FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2021002433> ?p ?o ?g. }

• W2021002433 endingPage "i119" @default.
• W2021002433 startingPage "i118" @default.
• W2021002433 abstract "Biological model: In this project, we investigated the control of radiation-induced genotoxic damage expression in somatic cells of the nematode Caenorhabditis elegans. We measured genotoxic damage in the C. elegans intestine by irradiating young larvae with 20 intestinal cells. Fourteen of these cells undergo exactly one nuclear division without cytoplasmic division leading to 14 binucleate cells. This nuclear division is synchronized and occurs at the first larval molt. Irradiation induces chromosome aberrations including dicentrics which we can quantify as stable anaphase bridges in the binucleate cells of young adult intestines. The endpoint is dose- and LET-dependent and we have demonstrated that individual intestinal cells have unique radiosensitivities.Results: The project has two components, a genetic screen for genes that control cell sensitivity and a microbeam component to directly probe individual cells. The genetic screen has identified several genes in NHEJ repair and telomere metabolism that modulate overall bridge frequency. Knockout mutants of cku-70, cku-80 and lig-4 greatly sensitize animals for anaphase bridge induction. A statistical method was used to determine whether induction of bridges was strictly random and cell autonomous and we determined that expression of bridges in pairs of cells was, in fact, non-random which suggested that signaling between cells affected the pattern of bridge expression. This allowed us to conduct an RNAi and mutation screen for genes that control the signaling (block non-random distributions) and several candidates have been identified.To directly test the notion that signaling of genotoxic damage occurs, we conducted experiments with alpha particles collimated through slits in metal foils and showed that genotoxic damage could be expressed many cell diameters away from a partial body exposure site. Thus, an in vivo bystander effect was demonstrated. Dose targeting was then improved to small regional exposures and eventually to individual cell targeting using 2 MeV protons from the microbeam facility at Texas A&M University. We now employ a green fluorescent protein (GFP)-expressing transgenic worm (rrIs1[elt-2::GFP]) to target GFP-positive gut cells via the gut-specific transcription factor elt-2. This allows alignment of the cell of interest over the microbeam aperture under appropriate fluorescence illumination.Microbeam irradiation experiments for many pairwise combinations of cell signal transmission and reception (observed as expression of anaphase bridges) have been conducted and several interesting patterns emerge. (i) The signaling pattern is cell-specific and does not simply reflect cell–cell distance or require direct contact between cell pairs. (ii) The signal range can be as far as from cell pair 2 to cell pair 8 (>100 µm). (iii) There appears to be a functional compartment boundary at the pharynx/intestine valve as even high-dose exposures to the posterior pharyngeal bulb fail to induce bridges in nearby intestinal cells. (iv) The frequency of signal transmission and reception corresponds broadly to the overall frequency of bridges observed during whole-body irradiations which suggests that direct irradiation and ‘out-of-field’ effects may be additive. These patterns have been analyzed in terms of a cellular logic circuit map for signal transmission and reception.A dose–response for a subset of microbeam-targeted cells was measured over the range of 5–20 Gy. Controlled cell pair targeting was used to test the potential additivity of signals and we found that effects were supra-additive. Finally, preliminary measurements were conducted on GFP-expressing transgenic strains that bore cku-70(tm1524) III and smk-1(mn156) V mutations which confer enhanced radiosensitivity. Cku-70 is a Ku-70 ortholog while smk-1 is orthologous to the mammalian and Dictyostelium discoideum SMEK (suppressor of MEK null) protein. In the cku-70(0/0) strain, the severity of the bridges in bystander cells was enhanced, suggesting that signal recipient cells employ NHEJ repair pathways in the expression of anaphase bridges.Clinical trial registration number: Not applicable." @default.
• W2021002433 created "2016-06-24" @default.
• W2021002433 creator A5002484869 @default.
• W2021002433 creator A5003756153 @default.
• W2021002433 creator A5035861312 @default.
• W2021002433 creator A5072601511 @default.
• W2021002433 creator A5087250215 @default.
• W2021002433 creator A5087485821 @default.
• W2021002433 date "2014-02-28" @default.
• W2021002433 modified "2023-09-27" @default.
• W2021002433 title "Bystander signaling in C. elegans: proton microbeam studies" @default.
• W2021002433 doi "https://doi.org/10.1093/jrr/rrt178" @default.
• W2021002433 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3941528" @default.
• W2021002433 hasPublicationYear "2014" @default.
• W2021002433 type Work @default.
• W2021002433 sameAs 2021002433 @default.
• W2021002433 citedByCount "1" @default.
• W2021002433 countsByYear W20210024332016 @default.
• W2021002433 crossrefType "journal-article" @default.
• W2021002433 hasAuthorship W2021002433A5002484869 @default.
• W2021002433 hasAuthorship W2021002433A5003756153 @default.
• W2021002433 hasAuthorship W2021002433A5035861312 @default.
• W2021002433 hasAuthorship W2021002433A5072601511 @default.
• W2021002433 hasAuthorship W2021002433A5087250215 @default.
• W2021002433 hasAuthorship W2021002433A5087485821 @default.
• W2021002433 hasBestOaLocation W20210024331 @default.
• W2021002433 hasConcept C121332964 @default.
• W2021002433 hasConcept C185544564 @default.
• W2021002433 hasConcept C185592680 @default.
• W2021002433 hasConcept C19106626 @default.
• W2021002433 hasConcept C203014093 @default.
• W2021002433 hasConcept C2777152588 @default.
• W2021002433 hasConcept C2989005 @default.
• W2021002433 hasConcept C54516573 @default.
• W2021002433 hasConcept C71924100 @default.
• W2021002433 hasConcept C86803240 @default.
• W2021002433 hasConcept C95444343 @default.
• W2021002433 hasConceptScore W2021002433C121332964 @default.
• W2021002433 hasConceptScore W2021002433C185544564 @default.
• W2021002433 hasConceptScore W2021002433C185592680 @default.
• W2021002433 hasConceptScore W2021002433C19106626 @default.
• W2021002433 hasConceptScore W2021002433C203014093 @default.
• W2021002433 hasConceptScore W2021002433C2777152588 @default.
• W2021002433 hasConceptScore W2021002433C2989005 @default.
• W2021002433 hasConceptScore W2021002433C54516573 @default.
• W2021002433 hasConceptScore W2021002433C71924100 @default.
• W2021002433 hasConceptScore W2021002433C86803240 @default.
• W2021002433 hasConceptScore W2021002433C95444343 @default.
• W2021002433 hasIssue "suppl 1" @default.
• W2021002433 hasLocation W20210024331 @default.
• W2021002433 hasLocation W20210024332 @default.
• W2021002433 hasOpenAccess W2021002433 @default.
• W2021002433 hasPrimaryLocation W20210024331 @default.
• W2021002433 hasRelatedWork W2084405665 @default.
• W2021002433 hasRelatedWork W2115635125 @default.
• W2021002433 hasRelatedWork W2132335002 @default.
• W2021002433 hasRelatedWork W2186894066 @default.
• W2021002433 hasRelatedWork W2189302358 @default.
• W2021002433 hasRelatedWork W2384668018 @default.
• W2021002433 hasRelatedWork W2611229882 @default.
• W2021002433 hasRelatedWork W2614130638 @default.
• W2021002433 hasRelatedWork W401132504 @default.
• W2021002433 hasRelatedWork W54132039 @default.
• W2021002433 hasVolume "55" @default.
• W2021002433 isParatext "false" @default.
• W2021002433 isRetracted "false" @default.
• W2021002433 magId "2021002433" @default.
• W2021002433 workType "article" @default.