Spanish Validation of the Multidimensional Existential Meaning Scale: Which Dimension of Meaning in Life Is More Associated With Psychopathology in People With Mental Disorders?

BACKGROUND: To assess three dimensions of Meaning in Life (comprehension, purpose, and mattering) the Multidimensional Existential Meaning Scale (MEMS) was developed, however, the MEMS's factorial structure has not yet been confirmed in a Spanish-speaking sample. A question that remains unanswered is which of the three dimensions of MiL are associated with psychopathology in clinical samples. AIMS: (1) to analyze the psychometric properties of the MEMS in a Spanish non-clinical population, and (2) to identify which of the three dimensions of MiL shows the strongest relationship with depression, anxiety and positive affect in a clinical population. METHOD: The non-clinical sample, consisted of N = 1106 Spanish adults, and the clinical sample consisted of 88 adults diagnosed with mental disorders. A Confirmatory Factor Analysis and regression analysis were carried out. RESULTS: The three-factor model for the MEMS showed an acceptable fit, and full invariance across gender groups. In the clinical sample, the mattering dimension had the highest association with depression and anxiety, and purpose with positive affect. CONCLUSION: The MEMS is an adequate instrument to assess the three dimensions of meaning in Spanish-speaking participants. These results support the importance of evaluating the MiL construct from a multidimensional perspective in clinical samples.

Is Cybervictimization Associated with Body Dissatisfaction, Depression, and Eating Disorder Psychopathology?

Studies carried out in nonclinical samples have found an association between cyberbullying victimization and eating disorder (ED) psychopathology (negative emotions, low self-esteem, unhealthy eating behaviors, and body dissatisfaction); however, these previous studies were carried out with participants without an ED diagnosis. To extend the knowledge in this area of research, we aim to confirm these associations in two different samples: on the one hand, a sample composed of participants with ED diagnoses and, on the other hand, a sample composed of participants at high risk of ED. In study 1, the sample was composed of 80 participants diagnosed with EDs: 41.2 percent, n = 33, matched bulimia nervosa criteria; 33.8 percent, n = 27, matched anorexia nervosa restrictive criteria; and 25 percent, n = 20, matched eating disorder not otherwise specified. In study 2, the sample was composed of 156 participants at high risk of ED (elite athletes, both men and women). In both samples, the results indicated that cyberbullying victimization was positively correlated with ED psychopathology and depression. The model consisting of gender, body mass index, appearance evaluation, depression, and cyberbullying victimization was a significant predictor of ED psychopathology. This study suggests that cyberbullying victimization is a predictor of eating behaviors, attitudes, and symptoms associated with ED.

How FMN binds to anabaena apoflavodoxin: a hydrophobic encounter at an open binding site.

Molecular recognition begins when two molecules approach and establish interactions of certain strength. The mechanisms of molecular recognition reactions between biological molecules are not well known, and few systems have been analyzed in detail. We investigate here the reaction between an apoprotein and its physiological cofactor (apoflavodoxin and flavin mononucleotide) that binds reversibly to form a non-covalent complex (flavodoxin) involved in electron transfer reactions. We have analyzed the fast binding reactions between the FMN cofactor (and shorter analogs) and wild type (and nine mutant apoflavodoxins where residues interacting with FMN in the final complex have been replaced). The x-ray structures of two such mutants are reported that show the mutations are well tolerated by the protein. From the calculated microscopic binding rate constants we have performed a Phi analysis of the transition state of complex formation that indicates that the binding starts by interaction of the isoalloxazine-fused rings in FMN with residues of its hydrophobic binding site. In contrast, the phosphate in FMN, known to contribute most to the affinity of the final holoflavodoxin complex, is not bound in the transition state complex. Both the effects of ionic strength and of phosphate concentration on the wild type complex rate constant agree with this scenario. As suggested previously by nmr data, it seems that the isoalloxazine-binding site may be substantially open in solution. Interestingly, although FMN is a charged molecule, electrostatic interactions seem not to play a role in directing the binding, unlike what has been reported for other biological complexes. The binding can thus be best described as a hydrophobic encounter at an open binding site.

Salt-induced stabilization of apoflavodoxin at neutral pH is mediated through cation-specific effects.

Electrostatic contributions to the conformational stability of apoflavodoxin were studied by measurement of the proton and salt-linked stability of this highly acidic protein with urea and temperature denaturation. Structure-based calculations of electrostatic Gibbs free energy were performed in parallel over a range of pH values and salt concentrations with an empirical continuum method. The stability of apoflavodoxin was higher near the isoelectric point (pH 4) than at neutral pH. This behavior was captured quantitatively by the structure-based calculations. In addition, the calculations showed that increasing salt concentration in the range of 0 to 500 mM stabilized the protein, which was confirmed experimentally. The effects of salts on stability were strongly dependent on cationic species: K(+), Na(+), Ca(2+), and Mg(2+) exerted similar effects, much different from the effect measured in the presence of the bulky choline cation. Thus cations bind weakly to the negatively charged surface of apoflavodoxin. The similar magnitude of the effects exerted by different cations indicates that their hydration shells are not disrupted significantly by interactions with the protein. Site-directed mutagenesis of selected residues and the analysis of truncation variants indicate that cation binding is not site-specific and that the cation-binding regions are located in the central region of the protein sequence. Three-state analysis of the thermal denaturation indicates that the equilibrium intermediate populated during thermal unfolding is competent to bind cations. The unusual increase in the stability of apoflavodoxin at neutral pH affected by salts is likely to be a common property among highly acidic proteins.

The 'relevant' stability of proteins with equilibrium intermediates.

Proteins perform many useful molecular tasks, and their biotechnological use continues to increase. As protein activity requires a stable native conformation, protein stabilisation is a major scientific and practical issue. Towards that end, many successful protein stabilisation strategies have been devised in recent years. In most cases, model proteins with a two-state folding equilibrium have been used to study and demonstrate protein stabilisation. Many proteins, however, display more complex folding equilibria where stable intermediates accumulate. Stabilising these proteins requires specifically stabilising the native state relative to the intermediates, as these are expected to lack activity. Here we discuss how to investigate the 'relevant' stability of proteins with equilibrium intermediates and propose a way to dissect the contribution of side chain interactions to the overall stability into the 'relevant' and 'nonrelevant' terms. Examples of this analysis performed on apoflavodoxin and in a single-chain mini antibody are presented.