Master\u27s Recital: Judith Ross, Flute; Marcia Hishman, Piano; Ted Parge, Percussion; Tom Wang, Cello; January 27, 1976

Hayden AuditoriumTuesday EveningJanuary 27, 19768:15 p.m

Targeted neutralization of calmodulin in the nucleus blocks DNA synthesis and cell cycle progression

AbstractCalmodulin (CaM) is a major intracellular calcium binding protein which has been implicated in the regulation of cell proliferation. Previous studies using chemically synthesized CaM antagonists and anti-sense RNA indicated that CaM is important for initiation of DNA synthesis and cell cycle progression. However, these methods reduce total intracellular CaM and globally interfering with all the CaM-dependent processes. In order to explore the function of nuclear CaM during the cell cycle, a CaM inhibitor peptide was targeted to the nucleus of intact mammalian cells. Cell progression through S-phase was assessed by incorporation of the thymidine analogue, BrdU. Cells were transfected for 48 h with either the CaM inhibitor peptide gene or the control plasmid prior to analysis. Approx. 70% of the control cells incorporated BrdU. In striking contrast, double immunofluorescent labeling demonstrated that none of the cells expressing the CaM inhibitor peptide entered S-phase. This result indicates that neutralization of nuclear CaM by targeted expression of a CaM inhibitor peptide blocks DNA synthesis and cell cycle progression

Plasmacytoid dendritic cell interferon-alpha production to R-848 stimulation is decreased in male infants

BACKGROUND: Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). RESULTS: In this study, we identified sex differences in human infant pDC interferon-alpha production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-alpha production following R-848 challenge. CONCLUSIONS: Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy

Downregulation of Rap1GAP contributes to Ras transformation.

Although abundant in well-differentiated rat thyroid cells, Rap1GAP expression was extinguished in a subset of human thyroid tumor-derived cell lines. Intriguingly, Rap1GAP was downregulated selectively in tumor cell lines that had acquired a mesenchymal morphology. Restoring Rap1GAP expression to these cells inhibited cell migration and invasion, effects that were correlated with the inhibition of Rap1 and Rac1 activity. The reexpression of Rap1GAP also inhibited DNA synthesis and anchorage-independent proliferation. Conversely, eliminating Rap1GAP expression in rat thyroid cells induced a transient increase in cell number. Strikingly, Rap1GAP expression was abolished by Ras transformation. The downregulation of Rap1GAP by Ras required the activation of the Raf/MEK/extracellular signal-regulated kinase cascade and was correlated with the induction of mesenchymal morphology and migratory behavior. Remarkably, the acute expression of oncogenic Ras was sufficient to downregulate Rap1GAP expression in rat thyroid cells, identifying Rap1GAP as a novel target of oncogenic Ras. Collectively, these data implicate Rap1GAP as a putative tumor/invasion suppressor in the thyroid. In support of that notion, Rap1GAP was highly expressed in normal human thyroid cells and downregulated in primary thyroid tumors

Osteoblast-Derived FGF9 Regulates Skeletal Homeostasis

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three month old Fgf9OB −/− mice displayed a significant decrease in cancellous bone and bone formation in the distal femur and a significant decrease in cortical thickness at the TFJ. Strikingly, female Fgf9OB −/− mice did not display altered bone mass. Continuous treatment of mouse BMSCs with exogenous FGF9 inhibited mouse BMSC mineralization while acute treatment increased the proliferation of progenitors, an effect requiring the activation of Akt1. Our results suggest that mature OBs are an important source of FGF9, positively regulating skeletal homeostasis in male mice. Osteoblast-derived FGF9 may serve a paracrine role to maintain the osteogenic progenitor cell population through activation of Akt signaling

Perceived barriers to children’s active commuting to school: a systematic review of empirical, methodological and theoretical evidence

Active commuting to school (ACS) may increase children’s daily physical activity and help them maintain a healthy weight. Previous studies have identified various perceived barriers related to children’s ACS. However, it is not clear whether and how these studies were methodologically sound and theoretically grounded. The purpose of this review was to critically assess the current literature on perceived barriers to children’s ACS and provide recommendations for future studies. Empirically based literature on perceived barriers to ACS was systematically searched from six databases. A methodological quality scale (MQS) and a theory utilization quality scale (TQS) were created based on previously established instruments and tailored for the current review. Among the 39 studies that met the inclusion criteria, 19 (48.7%) reported statistically significant perceived barriers to child’s ACS. The methodological and theory utilization qualities of reviewed studies varied, with MQS scores ranging between 7 and 20 (Mean =12.95, SD =2.95) and TQS scores from 1 to 7 (Mean =3.62, SD =1.74). A detailed appraisal of the literature suggests several empirical, methodological, and theoretical recommendations for future studies on perceived barriers to ACS. Empirically, increasing the diversity of study regions and samples should be a high priority, particularly in Asian and European countries, and among rural residents; more prospective and interventions studies are needed to determine the causal mechanism liking the perceived factors and ACS; future researchers should include policy-related barriers into their inquiries. Methodologically, the conceptualization of ACS should be standardized or at least well rationalized in future studies to ensure the comparability of results; researchers’ awareness need to be increased for improving the methodological rigor of studies, especially in regard to appropriate statistical analysis techniques, control variable estimation, multicollinearity testing, and reliability and validity reporting. Theoretically, future researchers need to first ground their investigations in theoretical foundations; efforts should be devoted to make sure theories are used thoroughly and correctly; important theoretical constructs, in particular, need to be conceptualized and operationalized appropriately to ensure accurate measurement. By reviewing what has been achieved, this review offered insights for more sophisticated ACS studies in the future

Semibrittle seismic deformation in high-temperature mantle mylonite shear zone along the Romanche transform fault

Oceanic transform faults, a key element of plate tectonics, represent the first-order discontinuities along mid-ocean ridges, host large earthquakes, and induce extreme thermal gradients in lithosphere. However, the thermal structure along transform faults and its effects on earthquake generation are poorly understood. Here we report the presence of a 10- to 15-kilometer-thick in-depth band of microseismicity in 10 to 34 kilometer depth range associated with a high-temperature (700\ub0 to 900\ub0C) mantle below the brittle lithosphere along the Romanche mega transform fault in the equatorial Atlantic Ocean. The occurrence of the shallow 2016 moment magnitude 7.1 supershear rupture earthquake and these deep microearthquakes indicate that although large earthquakes occur in the upper brittle lithosphere, a substantial amount of deformation is accommodated in the semibrittle mylonitic mantle that resides at depths below the 600\ub0C isotherm. We also observe a rapid westward deepening of this band of seismicity indicating a strong lateral heterogeneity