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1.
Food Sci Nutr ; 9(9): 4863-4873, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34531998

RESUMO

The impact of storage temperature (6, 12, 20, 30℃) and period (2, 6, 10, 18, 26 weeks) on the texture, color, and sensory characteristics of dark and milk-filled chocolate bars was studied. Temperatures of 6 and 12℃ were the most suitable for bar storage; these samples were evaluated not to be significantly deteriorated by the storage period. The condition of samples stored at 20℃ started to deteriorate after 10 weeks in storage; the decline was observed mainly in meltdown rate and off-flavors, resulting in low overall acceptability. This effect was more evident in dark chocolate bars. Keeping the bars at 24℃ for 24h immediately after production (retemperation) improved the bar resistance to fat bloom, even if the decrease in the sensory quality was observed at the beginning of the storage period.

2.
Sci Transl Med ; 13(592)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952673

RESUMO

Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.


Assuntos
Acondroplasia , Aptâmeros de Nucleotídeos , Acondroplasia/tratamento farmacológico , Acondroplasia/genética , Animais , Desenvolvimento Ósseo , Diferenciação Celular , Condrócitos , Camundongos , Ratos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
3.
Foods ; 11(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35010156

RESUMO

The aim of this study was to use unconventional malts in beer production and observe their effect on the wort viscosity. Six malts were analysed in this study-barley, black barley, oat, wheat, rye, and corn. Firstly, the parameters of cereals were measured after the malting process in an experimental malting house and wort production. Samples were analysed in each phase of the mashing process. Carbohydrate contents and viscosities were analytically determined from the samples. The resulting values of the dynamic viscosity were significantly higher than the values obtained by other authors, ranging from 3.4 up to 35.5 mPa·s-1. This study also confirmed the hypothesis that states that the breakdown of carbohydrates leads to a decrease in viscosity. Values measured in the black barley malt sample were higher when compared with light barley malt. Unconventional malts had a higher viscosity and were thus more difficult to filter. If these types of malts are used it is recommended to add barley malts or malts with a higher enzyme activity to them.

4.
Cell Mol Life Sci ; 77(19): 3885-3903, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31820037

RESUMO

Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.


Assuntos
Proteínas de Fusão bcr-abl/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Motivos de Aminoácidos , Sítios de Ligação , Linhagem Celular Tumoral , Proteínas de Fusão bcr-abl/química , Proteínas de Fusão bcr-abl/genética , Células HEK293 , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Fosforilação , Análise Serial de Proteínas , Ligação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Domínios de Homologia de src
5.
Proc Natl Acad Sci U S A ; 116(10): 4316-4325, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782830

RESUMO

Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK.


Assuntos
Cílios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Animais , Sistemas CRISPR-Cas , Fatores de Crescimento de Fibroblastos/metabolismo , Células HEK293 , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Knockout , Modelos Animais , Simulação de Acoplamento Molecular , Células NIH 3T3 , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteômica , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Transdução de Sinais
6.
Sci Signal ; 11(548)2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30228226

RESUMO

Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Quinases da Família src/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/genética , Células HEK293 , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Fosforilação , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Quinases da Família src/genética
7.
Int J Comput Assist Radiol Surg ; 11(10): 1803-19, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27008472

RESUMO

PURPOSE: Quantitative description of hepatic microvascular bed could contribute to understanding perfusion CT imaging. Micro-CT is a useful method for the visualization and quantification of capillary-passable vascular corrosion casts. Our aim was to develop and validate open-source software for the statistical description of the vascular networks in micro-CT scans. METHODS: Porcine hepatic microvessels were injected with Biodur E20 resin, and the resulting corrosion casts were scanned with 1.9-4.7 [Formula: see text] resolution. The microvascular network was quantified using newly developed QuantAn software both in randomly selected volume probes (n = 10) and in arbitrarily outlined hepatic lobules (n = 4). The volumes, surfaces, lengths, and numbers of microvessel segments were estimated and validated in the same data sets with manual stereological counting. Calculations of tortuosity, radius histograms, length histograms, exports of the skeletonized vascular network into open formats, and an assessment of the degree of their anisotropy were performed. RESULTS: Within hepatic lobules, the microvessels had a volume fraction of 0.13 [Formula: see text] 0.05, surface density of 21.0 [Formula: see text] 2.0 [Formula: see text], length density of 169.0 [Formula: see text] 40.2 [Formula: see text], and numerical density of 588.5 [Formula: see text] 283.1 [Formula: see text]. Sensitivity analysis of the automatic analysis to binary opening, closing, threshold offset, and aggregation radius of branching nodes was performed. CONCLUSION: The software QuantAn and its source code are openly available to researchers working in the field of stochastic geometry of microvessels in micro-CT scans or other three-dimensional imaging methods. The implemented methods comply with reproducible stereological techniques, and they were highly consistent with manual counting. Preliminary morphometrics of the classical hepatic lobules in pig were provided.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Animais , Corrosão , Imageamento Tridimensional/métodos , Fígado/irrigação sanguínea , Software , Suínos
8.
J Sci Food Agric ; 95(11): 2264-70, 2015 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-25297972

RESUMO

BACKGROUND: Calibration models for the Fourier transform-near infrared (FT-NIR) instrument were developed for quick and non-destructive determination of oil and fatty acids in whole achenes of milk thistle. Samples with a range of oil and fatty acid levels were collected and their transmittance spectra were obtained by the FT-NIR instrument. Based on these spectra and data gained by the means of the reference method - Soxhlet extraction and gas chromatography (GC) - calibration models were created by means of partial least square (PLS) regression analysis. RESULTS: Precision and accuracy of the calibration models was verified via the cross-validation of validation samples whose spectra were not part of the calibration model and also according to the root mean square error of prediction (RMSEP), root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV) and the validation coefficient of determination (R(2) ). R(2) for whole seeds were 0.96, 0.96, 0.83 and 0.67 and the RMSEP values were 0.76, 1.68, 1.24, 0.54 for oil, linoleic (C18:2), oleic (C18:1) and palmitic (C16:0) acids, respectively. CONCLUSION: The calibration models are appropriate for the non-destructive determination of oil and fatty acids levels in whole seeds of milk thistle.


Assuntos
Calibragem , Ácidos Graxos/análise , Óleos de Plantas/análise , Sementes/química , Silybum marianum/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Reprodutibilidade dos Testes
9.
Springerplus ; 3: 156, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24790812

RESUMO

The positive effect of humic acids on the growth of plant roots is well known, however, the mechanisms and role of their physical structure in these processes have not been fully explained yet. In this work, South-Moravian lignite was oxidized by means of nitric acid and hydrogen peroxide to produce a set of regenerated humic acids. The elemental composition, solid state stability and solution characteristics were determined and correlated in vitro with their biological activity. A modified hydroponic method was applied to determine the effects of their potassium salts on Zea mays seedlings roots with respect to the plant weight, root length, root division, and starch and protein content. The relations between the determined parameters were evaluated through Principal Component Analysis and Pearson's correlation coefficients. The results indicated that the most important factor determining the biological activity of South-Moravian lignite potassium humates is related to the nature of self-assemblies, while the chemical composition had no direct connection with the root growth of Zea mays seedlings. It was demonstrated a controlled processing that provided humic substances with different chemical and physicochemical properties and variable biological activity.

10.
Chem Biodivers ; 5(3): 440-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18357552

RESUMO

Carotenoid-producing yeast species such as Rhodotorula glutinis and Sporobolomyces roseus efficiently accumulated selenium from the growth medium. It was observed that incorporation of selenium into yeast cells during the growth inhibited production of beta-carotenoid and other carotenoid precursors (torularhodin and torulene). The yeasts with high content of the carotenoid pigments and selenium may be used for the preparation of a new type of antioxidant formula that could be directly applied for various human and animal diets. We have demonstrated that such a formula can only be produced by separate processes of the cultivation of red yeasts and a subsequent sorption of selenium into the cells.


Assuntos
Antioxidantes/metabolismo , Basidiomycota/metabolismo , Carotenoides/biossíntese , Rhodotorula/metabolismo , Compostos de Selênio/metabolismo , Antioxidantes/farmacologia , Basidiomycota/efeitos dos fármacos , Biomassa , Carotenoides/química , Meios de Cultura/química , Meios de Cultura/farmacologia , Suplementos Nutricionais , Rhodotorula/efeitos dos fármacos , Compostos de Selênio/química , Compostos de Selênio/farmacocinética
11.
Z Naturforsch C J Biosci ; 63(11-12): 873-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19227837

RESUMO

The tolerance, sorption of nickel(II) ions, and changes in the production and composition of exopolymers of eight yeast strains grown under nickel presence with/without NaCl were studied. Strains of Pichia anomala and Candida maltosa known as the most resistant yeasts against nickel tolerated up to 3 mM Ni2+. NaCl addition decreased both the resistance of the yeast strains toward nickel ions and the sorption of metal ions into cells. All yeasts absorbed nickel predominantly into exopolymers (glycoproteins) and on the surface of cells. However, while the amount of polysaccharide moieties of exoglycoproteins of most of the resistant yeasts was induced by stress conditions, the ratio polysaccharide/protein in the exopolymers remained unchanged in the sensitive species Cystofilobasidium. The exopolymer composition might play a key role in yeast adaptation to stress conditions caused by heavy metal ions.


Assuntos
Candida/metabolismo , Níquel/metabolismo , Pichia/metabolismo , Microbiologia do Solo , Aclimatação , Adsorção , Basidiomycota/crescimento & desenvolvimento , Basidiomycota/metabolismo , Candida/crescimento & desenvolvimento , Citosol/metabolismo , Proteínas Fúngicas/metabolismo , Metais Pesados/metabolismo , Pichia/crescimento & desenvolvimento
12.
Z Naturforsch C J Biosci ; 57(7-8): 634-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12240989

RESUMO

Toxicity and accumulation of Cd2+ in yeasts were studied in eight different yeast species. The adaptation to toxic concentration of this metal was dependent on the production of extracellular yeast glycoproteins. The highest concentration of Cd2+ ions in the growth medium was tolerated by a Hansenula anomala, strain while the lowest tolerance was found by the strain of species Saccharomyces cerevisiae. Extracellular glycoproteins of Hansenula anomala absorbed nearly 90% of the total content of Cd2+ ions bound by yeast cells, while extracellular glycoproteins of Saccharomyces cerevisiae bound only 6% of the total amount of cadmium. This difference is caused by the variable composition of the saccharide moiety in the extracellular glycoproteins. The composition of extracellular glycoproteins changed during the adaptation of the yeast cells to the presence of Cd2+ ions.


Assuntos
Cádmio/farmacocinética , Leveduras/fisiologia , Absorção , Cryptococcus/fisiologia , Meios de Cultura , Pichia/fisiologia , Rhodotorula/fisiologia , Saccharomyces cerevisiae/fisiologia , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de Fourier
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