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1.
Proc Natl Acad Sci U S A ; 119(27): e2100036119, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35771940

ABSTRACT

Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.


Subject(s)
Adaptation, Physiological , Flowers , Gene-Environment Interaction , Phosphatidylcholines , Phospholipases A1 , Plant Proteins , Zea mays , Alleles , Chromosome Mapping , Flowers/genetics , Flowers/metabolism , Genes, Plant , Genetic Linkage , Phosphatidylcholines/metabolism , Phospholipases A1/classification , Phospholipases A1/genetics , Phospholipases A1/metabolism , Plant Proteins/classification , Plant Proteins/genetics , Plant Proteins/metabolism , Zea mays/genetics , Zea mays/growth & development
2.
Chest ; 157(4): 790-804, 2020 04.
Article in English | MEDLINE | ID: mdl-31785254

ABSTRACT

BACKGROUND: Clinical characteristics of the international population with severe asthma are unknown. Intercountry comparisons are hindered by variable data collection within regional and national severe asthma registries. We aimed to describe demographic and clinical characteristics of patients treated in severe asthma services in the United States, Europe, and the Asia-Pacific region. METHODS: The International Severe Asthma Registry retrospectively and prospectively collected data in patients with severe asthma (≥ 18 years old), receiving Global Initiative for Asthma (GINA) Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4. Baseline demographic and clinical data were collected from the United States, United Kingdom, South Korea, Italy, and the Severe Asthma Web-based Database registry (including Australia, Singapore, and New Zealand) from December 2014 to December 2017. RESULTS: We included 4,990 patients. Mean (SD) age was 55.0 (15.9) years, and mean (SD) age at asthma onset was 30.7 (17.7) years. Patients were predominantly female (59.3%) and white (72.6%), had never smoked (60.5%), and were overweight or obese (70.4%); 34.9% were at GINA Step 5; and 57.2% had poorly controlled disease. A total of 51.1% of patients were receiving regular intermittent oral corticosteroids, and 25.4% were receiving biologics (72.6% for those at GINA Step 5). Mean (SD) exacerbation rate was 1.7 (2.7) per year. Intercountry variation was observed in clinical characteristics, prescribed treatments, and biomarker profiles. CONCLUSIONS: Using a common data set and definitions, this study describes severe asthma characteristics of a large patient cohort included in multiple severe asthma registries and identifies country differences. Whether these are related to underlying epidemiological factors, environmental factors, phenotypes, asthma management systems, treatment access, and/or cultural factors requires further study.


Subject(s)
Asthma , Glucocorticoids/therapeutic use , Obesity/epidemiology , Asthma/diagnosis , Asthma/epidemiology , Asthma/physiopathology , Asthma/therapy , Comorbidity , Disease Progression , Female , Humans , International Cooperation , Male , Medication Therapy Management/statistics & numerical data , Middle Aged , Needs Assessment , Registries/statistics & numerical data , Severity of Illness Index , White People/statistics & numerical data
3.
Nat Commun ; 8(1): 1874, 2017 11 30.
Article in English | MEDLINE | ID: mdl-29187731

ABSTRACT

Maize was domesticated from lowland teosinte (Zea mays ssp. parviglumis), but the contribution of highland teosinte (Zea mays ssp. mexicana, hereafter mexicana) to modern maize is not clear. Here, two genomes for Mo17 (a modern maize inbred) and mexicana are assembled using a meta-assembly strategy after sequencing of 10 lines derived from a maize-teosinte cross. Comparative analyses reveal a high level of diversity between Mo17, B73, and mexicana, including three Mb-size structural rearrangements. The maize spontaneous mutation rate is estimated to be 2.17 × 10-8 ~3.87 × 10-8 per site per generation with a nonrandom distribution across the genome. A higher deleterious mutation rate is observed in the pericentromeric regions, and might be caused by differences in recombination frequency. Over 10% of the maize genome shows evidence of introgression from the mexicana genome, suggesting that mexicana contributed to maize adaptation and improvement. Our data offer a rich resource for constructing the pan-genome of Zea mays and genetic improvement of modern maize varieties.


Subject(s)
Evolution, Molecular , Genome, Plant/genetics , Zea mays/genetics , Haplotypes
4.
Front Plant Sci ; 3: 101, 2012.
Article in English | MEDLINE | ID: mdl-22654889

ABSTRACT

Flavonoids are specialized compounds widely distributed and with diverse functions throughout the plant kingdom and with several benefits for human health. In particular, flavonols, synthesized by flavonol synthase (FLS), protect plants against UV-B radiation and are essential for male fertility in maize and other plants. We have recently characterized a UV-B inducible ZmFLS1, corresponding to the first to be described in monocot plants. Interestingly, the new assembly of the B73 maize genome revealed the presence of a second putative FLS gene (ZmFLS2), with very high identity with ZmFLS1. ZmFLSs expression was analyzed in different maize tissues, and by combining electrophoretic mobility shift assays and transient expression experiments, we show that both genes are direct targets of anthocyanin (C1/PL1 + R/B) and 3-deoxy flavonoid (P1) transcriptional regulators. ZmFLS expression analyses show higher levels of both transcripts in high altitude landraces than inbred lines, and both genes are regulated by UV-B radiation in all lines analyzed. Moreover, the high sequence conservation of the ZmFLS promoters between maize lines suggests that the differences observed in ZmFLS expression are due to allelic variations in the transcription factors that regulate their activities. Finally, we generated pFLS1::FLS1-RFP transgenic plants and analyzed ZmFLS1 expression in different maize tissues; we found that this enzyme is localized in the ER and the perinuclear region.

5.
Phys Rev E Stat Nonlin Soft Matter Phys ; 70(3 Pt 2): 036311, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15524637

ABSTRACT

One efficient way of determining the bond strength of adhesives is to measure the force or the work required to separate two surfaces bonded by a thin adhesive film. We consider the case in which the thin film is not a conventional adhesive material but a high viscosity ferrofluid confined between two narrowly spaced parallel flat plates subjected to an external magnetic field. Our theoretical results demonstrate that both the peak adhesive force and the separation energy are significantly influenced by the action and symmetry properties of the applied field. Specifically, we show that the adhesive strength of a ferrofluid is reduced if the applied magnetic field is perpendicular to the plates or if the applied field is in plane and exhibits azimuthal symmetry. Conversely, the adhesive strength can be either enhanced or reduced if the applied field is in plane and is directed radially outward. This establishes an interesting connection between adhesion and ferrohydrodynamic phenomena, allowing the control of important adhesive properties by magnetic means.

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