ABSTRACT
Despite the importance of interregional skilled migration to regional development, few studies have explored its spatial spillover effects and their changes over time. Thus, employing the Spatial Durbin Model, we investigate the presence of regional spillovers of skilled migration at both national and sub-national levels in China. Especially, we focus on the regional difference and change in the spatial spillover. Although our results confirm positive spillover effects at the national level due to the strong mobility characteristic of skilled migrants, developed regions benefit more from spillovers of skilled migration than developing regions, and such effects are divergent in different regions over time. Our findings also indicate that changes in spatial spillovers among regions are closely associated with the mobility of economic factors in geography. Theoretically, by considering the spatial effects of skilled migration on the innovation output of recipient regions, we extend the labour economics literature into geographical economic agglomeration, especially innovation economic geography. Methodologically, we examine the spatial effects at both national and sub-national levels, and capture the spatial externalities; we also apply Maximum Likelihood estimation to assess the endogeneity issues to understand the mechanisms of spillover change over time. The study can be of significance for municipalities in the policy-making of attracting talents and promoting regional innovation.
ABSTRACT
BACKGROUND: Defects in the glycosylphosphatidylinositol (GPI) biosynthesis pathway can result in a group of congenital disorders of glycosylation known as the inherited GPI deficiencies (IGDs). To date, defects in 22 of the 29 genes in the GPI biosynthesis pathway have been identified in IGDs. The early phase of the biosynthetic pathway assembles the GPI anchor (Synthesis stage) and the late phase transfers the GPI anchor to a nascent peptide in the endoplasmic reticulum (ER) (Transamidase stage), stabilizes the anchor in the ER membrane using fatty acid remodeling and then traffics the GPI-anchored protein to the cell surface (Remodeling stage). RESULTS: We addressed the hypothesis that disease-associated variants in either the Synthesis stage or Transamidase+Remodeling-stage GPI pathway genes have distinct phenotypic spectra. We reviewed clinical data from 58 publications describing 152 individual patients and encoded the phenotypic information using the Human Phenotype Ontology (HPO). We showed statistically significant differences between the Synthesis and Transamidase+Remodeling Groups in the frequencies of phenotypes in the musculoskeletal system, cleft palate, nose phenotypes, and cognitive disability. Finally, we hypothesized that phenotypic defects in the IGDs are likely to be at least partially related to defective GPI anchoring of their target proteins. Twenty-two of one hundred forty-two proteins that receive a GPI anchor are associated with one or more Mendelian diseases and 12 show some phenotypic overlap with the IGDs, represented by 34 HPO terms. Interestingly, GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities. CONCLUSIONS: IGDs associated with Synthesis and Transamidase+Remodeling stages of the GPI biosynthesis pathway have significantly different phenotypic spectra. GPC2 and GPC6 genes may represent a GPI target of general disruption to the GPI biosynthesis pathway that contributes to the phenotypes of some IGDs.
