Radial glia regulate Cajal–Retzius cell positioning in the early embryonic cerebral cortex

AbstractThe organization of neocortex, along its radial axis, into a six-layered structure is one of the most exquisite features of the brain. Because of their strategic localization in the marginal zone, and their expression of reelin, a signal that controls spatial ordering of cortical layers, Cajal–Retzius (C-R) cells play a crucial role in cortical patterning along this axis. Yet, it remains less well understood how C-R cell targeting itself is regulated. At the onset of corticogenesis when C-R cells first arrive in the cortex via tangential migration, radial glia (RG) are the main cell type present. This suggests that RG may play a role in C-R cell localization. To test this, we used genetic approaches to perturb RG scaffold during early corticogenesis. We found that disrupting RG endfoot adhesion to basal lamina consistently results in C-R cell displacement. These displacements do not appear to result from primary defects in neural progenitor cell proliferation, deficits in the meninges or basement membrane, or cell autonomous defects in C-R cells. Instead, they show close temporal and spatial correlation with RG endfoot retraction. Moreover, ablation of RG via cell cycle blockade similarly results in local displacement of C-R cells. These lines of evidence thus indicate that, during early corticogenesis, RG play a primary role in regulating spatial targeting of C-R cells. Since RG are also neural progenitors as well as neuronal migration scaffolds, these findings suggest that, during nervous system development, neuroepithelial stem cells may not only be responsible for generating a diverse array of neuronal cell types and facilitating their radial migration. They may also, through regulating the placement of guidepost cells, coordinate spatial patterning of the nervous system along its radial axis

The N-end rule pathway is a sensor of heme

The conjugation of arginine, by arginyl-transferase, to N-terminal aspartate, glutamate or oxidized cysteine is a part of the N-end rule pathway of protein degradation. We report that arginyl-transferase of either the mouse or the yeast Saccharomyces cerevisiae is inhibited by hemin (Fe3+-heme). Furthermore, we show that hemin inhibits arginyl-transferase through a redox mechanism that involves the formation of disulfide between the enzyme's Cys-71 and Cys-72 residues. Remarkably, hemin also induces the proteasome-dependent degradation of arginyl-transferase in vivo, thus acting as both a "stoichiometric" and "catalytic" down-regulator of the N-end rule pathway. In addition, hemin was found to interact with the yeast and mouse E3 ubiquitin ligases of the N-end rule pathway. One of substrate-binding sites of the yeast N-end rule's ubiquitin ligase UBR1 targets CUP9, a transcriptional repressor. This site of UBR1 is autoinhibited but can be allosterically activated by peptides that bear destabilizing N-terminal residues and interact with two other substrate-binding sites of UBR1. We show that hemin does not directly occlude the substrate-binding sites of UBR1 but blocks the activation of its CUP9-binding site by dipeptides. The N-end rule pathway, a known sensor of short peptides, nitric oxide, and oxygen, is now a sensor of heme as well. One function of the N-end rule pathway may be to coordinate the activities of small effectors, both reacting to and controlling the redox dynamics of heme, oxygen, nitric oxide, thiols, and other compounds, in part through conditional degradation of specific transcription factors and G protein regulators

Design method for quasi-isotropic transformation materials based on inverse Laplace's equation with sliding boundaries

The deformation method of transformation optics has been demonstrated to be a useful tool, especially in designing arbitrary and nonsingular transformation materials. Recently, there are emerging demands for isotropic material parameters, arising from the broadband requirement of the designed devices. In this work, the deformation method is further developed to design quasi-isotropic/isotropic transformation materials. The variational functional of the inverse Laplace's equation is investigated and found to involve the smooth and quasi-conformal nature of coordinate transformation. Together with the sliding boundary conditions, the inverse Laplace's equation can be utilized to give transformations which are conformal or quasi-conformal, depending on functionalities of interest. Examples of designing an arbitrary carpet cloak and a waveguide with arbitrary cross sections are given to validate the proposed idea. Compared with other quasi-conformal methods based on grid generation tools, the proposed method unifies the design and validation of transformation devices, and thus is much convenient.Comment: 8 pages, 4 figure

Relating U(N)xU(N) to SU(N)xSU(N) Chern-Simons Membrane theories

By integrating out the U(1)_B gauge field, we show that the U(n)xU(n) ABJM theory at level k is equivalent to a Z_k identification of the (SU(n)xSU(n))/Z_n Chern-Simons theory, but only when n and k are coprime. As a consequence, the k=1 ABJM model for two M2-branes in R^8 can be identified with the N=8 (SU(2)xSU(2))/Z_2 theory. We also conjecture that the U(2)xU(2) ABJM model at k=2 is equivalent to the N=8 SU(2)xSU(2)-theory.Comment: 16 pages, Latex; v2: references added; v3: Clarifications adde

Optimal Synthesis of Horizontally Aligned Single-Walled Carbon Nanotubes and Their Biofunctionalization for Biosensing Applications

As an influential candidate for highly sensitive biomolecule sensor, which can capture disease related biomolecules, carbon nanotube is useful material due to its unique properties. To adopt as a sensing platform, it is strongly needed to find optimal refined synthetic condition. In order to find the optimal synthetic conditions of horizontally aligned CNT, we performed quantity control of themixed gases of H-2 and CH4 injected. We successfully find that the formation of amorphous-like carbon was critically affected by some gas condition such as the flow rate of injected gases and ratios of gas mixture. Moreover, it should be noted that our horizontally aligned carbon nanotube array platform developed would offer another potential in developing nanoscale light source, where light emission results from electron-hole carrier recombinationope

The Primary Target Organ of Cryptococcus gattii Is Different from That of Cryptococcus neoformans in a Murine Model

Cryptococcosis is caused by the opportunistic pathogen Cryptococcus neoformans or by the primary pathogen Cryptococcus gattii. Epidemiological studies suggest that patients infected with C. gattii mainly present with pulmonary disease, while those infected with C. neoformans commonly manifest meningoencephalitis. We compared the pathogenesis of the two species using the C. neoformans H99 and C. gattii R265 strains in a murine inhalation model. C. neoformans grew faster in the brain and caused death by meningoencephalitis, while C. gattii grew faster in the lungs and caused death without producing fulminating meningoencephalitis. Despite the consistent failure to recover R265 cells from blood, a fraction of the R265 population was detected in the extrapulmonary organs, including the brain. Upon intravenous (i.v. ) inoculation of 104 cells via the tail vein, however, C. gattii produced severe meningoencephalitis, demonstrating that C. gattii cells can efficiently cross the blood-brain barrier. Interestingly, i.v. inoculation with five cells caused brain infection in only 10% of C. gattii-infected mice, compared to 60% of mice infected with C. neoformans. In mice that had been initially inoculated via the pulmonary route and subsequently challenged intravenously, a protective effect was observed only in mice infected with C. gattii. C. neoformans cells grew 10 to 100 times faster than C. gattii cells in blood or serum collected from naive mice. The paucity of meningoencephalitis upon inhalation of C. gattii, therefore, may be partly due to an unknown factor(s) in the host’s blood coupled with immune protection that reduces dissemination to the brain and fosters lung infection