Inequality leads to the evolution of intolerance in reputation-based populations.

This work studies the impact of economic inequality on the evolution of intolerance through a reputation-based model of indirect reciprocity. Results show that economic inequality is a powerful enhancer of intolerance, inducing the escalation of out-group discrimination even without the presence of new intolerant mutants. It also generates behavior modifications within tolerant disfavored minorities: their members either relax punishments against the uncooperative or prioritize helping the wealthy, even suffering discrimination in return. On the other hand, the redistribution of wealth is proven as a viable solution to avoid the spread of intolerance as long as it increases equality and is implemented before intolerance permeates part of the population.

Consumption of Tritordeum Bread Reduces Immunogenic Gluten Intake without Altering the Gut Microbiota.

Gluten proteins are responsible for the wheat breadmaking quality. However, gluten is also related to human pathologies for which the only treatment is a gluten-free diet (GFD). GFD has gained popularity among individuals who want to reduce their gluten intake. Tritordeum is a cereal species that originated after crossing durum wheat with wild barley and differs from bread wheat in its gluten composition. In this work, we have characterized the immunogenic epitopes of tritordeum bread and results from a four-phase study with healthy adults for preferences of bread and alterations in the gut microbiota after consuming wheat bread, gluten-free bread, and tritordeum bread are reported. Tritordeum presented fewer peptides related to gluten proteins, CD-epitopes, and IgE binding sites than bread wheat. Participants rated tritordeum bread higher than gluten-free bread. Gut microbiota analysis revealed that the adherence to a strict GFD involves some minor changes, especially altering the species producing short-chain fatty acids. However, the short-term consumption of tritordeum bread does not induce significant changes in the diversity or community composition of the intestinal microbiota in healthy individuals. Therefore, tritordeum bread could be an alternative for healthy individuals without wheat-related pathologies who want to reduce their gluten consumption without harming their gut health.

Oral Consumption of Bread from an RNAi Wheat Line with Strongly Silenced Gliadins Elicits No Immunogenic Response in a Pilot Study with Celiac Disease Patients.

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD.

Tritordeum breads are well tolerated with preference over gluten-free breads in non-celiac wheat-sensitive patients and its consumption induce changes in gut bacteria.

BACKGROUND: The ingestion of wheat and other cereals are related to several gut disorders. The specific components responsible for non-celiac wheat-sensitivity (NCWS) may include gluten and other compounds. Tritordeum is a new cereal derived from crossing durum wheat with a wild barley species, which differs from bread wheat in its gluten composition. In the present work, we examined the response of NCWS patients to tritordeum bread Gastrointestinal symptoms as well as tritordeum acceptability, gluten immunogenic peptides excretion, and the composition and structure of the intestinal microbiota were evaluated. RESULTS: Gastrointestinal symptoms of the subjects showed no significant change between the gluten-free bread and the tritordeum bread. Participating subjects rated tritordeum bread higher than the gluten-free bread. Analysis of the bacterial gut microbiota indicated that tritordeum consumption does not alter the global structure and composition of the intestinal microbiota, and only a few changes in some butyrate-producing bacteria were observed. CONCLUSIONS: All the results derived from acceptability, biochemical and microbiological tests suggest that tritordeum may be tolerated by a sub-set of NCWS sufferers who do not require strict exclusion of gluten from their diet. © 2020 Society of Chemical Industry.

Signalling boosts the evolution of cooperation in repeated group interactions.

Many biological and social systems show significant levels of collective action. Several cooperation mechanisms have been proposed, yet they have been mostly studied independently. Among these, direct reciprocity supports cooperation on the basis of repeated interactions among individuals. Signals and quorum dynamics may also drive cooperation. Here, we resort to an evolutionary game-theoretical model to jointly analyse these two mechanisms and study the conditions in which evolution selects for direct reciprocity, signalling, or their combination. We show that signalling alone leads to higher levels of cooperation than when combined with reciprocity, while offering additional robustness against errors. Specifically, successful strategies in the realm of direct reciprocity are often not selected in the presence of signalling, and memory of past interactions is only exploited opportunistically in the case of earlier coordination failure. Differently, signalling always evolves, even when costly. In the light of these results, it may be easier to understand why direct reciprocity has been observed only in a limited number of cases among non-humans, whereas signalling is widespread at all levels of complexity.

The Human Digestive Tract Is Capable of Degrading Gluten from Birth.

The human gastrointestinal system has the capacity to metabolize dietary gluten. The capacity to degrade gliadin-derived peptide is present in humans from birth and increases during the first stages of life (up to 6-12 months of age). Fecal samples from 151 new-born and adult non-celiac disease (NCD) volunteers were collected, and glutenase and glianidase activities were evaluated. The capacity of total fecal proteins to metabolize 33-mer, 19-mer, and 13-mer gliadin peptides was also evaluated by high-performance liquid chromatography (HPLC). Feces from new-borns (meconium) showed glutenase and gliadinase activities, and peptidase activity against all three gliadin peptides. Maximal gluten degradative activity was observed in fecal samples from the youngest volunteers (0-12 months old). After the age of nine months, the gluten digestive capacity of gastrointestinal tract decreases and, from ±8 years old, individuals lose the ability to completely degrade toxic peptides. The gastrointestinal proteases involved in gluten digestion: elastase 2A, elastase 3B, and carboxipeptidase A1 are present from earlier stages of life. The human digestive tract contains the proteins capable of metabolizing gluten from birth, even before starting gluten intake. Humans are born with the ability to digest gluten and to completely degrade the potentially toxic gliadin-derived peptides (33-, 19-, and 13-mer).

Nuevos biomarcadores en la enfermedad celiaca / No disponible

Los avances en el conocimiento de la enfermedad celiaca han permitido disponer de marcadores para el diagnóstico como los anticuerpos antitransglutaminasa tisular y antigliadina deaminada. La amplia disponibilidad de estos anticuerpos junto con los estudios genéticos del HLA-DQ y la biopsia duodenal constituyen los pilares para el diagnóstico definitivo. Sin embargo, en ocasiones surgen dificultades tanto en el diagnóstico como en el seguimiento del paciente celiaco que no se resuelven con estas herramientas. En este artículo se revisa la evidencia científica junto con la posible utilidad clínica de diferentes biomarcadores. Se ha estructurado la revisión en aquellos que han sido evaluados desde el punto de vista fisiopatológico en relación con el daño intestinal o la respuesta inmunológica, junto con la utilidad clínica que pudieran tener en el diagnóstico y seguimiento de la enfermedad celiaca

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New celiac disease biomarkers.

Advances in the knowledge regarding celiac disease have enabled the development of diagnostic markers, such as anti-tissue transglutaminase and anti-deaminated gliadin antibodies. The wide availability of these antibodies, genetic studies of HLA-DQ and duodenal biopsies constitute the pillars necessary for a definitive diagnosis. However, difficulties sometimes arise in both the diagnosis and follow-up of celiac patients, which cannot be resolved using these tools. This article reviews the scientific evidence and possible clinical utility of different biomarkers. This review is structured according to biomarkers that have been evaluated pathophysiologically in relation to intestinal damage or immune response and their potential clinical utility in the diagnosis and follow-up of celiac disease patients.

Challenges to drug discovery for celiac disease and approaches to overcome them.

Introduction: The only available effective treatment for celiac disease (CD) is strict and long-term compliance with a gluten-free diet. Dietary gluten restriction must be strict and long term, but is difficult to achieve in many cases and alternative dietary strategies have been investigated in the past few years. Areas covered: This review highlights the progress that has been made in the development of new therapeutics for CD. Detailed information is provided on the targets of drugs for CD as their related mechanisms of action. The therapies are classified in five mechanisms: modification of gluten, intraluminal therapies, immunomodulation, intestinal permeability and modulation of adaptative response. The actual development phase and future approach are also described and discussed. Expert opinion: There are several limitations in each of the treatment targets related either through complications or the lack of complete response to a normal gluten containing diet. It is clear that the most desired therapy for celiac patients would induce gluten tolerance and progress has been made as per the treatments described herein. Therefore, it is shortly expected that curative or complimentary tools to a gluten free diet will be available that will improve the quality of life of CD sufferers.

Evolutionary dynamics of organised crime and terrorist networks.

Crime is pervasive into modern societies, although with different levels of diffusion across regions. Its dynamics are dependent on various socio-economic factors that make the overall picture particularly complex. While several theories have been proposed to account for the establishment of criminal behaviour, from a modelling perspective organised crime and terrorist networks received much less attention. In particular, the dynamics of recruitment into such organisations deserve specific considerations, as recruitment is the mechanism that makes crime and terror proliferate. We propose a framework able to model such processes in both organised crime and terrorist networks from an evolutionary game theoretical perspective. By means of a stylised model, we are able to study a variety of different circumstances and factors influencing the growth or decline of criminal organisations and terrorist networks, and observe the convoluted interplay between agents that decide to get associated to illicit groups, criminals that prefer to act on their own, and the rest of the civil society.

Individual perception dynamics in drunk games.

