The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.
HIV serostatus disclosure is a crucial decision, and often perceived as a double-edged sword for people living with HIV. This study was intended to determine the extent of disclosure according to interpersonal relationships, compare the characteristics of disclosure by modes of HIV transmission, and to describe perceived consequences after disclosure to Taiwanese families. Data were collected by in-depth interviews and chart reviews at HIV primary care clinics in a university hospital in southern Taiwan from 2004 to 2005. Of 105 male participants interviewed, 76 (72.4%) had disclosed their HIV status to at least one person, including 62% to an immediate family member and 21% to friends. The HIV disclosure rates were different in three groups divided by modes of transmission, 36% in men having sex with men (MSM), 34% in heterosexuals, and 21% in injection drug users (IDUs). MSM were more likely than heterosexual men or male IDUs to disclose their HIV status directly to friends immediately after leaning of their HIV diagnosis. Heterosexual men and male injection drug users often disclosed to their immediate families a few days after obtaining an HIV diagnosis. Perceived consequences after disclosure included: increased substantial support from family, assistance with medical and healthcare, encouragement of living positively with HIV, being rejected, treated as contagion, and condemnation. Disclosure of HIV-positive status in a family-oriented Taiwanese society is a complex process and different by the modes of transmission.
Many analytical methods use radial and rectangular systems to interpret unsteady‐state reservoir flow problems. However, there is no information currently available for irregularly shaped aquifers. For many practical cases the aquifer drainage shape is too complicated to be approximated by a circular or rectangular shape. This paper develops an image‐well method for predicting drawdown transient in an aquifer with irregularly shaped boundaries. Previously, the use of the image‐well method to predict drawdown transient was only possible for aquifer boundaries of regular shape.
In this paper, the well function is obtained by superposing the Theis solution of image wells in time. The image‐well method is first applied to regularly shaped aquifers. The validity of the approach is then proved by comparison of the calculated well functions with literature values for various regular drainage shapes. The proven method was applied to interpret a field pumping test and to characterize the reservoir boundaries with irregular shape.
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