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Genetics and genomics of exposure to high altitude
Published in Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson, Ward, Milledge and West's High Altitude Medicine and Physiology, 2021
Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson
HIFs are transcription factors that respond to changes in available oxygen in the cellular environment. A transcription factor is a protein that binds to a specific DNA sequence and regulates the transcription of genetic information from DNA to messenger RNA (mRNA). Increasing the rate of gene transcription is referred to as upregulation, while decreasing the rate of gene transcription is called downregulation. There are additional proteins such as coactivators that also play a role in transcription of DNA but typically do not contain DNA-binding domains.
General Aspects of Endocrine Physiology
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Receptor numbers in target cells alter considerably in a dynamic fashion, as they may be inactivated or destroyed; alternatively, they may be reactivated or increased. A decrease in the responsiveness of target tissue as a result of a decreased number of active receptors is known as down-regulation. This can result from inactivation of some receptor molecules or from decreased production of receptor molecules. Up-regulation may occur when increased receptors are available, usually caused by increased synthesis of receptor molecules due to the stimulating hormone. This usually results in an increased effect of the hormone.
The Molecular Basis of Action of Abused Substances
Published in Frank Lynn Iber, Alcohol and Drug Abuse as Encountered in Office Practice, 2020
Cells adjust to need by increasing or decreasing the numbers of receptors in the surface. If there are more receptors (up regulation), the cell becomes more sensitive to the hormone; the opposite is true for down regulation (fewer receptors).
Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure
Published in OncoImmunology, 2022
Tassilo L. A. Wachsmann, Anne K. Wouters, Dennis F. G. Remst, Renate S. Hagedoorn, Miranda H. Meeuwsen, Eline van Diest, Jeanette Leusen, Jürgen Kuball, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
To assess the expression of coinhibitory molecules on eTCR and CAR T cells after activation, we cocultured TCR and CAR T cells with ALL CM at E:T ratios of 1:1 or 1:3 for 72 h and assessed the expression of PD-1 and LAG3 by flow cytometry (Figure 4a). Interestingly, CAR T cells already displayed elevated levels of PD-1 ad LAG3 expression in the absence of antigenic stimulation (Figures 4b and 4c). After antigen exposure, both 1E9 TCR T cells and Ofa-28z CAR T cells upregulate PD-1 and LAG3 (Figure 4a). Notably, we observed differences in the extent of upregulation. Regarding PD-1, Ofa-28z CAR T cells express significantly higher levels of PD-1 at an E:T ratio of 1:3 as compared to 1E9 TCR T cells (Figure 4b). This is even more prominent concerning the expression of LAG3: while most (>90%) eTCR T cells as well as CAR T cells stained positive for LAG3 after exposure to an E:T ratio of 1:3 (Figure 3a), the expression level of LAG3 as indicated by gMFI was around threefold higher on Ofa-28z CAR T cells as compared to 1E9 TCR T cells (Figure 4c). FMC63-28z CAR T cells followed a pattern comparable to that of Ofa-28z CAR T cells. Taken together, the expression of PD-1 and LAG3 increases proportionally with antigen exposure on both eTCR T cells and CAR T cells, but to a greater extent on CAR T cells as compared to eTCR T cells.
Intratumoural administration of an NKT cell agonist with CpG promotes NKT cell infiltration associated with an enhanced antitumour response and abscopal effect
Published in OncoImmunology, 2022
Kef K Prasit, Laura Ferrer-Font, Olivia K Burn, Regan J Anderson, Benjamin J Compton, Alfonso J Schmidt, Johannes U Mayer, Chun-Jen J Chen, Nathaniel Dasyam, David S Ritchie, Dale I Godfrey, Stephen R Mattarollo, P Rod Dunbar, Gavin F Painter, Ian F Hermans
Antibody-mediated CD8 depletion studies highlighted a key role for CD8+ T cells in the antitumour activity of the combined treatment, which was supported by mass cytometry analysis showing enhanced activation and evidence of proliferation of CD8+ T cells and CD4+ T cells in tumours and dLNs at day 9, when tumours were yet to start regressing. However, by day 12, when the tumours had started to regress, expression of activation and proliferation markers were not as evident. In fact, when analysis was conducted by flow cytometry on day 12, no clear pattern of activation marker upregulation was detected. Nonetheless, analysis by immunohistochemistry showed increased CD8+ T cells in tumours administered the combined treatment, consistent with T cell-mediated antitumour activity.
TangNaiKang, herbal formulation, alleviates obesity in diabetic SHR/cp rats through modulation of gut microbiota and related metabolic functions
Published in Pharmaceutical Biology, 2022
Peng Tian, Lili Wu, Maya Kudo, Misa Hayashi, Lingling Qin, Ming Gao, Anlong Xu, Tonghua Liu
The most increased pathways include atrazine degradation, pentose and glucuronate interconversions, riboflavin metabolism, thiamine metabolism, tropane, piperidine, and pyridine alkaloid biosynthesis, and tyrosine metabolism. These pathways are at relatively low levels in the CON group. In the decreased pathways, the oxidative phosphorylation and the RNA degradation pathways are at relatively high levels in the CON group. These data suggest that metagenome changes play an important role in the protective effect of TNK formulation. Furthermore, the altered microbiota revealed a strong correlation between the intermediate products and process of SCFAs and glucose metabolism. Likewise, pentose and glucuronate interconversions were related to the glucuronate pathway and the synthesis of fatty acids and sterols. Also, riboflavin and thiamine, known as vitamin B1 and B2, respectively, are the key enzymes for glucose metabolism. They are important for glucose metabolism, oxidative metabolism, and cell stress response. We found that energy metabolism was disturbed in the CON group rats. Our findings showed that TNK formulation might alleviate the metabolism disorders through changes in gut microbiota. However, the whole mechanism of upregulation and downregulation of the pathways needs to be clarified.