Dual and opposing roles of primary cilia in medulloblastoma development.

Recent work has shown that primary cilia are essential for Hedgehog (Hh) signaling during mammalian development. It is also known that aberrant Hh signaling can lead to cancer, but the role of primary cilia in oncogenesis is not known. Cerebellar granule neuron precursors (GNPs) can give rise to medulloblastomas, the most common malignant brain tumor in children. The primary cilium and Hh signaling are required for GNP proliferation. We asked whether primary cilia in GNPs have a role in medulloblastoma growth in mice. Genetic ablation of primary cilia blocked medulloblastoma formation when this tumor was driven by a constitutively active Smoothened protein (Smo), an upstream activator of Hh signaling. In contrast, removal of cilia was required for medulloblastoma growth by a constitutively active glioma-associated oncogene family zinc finger-2 (GLI2), a downstream transcription factor. Thus, primary cilia are either required for or inhibit medulloblastoma formation, depending on the initiating oncogenic event. Remarkably, the presence or absence of cilia was associated with specific variants of human medulloblastomas; primary cilia were found in medulloblastomas with activation in HH or WNT signaling but not in most medulloblastomas in other distinct molecular subgroups. Primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of tumorigenesis

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host

Structure of the full-length TRPV2 channel by cryo-EM.

Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels

Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation: The Enantioselective α-Enolation of Aldehydes

The first enantioselective organocatalytic α-enolation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Chiral secondary amines react with aldehydes to form transient enamines that undergo selective one-electron oxidation to generate electrophilic radical cations. These SOMO-activated radical cations are susceptible to attack by ketone-derived enol silanes, rendering α-substituted-γ-ketoaldehyde products with uniformly high levels of asymmetric induction. Wide latitude in both the aldehyde and enolsilane component is readily accommodated, allowing generic access to a diverse assortment of enantioenriched 1,4-dicarbonyl compounds. This report highlights the potential of SOMO catalysis to enable the development of entirely new classes of asymmetric reactions that have no traditional catalytic equivalents

Photonic generation of high-frequency microwave signals utilizing a multi-transverse- mode vertical-cavity surface-emitting laser subject to two-frequency orthogonal optical injection

We study photonic microwave signal generation obtained when single- and multi-transverse-mode vertical-cavity surface-emitting lasers (VCSELs) are subject to two-frequency orthogonal optical injection. Our calculations show that broadly tunable microwave signals can be obtained in these systems. The response of the multi-transversemode VCSEL is enhanced with respect to that obtained with a similar single-transverse-mode VCSEL subject to the same two-frequency orthogonal optical injection. The extra degree of freedom given by the multi-transverse-mode operation of the VCSEL under two-frequency orthogonal optical injection enhances the performance of the photonic microwave generation system, because the higher-order transverse mode is excited with a much larger amplitude than that of the fundamental transverse mode. Periodic oscillations are obtained for a very wide range of frequency detunings between the optical injections and transverse modes. A relative maximum of the microwave signal amplitude is obtained when the frequency of one of the optical injections is very close to the frequency of the orthogonally polarized fundamental mode of the VCSEL. Periodic oscillations are demonstrated for symmetric and asymmetric values of the injection strengths. Wide tuning ranges, extended into the THz band, are obtained in our system. Our results show that the proposed microwave signal generation mechanism is independent of the polarization of the master lasers. © 2012 Optical Society of America.This work is supported by the Ministerio de Ciencia e Innovación under project TEC2009-14581-C02-02. A. Quirce was supported in part by the Fondo Social Europeo (FSE) under the programme Junta de Ampliación de Estudios (JAE-predoc). H. Lin acknowledges support from the National Science Foundation under Grant No. PHY-1068789.Peer Reviewe

Target recognitions in multiple camera CCTV using colour constancy

People tracking using colour feature in crowded scene through CCTV network have been a popular and at the same time a very difficult topic in computer vision. It is mainly because of the difficulty for the acquisition of intrinsic signatures of targets from a single view of the scene. Many factors, such as variable illumination conditions and viewing angles, will induce illusive modification of intrinsic signatures of targets. The objective of this paper is to verify if colour constancy (CC) approach really helps people tracking in CCTV network system. We have testified a number of CC algorithms together with various colour descriptors, to assess the efficiencies of people recognitions from real multi-camera i-LIDS data set via Receiver Operating Characteristics (ROC). It is found that when CC is applied together with some form of colour restoration mechanisms such as colour transfer, the recognition performance can be improved by at least a factor of two. An elementary luminance based CC coupled with a pixel based colour transfer algorithm, together with experimental results are reported in the present paper