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Zinc (Zn) is a major soil contaminant and high Zn levels can disrupt growth, survival, and reproduction of fungi. Some fungal species evolved Zn tolerance through cell processes mitigating Zn toxicity, though the genes and detailed mechanisms underlying mycorrhizal fungal Zn tolerance remain unexplored. To fill this gap in knowledge, we investigated the gene expression of Zn tolerance in the ectomycorrhizal fungus Suillus luteus. We found that Zn tolerance in this species is mainly a constitutive trait that can also be environmentally dependent. Zinc tolerance in S. luteus is associated with differences in expression of genes involved in metal exclusion and immobilization, as well as recognition and mitigation of metal-induced oxidative stress. Differentially expressed genes were predicted to be involved in transmembrane transport, metal chelation, oxidoreductase activity, and signal transduction. Some of these genes were previously reported as candidates for S. luteus Zn tolerance, while others are reported here for the first time. Our results contribute to understanding the mechanisms of fungal metal tolerance and pave the way for further research on the role of fungal metal tolerance in mycorrhizal associations.

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4-RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype.

Human-wildlife interactions are increasing in severity due to climate change and proliferating urbanization. Regions where human infrastructure and activity are rapidly densifying or newly appearing constitute novel environments in which wildlife must learn to coexist with people, thereby serving as ideal case studies with which to infer future human-wildlife interactions in shared landscapes. As a widely reviled and behaviorally plastic apex predator, the spotted hyena (Crocuta crocuta) is a model species for understanding how large carnivores navigate these human-caused landscapes of fear in a changing world. Using high-resolution GPS collar data, we applied resource selection functions and step selection functions to assess spotted hyena landscape navigation and fine-scale movement decisions in relation to social-ecological features in a rapidly developing region comprising two protected areas: Lake Nakuru National Park and Soysambu Conservancy, Kenya. We then used camera trap imagery and Barrier Behavior Analysis (BaBA) to further examine hyena interactions with barriers. Our results show that environmental factors, linear infrastructure, human-carnivore conflict hotspots, and human tolerance were all important predictors for landscape-scale resource selection by hyenas, while human experience elements were less important for fine-scale hyena movement decisions. Hyena selection for these characteristics also changed seasonally and across land management types. Camera traps documented an exceptionally high number of individual spotted hyenas (234) approaching the national park fence at 16 sites during the study period, and BaBA results suggested that hyenas perceive protected area boundaries semi-permeable electric fences as risky but may cross them out of necessity. Our findings highlight that the ability of carnivores to flexibly respond within human-caused landscapes of fear may be expressed differently depending on context, scale, and climatic factors. These results also point to the need to incorporate societal factors into multiscale analyses of wildlife movement to effectively plan for human-wildlife coexistence.

A combination therapy of preproinsulin (PPI) and immunomodulators (TGFβ+IL10) orally delivered via genetically modified Salmonella and anti-CD3 promoted glucose balance in in NOD mice with recent onset diabetes. The Salmonella bacteria were modified to express the diabetes-associated antigen PPI controlled by a bacterial promoter in conjunction with over-expressed immunomodulating molecules. The possible mechanisms of action of this vaccine to limit autoimmune diabetes remained undefined. In mice, the vaccine prevented and reversed ongoing diabetes. The vaccine-mediated beneficial effects were associated with increased numbers of antigen-specific CD4+CD25+Foxp3+ Tregs, CD4+CD49b+LAG3+ Tr1-cells, and tolerogenic dendritic-cells (tol-DCs) in the spleens and lymphatic organs of treated mice. Despite this, the immune response to Salmonella infection was not altered. Furthermore, the vaccine effects were associated with a reduction in islet-infiltrating lymphocytes and an increase in the islet beta-cell mass. This was associated with increased serum levels of the tolerogenic cytokines (IL10, IL2, and IL13) and chemokine ligand 2 (CCL2) and decreased levels of inflammatory cytokines (IFNγ, GM-CSF, IL6, IL12, and TNFα) and chemokines (CXCL1, CXCL2, and CXCL5). Overall, the data suggest that the Salmonella-based vaccine modulates the immune response, reduces inflammation, and promotes tolerance specifically to an antigen involved in autoimmune diabetes.

Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD+ naïve and IgD+ memory B cells in CVID patients. Here, no differences were observed in the percentages and proliferative responses of anergic IgD+IgM-CD27- B cells between CVID patients, with or without autoimmune disease, and the control group. Interestingly, in the compartment of memory B cells, the percentage of IgD+IgM- cells was higher only in CVID patients with allergic rhinitis/allergic asthma. Our results may indicate that anergic IgD+IgM-CD27- B cells may not be compromised in our CVID cohort. However, IgD+IgM- memory B cells may play a role in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients. Further studies are needed to better understand the participation of IgD+IgM- memory B cells in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients.

We determine the sensitivity of a current optimal solution to a combinatorial optimization problem to cost changes in a set of elements. In a recent study, the concept of regular set tolerances has been introduced for a combinatorial optimization problem and for three types of cost functions, namely sum, product, and bottleneck. A regular set tolerance is the supremum amount of cost changes that can be distributed in the most favorable way to multiple elements such as not to change the current optimal solution. In this paper, we introduce an alternative concept, namely the reverse set tolerance , which is a measure of the infimum amount of cost changes to multiple elements such that the current optimal solution becomes non-optimal. We characterize the specific cases in which reverse set upper and lower tolerances have positive values and in which they are infinite. We also show a criterion for the uniqueness of an optimal solution. Furthermore, we present bounds and exact formulas for reverse set upper and lower tolerances using the relation to their corresponding single tolerance counterparts. We discuss the similarities and differences in the results between regular and reverse set tolerances. Finally, we motivate this new concept by analyzing them for special combinatorial optimization problems with important practical applications. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen‐presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re‐establishing/inducing tolerance in immune‐mediated conditions. The generation of potent tolDC in vitro from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL‐10 conditioning has been proven to be the most efficient, as IL‐10‐modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL‐10 production, functional characterization of in vitro generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC‐based therapy, and finally new perspectives in the generation of effective tolDC. [ABSTRACT FROM AUTHOR]

