Enzymatic Strategies to Detoxify Gluten: Implications for Celiac Disease

Celiac disease is a permanent intolerance to the gliadin fraction of wheat gluten and to similar barley and rye proteins that occurs in genetically susceptible subjects. After ingestion, degraded gluten proteins reach the small intestine and trigger an inappropriate T cell-mediated immune response, which can result in intestinal mucosal inflammation and extraintestinal manifestations. To date, no pharmacological treatment is available to gluten-intolerant patients, and a strict, life-long gluten-free diet is the only safe and efficient treatment available. Inevitably, this may produce considerable psychological, emotional, and economic stress. Therefore, the scientific community is very interested in establishing alternative or adjunctive treatments. Attractive and novel forms of therapy include strategies to eliminate detrimental gluten peptides from the celiac diet so that the immunogenic effect of the gluten epitopes can be neutralized, as well as strategies to block the gluten-induced inflammatory response. In the present paper, we review recent developments in the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten

Occurrence of Fusarium species in asymptomatic barley plants grown in field conditions under differential phosphate regimes

Occurrence of genus Fusarium as endophytes in roots of healthy barley plants cultivated in fields under two levels of phosphorous (P) was examined. F. avenaceum, F. graminearum, F. konzum, F. oxysporum, F. sacchari, F. scirpi, F. solani were isolated from asymptomatic surface sterilized root tissues. F. konzum and F. solani were only present in the roots of fertilized plants, whereas F. sacchari was present in unfertilized plants. F. scirpi was isolated in highest frequency and relative density, and was higher under P deficiency suggesting that P availability would determinate the occurrence of this species, suggesting the possibility of their association with stressed plants. This is the first report on the occurrence of Fusarium spp. as endophytes in healthy barley plants. However, it remains to be determined whether Fusarium spp. isolated are nonpathogenic forms and beneficial to barley plants or latent pathogens that could produce disease symptoms in other conditions.Fil: Echeverria, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Moreno, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnolológico Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología. Laboratorio de Biología Funcional y Biotecnología; ArgentinaFil: Caputo Suarez, Carla Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; Argentin

Relevancia de la disponibilidad de azufre y removilización de asimilados sobre la calidad de la cebada cervecera

En la industria cervecera la calidad de los granos de cebada para su comercialización está determinada principalmente por el contenido proteico (relacionado con el contenido de nitrógeno) y el calibre (relacionado con el contenido de azúcares) de los mismos, sin embargo también depende del tipo de proteínas que contienen. En los cereales, la exportación de aminoácidos y azúcares desde los órganos vegetativos vía floema es una fuente importante de nitrógeno y carbono para los granos en desarrollo, adquiriendo mayor relevancia en suelos deficientes en nutrientes. Las deficiencias nutricionales que más comúnmente han afectado a los cultivos son las de nitrógeno y fósforo; sin embargo, en los últimos años se han comenzado a observar deficiencias de azufre en suelos de la región Pampeana, convirtiéndose así la fertilización azufrada en un nuevo foco de interés para los productores. En esta revisión breve hacemos hincapié en el modo en que la disponibilidad de azufre impacta sobre las características del grano y, consecuentemente, sobre la calidad maltera. A su vez, se discute el rol de la removilización sobre estos aspectos.Barley grain quality for brewing purposes is determined by parameters such as grain protein content (determined as total nitrogen content) and size (mostly determined by starch content), however, it also depends on the grain protein type. In cereals, amino acid and sugar exportations from the vegetative organs are a major source of nitrogen and carbon for developing grains, becoming more important in nutrient-deficient soils. Nitrogen and phosphorus are the most common nutritional deficiencies affecting crops, but more recently, sulphur deficiencies have also been observed in soils of the Pampas region, which makes sulphur fertilization a new point of interest for the producers. In this brief review we emphasize on how the sulphur availability influences grain characteristics and consequently on malting quality. In turn, the role of remobilization on these aspects is discussed.Fil: Veliz, Cintia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Roberts, Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Criado, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Echeverria, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Caputo Suarez, Carla Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; Argentin

Regulation of senescence-associated protease genes by sulphur availability according to barley (Hordeum vulgare L.) phenological stage

Background and Aims: Proteases are responsible for protein degradation during leaf senescence, allowing nutrients to be redirected to sink tissues. In a previous work, we reported that sulphur deficiency produced a delay in the leaf senescence of barley (Hordeum vulgare L.) plants, at both vegetative and reproductive stages. In this work, we analyse the effect of sulphur deficiency on the expression of several genes coding for proteases of different catalytic groups, which have been strongly associated with leaf senescence. Methods: Four independent experiments were performed in order to impose low sulphur availability conditions: one of steady-state sulphur deficiency during the vegetative stage and three of sulphur starvation during vegetative and reproductive stages. Key Results: Sulphur deficiency inhibited or reduced the senescence-associated induction of seven of the eight proteases analysed. Their induction, as well as senescence and phloem amino acid remobilization, could be achieved with senescence inducers such as methyl-jasmonate (a hormonal stimulus) and darkness, but with different rates of induction dependent on each gene. Sulphur deficiency also exerted an opposite effect on the expression of two cysteine-protease genes (HvSAG12 and HvLEGU) as well as on one serine-protease gene (HvSUBT) according to leaf age and plant phenological stages. All three genes were induced in green leaves but were repressed in senescent leaves of sulphur-deficient plants at the vegetative stage. At the reproductive stage, both cysteine-proteases were only repressed in senescent leaves, while the serine-protease was induced in green and senescent leaves by sulphur deficiency. Conclusions: Our results highlight the relevance of adequate sulphur nutrition in order to ensure leaf senescence onset and induction of protease genes, which will consequently impact on grain protein composition and quality. In addition, our results provide evidence that leaf age, plant developmental stage and the nature of the stress modulate the sulphur responses.Fil: Veliz, Cintia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Criado, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Galotta, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Roberts, Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Caputo Suarez, Carla Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; Argentin

