More than 15 years ago, mutations in the autoimmune regulator (AIRE) gene were identified as the cause of autoimmune polyglandular syndrome type 1 (APS1). It is now clear that this transcription ...factor has a crucial role in promoting self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery. In this Review, we highlight many of the recent advances in our understanding of the complex biology that is related to AIRE, with a particular focus on advances in genetics, molecular interactions and the effect of AIRE on thymic selection of regulatory T cells. Furthermore, we highlight new areas of biology that are potentially affected by this key regulator of immune tolerance.
Many biological organisms with exceptional freezing tolerance can resist the damages to cells from extra-/intracellular ice crystals and thus maintain their mechanical stability at subzero ...temperatures. Inspired by the freezing tolerance mechanisms found in nature, here we report a strategy of combining hydrophilic/oleophilic heteronetworks to produce self-adaptive, freeze-tolerant and mechanically stable organohydrogels. The organohydrogels can simultaneously use water and oil as a dispersion medium, and quickly switch between hydrogel- and organogel-like behaviours in response to the nature of the surrounding phase. Accordingly, their surfaces display unusual adaptive dual superlyophobic in oil/water system (that is, they are superhydrophobic under oil and superoleophobic under water). Moreover, the organogel component can inhibit the ice crystallization of the hydrogel component, thus enhancing the mechanical stability of organohydrogel over a wide temperature range (-78 to 80 °C). The organohydrogels may have promising applications in complex and harsh environments.
Quinoa (Chenopodium quinoa Willd.) originates in high altitude areas, such as the Andes, and has some inherent characteristics of cold, drought, and salinity tolerance, but is sensitive to high ...temperature.
To gain insight into the response mechanism of quinoa to high temperature stress, we conducted an extensive targeted metabolomic study of two cultivars, Dianli-3101 and Dianli-3051, along with a combined transcriptome analysis. A total of 794 metabolites and 54,200 genes were detected, in which the genes related to photosynthesis were found down-regulated at high temperatures, and two metabolites, lipids and flavonoids, showed the largest changes in differential accumulation. Further analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and transcription factors revealed that quinoa inhibits photosynthesis at high temperatures, and the possible strategies being used for high temperature stress management are regulation of heat stress transcription factors (HSFs) to obtain heat tolerance, and regulation of purine metabolism to enhance stress signals for rapid response to high temperature stress. The tolerant genotype could have an enhanced response through lower purine levels. The induction of the stress response could be mediated by HSF transcription factors. The results of this study may provide theoretical references for understanding the response mechanism of quinoa to high temperature stress, and for screening potential high temperature tolerant target genes and high temperature tolerant strains.
These findings reveal the regulation of the transcription factor family HSF and the purinergic pathway in response to high temperature stress to improve quinoa varieties with high temperature tolerance.
Salinity and drought are major limiting factors of wheat (Triticum aestivum) productivity worldwide. Here, we report the function of a wheat ERF transcription factor TaERF3 in salt and drought ...responses and the underlying mechanism of TaERF3 function. Upon treatment with 250 mm NaCl or 20% polyethylene glycol (PEG), transcript levels of TaERF3 were rapidly induced in wheat. Using wheat cultivar Yangmai 12 as the transformation recipient, four TaERF3‐overexpressing transgenic lines were generated and functionally characterized. The seedlings of the TaERF3‐overexpressing transgenic lines exhibited significantly enhanced tolerance to both salt and drought stresses as compared to untransformed wheat. In the leaves of TaERF3‐overexpressing lines, accumulation levels of both proline and chlorophyll were significantly increased, whereas H₂O₂ content and stomatal conductance were significantly reduced. Conversely, TaERF3‐silencing wheat plants that were generated through virus‐induced gene silencing method displayed more sensitivity to salt and drought stresses compared with the control plants. Real‐time quantitative RT‐PCR analyses showed that transcript levels of ten stress‐related genes were increased in TaERF3‐overexpressing lines, but compromised in TaERF3‐silencing wheat plants. Electrophoretic mobility shift assays showed that the TaERF3 protein could interact with the GCC‐box cis‐element present in the promoters of seven TaERF3‐activated stress‐related genes. These results indicate that TaERF3 positively regulates wheat adaptation responses to salt and drought stresses through the activation of stress‐related genes and that TaERF3 is an attractive engineering target in applied efforts to improve abiotic stress tolerances in wheat and other cereals.
The article from Mahr et al. on page 968 clarifies the contributions of major and minor histocompatibility antigens to the induction of mixed chimerism and allograft tolerance when using a clinically ...relevant noncytoreductive regimen.
