14 research outputs found
Alien Registration- Crabb, Harry M. (Portland, Cumberland County)
https://digitalmaine.com/alien_docs/24173/thumbnail.jp
Alien Registration- Crabb, Harry M. (Portland, Cumberland County)
https://digitalmaine.com/alien_docs/24173/thumbnail.jp
Alien Registration- Crabb, Harry M. (Portland, Cumberland County)
https://digitalmaine.com/alien_docs/24173/thumbnail.jp
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.
With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite's lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action
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Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia
Alien Registration- Crabb, Harry M. (Portland, Cumberland County)
https://digitalmaine.com/alien_docs/24173/thumbnail.jp
Alien Registration- Crabb, Harry M. (Portland, Cumberland County)
https://digitalmaine.com/alien_docs/24173/thumbnail.jp