Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention

Protracted crisis, food security and the fantasy of resilience in Sudan

In the past decade, food security and nutrition practices have become central in the promotion of resilience in protracted crises. Such approaches have been welcomed by the aid community because of their potential for linking relief and development. Social and political analysts, however, have criticized resilience approaches for failing to consider power relations and because they entail an acceptance of crisis or repeated risk. In this context, regimes of food security and nutrition practices have become increasingly targeted, privatized and medicalized, focussing on individual behaviour and responsibility rather than responsibility of the state or international actors. This article uses examples from Sudan to examine how and why the resilience ‘regime of practices’ has functioned as a form of neoliberal governmentality, and argues that it has created a fantasy in which conflict in Darfur is invisible. This allowed food aid to be withdrawn and removed the need for protection despite ongoing conflict and threats to livelihoods; thus crisis-affected populations have been abandoned

Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes