However, there is still uncertainty related to the etiology of the disease, and environmental factors, including early-life exposure to EDCs and maternal smoking, may increase susceptibility to weight gain and obesity (Heindel 2003; Heindel and vom Saal 2009; Porta et al. 2009b).
Nor does pregnancy increase susceptibility to parasites.
In our study, gene silencing of Itga8 and Fn1 was associated with a gain of susceptibility (Table 1).
Of note, RA-mediated remodelling of the ECM mimicked a gain of susceptibility, suggesting that matrix homeostasis and prion replication may be affected by common signalling pathways.
We next examined in a systematic gene silencing approach whether the loss of function of single candidates of the gene signature could recapitulate the gain of susceptibility observed upon RA differentiation of revertants (Fig 2 and Supplementary Table S4).
The RA-mediated downregulation of prion modifier genes led to a marked gain of susceptibility, suggesting that the rate of prion propagation is associated with transcriptional regulation of gene candidates.
Such an arrangement appears to offer several significant advantages, including a low ignition threshold, high gain, and less susceptibility to the deleterious effects of hydrodynamic and laser-plasma instabilities.
The maximum optical gain, including nonlinear susceptibility, is written as [26]: g_{text{tot}} = g_{text{m}}^{(1)} + g_{text{m}}^{(3)} = g_{text{m}}^{(1)} left[ {1 - varepsilon_{text{m}} varGamma S/V_{text{a}} } right] cong frac{{g_{text{m}}^{(1)} }}{{1 + varepsilon_{text{m}} varGamma S/V_{text{a}} }}, (7 where (varepsilon_{text{m}}) is the third-order nonlinear coefficient [27].
Seven distinct Eimeria species may infect chickens, causing enteric diseases that lead to diarrhoea, malabsorption, impaired weight gain and higher susceptibility to opportunistic diseases.
This RA-mediated phenotypic switch from prion-resistant to prion-susceptible cells (Supplementary Table S4) provided us with an experimental approach to identify gene candidates associated with a gain of prion susceptibility.
