Myosin-1a powers the sliding of apical membrane along microvillar actin bundles

Microvilli are actin-rich membrane protrusions common to a variety of epithelial cell types. Within microvilli of the enterocyte brush border (BB), myosin-1a (Myo1a) forms an ordered ensemble of bridges that link the plasma membrane to the underlying polarized actin bundle. Despite decades of investigation, the function of this unique actomyosin array has remained unclear. Here, we show that addition of ATP to isolated BBs induces a plus end–directed translation of apical membrane along microvillar actin bundles. Upon reaching microvillar tips, membrane is “shed” into solution in the form of small vesicles. Because this movement demonstrates the polarity, velocity, and nucleotide dependence expected for a Myo1a-driven process, and BBs lacking Myo1a fail to undergo membrane translation, we conclude that Myo1a powers this novel form of motility. Thus, in addition to providing a means for amplifying apical surface area, we propose that microvilli function as actomyosin contractile arrays that power the release of BB membrane vesicles into the intestinal lumen

A role for myosin-1A in the localization of a brush border disaccharidase

To gain insight regarding myosin-1A (M1A) function, we expressed a dominant negative fragment of this motor in the intestinal epithelial cell line, CACO-2BBE. Sucrase isomaltase (SI), a transmembrane disaccharidase found in microvillar lipid rafts, was missing from the brush border (BB) in cells expressing this fragment. Density gradient centrifugation, affinity purification, and immunopurification of detergent-resistant membranes isolated from CACO-2BBE cells and rat microvilli (MV) all indicate that M1A and SI reside on the same population of low density (∼1.12 g/ml) membranes. Chemical cross-linking of detergent-resistant membranes from rat MV indicates that SI and M1A may interact in a lipid raft complex. The functional significance of such a complex is highlighted by expression of the cytoplasmic domain of SI, which results in lower levels of M1A and a loss of SI from the BB. Together, these studies are the first to assign a specific role to M1A and suggest that this motor is involved in the retention of SI within the BB

Pay-performance sensitivity and accounting earnings management : an analysis of the companies listed in b3 from the perpective of corporate governance

No âmbito da governança corporativa, a remuneração executiva é considerada um mecanismo interno que pode ser utilizado para atenuar conflitos, alinhando interesses de administradores e proprietários ao tornar a remuneração dos executivos sensível ao desempenho da empresa (variação de seu valor de mercado). Contudo, a remuneração pode se tornar um mecanismo perverso, incentivando os administradores a utilizarem a discricionariedade contábil, medida a partir dos acrruals discricionários apropriados no resultado do período, para influenciar sua remuneração. O objetivo deste estudo é analisar se a sensibilidade da remuneração executiva (PPS) pode estar relacionada ao gerenciamento de resultados contábeis nas empresas listadas na B3, partindo da premissa de que, nas empresas com planos de remuneração mais atrelados ao desempenho (maior PPS), os gestores possuem maiores incentivos para gerenciarem resultados contábeis. A pesquisa se caracteriza como quantitativa, explicativa, e foi realizada através de análise documental, com uso de dados em painel, agrupados por séries temporais empilhadas. A amostra final compreendeu 80 empresas. Os principais resultados indicam que a PPS apresenta resultados negativos, de modo que uma variação no valor de mercado pode influenciar negativamente a remuneração. Os accruals discricionários apresentaram resultados negativos, indicando sua utilização para diminuir resultados. Com relação ao objetivo principal deste estudo, não foi possível constatar relação positiva entre os accruals discricionários e a PPS. Ativo total, endividamento, setores e PPS defasada são variáveis capazes de influenciar a PPS. Portanto para esta amostra, não foi possível constatar indícios de práticas de gerenciamento de resultados contábeis destinados a influenciar a remuneração executiva.In the scope of the corporative governance, the executive compensation is regarded as an internal mechanism that can be used to mitigate conflicts, aligning managers and owners’ interests by making the executives remuneration sensitive to the company’s performance (variation of its market). However, the compensation can become a wicked mechanism when encouraging managers to use the accounting discretionary, measured by the discretionary accruals suitable in the period results, to impact on the remuneration. This study aims to analyse if the sensitivity of the executive remuneration ( Pay-Performance Sensitivity - PPS) can be related to the managing of accounting results in the companies that are listed on B3, on the assumption that in companies with remuneration planning linked to the performance (PPS) its managers have more incentives to manage the accounting results. The research is characterized as quantitative, explanatory and was held through the documental analysis using data panel, grouped according to temporal series. The final sample has 80 companies. The main results show that PPS has negative results, which means that a variation in the market value can influence remuneration negatively. The discretionary accruals presented negative results indicating its use to diminish results. In Relation to the main goal of this study, it is not possible to stablished a positive relation between the discretionary accruals and PPS. Total assets, indebtedness, sections and lagged PPS are variables that can influence the PPS. Therefore, for the sample, it cannot be determined that evidences of accounting results managing practices are intended to affect the executive remuneration