Purpose: To report the oncological outcomes and the tolerance between 6 instillations and more than 6 cycles of hyperthermic intravesical chemotherapy(HIVEC) in patients with non-muscle invasive bladder cancer(NMIBC). Methods: This is a multicenter retrospective study from a national database including 9 expert centers. All patients treated with HIVEC between 2016 and 2023 for NMIBC were included. Patients were classified into two groups according to the total number of HIVEC instillations, including induction plus maintenance. Kaplan-Meier curves were computed to present survival outcomes. Results: 261 patients with a median follow-up of 25.5 months were included. 199(76.2%) and 62(23.8%) were treated by 6 and more than 6 cycles of HIVEC, respectively. The 2-years RFS(40.2% vs. 34.4%,p = 0.3) and the 2-years PFS(86% vs. 87%,p = 0.85) were similar between group treated with 6 and more than 6 instillations. 2-years CSS and OS were also similar between both groups. Univariate Cox regression showed no association between the number of bladder instillation and RFS (HR = 1.2 95%CI[0.8–1.84], p = 0.3) or PFS (HR = 0.8 95%CI[0.29–2.02], p = 0.2). In the group treated with more than 6 cycles, 2-years RFS and 2-years PFS were similar between patients who received induction plus maintenance compared to those treated with induction only. Finally, hematuria and urinary burning were significantly higher in the group treated by more than 6 cycles (21% vs. 8.5%(p < 0.01),and 29% vs. 17% (p = 0.03), respectively). Serious side effects(grade ≥ 3) are rare(3.1%) and similar in both groups. Conclusions: Results show no significant difference in two years RFS, PFS, CSS and OS according to number of instillations received, while toxicity profile seems better in the group receiving six instillations only. [ABSTRACT FROM AUTHOR]

Background: Calcium-dependent protein kinase (CDPK) plays a key role in cotton tolerance to abiotic stress. However, its role in cotton heat stress tolerance is not well understood. Here, we characterize the GhCDPK gene family and their expression profiles with the aim of identifying CDPK genes associated with heat stress tolerance. Results: This study revealed 48 GhCDPK members in the cotton genome, distributed on 18 chromosomes. Tree phylogenetic analysis showed three main clustering groups of the GhCDPKs. Cis-elements revealed many abiotic stress and phytohormone pathways conserved promoter regions. Similarly, analysis of the transcription factor binding sites (TFBDS) in the GhCDPK genes showed many stress and hormone related sites. The expression analysis based on qRT-PCR showed that GhCDPK16 was highly responsive to high-temperature stress. Subsequent protein-protein interactions of GhCDPK16 revealed predictable interaction with ROS generating, calcium binding, and ABA signaling proteins. Overexpression of GhCDPK16 in cotton and Arabidopsis improved thermotolerance by lowering ROS compound buildup. Under heat stress, GhCDPK16 transgenic lines upregulated heat-inducible genes GhHSP70, GHSP17.3, and GhGR1, as demonstrated by qRT-PCR analysis. Contrarily, GhCDPK16 knockout lines in cotton exhibited an increase in ROS accumulation. Furthermore, antioxidant enzyme activity was dramatically boosted in the GhCDPK16-ox transgenic lines. Conclusions: The collective findings demonstrated that GhCDPK16 could be a viable gene to enhance thermotolerance in cotton and, therefore, a potential candidate gene for improving heat tolerance in cotton. [ABSTRACT FROM AUTHOR]

Every year, unfavorable environmental factors significantly affect crop productivity and threaten food security. Plants are sessile; they cannot move to escape unfavorable environmental conditions, and therefore, they activate a variety of defense pathways. Among them are processes regulated by stress‐associated proteins (SAPs). SAPs have a specific zinc finger domain (A20) at the N‐terminus and either AN1 or C2H2 at the C‐terminus. SAP proteins are involved in many biological processes and in response to various abiotic or biotic constraints. Most SAPs play a role in conferring transgenic stress resistance and are stress‐inducible. The emerging field of SAPs in abiotic or biotic stress response regulation has attracted the attention of researchers. Although SAPs interact with various proteins to perform their functions, the exact mechanisms of these interactions remain incompletely understood. This review aims to provide a comprehensive understanding of SAPs, covering their diversity, structure, expression, and subcellular localization. SAPs play a pivotal role in enabling crosstalk between abiotic and biotic stress signaling pathways, making them essential for developing stress‐tolerant crops without yield penalties. Collectively, understanding the complex regulation of SAPs in stress responses can contribute to enhancing tolerance against various environmental stresses through several techniques such as transgenesis, classical breeding, or gene editing. [ABSTRACT FROM AUTHOR]

Capture and manipulation are an integral part of wildlife research and management. These practices, however, can affect animals either directly or indirectly, and studies should generally evaluate the consequences of captures to ensure animal welfare and reduce sampling bias. Here, we investigated the indirect, behavioural effects of live‐capture on escape response to humans in Alpine marmot Marmota marmota within the Stelvio National Park (central Italian Alps) over three seasons (2021–2023). We used flight initiation distance (FID) as a measure of escape response and tested it in relation to capture status using linear mixed modelling. Captures did not have any detectable effect on escape response, and FID was best explained by covariates such as starting distance, distance to nearest burrow, current behaviour during the observation and year of observation. It might be that, in marmots, escape response to humans is a rather inert behaviour. As such, although we cannot rule out unmeasured effects, capture may not represent an excessively traumatic experience which could trigger immediate behavioural modification. In turn, capture is unlikely to compromise animal welfare or cause scientific bias in studies investigating escape response in this species, at least over the short term. [ABSTRACT FROM AUTHOR]

