Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells

MASH1 and MASH2, mammalian homologues of the Drosophila neural determination genes achaete-scute, are members of the basic helix-loop-helix (bHLH) family of transcription factors. We show here that murine P19 embryonal carcinoma cells can be used as a model system to study the regulation and function of these genes. MASH1 and MASH2 display complementary patterns of expression during the retinoic-acid-induced neuronal differentiation of P19 cells. MASH1 mRNA is undetectable in undifferentiated P19 cells but is induced to high levels by retinoic acid coincident with neuronal differentiation. In contrast, MASH2 mRNA is expressed in undifferentiated P19 cells and is repressed by retinoic acid treatment. These complementary expression patterns suggest distinct functions for MASH1 and MASH2 in development, despite their sequence homology. In retinoic-acid-treated P19 cells, MASH1 protein expression precedes and then overlaps expression of neuronal markers. However, MASH1 is expressed by a smaller proportion of cells than expresses such markers. MASH1 immunoreactivity is not detected in differentiated cells displaying a neuronal morphology, suggesting that its expression is transient. These features of MASH1 expression are similar to those observed in vivo, and suggest that P19 cells represent a good model system in which to study the regulation of this gene. Forced expression of MASH1 was achieved in undifferentiated P19 cells by transfection of a cDNA expression construct. The transfected cells expressing exogenous MASH1 protein contained E-box-binding activity that could be super-shifted by an anti-MASH1 antibody, but exhibited no detectable phenotypic changes. Thus, unlike myogenic bHLH genes, such as MyoD, which are sufficient to induce muscle differentiation, expression of MASH1 appears insufficient to promote neurogenesis

Interview with David Johnson by Andrea L’Hommedieu

Biographical NoteDavid E. Johnson was born on July 20, 1947, to Evelyn Irene (Hale) and Frank Tivis Johnson in Hardtner, Kansas. His father operated a grain elevator and his mother worked at a department store. He was raised in Enid, Oklahoma, attending Enid High School, where he excelled at debate, and was graduated from the University of Oklahoma with a degree in journalism. He worked for Ed Muskie’s 1972 presidential campaign in the “boiler room” and on his Intergovernmental Relations Committee from 1972 to 1978, working with Al From. He then worked for the Carter administration and for the Department of Health and Human Services. He was administrative assistant to George Mitchell from 1981 to 1984. After a period of a few months in the governmental relations office of the Pharmaceutical Manufacturers Association, he became executive director of the Democratic Senatorial Campaign Committee (DSCC). Since 1987 until the time of this interview, worked in a Washington, D.C. lobbying firm; he also held the position of chair of the Board of Directors of the Mitchell Institute. SummaryInterview includes discussion of: the Muskie 1972 presidential race; working for the Carter administration; his interview with Senator Mitchell for the administrative assistant position in the coffee shop of the Portland Airport; arriving in the Senate office without anyone having been informed that he was hired; hired as executive director of the Democratic Senatorial Campaign Committee (DSCC); the 1982 U.S. Senate campaign; the challenges that Mitchell’s schedule and travel back to Maine presented; anecdote about Mitchell and a senator’s ID card; the tradition for the Senate staff to relax with a few beers in the office after their senator was safely out of the office for the weekend; the familial nature of the Senate staffs when members of the staff had long tenures; smoking in the office; Gayle Cory, how she took to “raising” Johnson, her expertise, and her role in holding the office together; the atmosphere of Mitchell’s office and his leadership style; Johnson’s role as chief of staff; criticism of Mitchell as a tax-and-spend Democrat and Mitchell’s index card response; answering the mail and how Mitchell enjoyed calling some of those who had written his office; Mitchell’s overall strategy of piecing many small elements together to accomplish his goals; and the development of the working relationship between Johnson and Mitchell

Differences in the Experience of Caregiving Between Spouse and Adult Child Caregivers in Dementia With Lewy Bodies.

Background and objectivesDementia caregiving has been associated with increased burden, depression, grief, a decreased sense of well-being and quality of life, and a weakening of social support. Little is known about the experience of caregiving in Dementia with Lewy Bodies (DLB). The present study examines differences in the caregiving experience of spouse versus adult child caregivers of individuals with DLB.Research design and methodsIn this cross-sectional analytic study of spouses (n = 255) and adult children (n = 160) caregivers of individuals with DLB, participants completed an online survey of burden, grief, depression, well-being, quality of life, and social support.ResultsAdult child caregivers were more likely to care for women (p < .001) and see the care recipient less often (p < .001) than spouses. Adult child caregivers reported lower quality of life (p < .001) and more caregiver burden (p < .009), but also greater social support (p < .001) than spouses. Between group analyses of caregiver type by disease severity demonstrated that spousal caregivers experience greater grief with advancing disease (p = .005), while adult child caregivers increase social support with advancing disease (p < .001).Discussion and implicationsSpouses and adult children experience DLB caregiving differently. This was explained by the younger age of the adult child caregiver, frequency of contact with the care recipient, and differences in the care recipient's characteristics, frequency of neuropsychiatric symptoms, and disease severity. DLB caregiver support for this population should target psychoeducation for complicated neuropsychiatric symptoms in the care recipient. Screening all DLB caregivers for burden, grief, and depression is suggested to identify those that may benefit most from intervention. Spouses specifically may benefit from interventions that target increasing social support, while adult child caregivers may benefit from interventions aimed at mitigating burden and improving quality of life

Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Employee Age as a Moderator of the Relationship Between Ambition and Work Role Affect

Past research has demonstrated a negative relationship between ambition, or the desire to get ahead, and job satisfaction. In the present paper, age was hypothesized to moderate the relationship between ambition and job satisfaction such that the relationship between ambition and satisfaction is more negative for older employees than for younger employees. Three studies, with three criterion variables (promotion satisfaction, extrinsic job satisfaction, overall job satisfaction), were used to test the hypothesis. Results indicated support for the hypothesized interaction. The discussion focuses on the implications of the results for organizational and individual career management strategies