Publications by authors named "G A Maul"

156 Publications

Optical communications downlink from a low-earth orbiting 1.5U CubeSat.

Opt Express 2019 Aug;27(17):24382-24392

In this article, we present the first demonstration of an optical communications downlink from a low-earth orbiting free-flying CubeSat. Two 1.5U vehicles, AC7-B&C, built under NASA's Optical Communications and Sensors Demonstration (OCSD) program were launched in November 2017 and subsequently placed into a 450-km, 51.6° inc. circular orbit. Pseudorandom data streams using on-off key (OOK) modulation were transmitted from AC-7B to a 40 cm aperture telescope located at sea level in El Segundo, CA. At 200 Mbps, without forward error correction (FEC), we achieved a 115-second link that was ~78% error free, with the remaining portion exhibiting an error rate below 1E-5. At the time of the engagement, the 1064-nm laser transmitter was operating at 2 W (half capacity) with a full width half maximum (FWHM) beam divergence of ~1 mrad, which was approximately double the anticipated pointing accuracy of the vehicle.
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http://dx.doi.org/10.1364/OE.27.024382DOI Listing
August 2019

Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter-regulated transcription site.

Mol Biol Cell 2013 May 13;24(9):1454-68. Epub 2013 Mar 13.

Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA.

Promyelocytic leukemia nuclear bodies (PML-NBs)/nuclear domain 10s (ND10s) are nuclear structures that contain many transcriptional and chromatin regulatory factors. One of these, Sp100, is expressed from a single-copy gene and spliced into four isoforms (A, B, C, and HMG), which differentially regulate transcription. Here we evaluate Sp100 function in single cells using an inducible cytomegalovirus-promoter-regulated transgene, visualized as a chromatinized transcription site. Sp100A is the isoform most strongly recruited to the transgene array, and it significantly increases chromatin decondensation. However, Sp100A cannot overcome Daxx- and α-thalassemia mental retardation, X-linked (ATRX)-mediated transcriptional repression, which indicates that PML-NB/ND10 factors function within a regulatory hierarchy. Sp100A increases and Sp100B, which contains a SAND domain, decreases acetyl-lysine regulatory factor levels at activated sites, suggesting that Sp100 isoforms differentially regulate transcription by modulating lysine acetylation. In contrast to Daxx, ATRX, and PML, Sp100 is recruited to activated arrays in cells expressing the herpes simplex virus type 1 E3 ubiquitin ligase, ICP0, which degrades all Sp100 isoforms except unsumoylated Sp100A. The recruitment Sp100A(K297R), which cannot be sumoylated, further suggests that sumoylation plays an important role in regulating Sp100 isoform levels at transcription sites. This study provides insight into the ways in which viruses may modulate Sp100 to promote their replication cycles.
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http://dx.doi.org/10.1091/mbc.E12-09-0669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639056PMC
May 2013

Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling.

EMBO J 2011 May 13;30(12):2465-76. Epub 2011 May 13.

School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

Microglia, the resident macrophages of the mammalian central nervous system, migrate to sites of tissue damage or infection and become activated. Although the persistent secretion of inflammatory mediators by the activated cells contributes to the pathogenesis of various neurological disorders, most activated microglia eventually undergo apoptosis through the process of activation-induced cell death (AICD). The molecular mechanism of AICD, however, has remained unclear. Here, we show that Daxx and mammalian Ste20-like kinase-1 (MST1) mediate apoptosis elicited by interferon-γ (IFN-γ) in microglia. IFN-γ upregulated the expression of Daxx, which in turn mediated the homodimerization, activation, and nuclear translocation of MST1 and apoptosis in microglial cells. Depletion of Daxx or MST1 by RNA interference also attenuated IFN-γ-induced cell death in primary rat microglia. Furthermore, the extent of IFN-γ-induced death of microglia in the brain of MST1-null mice was significantly reduced compared with that apparent in wild-type mice. Our results thus highlight new functions of Daxx and MST1 that they are the key mediators of microglial cell death initiated by the proinflammatory cytokine IFN-γ.
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http://dx.doi.org/10.1038/emboj.2011.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116283PMC
May 2011

Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program.

