mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate

Non-syndromic cleft lip with or without cleft palate (NSCLP), the most common human craniofacial malformation, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological, and epigenetic findings. Epigenetic variations associated with NSCLP have been identified; however, functional investigation has been limited. Here, we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a region in mir152 that is frequently hypomethylated in NSCLP cohorts (21–26%), leading to mir152 overexpression. mir152 overexpression in human neural crest cells led to downregulation of spliceosomal, ribosomal, and adherens junction genes. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial cartilage impairment. Also, we suggest that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogous palatal alterations. We therefore propose that mir152 hypomethylation, potentially induced by hypoxia in early development, is a novel and frequent predisposing factor to NSCLP

Caracterização química do autolisado de levedura de alambique e avaliação da aceitabilidade do pão de queijo adicionado do autolisado desidratado Chemical characterization of yeast autolysate and assessment of the acceptability of cheese buns containing dried autolysate

OBJETIVO: Esta pesquisa tem como objetivo estudar as propriedades do autolisado de levedura (Saccharomyces cerevisiae) proveniente de cachaça de alambique, investigando a composição centesimal, o perfil acídico e a análise microbiológica do material, bem como realizar análise sensorial do pão de queijo adicionado com o autolisado desidratado. MÉTODOS: O autolisado foi obtido pela lavagem e autólise da biomassa. A secagem foi realizada em secador de bandeja na temperatura de 70ºC. Realizaram-se as seguintes análises: caracterização físico-química (teor lipídico, proteico, fibras totais, fibras solúveis e insolúveis, e cinzas); composição de aminoácidos; análises microbiológicas do produto desidratado; e avaliação sensorial do pão de queijo contendo o autolisado desidratado, através de escala hedônica e teste de atitude. RESULTADOS: O autolisado desidratado apresentou: 1,2% de lipídeos; 24,7% de proteínas; 51,3% de fibras totais, sendo 2,4% de fibras solúveis e 48,9% de insolúveis; e 6,2% de cinzas. As análises microbiológicas mostraram-se dentro do limite recomendado pela Agência Nacional de Vigilância Sanitária. O perfil aminoacídico mostrou deficiência de histidina e metionina+cistina. A análise sensorial do pão de queijo mostrou boa aceitação, tendo apenas cor e aparência recebido notas baixas. A maioria dos participantes disse que "gosta disto e compraria de vez em quando". CONCLUSÃO: Os valores de proteína e aminoácidos encontrados na levedura de cachaça de alambique foram inferiores ao mostrado na literatura para levedura de cervejaria e destilaria de álcool etílico. A levedura desidratada estava microbiologicamente apta para consumo humano. A baixa aceitabilidade da aparência do pão de queijo provavelmente ocorreu pelo fato de os consumidores não estarem habituados à cor escura do produto. Trabalhos futuros poderão sugerir adição em outros produtos que apresentem aparência mais atrativa.<br>OBJECTIVE: This study aimed to study the properties of yeast (Saccharomyces cerevisiae) autolysate obtained from pot still rum, including centesimal composition, amino acid profile and microbiological analysis, and perform a sensory analysis of cheese buns (also known as Brazilian cheese bread or rolls) enriched with dried autolysate. METHODS: Autolysate was obtained by rinsing and autolyzing the biomass and dried on a tray dryer at 70º. Its composition was then determined (fat, protein, total fiber, soluble fiber, insoluble fiber, ash and amino acid contents) followed by microbiological analysis. Finally, cheese buns enriched with dried autolysate were submitted to sensory analysis using the hedonic scale and attitude test. RESULTS: Dried autolysate contained 1.2% fats; 24.7% proteins; 51.3% total fiber, where 2.4% was soluble and 48.9% was insoluble; and 6.2% ash. According to microbiological analysis, the product complied with the microbiological limits established by the Agência Nacional de Vigilância Sanitária. Amino acid profile showed that histidine and methionine-cystine levels were low. Sensory analysis indicated good acceptance of the cheese buns. Only their color and appearance received low scores. Most participants reported liking the cheese buns and willingness to buy them on occasion. CONCLUSION: The protein and amino acid levels found in pot still rum were lower than those reported in the literature for breweries and ethanol distilleries. Dried yeast was microbiologically suitable for human consumption. The low grades given to the appearance of the cheese buns were probably due to their unappealing dark color, as opposed to the usual pale yellow color. Future studies could suggest the addition of dried yeast to products whose visual appeal will not be as affected