Biology subjects

Arias, A.

Publications and source records attributed to Arias, A..

5 recordsLinked to original sources

bioRxiv2026

C1q from C1q+ tumor-associated myeloid cells promotes resistance to T-cell engagers and CAR T-cells and is induced by LIF and glucocorticoids

Immunotherapies, particularly T-cell engagers (TCEs) and CAR T-cells, have shown limited efficacy in solid tumors, partly due to an immunosuppressive tumor microenvironment (TME). However, the molecular mechanisms by which the TME impairs immunotherapy remain poorly understood. Here, we found that C1q generated by C1q tumor-associated myeloid cells (TAMs) plays a fundamental role in shaping the immunosuppressive TME in glioblastoma (GBM), one of the most aggressive tumors. C1q suppressed T-cell activation and impaired the activity of T-cell engagers (TCEs) and CAR T-cells. Genetic ablation of C1qa improved anti-tumor responses to TCEs and CAR T-cells. We used innovative patient-derived tumor tissue cultures (PDTTCs), which preserve an intact TME, from 19 GBM patients and identified the LIF cytokine as the main inducer of C1q. Moreover, we discovered that glucocorticoids cooperate with LIF to induce C1q. The identified C1q TAM signature overlapped with an anti-LIF gene signature, was associated with poor prognosis, and was enriched in mesenchymal GBMs with NF1 mutations. The blockade of LIF using an anti-LIF neutralizing antibody decreased the presence of C1q+ TAMs, and we found that the regulation of C1q by anti-LIF is conserved between human and mouse. Using the C1qa-/- GBM mouse model, we showed that C1q mediates the anti-tumor immune response induced by LIF blockade. Our findings identify C1q TAMs as key immunosuppressive players in GBM, impairing CAR T-cells and TCE activity, and position them as therapeutic targets to improve immunotherapy responses in this devastating disease.

cancer biology↗

bioRxiv2026

Isolation and characterization of Bagaza virus: insights into host adaptability and zoonotic potential.

Bagaza virus (BAGV) is an emerging orthoflavivirus that primarily infects wild birds, but its ability to infect other hosts remains poorly understood. We isolated BAGV RNA from the brain of a dead red-legged partridge and evaluated viral adaptation and replication kinetics in avian, mosquito, mammalian, and human cell lines. BAGV replicated efficiently in monkey, mosquito, duck, and selected human cell lines (HEK-293T and Huh7.5), whereas replication was limited in other human, hamster, and chicken fibroblast cell lines, indicating variable cellular susceptibility. These differences may reflect host-specific adaptation or distinct innate immune responses. Viral RNA replication complexes localized to the cytoplasm, as shown by immunocytochemical detection of dsRNA. Ribavirin treatment significantly reduced viral titers and RNA levels, demonstrating antiviral sensitivity. Together, these findings provide new insights into BAGV biology, host adaptability, and potential zoonotic risk, and support the development of antiviral strategies and improved epidemiological surveillance within a One Health framework.

microbiology↗

bioRxiv2026

Unraveling the Phylogenetic Complexities of Ischyropsalis C.L. Koch, 1839 (Opiliones: Dyspnoi: Ischyropsalididae) in the North Iberian Peninsula, with the description of three new species.

Ischyropsalis is a genus of harvestmen inhabiting both terrestrial and caves in central and southern Europe. The accepted number of species is controversial due to feature similarities and their strong sexual dimorphism. The northern part of the Iberian Peninsula harbours 11 accepted taxa, four of which are terrestrial, while the other seven exclusively live in caves. Some of these species have not been included in the only phylogenetic study conducted on this genus, so their taxonomic status has not been evaluated yet. In this context, we aim to unravel the phylogenetic relationships among the taxa within this genus, from the northern part of the Iberian Peninsula, by conducting morphological and phylogenetic analyses based on mitochondrial (COI) and nuclear (EF1-) molecular markers. Phylogenetic analyses revealed three previously undescribed species from karst caves in Cantabria and Asturias, herein described as I. damiani sp. nov., I. impressa sp. nov. and I. aguerana sp. nov.

zoology↗

bioRxiv2025

Mitophagy-related prohibitin 2 is an orthoflavivirus restriction factor targeted for degradation during infection