In this article, I select a number of Enlightenment figures and suggest that, despite inevitable contradictions, they should still serve as exemplars for a modern age of a series of values such as freedom, tolerance, and social justice. I believe, however, that The Enlightenment is, nevertheless, a work in progress. [ABSTRACT FROM AUTHOR]

Critical discourse studies do not often consider lateral power struggles between social groups with competing and intersecting interests, ideas and identities. As such, there is often little to no consideration of potentially detrimental outcomes or unintended consequences when proposing radical and transformative change. This paper therefore argues for critical relativism in CDS, considering intersecting power structures and struggles between potentially competing social groups. In illustration, this paper takes the case of ongoing antagonism over the socio-legal recognition of transgender identities in the West. Transgender identities are arguably more hotly debated at present than any other in relation to their socio-legal recognition and its perceived implications on other social groups. This paper therefore discusses how the interests of transgender socio-legal gender recognition intersect and compete with the interests of other social groups, whether in reality or only in perception. In so doing, this paper contends that the transformative impetus of CDS must account for the mechanisms and outcomes of lateral struggle. In a world of ever-increasing awareness of the interconnected systems of dominance and resistance, embedding critical relativism in CDS is imperative if it is to evolve and maintain relevance as an approach to meaningfully analysing discourse and championing social change. [ABSTRACT FROM AUTHOR]

The identification of genotypes with high yield and yield stability under drought is the first step towards the generation of novel lines with better adaptation to climate change variation. The aim of this work was to explore the efficiency of ten different drought tolerance indices to identify superior genotypes. Ten wheat genotypes were evaluated for two years under two irrigation regimes: control and water deficit. As expected, the water deficit reduced the phenotypic values, of the evaluated traits in tested wheat cultivars. Significant positive correlations were found considering the grain-yield under both regimes (Yp, Ys), and three drought tolerance indices (DTIs): the Mean Productivity Index (MP), the Stress Tolerance Index (STI) and the Geometric Mean Productivity (GMP). These correlations were confirmed in Bi-plot analysis and the graphical separation of tested genotypes associated with different performances in drought indices. MP, STI and GMP indices consistently selected BioInta 2002, Baguette 9 and BioInta 2004 as the drought tolerant materials, and conversely, Baguette P. 11, BioInta 1005 and Pampeano as drought susceptible materials. These analyses positionate MP, STI and GMP as appropriate tools to find genotypes with contrasting drought response to drought to later be incorporated as genetic resources into breeding programs. [ABSTRACT FROM AUTHOR]

Background: Chronic pain significantly impacts quality of life and poses substantial public health challenges. Buprenorphine, a synthetic analog of thebaine, is recognized for its potential in managing moderate to severe chronic pain with fewer side effects and a lower incidence of tolerance compared to traditional opioids. Objective: This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development. Methods: This retrospective observational study involved 246 patients prescribed buprenorphine transdermal patches. We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patientreported outcomes through the Patients' Global Impression of Change (PGIC). Any adverse events were also recorded. Results: Over the 36-month period, there was a significant reduction in NRS scores for both moderate and severe pain patients, demonstrating buprenorphine's sustained analgesic effect. Tolerance measurement indicated that no patients required increases in morphine-equivalent doses that would meet or exceed the FDA's threshold for opioid tolerance (60 mg/day of morphine or equivalent). Additionally, patient satisfaction was high, with the PGIC reflecting significant improvements in pain management and overall wellbeing. The side effects were minimal, with skin reactions and nausea being the most commonly reported but manageable adverse events. Conclusion: The study findings validate the long-term use of buprenorphine transdermal patches as an effective and safe option for chronic pain management, maintaining efficacy without significant tolerance development. These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations. [ABSTRACT FROM AUTHOR]

AbstractSalinity is harmful for crop development and productivity. The adoption of intercropping practice and microbial auxiliaries can combat the harmful actions of salt stress. The present study aimed to investigate the role of intercropping and co-application of arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) to protect barley and alfalfa against salt stress (120 mM NaCl). Results revealed that, under saline conditions, the applied intercropping system and AMF + PGPR co-inoculation enhanced shoot and root dry weight by 133% and 354% for barley and 410% and 471% for alfalfa, respectively, over their respective non-inoculated monocultures. Meanwhile, as compared to non-inoculated monocultures, the association of intercropping and AMF + PGPR co-application boosted antioxidant enzymes activity, namely superoxide dismutase and catalase, by 161% and 63% for barley and 316% and 113% for alfalfa, respectively. Additionally, the thousand-seed weight was increased by 77% in barley intercropped and inoculated with AMF + PGPR. This study highlights the potential of intercropping and AMF + PGPR as a promising solution to improve salt tolerance and crop productivity by increasing physiological capacity, boosting nutrient acquisition, and enhancing redox potential. [ABSTRACT FROM AUTHOR]

