Literatura científica selecionada sobre o tema "Sucrose Non-Fermentable"

Fermentable sugar for bioethanol production can be produced from molasses due to its high sucrose content but Ca2+ ions found in the molasses may affect the hydrolysis. Therefore, this paper was focused to study the effect of Ca2+ ions as CaO on sucrose hydrolysis using invertase and to obtain the kinetic parameters. The kinetic parameters (KM and Vmax) were obtained using a Lineweaver-Burk plot. The value of KM and Vmax parameters were 36.181 g/L and 21.322 g/L.h, respectively. The Ca2+ ions act as competitive inhibitor in sucrose hydrolysis using invertase. Therefore, the inhibition mechanism was followed the competitive inhibition mechanism. The value of inhibition constant was 0.833 g/g. These parameters were obtained from the non-substrate inhibition process because this study used the low substrate concentrations which means the fermentable sugar production was low. Hence, there were still more challenges to studying the simultaneous effect of substrate and Ca2+ on sucrose hydrolysis to produce high fermentable sugar. Copyright © 2019 BCREC Group. All rights reserved

Switch / sucrose non fermentable (SWI/SNF) related, matrix associated, actin dependent regulator of chromatin subfamily B member 1 (SMARCB1) deficient medullary renal cell carcinoma is an exceptionally discerned, aggressive carcinoma associated with deficiency of SMARCB1 or integrase interactor 1(INI1).

Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.

The frequent ingestion of fermentable sugars such as sucrose, fructose, glucose and maltose is conducive to the development of caries in the teeth of susceptible individuals. Natural and artificial alternatives to these sugars have been and continue to be developed as non/low-caloric sweeteners. The US Food and Drug Administration have approved four non-caloric sweeteners at present. However, there are several other non-caloric sweeteners being commonly used in other countries.A review of these sweeteners is provided with information on a promising new agent that has not yet gained FDA approval.

An economically viable production of second-generation bioethanol by recombinant xylose-fermenting Saccharomyces cerevisiae requires higher xylose fermentation rates and improved glucose–xylose co-consumption. Moreover, xylose-fermenting S. cerevisiae recognises xylose as a non-fermentable rather than a fermentable carbon source, which might partly explain why xylose is not fermented into ethanol as efficiently as glucose. This study proposes propagating S. cerevisiae on non-fermentable carbon sources to enhance xylose metabolism during fermentation. When compared to yeast grown on sucrose, cells propagated on a mix of ethanol and glycerol in shake flasks showed up to 50% higher xylose utilisation rate (in a defined xylose medium) and a double maximum fermentation rate, together with an improved C5/C6 co-consumption (on an industrial softwood hydrolysate). Based on these results, an automated propagation protocol was developed, using a fed-batch approach and the respiratory quotient to guide the ethanol and glycerol-containing feed. This successfully produced 71.29 ± 0.91 g/L yeast with an average productivity of 1.03 ± 0.05 g/L/h. These empirical findings provide the basis for the design of a simple, yet effective yeast production strategy to be used in the second-generation bioethanol industry for increased fermentation efficiency.

Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate.

A pursuit to find a healthy alternative to sucrose with less cariogenic potential, which can potentially lower the incidence of Early Childhood Caries (ECC), by means of comparison. Primary tooth enamel blocks (n=32) were randomly divided into four groups and exposed to 5% concentrations of the respective test groups (sucrose, xylitol, erythritol and stevia). All samples were inoculated with S. mutans standard strain (ATCC 25175) at room temperature. Analysis of Colony Forming Units (CFUs), acidity measurements (pH) and Scanning Electron Microscopy (SEM) observations were done after 6, 12, 18 and 24 h and compared. After 6 h, the marginal mean CFU count indicated equal S. mutans growth in all groups. Stevia showed lower CFU counts compared to other groups at 12, 18 and 24 h. The pH levels for all non-fermentable sugar substitutes (NSS) initially decreased but never below the critical pH=5.5 and stabilized from 12 to 18 h. The pH levels of sucrose dropped and remained below pH=5.5 at all time intervals. The SEM analysis of S. mutans supported the CFU results indicating growth in the presence of sucrose and reduction in the presence of the NSS.Compared to sucrose, xylitol, erythritol and stevia have less cariogenic potential with reduced growth of S. mutans and subsequent acidity levels. Stevia had the least cariogenic potential of all the NSS tested, followed by erythritol and then xylitol.

