411 research outputs found
Metasedimentary xenoliths in the lavas of the Timanfaya eruption(1730-1736. Lanzarote, Canary Islands):metamorphism and contamination processes
The xenoliths of dunites and other ultramafic rocks (peridotites ,wherlites..etc) are generated by contact metamorphism from sedimentary rocksproyecto FEDER "Aspectos educativos del volcanismo canario
Ministerio Educación Y Ciencia proyecto BTE2002-04017-Co2-1Peer reviewe
Development of an electroporation procedure for the generation of genetically modified mice using CRISPR/Cas9
Trabajo de fin de Grado. Grado en Biotecnología. Curso académico 2019-2020The house mouse (Mus musculus) has become the main animal model used in biomedical research, because of its physiological and genetical similarity with the human being. Over the last years, the development of the genomic editing tools has led to the generation of genetically modified (GM) mice, entailing great progress in research work.
Within these tools, the discovery and improvement of the CRISPR/Cas9 system has been particularly revolutionary due to its design´s simplicity, efficiency and versatility. Originally described as an adaptive immunity mechanism in bacteria and archaea, it is composed of two elements: the single-read ribonucleic acid (sgRNA) or RNA guide and the endonuclease Cas9. The first one is made up of a 20 nucleotides sequence called CRISPR ribonucleic acid (crRNA), which defines the system’s specificity and is linked to a structural sequence named trans-activating crRNA (tracrRNA). When this hybridizes with the target sequences, the nuclease produces a double-strand break (DSB), activating endogenous mechanisms of DNA repair. This involves the gene disruption, leading to knock-out models; or the insertion of homologous molecules, producing knock-in models.
The current strategy to produce GM mice is based on the microinjection of the CRISPR/Cas9 system components into one of the zygote’s pronuclei and its subsequent transfer to a female´s oviduct. The pronuclear microinjection is a quite slow process that requires expensive and sophisticated equipment and experienced personnel. As an alternative, we propose the use of electroporation to introduce the CRISPR/Cas9 system reagents in embryos and overcome the raised limitations.
Thus, we have checked that the application of high voltage short electrical pulses allows the preservation of zygote’s viability. In addition, these create transient cell membrane pores which sgRNA and Cas9 protein access across. Through the in vitro genotyping process it has been confirmed that these are capable of performing genomic editing on specific locus.
Finally, a specific sgRNA against tyrosinase gene (Tyr), involved in the mouse´s coat color, was designed. Therefore, the generation of albino and/or mosaic mice has allowed us to easily determine the editing and knock-out alleles’ generation efficiency with both techniques. It has been concluded that electroporation is a method as effective as pronuclear microinjection, so it could become its real substitute
Relevance of secretor status genotype and microbiota composition in susceptibility to rotavirus and norovirus infections in humans
Host genetic factors, such as histo-blood group antigens (HBGAs), are associated with susceptibility to norovirus (NoV) and rotavirus (RV) infections. Recent advances point to the gut microbiome as a key player necessary for a viral pathogen to cause infection. In vitro NoV attachment to host cells and resulting infections have been linked to interactions with certain bacterial types in the gut microbiota. We investigated the relationship between host genotype, gut microbiota, and viral infections. Saliva and fecal samples from 35 adult volunteers were analysed for secretor status genotype, the gut microbiota composition by 16S rRNA gene sequencing, and salivary IgA titers to NoV and RV. Higher levels of IgA against NoV and RV were related to secretor-positive status. No significant differences were found between the FUT2 genotype groups, although the multivariate analysis showed a significant impact of host genotype on specific viral susceptibilities in the microbiome composition. A specific link was found between the abundance of certain bacterial groups, such as Faecalibacterium and Ruminococcus spp., and lower IgA titers against NoV and RV. As a conclusion, we can state that there is a link between host genetics, gut microbiota, and susceptibility to viral infections in humans
Back propagation with balanced MSE cost Function and nearest neighbor editing for handling class overlap and class imbalance
The class imbalance problem has been considered a critical factor for designing and constructing the supervised classifiers. In the case of artificial neural networks, this complexity negatively affects the generalization process on under-represented classes. However, it has also been observed that the decrease in the performance attainable of standard learners is not directly caused by the class imbalance, but is also related with other difficulties, such as overlapping. In this work, a new empirical study for handling class overlap and class imbalance on multi-class problem is described. In order to solve this problem, we propose the joint use of editing techniques and a modified MSE cost function for MLP. This analysis was made on a remote sensing data . The experimental results demonstrate the consistency and validity of the combined strategy here proposedPartially supported by the Spanish Ministry of Education and Science under grants CSD2007–00018, TIN2009–14205–C04–04, and by Fundació Caixa Castelló–Bancaixa under grants P1–1B2009–04 and P1–1B2009–45; SDMAIA-010 of the TESJO and 2933/2010 from the UAE
A hybrid method to face class overlap and class imbalance on neural networks and multi-class scenarios
Class imbalance and class overlap are two of the major problems in data mining and machine learning. Several studies have shown that these data complexities may affect the performance or behavior of artificial neural networks. Strategies proposed to face with both challenges have been separately applied. In this paper, we introduce a hybrid method for handling both class imbalance and class overlap simultaneously in multi-class learning problems. Experimental results on five remote sensing data show that the combined approach is a promising method
Interfaces de usuario imaginadas: el camino de ida y vuelta entre la ciencia y la ficción
Memoria ID-0231. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017
Genome-wide search of nucleosome patterns using visual analytics.
