Multiscale Simulations of Phosphatidylinositol Bisphosphate: Understanding Its Biological Role Through Physical Chemistry

Proper functionality of biological membranes depends on the regulation of lipid composition and localization. Spatial localization of molecules within the lipid bilayer depends on both steric effects due to their acyl chains and attractive or repulsive interactions between lipid head groups, such as those mediated by the electrostatic charge of the lipid. Most eukaryotic lipids are zwitterionic or have a charge of -1 at physiological pH, but some lipids such as phosphatidylinositol bisphosphate (PtdInsP2) bear a net charge of -4. The ability of these highly charged lipids to interact with monovalent and divalent cations affects their spatial organization and temporal distribution on the cytoplasmic side of membranes. In turn, these lipids act as important effectors of apoptosis, inflammation, motility, and proliferation through their interactions with proteins at the membrane interface and transmembrane ion channels. We hypothesize that in some settings, the isomers of PtdInsP2 - PtdIns(3,5)P2 and PtdIns(4,5)P2 - act by changing the physical-chemical properties of the membrane rather than by specific biochemical binding to proteins. We also predict that PtdIns(3,5)P2 and PtdIns(4,5)P2 alter the mechanical of properties in distinct ways due to the larger size and altered charge distribution in the head group of PtdIns(3,5)P2. We used multiscale computational techniques, ranging from quantum-level electronic structure calculations to all-atom molecular dynamics simulations of bilayers to characterize the biological role of PtdInsP2. Our results demonstrate that the different roles of PtdIns(4,5)P2 and PtdIns(3,5)P2 in vivo are not simply determined by their localization, but also due to intrinsic factors different between them such as molecular size, propensity to bind cellular divalent cations, and the partial dehydration of those ions which may affect the ability of PtdIns(3,5)P2 and PtdIns(4,5)P2 to form phosphoinositide-rich clusters in vitro and in vivo

Reflective-verbal language and reverie in a qualitative interview

In contrast to dominant approaches to therapy research that look at outcomes and focus on large samples, another primary strand of research considers microphenomenal processes and focuses on small samples. This study contributes to the latter genre in regard to the implicit impact of language. Aim: This study aims to apply relational psychotherapeutic thinking about empathic dialogue, specifically the concepts of reflective-verbal language and reverie, to qualitative interviewing. Methodology: An example from a small-scale study about emotionally evocative language is reviewed in detail, focusing on the interviewer’s phenomenological experience of her conversation with a participant in a qualitative interview. Findings: The authors argue that the interviewer’s reflexive awareness of her reveries and the reflective verbal nature of the research dialogue gave her an alternative perspective on the participant’s (and her own) experience. Implications: The study highlights the value within research and practice of maintaining awareness of language at a microphenomenal level, using techniques based on the principles of psychological therapy

Psychoanalytic Dialogues

How do patients internalize new good object experience and how do these previously closed systems open up? What happens within and between analyst and patient that leads to the opening up of affective channels between them and allows consciousness to become transpersonal? The ways in which self-state experience becomes more fluid and cohesive, or less dissociated, is an affective process. This process occurs intersubjectively, as well as between self-states within each individual. When particular self-states come together between analyst and patient, especially those associated with pain and shame, disruption and instability may result within the mind-system (intrapsychic organization) of either or both partners. Managing the affective strain and psychic destabilization are vital tasks for the analyst and patient, in order for relationships between parts of the self (within one individual) to move from pain and hiddenness to compassionate recognition, thereby allowing and facilitating for parts of the self within the other individual to, in turn, move from pain and hiddenness to compassionate recognition. This is a core process of internal life, leading to the development of intimacy between self-states as well as between individuals. What moves patients from operating within the closed systems of enactments, characterized by old object relational patterns/transferences, rigidity, dissociation, narrowing of consciousness and deadening hypnoidal states, to the open systems of new object relational patterns characterized by fluidity, expansion of consciousness and greater complexity, association, and healing? How do the interiors of our patients become fertile ground for the development of new identifications based on good object experiences with us? In our understanding of enactment and how we find our way out with patients, we have come to appreciate the role of our own dissociative processes and how these processes align with unconscious aspects of the patient's internal object world. These dissociated elements arise from the complex interplay of our own internal object world with that of our patient, all within the context of the intersubjective field. The resulting enactments continue on unabated, until one of the partners is able to manage the affective strain and destabilization of identity that ensues, in order for what is dissociated to become conscious. The affective strain and destabilization of identity will, My thanks and gratitude t

Exploring conversational and physiological aspects of psychotherapy talk

This study is part of a larger exploration of ‘talk and cure’ that combines the examination of talk-in-interaction with nonverbal displays and measurements of the client’s and therapist’s autonomic arousal during therapy sessions. A key assumption of the study is that psychotherapy entails processes of intersubjective meaning-making that occur across different modalities and take place in both verbal/explicit and nonverbal/implicit domains. A single session of a psychodynamic psychotherapy is analyzed with a focus on the expression and management of affect, with an aim to describe key interactive events that promote change in both semantic and procedural domains. The clinical dialog is analyzed discursively, with a focus on the conversational processes through which new meanings are jointly constructed and affective states shared; detailed attention is paid to nonverbal displays of affiliation and affect. Furthermore, we explore whether the interactional patterns implicated in joint meaning-making, as revealed by analyzing the therapeutic conversation, have correlates in the autonomic arousal of the two protagonists, as reflected in their heart rates. Conversation analysis has still untapped potential to illuminate interactional patterns that underlie the practice of psychotherapy. In this exploratory study we suggest that discursive analyses of talk-in-interaction can be enriched through detailed focus on nonverbal displays as well as measures of physiological arousal. Drawing upon the analysis, we suggest that bringing the methodological strengths of language-based analysis into fertile dialog with embodied quantitative data can help our explorations of what’s really going on in psychotherapy