Biomedical subjects
Publications and source records attributed to S Coen.
The structure and dynamics of the domain walls separating segregated condensates in trapped mixtures of repulsive Bose-Einstein condensates are studied. Our work reveals that, under fairly general conditions, these domain walls behave as independent dynamical entities, which allows us to identify them as constituting a novel class of multicomponent solitons in Bose-Einstein condensates.
The p53 protein is subject to Mdm2-mediated degradation by the ubiquitin-proteasome pathway. This degradation requires interaction between p53 and Mdm2 and the subsequent ubiquitination and nuclear export of p53. Exposure of cells to DNA damage results in the stabilization of the p53 protein in the nucleus. However, the underlying mechanism of this effect is poorly defined. Here we demonstrate a key role for c-Abl in the nuclear accumulation of endogenous p53 in cells exposed to DNA damage. This effect of c-Abl is achieved by preventing the ubiquitination and nuclear export of p53 by Mdm2, or by human papillomavirus E6. c-Abl null cells fail to accumulate p53 efficiently following DNA damage. Reconstitution of these cells with physiological levels of c-Abl is sufficient to promote the normal response of p53 to DNA damage via nuclear retention. Our results help to explain how p53 is accumulated in the nucleus in response to DNA damage.
The p53 oncosuppressor protein regulates cell cycle checkpoints and apoptosis, but increasing evidence also indicates its involvement in differentiation and development. We had previously demonstrated that in the presence of differentiation-promoting stimuli, p53-defective myoblasts exit from the cell cycle but do not differentiate into myocytes and myotubes. To identify the pathways through which p53 contributes to skeletal muscle differentiation, we have analyzed the expression of a series of genes regulated during myogenesis in parental and dominant-negative p53 (dnp53)-expressing C2C12 myoblasts. We found that in dnp53-expressing C2C12 cells, as well as in p53(-/-) primary myoblasts, pRb is hypophosphorylated and proliferation stops. However, these cells do not upregulate pRb and have reduced MyoD activity. The transduction of exogenous TP53 or Rb genes in p53-defective myoblasts rescues MyoD activity and differentiation potential. Additionally, in vivo studies on the Rb promoter demonstrate that p53 regulates the Rb gene expression at transcriptional level through a p53-binding site. Therefore, here we show that p53 regulates myoblast differentiation by means of pRb without affecting its cell cycle-related functions.
Stable numerical convolution of the diffusion impulse time response with a Gaussian wave packet produces a wave packet whose delay time is governed by an eikonal equation where the diffusivity distribution plays the role of the square of the velocity distribution. Diffusion delay time tomography data can approximately image the diffusivity distribution by solving an inverse problem for the eikonal equation with multiple rays that traverse low diffusivity regions not traversed by earlier related methods, and consequently the resolution in such regions is improved. This is important for medical imaging.
Experiments previously performed on 32D and C2C12 cell lines indicated that wild type p53 (wtp53) protein has a role in granulocyte and myotube differentiation. Since these are immortal cells, we asked whether the inhibition of differentiation induced by the expression of dominant-negative p53 (dnp53) proteins was dependent on the immortalization-determined microenvironment. Thus, we evaluated the effects produced by interfering with the endogenous p53 gene in murine primary hemopoietic and muscle cells. Expression of dnp53 protein reduced the differentiation of bone marrow cells into granulocytes and macrophages. Moreover, p53 activation was measurable during the differentiation process of primary myoblasts, while interference with this activation led to a consistent slow down of terminal differentiation. Since the impairment of the differentiation was not accompanied by alterations in the cell cycle withdrawal and in the rate of apoptosis which are coupled with these types of differentiation, the data here reported support a specific role for p53 in the differentiation process. However, the difference in the intensity of inhibition between immortal and primary cells, i. e., complete versus slow down, respectively, suggests that the immortalization process might render the cells more sensitive to the loss of wtp53 activity for the differentiation process.
We describe a case study evaluation of Kansas LEAN, a statewide partnership with the mission of reducing risks for chronic diseases through dietary and exercise modification. We used a case study design to examine five primary questions related to process and outcome: (a) were the goals of the partnership important to constituents? (process), (b) were constituents satisfied with the partnership (process), (c) were community or systems changes (new or modified programs, policies, or practices) facilitated by partnership efforts (outcome)?, (d) were these changes important to the partnership's mission (outcome)?, and (e) what critical events helped facilitate community changes (outcome)? several measurement instruments--a monitoring and feedback system, constituent surveys, and semistructured interviews--were used to address key evaluation questions. Kansas LEAN is a strong statewide partnership with involvement from key representatives throughout Kansas. It is an ongoing, comprehensive health promotion program that plans and implements multiple components, in a variety of settings, to create awareness, behavior change, and a supportive environment. Kansas LEAN has facilitated several important community or systems changes related to its mission. We conclude with a discussion of the challenges of evaluating partnerships that seek to reduce risks for chronic diseases.
