Academic literacy study at the School of Veterinary Sciences of the National University of La Plata

Cuando nos referimos a alfabetización académica, hacemos referencia a los conocimientos necesarios para aprender en la universidad. Habiéndose realizado una evaluación diagnóstica en el curso de Patología General Veterinaria, se estudió esta problemática en los cursos de segundo año de la carrera de Medicina Veterinaria de la Facultad de Ciencias Veterinarias de la UNLP. Los objetivos del estudio incluyeron conocer qué importancia se da en los cursos de segundo año a la lectura y a la escritura, indagar en las ideas de los docentes al respecto, analizar las actividades de lectoescritura propuestas a los estudiantes y conocer las dificultades que éstos enfrentan ante la lectura y escritura de textos académicos. Para ello se analizaron las planificaciones y evaluaciones curriculares de cada curso, relatos de clases y textos escritos por estudiantes. Se realizaron observaciones de clase y se encuestó a docentes y estudiantes de segundo año. Los resultados muestran qué actividades de lectura y escritura están presentes, tanto en el curriculum práctico como en el formal, hallándose las actividades de escritura preponderantemente en la instancia de evaluación. Las encuestas docentes revelan ideas en transición entre la postura que no reconoce responsabilidad de la universidad en la alfabetización académica y la que sí lo hace. Las encuestas a estudiantes revelaron múltiples dificultades en la lectura, mientras que el análisis de sus escritos mostró dificultades en la escritura. El conocimiento de la situación actual permitirá diseñar proyectos de intervención tendientes a mejorarla, facilitando el proceso de incorporación de los estudiantes a la cultura académica.Academic literacy refers to the knowledge required for learning in college. Taken into account a previous diagnostic study in the Veterinary General Pathology course, in the present work we performed an evaluation of the academic literacy in the remaining courses of second year of the Veterinary Medicine Career, School of Veterinary Sciences, UNLP. Our objectives were to know the relevance given in the courses to reading and writing, to inquire into the teacher conceptions about the academic literacy, to analyze the literacy activities proposed, and to know the challenges they should go through during reading and writing academic texts. Here we analyze planning and evaluation of each course, class descriptions and texts written by students. Class observations and surveys directed to teachers and second-year students were made. The results showed that reading and writing activities are present in the practical curriculum as in the formal one. The writing activities are predominantly present in the evaluations. Surveys directed to teachers reveal teachers that recognize responsibility of the university in the academic literacy and teachers who do not. In addition, surveys directed to students revealed many difficulties in reading, while the analysis of writing showed some difficulties. Knowledge of the current situation will allow designing intervention projects aimed to facilitating the process of incorporation of students to the academic culture.Facultad de Ciencias Veterinaria

Academic literacy study at the School of Veterinary Sciences of the National University of La Plata

Cuando nos referimos a alfabetización académica, hacemos referencia a los conocimientos necesarios para aprender en la universidad. Habiéndose realizado una evaluación diagnóstica en el curso de Patología General Veterinaria, se estudió esta problemática en los cursos de segundo año de la carrera de Medicina Veterinaria de la Facultad de Ciencias Veterinarias de la UNLP. Los objetivos del estudio incluyeron conocer qué importancia se da en los cursos de segundo año a la lectura y a la escritura, indagar en las ideas de los docentes al respecto, analizar las actividades de lectoescritura propuestas a los estudiantes y conocer las dificultades que éstos enfrentan ante la lectura y escritura de textos académicos. Para ello se analizaron las planificaciones y evaluaciones curriculares de cada curso, relatos de clases y textos escritos por estudiantes. Se realizaron observaciones de clase y se encuestó a docentes y estudiantes de segundo año. Los resultados muestran qué actividades de lectura y escritura están presentes, tanto en el curriculum práctico como en el formal, hallándose las actividades de escritura preponderantemente en la instancia de evaluación. Las encuestas docentes revelan ideas en transición entre la postura que no reconoce responsabilidad de la universidad en la alfabetización académica y la que sí lo hace. Las encuestas a estudiantes revelaron múltiples dificultades en la lectura, mientras que el análisis de sus escritos mostró dificultades en la escritura. El conocimiento de la situación actual permitirá diseñar proyectos de intervención tendientes a mejorarla, facilitando el proceso de incorporación de los estudiantes a la cultura académica.Academic literacy refers to the knowledge required for learning in college. Taken into account a previous diagnostic study in the Veterinary General Pathology course, in the present work we performed an evaluation of the academic literacy in the remaining courses of second year of the Veterinary Medicine Career, School of Veterinary Sciences, UNLP. Our objectives were to know the relevance given in the courses to reading and writing, to inquire into the teacher conceptions about the academic literacy, to analyze the literacy activities proposed, and to know the challenges they should go through during reading and writing academic texts. Here we analyze planning and evaluation of each course, class descriptions and texts written by students. Class observations and surveys directed to teachers and second-year students were made. The results showed that reading and writing activities are present in the practical curriculum as in the formal one. The writing activities are predominantly present in the evaluations. Surveys directed to teachers reveal teachers that recognize responsibility of the university in the academic literacy and teachers who do not. In addition, surveys directed to students revealed many difficulties in reading, while the analysis of writing showed some difficulties. Knowledge of the current situation will allow designing intervention projects aimed to facilitating the process of incorporation of students to the academic culture.Facultad de Ciencias Veterinaria

TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer.

Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher's exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher's exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers

Analisi in silico della proteina CDKL5

Questo elaborato di laurea descrive l'analisi in silico della proteina Cyclin-Dependent Kinase-Like 5 (CDKL5). CDKL5 è coinvolta in processi di sviluppo neuronale, infatti mutazioni che alterano la funzione di questa proteina portano come risultato fenotipico ad anomalie nel sistema nervoso. Dato che non esiste una struttura cristallizzata rappresentativa di questa proteina, per prima cosa è stato creato un modello tridimensionale putativo rappresentativo della stessa. Oltre alla suddivisione in subdomini e la ricerca di siti funzionali, ottenuti grazie ad un multiallienamento strutturale con altri domini chinasici meglio conosciuti, il modello è stato caratterizzato da vari punti di vista, come ad esempio la conservazione e la superficie elettrostatica. Inoltre è stato possibile effettuare mutagenesi in silico in maniera da capire come le varianti naturali per un singolo amminoacido riscontrate in natura siano differenti da un punto di vista strutturale rispetto alla proteina wild type. Per alcune di queste mutazioni è stato possibile dare una spiegazione di come queste differenze strutturali si riflettano in differenze a livello funzionale. Infine, lo studio della lunga coda C-terminale, della quale ancora poco è noto in letteratura, ne ha permesso un'iniziale caratterizzazione funzionale

Beyond monogenic diseases: a first collection and analysis of digenic diseases

In the next generation sequencing era many bioinformatics tools have been developed for assisting scientists in their studies on the molecular basis of genetic diseases, often with the aim of identifying the pathogenic variants. As a consequence, in the last decades more than one hundred new disease-gene associations have been discovered. Nevertheless, the genetic basis of many genetic diseases yet remains undisclosed. It has been shown that many diseases considered as monogenic with an imperfect genotype-phenotype correlation or incomplete penetrance are, on the contrary, caused or modulated by more than one mutated gene, meaning that they are in fact oligogenic. Current bioinformatics methods used for identifying pathogenic variants are trained and fine-tuned for identifying a single variant responsible of a disease. This monogenic-oriented approach cannot be used to explore the impact of combinations of variants in different genes on the complexity and genetic heterogeneity of rare diseases. Digenic diseases are the simplest form of oligogenic disease and thus they can provide a conceptual bridge between monogenic and the poorly understood polygenic diseases.The ambition of this thesis is to collect and analyse digenic data, introducing this topic in the bioinformatics field where digenic diseases are still an unexplored branch. This can be divided in two steps: the first consists in the creation of a central repository containing detailed information on digenic diseases; the second is an analysis of their peculiarities, using machine learning methods for studying subclasses of digenic effects.In the first step we developed DIDA (DIgenic diseases DAtabase), a novel database that provides for the first time a curated collection of genes and associated variants involved in digenic diseases. Detailed information related to the digenic mechanism have been manually mined from the medical literature. All instances in DIDA were also assigned to two sub classes of digenic effects, annotated as true digenic (both genes are required for developing the disease) and composite classes (one gene is sufficient to produce the disease phenotype, the second one alters it or change significantly the age of onset).In the second step, we hypothesized that the digenic effect may be related to some biological properties characterizing digenic combinations. Using machine learning methods, we show that a set of variant, gene and higher-level features can differentiate between the true digenic and composite classes with high accuracy. Moreover, we show that a digenic effect decision profile, extracted from the predictive model, motivates why an instance is assigned to either of the two classes.Together, our results show that digenic disease data generates novel insights, providing a glimpse into the oligogenic realm.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects

Motivation: There are now many predictors capable of identifying the likely phenotypic effects of single nucleotide variants (SNVs) or short in-frame Insertions or Deletions (INDELs) on the increasing amount of genome sequence data. Most of these predictors focus on SNVs and use a combination of features related to sequence conservation, biophysical, and/or structural properties to link the observed variant to either neutral or disease phenotype. Despite notable successes, the mapping between genetic variants and their phenotypic effects is riddled with levels of complexity that are not yet fully understood and that are often not taken into account in the predictions, despite their promise of significantly improving the prediction of deleterious mutants. Results: We present DEOGEN, a novel variant effect predictor that can handle both missense SNVs and in-frame INDELs. By integrating information from different biological scales and mimicking the complex mixture of effects that lead from the variant to the phenotype, we obtain significant improvements in the variant-effect prediction results. Next to the typical variant-oriented features based on the evolutionary conservation of the mutated positions, we added a collection of protein-oriented features that are based on functional aspects of the gene affected. We cross-validated DEOGEN on 36 825 polymorphisms, 20 821 deleterious SNVs, and 1038 INDELs from SwissProt. The multilevel contextualization of each (variant, protein) pair in DEOGEN provides a 10% improvement of MCC with respect to current state-of-the-art tools.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Predicting digenic variant effects with DIDA

info:eu-repo/semantics/publishe

Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects

info:eu-repo/semantics/publishe

DIDA: A first database on digenic diseases

info:eu-repo/semantics/publishe

Predicting oligogenic effects using digenic disease data

info:eu-repo/semantics/publishe