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Ran is an abundant small G protein that has a central role in nuclear transport during interphase. Ran function depends on distinct pools of RanGTP in the nucleus and RanGDP in the cytoplasm, which are maintained by compartmentalisation of the nucleotide exchange and GTPase activating proteins for Ran. RCC1 (Regulator of Chromosome Condensation) is the only known guanine nucleotide exchange factor for Ran and is associated with chromatin. RanGAPl together with RanBPl are the primary GTPase activator proteins and are located in the cytoplasm.
Ran function in nuclear transport is clearly inactivated after the nuclear envelope has disassembled during mitosis. There is now evidence that Ran plays a role in organising the spindle. Experiments using well-characterised cell-free extracts from meiotic metaphase II arrested Xenopus eggs suggest that Ran regulates microtubules involved in spindle assembly (Carazo-Salas et al., 1999; Kalab et al., 1999; Ohba et al., 1999; Wilde & Zheng, 1999). These experiments demonstrate that high levels of RanGTP or GTP-locked forms of Ran result in aster formation and can cause formation of bipolar spindles in the absence of centrosomes or chromosomes. In contrast, reduction of RanGTP blocks centriole- and chromatin-dependent aster formation.
Although childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age.
To examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage.
Epidemiological data were analysed from the World Mental Health Surveys (n = 27017).
Four childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR)=1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity–PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood.
Childhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences.
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