Studies of kidney transplant recipients who have developed spontaneous and sustained tolerance have revealed an association with B cells. Unexpectedly tolerant individuals are characterized by ...increased numbers and frequencies of B cells in the blood and increased expression of genes associated with B cells in the blood and urine. Comparisons of the B cell repertoires of tolerant individuals and those receiving immunosuppression reveal that not only are the B cells more numerous but developmental differences result in a repertoire comprised of more naïve and transitional B cells in the tolerant cohort. B cells isolated from tolerant individuals also display functional differences compared to those from individuals receiving immunosuppression. Many of these differences may serve to suppress alloimmunity. Lastly a significant number of transplant recipients receiving standard immunosuppression display B cell-biased patterns of gene expression predictive of tolerance or a pro-tolerogenic state. Interestingly, this pattern is associated with improved renal allograft function. While recent studies have raised the concern that immunosuppressive drugs heavily influence B cell-based “signatures of tolerance”, a substantial body of work suggests that differences in B cells may be a useful tool for identifying tolerant kidney transplant recipients or guiding their immunosuppressive management.
Main conclusion
There is a need to integrate conceptual framework based on the current understanding of salt stress responses with different approaches for manipulating and improving salt tolerance ...in crop plants.
Soil salinity exerts significant constraints on global crop production, posing a serious challenge for plant breeders and biotechnologists. The classical transgenic approach for enhancing salinity tolerance in plants revolves by boosting endogenous defence mechanisms, often via a single-gene approach, and usually involves the enhanced synthesis of compatible osmolytes, antioxidants, polyamines, maintenance of hormone homeostasis, modification of transporters and/or regulatory proteins, including transcription factors and alternative splicing events. Occasionally, genetic manipulation of regulatory proteins or phytohormone levels confers salinity tolerance, but all these may cause undesired reduction in plant growth and/or yields. In this review, we present and evaluate novel and cutting-edge approaches for engineering salt tolerance in crop plants. First, we cover recent findings regarding the importance of regulatory proteins and transporters, and how they can be used to enhance salt tolerance in crop plants. We also evaluate the importance of halobiomes as a reservoir of genes that can be used for engineering salt tolerance in glycophytic crops. Additionally, the role of microRNAs as critical post-transcriptional regulators in plant adaptive responses to salt stress is reviewed and their use for engineering salt-tolerant crop plants is critically assessed. The potentials of alternative splicing mechanisms and targeted gene-editing technologies in understanding plant salt stress responses and developing salt-tolerant crop plants are also discussed.
The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ...ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo.
Defects associated with dimensional and geometric tolerance variability (tolerance problems) are often dealt with during the construction phase of projects. Despite the potentially severe ...consequences of those defects, tolerance management (TM) is a perennial challenge, and the construction industry lacks a systematic and practical process to provide insight into avoiding the reoccurrence of tolerance problems. The aim of this research is to present a conceptual framework to proactively reduce the reoccurrence of tolerance problems at stages preceding on site construction. The research uses an exploratory case study approach exploring TM in a civil engineering consultancy. Evidence was collated from semi-structured interviews and document analysis, and validated in a group interview. The data was analysed using thematic analysis. The study contributes to knowledge in engineering management by providing new insights into drawbacks of existing TM guidelines. It also describes a good practice application of TM by a civil engineering consultancy, and proposes a conceptual framework to improve TM, which provides a basis to develop more effective practical solutions for TM.
Main conclusion
Environmental-friendly techniques based on plant stress memory, cross-stress tolerance, and seed priming help sustainable agriculture by mitigating negative effects of dehydration ...stress.
The frequently uneven rainfall distribution caused by global warming will lead to more irregular and multiple abiotic stresses, such as heat stress, dehydration stress, cold stress or the combination of these stresses. Dehydration stress is one of the major environmental factors affecting the survival rate and productivity of plants. Hence, there is an urgent need to develop improved resilient varieties. Presently, technologies based on plant stress memory, cross-stress tolerance and priming of seeds represent fruitful and promising areas of future research and applied agricultural science. In this review, we will provide an overview of plant drought stress memory from physiological, biochemical, molecular and epigenetic perspectives. Drought priming-induced cross-stress tolerance to cold and heat stress will be discussed and the application of seed priming will be illustrated for different species.
The climate variability hypothesis posits that increased environmental thermal variation should select for thermal generalists, while stable environments should favor thermal specialists. This ...hypothesis has been tested on large spatial scales, such as latitude and elevation, but less so on smaller scales reflective of the experienced microclimate. Here, we estimated thermal tolerance limits of 75 species of amphibian tadpoles from an aseasonal tropical mountain range of the Ecuadorian Andes, distributed along a 3500 m elevational range, to test the climatic variability hypothesis at a large (elevation) and a small (microhabitat) scale. We show how species from less variable thermal habitats, such as lowlands and those restricted to streams, exhibit narrower thermal tolerance breadths than highland and pond‐dwelling species respectively. Interestingly, while broader thermal tolerance breadths at large scales are driven by higher cold tolerance variation (heat‐invariant hypothesis), at local scales they are driven by higher heat tolerance variation. This contrasting pattern may result from divergent selection on both thermal limits to face environmental thermal extremes at different scales. Specifically, within the same elevational window, exposure to extreme maximum temperatures could be avoided through habitat shifts from temporary ponds to permanent ponds or streams, while minimum peak temperatures remained invariable between habitats but steadily decreased with elevation. Therefore an understanding of the effects of habitat conversion is crucial for future research on resilience to climate change.
Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the ...duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.
Understanding how species' thermal limits have evolved across the tree of life is central to predicting species' responses to climate change. Here, using experimentally-derived estimates of thermal ...tolerance limits for over 2000 terrestrial and aquatic species, we show that most of the variation in thermal tolerance can be attributed to a combination of adaptation to current climatic extremes, and the existence of evolutionary 'attractors' that reflect either boundaries or optima in thermal tolerance limits. Our results also reveal deep-time climate legacies in ectotherms, whereby orders that originated in cold paleoclimates have presently lower cold tolerance limits than those with warm thermal ancestry. Conversely, heat tolerance appears unrelated to climate ancestry. Cold tolerance has evolved more quickly than heat tolerance in endotherms and ectotherms. If the past tempo of evolution for upper thermal limits continues, adaptive responses in thermal limits will have limited potential to rescue the large majority of species given the unprecedented rate of contemporary climate change.
OBJECTIVE: To report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new ...International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. RESEARCH DESIGN AND METHODS: All participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively). RESULTS: Overall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds. CONCLUSIONS: Although the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.
PDF
