scholarly journals Unexplored regulatory sequences of divergently paired GLA and HNRNPH2 loci pertinent to Fabry disease in human kidney and skin cells: Presence of an active bidirectional promoter

2020 ◽  
Vol 21 (2) ◽  
Author(s):  
Mohammed Al-Obaide ◽  
Ibtisam Al-Obaidi ◽  
Tetyana Vasylyeva
2016 ◽  
Vol 311 (5) ◽  
pp. F1015-F1024 ◽  
Author(s):  
Ester M. Pereira ◽  
Anatália Labilloy ◽  
Megan L. Eshbach ◽  
Ankita Roy ◽  
Arohan R. Subramanya ◽  
...  

Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of α-galactosidase A (α-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable α-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD.


2012 ◽  
Vol 11 (3) ◽  
pp. 260-269 ◽  
Author(s):  
Xinyi Wang ◽  
Yu-Ping Xiao ◽  
Anne Bouchut ◽  
Basima Al-Khedery ◽  
Hongbin Wang ◽  
...  

ABSTRACTRapid clonal antigenic variation inBabesia bovisinvolves thevarianterythrocytesurfaceantigen-1 (VESA1) protein expressed on the infected-erythrocyte surface. Because of the significance of this heterodimeric protein for demonstrated mechanisms of parasite survival and virulence, there is a need to understand how expression of thevesmultigene family encoding this protein is controlled. As an initial step toward this goal, we present here initial characterization of thevespromoter driving transcription of VESA1a and -1b subunits. A series of transfection constructs containing various sequence elements from thein vivolocus of activevestranscription (LAT) were used to drive expression of the firefly luciferase gene in a dual luciferase-normalized assay. The results of this approach reveal the presence of two bidirectional promoter activities within the 434-bp intergenic region (IGr), influenced by putative regulatory sequences embedded within the flankingves1α andves1β genes. Repressor-like effects on the apposing gene were observed for intron 1 of bothves1α andves1β. This effect is apparently not dependent upon intronic promoter activity and acts only incis. The expression of genes within thevesfamily is likely modulated by local elements embedded withinvescoding sequences outside the intergenic promoter region in concert with chromatin modifications. These results provide a framework to help us begin to understand gene regulation during antigenic variation inB. bovis.


Author(s):  
H. M. Sagara ◽  
S. A. Schliebe ◽  
M. C. Kong

Particle analysis by scanning electron microscopy with energy-dispersive x- ray analysis is one of the current methods used in crime laboratories to aid law enforcement in identifying individuals who have recently fired or handled a firearm. During the discharge of a firearm, the high pressure caused by the detonation of the cartridge materials forces a portion of the generated gases through leaks in the firing mechanism of the weapon. These gases contain residues of smokeless powder, primer mixture, and contributions from the projectile itself. The condensation of these hot gases form discrete, micrometer-sized particles, which can be collected, along with dry skin cells, salts, and other hand debris, from the hands of a shooter by a simple adhesive lift technique. The examination of the carbon-coated adhesive lifts consist of time consuming systematic searches for high contrast particles of spherical morphology with the characteristic elemental composition of antimony, barium and lead. A detailed list of the elemental compositions which match the criteria for gunshot residue are discussed in the Aerospace report.


2005 ◽  
Vol 173 (4S) ◽  
pp. 300-300
Author(s):  
Sreedhar Sagi ◽  
Lutz Trojan ◽  
Peter Aiken ◽  
Maurice S. Michel ◽  
Thomas Knoll

2005 ◽  
Vol 173 (4S) ◽  
pp. 103-103
Author(s):  
Adam G. Baseman ◽  
Andrew J. Kirsch ◽  
Fray F. Marshall ◽  
Haiyen E. Zhau ◽  
Leland W.K. Chung ◽  
...  

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