Prediction of rotational orientation of transmembrane helical segments of integral membrane proteins using new environment-based propensities for amino acids derived from structural analyses

α-Helical integral-membrane proteins (IMPs) play a key role in many biological processes, such as signal transduction, and are targets for >50% of current therapeutic drugs. In contrast to their significant abundance and biological importance, they comprise <1% of structurally solved proteins. In the absence of experimental evidence, molecular modeling of IMP structures is an alternative for providing structural information and aiding further experimental design. In the current work, we propose two new amino acid lipid-facing propensity scales derived from the structural analysis of a nonredundant set of water-soluble proteins. The new scales, π and δ, perform as well or better than published scales (Carugo's hydrophobicity and kPROT scales) in predicting the lipid-facing side of helical segments of a set of structurally solved IMPs, thus indicating (a) that the folding properties of water-soluble proteins and IMPs are similar, and (b) that the new scales will prove useful in modeling the transmembrane segments of IMPs.Dastmalchi, Siavoush; Beheshti, Samira; Morris, Michael B and Bret Church,

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages