Growth of Manufacturing Employment in Pakistan: A Comparative Analysis of Punjab and Sindh (Preliminary Results)

Provincial economic disparities in Pakistan are often discussed in political circles. Recently, these disparities have also caught the attention of economic planners. I However, very few professional studies have analysed the issue due to paucity of inter-provincial data. Moreover, the existing studies base their analysis on cross-sectional data obtained from various sources and cannot be used to analyse disparities in economic growth and its sources.2 The purpose of present paper is to provide an initial contribution to the analysis of provincial economic changes in Pakistan. Employment growths in the manufacturing sectors of Punjab and Sindh are analysed for the period 1980-87. Regional differences in employment growth are usually attributed to differences in industrial structure and also to differential impacts of regional-specific influences (infra-structure, policies, political situation, etc.) that determine competitiveness of a region. The present study analyses these two components of growth for Sindh and Punjab in order to explain differential growth in these provinces. Such an analysis is useful for provincial planning as it may help plan for a balanced growth

Autosomal-Recessive Hearing Impairment due to Rare Missense Variants within <i>S1PR2</i>

The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2