Siplizumab, a humanized anti‐CD2 monoclonal antibody, has been used in conditioning regimens for hematopoietic cell transplantation and tolerance induction with combined kidney‐bone marrow ...transplantation. Siplizumab‐based tolerance induction regimens deplete T cells globally while enriching regulatory T cells (Tregs) early posttransplantation. Siplizumab inhibits allogeneic mixed‐lymphocyte reactions (MLRs) in vitro. We compared the impact of siplizumab on Tregs versus other T cell subsets in HLA‐mismatched allogeneic MLRs using PBMCs. Siplizumab predominantly reduced the percentage of CD4+ and CD8+ effector memory T cells, which express higher CD2 levels than naïve T cells or resting Tregs. Conversely, siplizumab enriched proliferating CD45RA− FoxP3HI cells in MLRs. FoxP3 expression was stable over time in siplizumab‐containing cultures, consistent with enrichment for bona fide Tregs. Consistently, high‐throughput TCRβ CDR3 sequencing of sorted unstimulated and proliferating T cells in MLRs revealed selective expansion of donor‐reactive Tregs along with depletion of donor‐reactive CD4+ effector/memory T cells in siplizumab‐containing MLRs. These results indicate that siplizumab may have immunomodulatory functions that may contribute to its success in tolerance‐inducing regimens. Our studies also confirm that naïve in addition to effector/memory T cells contribute to the allogeneic MLR and mandate further investigation of the impact of siplizumab on alloreactive naïve T cells.
The anti‐CD2 monoclonal antibody (siplizumab) depletes alloreactive effector memory T cells, but spares and allows the expansion of donor‐specific regulatory T cells in vitro.
Because soil salinity is a major abiotic constraint affecting crop yield, much research has been conducted to develop plants with improved salinity tolerance. Salinity stress impacts many aspects of ...a plant's physiology, making it difficult to study in toto Instead, it is more tractable to dissect the plant's response into traits that are hypothesized to be involved in the overall tolerance of the plant to salinity.
We discuss how to quantify the impact of salinity on different traits, such as relative growth rate, water relations, transpiration, transpiration use efficiency, ionic relations, photosynthesis, senescence, yield and yield components. We also suggest some guidelines to assist with the selection of appropriate experimental systems, imposition of salinity stress, and obtaining and analysing relevant physiological data using appropriate indices. We illustrate how these indices can be used to identify relationships amongst the proposed traits to identify which traits are the most important contributors to salinity tolerance. Salinity tolerance is complex and involves many genes, but progress has been made in studying the mechanisms underlying a plant's response to salinity. Nevertheless, several previous studies on salinity tolerance could have benefited from improved experimental design. We hope that this paper will provide pertinent information to researchers on performing proficient assays and interpreting results from salinity tolerance experiments.
The International Workshop on Clinical Transplant Tolerance is a biennial meeting that aims to provide an update on the progress of studies of immunosuppression minimization or withdrawal in solid ...organ transplantation. The Fourth International Workshop on Clinical Tolerance was held in Pittsburgh, Pennsylvania, September 5‐6, 2019. This report is a summary of presentations on the status of clinical trials designed to minimize or withdraw immunosuppressive drugs in kidney, liver, and lung transplantation without subsequent evidence of rejection. All protocols had in common the use of donor or recipient cell therapy combined with organ transplantation. The workshop also included presentations of mechanistic studies designed to improve understanding of the cellular and molecular basis of tolerance and to identify potential predictors/biomarkers of tolerance. Strategies to enhance the safety of hematopoietic cell transplantation and to improve patient selection/risk stratification for clinical trials were also discussed.
This report summarizes the status of trials designed to minimize or withdraw immunosuppressive drugs in kidney, liver, and lung transplantation.
How to assess Drosophila cold tolerance Andersen, Jonas L.; Manenti, Tommaso; Sørensen, Jesper G. ...
Functional ecology,
January 2015, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Thermal tolerance may limit and therefore predict ectotherm geographic distributions. However, which of the many metrics of thermal tolerance best predict distribution is often unclear, even ...for drosophilids, which constitute a popular and well‐described animal model.
Five metrics of cold tolerance were measured for 14 Drosophila species to determine which metrics most strongly correlate with geographic distribution. The species represent tropical to temperate regions but all were reared under similar (common garden) conditions (20 °C). The traits measured were: chill coma temperature (CTmin), lethal temperature (LTe50), lethal time at low temperature (LTi50), chill coma recovery time (CCRT) and supercooling point (SCP).
Measures of CTmin, LTe50 and LTi50 proved to be the best predictors to describe the variation in realized latitudinal distributions (R2 = 0·699, R2 = 0·741 and 0·550, respectively) and estimated environmental cold exposure (R2 = 0·633, R2 = 0·641 and 0·511, respectively). Measures of CCRT also correlated significantly with estimated minimum temperature (R2 = 0·373), while the SCP did not. These results remained consistent after phylogenetically independent analysis or when applying nonlinear regression. Moreover, our findings were supported by a similar analysis based on existing data compiled from the Drosophila cold tolerance literature.
Trait correlations were strong between LTe50, LTi50 and CTmin, respectively (0·83 > R2 > 0·55). However, surprisingly, there was only a weak correlation between the entrance into coma (CTmin) and the recovery from chill coma (CCRT) (R2 = 0·256).
Considering the findings of the present study, data from previous studies and the logistical constraints of each measure of cold tolerance, we conclude that CTmin and LTe50 are superior measures when estimating the ecologically relevant cold tolerance of drosophilids. Of these two traits, CTmin requires less equipment, time and animals and thereby presents a relatively fast, simple and dynamic measure of cold tolerance.
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