Understanding the dynamics of scaffold-mediated signaling

AbstractMany signaling networks involve scaffold proteins that bind multiple kinases in kinase cascades. While scaffolds play a fundamental role in regulating signaling, few hypotheses regarding their function have been rigorously examined. Here, we used dynamical models of scaffold signaling to investigate the impact scaffolds have on network behavior. We considered two paradigms of scaffold assembly: as either the nucleation point for assembly of discrete multi-subunit proteins (the machine paradigm) or a platform upon which kinases independently associate (the ensemble paradigm). We found that several well-accepted hypotheses regarding the role of scaffolds in regulating signal response either do not hold or depend critically on the assembly paradigm employed. In addition to providing novel insights into the function of scaffold proteins, our work suggests experiments that could distinguish between assembly paradigms. Our findings should also inform attempts to target scaffold proteins for therapeutic intervention and the design of scaffolds for synthetic biology.

Download Full-text

The Importance of Flexible Relational Boundaries: The Role of Connectedness in Self-Compassion and Compassion for Others

Psi Chi Journal of Psychological Research ◽

10.24839/2325-7342.jn25.4.349 ◽

2020 ◽

Vol 25 (4) ◽

pp. 349-356

Author(s):

Kaitlin S. Snyder ◽

Andrew F. Luchner

Keyword(s):

Predictive Models ◽

Therapeutic Intervention ◽

Self Report ◽

Personal Relationships ◽

Personality Theory ◽

Personality Organization ◽

Self Compassion ◽

The Impact

Self-compassion and compassion for others have largely been studied independently. However, when studied as separate but related constructs, clear self-other differences emerge. Although intrapersonal and interpersonal differences are perhaps best explained through personality theory, specifically Blatt’s (2008) 2 polarities model, limited research has specifically examined the impact personality organization has on the capacity to extend compassion to oneself and others. The present study examined how personality organization according to 2-polarities model of personality is related to and impacts self-compassion and compassion for others. Participants (N = 226) completed a series of self-report questionnaires online to assess personality organization and compassion competencies. Results yielded 2 predictive models of compassion. Efficacy (+), self-criticism (−), and connectedness (−-) predicted self-compassion (R2 = .47, p < .001). Efficacy (+), self-criticism (−), and connectedness (+) predicted compassion for others (R2 = .36, p < .001). Model disparities elucidate key differences between the constructs, specifically that healthy and flexible relational boundaries are essential for self-compassion, while feelings of security and stability within personal relationships are more important for showing others compassion. Understanding how differences in personality proclivities relate to the nuances in self-compassion and compassion for others may aid therapeutic intervention targeting compassion capacities.

Download Full-text

Can Systems Biology Advance Clinical Precision Oncology?

Cancers ◽

10.3390/cancers13246312 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6312

Author(s):

Andrea Rocca ◽

Boris N. Kholodenko

Keyword(s):

Systems Biology ◽

Patient Specific ◽

Signaling Networks ◽

Precision Oncology ◽

Dynamical Models ◽

Molecular Alterations ◽

Environmental Perturbations ◽

Signal Transduction Networks ◽

Cancer Mutations ◽

The Impact

Precision oncology is perceived as a way forward to treat individual cancer patients. However, knowing particular cancer mutations is not enough for optimal therapeutic treatment, because cancer genotype-phenotype relationships are nonlinear and dynamic. Systems biology studies the biological processes at the systems’ level, using an array of techniques, ranging from statistical methods to network reconstruction and analysis, to mathematical modeling. Its goal is to reconstruct the complex and often counterintuitive dynamic behavior of biological systems and quantitatively predict their responses to environmental perturbations. In this paper, we review the impact of systems biology on precision oncology. We show examples of how the analysis of signal transduction networks allows to dissect resistance to targeted therapies and inform the choice of combinations of targeted drugs based on tumor molecular alterations. Patient-specific biomarkers based on dynamical models of signaling networks can have a greater prognostic value than conventional biomarkers. These examples support systems biology models as valuable tools to advance clinical and translational oncological research.

Download Full-text

Intergroup Threat and Outgroup Attitudes

Social Psychology ◽

10.1027/1864-9335/a000127 ◽

2013 ◽

Vol 44 (5) ◽

pp. 311-319 ◽

Cited By ~ 12

Author(s):

Marco Brambilla ◽

David A. Butz

Keyword(s):

Gay Men ◽

Social Group ◽

Welfare Recipients ◽

Intergroup Attitudes ◽

Social Policies ◽

Intergroup Threat ◽

Economic Threat ◽

The Impact ◽

General Climate

Two studies examined the impact of macrolevel symbolic threat on intergroup attitudes. In Study 1 (N = 71), participants exposed to a macrosymbolic threat (vs. nonsymbolic threat and neutral topic) reported less support toward social policies concerning gay men, an outgroup whose stereotypes implies a threat to values, but not toward welfare recipients, a social group whose stereotypes do not imply a threat to values. Study 2 (N = 78) showed that, whereas macrolevel symbolic threat led to less favorable attitudes toward gay men, macroeconomic threat led to less favorable attitudes toward Asians, an outgroup whose stereotypes imply an economic threat. These findings are discussed in terms of their implications for understanding the role of a general climate of threat in shaping intergroup attitudes.

Download Full-text