The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced ...pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.
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IJS, NUK, SBMB, UL, UM, UPUK
•Seven types of wheat and rye flours were characterized.•Flours presented moisture and ash contents below the recommended maximum limit.•Low lipid content was observed avoiding changes in flours’ ...smell and taste.•The microorganisms’ counting was not significantly different in both refined samples.•Micotoxins, aflatoxins and ochratoxin A were not detected in any of the flours.
Seven types of wheat and rye flours were studied regarding their physical and chemical properties, as well as the presence of mycotoxins and microorganisms. The results revealed that flours presented moisture and ash contents below the recommended maximum limit. They also presented a low lipid content, which helps avoiding changes in the flours’ smell and taste. From the microbiological analysis, comparing the refined rye and wheat flours, the counting in the analysed microorganisms was not significantly different. The whole flours presented high contents in almost all the tested microorganisms, highlighting the molds counting for the whole wheat flour and the aerobic plate counting for the whole rye flour. None of the samples presented Salmonella spp. Aflatoxins and ochratoxin A were not detected in any of the flours. To the best of our knowledge, this is the first characterization of wheat and rye flours for Portuguese consumers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work ...in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms. These are based on genetic engineering of human genomic safe harbors combined with an improved tetracycline-inducible system and CRISPR/Cas9 technology. We exemplify the efficacy of these methods in human pluripotent stem cells (hPSCs), and show that generation of sOPTiKD/KO hPSCs is simple, rapid and allows tightly controlled individual or multiplexed gene knockdown or knockout in hPSCs and in a wide variety of differentiated cells. Finally, we illustrate the general applicability of this approach by investigating the function of transcription factors (OCT4 and T), cell cycle regulators (cyclin D family members) and epigenetic modifiers (DPY30). Overall, sOPTiKD and sOPTiKO provide a unique opportunity for functional analyses in multiple cell types relevant for the study of human development.
The objective of this study was to evaluate the effect of body image dissatisfaction on symptoms of depressive disorder in adolescents. This is a cross-sectional study that included 2,162 adolescents ...ages 18-19 born in São Luís, Maranhão, Brazil, which was part of the joint RPS cohort (Brazilian birth cohorts of Ribeirão Preto-SP, Pelotas-RS, and São Luís-MA). Socioeconomic characteristics, nutritional status, mental health, and body image characteristics were evaluated. Body image was assessed by Stunkard's silhouettes scale. The presence of symptoms indicative of depressive disorder was investigated through a diagnostic interview MINI (Mini International Neuropsychiatric Interview). A theoretical model was built in a Directed Acyclic Graph (DAG) in order to investigate the relationship between the variables of the study. The relationship was estimated weighting the inverse probability of selection for the variables of adjustment: sex and nutritional status. Among the dissatisfied adolescents due to overweight, 66.54% were girls, 32.85% were overweight, and 11.99% were obese (P<0.01). There was a significant association between dissatisfaction due to overweight and symptoms of depressive disorder (P=0.01), and there was no evidence of the same association with dissatisfaction due to thinness. Therefore, only dissatisfaction due to overweight was associated with the symptoms of depressive disorder in the evaluated adolescents.
•Gamma and electron beam irradiation induce distinct changes in stored Portobello samples.•Gamma irradiation is associated with higher levels of sugars and ergosterol.•The highest assayed doses ...tended to increase the protein content.•Both irradiation types were effective preservation technologies for Portobello mushrooms.
Mushroom production and consumption is increasing, but high perishability still represents a major commercial drawback. Besides increasing the product shelf-life, conservation processes should be innocuous to consumers. Therefore, the effects of gamma and electron beam radiation on chemical and nutritional composition of fresh samples of Agaricus bisporus Portobello (a highly commercialized species) were assessed. Mushrooms were irradiated at 1, 2 or 5 kGy, and analyzed at different times (0, 4 and 8 days). In general, irradiation type had higher effect than irradiation dose. Gamma irradiation was associated with higher contents in sugars and ergosterol, while the 5 kGy dose, independently of irradiation source, was linked with higher protein levels. Nonetheless, irradiation might represent an effective preservation methodology for Portobello mushrooms, as it was effective in maintaining their chemical profiles (except for minor organic acids and saturated fatty acids) throughout the assayed time intervals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The XENON100 dark matter experiment Aprile, E.; Arisaka, K.; Arneodo, F. ...
Astroparticle physics,
April 2012, 2012-4-00, 20120401, Volume:
35, Issue:
9
Journal Article
Peer reviewed
Open access
► XENON100 is currently one of the most sensitive experiments to detect WIMP dark matter. ► Detector design and active/passive shielding reduce the radioactive background level. ► The event vertex of ...an interaction is reconstructed with a few mm precision. ► All position dependent signal corrections are presented in the paper. ► An energy scale exploiting the light-charge anti-correlation leads to an energy resolution competitive with NaI(Tl) crystals.
