Determination of estrogens in drinking water using HPLC-DAD

An analytical procedure for determination of estriol, 17β-estradiol, estrone and 17α-ethinylestradiol in drinking water is presented. The method employs solid phase extraction (SPE) and sample dechlorination as cleanup procedures, followed by HPLC-DAD analysis. Validation was carried out using RE No. 899/2003 guidelines established by the Agência Nacional de Vigilância Sanitária (National Agency of Sanitary Surveillance, Brazil), with some adaptations. The statistically evaluated results have shown that the method is selective, precise (0,06% to 19,40% CV) and accurate (91,52% to 109,41% average recoveries). The developed method was applied to the analysis of these contaminants in drinking water from São Luís, MA

Biogenesis and activity regulation of protein phosphatase 1

Protein phosphatase 1 (PP1) is expressed in all eukaryotic cells and catalyzes a substantial fraction of phosphoserine/threonine dephosphorylation reactions. It forms stable complexes with PP1-interacting proteins (PIPs) that guide the phosphatase throughout its life cycle and control its fate and function. The diversity of PIPs is huge (≈200 in vertebrates), and most of them combine short linear motifs to form large and unique interaction interfaces with PP1. Many PIPs have separate domains for PP1 anchoring, PP1 regulation, substrate recruitment and subcellular targeting, which enable them to direct associated PP1 to a specific subset of substrates and mediate acute activity control. Hence, PP1 functions as the catalytic subunit of a large number of multimeric holoenzymes, each with its own subset of substrates and mechanism(s) of regulation

Clinical and molecular characteristics of a novel rare de novo variant in PPP2CA in a patient with a developmental disorder, autism, and epilepsy

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, ar

Plasma cells are not restricted to the CD27+ phenotype:characterization of CD27-CD43+ antibody-secreting cells

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders. Conclusion: we characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.</p

LITERATURA E LEITURA LITERÁRIA NO ENSINO MÉDIO: Quebrar barreiras e ampliar fronteiras

O projeto de Ações Integradas: “Literatura e Leitura Literária no Ensino Médio- quebrar barreiras, ampliar fronteiras ”, visa demonstrar a importância da literatura eda leitura literária nos eixos da pesquisa, extensão e ensino, compondo a formaçãointegral do aluno do ensino médio regular e integrado. As ações desenvolvidaspelos membros do projeto são estratégias didáticas e lúdicas. Atuamos no âmbitoescolar das localidades de São Bento do Sul, especificamente na Escola deEducação Básica Celso Ramos Filho e no Instituto Federal Catarinense - CampusSão Bento do Sul

PP1 and PP2A use opposite phospho-dependencies to control distinct processes at the kinetochore

PP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalizing with substrates. At the kinetochore, however, both phosphatases localize to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modeling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviors and control different mitotic processes. Furthermore, our genome-wide analysis suggests that these major phosphatase families may have evolved to respond to phosphorylation inputs in opposite ways because many other PP1 and PP2A-B56-binding motifs are also phospho-regulated

Environmental potential assessment of MSWI bottom ash-based alkali-activated binders

Alkali-activated binders (AABs) stand out as a sustainable alternative to ordinary Portland cement (OPC) as they can be formulated using by-products or waste as raw materials. However, the presence of hazardous compounds in residues can lead to an increase in AABs' toxicity due to the highly alkaline media. Therefore, it is extremely important to evaluate their environmental risks to validate their use as building materials. This study environmentally assessed AABs prepared with two different fractions (0-30 mm and 8-30 mm) of weathered bottom ash (AA-WBA) from WtE plants. The potential leachate toxicity of AA-WBA was assessed using granular and monolithic leaching tests that simulated end-of-life and service life scenarios, respectively. Furthermore, an acute toxicity test with crustacean Daphnia magna as model organisms was conducted to determine the relationship between the leachate metal(loid) concentrations and the ecotoxicity of AA-WBA. The results showed higher metal(loid) concentrations in AA-WBA specimens prepared with the 0-30 mm fraction of WBA. The service life scenario revealed multiple metal(loid)-release mechanisms. The 48 h EC50 value (close to 10%; moderate toxicity) indicated that the use of the coarse fraction of WBA increased the immobilisation of the metal(loid)s. Finally, the correlation between the concentrations of some of the metal(loid)s and toxicity was demonstrated.The work is funded by the Spanish Government (BIA2017–83912- C2–1-R). The authors would like to thank the Catalan Government for the quality accreditation given to their research groups DIOPMA (2017 SGR 118), to SIRUSA and VECSA for supplying the MSWI Bottom Ash, and Befesa Company for supplying the PAVAL. Mr Alex Maldonado-Alameda is grateful to the Government of Catalonia for his research Grant (FI-DGR 2017). Dr Jessica Giro-Paloma is a Serra Húnter Fellow. Dr Araceli Rodríguez-Romero is supported by the Spanish grant Juan de la Cierva Incorporación referenced as IJC2018–037545-I

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Purpose: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. Methods: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported