scholarly journals Transport of the Dicyanogold(I) Anion

1994 ◽  
Vol 1 (5-6) ◽  
pp. 433-443 ◽  
Author(s):  
Katherine Tepperman ◽  
Yafei Zhang ◽  
Pamela W. Roy ◽  
Roger Floyd ◽  
Zheng Zhao ◽  
...  

We have shown that dicyanogold(I), [Au(CN)2]- is a common metabolite found in blood and urine samples of patients treated with different gold based drugs. Some patients have high levels of gold within their red blood cells (RBCs). Size exclusion and C18 reversed phase chromatography show that the majority of the gold in RBC lysates is bound to protein, but small molecules such as dicyanogold(I) and gold-glutathione complexes are also present. Dicyanogold incubation with red blood cells in vitro leads to a rapid and complete uptake of gold. This uptake is unaffected by DIDS, an inhibitor of the anion channel, but is blocked by the addition of external cyanide. Dicyanogold is also readily taken up by H9 cells, a continuous CD4+ cell line. This uptake is significantly inhibited by N-ethylmaleimide, suggesting a requirement for sulfhydryl groups. Dicyanogold inhibits the replication of the AIDS virus, HIV, in a cell culture model.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Lattke ◽  
Robert Goldstone ◽  
James K. Ellis ◽  
Stefan Boeing ◽  
Jerónimo Jurado-Arjona ◽  
...  

AbstractAstrocytes have essential functions in brain homeostasis that are established late in differentiation, but the mechanisms underlying the functional maturation of astrocytes are not well understood. Here we identify extensive transcriptional changes that occur during murine astrocyte maturation in vivo that are accompanied by chromatin remodelling at enhancer elements. Investigating astrocyte maturation in a cell culture model revealed that in vitro-differentiated astrocytes lack expression of many mature astrocyte-specific genes, including genes for the transcription factors Rorb, Dbx2, Lhx2 and Fezf2. Forced expression of these factors in vitro induces distinct sets of mature astrocyte-specific transcripts. Culturing astrocytes in a three-dimensional matrix containing FGF2 induces expression of Rorb, Dbx2 and Lhx2 and improves astrocyte maturity based on transcriptional and chromatin profiles. Therefore, extrinsic signals orchestrate the expression of multiple intrinsic regulators, which in turn induce in a modular manner the transcriptional and chromatin changes underlying astrocyte maturation.


2020 ◽  
Author(s):  
Michael Lattke ◽  
Robert Goldstone ◽  
Francois Guillemot

SummaryAstrocytes have diverse functions in brain homeostasis. Many of these functions are acquired during late stages of differentiation when astrocytes become fully mature. The mechanisms underlying astrocyte maturation are not well understood. Here we identified extensive transcriptional changes that occur during astrocyte maturation and are accompanied by chromatin remodelling at enhancer elements. Investigating astrocyte maturation in a cell culture model revealed that in vitro-differentiated astrocytes lacked expression of many mature astrocyte-specific genes, including genes for the transcription factors Rorb, Dbx2, Lhx2 and Fezf2. Forced expression of these factors in vitro induced distinct sets of mature astrocytes-specific transcripts. Culturing astrocytes with FGF2 in a three-dimensional gel induced expression of Rorb, Dbx2 and Lhx2 and improved their maturity based on transcriptional and chromatin profiles. Therefore extrinsic signals orchestrate the expression of multiple intrinsic regulators, which in turn induce in a modular manner the transcriptional and chromatin changes underlying astrocyte maturation.


mBio ◽  
2021 ◽  
Author(s):  
Linbo Zhao ◽  
Michael J. Imperiale

BK polyomavirus (BKPyV) generally establishes a persistent subclinical infection in healthy individuals but can cause severe disease in transplant recipients. While an in vitro model to study acute replication exists, no practical model with which to study BKPyV persistence is currently available.


Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).


2004 ◽  
Vol 171 (4S) ◽  
pp. 295-295
Author(s):  
Fernando C. Delvecchio ◽  
Ricardo M. Brizuela ◽  
Karen J. Byer ◽  
W. Patrick Springhart ◽  
Saeed R. Khan ◽  
...  

2013 ◽  
Vol 1 (Suppl. 1) ◽  
pp. A4.1
Author(s):  
Angela Storka
Keyword(s):  

2016 ◽  
Vol 16 (9) ◽  
pp. 1190-1197 ◽  
Author(s):  
Dziugas Meskelevicius ◽  
Kastytis Sidlauskas ◽  
Ruta Bagdonaviciute ◽  
Julius Liobikas ◽  
Daiva Majiene

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Donghoon Kang ◽  
Natalia V. Kirienko

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.


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