Control of amino acid transport into Chinese hamster ovary cells.

Amino acid transporters (AATs) represent a key interface between the cell and its environment, critical for all cellular processes: Energy generation, redox control, and synthesis of cell and product biomass. However, very little is known about the activity of different functional classes of AATs in Chinese hamster ovary (CHO) cells, how they support cell growth and productivity, and the potential for engineering their activity and/or the composition of amino acids in growth media to improve CHO cell performance in vitro. In this study, we have comparatively characterized AAT expression in untransfected and monoclonal antibody (MAb)-producing CHO cells using transcriptome analysis by RNA-seq, and mechanistically dissected AAT function using a variety of transporter-specific chemical inhibitors, comparing their effect on cell proliferation, recombinant protein production, and amino acid transport. Of a possible 56 mammalian plasma membrane AATs, 16 AAT messenger RNAs (mRNAs) were relatively abundant across all CHO cell populations. Of these, a subset of nine AAT mRNAs were more abundant in CHO cells engineered to produce a recombinant MAb. Together, upregulated AATs provide additional supply of specific amino acids overrepresented in MAb biomass compared to CHO host cell biomass, enable transport of synthetic substrates for glutathione synthesis, facilitate transport of essential amino acids to maintain active protein synthesis, and provide amino acid substrates for coordinated antiport systems to maintain supplies of proteinogenic and essential amino acids.

Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public.

STUDY OBJECTIVES: This study aimed to quantify the impact of excessive daytime sleepiness (EDS) on patient and patient's partner health-related quality of life in the form of utility values typically used in health economic evaluations. METHODS: A time trade-off study was conducted in a UK general population sample (representing a societal perspective) to elicit utility values, measured on a 0 to 1 scale, for health states with varying obstructive sleep apnea-associated EDS severity. In a time trade-off study, health states are described, and participants "trade off" time in a specific higher severity state for a shorter amount of time in full health. RESULTS: Overall, the sample consisted of 104 participants, who were interviewed and took part in the time trade-off exercise to elicit utility values for patient and partner residual EDS health states. The average utility score declined with increasing obstructive sleep apnea-associated EDS severity for both patient (no EDS, 0.926; mild EDS, 0.794; moderate EDS, 0.614; severe EDS, 0.546) and partner (no EDS, 0.955; mild EDS, 0.882; moderate EDS, 0.751; severe EDS, 0.670) health states. CONCLUSIONS: These results demonstrate the high impact that EDS in obstructive sleep apnea is estimated to have on patient and partner health-related quality of life. CITATION: Tolley K, Noble-Longster J, Mettam S, et al. Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public. J Clin Sleep Med. 2022;18(9):2237-2246.