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1.
PLoS One ; 19(4): e0297659, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635831

RESUMO

The trend of digital transformation fosters enterprise change, helps cultivate enterprises' own competitive advantages and is crucial to the advancement of sports enterprises' sustainable development in the framework of the emerging digital economy as a national strategy. However, there have been few empirical studies on the microlevel of digital transformation and its impact on the sustainability of sports organizations. Therefore, the sustainable growth dynamic model is used to construct indicators of corporate sustainability by referencing 48 sports corporations listed on Shanghai and Shenzhen A-shares markets and the New Third Board in China from 2012 to 2021. The intrinsic relationship between digital transformation and the sustainable development of sports enterprises and the underlying mechanism of action are explored by constructing a panel fixed effects model, a chain mediating effects model, and a panel threshold model. The most important contribution is as follows: To provide a useful reference for analyzing enterprise digital transformation, a more complete indicator indicating the extent of corporate digital transformation is built. The micro viewpoint broadens our awareness of sustainable development in sports organizations and deepens our understanding of the interaction model between sustainable development and enterprise digital transformation. This study provides methodical evidence and insights for an accurate understanding of digital transformation for sustainable enterprise development, looking into the "black box" of the mechanism between digital transformation and sustainable business development. The results show that digital transformation significantly aids sports enterprises in their pursuit of long-term sustainability. Heterogeneity tests demonstrate the pivotal role of digital transformation in advancing the sustained growth of sports firms and high-tech sports enterprises situated in the eastern region of China. Regarding transmission mechanisms, the chain mediating effect of enterprises' digital transformation on improved technological innovation and TFP, which in turn promote long-term business growth, has yet to be validated. Further examination exposes that within the context of the correlation between digital transformation and the sustainability of corporations, there is a single threshold effect based on financing restrictions and operational costs and a double threshold effect based on operational efficiency.


Assuntos
Comércio , Hidrolases , China , Pesquisa Empírica , Organizações
2.
PLoS One ; 19(3): e0301183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547149

RESUMO

The proliferation of cyber threats necessitates robust security measures to safeguard critical assets and data in today's evolving digital landscape. Small and Medium Enterprises (SMEs), which are the backbone of the global economy are particularly vulnerable to these threats due to inadequate protection for critical and sensitive information, budgetary constraints, and lack of cybersecurity expertise and personnel. Security Information and Event Management (SIEM) systems have emerged as pivotal tools for monitoring, detecting, and responding to security incidents. While proprietary SIEM solutions have historically dominated the market, open-source SIEM systems have gained prominence for their accessibility and cost-effectiveness for SMEs. This article presents a comprehensive study focusing on the evaluation of open-source SIEM systems. The research investigates the capabilities of these open-source solutions in addressing modern security challenges and compliance with regulatory requirements. Performance aspects are explored through empirical testing in simulated enterprise-grade SME network environments to assess resource utilization, and real-time data processing capabilities. By providing a rigorous assessment of the security and performance features of open-source SIEM systems, this research offers valuable insights to cybersecurity practitioners, organizations seeking cost-effective security solutions, and the broader academic community. The findings shed light on the strengths and limitations of these systems, aiding decision-makers in selecting the most suitable SIEM solution for their specific requirements while enhancing the cybersecurity posture of SMEs.


Assuntos
Orçamentos , Gestão da Informação , Segurança Computacional , Gerenciamento Clínico , Hidrolases
3.
Eur Rev Med Pharmacol Sci ; 28(5): 1741-1750, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497856

