bioRxiv Science⌕ Search

Biology subjects

Ferry, G.

Publications and source records attributed to Ferry, G..

4 recordsLinked to original sources

Live triatomine bug, vector of Trypanosoma cruzi (Chagas disease), found engorged in Lisbon hotel room: A first for Portugal and for Europe

Triatomine bugs are blood feeding insects that transmit the parasite Trypanosoma cruzi, causative agent of Chagas disease. The bugs are found primarily in the Americas with a few species in Asia and Africa. Here we report the first case of a live triatomine bug in Europe, found in a Lisbon hotel room. In August, 2025, the hotel room occupants discovered a triatomine bug perched on the headboard of their bed. Upon capture, bright red blood emerged from the bug; the occupants suspected that it had bitten them during the night. The bug was identified morphologically as triatomine species Hospesneotomae protracta, which was confirmed molecularly. Hospesneotomae protracta is native to the southwestern United States where it is a competent T. cruzi vector. Trypanosoma cruzi was not detected in this specimen. Although this case likely represents an accidental importation, it illustrates the ease with which disease vectors can be unknowingly transported globally. Ergo it is crucial to document and share these findings to prevent introductions of non-native arthropods of medical importance.

ecology↗

Functional avidity of anti-B7H3 CAR-T constructs predicts antigen density thresholds for triggering effector function

Chimeric Antigen receptor T cell (CAR-T) treatments for solid cancers have been compromised by limited expansion and survival in the tumor microenvironment following interaction with antigen-expressing target cells. Using B7H3 as a model antigen with broad clinical applicability, we evaluated the relationship between the antibody/antigen affinity of three clinical candidate binders and the three following functional characteristics: functional avidity, prolonged cytotoxicity in tumoroid re-stimulation assays, and in vivo anti-tumoral responses. BEHAV3D video-microscopy assessed distinct CAR-T cell behaviors at single cell resolution. T cell exhaustion did not dictate effector function. Rather, we demonstrated a threshold avidity of CAR-T / tumor cell interaction, characterized by longer cumulative CD8+ CAR-T / tumor target interaction times, and required for adequate CAR-T cell expansion to result in sustained tumor control upon re-challenge. These results provide new insights into design of CAR-T cells for antigen-dim cell targeting, and avoidance of antigen-dim tumor relapse.

bioengineering↗

Anti-GD2 antibody therapy alters the neuroblastoma tumor microenvironment and extends survival in TH-MYCN mice

BackgroundNeuroblastoma is a commonly lethal solid tumor of childhood and intensive chemoradiotherapy treatment cures ~50% of children with high-risk disease. The addition of immunotherapy using dinutuximab, a monoclonal antibody directed against the GD2 disialoganglioside expressed on neuroblasts, improves survival when incorporated into front-line therapy and shows robust activity in regressing relapsed disease when combined with chemotherapy. Still, many children succumb to neuroblastoma despite receiving dinutuximab-based immunotherapy, and efforts to counteract the immune suppressive signals responsible are warranted. Animal models of human cancers provide useful platforms to study immunotherapies. TH-MYCN transgenic mice are immunocompetent and develop neuroblastomas at autochthonous sites due to enforced MYCN expression in developing neural crest tissues. However, GD2-directed immunotherapy in this model has been underutilized due to the prevailing notion that TH-MYCN neuroblasts express insufficient GD2 to be targeted. MethodsTH-MYCN mice were treated with 14G2a (anti-GD2 antibody), isotype antibody, or phosphate buffered saline from day 14 of life until day 100 or signs of morbidity. Survival was recorded, and tumors were isolated in terminal surgeries for analysis of GD2 expression and immune cell frequencies. Tumors from untreated mice were explanted for generation into cell lines, and GD2 expression was recorded with serial passage in tissue culture. Immunocytology and immunoblotting were performed to evaluate for adrenergic and mesenchymal markers of neuroblasts. Survival curves compared using Kaplan-Meier method with a log-rank test for significance. Unpaired two-tailed Students t-tests used for comparison of groups in flow cytometry analysis. Results14G2a markedly extends survival in such TH-MYCN mice. Additionally, neuroblasts in 14G2a-treated mice have reduced GD2 expression and fewer macrophage and myeloid-derived suppressor cells in their tumor microenvironments. Neuroblasts in TH-MYCN-driven tumors express GD2 at levels comparable to human neuroblastomas but rapidly lose GD2 expression when explanted ex vivo to establish tumor cell lines. The loss of GD2 expression ex vivo is associated with a transition from an adrenergic to mesenchymal state that is maintained when reimplanted in vivo. ConclusionsOur findings support the utility of the TH-MYCN model to inform GD2-directed immunotherapy approaches for neuroblastoma as well as opportunities to investigate drivers of adrenergic to mesenchymal fate decisions.

cancer biology↗

Improving bioinformatics prediction of microRNA targets by ranks aggregation

microRNAs are non-coding RNAs which down-regulate a large number of target mRNAs and modulate cell activity. Despite continued progress, bioinformatics prediction of microRNA targets remains a challenge since available softwares still suffer from a lack of accuracy and sensitivity. Moreover, these tools show fairly inconsistent results from one another. Thus, in an attempt to circumvent these difficulties, we aggregated all human results of three important prediction algorithms (miRanda, PITA and SVmicrO) showing additional characteristics in order to rerank them into a single list. This database is freely available through a webtool called miRabel (http://bioinfo.univ-rouen.fr/mirabel/) which can take either a list of miRNAs, genes or signaling pathways as search inputs. Receiver Operating Characteristic curves and Precision-Recall curves analysis carried out using experimentally validated data and very large datasets show that miRabel significantly improves the prediction of miRNA targets compared to the three algorithms used separatly. Moreover, using the same analytical methods, miRabel shows significantly better predictions than other popular algorithms such as MBSTAR and miRWalk. Interestingly, a F-score analysis revealed that miRabel also significantly improves the relevance of the top results. The aggregation of results from different databases is therefore a powerful and generalizable approach to many other species to improve miRNA target predictions. Thus, miRabel is an efficient tool to accurately identify miRNA targets and integrate them into a biological context.

bioinformatics↗