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Celiac disease is a permanent intolerance to the gliadin fraction of wheat gluten and to similar barley and rye proteins that occurs in genetically susceptible subjects. After ingestion, degraded gluten proteins reach the small intestine and trigger an inappropriate T cell-mediated immune response, which can result in intestinal mucosal inflammation and extraintestinal manifestations. To date, no pharmacological treatment is available to gluten-intolerant patients, and a strict, life-long gluten-free diet is the only safe and efficient treatment available. Inevitably, this may produce considerable psychological, emotional, and economic stress. Therefore, the scientific community is very interested in establishing alternative or adjunctive treatments. Attractive and novel forms of therapy include strategies to eliminate detrimental gluten peptides from the celiac diet so that the immunogenic effect of the gluten epitopes can be neutralized, as well as strategies to block the gluten-induced inflammatory response. In the present paper, we review recent developments in the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten

Constitutive Differential Features of Type 2 Transglutaminase in Cells Derived from Celiac Patients and from Healthy Subjects

Type 2 transglutaminase (TG2) is a ubiquitous enzyme able to modify gliadin peptides introduced into the organism through the diet. By means of its catalytic activity, TG2 seems to have an important pathogenetic role in celiac disease (CD), an inflammatory intestinal disease caused by the ingestion of gluten-containing cereals. A strong autoimmune response to TG2 characterizes CD development. Anti-TG2 antibodies specifically derange the uptake of the α-gliadin peptide 31-43 by control, but not by celiac dermal fibroblasts, underlying some different constitutive features regarding TG2 in healthy and celiac subjects. Our aim was to investigate whether these differences depended on a different TG2 subcellular distribution and whether peptide 31-43 differentially regulated TG2 expression and activity in cells of the two groups of subjects. We found that TG2 was more abundantly associated with membranes of celiac fibroblasts than of control cells, in particular with the early endosomal and autophagic compartments. We also found that peptide 31-43 differentially affected TG2 expression and activity in the two groups of cells, activating TG2 more in control than in celiac cells and inducing TG2 expression in celiac cells, but not in control ones. The different TG2 subcellular localization and the different way the peptide 31-43 modulates TG2 activity and availability into control and CD cells suggested that TG2 is involved in the definition of a constitutive CD cellular phenotype, thus having an important and still undefined role in CD pathogenesis

Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management

Mutations impairing GSK3-mediated MAF phosphorylation cause cataract, deafness, intellectual disability, seizures, and a down syndrome-like facies

Transcription factors operate in developmental processes to mediate inductive events and cell competence, and perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, and growth. We report that a narrow spectrum of amino-acid substitutions within the transactivation domain of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a leucine zipper-containing transcription factor of the AP1 superfamily, profoundly affect development. Seven different de novo missense mutations involving conserved residues of the four GSK3 phosphorylation motifs were identified in eight unrelated individuals. The distinctive clinical phenotype, for which we propose the eponym Aymé-Gripp syndrome, is not limited to lens and eye defects as previously reported for MAF/Maf loss of function but includes sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth. Disease-causing mutations were demonstrated to impair proper MAF phosphorylation, ubiquitination and proteasomal degradation, perturbed gene expression in primary skin fibroblasts, and induced neurodevelopmental defects in an in vivo model. Our findings nosologically and clinically delineate a previously poorly understood recognizable multisystem disorder, provide evidence for MAF governing a wider range of developmental programs than previously appreciated, and describe a novel instance of protein dosage effect severely perturbing developmen

Whole-body vibration exercise improves functional parameters in patients with Osteogenesis imperfecta: a systematic review with a suitable approach

Background: Patients with osteogenesis imperfecta (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use under controlled circumstances. Improvements due to the wholebody vibration (WBV) exercises have been reported in strength, motion, gait, balance, posture and bone density in several osteopenic individuals, as in post-menopausal women or children with disabling conditions, as patients with OI. The aim of this investigation was to systematically analyse the current available literature to determine the effect of WBV exercises on functional parameters of OI patients.Materials and methods: Three reviewers independently accessed bibliographical databases. Searches were performed in the PubMed, Scopus, Science Direct and PEDro databases using keywords related to possible interventions (including WBV) used in the management of patients with osteogenesis imperfecta.Results: Three eligible studies were identified by searches in the analysed databases.Conclusion: It was concluded that WBV exercises could be an important option in the management of OI patients improving the mobility and functional parameters. However, further studies are necessary for establishing suitable protocols for these patients.Keywords: whole body vibration exercise, osteogenesis imperfecta, mobility, functional parameters, Database