Rare earth elements induce cytoskeleton-dependent and PI4P-associated rearrangement of SYT1/SYT5 endoplasmic reticulum-plasma membrane contact site complexes in Arabidopsis.

In plant cells, environmental stressors promote changes in connectivity between the cortical endoplasmic reticulum (ER) and the plasma membrane (PM). Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in interorganelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+- and lipid-binding protein 1 (CLB1/SYT7). This complex is enriched at ER-PM contact sites (EPCSs), has slow responses to changes in extracellular Ca2+, and displays severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositide species at the PM.

Efeito de uma associação de cepas probióticas contendo lactobacillus e bifidobacterium na modulação da microbiota intestinal em pacientes constipados / Effects of association of probiotic strains containing lactobacillus and bifidobacterium on modulation of the intestinal microbiota in constipated patients

Introdução: a constipação é uma doença crônica que afeta a população mundial, podendo ser consequência do desequilíbrio da microbiota intestinal, conhecida como disbiose. Nesse contexto, os probióticos vêm sendo utilizados com o objetivo de promover o seu equilíbrio, a fim de mantê-la saudável (eubiose). Objetivo: avaliar, em um estudo duplo-cego, randomizado, placebo-controlado, se o uso de uma associação de cepas probióticas contendo lactobacillus e bifidobacterium por 28 dias pode modular a microbiota intestinal em pacientes constipados. Método: a atividade da associação de cepas probióticas foi comparada com placebo (maltodextrina) após a suplementação por 28 dias. Os pacientes foram avaliados por meio da análise de metagenômica e da melhora dos sintomas relacionados à constipação. Os dados do perfil da população de microrganismos presentes no intestino dos pacientes foram correlacionados com os resultados da avaliação dos sintomas abdominais e da percepção de bem-estar geral. O aumento do número de evacuações e a melhora do trânsito intestinal foram avaliados durante o estudo. Resultados: as proporções do gênero Bifidobacterium no grupo teste e controle foram 0.45% vs 0.24% no final do estudo, respectivamente (p<0,05). Adicionalmente, a diferença entre os grupos que receberam associação de cepas probióticas contendo lactobacillus e bifidobacterium e placebo permaneceu também significativamente alta com relação às espécies de Lactobacillus (1,21% vs 0,12%) após 28 dias de tratamento (p<0,05). Além disso, os participantes que receberam o probiótico apresentaram uma tendência de melhora sintomática baseada na comparação da sua microbiota e as respostas oriundas da avaliação dos sintomas abdominais e bem-estar geral. Nenhum evento adverso grave foi relatado. Conclusão: a formulação probiótica modulou a microbiota intestinal de forma diferente do placebo nos participantes do estudo. O consumo dos probióticos aumentou significativamente as bactérias benéficas e reduziu as potencialmente maléficas, contribuindo para o equilíbrio da microbiota intestinal.

Introduction: constipation is a chronic disease that affects the world population, being a consequence of the imbalance of the intestinal microbiota, known as dysbiosis. In light of this context, the probiotics have been used to trigger microbiota intestinal balance, in order to keep it healthy (eubiose) Aim: to evaluate in a double-blind, randomized, placebo-controlled study whether the use of association of probiotic strains containing lactobacillus and bifidobacterium for 28 days can modulate the intestinal microbiota of the constipated participants. Methods: the activity of association of probiotic strains was compared to placebo (maltodextrin) after 28 days of consumption. The patients were evaluated by using metagenomics analyses and improved constipation symptoms. The dates of microorganisms population profile into patients gut were correlated with results of abdominal symptoms evaluation and well-being perception. The increase in the number of evacuations and the intestinal transit were evaluated during the study. Results: the proportions of the genus Bifidobacterium in the test groups and the control group were 0.45% vs 0.24% at the end of the study, respectively (p<0.05). Additionally, the difference between the groups that received association of probiotic strains containing lactobacillus and bifidobacterium and the placebo remained higher for species of the genus Lactobacillus (1.21% vs 0.12%) after 28 days of use (p<0.05). Furthermore, the participants who received the probiotic had a tendency to improve symptomatic based on comparisons of their microbiota and the responses provided patients' abdominal symptoms and well-being. There were no reports of serious adverse events during the study. Conclusion: the probiotic formulation modulated the intestinal microbiota differently from the placebo in constipated participants included in this study. The use of this probiotic significantly increased beneficial bacteria and decreased potentially harmful microbes, which contributed to the maintenance of a healthy intestinal microbiota.