Diversity in action: exchange of perspectives and reflections on taxonomies of individual differences.

Throughout the last 2500 years, the classification of individual differences in healthy people and their extreme expressions in mental disorders has remained one of the most difficult challenges in science that affects our ability to explore individuals' functioning, underlying psychobiological processes and pathways of development. To facilitate analyses of the principles required for studying individual differences, this theme issue brought together prominent scholars from diverse backgrounds of which many bring unique combinations of cross-disciplinary experiences and perspectives that help establish connections and promote exchange across disciplines. This final paper presents brief commentaries of some of our authors and further scholars exchanging perspectives and reflecting on the contributions of this theme issue.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

Translation position determination in ptychographic coherent diffraction imaging.

Accurate knowledge of translation positions is essential in ptychography to achieve a good image quality and the diffraction limited resolution. We propose a method to retrieve and correct position errors during the image reconstruction iterations. Sub-pixel position accuracy after refinement is shown to be achievable within several tens of iterations. Simulation and experimental results for both optical and X-ray wavelengths are given. The method improves both the quality of the retrieved object image and relaxes the position accuracy requirement while acquiring the diffraction patterns.

Quantitative X-ray wavefront measurements of Fresnel zone plate and K-B mirrors using phase retrieval.

A scanning coherent diffraction imaging method was used to reconstruct the X-ray wavefronts produced by a Fresnel zone plate (FZP) and by Kirkpatrick-Baez (KB) focusing mirrors. The ptychographical measurement was conducted repeatedly by placing a lithographed test sample at different defocused planes. The wavefronts, recovered by phase-retrieval at well-separated planes, show good consistency with numerical propagation results, which provides a self-verification. The validity of the obtained FZP wavefront was further confirmed with theoretical predictions.

Genetic selection for modulators of a retinoic-acid-responsive reporter in human cells.

We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARalpha suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3.

Genetic selection for modulators of the MAP kinase and beta-catenin growth-control pathways in mammalian cells.

Transdominant genetic selections can yield protein fragment and peptide modulators of specific biochemical pathways. In yeast, such screens have been highly successful in targeting the MAP (mitogen-activated protein) kinase growth-control pathway. We performed a similar type of selection aimed at recovery of modulators of the mammalian MAP kinase cascade. Two pathway activators were identified, fragments of the TrkB and Raf-1 kinases. In a second selection directed at the beta-catenin growth-control pathway, three different clones encoding cadherin fragments were recovered. In neither selection were peptide inhibitors observed. We conclude that some transdominant selections in mammalian cells can readily yield high-penetrance protein fragments, but may be less amenable to isolation of peptide inhibitors.

Enhanced expression of exogenous genes from retroviruses using HIV2/Tat.

The capacity to produce large amounts of protein in mammalian cells is important in several contexts, including large-scale generation of biologically useful proteins, gene therapy, and transdominant genetics in cultured cells. For transdominant genetics, retroviral vectors are especially useful for delivery of expression libraries. However, even the potent CMV promoter is often unable to stimulate single-copy production of protein beyond the 1 microM level. We have adapted the HIV2/Tat expression system to retroviral vectors to boost expression above levels attainable with CMV promoters. We show that the system produces protein levels in four cell types tested which exceed levels attained by wild-type CMV or modified CMV promoters. In one cell line, the increase is 10-fold above CMV. Coupled with a stable expressed protein, levels of about 4 microM can be produced from presumptive single-copy retroviral transductants, and 30 microM from multicopy transductants.