Biology subjects

Frausto, R. F.

Publications and source records attributed to Frausto, R. F..

4 recordsLinked to original sources

bioRxiv2026

cGMP signaling regulates context-dependent sensory valence in C. elegans

An animals response to chemosensory cues depends on the animals prior experience, internal state, or life stage. However, the molecular mechanisms that regulate sensory valence (i.e., whether a chemosensory cue is attractive or repulsive) remain poorly understood. We investigated the mechanisms that specify sensory valence using the responses of the free-living nematode Caenorhabditis elegans to carbon dioxide (CO2). C. elegans exhibits highly flexible responses to CO2: well-fed animals are repelled by CO2, while both starved animals and well-fed animals raised under high CO2 conditions are attracted to CO2. Here, we show that CO2 attraction in animals raised at high CO2 requires a cGMP signaling pathway that involves the cGMP-dependent protein kinase EGL-4. This pathway does not regulate CO2 response in starved animals, indicating that the role of EGL-4 in mediating CO2 attraction depends on satiety state. Cultivation under high CO2 conditions leads to increased cGMP levels in the CO2-detecting BAG neurons, consistent with a specific requirement for EGL-4 in high-CO2-cultivated animals. We also show that EGL-4 regulates CO2 valence by altering neuropeptide expression in BAG. Our results indicate that sensory valence is established in a context-dependent manner at the level of the primary sensory neuron.

neuroscience↗

bioRxiv2023

Nanocrystalline silver layer of knitted polyester outperforms other silver-containing wound dressings in an in vitro wound model

BackgroundSilver possesses cytotoxic properties against many microorganisms and is regularly used in wound care. Current evidence supporting the use of one type of silver-containing wound dressing (SCWD) is insufficient. MethodsTo examine the ability of selected SCWDs to inhibit the growth of two strains of bacteria (E. coli and S. aureus) commonly found in wounds, an in vitro wound model was used. Bacteria were applied to the surface of nutrient agar and a piece of each SCWD was applied to the bacteria. The plates were incubated at 37{degrees}C overnight. The zone of inhibition (ZI) around each SCWD was measured in cm2. ResultsThe mean ZI for Acticoat Flex-3 on E. coli was 1.59 {+/-} 0.15 cm2, which was significantly greater than that observed for Aquacel Ag (p<0.001), Mepilex Ag (p<0.0001), Mepitel Ag (p<0.001), Optifoam (p<0.0001) and Tegaderm Alginate Ag (p<0.01), but statistically indistinguishable from Maxorb II Ag. The mean ZI on S.aureus was 1.21 {+/-} 0.16 cm2, which was greater than Aquacel Ag (p<0.05), Mepilex (p<0.0001), Optifoam (p<0.0001) and Tegaderm Alginate Ag (p<0.05), but statistically indistinguishable from Maxorb II Ag or Mepitel Ag. ConclusionsOf the SCWDs tested, Acticoat Flex-3 demonstrated the most robust antimicrobial effect. Herein we show that Acticoat Flex-3 may provide the most wound protection against bacterial infection. In conclusion, these data provide clinicians with additional independent evidence to inform their clinical practice on the use of specific wound dressings. PRECISThe antimicrobial properties of Acticoat Flex-3, a dressing composed of nanocrystalline silver layer of knitted polyester, outperformed other silver-containing dressings against E. coli and S. aureus.

microbiology↗

bioRxiv2019

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

cell biology↗

bioRxiv2019

ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing

The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.

cell biology↗