Trypanosomatid RACK1 Orthologs Show Functional Differences Associated with Translation Despite Similar Roles in Leishmania Pathogenesis

RACK1 proteins belong to the eukaryote WD40-repeat protein family and function as spatial regulators of multiple cellular events, including signaling pathways, the cell cycle and translation. For this latter role, structural and genetic studies indicate that RACK1 associates with the ribosome through two conserved positively charged amino acids in its first WD40 domain. Unlike RACK1s, including Trypanosoma brucei RACK1 (TbRACK1), only one of these two positively-charged residues is conserved in the first WD40 domain of the Leishmania major RACK1 ortholog, LACK. We compared virulence-attenuated LACK single copy (LACK/-) L. major, with L. major expressing either two LACK copies (LACK/LACK), or one copy each of LACK and TbRACK1 (LACK/TbRACK1), to evaluate the function of these structurally distinct RACK1 orthologs with respect to translation, viability at host temperatures and pathogenesis. Our results indicate that although the ribosome-binding residues are not fully conserved in LACK, both LACK and TbRACK1 co-sedimented with monosomes and polysomes in LACK/LACK and LACK/TbRACK1 L. major, respectively. LACK/LACK and LACK/TbRACK1 strains differed in their sensitivity to translation inhibitors implying that minor sequence differences between the RACK1 proteins can alter their functional properties. While biochemically distinguishable, both LACK/LACK and LACK/TbRACK1 lines were more tolerant of elevated temperatures, resistant to translation inhibitors, and displayed robust pathogenesis in vivo, contrasting to LACK/- parasites

The Platonic-Freudian model of mind: Defining "self" and "other" as psychoinformatic primitives

As “nurtural” (rather than merely natural) kinds of human beings, people are complex and multifaceted. Any complete human science would require a complete theory of persons. Accomplishing the latter is the core objective of the present article. First, a feature list first laid out in [1] is summarized. This list is briefly critiqued. Next, the concept of person engaged with is expanded with the addition of nine novel features. These features follow from “holarchic psychoinformatics” [2], which was first propounded as a step forward from Sood’s analytic treatment of third-force, existential-humanistic psychology. Person is formalized as a function of self and other; they are also granted to be romantic, existential, humanistic, chemical, environmental, hedonic and eudaimonic (happiness-seeking), conservative, and liberal. These are in addition to persons being physical, biological, psychological, social, cultural, and spiritual. Sood’s holarchic view of persons is enlarged. Psychologically, augmented cognition as an established field of research and practice begets the formal studies of augmented affect, augmented behavior, and augmented motivation. All such interdisciplinary fields are required for the human-computer interactionist’s study of augmented mind, more broadly. Additionally, this article builds on the person-situation interaction framework formalized in [1]. It does so by adding a formalization following from the discussion of psychological situations put forward by Rauthmann, Sherman, and Funder in [3]. The formalization of psychological situations sets them as a function of cues, characteristics, and classes. Further psychological equations that follow from this article’s formalisms of person and situation, when considered along with Sood’s formulae for mind and behavior, are then presented