Topological Insulator Magnetic Tunnel Junctions: Quantum Hall Effect and Fractional Charge via Folding

We provide a characterization of tunneling between coupled topological insulators in 2D and 3D under the influence of a ferromagnetic layer. We explore conditions for such systems to exhibit integer quantum Hall physics and localized fractional charge, also taking into account interaction effects for the 2D case. We show that the effects of tunneling are topologically equivalent to a certain deformation or folding of the sample geometry. Our key advance is the realization that the quantum Hall or fractional charge physics can appear in the presence of only a \emph{single} magnet unlike previous proposals which involve magnetic domain walls on the surface or edges of topological insulators respectively. We give illustrative topological folding arguments to prove our results and show that for the 2D case our results are robust even in the presence of interactions.Comment: 5 pages, 2 figure

Fractional Spin Josephson Effect and Electrically Controlled Magnetization in Quantum Spin Hall Edges

We explore a spin Josephson effect in a system of two ferromagnets coupled by a tunnel junction formed of 2D time-reversal invariant topological insulators. In analogy with the more commonly studied instance of the Josephson effect for charge in superconductors, we investigate properties of the phase-coherent {\it spin} current resulting from the misalignment of the in-plane magnetization angles of the two ferromagnets. We show that the topological insulating barrier offers the exciting prospect of hosting a {\it fractional} spin Josephson effect mediated by bound states at the ferromagnet-topological insulator interface. We provide multiple perspectives to understand the $4\pi$ periodic nature of this effect. We discuss several measurable consequences, such as, the generation of a transverse voltage signal which allows for purely electrical measurements, an inverse of this effect where an applied voltage gives rise to a transverse spin-current, and a fractional AC spin-Josephson effect.Comment: 5 pages, 2 figures (v2:fixed typo, added reference

Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

<p>Abstract</p> <p>Background</p> <p>Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.</p> <p>Methods</p> <p>Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.</p> <p>Results</p> <p>Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.</p> <p>Conclusions</p> <p>SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.</p

Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila

<div><h3>Background</h3><p>Notch signaling is a highly conserved pathway in multi-cellular organisms ranging from flies to humans. It controls a variety of developmental processes by stimulating the expression of its target genes in a highly specific manner both spatially and temporally. The diversity, specificity and sensitivity of the Notch signaling output are regulated at distinct levels, particularly at the level of ligand-receptor interactions.</p> <h3>Methodology/Principal Findings</h3><p>Here, we report that the <em>Drosophila</em> gene <em>uninflatable</em> (<em>uif</em>), which encodes a large transmembrane protein with eighteen EGF-like repeats in its extracellular domain, can antagonize the canonical Notch signaling pathway. Overexpression of Uif or ectopic expression of a neomorphic form of Uif, Uif*, causes Notch signaling defects in both the wing and the sensory organ precursors. Further experiments suggest that ectopic expression of Uif* inhibits Notch signaling <em>in cis</em> and acts at a step that is dependent on the extracellular domain of Notch. Our results suggest that Uif can alter the accessibility of the Notch extracellular domain to its ligands during Notch activation.</p> <h3>Conclusions/Significance</h3><p>Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.</p> </div

Transforming Growth Factor β Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function

The transforming growth factor β (TGFβ) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGFβ type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGFβ ligands. Tgfbr1 null mice die embryonically, precluding functional characterization of TGFBR1 postnatally. To study TGFBR1–mediated signaling in female reproduction, we generated a mouse model with conditional knockout (cKO) of Tgfbr1 in the female reproductive tract using anti-Müllerian hormone receptor type 2 promoter-driven Cre recombinase. We found that Tgfbr1 cKO females are sterile. However, unlike its role in growth differentiation factor 9 (GDF9) signaling in vitro, TGFBR1 seems to be dispensable for GDF9 signaling in vivo. Strikingly, we discovered that the Tgfbr1 cKO females develop oviductal diverticula, which impair embryo development and transit of embryos to the uterus. Molecular analysis further demonstrated the dysregulation of several cell differentiation and migration genes (e.g., Krt12, Ace2, and MyoR) that are potentially associated with female reproductive tract development. Moreover, defective smooth muscle development was also revealed in the uteri of the Tgfbr1 cKO mice. Thus, TGFBR1 is required for female reproductive tract integrity and function, and disruption of TGFBR1–mediated signaling leads to catastrophic structural and functional consequences in the oviduct and uterus

Role of EZH2 in Uterine Gland Development

Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility