Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

PURPOSE: Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. METHODS: We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. RESULTS: PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. CONCLUSIONS: PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo

The K -factor: Individual Differences in Life History Strategy

Until recently, variations in life history strategy were studied exclusively at the species level. Although this domain of study has been extended to examine systematic differences in life history strategy among various human ethnic groupings, more recent evolutionary theories of human development and related behavioral genetic work imply substantial within-group individual variation in life history strategy. We constructed a latent variable model identifying a single common factor, denoted as K, which underlies a variety of otherwise disparate life history parameters. This “K-Factor” loaded 0.36 on childhood attachment to the biological father, −0.36 on childhood attachment to any non-biological father figure, 0.38 on adult romantic partner attachment, −0.51 on mating effort, −0.58 on Machiavellianism, and −0.41 on risk propensity. The bivariate correlations of the K-factor with higher-order personality factors were statistically significant, −0.24 with “Big Neuroticism” and −0.67 with “Big Psychoticism”, and approached significance, correlating 0.12, with “Big Extraversion”. The K-factor appears to be an underappreciated individual difference variable of major importance to human development.</p

Substance, History, and Politics

The aim of this article is to examine the relations between two approaches to the measurement of life history (LH) strategies: A traditional approach, termed here the biodemographic approach, measures developmental characteristics like birthweight, gestation length, interbirth intervals, pubertal timing, and sexual debut, and a psychological approach measures a suite of cognitive and behavioral traits such as altruism, sociosexual orientation, personality, mutualism, familial relationships, and religiosity. The biodemographic approach also tends not to invoke latent variables, whereas the psychological approach typically relies heavily upon them. Although a large body of literature supports both approaches, they are largely separate. This review examines the history and relations between biodemographic and psychological measures of LH, which remain murky at best. In doing so, we consider basic questions about the nature of LH strategies: What constitutes LH strategy (or perhaps more importantly, what does not constitute LH strategy)? What is gained or lost by including psychological measures in LH research? Must these measures remain independent or should they be used in conjunction as complementary tools to test tenets of LH theory? Although definitive answers will linger, we hope to catalyze an explicit discussion among LH researchers and to provoke novel research avenues that combine the strengths each approach brings to this burgeoning field