Microvilli give gut vesicles the brush-off

A surprising new function for intestinal cells in shaping their local environment

Influência do polimorfismo FokI do gene VDR no Transtorno do Espectro Autista

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Associação entre o polimorfismo foki do receptor de vitamina D (VDR) e o transtorno do espectro autista

O Transtorno do Espectro Autista (TEA) é um transtorno influenciado por fatores tanto genéticos quanto ambientais, mas as reais causas ainda não foram completamente elucidadas. A vitamina D parece ter algum papel na heterogeneidade do TEA, pois estudos mostraram níveis mais baixos de vitamina D em pessoas diagnosticadas com TEA em comparação a grupos controle, assim como em mulheres grávidas de crianças que viriam a desenvolver TEA em relação a outro grupo controle. A vitamina D atua no organismo principalmente através do calcitriol, sua forma ativa, que se liga com o Receptor de Vitamina D (VDR), atuando na homeostase do cálcio, regulação de citocinas e produção de peptídeos antimicrobianos. A variante FokI (rs2228570-C/T) causa uma alteração na atividade da proteína VDR: a proteína expressa pelo alelo F (C) possui maior atividade em relação a aquela expressa pelo alelo f (T). O objetivo desse trabalho foi analisar a variante FokI em pacientes com TEA, procurando uma possível associação com sintomatologia do TEA. A variante FokI do gene VDR foi avaliada em 149 crianças diagnosticadas com TEA. As amostras de DNA foram amplificadas por PCR, clivadas com a enzima FokI e genotipadas por eletroforese em gel de agarose 3%. A análise qui-quadrado foi utilizada para testar associações entre os genótipos e a sintomatologia. As frequências dos genótipos obtidos foram: 41,6% para F/F; 42,3% para F/f e 16,1% para f/f (distribuição em equilíbrio de Hardy-Weinberg). A presença de genótipos com o alelo f foi inicialmente associada com presença de convulsões (p=0,024; pc=0,24), ausência de ataques de pânico (p=0,010; pc=0,10) e ausência de comportamento autoagressivo (p=0,032; pc=0,32). Entretanto, as associações encontradas não permaneceram significantes após a correção de Bonferroni (pc). Novos estudos sobre o componente genético do TEA são essenciais para melhor entendimento do transtorno.Autism Spectrum Disorder (ASD) is a disorder influenced by both genetic and environmental components, but the real causes are still inconclusive. Vitamin D seems to have some role in ASD heterogeneity, with studies showing lower levels of vitamin D in ASD as compared to non-ASD individuals, as well as more vitamin D deficiency in mothers of ASD children during pregnancy as compared to non-ASD associated pregnancies. Vitamin D acts mostly through calcitriol, interacting with Vitamin D Receptor (VDR) and regulating calcium homeostasis, cytokine expression/repression, and antimicrobial peptides expression. The FokI variant (rs2228570-C/T) is known to alter VDR activity: the protein expressed by the F allele (C) has a higher activity as compared to the protein expressed by the f allele (T). This study aims to analyze the FokI variant in ASD patients, searching for an association with ASD symptomatology. The FokI variant of the VDR gene was genotyped in 149 individuals diagnosed with ASD. The DNA samples were amplified by PCR, cleaved by FokI enzyme, and genotyped by electrophoresis in a 3% agarose gel. The chi-squared analysis was used to test the association between genotypes and the symptoms. The genotype frequencies obtained were: 41.6% for F/F; 42.3% for F/f e 16.1% for f/f (the distribution was in Hardy-Weinberg equilibrium). The f allele was initially associated with presence of convulsion (p=0.024; pc=0.24), absence of panic attacks (p=0.010; pc=0.10) and absence of auto-aggressive behavior (p=0.032; pc=0.32). However, these associations lost statistical significance after Bonferroni correction (pc). More studies about ASD genetics are needed to a better understanding of this disorder