ABSTRACT
STRADalpha is a pseudokinase that forms a heterotrimeric complex with the scaffolding protein MO25 and the tumor suppressor serine threonine protein kinase LKB1. Mutations in the LKB1 gene are responsible for the Peutz-Jeghers Syndrome (PJS) characterized by a predisposition to hamartomatous polyps and hyperpigmentation of the buccal mucosa. Mutations in LKB1 have also been observed in some sporadic tumours unrelated to PJS. The LKB1/STRAD/MO25 complex is involved in the regulation of numerous signaling pathways including metabolism, proliferation and cellular polarity of human intestinal epithelial cells. Cell polarization, together with tissue-restricted transcription, represents the main feature of enterocyte differentiation. Since a full-length STRADalpha transcript has not been identified thus far in these cells, we evaluated the expression of endogenous STRADalpha in five colorectal cancer cell lines characterized by their diverse ability to differentiate in vitro. We report herein the discovery of several novel splice isoforms of STRADalpha that differentially affect the kinase activity, complex assembly, subcellular localization of LKB1 and the activation of the LKB1-dependent AMPK pathway.
Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Colorectal Neoplasms/metabolism , Protein Serine-Threonine Kinases/metabolism , AMP-Activated Protein Kinase Kinases , Adaptor Proteins, Vesicular Transport/genetics , Alternative Splicing , Cell Differentiation , Cell Line, Tumor , Cell Polarity , Enterocytes/cytology , Humans , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Serine-Threonine Kinases/analysis , Transcription, GeneticABSTRACT
OBJECTIVE: The present study evaluated the factors that contribute to stress and the psychological difficulties of the Italian military component of the United Nations Mission in Bosnia and Herzegovina. This group was compared with a homogeneous group stationed in Italy. METHODS: A cross-sectional study was performed in two groups of career military personnel: 452 subjects who were stationed in Bosnia as peacekeepers and 166 who were stationed in Italy. All subjects completed two multiple-choice questionnaires (a stress self-evaluation test and a socioeconomic questionnaire) during various periods of duty. RESULTS: The responses to the stress self-evaluation test indicated that the peacekeepers did not show a statistically significant increase in stress. Those who were affected by stress, though, indicated that the level was high. The principal variables that were associated with a greater level of stress were length of the mission, lack of recreational or athletic activities during the mission, more than three family members, and unemployment before enrollment. CONCLUSIONS: Peacekeepers come from an economically poor environment, have large families, and usually have a history of unemployment. Along with these preenrollment risk factors, the effective time spent in recreational activities and the length of the mission also influence stress levels. Individual and group techniques for stress management should be implemented.
Subject(s)
Burnout, Professional/etiology , Burnout, Professional/psychology , Military Personnel/psychology , Relief Work , Adult , Bosnia and Herzegovina , Cross-Sectional Studies , Employment , Family Characteristics , Humans , Italy , Leisure Activities , Logistic Models , Military Personnel/statistics & numerical data , Risk Factors , Socioeconomic Factors , Surveys and Questionnaires , Time Factors , United NationsABSTRACT
The Authors present three cases of Non-Hodgkin's Lymphoma (NHL) in pregnancy and discuss about problem of diagnosis and management of NHL in this condition. They stress that the diagnosis of NHL in pregnancy is delayed and the clinical progression of lymphoma is probably influenced by hormonal and immunological changes occurring during pregnancy. On the other hand the management of NHL is problematic because radiotherapy is potentially teratogenic. (By editorial staff).