The involvement of p53 protein in cell differentiation has been recently suggested by some observations made with tumor cells and the correlation found between differentiation and increased levels of p53. However, the effect of p53 on differentiation is in apparent contrast with the normal development of p53-null mice. To test directly whether p53 has a function in cell differentiation, we interfered with the endogenous wt-p53 protein of nontransformed cells of two different murine histotypes: 32D myeloid progenitors, and C2C12 myoblasts. A drastic inhibition of terminal differentiation into granulocytes or myotubes, respectively, was observed upon expression of dominant-negative p53 proteins. This inhibition did not alter the cell cycle withdrawal typical of terminal differentiation, nor p21(WAF1/CIP1) upregulation, indicating that interference with endogenous p53 directly affects cell differentiation, independently of the p53 activity on the cell cycle. We also found that the endogenous wt-p53 protein of C2C12 cells becomes transcriptionally active during myogenesis, and this activity is inhibited by p53 dominant-negative expression. Moreover, we found that p53 DNA-binding and transcriptional activities are both required to induce differentiation in p53-negative K562 cells. Taken together, these data strongly indicate that p53 is a regulator of cell differentiation and it exerts this role, at least in part, through its transcriptional activity.
Reducing purchase and consumption of higher-fat foods is an important health objective for the nation since these behaviors are associated with cardiovascular disease and some cancers. Public health agents attempt to promote health-related behaviors, such as purchases of lower-fat foods, by changing key features of relevant environments. This study examined the effects of a marketing intervention in a supermarket on customer purchases of lower-fat products. Customers of one store of a major supermarket chain participated in this study. Direct observations of customer purchases of lower-fat milk, salad dressings, and frozen desserts were conducted. The supermarket intervention consisted of prompting, product sampling, and price reduction (store coupons). Using an interrupted time series design with switching replications, we found low to moderate increases for the lower-fat counterparts of milk, frozen desserts, and salad dressing. The greatest increase in purchases was found with frozen desserts. Findings from this study suggest that prompting, product sampling, and price reduction can increase customer purchases of some lower-fat products. Implications of these findings for the development and evaluation of health marketing interventions are discussed.
In October 1993, the Tobacco-Free Wichita Coalition proposed ordinances to the Wichita City Council that would tightly control access of minors to tobacco and prohibit smoking in public places. The subsequent successful change in local health policy required the collaborative efforts of local and state organizations and health agencies. A simple random telephone survey commissioned and financed by the coalition demonstrated that 76 percent (95 percent CI = 72 percent to 80 percent) of adult Wichita-Sedgwick County residents favored enforced penalties for merchants selling tobacco to minors, and 62 percent (95 percent CI = 58 percent to 66 percent) favored a ban on tobacco vending machines. Fifty-four percent (95 percent CI = 50 percent to 58 percent) favored a smoking ban in all public places.
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BACKGROUND: Expression of exogenous wild-type p53 (wt-p53) protein in tumor cells can suppress the transformed phenotype whereas it does not apparently induce detrimental effects in non-transformed cells. This observation may provide a molecular basis for p53-mediated gene therapy of p53-sensitive cancers without the need for tumor targeting. METHODS: To understand the molecular mechanisms responsible for this different behavior in tumor versus normal cells, biochemical and functional analyses of exogenous wt-p53 protein were performed on non-transformed C2C12 myoblasts and their transformed counterparts, the C2-ras cells. RESULTS: The exogenous wt-p53 protein, which induced persistent growth arrest only in transformed C2-ras cells, was shown to be significantly more stable in transformed than in non-transformed cells. This different stability was due to different p53 proteolytic degradation. Moreover, constitutively, exogenous wt-p53 protein was found to be transcriptionally active only in C2-ras cells but it could also be activated in C2C12 cells by genotoxic damage. CONCLUSIONS: Non-transformed C2C12 cells present regulatory system(s) which control the expression and the activity of exogenously expressed wt-p53 protein probably through degradation and maintenance in a latent form. This regulatory system is lost/inactivated upon transformation.