Synthetic materials that assemble reversibly with polyanions under physiological conditions are of interest for a broad range of biotechnical applications. Cationic polymers are used widely as agents for the condensation of DNA, but polycations also introduce practical limitations in applications for which subsequent dissociation or disassembly of polycation/DNA complexes is desired. The design of cationic polymers that promote the release of associated DNA presents a challenge because it requires the introduction of functionality that is inherently opposed to that required for efficient DNA condensation. Here, we report the synthesis and biophysical characterization of linear poly(ethylenimine) (LPEI) functionalized with methyl ester side chains. The gradual hydrolysis of the ester functionality in these materials under physiologically relevant conditions results in a controlled reduction in cationic charge density and a change in the nature of the electrostatic interactions between the polymers and plasmid DNA, as determined by agarose gel electrophoresis. Using this approach, it is possible to mediate the dissociation of DNA from polymer over a period of hours to days by varying the mole percentage of methyl esters incorporated into the polymer. Polymers having a high degree of substitution (e.g., 80 or 100 mol %) release DNA more rapidly than less-substituted polymers (e.g., 40 and 60 mol % functionalized). Polymers having 20 mol % substitution did not release DNA in these experiments. These charge-shifting materials could provide a basis for the design and fabrication of polyelectrolyte complexes and assemblies that sustain the release of DNA in solution and at interfaces.

Low empathy has been implicated in antisocial, aggressive, and criminal behavior, especially among adolescents. Less understood is the extent to which empathy is amenable to treatment, and whether an improvement in empathy can mitigate the deleterious effects of known risk factors, such as childhood maltreatment. A sample of 11,000 serious juvenile offenders in long-term residential placement is leveraged to examine whether over cumulative traumatic exposure, measured by the adverse childhood experience (ACE) score, is associated with the initial level of empathy at admission to a residential program, and whether changes in empathy during treatment moderate the impact of ACEs on juvenile recidivism. Results show youth with higher ACE scores have less empathy at admission and both ACEs and empathy predict recidivism. Most importantly, large gains in empathy are able to dampen the effect of ACEs on recidivism.

We reported recently that the addition of ester-functionalized, "charge-shifting" side chains to linear poly(ethyleneimine) (LPEI) can be used to design polyamines that promote both self-assembly and self-disassembly with DNA in aqueous environments. This investigation sought to characterize the influence of charge-shifting side chains on the ability of LPEI to mediate cell transfection and understand the extent to which increases (or decreases) in levels of transfection could be understood in terms of time-dependent changes in the net charges of these polymers. We report that the addition of "charge-shifting" side chains to LPEI leads to significant increases in levels of LPEI-mediated transfection. In particular, polymer 1e, functionalized with 20 mol % ester-functionalized side chains, mediates levels of transgene expression in vitro up to 8-fold higher than LPEI. Experiments using an amide-functionalized analog of polymer 1e demonstrated that the esters in polymer 1e play an important role in promoting increased levels of transfection. These results, in combination with the results of additional gel electrophoresis experiments, provide support for the view that increases in transfection result from time-dependent changes in the net charge of polymer 1e and the disruption of ionic interactions in polyplexes. Additional support for this view is provided by the results of confocal microscopy experiments and measurements of fluorescence resonance energy transfer, which suggest that polymer 1e promotes the disruption of polyplexes in intracellular environments effectively. The approach reported here provides a means of addressing one important "late-stage" obstacle to polyplex-mediated transfection (polyplex unpackaging). If integrated successfully with methods that have been developed to address other important barriers to transfection, this general approach could lead to the development of multifunctional polyplexes that mimic more effectively the range of functions of viruses as agents for the delivery of DNA.

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Youth who are dually involved in both foster care and criminal justice systems represent a small minority of individuals with multi-problem risk profiles. Prior research has found that foster care youth are disproportionately more likely to be chronic offenders in both adolescence and emerging adulthood. However, the nature of this relationship remains theoretically underexplored and empirically underexamined, especially with respect to risk factors that may moderate the relationship. Using data from the Incarcerated Serious and Violent Young Offender Study, the criminal offending trajectories of 678 incarcerated youth were examined. A history of foster care predicted membership in a high rate chronic offending trajectory. This relationship was not moderated by parental maltreatment, negative self-identity, involvement in gang activity, or substance use versatility. Findings suggested a greater need for ongoing support for foster care youth during their transition to adulthood, regardless of their exposure to a range of other negative life circumstances.