Socio-Cultural Gender Norms and Economic Barriers in The Context of Rural High School Girls’ Dropout in Bangladesh: A Qualitative Study

While attending high schools, in Bangladesh, rural school girls face the pressure of socio-cultural gender norms and the barriers of economic deprivation. This paper aims to analyze the multifaceted connection between gender norms and economic deprivation of families in rural Bangladesh; and how the dynamics of the connection affect high school girls’ opportunities of further education. The paper identifies the major factors that lead girls to drop out of school. In-depth qualitative interview sessions were conducted with 5 rural high school dropout girls. The analysis incorporates both thematic and narrative analyses. The study finds that gender norms, socioeconomic realities, deprivation and poverty work as barriers; and affect girl’s future education by restricting girl’s opportunities and social mobility with the support of discriminatory gender norms and practices. Parents compromise on girls’ education by giving gender norms a priority. Instead of encouraging girls’ future education parents tend to ensure their daughter’s future in an early marriage. Among the financially challenged families, girls’ domestic duties are prioritized over their aspiration of getting education. Most parents are concerned about the sexual security/chastity of their girls, which also force girls to drop out of high schools. Few parents/guardians who encourage and support girls’ education usually take the initiative to bring changes by resisting social norms that obstruct and limit girls’ opportunities. The paper concludes that in the context of persistent socio-cultural gender norms, resistance against regressive gender ideologies and social norms are needed to bring positive changes in gender socialization

Misrepresentation Act 1967 (United Kingdom) sebagai model undang-undang salah nyata di Malaysia

Perundangan salah nyata dalam kontrak di Malaysia dikawal oleh seksyen 18 Akta Kontrak 1950. Walau bagaimanapun, disebabkan Akta ini telah lama digubal dan tidak dibuat pindaan, maka terdapat beberapa kelemahan yang perlu diberi perhatian. Dalam usaha untuk membuat penambahbaikan terhadap perundangan tersebut, maka Misrepresentation Act 1967 yang merupakan akta yang mengawal perbuatan salah nyata dalam kontrak di United Kingdom dilihat sesuai untuk dijadikan sebagai rujukan. Akta ini mengandungi enam seksyen yang merangkumi peruntukan remedi salah nyata serta pengecualian liabiliti salah nyata dalam kontrak. Sebelum tercetusnya Misrepresentation Act 1967, perbuatan salah nyata dalam kontrak di United Kingdom dikawal oleh common law dan ekuiti. Penggubalan Misrepresentation Act 1967 memperlihatkan kemajuan dalam sistem perundangan di United Kingdom dalam menangani perbuatan salah nyata dalam kontrak dan boleh dijadikan model bagi pindaan undang-undang salah nyata di Malaysia. Dengan mengguna pakai metode analisis kandungan melalui pendekatan perbandingan, artikel ini bertujuan melihat perkembangan Mispresentation Act 1967 serta signifikan perubahan akta tersebut di United Kingdom. Kajian mendapati penggubalan Misrepresentation Act 1967 menampakkan penyusunan semula undang-undang salah nyata dalam kontrak di United Kingdom yang lebih berstruktur dan sistematis, khususnya dalam aspek remedi dan pengecualian liabiliti salah nyata

Bioinformatics insights into the genes and pathways on severe COVID-19 pathology in patients with comorbidities

