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1.
Sci Total Environ ; 701: 134424, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726412

RESUMO

Over use of N fertilizers, most commonly as urea, had been seriously concerned as a major source of radiative N (Nr) for severe environment impacts through leaching, volatilization, and N2O emission from fertilized croplands. It had been well known that biochar could enhance N retention and use efficiency by crops in amended croplands. In this study, a granular biochar-mineral urea composite (Bio-MUC) was obtained by blending urea with green waste biochar supplemented with clay minerals of bentonite and sepiolite. This Bio-MUC material was firstly characterized by microscopic analyses with FTIR, SEM-EDS and STEM, subsequently tested for N leaching in water in column experiment and for N supply for maize in pot culture, compared to conventional urea fertilizer (UF). Microscopic analyses indicated binding of urea N to particle surfaces of biochar and clay minerals in the Bio-MUC composite. In the leaching experiment over 30 days, cumulative N release as NH4+-N and of dissolved organic carbon (DOC) was significantly smaller by >70% and by 8% from the Bio-MUC than from UF. In pot culture with maize growing for 50 days, total fresh shoot was enhanced by 14% but fresh root by 25% under Bio-MUC compared to UF. This study suggested that N in the Bio-MUC was shown slow releasing in water but maize growth promoting in soil, relative to conventional urea. Such effect could be related mainly to N retention by binding to biochar/mineral surfaces and partly by carbon bonds of urea to biochar in the Bio-MUC. Therefore, biochar from agro-wastes could be used for blending urea as combined organo/mineral urea to replace mineral urea so as to reduce N use and impacts on global Nr. Of course, how such biochar combined urea would impact N process in soil-plant systems deserve further field studies.

3.
Chemosphere ; 243: 125332, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751928

RESUMO

The potential of biochar to enhance phytorestoration of hexavalent chromium [Cr(VI)]-contaminated soils was investigated. Rooted cuttings of Ficus elastica Roxb. Ex Hornem were transplanted to soil treated with 0 or 25 mg kg-1 Cr(VI), ‒Cr and +Cr designations respectively, and amended with cattle manure-derived biochar at 0, 10 and 50 g kg-1. Plants were grown for 180 d in a temperature-controlled greenhouse. In the ‒Cr treatment, biochar addition enhanced plant growth without affecting plant water status, leaf nutrient levels, photochemical efficiency, or hormone levels. In the absence of biochar, Ficus growth in the +Cr treatment was stunted, exhibiting decreased leaf and root relative water content and photochemical efficiency. Adding biochar to +Cr soil resulted in decreased Cr uptake into plant tissues and alleviated the toxic effects of soil Cr(VI) on plant growth and physiology, including decreased leaf lipid peroxidation. High-resolution electron microscopy and spectroscopy elucidated the biochar role in decreasing Cr mobility, bioavailability, and phytotoxicity. Spectroscopic evidence is suggestive that biochar mediated the reduction of Cr(VI) to Cr(III), which was subsequently incorporated into organomineral agglomerates formed at biochar surfaces. The dual function of biochar in improving F. elastica performance and detoxifying Cr(VI) demonstrates that biochar holds much potential for enhancing phytorestoration of Cr(VI)-contaminated soils.

4.
Biochim Biophys Acta Proteins Proteom ; 1868(2): 140320, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756433

RESUMO

In recent years, metagenomic strategies have been widely used to isolate and identify new enzymes from uncultivable components of microbial communities. Among these enzymes, various lipases have been obtained from metagenomic libraries from different environments and characterized. Although many of these lipases have characteristics that could make them interesting for application in biocatalysis, relatively little work has been done to evaluate their potential to catalyze industrially important reactions. In the present article, we highlight the latest research on lipases obtained through metagenomic tools, focusing on studies of activity and stability and investigations of application in biocatalysis. We also discuss the challenges of metagenomic approaches for the bioprospecting of new lipases.

5.
Ann Intern Med ; 171(9): 682, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31683281
6.
Disabil Rehabil ; : 1-7, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600094

RESUMO

Background: An association between end-stage renal failure and exercise intolerance exists. Whether live kidney donation impacts on exercise tolerance is unknown. Here recovery post renal transplant and donation using cardiopulmonary exercise testing is investigated. Methods: Renal donors (n = 28) and recipients (n = 24) undertook a cardiopulmonary exercise test, Duke activity score index and patient reported health score questionnaires pre-operatively and in the 7th and 14th week post-operatively. Anaerobic threshold, peak oxygen uptake and ventilatory equivalents were measured in relation to activity and reported health scores. Haemoglobin and renal function was recorded. Results: Recipients showed impaired cardiopulmonary function compared to donors with lower anaerobic threshold (10.5 vs. 14.4 ml/kg/min) and peak oxygen uptake (18.5 vs 23.0 ml/kg/min). Post-operatively the anaerobic threshold of recipients improved and normalised by the 14th week, whereas that in donors fell by ∼20% by the 7th (mean 11.4 ml/kg/min), recovering by the 14th (mean 15.6 ml/kg/min). Reported health but not activity scores showed similar changes. Conclusions: Recovery following renal transplantation and donation differ. Transplantation improves renal function resulting in an increase in anaerobic threshold and peak oxygen uptake which essentially normalise by the 14th week post-operatively. Donors suffer a 20% reduction in cardiopulmonary reserve post-operatively, which recovers by the 14th week, suggesting no associated chronic exercise intolerance. IMPLICATIONS FOR REHABILITATION Cardiopulmonary exercise testing is a real-time predictor of functional capacity and thus is used as a pre-operative tool to measure physiological fitness and predict outcomes. Renal failure is associated with exercise intolerance and transplantation is transformational in terms of quality of life, longevity and healthcare cost. Live - related renal donation is increasingly available but whether donation itself carries a long-term health burden has not been previously well established. This study suggests that renal donation is not associated with long-term cardiopulmonary compromise and patients who donate their kidneys recover their previous fitness within 14 weeks.

7.
Clin Transl Sci ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31654487

RESUMO

Bruton's tyrosine kinase (BTK) is a key regulator of B cell receptor and Fc receptor signaling, and a rational therapeutic target for autoimmune diseases. This first-in-human phase I, double-blind, placebo-controlled trial investigated the safety, tolerability, pharmacokinetics (PK), target occupancy, and effects on QT interval of evobrutinib, a highly selective, oral inhibitor of BTK, in healthy subjects. This dose escalation trial consisted of two parts. Part 1 included 48 subjects in 6 ascending dose cohorts (25, 50, 100, 200, 350, and 500 mg) randomized to a single dose of evobrutinib or placebo. Part 2 included 36 subjects in 3 ascending dose cohorts (25, 75, and 200 mg/day) randomized to evobrutinib or placebo once daily for 14 days. Safety and tolerability, as well as PK and target occupancy (total and free BTK in peripheral blood mononuclear cells), were assessed following single and multiple dosing. PK parameters were determined by noncompartmental methods. QT interval was obtained from 12-lead electrocardiogram recordings and corrected for heart rate by Fridericia's method (QTcF). Treatment-emergent adverse events (TEAEs) were mostly mild, occurring in 25% of subjects after single dosing, and 48.1% after multiple dosing. There was no apparent dose relationship regarding frequency or type of TEAE among evobrutinib-treated subjects. Absorption was rapid (time to reach maximum plasma concentration (Tmax ) ~ 0.5 hour), half-life short (~ 2 hours), and PK dose-proportional, with no accumulation or time dependency on repeat dosing. BTK occupancy was dose-dependent, reaching maximum occupancy of > 90% within ~ 4 hours after single doses ≥ 200 mg; the effect was long-lasting (> 50% occupancy at 96 hours with ≥ 100 mg). After multiple dosing, full BTK occupancy was achieved with 25 mg, indicating slow turnover of BTK protein in vivo. Concentration-QTcF analyses did not show any impact of evobrutinib concentration on corrected QT (QTc). In summary, evobrutinib was well-tolerated, showed linear and time-independent PK, induced long-lasting BTK inhibition, and was associated with no prolongation of QT/QTc interval in healthy subjects. Evobrutinib is, therefore, suitable for investigation in autoimmune diseases.

8.
Curr Opin Struct Biol ; 59: 151-158, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521910

RESUMO

RNA structure underpins many essential functions in biology. New chemical reagents and techniques for probing RNA structure in living cells have emerged in recent years. High-throughput, genome-wide techniques such as Structure-seq2 and DMS-MaPseq exploit nucleobase modification by dimethylsulfate (DMS) to obtain complete structuromes, and are applicable to multiple domains of life and conditions. New reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), glyoxal, and nicotinoyl azide (NAz) greatly expand the capabilities of nucleobase probing in cells. Additionally, ribose-targeting reagents in selective 2'-hydroxyl acylation and primer extension (SHAPE) detect RNA flexibility in vivo. These techniques, coupled with crosslinking nucleobases in psoralen analysis of RNA interactions and structures (PARIS), provide new and diverse ways to elucidate RNA secondary and tertiary structure in vivo and genome-wide.

9.
Chemistry ; 25(57): 13099-13103, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31538384

RESUMO

NaBHT (sodium butylated hydroxytoluene), a hindered and soluble base for the efficient arylation of various base-sensitive amines and (hetero)aryl halides has been found to have an unanticipated role as a hydride donor to reduce (hetero)aryl halides and allylic acetates. Mechanistic studies have uncovered that NaBHT, but not BHT, can deliver multiple hydrides through oxidation of the benzylic methyl group in NaBHT to the aldehyde. Further, performing the reduction with NaBHT-d20 has revealed that the redox-active benzylic position is not the only hydride donor site from NaBHT with one hydride in three coming, presumably, from the tert-butyl groups. The reduction works well under mild conditions and, incredibly, only consumes 20 percent of the NaBHT in the process; the remaining 80 percent can be readily recovered in pure form and reused. This, combined with the low cost of the material in ton-scale quantity, makes it practical and attractive for wider use in industry at scale.

10.
J Manag Care Spec Pharm ; 25(10): 1073-1077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556829

RESUMO

Estimating medication adherence through the use of pharmacy claims-based adherence calculations such as medication possession ratio (MPR) and proportion of days covered (PDC) plays a significant role in specialty pharmacy practice. Although MPR and PDC are frequently used in clinical practice, calculation methodologies vary, making meaningful comparisons of adherence rates difficult. In addition, MPR and PDC are increasingly used by insurance companies, pharmacies, accrediting bodies, and drug manufacturers to demonstrate quality differences or clinical benefit across the specialty pharmacy industry. Therefore, recognizing the source and effect of calculation variability is necessary to fully understand reported adherence results. This article highlights the challenges in standardizing adherence methodologies, minimum methodology considerations that should be reported with MPR and PDC results, and key elements to consider when interpreting and applying adherence results. Further, recommendations are provided to promote a more consistent description of calculation methods and to aid pharmacies in adherence measure analysis, interpretation, and application to practice, with a focus on specialty pharmacy programs. A detailed description of methodology as outlined in this article must be provided to ensure reproducibility, external validation, and scientific rigor. In the absence of standardization, specialty pharmacies should be prudent in their use of adherence calculations as a clinical benchmarking tool or comparative quality indicator with outside organizations. Furthermore, specialty pharmacies should consider using current adherence measure calculations to identify and provide targeted interventions to patients with potential adherence problems and strive to better demonstrate ties between adherence measures and direct clinical and cost outcomes. DISCLOSURES: No outside funding supported the writing of this article. Anguiano is a speaker and research consultant for United Therapeutics. The other authors have nothing to disclose.

11.
Enzyme Microb Technol ; 130: 109365, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421722

RESUMO

Layered double hydroxides (LDHs) are cheap materials suitable for immobilization of enzymes. In this study, we prepared Zn/Al-Cl LDHs with different Zn:Al molar ratios for immobilization of the lipase from Pseudomonas cepacia. The best values for activity retention (188%), immobilization efficiency (96%) and hydrolytic activity in organic medium (279 U g-1) were obtained with a molar ratio of Zn:Al of 4:1, a protein loading of 162 mg g-1 and Tris-HCl buffer (10 mmol L-1, pH 7.5) as the solvent for preparing the lipase solution. The immobilized lipase keeps its activity when stored at 4 °C during 30 days. The immobilized lipase gave a conversion of 50% in 1 h for the kinetic resolution of the alcohol rac-1-phenylethanol, with both ees and eep higher than 99% and E higher than 200. In the reutilization study, 30 successive 1-h kinetic resolutions were done with the same batch of immobilized enzyme. For all 30 resolutions, 50% conversion was maintained, with ees and eep higher than 99% and E higher than 200. These are promising results that lay the basis for further studies of immobilization of lipases onto LDHs for applications in organic media.

12.
J Pediatr Gastroenterol Nutr ; 69(5): 539-543, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31335835

RESUMO

OBJECTIVES: Stricturing duodenal Crohn disease (CD) is a rare but serious presentation of CD causing significant morbidity. We aim to provide the first robust incidence data and case studies on this severe presentation in children. METHODS: A regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland was captured over a 19-year period (1999-2018). A retrospective review was conducted on the medical records of all patients together with a review of the available literature and consensus guidelines. Incidence rates for all CD and for duodenal stricturing CD were calculated. RESULTS: A total of 247 new cases of paediatric CD were diagnosed within the study period. Median age at diagnosis was 12.5 years with 62% male predominance. Overall paediatric CD incidence rate was 5.70/100,000/year with a specific duodenal B2 phenotype disease incidence rate of 0.05/100,000/year; representing 0.8% of incident cases at diagnosis. Two incident cases of stricturing duodenal CD presented with systemic symptoms of weight loss, abdominal pain, anorexia, and lethargy, together with persistent vomiting suggestive of obstruction. Both cases partially responded to intensive medical therapy but eventually required laparoscopic gastroduodenostomy. A detailed literature search confirmed there are no paediatric incidence data, guidelines, or case reports relating to duodenal stricture as either a presentation or complication of CD. CONCLUSIONS: Duodenal structuring disease is a rare but serious presentation of CD causing significant morbidity and not currently covered in the paediatric literature or consensus guidelines. Best practice medical and surgical management remain uncertain and require further research.

13.
Methods Mol Biol ; 2009: 169-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31152403

RESUMO

A family of zDHHC protein acyltransferase (PAT) enzymes catalyze the S-palmitoylation of target proteins via a two-step mechanism. The first step involves transfer of palmitate from the palmitoyl-CoA donor to the active site cysteine of the zDHHC PAT enzyme, releasing reduced CoA (CoASH). In the second step, the palmitoyl-PAT intermediate thioester reacts with a cysteine side chain within the target substrate to produce the palmitoylated substrate product or, in the absence of a protein substrate, the palmitoyl-PAT intermediate thioester is hydrolyzed and releases palmitate. Formation and resolution of the palmitoyl-PAT intermediate complex (autopalmitoylation) is measured using a coupled enzyme system that monitors the production of CoASH via reduction of NAD+ by the α-ketoglutarate dehydrogenase complex. This assay can be used to isolate and characterize modulators of autopalmitoylation and is scalable to high-throughput screening (HTS). A second fluorescence-based assay is described that monitors the hydrolysis of the palmitoyl-PAT thioester linked intermediate by thin-layer chromatography using a palmitoyl-CoA analog, BODIPY®-C12:0-CoA, as a substrate. These two assays provide a methodology to quantify the first enzymatic step of the two-step zDHHC PAT reaction.

14.
Int J Biol Macromol ; 137: 442-454, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254575

RESUMO

LipMF3 is a new lipase isolated from a metagenomic library derived from a fat-contaminated soil. It belongs to the lipase subfamily I.1 and has identities of 68% and 67% with lipases of Chromobacterium violaceum and C. amazonense, respectively. Genes encoding LipMF3 and its cognate foldase, LifMF3, were cloned and co-expressed in Escherichia coli. The highest hydrolytic activity of purified Lip-LifMF3 was at 40 °C and pH 6.5. Under these conditions, the highest activity was against tributyrin (1650 U mg-1), but it also had high activity against olive oil (862 U mg-1). It was stable in hydrophilic organic solvents (25%, v/v in water) with residual activity around 100% after 24 h. It also showed stability over a wide pH range (5.5 to 11) with residual activity above 80% after 24 h. Lip-LifMF3 was immobilized by covalent bonding onto Immobead 150P and by adsorption onto Sepabeads FP-BU. The latter preparation gave the best results, producing 94% conversion after 5 h for the synthesis of ethyl oleate and a 90% enantiomeric excess of the product (R)­1­phenylethyl acetate for the kinetic resolution of (R,S)­1­phenyl­1­ethanol. The results obtained in this work provide a basis for the development of applications of Lip-LifMF3 in biocatalysis.

15.
Blood ; 134(3): 304-316, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31043425

RESUMO

Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGVHD and to better classify graft-versus-host disease (GVHD) syndromes but have not been validated in patients <18 years of age. The objectives of this prospective multi-institution study were to determine: (1) whether the NIH-CC could be used to diagnose pediatric cGVHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGVHD and L-aGVHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGVHD and L-aGVHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years of age before conditioning and prospectively followed them for 1 year posttransplant for development of cGVHD. Centers justified their cGVHD diagnosis according to the NIH-CC using central review and a study adjudication committee. A total of 28.2% of reported cGVHD cases was reclassified, usually as L-aGVHD, following study committee review. Similar incidence of cGVHD and L-aGVHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGVHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GVHD and peripheral blood grafts are major risk factors for cGVHD and L-aGVHD, with recipients ≥12 years of age being at risk for cGVHD. Applying the NIH-CC in pediatrics is feasible and reliable; however, further refinement of the criteria specifically for children is needed.

16.
Chemistry ; 25(26): 6508-6512, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30972856

RESUMO

We report a general and rapid chemoselective Kumada-Tamao-Corriu (KTC) cross-coupling of aryl bromides in the presence of chlorides or triflates with functionalized Grignard reagents at 0 °C in 15 min by using Pd-PEPPSI-IPentCl (C4). Nucleophiles and electrophiles (or both) can contain Grignard-sensitive functional groups (-CN, -COOR, etc.). Control experiments together with DFT calculations suggest that transmetallation is rate limiting for the selective cross-coupling of Br in the presence of Cl/OTf with functionalized Grignard reagents. One-pot sequential KTC/KTC cross-couplings with bromo-chloro arenes have been demonstrated for the first time. We also report the one-pot sequential KTC/Negishi cross-couplings using C4 showcasing the versatility of this methodology.

17.
Braz J Microbiol ; 50(3): 619-624, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31001795

RESUMO

Burkholderia contaminans LTEB11 is a Gram-negative betaproteobacterium isolated as a contaminant of a culture in mineral medium supplemented with vegetable oil. Here, we report the genome sequence of B. contaminans LTEB11, identifying and analyzing the genes involved in its lipolytic machinery and in the production of other biotechnological products.


Assuntos
Burkholderia/genética , Genoma Bacteriano , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biotecnologia , Burkholderia/classificação , Burkholderia/enzimologia , Burkholderia/metabolismo , Esterases/genética , Esterases/metabolismo , Lipase/genética , Lipase/metabolismo , Análise de Sequência de DNA
18.
Ann Intern Med ; 170(6): 429, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30884511
19.
Adv Biochem Eng Biotechnol ; 169: 27-50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828754

RESUMO

In this review, we describe our experience in building a pilot-scale packed-bed solid-state fermentation (SSF) bioreactor, with provision for intermittent mixing, and the use of this bioreactor to produce pectinases and lipases by filamentous fungi. We show that, at pilot scale, special attention must be given to several aspects that are not usually problematic when one works with laboratory-scale SSF bioreactors. For example, it can be a challenge to produce large amounts of inoculum if the fungus does not sporulate well. Likewise, at larger scales, the air preparation system needs as much attention as the bioreactor itself. Sampling can also be problematic if one wishes to avoid disrupting the bed structure. In the fermentations carried out in the pilot bioreactor, when the substrate bed contained predominantly wheat bran, the bed shrank away from the walls, providing preferential flow paths for the air and necessitating agitation of the bed. These problems were avoided by using beds with approximately 50% of sugarcane bagasse. We also show how a mathematical model that describes heat and water transfer in the bed can be a useful tool in developing appropriate control schemes. Graphical Abstract.


Assuntos
Reatores Biológicos , Fermentação , Fungos/enzimologia , Microbiologia Industrial/instrumentação , Fungos/crescimento & desenvolvimento , Temperatura Alta , Modelos Teóricos , Saccharum/microbiologia , Água/química
20.
Clin Transl Sci ; 12(5): 459-469, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30920122

RESUMO

Sorafenib is an oral multikinase inhibitor approved for the treatment of differentiated thyroid carcinoma (DTC), renal cell carcinoma, and hepatocellular carcinoma. In the phase III DECISION trial in patients with DTC, sorafenib exposure and the incidence of some adverse events (AEs) were higher than in previous trials; therefore, we analyzed exposure-response relationships, including progression-free survival (PFS) and selected AEs in patients with DTC. A novel, stratified prediction-corrected visual predictive check (pc-VPC) was developed to show robustness of the exposure-response relationships. Time-to-event simulations confirmed the benefit of the recommended dosing schedule of 800 mg/day: initial doses of 800 mg/day were associated with the highest PFS, whereas lower doses (600 or 400 mg/day) were associated with improved tolerability but reduced PFS. A simulated dose-reduction strategy of 800 mg/day for an initial two cycles followed by dose reductions seemed likely to maintain efficacy while possibly mitigating selected AEs (e.g., diarrhea and hand-foot skin reactions).

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