Biology subjects

Fiore, A.

Publications and source records attributed to Fiore, A..

3 recordsLinked to original sources

bioRxiv2023

A fluorescent reporter model for the visualization and characterization of TDC

TDC are hematopoietic cells that combine dendritic cell (DC) and conventional T cell markers and functional properties. They were identified in secondary lymphoid organs (SLOs) of naive mice as cells expressing CD11c, major histocompatibility molecule (MHC)-II, and the T cell receptor (TCR) {beta} chain. Despite thorough characterization as to their potential functional properties, a physiological role for TDC remains to be determined. Unfortunately, using CD11c as a marker for TDC has the caveat of its upregulation on different cells, including T cells, upon activation. Therefore, a more specific marker is needed to further investigate TDC functions in peripheral organs in different pathological settings. Here we took advantage of Zbtb46-GFP reporter mice to explore the frequency and localization of TDC in peripheral tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDC identified with this reporter model have a gene signature that is distinct from conventional T cells and DC. In addition, frequency and total numbers of TDC in the SLOs recapitulated those found using CD11c as a marker. This reporter model allowed for identification of TDC in situ not only in SLOs but also in the liver and lung of naive mice. Interestingly, we found that TDC numbers in the SLOs increased upon viral infection, suggesting that TDC might play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDC in several pathological contexts, including infection and cancer.

immunology↗

bioRxiv2022

Circulating U13 small nucleolar RNA as a candidate biomarker for Huntington's disease

Background and ObjectivesFluid biomarkers are a recent field of interest in Huntington disease (HD). We focused on small circulating RNAs from plasma of subjects with prodromal (pre-HD) and overt disease by a two-stage approach: an unbiased investigation by an array method and a validation study to quantify a significant small nucleolar RNA. MethodsThrough Affymetrix Gene-Chip-miRNA-Array we performed an exploratory study on 9 HD patients, 8 healthy subjects (HS) and 5 psychiatric patients (PP; who share drugs with HD patients, to control for iatrogenic effects). Through real time PCR we validated the results in an independent population of 24 HD patients, 15 pre-HD, 24 PP, 28 Alzheimers disease (AD) patients (added to control the disease-specificity of our finding) and 23 HS. A bioinformatic analysis was also performed to interpret our finding. ResultsThe microarray results showed a significant signal for U13 small nucleolar RNA (SNORD13) that was increased in plasma of HD patients compared to controls (fold change, 1.54, p =0.003 HD vs. HS, and fold change 1.44 p = 0.0026 HD vs. PP). In the validation population the significant increase in HD patients was evident compared to both pre-HD and the three control groups (p<0.00001). The plasma levels of SNORD13 correlated with the status of mutant huntingtin carrier and the disease duration (respectively R=0.69; p<0.000001; R=0.49; p=0.015). Through receiver operating characteristic (ROC) curve analysis, we showed high accuracy of plasmatic SNORD13 in discriminating HD patients from pre-HD and control groups (AUC=0.963), outperforming values reported in another study for intrathecal or plasmatic mutant huntingtin and neurofilament light chain as biomarkers of overt HD. The bioinformatic analysis on SNORD13 interactome and pathway analysis showed enrichments for factors involved in nuclear functions beyond the ribosome biogenesis. DiscussionWe report the unprecedented finding of a potential role of small nucleolar RNAs in HD. Circulating SNORD13 seems a good biomarker for clinical purposes. It seems to be specific for HD and to peripherally report a plausible tipping point in the pathogenic cascade at neuronal level, possibly paving the way for new therapeutic targets.

neuroscience↗

bioRxiv2022

Combination of the Systemin peptide with the beneficial fungus Trichoderma afroharzianum T22 improves plant defense responses against pests and diseases

Trichoderma spp. are among the most widely used plant beneficial fungi in agriculture. A novel approach to enhance their effectiveness in plant defense is to use the fungi in combination with bioactive molecules including plant-derived compounds. Here, we show that plant treatment with Trichoderma afroharzianum (strain T22) and Systemin (Sys), a tomato plant peptide active in triggering plant defense, confers protection against the fungal pathogens Fusarium oxysporum, Botrytis cinerea and the insect pest Tuta absoluta. The observed defensive response was associated with increased accumulation of metabolites and transcripts involved in the Jasmonic acid (JA) pathway. Our findings suggest that the innovative combination of T. afroharzianum T22 and Sys can result in a more effective and robust control of different biotic stress agents.

genetics↗