2,338 research outputs found

    Transthyretin: No association between serum levels or gene variants and schizophrenia

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    It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.http://www.sciencedirect.com/science/article/B6T8T-4K12CM6-2/1/78223a224d1392e250f7562405e6796

    Comparing different packaging conditions on quality stability of high-pressure treated Serra da Estrela cheeses during cold storage

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    Serra da Estrela cheese with a Protected Designation of Origin (PDO) is a traditional cheese that is wrapped in paper without vacuum. High-pressure processing (HPP), which requires vacuum packaging of the cheese, has been used for its cold pasteurization to overcome safety issues. In this study, two packaging systems were studied: non-vacuum greaseproof paper wrapping package and vacuum packaging in plastic film. Lactococci, lactobacilli, enterococci, and total mesophiles reached ca. 8 log cfu g−1 and 4–6 log cfu g−1 in control (unpasteurized) and HPP-treated cheeses, respectively, with no significant differences between packaging systems. Spoilage microorganisms' viable cell numbers were reduced to 5 log cfu g−1 in non-vacuum paper-wrapped cheeses. A vacuum-packaging system enabled better control of cheese proteolysis, which was revealed to be closer to that of the original control cheese values at the end of the 10-month storage period. In addition, cheese stored under vacuum film packaging became harder than non-vacuum paper-wrapped cheeses at each time point. Overall, conventional non-vacuum paper wrapping is adequate for short storage periods (<3 months), but for long periods vacuum packaging in plastic film is preferable.info:eu-repo/semantics/publishedVersio

    Adaptation of Saccharomyces cerevisiae to high pressure (15, 25 and 35 MPa) to enhance the production of bioethanol

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    Saccharomyces cerevisiae is a yeast of great importance in many industries and it has been frequently used to produce food products and beverages. More recently, other uses have also been described for this microorganism, such as the production of bioethanol, as a clean, renewable and sustainable alternative fuel. High pressure processing (HPP) is a technology that has attracted a lot of interest and is increasingly being used in the food industry as a non-thermal method of food processing. However, other applications of high pressure (HP) are being studied with this technology in different areas, for example, for fermentation processes, because microbial cells can resist to pressure sub-lethal levels, due to the development of different adaptation mechanisms. The present work intended to study the adaptation of S. cerevisiae to high pressure, using consecutive cycles of fermentation under pressure (at sub-lethal levels), in an attempt to enhance the production of bioethanol. In this context, three pressure levels (15, 25 and 35 MPa) were tested, with each of them showing different effects on S. cerevisiae fermentation behavior. After each cycle at 15 and 25 MPa, both cell growth and ethanol production showed a tendency to increase, suggesting the adaptation of S. cerevisiae to these pressure levels. In fact, at the end of the 4th cycle, the ethanol production was higher under pressure than at atmospheric pressure (0.1 MPa) (8.75 g.L−1 and 10.69 g.L−1 at 15 and 25 MPa, respectively, compared to 8.02 g.L−1 at atmospheric pressure). However, when the pressure was increased to 35 MPa, cell growth and bioethanol production decreased, with minimal production after the 4 consecutive fermentation cycles. In general, the results of this work suggest that consecutive cycles of fermentation under sub-lethal pressure conditions (15 and 25 MPa) can stimulate adaptation to pressure and improve the bioethanol production capacity by S. cerevisiae; hence, this technology can be used to increase rates, yields and productivities of alcoholic fermentation.info:eu-repo/semantics/publishedVersio

    In vitro and in vivo effects of SerpinA1 on the modulation of Transthyretin proteolysis

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    Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly, amyloid deposits can be composed mainly of full-length TTR or contain a mixture of both cleaved and full-length TTR, particularly in the heart. The fragmentation pattern at Lys48 suggests the involvement of a serine protease, such as plasmin. The most common TTR variant, TTR V30M, is susceptible to plasmin-mediated proteolysis, and the presence of TTR fragments facilitates TTR amyloidogenesis. Recent studies revealed that the serine protease inhibitor, SerpinA1, was differentially expressed in hepatocyte-like cells (HLCs) from ATTR patients. In this work, we evaluated the effects of SerpinA1 on in vitro and in vivo modulation of TTR V30M proteolysis, aggregation, and deposition. We found that plasmin-mediated TTR proteolysis and aggregation are partially inhibited by SerpinA1. Furthermore, in vivo downregulation of SerpinA1 increased TTR levels in mice plasma and deposition in the cardiac tissue of older animals. The presence of TTR fragments was observed in the heart of young and old mice but not in other tissues following SerpinA1 knockdown. Increased proteolytic activity, particularly plasmin activity, was detected in mice plasmas. Overall, our results indicate that SerpinA1 modulates TTR proteolysis and aggregation in vitro and in vivo.This research was funded by COMPETE 2020 of PT2020 through the European Regional Development Fund (ERDF), “NETDIAMOND—New Targets in DIAstolic heart failure: from coMOrbidities to persoNalizeD medicine” project financed by the European Structural and Investment Funds (ESIF), through the Programa Operacional Regional (POCI-01-0145-FEDER-016385) and HEALTHUNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological, and infectious diseases, NORTE- 01-0145-FEDER-000039. FB was supported by FCT—Fundação para a Ciência e Tecnologia/MEC— Ministério da Educação e Ciência with a PhD fellowship (SFRH/BD/123674/2016)

