Characterization of a single genomic locus encoding the clustered protocadherin receptor diversity in Xenopus tropicalis

Clustered protocadherins (cPcdhs) constitute the largest subgroup of the cadherin superfamily (Hulpiau & van Roy, 2009) and in mammals are grouped into clusters of alpha-, beta- and gamma-types. Tens of tandemly-arranged paralogous Pcdh genes of the protocadherin clusters generate a substantial diversity of receptor isoforms. cPcdhs are known to have important roles in neuronal development and genetic alterations of cPcdhs have been found to be associated with several neurological diseases. Here, we present a first characterization of cPcdhs in Xenopus tropicalis (X. tropicalis). We determined and annotated all cPcdh isoforms revealing that they are present in a single chromosomal locus. We validated a total of 96 isoforms, which we show are organized in three distinct clusters. The X. tropicalis cPcdh locus is composed of one alpha- and two distinct gamma-protocadherin clusters (pcdh-gamma1 and pcdh-gamma2). Bioinformatics analyses assisted by genomic BAC clone sequencing showed that the X. tropicalis alpha- and gamma-protocadherins are conserved at the cluster level, but unlike mammals, X. tropicalis does not contain a beta-protocadherin cluster. In contrast, the number of gamma-protocadherin isoforms has expanded possibly due to lineage-specific gene duplications. Interestingly, the number of X. tropicalis alpha-protocadherins is identical between X. tropicalis and mouse. Moreover, we find highly conserved as well as novel promoter elements potentially involved in regulating the cluster-specific expression of clustered protocadherin isoforms. This study provides important information for the understanding of the evolutionary history of cPcdh genes and future mechanistic studies. It provides an annotated X. tropicalis cPcdh genomic map and a first molecular characterization essential for functional and comparative studies

Suppression of mid-infrared plasma resonance due to quantum confinement in delta-doped silicon

The classical Drude model provides an accurate description of the plasma resonance of three-dimensional materials, but only partially explains two-dimensional systems where quantum mechanical effects dominate such as P:$\delta$-layers - atomically thin sheets of phosphorus dopants in silicon that induce novel electronic properties beyond traditional doping. Previously it was shown that P:$\delta$-layers produce a distinct Drude tail feature in ellipsometry measurements. However, the ellipsometric spectra could not be properly fit by modeling the $\delta$-layer as discrete layer of classical Drude metal. In particular, even for large broadening corresponding to extremely short relaxation times, a plasma resonance feature was anticipated but not evident in the experimental data. In this work, we develop a physically accurate description of this system, which reveals a general approach to designing thin films with intentionally suppressed plasma resonances. Our model takes into account the strong charge density confinement and resulting quantum mechanical description of a P:$\delta$-layer. We show that the absence of a plasma resonance feature results from a combination of two factors: i), the sharply varying charge density profile due to strong confinement in the direction of growth; and ii), the effective mass and relaxation time anisotropy due to valley degeneracy. The plasma resonance reappears when the atoms composing the $\delta$-layer are allowed to diffuse out from the plane of the layer, destroying its well-confined two-dimensional character that is critical to its novel electronic properties

Modeling the ocean effect of geomagnetic storms

At coastal sites, geomagnetic variations for periods shorter than a few days are strongly distorted by the conductivity of the nearby sea-water. This phenomena, known as the ocean (or coast) effect, is strongest in the magnetic vertical component. We demonstrate the ability to predict the ocean effect of geomagnetic storms at geomagnetic observatories. The space-time structure of the storm is derived from the horizontal components at worldwide distributed observatories from which we predict the vertical component using a model of the Earth's conductivity that a) only depends on depth, and b) includes the conductivity of the sea-water. The results for several strong geomagnetic storms (including the "Bastille Day" event of July 14-15, 2000) show much better agreement (improvement by up to a factor of 2.5) between the observed and the modeled magnetic vertical component at coastal sites if the oceans are considered. Our analysis also indicates a significant local time asymmetry (i.e., contributions from spherical harmonics other than P-I(0)), especially during the main phase of the storm

Realizations of Real Low-Dimensional Lie Algebras

Using a new powerful technique based on the notion of megaideal, we construct a complete set of inequivalent realizations of real Lie algebras of dimension no greater than four in vector fields on a space of an arbitrary (finite) number of variables. Our classification amends and essentially generalizes earlier works on the subject. Known results on classification of low-dimensional real Lie algebras, their automorphisms, differentiations, ideals, subalgebras and realizations are reviewed.Comment: LaTeX2e, 39 pages. Essentially exetended version. Misprints in Appendix are correcte

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa