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Maltais R.,Endocrinology and Nephrology Unit | Maltais R.,Laval University | Trottier A.,Endocrinology and Nephrology Unit | Trottier A.,Laval University | And 12 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2015

The chemical synthesis of four stereoisomers (compounds 5a-d) of 16β-(m-carbamoylbenzyl)-estradiol, a potent reversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), and two intermediates (compounds 3a and b) was performed. Assignment of all nuclear magnetic resonance signals confirmed the stereochemistry at positions 13, 16 and 17. Nuclear overhauser effects showed clear correlations supporting a C-ring chair conformation for 5a and b and a C-ring boat conformation for 5c and d. These compounds were tested as 17β-HSD1 inhibitors and to assess their proliferative activity on estrogen-sensitive breast cancer cells (T-47D) and androgen-sensitive prostate cancer cells (LAPC-4). Steroid derivative 5a showed the best inhibitory activity for the transformation of estrone to estradiol (95, 82 and 27%, at 10, 1 and 0.1. μM, respectively), but like the other isomers 5c and d, it was found to be estrogenic. The intermediate 3a, however, was weakly estrogenic at 1. μM, not at all at 0.1. μM, and showed an interesting inhibitory potency on 17β-HSD1 (90, 59 and 22%, at 10, 1 and 0.1. μM, respectively). As expected, no compound showed an androgenic activity. The binding modes for compounds 3a and b, 5a-d and CC-156 were evaluated from molecular modeling. While the non-polar interactions were conserved for all the inhibitors in their binding to 17β-HSD1, differences in polar interactions and in binding conformational energies correlated to the inhibitory potencies. © 2015 Elsevier Ltd.


Ruiz-Fernandez D.,University of Alicante | Marin-Alonso O.,University of Alicante | Soriano-Paya A.,University of Alicante | Garcia-Perez J.D.,Ibis Bio
The Scientific World Journal | Year: 2014

The growing demand for physical rehabilitation processes can result in the rising of costs and waiting lists, becoming a threat to healthcare services' sustainability. Telerehabilitation solutions can help in this issue by discharging patients from points of care while improving their adherence to treatment. Sensing devices are used to collect data so that the physiotherapists can monitor and evaluate the patients' activity in the scheduled sessions. This paper presents a software platform that aims to meet the needs of the rehabilitation experts and the patients along a physical rehabilitation plan, allowing its use in outpatient scenarios. It is meant to be low-cost and easy-to-use, improving patients and experts experience. We show the satisfactory results already obtained from its use, in terms of the accuracy evaluating the exercises, and the degree of users' acceptance. We conclude that this platform is suitable and technically feasible to carry out rehabilitation plans outside the point of care. © 2014 Daniel Ruiz-Fernandez et al.


Nigg M.,University Laval | Laroche J.,University Laval | Laroche J.,Ibis Bio | Landry C.R.,University Laval | Bernier L.,University Laval
G3: Genes, Genomes, Genetics | Year: 2015

Fungal dimorphism is a complex trait and our understanding of the ability of fungi to display different growth morphologies is limited to a small number of model species. Here we study a highly aggressive dimorphic fungus, the ascomycete Ophiostoma novo-ulmi, which is a model in plant pathology and the causal agent of Dutch elm disease. The two growth phases that this fungus displays, i.e., a yeast phase and mycelial phase, are thought to be involved in key steps of disease development. We used RNAseq to investigate the genome-wide gene expression profiles that are associated with yeast and mycelial growth phases in vitro. Our results show a clear molecular distinction between yeast and mycelial phase gene expression profiles. Almost 12% of the gene content is differentially expressed between the two phases, which reveals specific functions related to each growth phase. We compared O. novo-ulmi transcriptome profiles with those of two model dimorphic fungi, Candida albicans and Histoplasma capsulatum. Few orthologs showed similar expression regulation between the two growth phases, which suggests that, globally, the genes associated with these two life forms are poorly conserved. This poor conservation underscores the importance of developing specific tools for emerging model species that are distantly related to the classical ones. Taken together, our results provide insights into transcriptome regulation and molecular specificity in O. novo-ulmi and offer a new perspective for understanding fungal dimorphism. © 2015 Nigg et al.


Ouellet Y.H.,Ibis Bio | Ndiaye C.T.,Ibis Bio | Gagne S.M.,Ibis Bio | Sebilo A.,Ibis Bio | And 6 more authors.
Journal of Inorganic Biochemistry | Year: 2016

As part of the machinery to acquire, internalize and utilize heme as a source of iron from the host, some bacteria possess a canonical heme oxygenase, where heme plays the dual role of substrate and cofactor, the later catalyzing the cleavage of the heme moiety using O2 and electrons, and resulting in biliverdin, carbon monoxide and ferrous non-heme iron. We have previously reported that the Escherichia coli O157:H7 ChuS protein, which is not homologous to heme oxygenases, can bind and degrade heme in a reaction that releases carbon monoxide. Here, we have pursued a detailed characterization of such heme degradation reaction using stopped-flow UV-visible absorption spectrometry, the characterization of the intermediate species formed in such reaction by EPR spectroscopy and the identification of reaction products by NMR spectroscopy and Mass spectrometry. We show that hydrogen peroxide (in molar equivalent) is the key player in the degradation reaction, at variance to canonical heme oxygenases. While the initial intermediates of the reaction of ChuS with hydrogen peroxide (a ferrous keto π neutral radical and ferric verdoheme, both identified by EPR spectroscopy) are in common with heme oxygenases, a further and unprecedented reaction step, involving the cleavage of the porphyrin ring at adjacent meso-carbons, results in the release of hematinic acid (a monopyrrole moiety identified by NMR spectroscopy), a tripyrrole product (identified by Mass spectrometry) and non-heme iron in the ferric oxidation state (identified by EPR spectroscopy). Overall, the unprecedented reaction of E. coli O157:H7 ChuS provides evidence for a novel heme degradation activity in a Gram-negative bacterium. © 2015 Elsevier Inc. All rights reserved.


PubMed | University of Alicante and Ibis Bio
Type: | Journal: TheScientificWorldJournal | Year: 2014

The growing demand for physical rehabilitation processes can result in the rising of costs and waiting lists, becoming a threat to healthcare services sustainability. Telerehabilitation solutions can help in this issue by discharging patients from points of care while improving their adherence to treatment. Sensing devices are used to collect data so that the physiotherapists can monitor and evaluate the patients activity in the scheduled sessions. This paper presents a software platform that aims to meet the needs of the rehabilitation experts and the patients along a physical rehabilitation plan, allowing its use in outpatient scenarios. It is meant to be low-cost and easy-to-use, improving patients and experts experience. We show the satisfactory results already obtained from its use, in terms of the accuracy evaluating the exercises, and the degree of users acceptance. We conclude that this platform is suitable and technically feasible to carry out rehabilitation plans outside the point of care.


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