Reflexiones sobre el diseño de una asignatura de educación en el grado de ingeniería informática

La informática es una de las áreas de conocimiento que más rápido están cambiando. Estos cambios requieren una formación continua, especializada y adaptativa. Más allá de las salidas profesionales como docente en enseñanza reglada, que requieren de formación especializada, existe la necesidad de formación y actualización de profesionales de diversos ámbitos en nuevas herramientas, procedimientos y conocimientos por parte de personas que conozcan la parte técnica y que a su vez sean capaces de realizar una formación de alta calidad. La educación es una salida profesional con cada vez más peso y que no se suele tratar en los estudios de Grado en Ingeniería Informática. Este póster presenta a la comunidad unas reflexiones sobre cómo debería ser una asignatura de educación de la informática que formara parte del plan de estudios del grado.Informatics is one of the fastest changing areas of knowledge. These changes require continuous, specialized and adaptive training. Beyond the profesional opportunities as a teacher in formal education, which require specialized training, there is a need for training and updating of professionals in different fields into new tools, procedures and knowledge by people who know the technical side but who also are capable of providing high quality training. Education is, therefore, an increasingly in-demand professional opportunity for graduates in the Degree of Informatics Engineering, but it is not usually addressed into the curriculum. This poster aims to share with the community some reflections on how it should be a subject of informatics education as part of the curriculum of the undergraduate degree

Propionate fermentative genes of the gut microbiome decrease in inflammatory bowel disease

Changes in the gut microbiome have been associated with inflammatory bowel disease. A protective role of short chain fatty acids produced by the gut microbiota has been suggested as a causal mechanism. Nevertheless, multi-omic analyses have failed to identify a clear link between changes in specific taxa and disease states. Recently, metagenomic analyses unveiled that gut bacterial species have a previously unappreciated genomic diversity, implying that a geno-centric approach may be better suited to identifying the mechanisms involved. Here, we quantify the abundance of terminal genes in propionate-producing fermentative pathways in the microbiome of a large cohort of healthy subjects and patients with inflammatory bowel disease. The results show that propionate kinases responsible for propionate production in the gut are depleted in patients with Crohn's disease. Our results also indicate that changes in overall species abundances do not necessarily correlate with changes in the abundances of metabolic genes, suggesting that these genes are not part of the core genome. This, in turn, suggests that changes in strain composition may be as important as changes in species abundance in alterations of the gut microbiome associated with pathological conditions.Funding: This work was funded by project BFU2017-86378-P from the Spanish Ministry of Science and Innovation (MCINN) to F.d.l.C

A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.Funding: This work was supported by grants from the Spanish Ministry of Science and Technology (grant BFU2017-86378-P) (to FdlC), Fondo Investigaciones Sanitarias (PI18/01304) (to JC), Gilead Fellowship programme 2018 (to JC)

Structural basis of direct and inverted DNA sequence repeat recognition by helix-turn-helix transcription factors

Some transcription factors bind DNA motifs containing direct or inverted sequence repeats. Preference for each of these DNA topologies is dictated by structural constraints. Most prokaryotic regulators form symmetric oligomers, which require operators with a dyad structure. Binding to direct repeats requires breaking the internal symmetry, a property restricted to a few regulators, most of them from the AraC family. The KorA family of transcriptional repressors, involved in plasmid propagation and stability, includes members that form symmetric dimers and recognize inverted repeats. Our structural analyses show that ArdK, a member of this family, can form a symmetric dimer similar to that observed for KorA, yet it binds direct sequence repeats as a non-symmetric dimer. This is possible by the 180° rotation of one of the helix-turn-helix domains. We then probed and confirmed that ArdK shows affinity for an inverted repeat, which, surprisingly, is also recognized by a non-symmetrical dimer. Our results indicate that structural flexibility at different positions in the dimerization interface constrains transcription factors to bind DNA sequences with one of these two alternative DNA topologies.FUNDING This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness [BIO2016-77883-C2-2- P and FIS2015-72574-EXP (AEI/FEDER, EU), to D.R.B., BFU2017-86378-P to F.dlC.] and by the Spanish Ministry of Science (MCI/AEI/FEDER,UE) [PGC2018-093885- BI00 and PID2021-122164NB-I00 to G.M., PID2020- 117028GB-I00 to D.R.B. and PID2019-110216GB-I00 to R. F-L.]. Conflict of interest statement. None declared. ACKNOWLEDGEMENTS Structural experiments were performed at the BL16 beamline at the ESRF European Synchrotron Radiation Facility (France) with the collaboration of EMBL staff, at the PROXIMA beamline at the SOLEIL Synchrotron (France) with the collaboration of SOLEIL staff, and at the XALOC beamline at the ALBA Synchrotron Radiation Facility (Spain) with the collaboration of ALBA staff. We are grateful to Carlos Revilla and Matilde Cabezas at the University of Cantabria for their technical assistance. Author contributions: R.F-L., F.dlC. and G.M. designed the research; L.G-M., R.R. and I.dC. performed the research; R.F-L., D.R.B., F.dlC and G.M analysed the data; and R.F.L., F.dlC. and G.M. wrote the manuscript. All authors reviewed the results and approved the final version of the manuscript

The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer—A GEICO Study

Genomic instability; Machine learningInestabilidad genómica; Aprendizaje automáticoInestabilitat genòmica; Aprenentatge automàticGenomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87–159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.This research was partially funded by GVA Grants “Subvencions per a la realització de projectes d’i+d+i desenvolupats per grups d’investigació emergents (GV/2020/158)” and “Ayudas para la contratación de personal investigador en formación de carácter predoctoral” (ACIF/2016/008) and “Beca de investigación traslacional Andrés Poveda 2020” from GEICO group. This study was awarded the Prize “Antonio Llombart Rodriguez-FINCIVO 2020” from the Royal Academy of Medicine of the Valencian Community

Conjugation inhibitors effectively prevent plasmid transmission in natural environments

Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance.Acknowledgments: The work performed by the de la Cruz research group was supported by the European Union Seventh Framework Program (FP7-HEALTH-2011-single-stage) “Evolution and Transfer of Antibiotic Resistance” (EvoTAR), grant agreement number 282004. The work performed by C.P.-G. and M.G. was supported by Ph.D. fellowships funded by the University of Cantabria. The work performed by the B.G.-Z. laboratory was supported by The EFFORT project (www.effort-against-amr.eu) FP7-KBBE-2013-7, grant agreement 613754

COPLA, a taxonomic classifier of plasmids

Background: Plasmids are mobile genetic elements, key in the dissemination of antibiotic resistance, virulence determinants and other adaptive traits in bacteria. Obtaining a robust method for plasmid classification is necessary to better understand the genetics and epidemiology of many pathogens. Until now, plasmid classification systems focused on specific traits, which limited their precision and universality. The definition of plasmid taxonomic units (PTUs), based on average nucleotide identity metrics, allows the generation of a universal plasmid classification scheme, applicable to all bacterial taxa. Here we present COPLA, a software able to assign plasmids to known and novel PTUs, based on their genomic sequence. Results: We implemented an automated pipeline able to assign a given plasmid DNA sequence to its cognate PTU, and assessed its performance using a sample of 1000 unclassified plasmids. Overall, 41% of the samples could be assigned to a previously defined PTU, a number that reached 63% in well-known taxa such as the Enterobacterales order. The remaining plasmids represent novel PTUs, indicating that a large fraction of plasmid backbones is still uncharacterized. Conclusions: COPLA is a bioinformatic tool for universal, species-independent, plasmid classification. Offered both as an automatable pipeline and an open web service, COPLA will help bacterial geneticists and clinical microbiologists to quickly classify plasmids.This work was supported by the Spanish Ministry of Science and Innovation [PID2020-117923GB-I00 to FdlC]; the Spanish Ministry of Economy, Industry and Competitiveness [DI-17-09164 to SR-S]; and USA Centers for Disease Control and Prevention [200-2019-06679 to FdlC]. The funders had no role in the design of the study, nor in the collection, analysis, and interpretation of data, nor in writing the manuscript included in this submission

Patterns of Differentially Expressed circRNAs in Human Thymocytes

Circular RNAs (circRNAs) are suggested to play a discriminative role between some stages of thymocyte differentiation. However, differential aspects of the stage of mature single-positive thymocytes remain to be explored. The purpose of this study is to investigate the differential expression pattern of circRNAs in three different development stages of human thymocytes, including mature single-positive cells, and perform predictions in silico regarding the ability of specific circRNAs when controlling the expression of genes involved in thymocyte differentiation. We isolate human thymocytes at three different stages of intrathymic differentiation and determine the expression of circRNAs and mRNA by RNASeq. We show that the differential expression pattern of 50 specific circRNAs serves to discriminate between the three human thymocyte populations. Interestingly, the downregulation of RAG2, a gene involved in T-cell differentiation in the thymus, could be simultaneously controlled by the downregulation of two circRNASs (hsa_circ_0031584 and hsa_circ_0019079) through the hypothetical liberation of hsa-miR-609. Our study provides, for the first time, significant insights into the usefulness of circRNAs in discriminating between different stages of thymocyte differentiation and provides new potential circRNA-miRNA-mRNA networks capable of controlling the expression of genes involved in T-cell differentiation in the thymus.This work was financed by grants from the Spanish Ministry of Science, Innovation and Universities (MCIU)(RTI2018- 093330-B-I00; MCIU/FEDER, EU), Ramón Areces Foundation (CIVP19S7917); Autonomous Community of Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM); the Spanish Association Against Cancer (AECC, 2018; PROYE18054PIRI); and the Spanish Ministry (Juan de la Cierva Grant IJCI-2016-29155). Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged.S

Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort

[Background and Aims] Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. [Methods] A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. [Results] None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. [Conclusions] Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.This study was supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). CIBERehd and Red Genómica del Cáncer are funded by Instituto de Salud Carlos III

Immobilization of Aspergillus niger lipase on chitosan-coated magnetic nanoparticles using two covalent-binding methods

Aspergillus niger lipase immobilization by covalent binding on chitosan-coated magnetic nanoparticles (CMNP), obtained by one-step co-precipitation, was studied. Hydroxyl and amino groups of support were activated using glycidol and glutaraldehyde, respectively. Fourier transform infrared spectrometry, high-resolution transmission electron microscopy and thermogravimetric analysis confirmed reaction of these coupling agents with the enzyme and achievement of a successful immobilization. The derivatives showed activities of 309.5 ± 2.0 and 266.2 ± 2.8 U (g support)(-1) for the CMNP treated with glutaraldehyde and with glycidol, respectively. Immobilization enhanced the enzyme stability against changes of pH and temperature, compared to free lipase. Furthermore, the kinetic parameters K m and V max were determined for the free and immobilized enzyme. K m value quantified for enzyme immobilized by means of glutaraldehyde was 1.7 times lowers than for free lipase. High storage stability during 50 days was observed in the immobilized derivatives. Finally, immobilized derivatives retained above 80% of their initial activity after 15 hydrolytic cycles. The immobilized enzyme can be applied in various biotechnological processes involving magnetic separation.Fil: Osuna, Yolanda. Universidad Autónoma de Coahuila; MéxicoFil: Sandoval, José. Universidad Autónoma de Coahuila; MéxicoFil: Saade, Hened. Centro de Investigación en Química Aplicada; MéxicoFil: López, Raúl G.. Centro de Investigación en Química Aplicada; MéxicoFil: Martinez, José L.. Universidad Autónoma de Coahuila; MéxicoFil: Colunga, Edith M.. Universidad Autónoma de Coahuila; MéxicoFil: de la Cruz, Gabriela. Universidad Autónoma de Coahuila; MéxicoFil: Segura, Elda P.. Universidad Autónoma de Coahuila; MéxicoFil: Arevalo, Fernando Javier. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zon, María Alicia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez, Hector. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ilyina, Anna. Universidad Autónoma de Coahuila; Méxic