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Martin-Banderas L.,University of Seville | Holgado M.A.,University of Seville | Duran-Lobato M.,University of Seville | Infante J.J.,Bionaturis | Fernandez-Arevalo M.,University of Seville
Current Medicinal Chemistry | Year: 2016

Lysosomal storage diseases (LSDs) comprise a group of rare inherited chronic syndromes that cause deficiency of specific native enzymes within the lysosomes. The macromolecular compounds that are usually catabolized by lysosomal enzymes are accumulated within these organelles, causing progressive damage to tissues, skeleton and organs and, in several cases, the central nervous system (CNS). The damage caused by substrate accumulation finally results in physical deterioration, functional impairment and potential death. Up to date, the most promising therapy for most LSDs is enzyme-replacement therapy (ERT), which provides patients with the corresponding active enzyme. However, these enzymes do not have enough stability in blood, the treatment must be therefore periodically administrated by i.v. infusion under medical supervision, and immunogenicity issues are frequent. In addition, affected areas within the CNS, where the blood-brain barrier (BBB) is a major obstacle, cannot be reached by the enzymes. Nanotechnology can provide useful carriers to successfully protect and preserve enzymes, and transport them through the BBB towards brain locations. Several strategies based on targeting specific receptors on the BBB have led to nanoparticles that successfully carry sensitive molecules to the brain. Then, the main LSDs are described and a thorough review of nanotechnology strategies +for brain delivery studied up to date is presented. © 2016 Bentham Science Publishers.

PubMed | French Institute of Health and Medical Research, Biobide, Bionaturis, Donogh OBrien BioConsulting and Sanofi S.A.
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015

The formation of new vessels in the tumor, termed angiogenesis, is essential for primary tumor growth and facilitates tumor invasion and metastasis. Hypoxia has been described as one trigger of angiogenesis. Indeed, hypoxia, which is characterized by areas of low oxygen levels, is a hallmark of solid tumors arising from an imbalance between oxygen delivery and consumption. Hypoxic conditions have profound effects on the different components of the tumoral environment. For example, hypoxia is able to activate endothelial cells, leading to angiogenesis but also thereby initiating a cascade of reactions involving neutrophils, smooth muscle cells, and fibroblasts. In addition, hypoxia directly regulates the expression of many genes for which the role and the importance in the tumoral environment remain to be completely elucidated. In this study, we used a method to selectively label sialoglycoproteins to identify new membrane and secreted proteins involved in the adaptative process of endothelial cells by mass spectrometry-based proteomics. We used an in vitro assay under hypoxic condition to observe an increase of protein expression or modifications of glycosylation. Then the function of the identified proteins was assessed in a vasculogenesis assay in vivo by using a morpholino strategy in zebrafish. First, our approach was validated by the identification of sialoglycoproteins such as CD105, neuropilin-1, and CLEC14A, which have already been described as playing key roles in angiogenesis. Second, we identified several new proteins regulated by hypoxia and demonstrated for the first time the pivotal role of GLUT-1, TMEM16F, and SDF4 in angiogenesis.

Infante J.J.,Bionaturis | Law G.L.,University of Washington | Wang I.-T.,University of Pennsylvania | Chang H.-W.E.,Cornell University | Young E.T.,University of Washington
Molecular Microbiology | Year: 2011

Transcriptional regulation of Snf1-dependent genes occurs in part by histone-acetylation-dependent binding of the transcription factor Adr1. Analysis of previously published microarray data indicated unscheduled transcription of a large number of Snf1- and Adr1-dependent genes when either the histone H3 or H4 tail was deleted. Quantitative real-time PCR confirmed that the tails were important to preserve stringent transcriptional repression of Snf1-dependent genes when glucose was present. The absence of the tails allowed Adr1 and RNA Polymerase II to bind promoters in normally inhibitory conditions. The promoters escaped glucose repression to a limited extent and the weak constitutive ADH2 transcription induced by deletion of the histone tails was transcription factor- and Snf1-independent. These effects were apparently due to a permissive chromatin structure that allowed transcription in the absence of repression mediated by the histone tails. Deleting REG1, and thus activating Snf1 in the H3 tail mutant enhanced transcription in repressing conditions, indicating that Snf1 and the H3 tail influence transcription independently. Deleting REG1 in the histone H4 tail mutant appeared to be lethal, even in the absence of Snf1, suggesting that Reg1 and the H4 tail have redundant functions that are important for cell viability. © 2011 Blackwell Publishing Ltd.

