Biology subjects

Pereira, J. L.

Publications and source records attributed to Pereira, J. L..

3 recordsLinked to original sources

bioRxiv2024

Emergence of potato virus Y outbreaks in tomatoes in Brazil, the disease and spread

The emergence of Mexican Fire disease in Brazilian tomato fields, attributed to potato virus Y (PVY), has raised concerns. Characterized by severe necrosis on median leaves, the definitive etiological agent of this disease remained unverified despite PVY detection in symptomatic plants. Our study aimed to elucidate the causal agent, occurrence, spread, and symptomatology of Mexican Fire. Deep sequencing of tomato leaves with typical necrotic symptoms confirmed the association with PVY, reinforcing its role as the causal agent. Serological tests with a PVY-specific polyclonal antibody consistently correlated symptoms with virus presence in a fresh market tomato field, with higher PVY incidence near older tomato and maize plants. Necrotic leaf distribution analysis revealed a predominant occurrence in median leaves, progressing upwards. Deep sequencing of symptomatic field samples exclusively detected PVY, reaffirming its role in symptom induction. Importantly, PVY inoculation under field and greenhouse conditions fulfilled Kochs Postulates, triggering leaf necrosis. Our findings unequivocally establish PVY as the causal agent of Mexican Fire disease, shedding light on its etiology, incidence, spread, and symptom expression, crucial for effective disease management strategies.

plant biology↗

bioRxiv2024

Transgenic αβ TCR tonic signaling is leukemogenic while strong stimulation is leukemia-suppressive

The pre-T cell receptor (TCR) and TCR complexes are frequently expressed in T-cell acute lymphoblastic leukemia (T-ALL), an aggressive T cell precursor malignancy. Although mutations in TCR components are infrequent in T-ALL, earlier research indicated that transgenic {beta} TCR expression in mouse T cell precursors promoted T-ALL development. However, we recently found that stimulation of TCR signaling in T-ALL induced leukemic cell apoptosis and suppressed leukemia. Our aim was to elucidate if a given {beta} TCR complex has a dual role in leukemogenesis depending on the nature of the stimulus. We demonstrate that transgenic expression of the Marilyn {beta} TCR, specific for the H-Y male antigen presented by major histocompatibility complex class II, triggers T-ALL development exclusively in female mice. This T-ALL exhibited Notch1 mutations, Cdkn2a copy number loss, immature immunophenotype and infiltrated both lymphoid and non-lymphoid organs. Furthermore, leukemic cells expressed surface CD5, a marker of tonic TCR signaling. T-ALL efficiently developed in Rag2-deficient Marilyn transgenic females, indicating that Rag2-mediated recombination is not implicated in this T-ALL model. Remarkably, exposure of Marilyn female T-ALL to male antigen in recipient mice resulted in T-ALL apoptosis and prolonged mouse survival. These findings underscore that the same {beta} TCR complex has a dual role in T-ALL in that its tonic stimulation is leukemogenic, while strong stimulation is leukemia-suppressive.

cancer biology↗

bioRxiv2024

Antibody targeting of surface PSGL-1 glycoprotein leads to lymphoma apoptosis and tumorigenesis inhibition

Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer (NK) cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma (CTCL) cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma (BL) cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.

cancer biology↗