RESUMO

OBJECTIVE: To evaluate the prevalence of bifid mandibular canals (BMC) using cone-beam computed tomography (CBCT) in the Saudi population subset. MATERIALS AND METHODS: In the study, three hundred and forty-three CBCT scans (661 sides) were evaluated for the presence of BMC, involving 162 males and 181 females. Tomographic acquisitions were performed on the device Planmeca®. The image analysis was performed on the Planmeca Romexis® software, aided by image filters associated with transverse, oblique, and panoramic reconstruction cuts for analysis of the BMC. Naitoh's classification (2009) was employed to classify mandibular canals. The prevalence of BMC was determined according to location, gender, and age of participants. The data were analyzed with Chi-square and one-way ANOVA tests at a significance level of 95%. RESULTS: The BMC was observed in 37 (12.34%) out of 343 participants, of whom 20 (54.05%) were males and 17 (45.94%) were females. There was no significant difference in the proportion of bifid canals in both genders and various age groups. The most common BMC was the retromolar canal type, with 56.75% occurrence. The dental canal type was observed in 18.91% of BMC participants. The presence of a forward canal without confluence was observed in 16.21% of participants in the BMC, whereas a forward canal with confluence was noted in 8.10% of participants. CONCLUSIONS: The prevalence of bifid mandibular canals (BMC) within a subset of the Saudi population was 12.3%. The retromolar canal was identified as the most frequently occurring type, accounting for 56.7% of cases. No significant variations in BMC prevalence were observed concerning age and gender. Consequently, it is strongly advised to conduct a thorough assessment of the mandibular canal and its potential variations using CBCT imaging before undertaking mandibular surgical procedures, in order to minimize the risk of complications.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Canal Mandibular , Humanos , Feminino , Masculino , Estudos Retrospectivos , Hidrolases , Processamento de Imagem Assistida por Computador
4.
Medicine (Baltimore) ; 102(35): e34436, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656999

RESUMO

BACKGROUND: One of the most prevalent infections with a significant disease burden is urinary tract infections (UTIs), which occurs in approximately 50% of women at least once in their lifetime. Antimicrobial resistance to pathogens causing UTIs is expanding worldwide and has been associated with increased use of broad-spectrum antibiotics, including carbapenems, leading to significant costs for insurance and healthcare systems. The emergence of resistance to carbapenems has led to an increasing need for and interest in carbapenem-sparing strategies, including the use of narrow-spectrum antibiotics, such as temocillin. Temocillin has a strong bactericidal effect, along with high tolerability and a good safety profile. It is also stable toward most extended-spectrum beta-lactamases (ESBL). The purpose of our study was to design a budget impact analysis (BIA) model and estimate the budget impact of temocillin insurance coverage for the treatment of UTIs caused by ESBL-producing bacteria from the perspective of the payer. METHODS: The BIA model with insurance payer perspective was used to estimate the impact of temocillin insurance coverage on the treatment of UTIs caused by ESBL-producing bacteria over a 1-year time horizon in Iran. Direct medicine costs, hospitalization and paraclinical costs, and side effect costs were considered in this model. To assess the impact of uncertainty on the model inputs, 1-way sensitivity analyses were performed. RESULTS: The model demonstrates that inclusion of temocillin in insurance coverage, decreasing treatment costs from $36 million to $34 million, will result in overall savings of > $1.9 million and lead to > $9 million savings in insurance costs for antimicrobial resistance. CONCLUSION: The inclusion of temocillin in the insurance coverage in Iran for patients developing UTIs caused by ESBL-producing bacteria would be cost-saving for insurance and decrease the risk associated with emerging antimicrobial resistance.


Assuntos
Cobertura do Seguro , Infecções Urinárias , Humanos , Feminino , Irã (Geográfico) , Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Carbapenêmicos , Hidrolases
5.
Br J Cancer ; 129(10): 1625-1633, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37758837

RESUMO

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/patologia , Antígeno Prostático Específico , Prostatectomia/métodos , Hidrolases , Imageamento por Ressonância Magnética/métodos , Medição de Risco
6.
Environ Sci Pollut Res Int ; 30(3): 7040-7055, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36029442

RESUMO

Chlorpyrifos (CP), a broad-spectrum organophosphorus insecticide, is known for deleterious effects on soil enzymatic activities. Hence, the present study aims to examine the resilience effect of biochar (BC) aided Pelargonium graveolens L. plantation on enzymatic activities of chlorpyrifos contaminated soil. The two chlorpyrifos contaminated agriculture soils (with concentrations: S1: 46.1 and S2: 95.5 mg kg-1) were taken for the pot experiment. The plant biomass, plant growth parameters, soil microbial biomass, and enzymatic activities such as alkaline phosphatase, N-acetyl glucosaminidase, aryl sulphatase, cellulase, ß-glucosidase, dehydrogenase, phenoloxidase, and peroxidase enzymes were  examined. Ecoenzyme activities and their stoichiometry were used to enumerate the different indices including geometric mean, weighted mean, biochemical activity indices, integrated biological response, treated-soil quality index, and vector analysis in all treatments. The results of the study demonstrated that the biochar incorporation enhanced the tolerance of P. graveolens (from 42-45% to 55-67%) in chlorpyrifos contaminated soil and reduced the CP accumulation in plants. A reduction in the inhibitory effect of chlorpyrifos on soil enzymatic activities and plant growth by BC incorporation was observed along with an increase in the activities of ecoenzymes (16.7-18.6%) in soil. The investigation indicated more microbial investments in C and P than that in N acquisition under CP stress. The BC amendment catalyzed the activities of lignin and cellulose-degrading enzymes and enhanced nutrition acquisition. The CP contamination and BC amendment have no significant effect on the oil quality of P. graveolens. The study demonstrated that BC-aided P. graveolens plantation offers sustainable phytotechnology for CP contaminated soil with an economic return.


Assuntos
Clorpirifos , Inseticidas , Pelargonium , Poluentes do Solo , Inseticidas/análise , Solo , Compostos Organofosforados , Carvão Vegetal , Hidrolases , Poluentes do Solo/análise
7.
Sci Total Environ ; 861: 160605, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36460103

RESUMO

Paichongding (IPP) and cycloxaprid (CYC) have been effectively used as the alternative products of imidacloprid (IMI) against IMI-resistant insects and exhibit a great market potential. However, risk assessment of IPP and CYC for non-target organisms, especially ecological risk assessment for non-target aquatic organisms, is still lacking. Here, we predicted the toxicity and potential risks of IPP, CYC, and their transformation products (TPs) to hydrobionts. The results indicated that IPP and CYC could generate 428 and 113 TPs, respectively, via aerobic microbial transformation. Nearly half of the IPP TPs and nearly 41 % of the CYC TPs exhibited high or moderate toxicity to Daphnia or fish. Moreover, we found that IPP, CYC, and 80 TPs of them posed potential risks to aquatic ecosystems. Almost all harmful TPs contained a 6-chloropyridine ring structure, suggesting that this structure may be associated with the strong toxicity of these TPs to aquatic organisms, and these TPs (IPP-TP2 or CYC-TP2, IPP-TP197 or CYC-TP71, IPP-TP198 or CYC-TP72, and IPP-TP212 or CYC-TP80) may appear in aquatic environments as final products. The risks posed by these TPs to aquatic ecosystems require more attention. This study provides insights into the toxicity and ecological risks of IPP and CYC.


Assuntos
Inseticidas , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Inseticidas/química , Ecossistema , Neonicotinoides/toxicidade , Hidrolases , Organismos Aquáticos , Medição de Risco , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
8.
Enzyme Microb Technol ; 162: 110142, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36274424

RESUMO

Enzymatic degradation of poly(ethylene terephthalate) (PET) has emerged as a promising route for ecofriendly biodegradation of plastic waste. Several discontinuous activity assays have been developed for assessing PET hydrolyzing enzymes, usually involving manual sampling at different time points during the course of the enzymatic reaction. In this work, we present a novel, compartmentalized UV absorbance assay for continuous detection of soluble hydrolysis products released during enzymatic degradation of PET. The methodology is based on removal of the walls separating two diagonally adjacent wells in UV-transparent microplates, to ensure passage of soluble enzymatic hydrolysis products between the two adjacent wells: One well holds an insoluble PET disk of defined dimensions and the other is used for continuous reading of the enzymatic product formation (at 240 nm). The assay was validated by quantifying the rate of mixing of the soluble PET degradation product BHET (bis(2-hydroxyethyl) terephthalate) between the two adjacent wells. The assay validation also involved a simple adjustment for water evaporation during prolonged assays. With this new assay, we determined the kinetic parameters for two PET hydrolases, DuraPETase and LCCICCG, and verified the underlying assumption of steady-state reaction rates. This new continuous assay enables fast exploration and robust kinetic characterization of PET degrading enzymes.


Assuntos
Ácidos Ftálicos , Polietilenotereftalatos , Polietilenotereftalatos/metabolismo , Ácidos Ftálicos/metabolismo , Hidrolases/metabolismo , Etilenos
9.
Cancer ; 127(24): 4585-4593, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34415578

RESUMO

BACKGROUND: Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models. METHODS: This was a global, multicenter, open-label, single-arm, phase 2 trial of ADI-PEG 20 and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child-Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression-free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI-PEG-20 intramuscularly weekly at 36 mg/m2 . RESULTS: In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30-85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval [CI], 5.0%-15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progression-free survival was 3.8 months (95% CI, 1.8-6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6-20.9 months). The most common grade ≥3 treatment-related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%). CONCLUSIONS: Concurrent mFOLFOX6 plus ADI-PEG 20 exhibited limited antitumor activity in patients with treatment-refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued. LAY SUMMARY: Arginine is an important nutrient for hepatocellular carcinoma (HCC). The depletion of arginine with pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, appeared to make chemotherapy (FOLFOX) work better in animal models of HCC and in patients with HCC on an early phase clinical trial. To formally test this hypothesis in the clinical setting, a large, global, phase 2 clinical trial was conducted of ADI-PEG 20 and FOLFOX in the treatment of patients with refractory HCC. The study showed limited activity of ADI-PEG 20 and FOLFOX in advanced HCC and was stopped early.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Hidrolases/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico
10.
Proteins ; 89(10): 1340-1352, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34075621

RESUMO

Recently, a bacterium strain of Ideonella sakaiensis was identified with the uncommon ability to degrade the poly(ethylene terephthalate) (PET). The PETase from I. sakaiensis strain 201-F6 (IsPETase) catalyzes the hydrolysis of PET converting it to mono(2-hydroxyethyl) terephthalic acid (MHET), bis(2-hydroxyethyl)-TPA (BHET), and terephthalic acid (TPA). Despite the potential of this enzyme for mitigation or elimination of environmental contaminants, one of the limitations of the use of IsPETase for PET degradation is the fact that it acts only at moderate temperature due to its low thermal stability. Besides, molecular details of the main interactions of PET in the active site of IsPETase remain unclear. Herein, molecular docking and molecular dynamics (MD) simulations were applied to analyze structural changes of IsPETase induced by PET binding. Results from the essential dynamics revealed that the ß1-ß2 connecting loop is very flexible. This loop is located far from the active site of IsPETase and we suggest that it can be considered for mutagenesis to increase the thermal stability of IsPETase. The free energy landscape (FEL) demonstrates that the main change in the transition between the unbound to the bound state is associated with the ß7-α5 connecting loop, where the catalytic residue Asp206 is located. Overall, the present study provides insights into the molecular binding mechanism of PET into the IsPETase structure and a computational strategy for mapping flexible regions of this enzyme, which can be useful for the engineering of more efficient enzymes for recycling plastic polymers using biological systems.


Assuntos
Proteínas de Bactérias/metabolismo , Burkholderiales/metabolismo , Hidrolases/metabolismo , Polietilenotereftalatos/metabolismo , Biocatálise , Hidrólise
11.
Methods Mol Biol ; 2278: 209-223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33649959

RESUMO

Bifidogenic effect is a main target for the assessment of prebiotic activity. pH-controlled batch processes of bifidobacteria and fecal microbiota are herein presented. Growth of bifidobacteria, carbohydrate breakdown and consumption, organic acid production, and activity of specific glycosyl hydrolases involved in the hydrolysis of di-, oligo-, or polysaccharides are exploited to study and compare substrate preference of bifidobacteria for candidate prebiotics.


Assuntos
Bifidobacterium/metabolismo , Polissacarídeos Bacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Técnicas de Cultura Celular por Lotes/métodos , Bifidobacterium/química , Bifidobacterium/crescimento & desenvolvimento , Reatores Biológicos , Metabolismo dos Carboidratos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia por Troca Iônica/métodos , Cromatografia em Camada Fina/métodos , Ensaios Enzimáticos/métodos , Fermentação , Microbioma Gastrointestinal , Humanos , Hidrolases/metabolismo , Hidrólise , Polissacarídeos Bacterianos/análise
12.
Appl Microbiol Biotechnol ; 104(13): 6013-6022, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32367311

RESUMO

Directed evolution has become an important method to unleash the latent potential of enzymes to make them uniquely suited for human purposes. However, the need for a large reagent volume and sophisticated instrumentation hampers its broad implementation. In an attempt to address this problem, here we report a paper-based high-throughput screening approach that should find broad application in generating desired enzymes. As an example case, the dehalogenation reaction of the halohydrin dehalogenase was adopted for assay development. In addition to visual detection, quantitative measurements were performed by measuring the color intensity of an image that was photographed by a smartphone and processed using ImageJ free software. The proposed method was first validated using a gold standard method and then applied to mutagenesis library screening with reduced consumption of reagents (i.e., ≤ 10 µl per assay) and a shorter assay time. We identified two active mutants (P135A and G137A) with improved activities toward four tested substrates. The assay not only consumes less reagents but also eliminates the need for expensive instrumentation. The proposed method demonstrates the potential of paper-based whole-cell screening coupled with digital image colorimetry as a promising approach for the discovery of industrially important enzymes.Key Points• A frugal method was developed for directed enzyme evolution.• Mutagenesis libraries were successfully screened on a paper platform.• Smartphone imaging was efficiently used to measure enzyme activities.


Assuntos
Evolução Molecular Direcionada/métodos , Ensaios de Triagem em Larga Escala/métodos , Papel , Catálise , Colorimetria , Evolução Molecular Direcionada/economia , Evolução Molecular Direcionada/normas , Escherichia coli/genética , Escherichia coli/metabolismo , Biblioteca Gênica , Ensaios de Triagem em Larga Escala/economia , Ensaios de Triagem em Larga Escala/normas , Hidrolases/genética , Hidrolases/metabolismo , Mutagênese , Mutação , Reprodutibilidade dos Testes , Smartphone
13.
Genes (Basel) ; 10(5)2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100963

RESUMO

Plastics have become an important environmental concern due to their durability and resistance to degradation. Out of all plastic materials, polyesters such as polyethylene terephthalate (PET) are amenable to biological degradation due to the action of microbial polyester hydrolases. The hydrolysis products obtained from PET can thereby be used for the synthesis of novel PET as well as become a potential carbon source for microorganisms. In addition, microorganisms and biomass can be used for the synthesis of the constituent monomers of PET from renewable sources. The combination of both biodegradation and biosynthesis would enable a completely circular bio-PET economy beyond the conventional recycling processes. Circular strategies like this could contribute to significantly decreasing the environmental impact of our dependence on this polymer. Here we review the efforts made towards turning PET into a viable feedstock for microbial transformations. We highlight current bottlenecks in degradation of the polymer and metabolism of the monomers, and we showcase fully biological or semisynthetic processes leading to the synthesis of PET from sustainable substrates.


