC2s could induce regulatory T cells, the absence of LCs during EPIT impaired treatment efficacy, indicating their crucial role in skin-induced tolerance.

Maturation and Desiccation Tolerance in Seeds of Sesbania virgata (Cav.) Pers.

The maturation process of Sesbania virgata seeds was investigated through fruits and seeds at different maturation stages, where they were described morphologically. For the seeds, fresh and dry mass and moisture were determined and structural analysis of the tegument under a light microscope was performed. Germination tests in the presence and absence of drying and the electrophoretic profile of heat resistant proteins were also performed. The results showed that the seeds reached physiological maturity at 44 days after anthesis (DAA), evidencing a secondary cell wall. The acquisition of desiccation tolerance was observed at 44 DAA, with the seeds responding to the drying treatment. Protein bands were observed from 32 DAA, which remained constant until the end of maturation. These results allowed the characterization of the development and acquisition of desiccation tolerance in S. virgata seeds.

Effects of seed hydration memory on initial growth under water deficit of cactus from two populations that occur in different ecosystems in Northeast Brazil

Discontinuity during the rehydration process of seeds that germinate in arid and semi‐arid ecosystems leads to the occurrence of hydration and dehydration cycles (HD cycles). HD cycles play an important role in the persistence and dynamics of plants in these ecosystems. Pilosocereus catingicola subsp. salvadorensis is a cactus that occurs in different ecosystems of northeast Brazil. This species is submitted to different environmental conditions, such as irregularity of soil water availability. This factor directly influences seed production, germination and establishment of new individuals in these ecosystems. The aim of this study was to evaluate the effects of HD cycles on the initial growth of P. catingicola subsp. salvadorensis seedlings from different ecosystems under water‐deficit conditions. Seeds collected in two different ecosystems were submitted to 0, 1, 2 and 3 HD cycles and seedlings from these seeds were submitted to water‐deficit treatments. HD cycles had effects not only during germination, but also in the initial growth and establishment of seedlings. Seeds from different populations had distinct responses to HD cycles and water‐deficit treatments. These effects, as acquisition of a greater tolerance of water deficit, were differentiated between populations of the same species that are established in different ecosystems. The effects of HD cycles interfere directly with seedling recruitment dynamics and the maintenance of these populations.

Maintaining T cell tolerance of alloantigens: Lessons from animal studies.

Achieving host immune tolerance of allogeneic transplants represents the ultimate challenge in clinical transplantation. It has become clear that different cells and mechanisms participate in acquisition versus maintenance of allograft tolerance. Indeed, manipulations which prevent tolerance induction often fail to abrogate tolerance once it has been established. Hence, elucidation of the immunological mechanisms underlying maintenance of T cell tolerance to alloantigens is essential for the development of novel interventions that preserve a robust and long lasting state of allograft tolerance that relies on T cell deletion in addition to intra-graft suppression of inflammatory immune responses. In this review, we discuss some essential elements of the mechanisms involved in the maintenance of naturally occurring or experimentally induced allograft tolerance, including the newly described role of antigen cross-dressing mediated by extracellular vesicles.

Challenges for high rate signal processing for the NUMEN experiment

The objective of the research and development activities, regarding the upgrade of the MAGNEX focal plane detector (FPD) and the development of the γ detector array for the NUMEN project, is the construction of new detectors capable to fulfil the requirements of high event rate, radiation tolerance and data acquisition and transmission bandwidth deriving from the upgrade of the Superconducting Cyclotron at INFN Laboratori Nazionali del Sud. The design of the front-end (FE) and read-out (RO) electronics has been performed in parallel with that of the new tracker. The design of the new segmented anode and the architecture of the front-end and read-out electronics are presented.

Study of Specific IgE and IgG4 Levels Regarding the Acquisition of Tolerance in Patients Allergic to Eggs

In recent decades we have witnessed an increase in allergic diseases in general, and food allergy in particular, which is the most common cause of anaphylaxis in children. In our midst, in the small child, egg allergy is the most common food allergy followed by cow's milk and fish.

Predictors of Persistent Wheat Allergy in Children: A Retrospective Cohort Study

Background: Wheat allergy is the third most common food allergy that develops during infancy in Japan. To identify factors associated with persistent wheat allergy, we assessed the rate of tolerance acquisition among Japanese children aged less than 6 years with an immediate-type wheat allergy using the oral food challenge (OFC) method. Methods: This retrospective cohort study included 83 children (born in 2005–2006) who had a history of immediate-type allergic reaction to wheat and were followed until 6 years of age. The subjects were divided to form “tolerant” (n = 55; tolerance acquired by 6 years of age) and “allergic” (n = 28; tolerance not acquired by 6 years of age) groups based on their OFC results. Results: The rates of tolerance acquisition to 200 g of udon noodles at 3, 5, and 6 years of age were 20.5% (17/83), 54.2% (45/83), and 66.3% (55/83), respectively. The total number of anaphylactic reactions experienced prior to 3 years of age in response to all foods (p < 0.01) and to wheat (p = 0.043) was significantly higher in the allergic than in the tolerant group. Wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) levels were significantly higher in the allergic group than in the tolerant group (p < 0.01), and wheat-specific IgE levels were more likely to increase after infancy in the allergic group. Conclusions: A history of anaphylaxis to all foods including wheat and/or a high level of wheat- or ω-5 gliadin-specific IgE antibodies were identified as risk factors for persistent wheat allergy.