We study the effects of individual perceptions of payoffs in two-player games. In particular we consider the setting in which individuals' perceptions of the game are influenced by their previous experiences and outcomes. Accordingly, we introduce a framework based on evolutionary games where individuals have the capacity to perceive their interactions in different ways. Starting from the narrative of social behaviors in a pub as an illustration, we first study the combination of the Prisoner's Dilemma and Harmony Game as two alternative perceptions of the same situation. Considering a selection of game pairs, our results show that the interplay between perception dynamics and game payoffs gives rise to nonlinear phenomena unexpected in each of the games separately, such as catastrophic phase transitions in the cooperation basin of attraction, Hopf bifurcations and cycles of cooperation and defection. Combining analytical techniques with multiagent simulations, we also show how introducing individual perceptions can cause nontrivial dynamical behaviors to emerge, which cannot be obtained by analyzing the system at a macroscopic level. Specifically, initial perception heterogeneities at the microscopic level can yield a polarization effect that is unpredictable at the macroscopic level. This framework opens the door to the exploration of new ways of understanding the link between the emergence of cooperation and individual preferences and perceptions, with potential applications beyond social interactions.

The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile.

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.

Nuevas terapias en la enfermedad celiaca y sus complicaciones / New coeliac disease treatments and their complications

El único tratamiento aceptado para la enfermedad celiaca es el seguimiento de forma estricta de la dieta sin gluten. Este tipo de dieta puede ocasionar una disminución de la calidad de vida de los pacientes, dificultades sociales y económicas. Por lo tanto, son frecuentes las transgresiones dietéticas que pueden perpetuar el daño intestinal. En los últimos años se han desarrollado numerosos tratamientos, dirigidos hacia diferentes dianas en la patogenia de la enfermedad celiaca: modificación del gluten para conseguir un gluten no inmunogénico, terapias endoluminales que degraden el gluten en la luz intestinal, favorecer la tolerancia al gluten, modulación de la permeabilidad intestinal o regulación de la respuesta inmune adaptativa. En esta revisión se evalúan estas líneas terapéuticas que se están investigando para la enfermedad celiaca y los tratamientos enfocados al control de las complicaciones de la enfermedad, como la enfermedad celiaca refractaria (AU)

The only accepted treatment for coeliac disease is strict adherence to a gluten-free diet. This type of diet may give rise to reduced patient quality of life with economic and social repercussions. For this reason, dietary transgressions are common and may elicit intestinal damage. Several treatments aimed at different pathogenic targets of coeliac disease have been developed in recent years: modification of gluten to produce non-immunogenic gluten, endoluminal therapies to degrade gluten in the intestinal lumen, increased gluten tolerance, modulation of intestinal permeability and regulation of the adaptive immune response. This review evaluates these coeliac disease treatment lines that are being researched and the treatments that aim to control disease complications like refractory coeliac disease (AU)

New coeliac disease treatments and their complications. / Nuevas terapias en la enfermedad celiaca y sus complicaciones.

The only accepted treatment for coeliac disease is strict adherence to a gluten-free diet. This type of diet may give rise to reduced patient quality of life with economic and social repercussions. For this reason, dietary transgressions are common and may elicit intestinal damage. Several treatments aimed at different pathogenic targets of coeliac disease have been developed in recent years: modification of gluten to produce non-immunogenic gluten, endoluminal therapies to degrade gluten in the intestinal lumen, increased gluten tolerance, modulation of intestinal permeability and regulation of the adaptive immune response. This review evaluates these coeliac disease treatment lines that are being researched and the treatments that aim to control disease complications like refractory coeliac disease.

Tritordeum: a novel cereal for food processing with good acceptability and significant reduction in gluten immunogenic peptides in comparison with wheat.

BACKGROUND: Tritordeum is a novel cereal obtained from the hybridization between durum wheat and a wild barley. This study evaluates acceptance, digestibility and immunotoxic properties of tritordeum, a novel cereal for food processing. Nineteen healthy volunteers participated in a study with different diets to compare tritordeum bread with wheat and gluten-free breads. RESULTS: Tritordeum breads had a similar acceptance to the wheat bread usually consumed, and the acceptance was significantly higher than the gluten-free bread and standardized wheat bread supplied in the study. There was no evidence for gastrointestinal symptoms among volunteers during the study. The reductions in the numbers of immunogenic epitopes in tritordeum in comparison with wheat were 78% for α-gliadins, 57% for γ-gliadins and 93% for ω-gliadins. The analysis of gluten immunogenic peptides (GIP) in stool samples showed a significantly lower excretion in the tritordeum ingestion phase than in the wheat ingestion phase. CONCLUSIONS: These results suggest that tritordeum may be an option of interest for general food processing, and especially for those who want to reduce their intake of gluten. However, it is not suitable for celiac disease sufferers as it contains gluten. © 2017 Society of Chemical Industry.