Assuntos
Plásticos Biodegradáveis/química , Polietilenotereftalatos/química , Reciclagem/métodos , Biodegradação Ambiental , Genes Microbianos/genética , Hidrolases/química , Hidrólise , Plásticos/química , Polímeros/química
14.
Acta Crystallogr F Struct Biol Commun ; 75(Pt 3): 148-152, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30839287

RESUMO

The enzymes involved in folate metabolism are key drug targets for cell-growth modulation, and accurate crystallographic structures provide templates to be exploited for structure-based ligand design. In this context, three ternary complex structures of human methylenetetrahydrofolate dehydrogenase/cyclohydrolase have been published [Schmidt et al. (2000), Biochemistry, 39, 6325-6335] and potentially represent starting points for the development of new antifolate inhibitors. However, an inspection of the models and the deposited data revealed deficiencies and raised questions about the validity of the structures. A number of inconsistencies relating to the publication were also identified. Additional refinement was carried out with the deposited data, seeking to improve the models and to then validate the complex structures or correct the record. In one case, the inclusion of the inhibitor in the structure was supported and alterations to the model allowed details of enzyme-ligand interactions to be described that had not previously been discussed. For one weak inhibitor, the data suggested that the ligand may adopt two poses in the binding site, both with few interactions with the enzyme. In the third case, that of a potent inhibitor, inconsistencies were noted in the assignment of the chemical structure and there was no evidence to support the inclusion of the ligand in the active site.


Assuntos
Hidrolases/química , Metilenotetra-Hidrofolato Desidrogenase (NADP)/química , Sítios de Ligação , Cristalografia por Raios X , Antagonistas do Ácido Fólico/química , Humanos , Ligação de Hidrogênio , Ligantes , Conformação Proteica
15.
Int J Food Sci Nutr ; 69(2): 165-175, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28691595

RESUMO

The aim of this study was to apply the enzymatic treatment and fermentation by Pediococcus acidilactici BaltBio01 strain for industrial cereal by-products conversion to food/feed bioproducts with high amount of probiotic lactic acid bacteria (LAB). LAB propagated in potato media and spray-dried remained viable during 12 months (7.0 log10 cfu/g) of storage and was used as a starter for cereal by-products fermentation. The changes of microbial profile, biogenic amines (BAs), mycotoxins, lactic acid (L+/D-), lignans and alkylresorcinols (ARs) contents in fermented cereal by-product were analysed. Cereal by-products enzymatic hydrolysis before fermentation allows to obtain a higher count of LAB during fermentation. Fermentation with P. acidilactici reduce mycotoxins content in fermented cereal by-products. According to our results, P. acidilactici multiplied in potato juice could be used for cereal by-products fermentation, as a potential source to produce safer food/feed bioproduct with high amount of probiotic LAB for industrial production.


Assuntos
Ração Animal/microbiologia , Grão Comestível/metabolismo , Alimentos Fermentados/microbiologia , Aditivos Alimentares/metabolismo , Hidrolases/metabolismo , Pediococcus acidilactici/metabolismo , Probióticos/metabolismo , Alquilação , Ração Animal/efeitos adversos , Ração Animal/análise , Ração Animal/economia , Animais , Aminas Biogênicas/efeitos adversos , Aminas Biogênicas/análise , Aminas Biogênicas/metabolismo , Grão Comestível/efeitos adversos , Grão Comestível/química , Grão Comestível/economia , Fermentação , Alimentos Fermentados/efeitos adversos , Alimentos Fermentados/análise , Alimentos Fermentados/economia , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/química , Aditivos Alimentares/economia , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos , Indústria de Processamento de Alimentos/economia , Humanos , Hidrolases/efeitos adversos , Hidrólise , Resíduos Industriais/economia , Letônia , Lignanas/efeitos adversos , Lignanas/análise , Lignanas/metabolismo , Viabilidade Microbiana , Micotoxinas/isolamento & purificação , Micotoxinas/metabolismo , Micotoxinas/toxicidade , Pediococcus acidilactici/crescimento & desenvolvimento , Probióticos/efeitos adversos , Resorcinóis/efeitos adversos , Resorcinóis/análise , Resorcinóis/metabolismo
16.
Stem Cell Reports ; 9(2): 499-512, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28757167

RESUMO

Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah-/-) mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps.


Assuntos
Transdiferenciação Celular/genética , Reprogramação Celular/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Fatores de Transcrição/genética , Animais , Biomarcadores , Linhagem da Célula , Transplante de Células , Células Cultivadas , Imunofluorescência , Expressão Gênica , Hidrolases/deficiência , Imunofenotipagem , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Medicina Regenerativa , Fatores de Transcrição/metabolismo
17.
Appl Microbiol Biotechnol ; 100(5): 2213-24, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26521250

RESUMO

This study reports enzymatic hydrolysis of the biomass of the giant reed (Arundo donax L.) after ammonia fibre expansion (AFEX) pretreatment. In particular, the capacity of the arabinofuranosidase from the fungus Pleurotus ostreatus recombinantly expressed in Pichia pastoris rPoAbf, its evolved mutant rPoAbf F435Y/Y446F and the endo-cellulase from Streptomyces sp. G12 CelStrep recombinantly expressed in Escherichia coli to enhance the hydrolysis of AFEX-treated A. donax was investigated, using the corn stover as reference feedstock. The investigated enzymes were assayed using a mixture of purified cellulases (CBHI, CBHII, EGI and ßG), endoxylanases (LX3, LX4) and accessory hemicellulases (LarbF and LßX) as reference enzyme mixture and substituting EGI with rCelStrep and LarbF with rPoAbf or rPoAbf F435Y/Y446F. The use of rPoAbf F435Y/Y446F in the substitution of LarbF led to improvements in sugar conversion, giving a glucan, xylan and arabinan conversion after 72 h of around 62, 63 and 80 %, respectively, similar or higher than those (44, 66 and 55 %) achieved by 72 h hydrolysis with commercial enzymes Novozymes Cellic®, Ctec3 and Htec3. The enzymes rPoAbf, rPoAbf F435Y/Y446F and rCelStrep were also investigated for their effect on hydrolysis of AFEX-pretreated A. donax by addition to commercial enzyme mixture Novozymes Cellic®, Ctec3 and Htec3, and it was shown that the addition of rPoAbf and its evolved mutant rPoAbf F435Y/Y446F enhanced both xylan and arabinan conversions, which achieved 80 % after 6 days of saccharification with rPoAbf F435Y/Y446F.


Assuntos
Amônia/metabolismo , Bactérias/enzimologia , Celulose/metabolismo , Fungos/enzimologia , Hidrolases/metabolismo , Poaceae/química , Poaceae/efeitos dos fármacos , Bactérias/genética , Biotransformação , Fungos/genética , Expressão Gênica , Hidrolases/genética , Hidrólise , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
18.
Bioresour Technol ; 187: 37-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25836372

RESUMO

Solid-liquid separation of intermediate process slurries is required in some process configurations for the conversion of lignocellulosic biomass to transportation fuels. Thermochemically pretreated and enzymatically hydrolyzed corn stover slurries have proven difficult to filter due to formation of very low permeability cakes that are rich in lignin. Treatment of two different slurries with polyelectrolyte flocculant was demonstrated to increase mean particle size and filterability. Filtration flux was greatly improved, and thus scaled filter unit capacity was increased approximately 40-fold compared with unflocculated slurry. Although additional costs were accrued using polyelectrolyte, techno-economic analysis revealed that the increase in filter capacity significantly reduced overall production costs. Fuel production cost at 95% sugar recovery was reduced by $1.35 US per gallon gasoline equivalent for dilute-acid pretreated and enzymatically hydrolyzed slurries and $3.40 for slurries produced using an additional alkaline de-acetylation preprocessing step that is even more difficult to natively filter.


