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Romero, L.

Publications and source records attributed to Romero, L..

2 recordsLinked to original sources

Climatic niche conservatism in a clade of disease vectors (Diptera: Phlebotominae)

Sandflies of the family Psychodidae show notable diversity in both disease vector status and climatic niche. Some species (in the subfamily Phlebotominae) transmit Leishmania parasites, responsible for the disease leishmaniasis. Other Psychodidae species do not. Psychodid species ranges can be solely tropical, confined to the temperate zones, or span both. Studying the relationship between the evolution of disease vector status and that of climatic niche affords an understanding not only of the climate conditions associated with the presence and species richness of Leishmania vectors, but also allows the study of the extent to which psychodid flies climatic niches are conserved, in a context with implications for global human health. We obtained observation site data, and associated climate data, for 223 psychodid species to understand which aspects of climate most closely predict distribution. Temperature and seasonality are strong determinants of species occurrence within the clade. We built a mitochondrial DNA phylogeny of Psychodidae, and found a positive relationship between pairwise genetic distance and climate niche differentiation, which indicates strong niche conservatism. This result is also supported by strong phylogenetic signals of metrics of climate differentiation. Finally, we used ancestral trait reconstruction to infer the tropicality (i.e., proportion of latitudinal range in the tropics minus the proportion of the latitudinal range in temperate areas) of ancestral species, and counted transitions to and from tropicality states, finding that tropical and temperate species respectively produced almost entirely tropical and temperate descendant species, a result consistent for vector and non-vector species. Taken together, these results imply that while vectors of Leishmania can survive in a variety of climates, their climate niches are strongly predicted by phylogeny.

evolutionary biology↗

MIRO2 regulates prostate cancer cell growth via GCN1-dependent stress signaling

There is a continued need to identify novel therapeutic targets to prevent the mortality associated with prostate cancer. In this context, we discovered a novel mitochondrial signaling pathway that controls androgen-independent and androgen-sensitive prostate cancer cell growth. Mitochondrial Rho GTPase 2 (MIRO2) mRNA was upregulated in prostate cancer compared to localized tumors, and higher MIRO2 levels were correlated with poor patient survival. Using human cell lines that represent AR-independent or androgen-sensitive prostate cancer, we show that MIRO2 depletion impaired cell growth, colony formation and tumor growth in mice. Network analysis of MIRO2s binding partners identified metabolism, cell cycle, and cellular responses to extracellular stimuli amongst the top over-represented pathways. The top hit on our screen was General Control Non-derepressible 1 (GCN1). GCN1 was overexpressed in prostate cancer and MIRO2-GCN1 interacted in prostate cancer cell lines and in primary prostate cancer cells. Our results showed that MIRO2 is necessary for efficient GCN1-mediated GCN2 kinase activation and signaling, triggering translation of the transcription factor ATF4. Importantly, MIRO2 controlled ATF4 levels and transcriptional activity both in amino acid replete and depleted conditions. Furthermore, MIRO2s effect on regulating prostate cancer cell growth was partially mediated by ATF4. Finally, activation of GCN2 and ATF4 expression were correlated with MIRO2 expression in prostate cancer xenografts. Overall, we propose a new mechanism driving prostate cancer growth of both AR-independent and androgen-sensitive tumors.

cancer biology↗