The XENON100 dark matter experiment uses liquid xenon (LXe) in a time projection chamber (TPC) to search for xenon nuclear recoils resulting from the scattering of dark matter Weakly Interacting Massive Particles (WIMPs). In this paper we present a detailed description of the detector design and present performance results, as established during the commissioning phase and during the first science runs.
The active target of XENON100 contains 62kg of LXe, surrounded by an LXe veto of 99kg, both instrumented with photomultiplier tubes (PMTs) operating inside the liquid or in xenon gas. The LXe target and veto are contained in a low-radioactivity stainless steel vessel, embedded in a passive radiation shield and is installed underground at the Laboratori Nazionali del Gran Sasso (LNGS), Italy. The experiment has recently published results from a 100 live-days dark matter search. The ultimate design goal of XENON100 is to achieve a spin-independent WIMP-nucleon scattering cross section sensitivity of σ=2×10−45cm2 for a 100GeV/c2 WIMP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background and Objective
Periodontitis may promote harmful systemic effects such as changes in hepatic tissues. The purpose of this study was to investigate whether the steatosis and oxidative stress ...caused by experimental periodontitis are reversible in the liver.
Material and Methods
Twenty‐four rats were divided into three groups: control, periodontitis and P20‐20 (20 days with experimental periodontitis and 20 days without experimental periodontitis, to verify the reversibility of hepatic injuries). The following parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar bone loss for periodontal tissues; liver weights, histopathological scores for steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde, total cholesterol and triglyceride concentrations in hepatic tissues; and blood levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma‐glutaryl transferase, total cholesterol and random glucose.
Results
Gingival bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss parameters demonstrated the development of periodontitis. There was a significant reduction in the steatosis score of animals from the P20‐20 group when compared with the periodontitis group. P20‐20 group presented significantly higher glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol (both in blood and hepatic tissue) and triglyceride concentrations compared with the periodontitis group. For levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma‐glutaryl transferase and random glucose, a significant difference between the groups was not observed.
Conclusion
Our results demonstrate that the microvesicular steatosis caused by periodontitis in rats is reversible after removal of the ligature, which is associated with the increase in oxidative stress and lipid peroxidation in the liver.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Strawberry (Fragaria x ananassa Duch.) is a highly perishable fruit whose characteristics make it susceptible to developing microorganisms. Plant extracts have been studied as an alternative to ...pesticides to control spoilage microorganisms, responding to the expectation of the population seeking a healthier way of life. The fungus Botrytis cinerea is a facultative pathogen of vegetables, which can affect all stages of the development of several fruits, such as the strawberry, where it causes gray rot. Trichilia catigua (catuaba), Paullinia cupana (guarana), Stryphnodendron barbatiman (barbatimão), and Caesalpinia peltophoroides (sibipiruna) are planted in the Brazilian flora and have demonstrated pharmacological properties in their extracts. This work aimed to treat strawberries with a biodegradable film containing extracts of these species to evaluate strawberry conservation. There were notable distinctions in mass loss between the extract-treated and control samples. The pH, total acidity (TA), and soluble solids parameters exhibited consistently significant means across both sets of samples. Luminosity increased over the course of days in the color parameters, with the exception of strawberries coated with guarana. The red color showed greater intensity, except for those coated with barbatimão extract. Considering the results, it is possible to conclude that the coatings used can become an alternative to enhance the conservation of strawberries.
The effect of oven-drying at 25, 40 and 60 °C was evaluated on three macroalgae of relevance in Europe, namely
,
sp. and
, with respect to quality aspects, including their potential to be exploited ...as a source of valuable compounds. Notably, as compared to freeze-drying, oven-drying at 25 °C promoted the extraction of chlorophylls and carotenoids from
, as well as those of phycoerythrin and chlorophyll
from
sp., while 40 °C favored the recovery of fucoxanthin and pheophytin
from
. On the other hand, the use of oven-drying had a negative impact on the extraction of phenolic compounds from this alga, also diminishing the antioxidant activity of the resulting extracts. Instead, the impact of oven-drying of raw material on the recovery of specific polysaccharides differed among the macroalgae. While the amounts of ulvans and fucoidans obtained from macroalgae dried at higher temperatures tended to be superior, the recovery of agar was not affected with the drying temperatures applied to
sp. The overall results showed that oven-drying might serve as a good alternative to stabilize
,
sp. and
, especially if extraction of pigments and polysaccharides is aimed, thought the appropriate temperature applied must be adapted for each macroalgae.