    Novel hydroxyamides and amides containing D-glucopyranose or D-fructose units: biological assays in MCF-7 and MDST8 cell lines

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    A novel library of 15 compounds, hydroxyamides and amides containing a β-d-glucopyranose (d-Gluc) or a β-d-fructose (d-Fruc) units was designed and synthesized for antiproliferative assays in breast (MCF-7) and colon (MDST8) cancer cell lines. Twelve of them were hydroxyamides and were successfully synthesized from β-d-glucuronic acid (d-GluA). Six of these hydroxyamides which were acetylated hydroxy-β-d-glucopyranuronamide 2a–2f (1st Family) and the other six were their respective isomers, that is, hydroxy-β-d-fructuronamide 3a–3f (2nd Family), obtained by acid–base catalyzed isomerization. These compounds have the general structure, d-Glucsingle bondCdouble bond; length as m-dashONHsingle bondCHRsingle bond(CH2)nsingle bondOH and d-Frucsingle bondCdouble bond; length as m-dashONHsingle bondCHRsingle bond(CH2)nsingle bondOH, where R = an aromatic, alkyl or a hydrogen substituent, with n = 0 or 1. Eight of these contained a chiral aminoalcohol group. Three compounds were amides containing a d-glucopyranose unit (3rd Family). SAR studies were conducted with these compounds. Antiproliferative studies showed that compound 4a, the bromo-amide containing the β-d-glucopyranose ring, potently inhibits the proliferation of the MDST8 cells. Five compounds (2e, 2f, 3d, 3e, and 3f) were shown to potently selectively inhibit the proliferation of the MCF-7 cells. Compound 4b was the only one showing inhibition in both cell lines. In general, the more active compounds were the amides and hydroxyamides containing the β-d-fructose moiety, and containing an alkyl group or hydrogen. Half-inhibitory concentrations (IC50) of between 0.01 and 10 μM, were observed

    EPIDEMIOLOGICAL PROFILE OF ARBOVIROSIS IN THE STATE OF MARANHÃO: DENGUE FROM 2010 TO 2020

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    Dengue is an arbovirus considered a growing problem in relation to public health worldwide. With this, the objective of this work is to describe, in a retrospective and analytical way, the epidemiological profile and the spatial distribution of dengue cases in the state of Maranhão between the years 2010 to 2020. This quantitative and retrospective study used secondary data provided by the State Department of Health (SES-MA) of confirmed and notified cases of the disease in a time frame between 2010 and 2020. In addition, geoprocessing techniques were also used to spatialize the data. The results indicate that there were oscillations in relation to confirmed and reported cases throughout this period in the state, especially in the north and southwest regions. Thus, Maranhão reveals a critical state in relation to the occurrence of the disease, which is possibly associated with environmental factors, infrastructure and lack of public policies related to basic sanitation.info:eu-repo/semantics/publishedVersio

    The combined effect of pressure and temperature on kefir production - a case study of food fermentation in unconventional conditions

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    Food fermentation under pressure has been studied in recent years as a way to produce foods with novel properties. The purpose of this work was to study kefir production under pressure (7–50 MPa) at different temperatures (17–32 °C), as a case study of unconventional food fermentation. The fermentation time to produce kefir was similar at all temperatures (17, 25, and 32 °C) up to 15 MPa, compared to atmospheric pressure. At 50 MPa, the fermentation rate was slower, but the difference was reduced as temperature increased. During fermentation, lactic and acetic acid concentration increased while citric acid decreased. The positive activation volumes (Va) obtained indicate that pressure decreased the fermentation rate, while the temperature rise led to the attenuation of the pressure effect (lower Va). On the other hand, higher activation energies (Ea) were observed with pressure increase, indicating that fermentation became more sensitive to temperature. The condition that resulted in a faster fermentation, higher titratable acidity, and higher concentration of lactic acid was 15 MPa/32 °C. As the authors are aware, this is the second work in the literature to study the combined effect of pressure and temperature on a fermentative process.info:eu-repo/semantics/publishedVersio
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