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31.
Sofia Sisay Gareth Pryce Samuel J. Jackson Carolyn Tanner Ruth A. Ross Gregory J. Michael David L. Selwood Gavin Giovannoni David Baker 《PloS one》2013,8(10)
Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2
tm1Zim) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2
Dgen) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2
tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some transgenic/gene knockout and other studies on low-EAE susceptibility backgrounds with inconsistent disease course and susceptibility. 相似文献
32.
Sandro L. Pereira Mário Gr?os Ana Sofia Rodrigues Sandra I. Anjo Rui A. Carvalho Paulo J. Oliveira Ernest Arenas Jo?o Ramalho-Santos 《PloS one》2013,8(12)
The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/differentiation. 相似文献
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Geromy G. Moore Jacalyn L. Elliott Rakhi Singh Bruce W. Horn Joe W. Dorner Eric A. Stone Sofia N. Chulze German G. Barros Manjunath K. Naik Graeme C. Wright Kerstin Hell Ignazio Carbone 《PLoS pathogens》2013,9(8)
Aflatoxins are produced by Aspergillus flavus and A. parasiticus in oil-rich seed and grain crops and are a serious problem in agriculture, with aflatoxin B1 being the most carcinogenic natural compound known. Sexual reproduction in these species occurs between individuals belonging to different vegetative compatibility groups (VCGs). We examined natural genetic variation in 758 isolates of A. flavus, A. parasiticus and A. minisclerotigenes sampled from single peanut fields in the United States (Georgia), Africa (Benin), Argentina (Córdoba), Australia (Queensland) and India (Karnataka). Analysis of DNA sequence variation across multiple intergenic regions in the aflatoxin gene clusters of A. flavus, A. parasiticus and A. minisclerotigenes revealed significant linkage disequilibrium (LD) organized into distinct blocks that are conserved across different localities, suggesting that genetic recombination is nonrandom and a global occurrence. To assess the contributions of asexual and sexual reproduction to fixation and maintenance of toxin chemotype diversity in populations from each locality/species, we tested the null hypothesis of an equal number of MAT1-1 and MAT1-2 mating-type individuals, which is indicative of a sexually recombining population. All samples were clone-corrected using multi-locus sequence typing which associates closely with VCG. For both A. flavus and A. parasiticus, when the proportions of MAT1-1 and MAT1-2 were significantly different, there was more extensive LD in the aflatoxin cluster and populations were fixed for specific toxin chemotype classes, either the non-aflatoxigenic class in A. flavus or the B1-dominant and G1-dominant classes in A. parasiticus. A mating type ratio close to 1∶1 in A. flavus, A. parasiticus and A. minisclerotigenes was associated with higher recombination rates in the aflatoxin cluster and less pronounced chemotype differences in populations. This work shows that the reproductive nature of the population (more sexual versus more asexual) is predictive of aflatoxin chemotype diversity in these agriculturally important fungi. 相似文献
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Sofia Benfeito Catarina Oliveira Pedro Soares Carlos Fernandes Tiago Silva José Teixeira Fernanda Borges 《Mitochondrion》2013,13(5):427-435
The therapeutic potential of natural phenolic antioxidants in human diseases associated with oxidative damage has received great attention to date. Appraisal of literature evidences that, in general, antioxidant therapy has enjoyed relative successes in preclinical studies but little benefits in human intervention studies or clinical trials. In fact, despite the huge, largely untapped potential therapeutic benefit of natural phenolic antioxidants, such as vitamins, non-flavonoid and flavonoid compounds, they appear not to be suitable drug candidates. The problem may be related, among others, to their non-drug-likeness properties. Though controversial the results obtained so far confirm the importance of exploring phenolic natural systems as safe templates for the design of new antioxidants. To support the assumption an outlook of the lead structural optimization process to improve ADME properties was given by means of natural hydroxycinnamic acids as a case study. The optimization of drug physicochemical properties and the development of appropriate delivery antioxidant systems can provide in the next future a way out to attain effective therapeutic antioxidant agents. 相似文献
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Joana Dias Sofia Martins Susana Carvalho Olinda Marques Ana Antunes 《Endocrinología y nutrición》2013,60(5):245-248
Background/objectiveMauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS.Materials and methodsA retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed.ResultsFrom a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13–17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia.ConclusionsAlthough MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control. 相似文献
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Cláudia S. Nóbrega Manolis Matzapetakis Sofia R. Pauleta 《Biomolecular NMR assignments》2013,7(2):311-314
Lipid-modified azurin (Laz) from Neisseria gonorrhoeae is a type 1 copper protein proposed to be the electron donor to several enzymes involved in the resistance mechanism to reactive oxygen and nitrogen species. Here we report the backbone and side-chain resonance assignment of Laz in the reduced form, which has been complete at 97 %. The predicted secondary structure indicates that this protein belongs to the azurin subfamily of type 1 copper proteins. 相似文献
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