The packaging of genomic DNA into nucleosomes creates a barrier to transcription that can be relieved through ATP-dependent chromatin remodeling via complexes such as the switch-sucrose non-fermentable (SWI-SNF) chromatin remodeling complex. The SWI-SNF complex remodels chromatin via conformational or positional changes of nucleosomes, thereby altering the access of transcriptional machinery to target genes. The SWI-SNF complex has limited ability to bind to sequence-specific elements, and, therefore, its recruitment to target loci is believed to require interaction with DNA-associated transcription factors. The Cdx family of homeodomain transcript ion factors (Cdx1, Cdx2, and Cdx4) are essential for a number of developmental programs in the mouse. Cdx1 and Cdx2 also regulate intestinal homeostasis throughout life. Although a number of Cdx target genes have been identified, the basis by which Cdx members impact their transcription is poorly understood. We have found that Cdx members interact with the SWI-SNF complex and make direct contact with Brg1, a catalytic member of SWI-SNF. Both Cdx2 and Brg1 co-occupy a number of Cdx target genes, and both factors are necessary for transcriptional regulation of such targets. Finally, Cdx2 and Brg1 occupancy occurs coincident with chromatin remodeling at some of these loci. Taken together, our findings suggest that Cdx transcription factors regulate target gene expression, in part, through recruitment of Brg1-associated SWI-SNF chromatin remodeling activity.

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal tumor of unclear origin and uncertain lineage characterized by a prevalent epithelioid morphology. The only recurrent genetic alteration reported in ES as yet is the functional inactivation of SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1), a key component of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes. How SMARCB1 deficiency dictates the clinicopathological characteristics of ES and what other molecular defects concur to its malignant progression is still poorly understood. This review summarizes the recent findings about ES pathobiology, including defects in chromatin remodeling and other signaling pathways and their role as therapeutic vulnerabilities.

