The plant shoot body plan is highly variable, depending on the degree of branching. Characterization of the max1-max4 mutants of Arabidopsis demonstrates that branching is regulated by at least one carotenoid-derived hormone. Here we show that all four MAX genes act in a single pathway, with MAX1, MAX3, and MAX4 acting in hormone synthesis, and MAX2 acting in perception. We propose that MAX1 acts on a mobile substrate, downstream of MAX3 and MAX4, which have immobile substrates. These roles for MAX3, MAX4, and MAX2 are consistent with their known molecular identities. We identify MAX1 as a member of the cytochrome P450 family with high similarity to mammalian Thromboxane A2 synthase. This, with its expression pattern, supports its suggested role in the MAX pathway. Moreover, the proposed enzymatic series for MAX hormone synthesis resembles that of two already characterized signal biosynthetic pathways: prostaglandins in animals and oxilipins in plants.
SYNOPSISThis work describes the formation of discrete micelles (= 0.1 pm) from ABA poly-(oxyethylene-b-isoprene-b-oxyethylene) block copolymers in water. An efficient labeling of the micelles by polymerization of [ 14C] -styrene within the hydrophobic core is also described. These micellar nanoparticles are being considered as promising materials for controlled release and/or site-specific drug delivery systems. In experimental animals the micelles remained in circulation with a half-life in excess of 50 h. Our results demonstrate the advantages of using block copolymers for the preparation of "perfect" biocompatible surfaces such as are required for well-tolerated, long-circulating particulate drug carriers.
Critical illness in COVID-19 is caused by inflammatory lung injury, mediated by the host immune system. We and others have shown that host genetic variation influences the development of illness requiring critical care or hospitalisation following SARS-Co-V2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study is designed to compare genetic variants in critically-ill cases with population controls in order to find underlying disease mechanisms.
Here, we use whole genome sequencing and statistical fine mapping in 7,491 critically-ill cases compared with 48,400 population controls to discover and replicate 22 independent variants that significantly predispose to life-threatening COVID-19. We identified 15 new independent associations with severe COVID-19, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type secretor status (FUT2).
Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating expression of multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in severe disease.
We show that comparison between critically-ill cases and population controls is highly efficient for genetic association analysis and enables detection of therapeutically-relevant mechanisms of disease. Therapeutic predictions arising from these findings require testing in clinical trials.
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