Simple Summary: How people feel about large carnivores can be critical in determining the success of conservation efforts. In some cases, people's attitudes towards large carnivores are more influenced by policies dictating how people can interact with those species rather than the species themselves. Yet, the connections between policy and tolerance of large carnivores remain unclear. To better understand these connections, we surveyed residents of northern Wisconsin, USA, about wolves Canis lupus and wolf policies. We grouped survey respondents based on their general attitudes towards wolves and assessed whether respondents expected their tolerance of wolves to improve under different policy scenarios. Hunters, people with generally negative or ambivalent attitudes towards wolves, and people with wildlife conflict experience were more likely to expect their tolerance to improve under policy scenarios that allowed for the regulated killing of wolves under certain circumstances. However, we also observed important nuances in the relationship between tolerance of wolves and wolf policy. Large carnivore conservationists must balance conservation objectives with the preferences of local people. The fulcrum of this balance may shift over time as local preferences or species status change. Thus, monitoring local policy preferences may be just as important as carnivore population monitoring. Success in large carnivore conservation often hinges on local residents' tolerance towards those species. Feelings of powerlessness and frustration with wildlife policies can lead to intolerance of the species. In extreme cases, intolerance may manifest in poaching. Thus, changes in policy may influence the tolerance of wildlife. To examine the connections between policy and tolerance, we examined how policy scenarios influenced anticipated changes in tolerance to wolves Canis lupus. We administered a survey in 2015–2016 in the core wolf range within northern Wisconsin, USA. Using hierarchical cluster analysis, we clustered respondents into groups based on their current tolerance of wolves. We evaluated the behavioral intentions of the clusters and examined the influence of policy scenarios on respondents' anticipated changes in tolerance. Finally, using an information-theoretic model selection framework, we assessed the effects of tolerance clusters and demographic factors. The respondents were clustered into three clusters relative to their current tolerance towards wolves: positive, ambivalent, and negative. Each cluster exhibited significantly different behavioral intentions and anticipated changes in tolerance for all scenarios. In all scenarios, respondents who already held positive attitudes towards wolves were significantly less likely to report expected changes in tolerance toward wolves following changes in wolf management. However, respondents who held ambivalent or negative attitudes towards wolves were significantly more likely to report expected changes in tolerance towards wolves following changes in wolf management. Regarding a regulated wolf hunting and trapping season, we observed a Simpson's Paradox, wherein, when examined in aggregate, no clear pattern emerged, but when examined at the cluster level, important and intuitive patterns emerged. Our demographic model results suggest that policy changes resulting in greater state management authority over wolves, especially authority to implement certain forms of legal killing of wolves, could result in significant increases in tolerance for individuals who identify as hunters, have lost livestock to a predator, or are currently ambivalent or negative towards wolves. Our work elucidates the nuanced relationship between tolerance of wildlife and wildlife policy and identifies a potential ecological fallacy. [ABSTRACT FROM AUTHOR]

The rise of antibiotic tolerance in bacteria harboring genetic elements conferring resistance to antibiotics poses an increasing threat to public health. However, the primary factors responsible for the emergence of antibiotic tolerance and the fundamental molecular mechanisms involved remain poorly comprehended. Here, we demonstrate that the commonly utilized food additive Benzaldehyde (BZH) possesses the capacity to induce a significant level of fluoroquinolone tolerance in vitro among resistant Escherichia coli. Our findings from animal models reveal that the pre-administration of BZH results in an ineffective eradication of bacteria through ciprofloxacin treatment, leading to similar survival rates and bacterial loads as observed in the control group. These results strongly indicate that BZH elicits in vivo tolerance. Mechanistic investigations reveal several key factors: BZH inhibits the formation of bacterial flagella and releases proton motive force (PMF), which aids in expelling antibiotics from within cells to reducing their accumulation inside. In addition, BZH suppresses bacterial respiration and inhibits the production of reactive oxygen species (ROS). Moreover, exogenous pyruvate successfully reverses BZH-induced tolerance and restores the effectiveness of antibiotics, highlighting how crucial the pyruvate cycle is in combating antibiotic tolerance. The present findings elucidate the underlying mechanisms of BZH-induced tolerance and highlight potential hazards associated with the utilization of BZH. [ABSTRACT FROM AUTHOR]

Traditional wet plug charging for autonomous underwater vehicles (AUVs) limits its application. Inductive power transfer (IPT) is an effective solution to this problem. This paper proposes an arc‐shaped magnetic coupler incorporated with solenoid coils to achieve a stable and efficient output against rotational misalignment for charging AUV. The novel magnetic coupler consists of two solenoid coils and an arc‐shaped coil with a reverse winding, guaranteeing a relatively constant total mutual inductance and decoupling from each other. This magnetic coupler has the characteristics of a compact structure, an ultra‐wide coupling range, and a relatively stable equivalent mutual inductance. The experimental IPT prototype can deliver 1.29 kW with a dc–dc efficiency of 93% under the fully aligned case and 1.2 kW with a dc–dc efficiency of 91% under the misaligned case. [ABSTRACT FROM AUTHOR]

This study focused on mitigating effects of an animal-derived biostimulant on sugar beet plantlets subjected to drought stress. The experiment was performed at the Seed Science and Technology Laboratory of the Eskişehir Osmangazi University, Faculty of Agriculture, Department of Field Crops, in 2024. It was established by the randomized plot 2x5 factorial experimental design (ANOVA) with four replications. The sugar beet cultivar Mohican was sprayed by an animalderived biostimulant (Andolamin®) containing 11% amino acids. Different levels of the biostimulant (control, 12.5, 25, 50, and 75 mL/L) were treated twice at 2-day intervals. Morphological and physiological measurements were made at 7 days after the first application on sugar beet plants grown under two irrigation regimes (water deficit (WD) 50% of field capacity and well-watered (WW) 80% of field capacity). The findings showed that drought had a hazardous impact on sugar beet's number of leaves (NL), fresh (LFW) and leaf dry weight (LDW), relative water content (RWC), and leaf area (LA). Leaf surface temperature (LST), chlorophyll content (Chl), and electrolyte leakage (EL) were higher in plants under water deficit. Foliar biostimulant application mitigated the effect of drought stress on seedlings through improving LFW, LDW, Chl, EL, and LA. On the other hand, biostimulant treatment had no significant effects on NL, and RWC in seedlings exposed to drought stress. It was concluded that animal-derived biostimulant application may be used for alleviating the harmful effects of drought stress and may stimulate the growth of sugar beet seedlings. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the single and combined effects of Si exogenous treatment and Bacillus subtilis subsp. subtilis M1 strain inoculation on rosemary tolerance to low phosphorus (P) availability. Hence, rosemary plants were fertilized with 250 µmol Ca3HPO4 (stressed plants) or 250 µmol KH2PO4 (control plants) under Si treatment and B. subtilis M1 strain inoculation. P starvation negatively affected rosemary growth and its P nutrition. However, exogenous Si supply or B. subtilis M1 strain inoculation significantly (P  < 0.001) alleviated the deficiency-induced effects and significantly improved rhizogenesis, acid phosphatase activity, P uptake, and eventually dry weight of shoot and root. Moreover, Si-treatment and/or B. subtilis M1 strain inoculation significantly (P < 0.001) reduced the oxidative damage, in terms of malondialdehyde and hydrogen peroxide accumulation. This was found positively correlated with the higher superoxide dismutase activity, and the elevated non-enzymatic antioxidant molecules accumulation, including total polyphenols in Si-treated and inoculated P-deficient plants. Taken together, Si supplementation and/or B. subtilis M1 strain inoculation could be a good strategy to sustain rosemary plant growth under P starvation conditions. [ABSTRACT FROM AUTHOR]

