Vimentin, a member of the intermediate filament protein family, is regulated both developmentally and tissue specifically. It is also a marker of the metastatic potential of many tumor cells. Pre viously, the human vimentin promoter has been shown to contain multiple elements for the binding of both positive- and negative-acting regulatory factors. Transient transfection analysis of various vimentin 5'-end promoter sequences and mutants thereof fused to a reporter gene further defined two regulatory elements, a positive element that binds Sp1 and a negative element that binds the protein ZBP-89. ZBP-89 has been shown to be either a repressor or an activator of gene expression, depending on the promoter. Here, we show that for vimentin, both ZBP-89 and ZBP-99 repress reporter gene expression in Schneider (S2) cells. Deletion constructs confirm that the glutamine-rich region of Sp1 is required to enhance vimentin transcription, whereas the N-terminus of ZBP-89 is required to interact with Sp1 and repress gene expression. The overexpression of hTAF(II)130 can alleviate ZBP-89 repression in S2 cells, suggesting how ZBP-89 might serve to block gene expression.
Vimentin exhibits a complex pattern of developmentaland tissue-specific expression and is aberrantly expressed in most metastatic tumors. The human vimentin promoter contains multiple DNA elements, some of which enhance gene expression and one that inhibits. A silencer element (at À319) binds the repressor ZBP-89. Further upstream (at À757) is an element, which acts positively in the presence of the silencer element and, thus, is referred to as an antisilencer (ASE). Previously, we showed that Stat1a binds to this element upon induction by IFN-c. However, substantial binding and reporter gene activity was still present in nontreated cells. Here, we have found that Stat3 binds to the ASE element in vitro. Transfection experiments in COS-1 cells with various vimentin promoter--reporter constructs show that gene activity is dependent upon the cotransfection and activation of Stat3. Moreover, activated Stat3 can overcome ZBP-89 repression. Coimmunoprecipitation studies demonstrate that Stat3 and ZBP-89 can interact and confocal microscopy detects these factors to be colocalized in the nucleus. Moreover, a correlation exists between the presence of activated Stat3 and vimentin expression in MDA-MB-231 cells, which is lacking in MCF7 cells where vimentin is not expressed. In the light of these results, we propose that the interaction of Stat3 and ZBP-89 may be crucial for overcoming the effects of the repressor ZBP-89, which suggests a novel mode for Stat3 gene activation.
Background: Mental and psychological health of adolescents in general and prospective medical students in particular is a priority area to investigate as it affects wellbeing of the future doctors. Objectives: The current research was conducted to screen first year medical students accepted for enrollment at Alexandria Faculty of Medicine to identify those with a high probability of having psychological distress before the start of academic courses as well as explore the sources of stress among them.
Methods.A cross sectional survey of 779 high school graduates accepted for admission to Alexandria Faculty of medicine was conducted. Participants were approached on the days of obligatory pre-enrollment medical examination. The translated Arabic version of DASS 21 questionnaire was used to screen students for three negative emotional symptoms namely depression, anxiety and stress. Inquiry about age, sex, residency and type of high school was added. Results: More than a tenth of studied medical students (12.6%) suffered from severe or profound stress and 29.1% of them had mild to moderate stress. Moreover, one fifth (20%) of studied students were severely anxious and less than one third (29.3%) had mild to moderate anxiety. Severe and profound depression was diagnosed among 14.3% of students whereas, 18.7% them were moderately depressed. No association was found between any of studied negative emotional symptoms and the students' educational background or their residency. Conclusion: Nearly half of the prospective medical students might have some sort of psychological distress before starting their study in the Faculty of Medicine. They should be investigated to verify diagnosis and start intervention to minimize its adverse effects on academic performance and advancement at the faculty. Stress management courses should be considered for all medical students.
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