Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human

National Oceanic and Atmospheric Administration Report 59

This is an observational report on captive seal pups along Green Island and Sand Island during the 1981 population observations. Some pups were flipper-tagged after weaning, five females were kept in a large beach enclosure for observation, then released September 2nd

A Meaning-Based Approach to Humility: Relationship Affirmation Reduces Worldview Defense

Humans are notoriously resistant to changing their longstanding beliefs and often act defensively when they encounter individuals holding divergent beliefs. We introduce a meaning-based approach to humility (e.g., reduced defensiveness) with the claim that the desire for meaning motivates individuals to ardently defend their central beliefs. We propose that affirming meaning prior to encountering attitudinally-dissimilar individuals should reduce defensiveness (e.g., less negative attitudes toward those who challenge their beliefs). Christian undergraduates (N = 79) were randomly assigned to a relationship affirmation, self-affirmation, or neutral priming condition, and then received negative feedback from an ostensibly antireligious individual (i.e., outgroup member) after writing an essay explicating their beliefs about an important social or cultural topic. Relationship affirmation reduced defensiveness via more positive ratings of the individual who derogated their beliefs, providing initial evidence for our theoretical approach. Implications for a meaning-based approach to humility are discussed

Internet-guided cognitive, behavioral and chronobiological interventions in depression-prone insomnia subtypes:protocol of a randomized controlled prevention trial

Background: Major depressive disorder is among the most burdening and costly chronic health hazards. Since its prognosis is poor and treatment effectiveness is moderate at best, prevention would be the strategy of first choice. Insomnia may be the best modifiable risk factor. Insomnia is highly prevalent (4-10%) and meta-analysis estimates ±13% of people with insomnia to develop depression within a year. Among people with insomnia, recent work identified three subtypes with a particularly high lifetime risk of depression. The current randomized controlled trial (RCT) evaluates the effects of internet-guided Cognitive Behavioral Therapy for Insomnia (CBT-I), Chronobiological Therapy (CT), and their combination on insomnia and the development of depressive symptoms. Methods: We aim to include 120 participants with Insomnia Disorder (ID) of one of the three subtypes that are more prone to develop depression. In a two by two factorial repeated measures design, participants will be randomized to CBT-I, CT, CBT-I + CT or treatment as usual, and followed up for one year. The primary outcome is the change, relative to baseline, of the severity of depressive symptoms integrated over four follow-ups spanning one year. Secondary outcome measures include a diagnosis of major depressive disorder, insomnia severity, sleep diaries, actigraphy, cost-effectiveness, and brain structure and function. Discussion: Pre-selection of three high-risk insomnia subtypes allows for a sensitive assessment of the possibility to prevent the development and worsening of depressive symptoms through interventions targeting insomnia. Trial registration: Netherlands Trial Register (NL7359). Registered on 19 October 2018