Salt stress poses a substantial threat to fruit cultivation in arid and semi-arid regions. An essential aspect of mitigating this challenge involves understanding the adaptive changes in plants under salinity conditions. In this study, salinity stress (0, 20, 40, and 80 mM) induced in Ankara and Deveci pear varieties grafted onto OH×F 97, OH×F 333, and BA 29 rootstocks. Plant height and diameter, stomatal conductance, photosynthetic pigments and K+/Na+ ratio exhibited a decreasing trend, indicating the impact of salt stress. Conversely, the salt stress index and the activities of antioxidant enzymes including superoxide dismutase, catalase, and ascorbate peroxidase showed an increasing trend, highlighting the plant’s defense mechanisms against oxidative stress. In our comprehensive evaluation, the Deveci × OH×F 97 demonstrated a higher level of tolerance to sodium chloride stress compared to other combinations. Notably, combinations involving the BA 29, particularly Ankara × BA 29, exhibited more pronounced damage under NaCl stress. An intriguing finding was the announced response of enzymatic antioxidants, where despite a higher increase in SOD activity in the Deveci × OH×F 97, CAT and APX activities were generally higher in the Ankara × BA 29. This suggests the effective operation of enzymatic antioxidants in ameliorating oxidative damage in cells exposed to NaCl stress, irrespective of the overall stress tolerance of the plant, within the Pyrus. This study contributes valuable insights into the complex interplay between pear varieties, rootstocks, and NaCl stress, providing a foundation for informed decision-making in orchard management practices to enhance the resilience of pear cultivation in challenging environmental conditions. [ABSTRACT FROM AUTHOR]

Rodents can cause considerable changes in plant community composition. However, relationships between shifts in species dominance and plant functional traits caused by rodents have seldom been investigated, especially for belowground functional traits. In this study, a set of enclosures was constructed to analyze the effects of 10 years of Brandt's voles' activities on the defense strategies and dominant position changes of three gramineous plants (Leymus chinensis, Stipa krylovii, and Cleistogenes squarrosa) in Inner Mongolia. Here, we measured the dominance, biomass, and fourteen functional traits of three plants. The effects of Brandt's voles on dominance, biomass, and functional traits were analyzed, and then we explored the effect of functional traits on plant dominance by using the structural equation model. Results showed that long‐term feeding by Brandt's voles resulted in a significant decrease in the dominance of L. chinensis and S. krylovii, whereas C. squarrosa was positively affected. The belowground biomass of L. chinensis and S. krylovii was higher in the vole treatment, which showed that they were increasing their escape characteristics. The leaf thickness of L. chinensis and the leaf C:N ratio of S. krylovii significantly increased, while the specific leaf area of C. squarrosa significantly decreased. All three gramineous showed increased resistance traits in response to Brandt's voles, which positively affected their dominance. Tolerance‐related traits of S. krylovii significantly increased, with the increasing growth rate of root length contributing to enhancing its dominance. We highlight that selective feeding by rodents led to the selection of different defense strategies by three gramineous plants, and that changes in biomass allocation and functional traits in the different species affected plant dominance, driving changes in the plant communities. [ABSTRACT FROM AUTHOR]

Wildlife conservation depends on supportive social as well as biophysical conditions. Social identities such as hunter and nonhunter are often associated with different attitudes toward wildlife. However, it is unknown whether dynamics within and among these identity groups explain how attitudes form and why they differ. To investigate how social identities help shape wildlife‐related attitudes and the implications for wildlife policy and conservation, we built a structural equation model with survey data from Montana (USA) residents (n = 1758) that tested how social identities affect the relationship between experiences with grizzly bears (Ursus arctos horribilis) and attitudes toward the species. Model results (r2 = 0.51) demonstrated that the hunter identity magnified the negative effect of vicarious property damage on attitudes toward grizzly bears (β = −0.381, 95% confidence interval [CI]: −0.584 to −0.178, p < 0.001), which in turn strongly influenced acceptance (β = −0.571, 95% CI: −0.611 to −0.531, p < 0.001). Our findings suggested that hunters' attitudes toward grizzly bears likely become more negative primarily because of in‐group social interactions about negative experiences, and similar group dynamics may lead nonhunters to disregard the negative experiences that out‐group members have with grizzly bears. Given the profound influence of social identity on human cognitions and behaviors in myriad contexts, the patterns we observed are likely important in a variety of wildlife conservation situations. To foster positive conservation outcomes and minimize polarization, management strategies should account for these identity‐driven perceptions while prioritizing conflict prevention and promoting positive wildlife narratives within and among identity groups. This study illustrates the utility of social identity theory for explaining and influencing human–wildlife interactions. [ABSTRACT FROM AUTHOR]

Several reports have highlighted the dichotomous nature of the Interleukin-33 (IL-33) system in cardiac and lung disease, where this cytokine can exert both protective effects and drive pro-inflammatory responses in a context-specific manner. This State-of-the-Art review focuses on preclinical mechanistic studies of the IL-33 system in development of allograft rejection in heart and lung transplantation. We address the scope of potential cellular sources of IL-33 and pathways for cellular release that may impact the study of this cytokine system in transplant models. We then highlight soluble IL-33 receptor as a biomarker in cardiac allograft rejection and detail preclinical models that collectively demonstrate a role for this cytokine in driving type-2 immune programs to protect cardiac allografts. We contrast this with investigation of IL-33 in lung transplantation, which has yielded mixed and somewhat conflicting results when comparing human studies with preclinical models, which have implicated the IL-33 system in both allograft tolerance and acceleration of chronic rejection. We summarize and interpret these results in aggregate and provide future directions for study of IL-33 in heart and lung transplantation. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of our study was to determine whether granzyme B-expressing regulatory B cells (GZMB+ B cells) are enriched in the blood of transplant patients with renal graft tolerance. To achieve this goal, we analysed two single-cell RNA sequencing (scRNAseq) datasets: (1) peripheral blood mononuclear cells (PBMCs), including GZMB+ B cells from renal transplant patients, i.e., patients with stable graft function on conventional immunosuppressive treatment (STA, n = 3), drug-free tolerant patients (TOL, n = 3), and patients with antibody-mediated rejection (ABMR, n = 3), and (2) ex-vivo-induced GZMB+ B cells from these groups. In the patient PBMCs, we first showed that natural GZMB+ B cells were enriched in genes specific to Natural Killer (NK) cells (such as NKG7 and KLRD1) and regulatory B cells (such as GZMB, IL10, and CCL4). We performed a pseudotemporal trajectory analysis of natural GZMB+ B cells and showed that they were highly differentiated B cells with a trajectory that is very different from that of conventional memory B cells and linked to the transcription factor KLF13. By specifically analysing GZMB+ natural B cells in TOLs, we found that these cells had a very specific transcriptomic profile associated with a reduction in the expression of HLA molecules, apoptosis, and the inflammatory response (in general) in the blood and that this signature was conserved after ex vivo induction, with the induction of genes associated with migration processes, such as CCR7, CCL3, or CCL4. An analysis of receptor/ligand interactions between these GZMB+/− natural B cells and all of the immune cells present in PBMCs also demonstrated that GZMB+ B cells were the B cells that carried the most ligands and had the most interactions with other immune cells, particularly in tolerant patients. Finally, we showed that these GZMB+ B cells were able to infiltrate the graft under inflammatory conditions, thus suggesting that they can act in locations where immune events occur. [ABSTRACT FROM AUTHOR]

Problem: Preeclampsia (PE) and fetal growth restriction (FGR) are often associated with maternal inflammation and an increased risk of cardiovascular and metabolic disease in the affected mothers. The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications. Method of Study: Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor. Cytokine release from monocytes following exposure to lipopolysaccharide (LPS) and the presence of lysine 4‐trimethylated histone 3 (H3K4me3) within TNF promoter sequences were evaluated. Single‐cell transcriptomic profiles of circulating monocytes from women with PE or uncomplicated pregnancies were assessed. Results: Monocytes from women with PE or FGR exhibited increased IL‐10 secretion and decreased IL‐1β and GM‐CSF secretion in response to LPS. While TNFα secretion was not significantly different in cultures of control monocytes versus those from complicated pregnancies with or without LPS exposure, monocytes from complicated pregnancies had significantly decreased levels of H3K4me3 associated with TNF promoter sequences. Cluster quantification and pathway analysis of differentially expressed genes revealed an increased proportion of anti‐inflammatory myeloid cells and a lower proportion of inflammatory non‐classical monocytes among the circulating monocyte population in women with PE. Conclusions: Monocytes from women with PE and FGR exhibit an immune tolerance phenotype before initiation of labor. Further investigation is required to determine whether this tolerogenic phenotype persists after the affected pregnancy and contributes to increased risk of subsequent disease. [ABSTRACT FROM AUTHOR]

Pest attack is an important biotic threat to sorghum productivity, and one of the main insect pests of grain sorghum is sugarcane borer (SCB) Diatraea saccharalis. Despite the importance of this insect species, little is known about the relationship between SCB infestation and reduction in sorghum grain yield, as well as on the gain threshold and economic injury level for decision making of pest control. This study evaluated the influence of SCB infestation on plant performance and grain production in three commercial grain sorghum hybrids. Hybrids AG1090, BRS 373, and DKB 590 were planted in three crop seasons in Sete Lagoas, Brazil, and six treatments were assessed in the experiments, consisting of three grain sorghum hybrids with and without the insecticide chlorantraniliprole at 52.5 g a.i. ha−1 under SCB natural infestation. The parameters evaluated on sorghum plants were the length of tunnels, plant height, length and weight of panicles, stem borer injury, and grain yield. The infestation of SCB was higher when sorghum plants were not treated with insecticide, resulting in lower productivity. The use of insecticide increased plant height, reduced tunnel length, and increased panicle length and weight. Hybrids only affected panicle weight. The hybrid that presented the highest panicle weight when using the insecticide was AG 1090. Hybrids AG 1090 and DKB 590 showed reduced grain production with increasing gallery length, whereas BRS 373 did not show a significant correlation, which may suggest a certain level of tolerance to SCB attack. This is the first study that determines the gain threshold and economic injury level and that effectively shows how much grain yield is lost by SCB attack in grain sorghum hybrids. [ABSTRACT FROM AUTHOR]

Aim: To explore the correlations between examination tolerance and anxiety, knowledge needs and examination cooperation in sedation‐free gastroscopy examinees. Design: Cross‐sectional survey using convenience sampling. Methods: A total of 170 healthy adults who underwent sedation‐free gastroenteroscopy were asked to complete a visual analogue scale (VAS) to rate their examination tolerance, the state anxiety questionnaire (S‐AI), a newly designed knowledge needs questionnaire and a cooperation questionnaire. Results: The VAS score was 4.47 ± 1.96, the state anxiety score was 39.46 ± 9.81, the total score for knowledge needs was 44.89 ± 11.02, and the average cooperation score was 2.47 ± 0.38. The VAS score during the examination positively correlated with the pretest state anxiety score and pretest knowledge needs score and negatively correlated with the examination cooperation score. The results of multiple linear regression analysis showed that after undergoing the examination for the first time, anxiety, body position and swallowing control were the main factors influencing the examination tolerance of sedation‐free gastroscopy examinees. Patient or Public Contribution: We would like to thank the staff and patients of the participating hospital for their assistance and cooperation in performing the current study. [ABSTRACT FROM AUTHOR]

