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Biology subjects

Heininen, J.

Publications and source records attributed to Heininen, J..

3 recordsLinked to original sources

Modifications of the 22A apoA-I mimetic peptide sequence improve the anti-atherosclerotic properties of synthetic HDL

Synthetic high-density lipoprotein (sHDL) constituted of apolipoprotein A-I (apoA-I) mimetic peptides and phospholipids are nanometer-scale particles designed to recreate biological functions of HDL particles in the context of cardiovascular disease. Particularly, the therapeutic efficacy of sHDL particles is attributed to their ability to promote reverse cholesterol transport (RCT), a process where accumulated cholesterol is transported from peripheral tissues to the liver for elimination. Here, we designed two novel apoA-I mimetic peptides (22A-F and 22A-P-18A) by modifying the sequence of the well-studied apoA-I mimetic peptide 22A. These modifications were intended to improve cholesterol efflux from macrophages in vitro and structural stability of sHDL particles in human plasma while preserving their ability to activate lecithin-cholesterol acyltransferase (LCAT). We performed a systematic examination of the potency of sHDL particles made with these peptides in cellular cholesterol efflux, activation of LCAT, plasma HDL remodeling and proteolytic stability. Our study highlights that these modifications improve cholesterol efflux and, in the case of 22A-P-18A, also cholesterol esterification rate by LCAT but they do not appear to influence HDL remodeling in human plasma. Nonetheless, the LCAT activity assay conducted in human plasma suggest that intact sHDL particles are present and are likely the primary contributors to the increased cholesterol esterification rate, rather than the pre-{beta} HDL fraction generated through HDL remodeling. These findings offer new mechanistic insights into how specific peptide modifications affect key steps in RCT, laying the groundwork for future studies to explore their functional relevance in atherosclerosis and HDL-based drug delivery applications.

pharmacology and toxicology↗

Photosynthetic adjustments maintain lettuce growth under dynamically changing lighting in controlled indoor farming setups

Studies have uncovered delicate mechanisms that enable plant acclimation to fluctuating light. Translating the knowledge to controlled environment agriculture could advance the development of cost-effective dynamic lighting strategies, but the effects of varying light intensities on vegetable crops remain poorly understood. Here we recorded chlorophyll fluorescence, photosynthetic activity, metabolic responses, and growth of lettuce (Lactuca sativa L.) cv. Katusa under dynamic lighting. The light intensity was varied at different times of the photoperiod with uniform daily light integral. Three setups, including a plant phenotyping facility, a small-scale vertical farm testbed and a larger-scale vertical farm were utilized to address the physiological responses and scalability of lighting strategies. We found that dynamic lighting supported lettuce cv. Katusa growth in all three indoor cultivation setups, even under artificial "split-night" regimes where the photoperiod was interrupted by two periods of darkness. The lettuce plants displayed delicate adjustments in photosynthetic light reactions and carbon metabolism, the latter of which followed the cumulative daily light integral under different lighting regimes. However, the overall metabolic composition of lettuce leaves did not respond to the changing light intensities. Our findings support the conclusion that dynamic lighting enables cost-effective lighting via optimization of electricity use in indoor cultivation. HighlightPhotosynthetic adjustments maintain lettuce (Lactuca sativa L.) cv. Katusa growth under dynamic lighting. This enables cost-effective cultivation via optimization of electricity use in controlled environment agriculture.

plant biology↗

Targeted and Untargeted Amine Metabolite Quantitation in Single Cells with Isobaric Multiplexing

We developed a single cell amine analysis approach utilizing isobarically multiplexed samples of 6 individual cells along with analyte abundant carrier. This methodology was applied for absolute quantitation of amino acids and untargeted relative quantitation of amines in a total of 108 individual cells using nanoflow LC with high-resolution mass spectrometry. Together with individually determined cell sizes, this provides the first absolute quantification of intracellular metabolites within individual cells. The targeted method was partially validated for 10 amino acids with limits of detection in low attomoles, linear calibration range covering analyte amounts typically from 30 amol to 120 fmol, and correlation coefficients (R) above 0.99. Using the cell sizes determined during dispensing, millimolar intracellular concentrations were determined. The untargeted approach yielded 249 features that were detected in at least 25% of the single cells, providing modest cell type separation on principal component analysis. Using Greedy forward selection with regularized least squares, a sub-selection of 100 features explaining most of the difference, was determined. These features were annotated using MS2 from analyte standards and accurate mass with library search. The approach provides accessible, sensitive, and high-throughput method with the potential to be expanded also to other forms of ultrasensitive analysis.

biochemistry↗