Search results for: Vanesa Lotersztein

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

Procedia PDF Downloads 92

Authors: Guerrero Ramírez Sandra, Ramos Salinas Norma Maricela, Muriel Amezcua Vanesa

Abstract:

This article presents the beginning of a wider study that intends to demonstrate how within organizations of the automotive industry from the city of Querétaro. Knowledge management and technological management are required, as well as people’s initiative and the interaction embedded at the interior of it, with the appropriate environment that facilitates information conversion with wide information technologies management (ITM) range. A company was identified for the pilot study of this research, where descriptive and inferential research information was obtained. The results of the pilot suggest that some respondents did noted entity the knowledge management topic, even if staffs have access to information technology (IT) that serve to enhance access to knowledge (through internet, email, databases, external and internal company personnel, suppliers, customers and competitors) data, this implicates that there are Knowledge Management (KM) problems. The data shows that academically well-prepared organizations normally do not recognize the importance of knowledge in the business, nor in the implementation of it, which at the end is a great influence on how to manage it, so that it should guide the company to greater in sight towards a competitive strategy search, given that the company has an excellent technological infrastructure and KM was not exploited. Cultural diversity is another factor that was observed by the staff.

Keywords: Knowledge Management (KM), Technological Knowledge Management (TKM), Technology Information Management (TI), access to knowledge

Procedia PDF Downloads 498