Cognitive Flexibility and Emotion Regulation in Eating Disorder Patients with Comorbid Generalized Anxiety and Posttraumatic Stress Symptoms.

Research has found that difficulties in emotion regulation negatively impact mental health, whereas cognitive flexibility may promote stress resilience and positive mental health. Little is known about cognitive flexibility and emotion regulation in people with comorbid eating disorder (ED) and anxiety and stress disorders. A transdiagnostic ED population (N=227) at an outpatient ED treatment facility completed several self-report instruments that measured cognitive flexibility, emotion regulation difficulties, posttraumatic stress disorder (PTSD) symptoms, and generalized anxiety disorder (GAD) symptoms upon admission. We investigated cognitive flexibility and emotion regulation differences for those with an ED without comorbidity and those with various combinations of comorbidity. In a one-way between-groups ANOVA, we investigated differences in cognitive flexibility for those with GAD, PTSD, neither, and both comorbidities. We found a statistically significant difference between these groups, with mean cognitive flexibility inventory scores being the lowest in the group with both comorbidities. However, when controlling for emotion regulation, a one-way between-groups ANCOVA indicated no significant differences in cognitive flexibility between comorbidity groups F(3,222)=1.20,p=.31 Partial η2=.02. Though self-reported cognitive flexibility levels differ among ED patients with and without comorbidities, it appears that these differences are better explained by emotion regulation. Therefore, addressing emotion regulation early in treatment for all individuals with EDs, regardless of comorbidity. Further research is needed to understand the impact of treating emotion regulation on ED treatment engagement, dropout, and effectiveness.

Does Terminology Matter When Measuring Stigmatizing Attitudes About Weight? Validation of a Modified Attitudes Toward Obese Persons Scale.

Commonly used medical terms like "obesity" and "overweight" have been identified as stigmatizing. Thus, this study sought to revise a commonly used measure of weight stigmatizing attitudes, the Attitudes Toward Obese Persons (ATOP) scale. We compared the original terminology in the ATOP (e.g., "obese")to a Modified version using neutral terms (e.g., "higher weight"). We randomized participants (N = 599) to either receive the original or Modified ATOP and compared their scores. There was no significant difference between the scores of participants who received the original ATOP and the Modified ATOP, t(597) = -2.46, p = .550. Through principal component analysis, we found the Modified ATOP is best used as a 13-item unidimensional measure. Findings suggest a Modified version of the ATOP with neutral language is suitable for assessing negative attitudes about higher-weight people without sacrificing psychometric properties. Further examination of the terminology used in weight stigma measures is needed to determine how to best assess weight stigma without reinforcing stigmatizing attitudes. The findings of the present study suggest that the use of neutral terms in measures of anti-fat bias is a promising solution that warrants further investigation.

Enhanced Facilitated Diffusion of Membrane-Associating Proteins under Symmetric Confinement.

The facilitated surface diffusion of transiently adsorbing molecules in a planar confined microenvironment (i.e., slit-like confinement) is highly relevant to biological phenomena, such as extracellular signaling, as well as numerous biotechnology systems. Here, we studied the surface diffusion of individual proteins confined between two symmetric lipid bilayer membranes, under a continuum of confinement heights, using single-molecule tracking and convex lens-induced confinement as well as hybrid, kinetic Monte Carlo simulations of a generalized continuous time random walk process. Surface diffusion was observed to vary non-monotonically with confinement height, exhibiting a maximum at a height of ∼750 nm, where diffusion was nearly 40% greater than that for a semi-infinite system. This demonstrated that planar confinement can, in fact, increase surface diffusion, qualitatively validating previous theoretical predictions. Simulations reproduced the experimental results and suggested that confinement enhancement of surface diffusion for symmetric systems is limited to cases where the adsorbate exhibits weak surface sticking.

Cadherin cis and trans interactions are mutually cooperative.

Cadherin transmembrane proteins are responsible for intercellular adhesion in all biological tissues and modulate tissue morphogenesis, cell motility, force transduction, and macromolecular transport. The protein-mediated adhesions consist of adhesive trans interactions and lateral cis interactions. Although theory suggests cooperativity between cis and trans bonds, direct experimental evidence of such cooperativity has not been demonstrated. Here, the use of superresolution microscopy, in conjunction with intermolecular single-molecule Förster resonance energy transfer, demonstrated the mutual cooperativity of cis and trans interactions. Results further demonstrate the consequent assembly of large intermembrane junctions, using a biomimetic lipid bilayer cell adhesion model. Notably, the presence of cis interactions resulted in a nearly 30-fold increase in trans-binding lifetimes between epithelial-cadherin extracellular domains. In turn, the presence of trans interactions increased the lifetime of cis bonds. Importantly, comparison of trans-binding lifetimes of small and large cadherin clusters suggests that this cooperativity is primarily due to allostery. The direct quantitative demonstration of strong mutual cooperativity between cis and trans interactions at intermembrane adhesions provides insights into the long-standing controversy of how weak cis and trans interactions act in concert to create strong macroscopic cell adhesions.

Cadherin clusters stabilized by a combination of specific and nonspecific cis-interactions.

We demonstrate a combined experimental and computational approach for the quantitative characterization of lateral interactions between membrane-associated proteins. In particular, weak, lateral (cis) interactions between E-cadherin extracellular domains tethered to supported lipid bilayers, were studied using a combination of dynamic single-molecule Förster Resonance Energy Transfer (FRET) and kinetic Monte Carlo (kMC) simulations. Cadherins are intercellular adhesion proteins that assemble into clusters at cell-cell contacts through cis- and trans- (adhesive) interactions. A detailed and quantitative understanding of cis-clustering has been hindered by a lack of experimental approaches capable of detecting and quantifying lateral interactions between proteins on membranes. Here single-molecule intermolecular FRET measurements of wild-type E-cadherin and cis-interaction mutants combined with simulations demonstrate that both nonspecific and specific cis-interactions contribute to lateral clustering on lipid bilayers. Moreover, the intermolecular binding and dissociation rate constants are quantitatively and independently determined, demonstrating an approach that is generalizable for other interacting proteins.

Cadherin Extracellular Domain Clustering in the Absence of Trans-Interactions.

While both cis and trans (adhesive)-interactions cooperate in the assembly of intercellular adhesions, computational simulations have predicted that two-dimensional confinement may promote cis-oligomerization, in the absence of trans-interactions. Here, single-molecule tracking of cadherin extracellular domains on supported lipid bilayers revealed the density-dependent formation of oligomers and cis-clusters in the absence of trans-interactions. Lateral oligomers were virtually eliminated by mutating a putative cis (lateral) binding interface. At low cadherin surface coverage, wild-type and mutant cadherin diffused rapidly, consistent with the motion of a lipid molecule within a cadherin-free supported bilayer and with cadherins diffusing as monomers. Although the diffusion of mutant cadherin did not change appreciably with increasing surface coverage, the average short-time diffusion coefficient of wild-type cadherin slowed significantly above a fractional surface coverage of ∼0.01 (∼1100 molecules/µm2). A detailed analysis of molecular trajectories suggested the presence of a broad size distribution of cis-cadherin oligomers. These findings verify predictions that two-dimensional confinement promotes cis-oligomerization, in the absence of trans-interactions.