[EN]The Burrows-Wheeler transform (BWT) is widely used for the fast alignment of high-throughput sequence data. This method also has potential applications in other areas of bioinformatics, and it can be specially useful for the fast searching of patterns on coverage data from different sources.
We present a nucleosome pattern search method that converts levels of nucleosomal occupancy to a sequence-like format to which BWT searches can be applied. The method is embedded in a nucleosome map browser, 'Nucleosee', an interactive visual tool specifically designed to enhance BWT searches, giving them context and making them suitable for visual discourse analysis of the results. The proposed method is fast, flexible and sufficiently generic for the exploration of data in a broad and interactive way.
The proposed algorithm and visual browser are available for testing at http://cpg3.der.usal.es/nucleosee. The source code and installation packages are also available at https://github.com/rodrigoSantamaria/nucleosee.
Supplementary data are available at Bioinformatics online
Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion
Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1-3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators
Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease
Multiple evidences suggest that mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease via the selective cell death of dopaminergic neurons, such as that which occurs after prolonged exposure to the mitochondrial electron transport chain (ETC) complex I inhibitor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP). However, the effects of chronic MPTP on the ETC complexes and on enzymes of lipid metabolism have not yet been thoroughly determined. To face these questions, the enzymatic activities of ETC complexes and the lipidomic profile of MPTP-treated non-human primate samples were determined using cell membrane microarrays from different brain areas and tissues. MPTP treatment induced an increase in complex II activity in the olfactory bulb, putamen, caudate, and substantia nigra, where a decrease in complex IV activity was observed. The lipidomic profile was also altered in these areas, with a reduction in the phosphatidylserine (38:1) content being especially relevant. Thus, MPTP treatment not only modulates ETC enzymes, but also seems to alter other mitochondrial enzymes that regulate the lipid metabolism. Moreover, these results show that a combination of cell membrane microarrays, enzymatic assays, and MALDI-MS provides a powerful tool for identifying and validating new therapeutic targets that might accelerate the drug discovery process.This research has been supported by grants from the regional Basque Government ITI1454-22 awarded to the “Neurochemistry and Neurodegeneration” consolidated research group and ISCIII Spanish Ministry for Health PI20/00153 and co-funded by the European Union (ERDF “A way to make Europe”), a grant from the Ministry of Economy and Competitiveness (IPT-2011-1205) and Scholarship Program for the Transition from Educational to Occupational Word (UPV-Basque Government)
Land-use change and windstorms legacies drove the recolonization dynamics of laurel forests in Tenerife, Canary islands
Laurel forests are quite relevant for biodiversity conservation and are among the island ecosystems most severely damaged by human activities. In the past, Canary laurel forests have been greatly altered by logging, livestock and agriculture. The remains of laurel forests are currently protected in the Canary Islands (Spain). However, we miss basic information needed for their restoration and adaptive management, such as tree longevity, growth potential and responsiveness to natural and anthropogenic disturbances. Using dendrochronological methods, we studied how forest dynamic is related to land-use change and windstorms in two well-preserved laurel forests on Tenerife Island. Wood cores were collected from over 80 trees per stand at three stands per forest. We used ring-width series to estimate tree ages and calculate annual basal area increments (BAI), cumulative diameter increases, and changes indicative of released and suppressed growth. Twelve tree species were found in all stands, with Laurus novocanariensis, Ilex canariensis and Morella faya being the most common species. Although some individuals were over 100 years old, 61.8%–88.9% of the trees per stand established between 1940 and 1970, coinciding with a post-war period of land abandonment, rural exodus and the onset of a tourism economy. Some trees have shown growth rates larger than 1 cm diameter per year and most species have had increasing BAI trends over the past decades. Strong growth releases occurred after windstorms at both sites, but the effects of windstorms were site-dependent, with the 1958 storm affecting mainly the eastern tip of the island (Anaga massif) and the 1991 storm the western tip (Teno massif). Given the great ability of laurel forest trees to establish after land use cessation and to increase growth after local disturbances such as windstorms, passive restoration may be sufficient to regenerate this habitat in currently degraded areas.12 página
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