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Biology subjects

Taresco, V.

Publications and source records attributed to Taresco, V..

3 recordsLinked to original sources

Single-shot light-field microscopy captures delivery-dependent dye and autofluorescence patterns in Caenorhabditis elegans

Three-dimensional imaging of live Caenorhabditis elegans commonly relies on sequential z-stack acquisition, which can be slow and susceptible to movement and photobleaching. Here, we used light-field microscopy to capture dye and delivery-dependent fluorescence patterns across intact adult worms in a single exposure per channel. With a 40x/1.20 NA water-immersion objective, each reconstructed dataset contained 121 axial slices spanning 109 {micro}m at 0.91 {micro}m spacing. In a representative adult, nematode signal extended from 40.88 to 85.4 {micro}m, corresponding to approximately 44.5 {micro}m of captured axial depth without sequential z scanning. Three fluorescence channels were acquired with a summed exposure time of 112 ms across a 685 x 1010 {micro}m field of view. FM1-43 labelled intestinal, cuticular and vesicular structures, FM4-64 highlighted ingested bacteria and intestinal compartments, and Nile Red revealed vesicular and broader whole-organism fluorescence. Intrinsic blue and green autofluorescence signals were also resolved. These observations demonstrate rapid single-shot acquisition of whole-organism three-dimensional fluorescence information and show how delivery route influences the spatial distribution of commonly used fluorescent probes in C. elegans.

biophysics↗

Development of bioactive electrospun scaffolds suitable to support skin fibroblasts and release Lucilia sericata maggot excretion/secretion

Larval therapy has been reported to exert beneficial actions upon chronic wound healing by promoting granulation tissue formation, antimicrobial activity and degrading necrotic tissue. However, the use of live maggots is problematic for patient acceptance, and thus there is a need to develop materials which can adsorb and release therapeutic biomolecules from maggot secretions. Here we describe the fabrication of a novel bioactive scaffold that can be loaded with Lucilia sericata maggot excretion/secretion (L. sericata maggot E/S) for wound therapy, and which also provides structural stability for mammalian cell-growth and migration. We show that electrospun scaffolds can be prepared from polycaprolactone-poly (ethylene glycol)-block copolymer (PCL-b-PEG) blended with PCL, to form fibres with average diameters of ~4 m. We further demonstrate that the fibres are able to be loaded with L. sericata maggot E/S, in order to influence fibroblast migration through protease activity. Finally, we show that after 21 days, the cumulative amount of released L. sericata maggot E/S was ~14 g/mL from PCL-b-PEG/PCL scaffolds and that the protease activity of L. sericata maggot E/S was preserved when PCL-b-PEG/PCL scaffolds were used as the release platform.

bioengineering↗

Interaction of HelQ helicase with RPA modulates RPA-DNA binding and stimulates HelQ to unwind DNA through a protein roadblock.

Cells reactivate compromised DNA replication forks using enzymes that include DNA helicases for separating DNA strands and remodelling protein-DNA complexes. HelQ helicase promotes replication-coupled DNA repair in mammals in a network of interactions with other proteins. We report newly identified HelQ helicase activities, when acting alone and when interacting with RPA. HelQ helicase was strongly inhibited by a DNA-protein barrier (BamHIE111A), and by an abasic site in the translocating DNA strand. Interaction of HelQ with RPA activated DNA unwinding through the protein barrier, but not through the abasic site. Activation was lost when RPA was replaced with bacterial SSB or DNA binding-defective RPA, RPAARO1. We observed stable HelQ-RPA-DNA ternary complex formation, and present evidence that an intrinsically disordered N-terminal region of HelQ (N-HelQ) interacts with RPA, destabilising RPA-DNA binding. Additionally, SEC-MALS showed that HelQ multimers are converted into catalytically active dimers when ATP-Mg2+ is bound. HelQ and RPA are proposed to jointly promote replication fork recovery by helicase-catalysed displacement of DNA-bound proteins, after HelQ gains access to ssDNA through its N-terminal domain interaction with RPA.

biochemistry↗