262,362 research outputs found
24-Nor-allobetulins possess strong α-glucosidase inhibitory activity
No full textA series of 24-nor-allobetulin derivatives holding 3β-hydroxy-, oxime, methoxyoxime, lactame and 4-bromobenzylidene substituents have been synthesized and their differences in the NMR spectra were studied in detail. It was revealed that 3-oxo-24-nor-allobetulin loses selectivity in the reaction of oximation and forms a mixture of Z/E oximes (and methoxyoximes) in contract to the related derivatives of native scaffold (that forms only E-isomers). The screening of α-glucosidase inhibitory activity revealed that 24-nor-allobetulins are more active than allobetulins. The lead 3-oxo-24-nor-allobetulin with IC50 0.49 µM was more than 60-fold and 500-fold active than acarbose and 3-oxo-allobetulin, respectively. We can conclude that the removal of the C-24 methyl group significantly increased the antidiabetic effect and 24-nor-allobetulins should be identified as the new and promising scaffolds as α-glucosidase inhibitors on the basis of triterpenoids.</p
Dynamic augmentation of SCORM pre-authored course materials with adaptive links to supplementary resources
No full textIn a SCORM compliant courseware, content and the pedagogic approach to be taken are predefined by the course author. As a consequence, users are unable to learn according to their preferences, and implicitly they will all encounter the same learning experience. Recent attempts to personalise learning in SCORM often resulted in either modifying or substituting SCORM specification elements. Nonetheless, SCORM is a widely-used solution to interoperability problems. For this reason, this work focuses on supplementing SCORM rather than redefining it. This is accomplished by dynamically associating each pre-authored learning material in a SCORM package with adaptive links to relevant supplementary resources upon delivery. As a result, we have developed a Personalised Link Service (PLS) to deliver these links into user’s SCORM-compliant learning environment. In this paper, we present the design of a PLS authoring architecture which enables the automatic generation of a concept map from a SCORM package and consequently links to alternative learning resources, and a PLS run-time service oriented architecture which delivers these alternative resources, alongside the SCORM defined resources, according to a user model. We demonstrate the feasibility of our architecture by implementing a service to support a simple notion of a user model (Preferred Learning style)
Temporal monitoring of the nor-1 (aflD) gene of Aspergillus flavus in relation to aflatoxin B-1 production during storage of peanuts under different water activity levels
No full textAims: A relative quantification system (RQ-PCR) was used to monitor the
correlations between the activity of the nor-1 (=aflD) gene of Aspergillus
flavus using real-time PCR in relation to phenotypic aflatoxin B-1 (AFB(1))
production and populations of A. flavus in stored peanuts at three water
activity levels (a(w), 0.95, 0.90 and 0.85) for 6 weeks. Methods and Results:
Real-time PCR was used to amplify the nor-1 gene (target gene), and benA56
(beta-tubulin gene) used as a control gene. Expression of three structural
genes, nor-1 (=aflD), ver-1 (=aflM), and omtA (=aflP), and the regulatory gene
aflR of the aflatoxin biosynthetic pathway were also assayed. There were
significant differences between nor-1 gene expression at the three a(w) levels;
higher expression at 0.90 a(w) in weeks 1-3, when compared to 0.95. In contrast,
in the driest treatment (0.85 a(w)) none or very low nor-1 expression occurred.
The populations of A. flavus colony-forming units (CFUs g(-1)) increased over
time with the highest at 0.95 a(w). Highest AFB(1) production was at 0.90 and
0.95 a(w) from weeks 3-6. A(w) had a significant effect on aflR transcription at
0.95 a(w) over the 6-week period, while at 0.90 a(w), only in the last 2 weeks.
Conclusions: Correlations between different factors showed that log AFB(1) x log
CFUs, log AFB(1) x a(w), and log CFUs x a(w) were statistically significant,
while log CFUs x RQ-PCR and RQ-PCR x a(w) were not. The AflR gene may not have
an important role in the regulation of nor-1 expression in food matrices (e. g.
peanuts). Significance and Impact of the study: Determination of correlations
between nor-1 expression and aflatoxin production by A. flavus in raw peanuts
under different a(w) levels could be helpful to predict potential risk of
aflatoxin production during storage of this hygroscopic food product and
minimize contamination with the AFB(1)
Expressão, purificação e caracterização estrutural inicial do receptor órfão nuclear NOR-1 de rato
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em BiotecnologiaO receptor órfão nuclear NOR-1 é um membro uma superfamília composta por um grupo de fatores de transcrição envolvidos na resposta a esteróides, ácidos graxos, ácidos retinóicos, e outras moléculas lipofílicas. A subfamília de NOR-1está implicada na proliferação celular, diferenciação, apoptose, condrosarcomas, processos inflamatórios e de aterogênese. O receptor NOR-1 é um órfão de ligante atuando sobre a transativação gênica. Até hoje, nenhum ligante é conhecido para este receptor. A estrutura tridimensional do domínio LBD homólogo, Nurr1, foi resolvida através de técnicas de cristalografia. Surpreendentemente, a estrutura não apresentou a cavidade típica de interação com ligantes, nem um sítio de ligação clássico para co-fatores. Com a finalidade de estudar estruturalmente um outro membro da subfamília NR4, dois de seus domínios AF-1 e LBD foram os focos deste trabalho, realizando-se experimentos de expressão, purificação, e análises preliminares de estrutura por UV e Dicroísmo Circular (CD). O domínio LBD de NOR-1 foi purificado com alto grau de pureza, rendendo 3 mg/litro de meio de cultivo e sua estrutura foi avaliada por UV e CD apresentando um conteúdo de a-hélices de 52 % compatível a estrutura 3D do seu homólogo Nurr1. A desnaturação térmica, monitorada por UV e CD, sugere um correto enovelamento para proteína LBD recombinante
Control of Aflatoxin Production of Aspergillus flavus and Aspergillus parasiticus Using RNA Silencing Technology by Targeting aflD (nor-1) Gene.
No full textAspergillus flavus and Aspergillus parasiticus are important pathogens of cotton,
corn, peanuts and other oil-seed crops, producing toxins both in the field and
during storage. We have designed three siRNA sequences (Nor-Ia, Nor-Ib, Nor-Ic)
to target the mRNA sequence of the aflD gene to examine the potential for using
RNA silencing technology to control aflatoxin production. Thus, the effect of
siRNAs targeting of two key genes in the aflatoxin biosynthetic pathway, aflD
(structural) and aflR (regulatory gene) and on aflatoxin B(1 )(AFB(1)), and
aflatoxin G(1) (AFG(1)) production was examined. The study showed that Nor-Ib
gave a significant decrease in aflD mRNA, aflR mRNA abundance, and AFB(1)
production (98, 97 and 97% when compared to the controls) in A. flavus NRRL3357,
respectively. Reduction in aflD and aflR mRNA abundance and AFB(1 )production
increased with concentration of siRNA tested. There was a significant inhibition
in aflD and AFB(1) production by A. flavus EGP9 and AFG(1 )production by A.
parasiticus NRRL 13005. However, there was no significant decrease in AFG(1)
production by A. parasiticus SSWT 2999. Changes in AFB(1) production in relation
to mRNA levels of aflD showed a good correlation (R = 0.88; P = 0.00001);
changes in aflR mRNA level in relation to mRNA level of aflD also showed good
correlation (R = 0.82; P = 0.0001). The correlations between changes in aflR and
aflD gene expression suggests a strong relationship between these structural and
regulatory genes, and that aflD could be used as a target gene to develop
efficient means for aflatoxin control using RNA silencing technolo
Nor-triterpenoids from the fruiting bodies of <i>Ganoderma lucidum</i> and their inhibitory activity against FAAH
No full textTwo new nor-triterpenoids ganodrenol A (1), B (2), and a new natural product ganodrenol C (3), along with three known nor-triterpenoids (4–6) were isolated from the fruiting bodies of Ganoderma lucidum. The chemical structures of these isolates were determined by 1 D and 2 D NMR, HRESIMS, and X-ray crystallography analysis. The inhibitory effects of isolated triterpenoids (1–6) against FAAH were evaluated by an in vitro assay, and compound 4 showed an inhibition rate of 70.27%. In addition, the cytotoxic effect of compounds (1–6) was evaluated against LOVO, MCF-7, and RAW264.7 cells, which displayed no significant cytotoxicity.</p
Anàlisi de l'expressió de NOR-1 en les cèl·lules musculars llises i de la seva implicació en la proliferació cel·lular
No full text[cat] Dado que las células musculares lisas vasculares (CMLV) juegan un papel clave en el desarrollo de la aterosclerosis, conocer los genes que regulan la proliferación y migración de estas células pude conducir a encontrar nuevas dianas farmacológicas para tratar esta patología. Nosotros descubrimos que el receptor nuclear huérfano NOR-1/NR4A3 se encuentra expresado en CMLV estimuladas con suero y distintos mitógenos. Entre los componentes del suero cabe destacar como principal inductor de NOR-1 las lipoproteínas de baja densidad (LDL) y en menor medida las lipoproteínas de muy baja densidad (VLDL). Por otra parte, distintos factores de crecimiento en especial la trombina y el PDGF, ambos generados en eventos trombóticos, también inducen la expresión de este origen. Los mecanismos moleculares que regulan este proceso son complejos; participan proteínas G sensibles a la toxina pertusis, incrementos en la concentración citosólica de calcio y activación de distintas proteínas quinasas como la PKC, la PKA y MAPKs como la ERK y la p38 MAPK. Estas quinasas pueden activar directa o indirectamente (dependiendo del tipo y contexto celular), al factor de transcripción CREB. Nosotros observamos por primera vez que las LDL son capaces de inducir la activación de CREB y que este mecanismo es dependiente tanto del calcio como de la PKC. CREB se une al promotor de NOR-1 mediante su interacción con tres cajas CRE; además CREB es esencial en la actividad de este promotor, tal como analizamos mediante la cotransfección de un dominante negativo de CREB así como eliminando las cajas CRE por mutagénesis dirigida. Para evaluar el papel de NOR-1 en la proliferación celular, usamos oligodeoxinucleótidos (ODN) antisentido para inhibir la expresión de este gen. Analizamos de manera independiente dos ODN los cuales disminuyen de forma específica a la expresión de NOR-1. En estas condiciones, estos ODN inhiben la síntesis de DNA inducida tanto por el suero como por las LDL. Además, mediante citometría de flujo in vitro de reparación tisular, el bloqueo de la expresión de NOR-1 produce una inhibición de la capacidad de las células para recuperar el área dañada. De todos estos resultados se pude concluir que NOR-1 regula la proliferación de las CMLV y que por tanto podría ser una nueva diana terapéutica en las patologías en que este involucrada una excesiva proliferación de estas células
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Figure 3.6: NOR gates: (a) 2-input NOR gate; (b) Truth table; (c) 3- and 4-input NOR gates.
No full textFigure 3.6: NOR gates: (a) 2-input NOR gate; (b) Truth table; (c) 3- and 4-input NOR gates. The animation shows all possible values of inputs to the 2-input NOR gate and the output each set of input values generates
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