Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands

2005 ◽  
Vol 25 (2-3) ◽  
pp. 201-209 ◽  
Author(s):  
Teréz Márián ◽  
László Balkay ◽  
Gábor Szabó ◽  
Zoárd T. Krasznai ◽  
Zoltán Hernádi ◽  
...  
2021 ◽  
Vol 22 (14) ◽  
pp. 7522
Author(s):  
Yassin Elfaki ◽  
Juhao Yang ◽  
Julia Boehme ◽  
Kristin Schultz ◽  
Dunja Bruder ◽  
...  

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.


2017 ◽  
Vol 14 (7) ◽  
pp. 458 ◽  
Author(s):  
Perrine Dranguet ◽  
Vera I. Slaveykova ◽  
Séverine Le Faucheur

Environmental contextMercury (Hg) is a major environmental contaminant due to its toxicity, accumulation and biomagnification along the food chain. We demonstrate that Hg accumulation by biofilms, one possible entry point for Hg into food webs, is rapid and depends on biofilm structure and composition. These findings have important implications for the understanding of Hg bioavailability and effects towards aquatic microorganisms. AbstractMercury contamination is of high concern due to its bioaccumulation, toxicity and biomagnification along the food chain. Biofilms can accumulate Hg and contribute to its incorporation in freshwater food webs. Nevertheless, the accumulation kinetics of Hg by biofilms is not well described and understood. The aim of the present study was thus to gain mechanistic understanding of Hg accumulation by biofilms. Kinetics of Hg uptake by biofilms of different ages (e.g. different compositions) was characterised by determining Hg contents in biofilms with and without a cysteine-washing step. Hg accumulation was rapid in both biofilms, with the uptake rate constant of the younger biofilm 10 times higher than that of the older biofilm. Moreover, accumulated Hg reached a plateau at 24h exposure in the younger biofilm, whereas it increased linearly in the older biofilm. The observed difference in Hg uptake by the studied biofilms is likely a result of the difference in biofilm thickness (and thus Hg diffusion inside the biofilm matrix) and microbial composition. These findings have important implications for the understanding of Hg bioavailability and effects towards aquatic microorganisms.


1997 ◽  
Vol 77 (2) ◽  
pp. 545-590 ◽  
Author(s):  
W. D. Stein

Most cancer deaths result from the cancer's either being intrinsically resistant to chemotherapeutic drugs or becoming resistant after being initially sensitive. Often, in cells grown in cell culture, drug resistance correlates with the presence of one or more of the so-called P-glycoproteins or multidrug resistance proteins, products of the mdr family of genes. This review is largely concerned with the transport kinetics of the P-glycoproteins. We first present a brief overview of the P-glycoproteins, their properties, and their clinical significance. Later sections of the review expand on this material with special emphasis on the substrates of P-glycoprotein and how they cross the cell membrane, on the transport kinetics of the P-glycoprotein, on reversers of its action, and on its activity as an ATPase. In a final section, we consider the mechanism of action of P-glycoprotein as an actively transporting membrane pump. The characteristic of P-glycoprotein considered the most difficult to explain is its very broad specificity (or lack of specificity), but there are precedents for this property in well-known proteins such as serum albumin, which binds a range of molecular types, including substrates and reversers of P-glycoprotein, seemingly as broad as does P-glycoprotein. Pointing out this analogy does not provide a molecular explanation for the substrate-binding properties of P-glycoprotein but does make those properties more assimilable.


2013 ◽  
Vol 112 (6) ◽  
pp. 401-411 ◽  
Author(s):  
Ulla Mårs ◽  
Roland d'Argy ◽  
Karin Hallbeck ◽  
Anna Miller‐Larsson ◽  
Staffan Edsbäcker

2011 ◽  
Vol 178-179 ◽  
pp. 404-409
Author(s):  
Mykola Kras'ko ◽  
Anatolii Kraitchinskii ◽  
Andrii Kolosiuk ◽  
Volodymyr Neimash ◽  
Vasyl Voitovych ◽  
...  

Accumulation kinetics of vacancy-oxygen (VO) complexes in Czochralski (Cz) n-Si at 360 °C and 1 MeV electron pulse irradiation has been investigated. It is shown that during the irradiation and simultaneous generation and annealing of VO centers, the accumulation kinetics has non-linear dependence with saturation. It is found that there is a maximal concentration of VO centers, which depends on the radiation intensity (J) and temperature as well. It is also established the annealing of VO centers can substantially be stimulated by the intensity of electron irradiation. An increase of J from 1.25×1015 to 1.25×1016 electrons/(сm2s) does not influence the generation efficiency of VO, though it accelerates their annealing by more than one order of magnitude.


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