LITERACY EDUCATION URGENCY FOR CENTENNIAL GENERATION IN INDUSTRIAL REVOLUTION 4.0

When talking about children’s abilities, they indeed cannot be separated from their educational or training background. Moreover, he has entered the working age that must have productivity in his work, especially at this time, where the era has entered the industrial revolution 4.0. The industrial revolution 4.0 is marked by the development of digitalization in various lines of life. On the one hand, the industrial revolution 4.0 had many positive impacts. However, on the other hand, as the McKinsey Global Institute states that as a result of the 4.0 industrial revolution in the next five years, there will be 52.6 million jobs that will decline and even disappear. This certainly will be a challenge for the centennial generation (children born from 1996-2011) at this time, which they have to survive with the existing conditions and situations. This paper will discuss several factors that describe and address issues such as what is meant by the centennial generation, literacy, and the urgency of literacy education for the centennial generation in the digital age. According to authors, thi is essential to discuss, given the increasingly rapid development and technological progress resulting in the loss of much work.

Identidication of Genes in Hearing Loss With or Without Inter-Locus Heterogeniety

Deafness is one of the most common human genetic disorders and exhibits high genetic heterogeneity. The prevalence of hearing loss is very high; about 5% people suffer from hearing loss worldwide. The estimated incidence of hearing loss is approximately 7 to 8 individuals per 1000 in Pakistan. Genetic hearing loss is known to have high inter- and intrafamilial heterogeneity. There are more than 64 known genes with thousands of mutations for non-syndromic recessively inherited hearing loss. Some genes involved in moderate to severe hearing loss have been identified in Pakistani population. However, many individuals with this phenotype do not currently have a genetic diagnosis which emphasizes the need for continued research. Participants from seventeen families were included in the current study and most of affected individuals in these families had moderate to severe degree of hearing loss. The criteria of ascertaining a family included multiple affected individuals, consanguinity of parents, a recessive mode of inheritance and less than profound degree of hearing loss. Homozygosity mapping and targeted custom capture were carried out for known deafness genes. This was followed by exome sequencing. Known as well as novel variants were identified in the deafness genes. Variants in SLC26A4 were the most common in this cohort. Pathogenic variants in GJB2, TMC1, MYO15A, CLDN14, TMPRSS3 and SLC52A3 were also found to segregate in the participating families. In a family PKSN3, exome data revealed a variant in a novel hearing loss gene DFNBX2. It was a frameshift mutation which was found segregating with moderate to severe degree of hearing loss. The variant was predicted to introduce a premature stop codon which may lead to nonsense mediated decay of the mRNA. DFNBX2 was localized to the tips and at the base of the sterocilia in the cochlea as determined by immunohistochemistry in mice. DFNBX2 also co-localized with tubulin in the inner ear of mice which suggests the role of this protein in contributing to the cytoskeleton of these cells. SNP genotyping was performed for six families, HLAI-22, HLAM01, HLGM02, HLAM03, HLAM12 and HLAM13 for which no pathogenic variant was identified in the exome data. For family HLAI-22, a linkage interval was mapped on chromosome 12. A noncoding iv variant in 5′ UTR of a gene DFNBX3 was identified within the linkage interval. DFNBX3 has a well-established role in the development of the inner ear, though variants of this gene have not been described in hearing loss. It is expressed in the inner ear at embryonic stages and the expression is continued after the development of the inner ear structures. The variant was predicted to disrupt the two regulatory RNA motifs, terminal oligopyrimidine tract (TOP) and the internal ribosome entry sites of the gene. Therefore, the variant can affect posttranslational modifications and may cause unregulated translation. Intra-familial heterogeneity was observed in three families HLAM08, HLAM01 and HLAM12 which made the identification of causative variant difficult. In family HLAM08 known variant in TMPRSS3 was found causative for two of three affected individuals hearing loss. In a few affected individuals of families HLAM01 and HLAM12, founder mutations of SLC26A4 were identified which could account for their hearing loss. However, no single region of shared homozygosity was identified for remaining four affected individuals of family HLAM01 and six affected individual of family HLAM12 which indicates further genetic heterogeneity in these families. In families HLGM02, HLAM03 and HLAM13, single linkage intervals were mapped on chromosomes 1, 19 and 9 respectively by SNP genotyping. However, no variants were identified after sequencing the uncovered exons located in the respective linkage intervals. These families in which the current study failed to yield the pathogenic variants can be investigated further using whole genome sequencing on several affected and unaffected individuals. This will be helpful to identify pathogenic variants and will broaden the understanding of moderate to severe hearing loss.