Duodenal mucosa FOXP3 expression in different etiologies of lymphocytic duodenosis.

BACKGROUND/AIMS: In celiac disease there is an increase of lymphocytes expressing FOXP3 in the intestinal mucosa associated with varying degrees of villous atrophy. Our aim was to evaluate FOXP3 expression in duodenal mucosa with lymphocytic enteritis according to aetiology and correlation with lymphocytes T-γδ. METHODS: We compared three adult patient groups suffering lymphocytic enteritis: celiacs following a gluten-free diet (n=12), first-degree relatives of celiac patients with genetic risks (n=14) and patients with functional dyspepsia (n=14), along with a control group not suffering from duodenal enteritis (n=16). The population of duodenal lymphocytes was analysed by immunohistochemistry assays for CD3+ characterisation and FOXP3 expression. Quantification of lymphocytes T-γδ in duodenal mucosa was performed by flow cytometry in fresh tissue samples. RESULTS: Presence of lymphocytes T-γδ was significantly higher in the group of celiac individuals compared to the group of relatives of these individuals (37.44 vs 5,52: p<0.0001) and the group with functional dyspepsia (37.44 vs 11.76: p=0.008). FOXP3 expression was also significantly higher in the celiac group than in the groups of relatives (18.85 vs 6.31; p=0.001) and functional dyspepsia patients (18.85 vs 7.61; p=0.023). The proportion of lymphocytes T-γδ and FOXP3- expressing lymphocytes was similar in the control group to that in the relatives or functional dyspepsia groups. CONCLUSIONS: Lymphocytic enteritis associated to celiac disease shows an increase of FOXP3 expression and lymphocytes T-γδ that is not detected in other etiologies of enteritis.

Hemorragia intracerebral por cavernoma frontal / Intracerebral hemorrhage caused by frontal cavernoma

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The human digestive tract has proteases capable of gluten hydrolysis.

OBJECTIVE: To identify, purify, and characterize the proteins responsible for glutenase activity in the feces of healthy subjects and patients with celiac disease (CD). METHODS: Sixteen subjects were included in this study; 8 were healthy with no known food intolerances, and 8 were treated CD patients on a gluten-free diet. Fecal samples were homogenized, and precipitated proteins were purified by chromatography. Glutenase activity was evaluated by bioassays, zymography, and high-performance liquid chromatography with immunogenic 33-mer, 19-mer, and 13-mer gliadin peptides. RESULTS: The gastrointestinal elastase 3B (CEL3B), elastase 2A (CEL2A), and carboxypeptidase A1 (CBPA1) enzymes degraded human gluten. These proteins fully hydrolyzed 13-mer and 19-mer gliadin peptides that trigger immune-mediated enteropathy in individuals genetically predisposed to CD and partially digested a 33-mer. Feces from patients with CD showed more glutenase activity than feces from individuals without CD (171-466% higher). Peptidase activity against the gliadin peptides also increased in patients with CD. CONCLUSION: The digestive tracts of patients with CD and healthy subjects have enzymatic machinery needed for gluten degradation. Patients with CD showed more gluten hydrolysis than did healthy individuals, although, in both cases, a fraction of 33-mer peptide remained intact. Gliadin peptides derived from gastrointestinal digestion, especially the 33-mer, can potentially be used by commensal microbiota from both CD-positive and CD-negative individuals, and differences in bacterial hydrolysis can modify its immunogenic capacity.

When agreement-accepting free-riders are a necessary evil for the evolution of cooperation.

Agreements and commitments have provided a novel mechanism to promote cooperation in social dilemmas in both one-shot and repeated games. Individuals requesting others to commit to cooperate (proposers) incur a cost, while their co-players are not necessarily required to pay any, allowing them to free-ride on the proposal investment cost (acceptors). Although there is a clear complementarity in these behaviours, no dynamic evidence is currently available that proves that they coexist in different forms of commitment creation. Using a stochastic evolutionary model allowing for mixed population states, we identify non-trivial roles of acceptors as well as the importance of intention recognition in commitments. In the one-shot prisoner's dilemma, alliances between proposers and acceptors are necessary to isolate defectors when proposers do not know the acceptance intentions of the others. However, when the intentions are clear beforehand, the proposers can emerge by themselves. In repeated games with noise, the incapacity of proposers and acceptors to set up alliances makes the emergence of the first harder whenever the latter are present. As a result, acceptors will exploit proposers and take over the population when an apology-forgiveness mechanism with too low apology cost is introduced, and hence reduce the overall cooperation level.

Pseudopoliposis colónica en enfermedad inflamatoria intestinal / Colonic pseudopolyposis in inflammatory bowel disease

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