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Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.
Despite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.