Risk factors of disordered eating in adolescent girls from a community sample: a multidimensional approach.

BACKGROUND: Eating disorders (ED) are severe, chronic, and complex in nature mental illnesses that are difficult to treat. One of the ways to stave off EDs is by screening among adolescents to preempt the development of clinical forms of ED in risk groups. AIM: 1) to investigate the prevalence of ED risk among adolescent girls and compare subgroups at high and low risk of ED; 2) to investigate using a multidimensional approach those variables that can interact with temperament and character traits to predict ED symptomatology. METHODS: The cross-sectional observational self-report study of a community sample of adolescent girls 1217 years old (n=298; M=14.771.13) was carried out in the city of Ryazan, Russia. The Russian versions of Eating Attitudes Test and Cloningers Temperament and Character Inventory-Revised were used. In addition, an original questionnaire (Risk Factors of Eating Disorders) was developed. Regression models (to test for significant moderation) and path analysis (to test for significant mediations) were used. RESULTS: Girls at risk of developing EDs are characterized by a heightened level of concern about weight and dissatisfaction with their body, tend to suffer from low self-directedness, higher novelty seeking and tendency to higher harm avoidance, display high alexithymia, experience self-distrust, negative emotionality and are dissatisfied with family relationships. They also suffer from low self-esteem and tend to be perfectionism and engage in risk behavior. Significant moderating effects were uncovered between the following ED risk factors: (1) self-distrust/risk behavior and BMI; (2) alexithymia/negative emotionality/self-esteem and cooperativeness; and (3) negative emotionality/risk behavior and self-transcendence. Family relationship dissatisfaction mediates the association between self-directedness/cooperativeness/self-transcendence and disordered eating. CONCLUSION: There are various mutual influences between the numerous ED risk and prevention factors, which all together determine the paths between the predictors and final outcome.

Constitutive and activation-dependent phosphorylation of lymphocyte phosphatase-associated phosphoprotein (LPAP).

Lymphocyte phosphatase-associated phosphoprotein (LPAP) is a small transmembrane protein expressed exclusively in lymphocytes. LPAP is a component of a supramolecular complex composed of the phosphatase CD45, the co-receptor CD4, and the kinase Lck. In contrast to its immunologically important partners, the function of LPAP is unknown. We hypothesized that the biological role of LPAP may be determined by analyzing LPAP phosphorylation. In the present study, we identified LPAP phosphorylation sites by site-directed mutagenesis, phospho-specific antibodies, and protein immunoprecipitation coupled to mass spectrometry analysis. Our results confirmed previous reports that Ser-99, Ser-153, and Ser-163 are phosphorylated, as well as provided evidence for the phosphorylation of Ser-172. Using various SDS-PAGE techniques, we detected and quantified a set of LPAP phosphoforms that were assigned to a combination of particular phosphorylation events. The phosphorylation of LPAP appears to be a tightly regulated process. Our results support the model: following phorbol 12-myristate 13-acetate (PMA) or TCR/CD3 activation of T cells, LPAP is rapidly dephosphorylated at Ser-99 and Ser-172 and slowly phosphorylated at Ser-163. Ser-153 exhibited a high basal level of phosphorylation in both resting and activated cells. Therefore, we suggest that LPAP may function as a co-regulator of T-cell signaling.

Lymphocyte phosphatase-associated phosphoprotein proteoforms analyzed using monoclonal antibodies.

Phosphatase CD45 regulates the activation of lymphocytes by controlling the level of receptor and signal molecule phosphorylation. However, it remains unknown which molecules mediate the phosphatase activity of CD45. A candidate for such a molecule is a small transmembrane adapter protein called lymphocyte phosphatase-associated phosphoprotein (LPAP). LPAP forms a supramolecular complex that consists of not only CD45 molecule but also CD4 and Lck kinase. The function of LPAP has not been defined clearly. In our study, we determined the pattern of LPAP expression in various cell types and characterized its proteoforms using new monoclonal antibodies generated against the intracellular portion of the protein. We show that LPAP is a pan-lymphocyte marker, and its expression in cells correlates with the expression of CD45. The majority of T, B and NK cells express high levels of LPAP, whereas monocytes, granulocytes, monocyte-derived dendritic cells, platelets and red blood cells are negative for LPAP. Using one- and two-dimensional protein gel electrophoresis, we demonstrate that LPAP has at least four sites of phosphorylation. The resting cells express at least six different LPAP phosphoforms representing mono-, di- and tri-phosphorylated LPAP. T and B cells differ in the distribution of the protein between phosphoforms. The activation of lymphocytes with PMA reduces the diversity of phosphorylated forms. Our experiments on Lck-deficient Jurkat cells show that Lck kinase is not involved in LPAP phosphorylation. Thus, LPAP is a dynamically phosphorylated protein, the function of which can be understood, when all phosphosites and kinases involved in its phosphorylation will be identified.