Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells.

MicroRNAs are often associated with the pathogenesis of many cancers, including head and neck squamous cell carcinoma (HNSCC). In particular, microRNA-21 (miR-21) appears to have a critical role in tumor cell survival, chemoresistance and HNSCC progression. In this study, we investigated matrix hyaluronan (HA)-induced CD44 (a primary HA receptor) interaction with the stem cell markers, Nanog and Stat-3, in HNSCC cells (HSC-3 cells). Our results indicate that HA binding to CD44 promotes Nanog-Stat-3 (also tyrosine phosphorylated Stat-3) complex formation, nuclear translocation and transcriptional activation. Further analyses reveal that miR-21 is controlled by an upstream promoter containing Stat-3 binding site(s), while chromatin immunoprecipitation assays demonstrate that stimulation of miR-21 expression by HA/CD44 signaling is Nanog/Stat-3-dependent in HNSCC cells. This process results in a decrease of a tumor suppressor protein (PDCD4), and an upregulation of i nhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in HSC-3 cells. Treatment of HSC-3 cells with Nanog- and/or Stat-3-specific small interfering RNAs effectively blocks HA-mediated Nanog-Stat-3 signaling events, abrogates miR-21 production and increases PDCD4 expression. Subsequently, this Nanog-Stat-3 signaling inhibition causes downregulation of survival protein (IAP) expression and enhancement of chemosensitivity. To further evaluate the role of miR-21 in tumor cell-specific functions, HSC-3 cells were also transfected with a specific anti-miR-21 inhibitor in order to silence miR-21 expression and block its target functions. Our results demonstrate that anti-miR-21 inhibitor not only upregulates PDCD4 expression but also decreases IAP expression and enhances chemosensitivity in HA-treated HNSCC cells. Together, these findings indicate that the HA-induced CD44 interaction with Nanog and Stat-3 has a pivotal role in miR-21 production leading to PDCD4 reduction, IAP upregulation and chemoresistance in HNSCC cells. This novel Nanog/Stat-3 signaling pathway-specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of HA/CD44-activated HNSCC

Challenges in experimental data integration within genome-scale metabolic models

A report of the meeting "Challenges in experimental data integration within genome-scale metabolic models", Institut Henri Poincar\'e, Paris, October 10-11 2009, organized by the CNRS-MPG joint program in Systems Biology.Comment: 5 page

A streamwise-constant model of turbulent pipe flow

A streamwise-constant model is presented to investigate the basic mechanisms responsible for the change in mean flow occuring during pipe flow transition. Using a single forced momentum balance equation, we show that the shape of the velocity profile is robust to changes in the forcing profile and that both linear non-normal and nonlinear effects are required to capture the change in mean flow associated with transition to turbulence. The particularly simple form of the model allows for the study of the momentum transfer directly by inspection of the equations. The distribution of the high- and low-speed streaks over the cross-section of the pipe produced by our model is remarkably similar to one observed in the velocity field near the trailing edge of the puff structures present in pipe flow transition. Under stochastic forcing, the model exhibits a quasi-periodic self-sustaining cycle characterized by the creation and subsequent decay of "streamwise-constant puffs", so-called due to the good agreement between the temporal evolution of their velocity field and the projection of the velocity field associated with three-dimensional puffs in a frame of reference moving at the bulk velocity. We establish that the flow dynamics are relatively insensitive to the regeneration mechanisms invoked to produce near-wall streamwise vortices and that using small, unstructured background disturbances to regenerate the streamwise vortices is sufficient to capture the formation of the high- and low-speed streaks and their segregation leading to the blunting of the velocity profile characteristic of turbulent pipe flow

Acknowledgements

The allocation of time is a crucial decision that influences many aspects of household welfare. According to standard theory it depends on the potential wage rate of spouses relative to their domestic productivity. A major problem, however, is that individual productivities are not observed. As a consequence, an important source of difference in household living standards alongside with heterogeneity in preferences and wage rates, cannot be accounted for. This paper presents a new methodology to estimate individual domestic productivity based on the informational content of a standard time use survey, with time inputs observable but domestic output immeasurable. It provides empirical evidence based on a sample of French two-earner couples. As a test of the empirical validity of this approach, the paper shows that the estimate of female domestic productivity is a significant variable in explaining the overall intra-household distribution of resources

Generic metrics and the mass endomorphism on spin three-manifolds

Let $(M,g)$ be a closed Riemannian spin manifold. The constant term in the expansion of the Green function for the Dirac operator at a fixed point $p\in M$ is called the mass endomorphism in $p$ associated to the metric $g$ due to an analogy to the mass in the Yamabe problem. We show that the mass endomorphism of a generic metric on a three-dimensional spin manifold is nonzero. This implies a strict inequality which can be used to avoid bubbling-off phenomena in conformal spin geometry.Comment: 8 page

A characterization of Dirac morphisms

Relating the Dirac operators on the total space and on the base manifold of a horizontally conformal submersion, we characterize Dirac morphisms, i.e. maps which pull back (local) harmonic spinor fields onto (local) harmonic spinor fields.Comment: 18 pages; restricted to the even-dimensional cas