Cancer Res 2010 Dec 30;70(23):9991-10001. Epub 2010 Nov 30.

The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Identifying the functions of proteins, which associate with specific subnuclear structures, is critical to understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML nuclear bodies, which colocalizes with Daxx and the proto-oncogenic PML. Sp100 isoforms contain SAND, PHD, Bromo, and HMG domains and are highly sumoylated, all characteristics suggestive of a role in chromatin-mediated gene regulation. A role for Sp100 in oncogenesis has not been defined previously. Using selective Sp100 isoform-knockdown approaches, we show that normal human diploid fibroblasts with reduced Sp100 levels rapidly senesce. Subsequently, small rapidly dividing Sp100 minus cells emerge from the senescing fibroblasts and are found to be highly tumorigenic in nude mice. The derivation of these tumorigenic cells from the parental fibroblasts is confirmed by microsatellite analysis. The small rapidly dividing Sp100 minus cells now also lack ND10/PML bodies, and exhibit genomic instability and p53 cytoplasmic sequestration. They have also activated MYC, RAS, and TERT pathways and express mesenchymal to epithelial transdifferentiation (MET) markers. Reintroduction of expression of only the Sp100A isoform is sufficient to maintain senescence and to inhibit emergence of the highly tumorigenic cells. Global transcriptome studies, quantitative PCR, and protein studies, as well as immunolocalization studies during the course of the transformation, reveal that a transient expression of stem cell markers precedes the malignant transformation. These results identify a role for Sp100 as a tumor suppressor in addition to its role in maintaining ND10/PML bodies and in the epigenetic regulation of gene expression.
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http://dx.doi.org/10.1158/0008-5472.CAN-10-1483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059726PMC
December 2010

LIM protein Ajuba functions as a nuclear receptor corepressor and negatively regulates retinoic acid signaling.

Proc Natl Acad Sci U S A 2010 Feb 26;107(7):2938-43. Epub 2010 Jan 26.

The Wistar Institute, Philadelphia, PA 19104, USA.

Corepressors play an essential role in nuclear receptor-mediated transcriptional repression. In general, corepressors directly bind to nuclear receptors via CoRNR boxes (L/I-X-X-I/V-I) in the absence of ligand and appear to act as scaffolds to further recruit chromatin remodeling complexes to specific target genes. Here, we describe the identification of the multiple LIM domain protein Ajuba as a unique corepressor for a subset of nuclear hormone receptors. Ajuba contains functional nuclear-receptor interacting motifs and selectively interacts with retinoic acid receptors (RARs) and rexinoid receptor (RXRs) subtypes in a ligand-dependent manner. Simultaneous mutation of these motifs abolishes RAR binding and concomitantly leads to loss of repression on RARE reporter genes. P19 cells depleted of Ajuba are highly sensitized to all-trans retinoic acid (atRA)-induced transcription and differentiation. In the absence of atRA, Ajuba can be readily found at the RARE control elements of RAR endogenous target genes. Stimulation of cells with atRA results in the dissociation of Ajuba from these regions. Moreover, we observed that coexpression of the known Ajuba binding partner Prmt5 (protein arginine methyltransferase-5) inhibited the Ajuba/RAR interaction. The high-affinity Ajuba-RAR/RXR interaction site overlaps the region responsible for Ajuba/Prmt5 binding, and thus binding appears to be mutually exclusive, providing a potential mechanism for these observations. Identification of Ajuba as a unique corepressor for nuclear receptors sheds new light on mechanisms for nuclear receptor-mediated repression and provides a unique target for developing more effective therapeutics to modulate this important pathway.
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http://dx.doi.org/10.1073/pnas.0908656107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840334PMC
February 2010
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