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Shear Stress, Mechanosensors, and Atherosclerosis
Published in Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Modern Mechanobiology, 2021
Integrins are also specialized mechanosensors on the EC membrane surface that connect extracellular matrix and cytoskeleton [85, 86]. They are formed as a heterodimer of α and β subunits, which is critical for ligand binding, EC/extracellular matrix interaction, and intracellular signaling [33]. ECs plated on different cellular matrixes (such as collagen, fibronectin, fibrinogen, laminin, and gelatin) respond differently in response to various patterns of shear stress in terms of regulation of different integrin isoforms [33, 87, 88]. For example, a recent study by Yang et al. has shown that ECs plated on fibronectin and laminin respond differently to disturbed shear stress in patterns of the activation of integrins (β1 and β3), transforming growth factor-β/smad2, and NF-κB-dependent inflammatory gene expression [89]. Integrin β1 also serves as a membrane receptor for guidance molecule Semaphorin 7A and is involved in Semaphorin 7A–mediated proatherogenic events via the FAK7/MAPK8/NF-κB pathway [90]. Although the application of shear stress does not directly activate integrins, integrins do share the property of mechanosensors, possibly specialized mechanosensors [33]. In 2013, Yang et al. showed that shear stress increases apical eNOS activity via integrin β1 and caveolae [91]. A recent study has shown that fluid shear stress promotes the interaction between integrin β3 and Gα13, inhibiting RhoA and YAP activation [19]. Moreover, pharmacological activation of integrin by giving MnCl2 to hyperlipidemic mice decreased atherosclerotic plaque formation [19], indicating the therapeutic potential to treat atherosclerosis by targeting integrin β3 and/or integrin β3/Gα13 interaction.
Posthumanism: Creation of ‘New Men’ Through Technological Innovation
Published in The New Bioethics, 2021
The environment influences intelligence and disentangling the contributions of genes from that of the environment is difficult; it might also influence how heritable IQ is. It is not just that both nature and nurture matter, but that they influence each other in different ways in different people. Reviews of the field of intelligence found that heritability of IQ varies significantly by social class. The importance of the environment for IQ is established by a 12-point to 18-point increase in IQ when children are adopted from working-class to middle-class homes (Nisbett et al. 2012a). Moreover, group differences in IQ are best understood as environmental in origin (Nisbett et al. 2012b). A case–control GWAS consisting of 1238 individuals of extremely high IQ and 8172 unselected population-based controls identified an SNP with the highest heritability known for a cognitive phenotype. Three variants in the ADAM12 locus encoding disintegrin and metalloproteinase domain-containing protein 12 were associated with extremely high IQ, as well as with the Plexin protein-expressing gene family plexins of the plexin-semaphorin pathway. This pathway has been linked to axon guidance, mental disability and neural connectivity, axon regeneration in the central nervous system, bone disorders, cancer and inflammatory diseases (Zabaneh et al. 2018).