Assuntos
Carboidratos/economia , Carboidratos/isolamento & purificação , Hidrolases/química , Esgotos/química , Extração em Fase Sólida/métodos , Zea mays/química , Simulação por Computador , Hidrolases/economia , Hidrólise , Modelos Econômicos , Componentes Aéreos da Planta/química , Estados Unidos
19.
J Basic Microbiol ; 55(3): 363-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24002962

RESUMO

The disposal of hexachlorocyclohexane (HCH) muck has created large number of HCH dumpsites all over the world from where the harmful HCH isomers are leaking into the environment. Bacteria have evolved at such contaminated sites that have the ability to degrade HCH. Degradation of various HCH isomers in bacterial strains is mediated primarily by two genes: linA and linB which encode dehydrochlorinase and haloalkane dehalogenase respectively. In this study we explored one such highly contaminated HCH dumpsite located in Lucknow, Uttar Pradesh, India. To assess the biostimulation potential of the contaminated site, microbial diversity study and real-time PCR based quantification of lin genes was carried out. The soil samples from dumpsite and surrounding areas were found to be highly contaminated with HCH residue levels as high as 1.8 × 10(5) mg kg(-1). The residues were detected in areas upto 13 km from the dumpsite. Sphingomonads, Chromohalobacter, and Marinobacter were the dominant genera present at the dump-site. Role of Sphingomonads in HCH degradation has been well documented. The highest copy numbers of linA and linB genes as determined using real-time PCR were 6.2 × 10(4) and 5.3 × 10(5), respectively, were found in sample from the dump site. The presence of Sphingomonads, linA, and linB genes from HCH contaminated soil indicates the presence of indigenous bacterial communities capable of HCH degradation.


Assuntos
Bactérias/genética , Bactérias/isolamento & purificação , Poluição Ambiental , Locais de Resíduos Perigosos , Hexaclorocicloexano/metabolismo , Hidrolases/genética , Liases/genética , Sequência de Aminoácidos , Bactérias/metabolismo , Biodegradação Ambiental , Biodiversidade , Chromohalobacter/genética , Chromohalobacter/isolamento & purificação , Dosagem de Genes , Variação Genética , Hexaclorocicloexano/análise , Hidrolases/química , Índia , Liases/química , Marinobacter/genética , Marinobacter/isolamento & purificação , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Microbiologia do Solo
20.
J. appl. oral sci ; 22(6): 560-568, Nov-Dec/2014. tab, graf
Artigo em Inglês | LILACS, BBO | ID: lil-732581

RESUMO

Objectives To assess the relationships among alkali production, diet, oral health behaviors, and oral hygiene. Methods Data from 52 subjects including demographics, diet, and oral hygiene scores were analyzed against the level of arginine and urea enzymes in plaque and saliva samples. An oral habit survey was completed that included: use of tobacco (TB), alcohol (AH), sugary drinks (SD), and diet. Alkali production through arginine deiminase (ADS) and urease activities were measured in smooth-surface supragingival dental plaque and un stimulated saliva samples from all subjects. ADS and urease activities were measured by quantification of the ammonia generated from the incubation of plaque or saliva samples. Spearman correlations were used to compute all associations. Results Participants in the lowest SES (Socio-economic status) group had the habit of consuming sugary drinks the most and had the highest rate of tobacco use. Males consumed significantly more alcohol than females. No significant relationship was found between age or gender and alkali production. Higher rates of sugary drink consumption and tobacco use were significantly related to lower alkali production. Conclusion The study showed a relationship between alkali production and oral hygiene, diet, and certain oral health behaviors. Poor oral hygiene was significantly associated with age, lower SES, tobacco use, and alcohol, and sugary drinks consumption. Clinical relevance Certain oral health behaviors have an impact on oral hygiene and on alkali production; it is important to address these factors with patients as a strategy for caries control. .


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Álcalis/análise , Comportamento Alimentar , Boca/química , Higiene Bucal , Fatores Etários , Consumo de Bebidas Alcoólicas/efeitos adversos , Álcalis/metabolismo , Carboidratos/efeitos adversos , Cárie Dentária/etiologia , Cárie Dentária/prevenção & controle , Hidrolases/análise , Hidrolases/metabolismo , Fatores de Risco , Saliva/química , Fumar/efeitos adversos , Fatores Socioeconômicos , Estatísticas não Paramétricas , Urease/análise , Urease/metabolismo
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