Background: Coronavirus disease (COVID-19) infection is known for its severe clinical pathogenesis among individuals with pre-existing comorbidities. However, the molecular basis of this observation remains elusive. Thus, this study aimed to map key genes and pathway alterations in patients with COVID-19 and comorbidities using robust systems biology approaches.Methods: The publicly available genome-wide transcriptomic datasets from 120 COVID-19 patients, 281 patients suffering from different comorbidities (like cardiovascular diseases, atherosclerosis, diabetes, and obesity), and 252 patients with different infectious diseases of the lung (respiratory syncytial virus, influenza, and MERS) were studied using a range of systems biology approaches like differential gene expression, gene ontology (GO), pathway enrichment, functional similarity, mouse phenotypic analysis and drug target identification.Results: By cross-mapping the differentially expressed genes (DEGs) across different datasets, we mapped 274 shared genes to severe symptoms of COVID-19 patients or with comorbidities alone. GO terms and functional pathway analysis highlighted genes in dysregulated pathways of immune response, interleukin signaling, FCGR activation, regulation of cytokines, chemokines secretion, and leukocyte migration. Using network topology parameters, phenotype associations, and functional similarity analysis with ACE2 and TMPRSS2—two key receptors for this virus-we identified 17 genes with high connectivity (CXCL10, IDO1, LEPR, MME, PTAFR, PTGS2, MAOB, PDE4B, PLA2G2A, COL5A1, ICAM1, SERPINE1, ABCB1, IL1R1, ITGAL, NCAM1 and PRKD1) potentially contributing to the clinical severity of COVID-19 infection in patients with comorbidities. These genes are predicted to be tractable and/or with many existing approved inhibitors, modulators, and enzymes as drugs.Conclusion: By systemic implementation of computational methods, this study identified potential candidate genes and pathways likely to confer disease severity in COVID-19 patients with pre-existing comorbidities. Our findings pave the way to develop targeted repurposed therapies in COVID-19 patients

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients

First Comprehensive In Silico

GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases

Induced pluripotent stem cell modelling of HLHS underlines the contribution of dysfunctional NOTCH signalling to impaired cardiogenesis

Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype. Our data indicate that HLHS-iPSC have a reduced ability to give rise to mesodermal, cardiac progenitors and mature cardiomyocytes and an enhanced ability to differentiate to smooth muscle cells. HLHS-iPSC-derived cardiomyocytes are characterised by a lower beating rate, disorganised sarcomeres and sarcoplasmic reticulum and a blunted response to isoprenaline. Whole exome sequencing of HLHS fibroblasts identified deleterious variants in NOTCH receptors and other genes involved in the NOTCH signalling pathway. Our data indicate that the expression of NOTCH receptors was significantly downregulated in HLHS-iPSC-derived cardiomyocytes alongside NOTCH target genes confirming downregulation of NOTCH signalling activity. Activation of NOTCH signalling via addition of Jagged peptide ligand during the differentiation of HLHS-iPSC restored their cardiomyocyte differentiation capacity and beating rate and suppressed the smooth muscle cell formation. Together, our data provide firm evidence for involvement of NOTCH signalling in HLHS pathogenesis, reveal novel genetic insights important for HLHS pathology and shed new insights into the role of this pathway during human cardiac developmen

Socio-Cultural Gender Norms and Economic Barriers in the Context of Rural High School Girls' Dropout in Bangladesh: A Qualitative Study

While attending high schools, in Bangladesh, rural school girls face the pressure of socio-cultural gender norms and the barriers of economic deprivation. This paper aims to analyze the multifaceted connection between gender norms and economic deprivation of families in rural Bangladesh; and how the dynamics of the connection affect high school girls' opportunities of further education. The paper identifies the major factors that lead girls to drop out of school. In-depth qualitative interview sessions were conducted with 5 rural high school dropout girls. The analysis incorporates both thematic and narrative analyses. The study finds that gender norms, socioeconomic realities, deprivation and poverty work as barriers; and affect girl's future education by restricting girl's opportunities and social mobility with the support of discriminatory gender norms and practices. Parents compromise on girls' education by giving gender norms a priority. Instead of encouraging girls' future education parents tend to ensure their daughter's future in an early marriage. Among the financially challenged families, girls' domestic duties are prioritized over their aspiration of getting education. Most parents are concerned about the sexual security/chastity of their girls, which also force girls to drop out of high schools. Few parents/guardians who encourage and support girls' education usually take the initiative to bring changes by resisting social norms that obstruct and limit girls' opportunities. The paper concludes that in the context of persistent socio-cultural gender norms, resistance against regressive gender ideologies and social norms are needed to bring positive changes in gender socialization

Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is −8.5 kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >−9.20 kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients. Keywords: Curcumin analogue, EGFR genetic, Molecular docking, Novel compound, Mutation