De nos jours, la communauté scientifique s'accorde sur la nécessité de diagnostics et de thérapies personnalisés pour les patients atteints de cancer, conçus par des études translationnelles combinant approches expérimentales et statistiques. Les défis actuels incluent la validation de modèles expérimentaux précliniques et leur profilage multi-omiques, ainsi que la conception de méthodes bioinformatiques et mathématiques dédiées pour identifier les combinaisons de médicaments optimales pour chaque patient.Cette thèse a visé à concevoir de telles approches statistiques pour analyser différents types de données à grande échelle et les intégrer afin d'identifier les vulnérabilités ciblables des lignées cancéreuses. Nous nous sommes focalisés sur les altérations du complexe de remodelage de la chromatine SWI/SNF, muté dans ~20 % des cancers, pour lesquels aucune thérapie efficace n'est disponible. Nous avons utilisé un panel de lignées cellulaires isogéniques HAP1 mutées pour les sous-unités du complexe SWI/SNF ou d'autres enzymes épigénétiques, pour lesquelles des données de transcriptomique, protéomique et de criblage de médicaments étaient disponibles.Nous avons travaillé sur quatre axes méthodologiques. Premièrement, nous avons conçu une méthodologie optimisée d'enrichissement pour détecter les voies de régulation différentiellement activées entre mutants et type sauvage. Ensuite, nous avons croisé les résultats des criblages de médicaments et les bases d'interaction gène-médicament, pour inférer des voies de régulation ciblables spécifiquement chez les lignées mutantes. Ensuite, la validation de ces cibles potentielles a été réalisée à l'aide d'une nouvelle méthode détectant la létalité synthétique à partir de données transcriptomiques et CRISPR de lignées cancéreuses indépendantes du projet DepMap. Enfin, en vue de l'optimisation de thérapies multi-agents, nous avons conçu une première représentation digitale des voies de régulation ciblables pour les tumeurs mutées SMARCA4, en construisant un réseau dirigé d'interaction protéine-protéine reliant les cibles inférées des analyses multi-omiques HAP1 et CRISPR DepMap. Nous avons utilisé la base de données OmniPath pour récupérer les interactions protéiques directes et ajouté les protéines liant celles présentes dans le réseau avec l'algorithme Neko.Ces développements méthodologiques ont été appliqués aux ensembles de données disponibles pour le panel HAP1. En utilisant notre méthodologie d'enrichissement optimisée, nous avons identifié le Métabolisme des protéines comme la catégorie de voies de régulation la plus fréquemment dérégulée dans les lignées SWI/SNF-KO. Ensuite, l'analyse de criblage de médicaments a révélé des médicaments cytotoxiques et épigénétiques ciblant sélectivement les mutants SWI/SNF, notamment les inhibiteurs de CBP/EP300 ou de la respiration mitochondriale, également identifiés comme létaux synthétiques par notre analyse CRISPR DepMap. Ces résultats ont été validés dans deux modèles expérimentaux isogéniques indépendants. L'analyse CRISPR DepMap a également été utilisée pour identifier des interactions létales synthétiques dans le glioblastome, qui se sont révélées pertinentes pour des lignées cellulaires dérivées de patients et sont en cours de validation.En résumé, nous avons développé des méthodes computationnelles pour intégrer des données d'expression multi-omiques avec des criblages de médicaments et des tests CRISPR, et identifié de nouvelles vulnérabilités chez les mutants SWI/SNF, qui ont été validées expérimentalement. Cette étude était limitée à l'identification de monothérapies efficaces. Pour l'avenir, nous proposons de concevoir des modèles mathématiques représentant les réseaux de protéines ciblables à l'aide d'équations différentielles et de les utiliser dans des procédures d'optimisation numérique et d'apprentissage automatique pour étudier les cibles médicamenteuses concomitantes et personnaliser les combinaisons de médicaments
Nowadays the cancer community agrees on the need for patient-tailored diagnostics and therapies, which calls for the design of translational studies combining experimental and statistical approaches. Current challenges include the validation of preclinical experimental models and their multi-omics profiling, along with the design of dedicated bioinformatics and mathematical pipelines (i.e. dimension reduction, multi-omics integration, mechanism-based digital twins) for identifying patient-specific optimal drug combinations.To address these challenges, we designed bioinformatics and statistical approaches to analyze various large-scale data types and integrate them to identify targetable vulnerabilities in cancer cell lines. We developed our pipeline in the context of alterations of the SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SWI/SNF mutations occur in ~20% of all cancers, but such malignancies still lack efficient therapies. We leveraged a panel of HAP1 isogenic cell lines mutated for SWI/SNF subunits or other epigenetic enzymes for which transcriptomics, proteomics and drug screening data were available.We worked on four methodological axes, the first one being the design of an optimized pathway enrichment pipeline to detect pathways differentially activated in the mutants against the wild-type. We developed a pruning algorithm to reduce gene and pathway redundancy in the Reactome database and improve the interpretability of the results. We evidenced the bad performance of first-generation enrichment methods and proposed to combine the topology-based method ROntoTools with pre-ranked GSEA to increase enrichment performance .Secondly, we analyzed drug screens, processed drug-gene interaction databases to obtain genes and pathways targeted by effective drugs and integrated them with proteomics enrichment results to infer targetable vulnerabilities selectively harming mutant cell lines. The validation of potential targets was achieved using a novel method detecting synthetic lethality from transcriptomics and CRISPR data of independent cancer cell lines in DepMap, run for each studied epigenetic enzyme. Finally, to further inform multi-agent therapy optimization, we designed a first digital representation of targetable pathways for SMARCA4-mutated tumors by building a directed protein-protein interaction network connecting targets inferred from multi-omics HAP1 and DepMap CRISPR analyses. We used the OmniPath database to retrieve direct protein interactions and added the connecting neighboring genes with the Neko algorithm.These methodological developments were applied to the HAP1 panel datasets. Using our optimized enrichment pipeline, we identified Metabolism of proteins as the most frequently dysregulated pathway category in SWI/SNF-KO lines. Next, the drug screening analysis revealed cytotoxic and epigenetic drugs selectively targeting SWI/SNF mutants, including CBP/EP300 or mitochondrial respiration inhibitors, also identified as synthetic lethal by our Depmap CRISPR analysis. Importantly, we validated these findings in two independent isogenic cancer-relevant experimental models. The Depmap CRISPR analysis was also used in a separate project to identify synthetic lethal interactions in glioblastoma, which proved relevant for patient-derived cell lines and are being validated in dedicated drug screens.To sum up, we developed computational methods to integrate multi-omics expression data with drug screening and CRISPR assays and identified new vulnerabilities in SWI/SNF mutants which were experimentally revalidated. This study was limited to the identification of effective single agents. As a future direction, we propose to design mathematical models representing targetable protein networks using differential equations and their use in numerical optimization and machine learning procedures as a key tool to investigate concomitant druggable targets and personalize drug combinations

Abstract The Snfl class of serine-threonine protein kinases are found in yeast, mammals, and plants, and share a common role in the regulation of certain key enzymes of carbon metabolism (Hardie et al. 1994). In yeast, Snflp phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and glycogen synthase (GS) (Woods et al. 1994; Hardy et al. 1994). It is also an indispensable part of a signal transduction pathway required for the derepression of a number of genes involved in the utilization of alternative carbon sources in response to glucose deprivation (reviewed by Gancedo 1992). This pathway has not been entirely elucidated and the mechanism by which the signal is created in response to glucose levels is not known. It has been hypothesized that a weak protein kinase activity associated with hexokinase may be indicative of a role for this enzyme in the perception of glucose levels (Ma et al. 1989a,b; Rose et al. 1991). Alternatively, glucose flux through glycolysis rather than glucose levels per se may be the relevant parameter for triggering and reversing glucose repression (Ronne 1995). snfl mutants are unable to utilize a variety of carbon sources, including sucrose, fructose, maltose, and non-fermentable carbon sources such as ethanol and glycerol. They are also defective in sporulation and the heat-shock response (Johnston and Carlson 1992; Thompson-Jaeger et al. 1991).