Copper Chelation Represses the Vascular Response to Injury

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of the Cu2+ chelator tetrathiomolybdate was able to reduce neointimal thickening after balloon injury in the rat. Interestingly, although immunohistochemical analysis of control neointimal sections exhibited prominent staining for MAC1, IL-1alpha, S100A13, and the acidic phospholipid phosphatidylserine, similar sections obtained from tetrathiomolybdate-treated animals did not. Further, adenoviral gene transfer of the IL-1 receptor antagonist during vascular injury also significantly reduced the area of neointimal thickening. Our data suggest that intracellular copper may be involved in mediating the response to injury in vivo by its ability to regulate the stress-induced release of IL-1alpha by using the nonclassical export mechanism employed by human peripheral blood mononuclear cells in vitro

Lilliput

Catalog for the exhibition Lilliput held at the Seton Hall University Walsh Gallery, June 8 - July 24, 2009. Curated by Jeanne Brasile and Asha Ganpat. Includes an essay by Jeanne Brasile and Asha Ganpat. Includes color illustrations

Final report on LDRD project: Semiconductor surface-emitting microcavity laser spectroscopy for analysis of biological cells and microstructures

This article discusses a new intracavity laser technique that uses living or fixed cells as an integral part of the laser. The cells are placed on a GaAs based semiconductor wafer comprising one half of a vertical cavity surface-emitting laser. After placement, the cells are covered with a dielectric mirror to close the laser cavity. When photo-pumped with an external laser, this hybrid laser emits coherent light images and spectra that depend sensitively on the cell size, shape, and dielectric properties. The light spectra can be used to identify different cell types and distinguish normal and abnormal cells. The laser can be used to study single cells in real time as a cell-biology lab-on-a-chip, or to study large populations of cells by scanning the pump laser at high speed. The laser is well-suited to be integrated with other micro-optical or micro-fluidic components to lead to micro-optical-mechanical systems for analysis of fluids, particulates, and biological cells

A switch in numb isoforms is a critical step in cortical development

Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb-null state with antisense morpholino, followed by the re-expression of specific numb isoforms. The re-expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete-scute homologue (MASH1) expression, concurrent with the appearance of the microtubule[corrected]-associated [corrected] protein-2-positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strengthNRC publication: Ye

Insulin acts as both a selective survival factor for cortical neural stem cells with myogenic potential and an instructive myogenic differentiation signal.

NRC publication: Ye