Since 2012, growers of coriander, Coriandrum sativum L., in Israel have been suffering from summer wilting that can result in entire fields collapsing. The current study aimed to determine the cause of the phenomenon and find a genetic solution to the problem. The disease was reproduced in a growth chamber using naturally-infested soil from a commercial field. Wilt became apparent within two weeks, and after ten weeks, all plants died compared to plants in sterilized soil from the same source. Fusarium oxysporum was isolated from infected plants, and Koch's postulates were completed. Sequence analysis of the Elongation Factor (EF1α) encoding gene of the pathogen had a 99.54% match to F. oxysporum f. sp. coriandrii. Several coriander varieties were screened for resistance or tolerance to the disease. In four independent experiments, only the cultivar 'Smadi' showed high tolerance, while other genotypes were susceptible. In a trial in a naturally infested field, the cultivar 'Smadi' outperformed the commercial cultivar 'Blair'. 'Smadi' provides a cropping solution to many Israeli farmers, yet this winter cultivar bolts early in the summer. There is a further need to characterize the tolerance mechanism and inheritance for informed breeding of late-bolting Fusarium-resistant coriander. [ABSTRACT FROM AUTHOR]

The olive tree (Olea europaea L.) is an evergreen tree that occupies 19% of the woody crop area and is cultivated in 67 countries on five continents. The largest olive production region is concentrated in the Mediterranean basin, where the olive tree has had an enormous economic, cultural, and environmental impact since the 7th century BC. In the Mediterranean region, salinity stands out as one of the main abiotic stress factors significantly affecting agricultural production. Moreover, climate change is expected to lead to increased salinization in this region, threatening olive productivity. Salt stress causes combined damage by osmotic stress and ionic toxicity, restricting olive growth and interfering with multiple metabolic processes. A large variability in salinity tolerance among olive cultivars has been described. This paper aims to synthesize information from the published literature on olive adaptations to salt stress and its importance in salinity tolerance. The morphological, physiological, biochemical, and molecular mechanisms of olive tolerance to salt stress are reviewed. [ABSTRACT FROM AUTHOR]

Drought poses a significant challenge to plant growth and productivity, particularly in arid regions like northern Kazakhstan. Dehydration-responsive element-binding (DREB) transcription factors play an important role in plant response to drought and other abiotic stresses. In Arabidopsis thaliana, the DREB subfamily consists of six groups, designated DREB1 to DREB6. Among these, DREB2 is primarily associated with drought and salinity tolerance. In the chickpea genome, two DREB genes, CaDREB2c and CaDREB2h, have been identified, exhibiting high sequence similarity to Arabidopsis DREB2 genes. We investigated the nucleotide sequences of CaDREB2c and CaDREB2h genes in several chickpea cultivars commonly grown in northern Kazakhstan. Interestingly, the CaDREB2h gene sequence was identical across all varieties and corresponded to the sequence deposited in the GenBank. However, the CaDREB2c gene sequence exhibited variations among the studied varieties, categorized into three groups: the first group (I), comprising 20 cultivars, contained a CaDREB2c gene sequence identical to the GenBank (Indian cultivar CDC Frontier). The second group (II), consisting of 4 cultivars, had a single synonymous substitution (T to C) compared to the deposited CaDREB2c gene sequence. The third group, encompassing 5 cultivars, displayed one synonymous substitution (C to T) and two non-synonymous substitutions (G to T and G to A). Furthermore, we assessed the gene expression patterns of CaDREB2c and CaDREB2h in different chickpea varieties under drought conditions. Chickpea cultivars 8 (III), 37 (I), 6 (III), and 43 (I) exhibited the highest drought resistance. Our analysis revealed a strong positive correlation between drought resistance and CaDREB2h gene expression under drought stress. Our findings suggest that the chickpea's adaptive responses to water deprivation are associated with changes in CaDREB2 gene expression. To further elucidate the mechanisms underlying drought tolerance, we propose future research directions that will delve into the molecular interactions and downstream targets of CaDREB2 genes. [ABSTRACT FROM AUTHOR]

The accumulation of salt in arable lands is a source of significant abiotic stress, contributing to a 10% decline in the world's total arable lands and threatening food productivity and the sustainability of agriculture. About 76 million hectares of productive land are estimated to have been affected by human-induced salinization such as extreme salt deposits in soil, which are mainly caused by the actions of humans. For instance, continued irrigation and the frequent use of chemical fertilizers need to be understood. To ensure food availability, it is essential to improve upon traditional farming methods using current technologies to facilitate the reclamation of saline-affected arable lands to achieve high and sustainable food production. This review details current innovative strategies such as the modification of metabolic pathways, manipulation of antioxidant pathways, genetic engineering, RNA interference technology, engineered nanoparticles, arbuscular mycorrhizal fungi (AMF), organic amendments, and trace elements for improving saline marginal lands. These strategies were identified to have contributed to the improvement of plants salinity tolerance in diverse ways. For instance, the accumulation of plant metabolites such as amino acids, sugars, polyols, organic acids, saponins, anthocyanins, polyphenols, and tannins detoxify plants and play crucial roles in mitigating the detrimental effects of oxidative damage posed by salinity stress. Multiple plant miRNAs encoding the up- and down-regulation of single- and multi-ion transporters have been engineered in plant species to enhance salt tolerance. Nanomaterials and plant root system colonized by arbuscular mycorrhizal increase water uptake, photosynthetic efficiency, and biomass allocation in plants exposed to saline stress by excluding 65 percent of the Na+ uptake and enhancing K+ uptake by 84.21 percent. Organic amendments and trace elements reduced salinity concentrations by 22 percent and improved growth by up to 84 percent in maize subjected to salinity stress. This study also discusses how researchers can use these strategies to improve plants growth, development, and survival in saline soil conditions to enhance the productivity and sustainability of agriculture. The strategies discussed in this study have also proven to be promising approaches for developing salinity stress tolerance strategies for plants to increase agricultural productivity and sustainability. [ABSTRACT FROM AUTHOR]

This article investigates how avatars in the metaverse can be used for peer evaluation in a sustainable educational setting. The goal is to find the best alternative modes of assessment (one-to-many/many-to-one) to evaluate the design of a sustainable educational environment. The research also explores how learners' avatars influence the development of tolerance and respect for others within the metaverse. The study involved 36 female graduates from King Faisal University's College of Education. A quasi-experimental design with two experimental groups was employed to assess performance. Through a product quality card and applying a tolerance (IPTS) scale for data collection. The preliminary findings indicate that the avatars within the (one-to-many) group demonstrated better performance and showed an increase in tolerance values after the intervention, compared to their counterparts (many-to-one) as an alternative mode of assessment, in the development of a sustainable Edu-Metaverse environment. The research validated that avatars enhance positive attitudes and behaviors, thereby providing insights for developing more effective educational interventions and contributing to enhancing the user experience and implementation of sustainable educational initiatives through a metaverse. [ABSTRACT FROM AUTHOR]

This study investigates the growth tolerance mechanisms of Chlorella pyrenoidosa to 3-fluorophenol and its removal efficiency by algal cells. Our results indicate that C. pyrenoidosa can tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed by promotion of growth. In C. pyrenoidosa cells, the activities of superoxide dismutase (SOD) and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were higher than or comparable to the control group. Metabolic analysis revealed that the 3-fluorophenol treatment activated pathways, such as glycerol phospholipid metabolism, autophagy, glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, and phenylpropanoid biosynthesis, contributed to the stabilization of cell membrane structures and enhanced cell repair capacity. After 240 h of treatment, over 50% of 3-fluorophenol was removed by algal cells, primarily through adsorption. Thus, C. pyrenoidosa shows potential as an effective biosorbent for the bioremediation of 3-fluorophenol. [ABSTRACT FROM AUTHOR]

For decades, developing countries have faced international pressure to adopt the techniques and tactics consistent with the drug war. These have had profound and adverse consequences. While cannabis prohibition and drug control generally are topics that lend themselves to established comparative studies, engaging cannabis as a substantive topic engages numerous aspects of criminal justice systems. In this paper, we link cannabis to concepts related to recent formulations of international criminology. Next, we outline how the history of cannabis prohibition requires adopting a more critical global lens and consider the role of legal technical assistance to support countries renegotiating cannabis control in the twenty-first century. Beyond the formal tools and informal techniques commonly used within legal technical assistance, we argue expanding tolerance can disrupt the tendency for reform to expand social control. While embracing tolerance may serve as an antidote to some penal modalities, this must be combined with policies that regulate the aversion many feel toward cannabis and people who use it. Harm reduction provides a useful frame to combine these concepts and orient critical models of international criminology. [ABSTRACT FROM AUTHOR]

Summary Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE‐ and non‐IgE‐mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE‐ and non‐IgE‐mediated food allergies and considers the potential future investigations in this context. [ABSTRACT FROM AUTHOR]

Background: 2-Phenylethanol (2-PE) is one of the most widely used spices. Recently, 2-PE has also been considered a potential aviation fuel booster. However, the lack of scientific understanding of the 2-PE biosynthetic pathway and the cellular response to 2-PE cytotoxicity are the most important obstacles to the efficient biosynthesis of 2-PE. Results: Here, metabolic engineering and tolerance engineering strategies were used to improve the production of 2-PE in Komagataella phaffii. First, the endogenous genes encoding the amino acid permease GAP1, aminotransferase AAT2, phenylpyruvate decarboxylase KDC2, and aldehyde dehydrogenase ALD4 involved in the Ehrlich pathway and the 2-PE stress response gene NIT1 in K. phaffii were screened and characterized via comparative transcriptome analysis. Subsequently, metabolic engineering was employed to gradually reconstruct the 2-PE biosynthetic pathway, and the engineered strain S43 was obtained, which produced 2.98 g/L 2-PE in shake flask. Furthermore, transcriptional profiling analyses were utilized to screen for novel potential tolerance elements. Our results demonstrated that cells with knockout of the PDR12 and C4R2I5 genes exhibited a significant increase in 2-PE tolerance. To confirm the practical applications of these results, deletion of the PDR12 and C4R2I5 genes in the hyper 2-PE producing strain S43 dramatically increased the production of 2-PE by 18.12%, and the production was 3.54 g/L. Conclusion: This is the highest production of 2-PE produced by K. phaffii via l-phenylalanine conversion. These identified K. phaffii endogenous elements are highly conserved in other yeast species, suggesting that manipulation of these homologues might be a useful strategy for improving aromatic alcohol production. These results also enrich the understanding of aromatic compound biosynthetic pathways and 2-PE tolerance, and provide new elements and strategies for the synthesis of aromatic compounds by microbial cell factories. [ABSTRACT FROM AUTHOR]

The clonal selection theory (CST) is the centrepiece of the current paradigm used to explain immune recognition and memory. Throughout the past decades, the original CST had been expanded and modified to explain new experimental evidences since its original publication by Burnet. This gave origin to new paradigms that govern experimental immunology nowadays, such as the associative recognition of antigen model and the stranger/danger signal model. However, these new theories also do not fully explain experimental findings such as natural autoimmune immunoglobulins, idiotypic networks, low and high dose tolerance, and dual‐receptor T and B cells. To make sense of these empirical data, some authors have been trying to change the paradigm of immune cognition using a systemic approach, analogies with brain processing and concepts from second‐order cybernetics. In the present paper, we review the CST and some of the theories/hypotheses derived from it, focusing on immune recognition. We point out their main weaknesses and highlight arguments made by their opponents and believers. We conclude that, until now, none of the proposed theories can fully explain the totality of immune phenomena and that a theory of everything is needed in immunology. [ABSTRACT FROM AUTHOR]