FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3049038961> ?p ?o ?g. }

• W3049038961 abstract "Abstract Background Distal arthrogryposis (DA) is a group of autosomal dominant skeletal muscle diseases characterized by congenital contractures of distal limb joints. The most common cause of DA is a mutation of the embryonic myosin heavy chain gene, MYH3 . Human phenotypes of DA are divided into the weakest form–DA1, a moderately severe form–DA2B (Sheldon-Hall Syndrome), and a severe DA disorder–DA2A (Freeman-Sheldon Syndrome). As models of DA1 and DA2B do not exist, their disease mechanisms are poorly understood. Methods We produced the first models of myosin-based DA1 (F437I) and DA2B (A234T) using transgenic Drosophila melanogaster and performed an integrative analysis of the effects of the mutations. Assessments included lifespan, locomotion, ultrastructural analysis, muscle mechanics, ATPase activity, in vitro motility, and protein modeling. Results We observed significant defects in DA1 and DA2B Drosophila flight and jump ability, as well as myofibril assembly and stability, with homozygotes displaying more severe phenotypes than heterozygotes. Notably, DA2B flies showed dramatically stronger phenotypic defects compared to DA1 flies, mirroring the human condition. Mechanical studies of indirect flight muscle fibers from DA1 heterozygotes revealed reduced power output along with increased stiffness and force production, compared to wild-type controls. Further, isolated DA1 myosin showed significantly reduced myosin ATPase activity and in vitro actin filament motility. These data in conjunction with our sinusoidal analysis of fibers suggest prolonged myosin binding to actin and a slowed step associated with Pi release and/or the power stroke. Our results are supported by molecular modeling studies, which indicate that the F437I and A234T mutations affect specific amino acid residue interactions within the myosin motor domain that may alter interaction with actin and nucleotide. Conclusions The allele-specific ultrastructural and locomotory defects in our Drosophila DA1 and DA2B models are concordant with the differential severity of the human diseases. Further, the mechanical and biochemical defects engendered by the DA1 mutation reveal that power production, fiber stiffness, and nucleotide handling are aberrant in F437I muscle and myosin. The defects observed in our DA1 and DA2B Drosophila models provide insight into DA phenotypes in humans, suggesting that contractures arise from prolonged actomyosin interactions." @default.
• W3049038961 created "2020-08-21" @default.
• W3049038961 creator A5034292441 @default.
• W3049038961 creator A5034340181 @default.
• W3049038961 creator A5049627569 @default.
• W3049038961 creator A5057534434 @default.
• W3049038961 creator A5057637759 @default.
• W3049038961 creator A5065962398 @default.
• W3049038961 creator A5078382290 @default.
• W3049038961 creator A5090857943 @default.
• W3049038961 creator A5053548534 @default.
• W3049038961 date "2020-08-15" @default.
• W3049038961 modified "2023-09-26" @default.
• W3049038961 title "Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism" @default.
• W3049038961 cites W1482991584 @default.
• W3049038961 cites W1573544812 @default.
• W3049038961 cites W1740125121 @default.
• W3049038961 cites W1983769965 @default.
• W3049038961 cites W1993272332 @default.
• W3049038961 cites W1994528729 @default.
• W3049038961 cites W1995522759 @default.
• W3049038961 cites W1998642974 @default.
• W3049038961 cites W1999801226 @default.
• W3049038961 cites W2015546067 @default.
• W3049038961 cites W2018365501 @default.
• W3049038961 cites W2030022617 @default.
• W3049038961 cites W2037015001 @default.
• W3049038961 cites W2038103542 @default.
• W3049038961 cites W2050062231 @default.
• W3049038961 cites W2055158614 @default.
• W3049038961 cites W2061697902 @default.
• W3049038961 cites W2067381583 @default.
• W3049038961 cites W2067425020 @default.
• W3049038961 cites W2067707302 @default.
• W3049038961 cites W2076753632 @default.
• W3049038961 cites W2083668285 @default.
• W3049038961 cites W2094122561 @default.
• W3049038961 cites W2101768262 @default.
• W3049038961 cites W2104938956 @default.
• W3049038961 cites W2105337558 @default.
• W3049038961 cites W2111347055 @default.
• W3049038961 cites W2113978444 @default.
• W3049038961 cites W2121561836 @default.
• W3049038961 cites W2131750624 @default.
• W3049038961 cites W2142289251 @default.
• W3049038961 cites W2142883438 @default.
• W3049038961 cites W2147495164 @default.
• W3049038961 cites W2152315657 @default.
• W3049038961 cites W2159494281 @default.
• W3049038961 cites W2169663251 @default.
• W3049038961 cites W2266557121 @default.
• W3049038961 cites W2276412916 @default.
• W3049038961 cites W2290332073 @default.
• W3049038961 cites W2460509314 @default.
• W3049038961 cites W2754612036 @default.
• W3049038961 cites W2898987541 @default.
• W3049038961 cites W2899430258 @default.
• W3049038961 cites W2918727356 @default.
• W3049038961 doi "https://doi.org/10.1186/s13395-020-00241-6" @default.
• W3049038961 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7429702" @default.
• W3049038961 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32799913" @default.
• W3049038961 hasPublicationYear "2020" @default.
• W3049038961 type Work @default.
• W3049038961 sameAs 3049038961 @default.
• W3049038961 citedByCount "4" @default.
• W3049038961 countsByYear W30490389612021 @default.
• W3049038961 countsByYear W30490389612022 @default.
• W3049038961 crossrefType "journal-article" @default.
• W3049038961 hasAuthorship W3049038961A5034292441 @default.
• W3049038961 hasAuthorship W3049038961A5034340181 @default.
• W3049038961 hasAuthorship W3049038961A5049627569 @default.
• W3049038961 hasAuthorship W3049038961A5053548534 @default.
• W3049038961 hasAuthorship W3049038961A5057534434 @default.
• W3049038961 hasAuthorship W3049038961A5057637759 @default.
• W3049038961 hasAuthorship W3049038961A5065962398 @default.
• W3049038961 hasAuthorship W3049038961A5078382290 @default.
• W3049038961 hasAuthorship W3049038961A5090857943 @default.
• W3049038961 hasBestOaLocation W30490389611 @default.
• W3049038961 hasConcept C125705527 @default.
• W3049038961 hasConcept C181199279 @default.
• W3049038961 hasConcept C23265538 @default.
• W3049038961 hasConcept C2778021804 @default.
• W3049038961 hasConcept C2781111119 @default.
• W3049038961 hasConcept C54355233 @default.
• W3049038961 hasConcept C55493867 @default.
• W3049038961 hasConcept C6997183 @default.
• W3049038961 hasConcept C7301908 @default.
• W3049038961 hasConcept C86803240 @default.
• W3049038961 hasConcept C95444343 @default.
• W3049038961 hasConceptScore W3049038961C125705527 @default.
• W3049038961 hasConceptScore W3049038961C181199279 @default.
• W3049038961 hasConceptScore W3049038961C23265538 @default.
• W3049038961 hasConceptScore W3049038961C2778021804 @default.
• W3049038961 hasConceptScore W3049038961C2781111119 @default.
• W3049038961 hasConceptScore W3049038961C54355233 @default.
• W3049038961 hasConceptScore W3049038961C55493867 @default.
• W3049038961 hasConceptScore W3049038961C6997183 @default.
• W3049038961 hasConceptScore W3049038961C7301908 @default.
• W3049038961 hasConceptScore W3049038961C86803240 @default.
• W3049038961 hasConceptScore W3049038961C95444343 @default.

• next