Matters of the heart

What does it take to make a heart? Even in the fruit fly, in which matters of the heart don’t extend to either pop music or pulp fiction, making a heart requires big decisions and processes of surprising complexity

Modulation of human JAK-STAT pathway signaling by functionally conserved regulators

Both the core JAK-STAT pathway components and their in vivo roles have been widely conserved between vertebrates and invertebrate models such as Drosophila melanogaster. Misregulation of JAK-STAT pathway activity has also been identified as a key factor in the development of multiple human malignancies. Recently, whole genome RNA interference (RNAi) screens in cultured Drosophila cells have identified both positively and negatively acting JAK-STAT pathway regulators. Here, we describe the analysis of 73 human genes representing homologs of 56 Drosophila genes originally identified by genome-wide RNAi screening as regulators of JAK-STAT signaling. Using assays for human STAT1 and STAT3 protein levels and phosphorylation status, as well as assays measuring the expression of endogenous STAT1 and STAT3 transcriptional targets, we have tested siRNAs targeting these 73 human genes and have identified potential JAK-STAT pathway regulatory roles in 69 (95%) of these. The genes identified represent a wide range of human JAK-STAT pathway regulators and include genes not previously known to modulate this signaling cascade. These results underline the value of model system based approaches for the identification of pathway regulators and have led to the identification of loci whose misregulation may ultimately be implicated in JAK-STAT pathway-mediated human disease

Lower and upper estimates on the excitation threshold for breathers in DNLS lattices

We propose analytical lower and upper estimates on the excitation threshold for breathers (in the form of spatially localized and time periodic solutions) in DNLS lattices with power nonlinearity. The estimation depending explicitly on the lattice parameters, is derived by a combination of a comparison argument on appropriate lower bounds depending on the frequency of each solution with a simple and justified heuristic argument. The numerical studies verify that the analytical estimates can be of particular usefulness, as a simple analytical detection of the activation energy for breathers in DNLS lattices.Comment: 10 pages, 3 figure

Drosophila SOCS Proteins

The importance of signal transduction cascades such as the EGFR and JAK/STAT pathways for development and homeostasis is highlighted by the high levels of molecular conservation maintained between organisms as evolutionary diverged as fruit flies and humans. This conservation is also mirrored in many of the regulatory mechanisms that control the extent and duration of signalling in vivo. One group of proteins that represent important physiological regulators of both EGFR and JAK/STAT signalling is the members of the SOCS family. Only 3 SOCS-like proteins are encoded by the Drosophila genome, and despite this low complexity, Drosophila SOCS proteins share many similarities to their human homologues. SOCS36E is both a target gene and negative regulator of JAK/STAT signalling while SOCS44A and SOCS36E represent positive and negative regulators of EGFR signalling. Here we review our current understanding of Drosophila SOCS proteins, their roles in vivo, and future approaches to elucidating their functions

Some homogenization and corrector results for nonlinear monotone operators

This paper deals with the limit behaviour of the solutions of quasi-linear equations of the form \ \ds -\limfunc{div}\left(a\left(x, x/{\varepsilon _h},Du_h\right)\right)=f_h on $\Omega$ with Dirichlet boundary conditions. The sequence $(\varepsilon _h)$ tends to $0$ and the map $a(x,y,\xi )$ is periodic in $y$, monotone in $\xi$ and satisfies suitable continuity conditions. It is proved that $u_h\rightarrow u$ weakly in $H_0^{1,2}(\Omega )$, where $u$ is the solution of a homogenized problem \ -\limfunc{div}(b(x,Du))=f on $\Omega$. We also prove some corrector results, i.e. we find $(P_h)$ such that $Du_h-P_h(Du)\rightarrow 0$ in $L^2(\Omega ,R^n)$

Correctors for some nonlinear monotone operators

In this paper we study homogenization of quasi-linear partial differential equations of the form -\mbox{div}\left( a\left( x,x/\varepsilon _h,Du_h\right) \right) =f_h on $\Omega$ with Dirichlet boundary conditions. Here the sequence $\left( \varepsilon _h\right)$ tends to $0$ as $h\rightarrow \infty$ and the map $a\left( x,y,\xi \right)$ is periodic in $y,$ monotone in $\xi$ and satisfies suitable continuity conditions. We prove that $u_h\rightarrow u$ weakly in $W_0^{1,p}\left( \Omega \right)$ as $h\rightarrow \infty ,$ where $u$ is the solution of a homogenized problem of the form -\mbox{div}\left( b\left( x,Du\right) \right) =f on $\Omega .$ We also derive an explicit expression for the homogenized operator $b$ and prove some corrector results, i.e. we find $\left( P_h\right)$ such that $Du_h-P_h\left( Du\right) \rightarrow 0$ in $L^p\left( \Omega, \mathbf{R}^n\right)$

Modulation of human JAK-STAT pathway signaling by functionally conserved regulators

Both the core JAK-STAT pathway components and their in vivo roles have been widely conserved between vertebrates and invertebrate models such as Drosophila melanogaster. Misregulation of JAK-STAT pathway activity has also been identified as a key factor in the development of multiple human malignancies. Recently, whole genome RNA interference (RNAi) screens in cultured Drosophila cells have identified both positively and negatively acting JAK-STAT pathway regulators. Here, we describe the analysis of 73 human genes representing homologs of 56 Drosophila genes originally identified by genome-wide RNAi screening as regulators of JAK-STAT signaling. Using assays for human STAT1 and STAT3 protein levels and phosphorylation status, as well as assays measuring the expression of endogenous STAT1 and STAT3 transcriptional targets, we have tested siRNAs targeting these 73 human genes and have identified potential JAK-STAT pathway regulatory roles in 69 (95%) of these. The genes identified represent a wide range of human JAK-STAT pathway regulators and include genes not previously known to modulate this signaling cascade. These results underline the value of model system based approaches for the identification of pathway regulators and have led to the identification of loci whose misregulation may ultimately be implicated in JAK-STAT pathway-mediated human disease

Detailed Spectroscopic and Photometric Analysis of DQ White Dwarfs

We present an analysis of spectroscopic and photometric data for cool DQ white dwarfs based on improved model atmosphere calculations. In particular, we revise the atmospheric parameters of the trigonometric parallax sample of Bergeron et al.(2001), and discuss the astrophysical implications on the temperature scale and mean mass, as well as the chemical evolution of these stars. We also analyze 40 new DQ stars discovered in the first data release of the Sloan Digital Sky Survey.Comment: 6 pages,3 figures, 14th European Workshop on White Dwarfs, ASP Conference Series, in pres