Three Poems from The Elder Project, Vernon School District 22

Poetry by Vernon School District secondary students and their elders, in collaboration with The Elder Project organized by Wendy Morton and Sandra Lynxleg

Gene editing enables rapid engineering of complex antibiotic assembly lines

From Springer Nature via Jisc Publications RouterHistory: received 2021-09-09, accepted 2021-11-02, registration 2021-11-08, pub-electronic 2021-11-25, online 2021-11-25, collection 2021-12Publication status: PublishedFunder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/L013754/1, BB/N023536/1Abstract: Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics and other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases is very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited to rapidly engineer one of the most complex megasynthase assembly lines in nature, the 2.0 MDa NRPS enzymes that deliver the lipopeptide antibiotic enduracidin. Gene editing was used to exchange subdomains within the NRPS, altering substrate selectivity, leading to ten new lipopeptide variants in good yields. In contrast, attempts to engineer the same NRPS using a conventional homologous recombination-mediated gene knockout and complementation approach resulted in only traces of new enduracidin variants. In addition to exchanging subdomains within the enduracidin NRPS, subdomains from a range of NRPS enzymes of diverse bacterial origins were also successfully utilized

Gene-environment correlation in the development of adolescent substance abuse: Selection effects of child personality and mediation via contextual risk factors

We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14, and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11—willingness to follow rules and endorse conventional values—predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11—social engagement and assurance, thrill-seeking, and stress resilience— also predicted substance abuse directly, but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse

Missing Migrants in the Mediterranean : Addressing the Humanitarian Crisis Summary report

The Mediterranean Missing research project has sought to understand both the impact on families of having a relative missing in migration, and the law, policy and practice around the identification of bodies of dead migrants in Italy and Greece. Interviews with families of missing migrants from five countries confirmed the huge impact of not knowing the fate of loved ones, with families tortured by ambiguity and suffering a range of emotional and psychological consequences. In Lesbos, Greece, and Sicily, Italy, interviews with authorities, civil society and others confirm the presence of a policy vacuum around the issue of the missing, despite the duties on states imposed by human rights law. Investigation of deaths is inadequate, with effective post-mortem data collection and management challenged by the huge numbers of migrants , in some cases sufficiently to compromise future identification. In both Greece and Italy, response is characterised by a policy vacuum, with a large number of agencies with overlapping mandates lacking coordination. Whilst in Italy a dedicated Commission and its partners have demonstrated what can be done with appropriate resources, there is a need to ensure that all the dead benefit from such an approach. A constraint in both contexts remains the lack of outreach to families of the missing, who can provide ante-mortem data to enable identification, and who should anyway be at the centre of all efforts to address the issue and identify the dead