1.Orthoflaviviruses (OFVs) are the primary cause of arboviral disease worldwide, leading to large numbers of hospitalisations, sequelae and deaths associated. Viral genome replication is catalysed by non-structural protein 5 (NS5), the largest and most conserved protein in these viruses. Here, we used quantitative proteomics to identify host cell interactors of Zika virus (ZIKV), Usutu virus (USUV), and West Nile virus (WNV) NS5 proteins. A total of 141 proteins were detected in the analysis, being 26 of them associated with all three NS5s. Downregulation of myoferlin and LGALS3BP led to decreases in the virus yields, indicating that their presence is needed for efficient virus replication. Conversely, silencing of mitophagy-related prohibitin 2 (PHB2) resulted in significant increases in ZIKV and USUV titres and genomic RNA. Supporting a connection between this antiviral behaviour and mitophagy, an inhibitor of this pathway also led to larger virus titres and viral RNA copies. During infection, PHB2 protein levels gradually decreased, becoming transiently undetectable, and suggesting that it is specifically targeted by the virus for degradation. Ectopic expression of NS5 alone did not affect PHB2 intracellular abundance, however a significant decrease was observed in cells expressing the viral protease NS2B/NS3. Its elimination, was more pronounced in cells where both viral enzymes were co-expressed, supporting that NS5 could be assisting PHB2 recognition by NS2B/NS3. Overall, our results support that PHB2 is an orthoflaviviral restriction factor which is targeted for degradation to favour viral replication. 2. IMPORTANCEOrthoflaviviruses (OFVs) are one of the main causes of disease transmitted by mosquitoes, with millions of infections occurring annually, and large numbers of deaths associated. Some important members include viruses causing dengue, yellow fever, and Zika-associated disease (e.g. microcephaly). OFVs contain a genome which is copied by a highly conserved viral protein termed NS5. Prohibitin 2 (PHB2) is a host cellular protein involved in different cellular processes including mitophagy, a mechanism to remove damaged mitochondria. Here, we show that human PHB2 interacts with orthoflaviviral NS5. Depletion of PHB2 results in increased viral yields, suggesting that this protein restricts orthoflaviviral infection. We found that PHB2 is targeted for degradation by the orthoflaviviral protease in a process aided by NS5, supporting that several viral proteins act concertedly to eliminate PHB2, counteracting its antiviral activity, and thus favouring infection.

microbiology↗

bioRxiv2024

Using deep learning to predict internalizing problems from brain structure

Internalizing problems (e.g., anxiety and depression) are associated with a wide range of adverse outcomes. While some predictors of internalizing problems are known (e.g., their frequent co-occurrence with neurodevelopmental (ND) conditions), the biological markers of internalizing problems are not well understood. Here, we used deep learning, a powerful tool for identifying complex and multi-dimensional brain-behaviour relationships, to predict cross-sectional and worsening longitudinal trajectories of internalizing problems. Data were extracted from four large-scale datasets: the Adolescent Brain Cognitive Development study, the Healthy Brain Network, the Human Connectome Project Development study, and the Province of Ontario Neurodevelopmental network. We developed deep learning models that used measures of brain structure (thickness, surface area, and volume) to (a) predict clinically significant internalizing problems cross-sectionally (N=14,523); and (b) predict subsequent worsening trajectories (using the reliable change index) of internalizing problems (N=10,540) longitudinally. A stratified cross-validation scheme was used to tune, train, and test the models, which were evaluated using the area under the receiving operating characteristic curve (AUC). The cross-sectional model performed well across the sample, reaching an AUC of 0.80[95% CI: 0.71,0.88]. For the longitudinal model, while performance was sub-optimal for predicting worsening trajectories in a sample of the general population (AUC=0.66[0.65,0.67]), good performance was achieved in a small, external test set of primarily ND conditions (AUC=0.80[0.78,0.81]), as well as across all ND conditions (AUC=0.73[0.70,0.76]). Deep learning with features of brain structure is a promising avenue for biomarkers of internalizing problems, particularly for individuals who have a higher likelihood of experiencing difficulties.

neuroscience↗