Rodriguez M.E.,University of Cádiz | Infante J.J.,University of Cádiz | Infante J.J.,Bionaturis | Molina M.,S.L. Sanlucar de Barrameda | And 3 more authors.
Journal of Applied Microbiology | Year: 2010

Aims: To analyse the diversity of wild yeast in spontaneous fermentations of a white wine and to select the most suitable autochthonous starter yeasts. The selected yeasts would be used for inoculation of industrial fermentations in several years. Methods and Results: Yeasts were characterized by applying electrophoretic karyotyping. This technique was chosen because it can reveal the large-scale mutations in the yeast genome induced by gross chromosomal rearrangements. This type of mutation is considered one of the main forces behind the rapid evolution of industrial yeasts. A heterogeneous population of yeast strains was observed in the spontaneous fermentations during two consecutive years. Four of the most abundant strains were isolated and tested for microbiological features of industrial importance. The selected autochthonous strains were used as starter yeasts for the following 7 years. In the majority of these experiences, we obtained homogeneous yeast populations, in which the karyotype of one of the inoculated strains - karyotype V - emerged as clearly dominant. Conclusions: The inoculation of the selected strain with karyotype V and a proper handling of the inoculum scaling-up process led to the substitution of the spontaneous fermentations by controlled fermentations producing a highly satisfactory final product. Significance and Impact of the Study: We monitored the wine yeast population of an industrial system for a total of 9 years. Our work is one of the first examples made at industrial scale showing how molecular techniques can be successfully applied to improve the efficiency of the winemaking process. © 2009 The Authors.

Rodriguez M.E.,University of Cádiz | Infante J.J.,Bionaturis | Molina M.,Bodegas Barbadillo S. L. Sanlucar de Barrameda Cadiz | Rebordinos L.,University of Cádiz | Cantoral J.M.,University of Cádiz
International Journal of Food Microbiology | Year: 2011

The analysis of restriction fragment length polymorphism of mitochondrial DNA (mtDNA-RFLP) has been applied as a test to monitor the abundance of the starter yeast strain during industrial wine fermentations without previous isolation of yeast colonies. For white wine fermentations, we performed a rapid assay consisting in taking a sample of fermenting must, purifying the DNA from harvested cells, and obtaining the restriction patterns by digestion with the endonuclease HinfI. The same protocol, but adding an overnight cultivation step before DNA purification, was also applied to red wine fermentations. The results were compared with those obtained from the subsequent characterisation of strains, for the same samples, by analysis of the electrophoretic karyotype of isolated yeast colonies. In all cases, when the inoculated strain was dominant within the yeast population, the rapid assay anticipated the result by showing the coincidence between the restriction profiles obtained from both total cells and the inoculated strain. The results were obtained at 11 or 23. h after sampling for white- or red-wine fermentations respectively. This method allows a rapid intervention of the wine-producer if the presence of the inoculated yeasts has suffered a sudden decrease in any phase of the fermentation process. © 2010 Elsevier B.V.

Rodriguez M.E.,University of Cádiz | Infante J.J.,Bionaturis | Mesa J.J.,Bodegas Barbadillo S. L. C Luis Eguilar | Rebordinos L.,University of Cádiz | Cantoral J.M.,University of Cádiz
Open Biotechnology Journal | Year: 2013

The flor yeasts (Saccharomyces cerevisiae) form a biofilm, known as flor velum, on the surface of fino-type sherry wine at the end of the alcoholic fermentation. These film-forming yeasts are responsible for the oxidative transformation of alcohol to acetaldehyde, together with other reactions, which produce the characteristic flavours and aromas of these wines. In this study, we examine the enological behaviour of eight flor yeast strains biofilms in biological aging experiments carried out in the laboratory. Strains with identical chromosomal and mitochondrial DNA patterns and the same origin showed a more closely-related enological behaviour. But the kinetics of growth and acetaldehyde accumulation in the wine were found to be strain-dependent. Moreover, some strains were marked by high acetaldehyde accumulation in their pure cultures during the various phases of the biofilm development. These results provide valuable knowledge for planning technical strategies to improve the biological aging process in the sherry wine industry. © Rodríguez et al.

Infante J.J.,Bionaturis | Law G.L.,University of Washington | Young E.T.,University of Washington
Methods in Molecular Biology | Year: 2012

The nucleosome-scanning assay (NuSA) couples isolation of mononucleosomal DNA after micrococcal nuclease (MNase) digestion with quantitative real-time PCR (qPCR) to map nucleosome positions in chromatin. It is a relatively simple, rapid procedure that can produce a high-resolution map of nucleosome location and occupancy and thus is suitable for analyzing individual promoters in great detail. The analysis can also quantify the protection of DNA sequences due to interaction with proteins other than nucleosomes and show how this protection varies when conditions change. When coupled with chromatin immunoprecipitation (ChIP), NuSA can identify histone variants and modifications associated with specific nucleosomes. © 2012 Springer Science+Business Media, LLC.

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By Bionaturis Press|January 12th, 2016|Blog english, Press Releases| BIOMAP is a consortium led by Laboratories Rovy that includes Vivacell Biotechnology Spain, Vaxdyn, and Bionaturis The Feder-Interconecta Programme, via the Centre for the Development of Industrial Technology (CDTI, in Spanish), has granted Bionaturis 572.988 for this biomedicine development initiative ...

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