Biology subjects

Campello, S.

Publications and source records attributed to Campello, S..

3 recordsLinked to original sources

bioRxiv2022

Group dynamics and habitat use of the Giant Otter, Pteronura brasiliensis (Zimmermann, 1780), in seasonally flooded forest in the Araguaia River, Central Brazil: A 10-years study.

We carried out monthly surveys of the giant otter population between 2010 and 2020 in a study area comprised of 1,500 hectares of igapo flooded forest with oxbow lakes in the Cantao region of central Brazil. We recorded 16-32 resident adults in the study area each year, distributed in 4-8 groups. Resident groups exhibited extensive home range overlap, with each group using several lakes and larger lakes used in rotation by up to six groups. Dens and campsites were also shared by multiple groups, but lakes were used by only one group at a time, and encounters between groups were very rare. 24 adult otters were observed to join an existing group. Some individuals changed groups multiple times. Resident adult turnover was high. Each year an average of 36% of resident adults were new immigrants, and 72% of groups left the area within two years. Resident groups had, on average, one litter every three years, and annual cub production showed high variability and a negative correlation to the number of new immigrants in the area. No pairs of giant otters reproduced successfully during the study. Groups of three otters formed through the recruitment of an adult individual by an existing pair and reproduced as successfully as larger groups. Group dynamics and territorial behavior in the Cantao flooded forest ecosystem, where optimal giant otter habitat is continuous in all directions, were found to be different from that reported in areas composed of patchy (isolated oxbow lakes) or linear (rivers) habitat. This suggest that giant otter social and territorial behavior is plastic and adapts to the spatial characteristics of the habitat.

animal behavior and cognition↗

bioRxiv2021

PLK1 inhibition selectively kills ARID1A deficient cells through uncoupling of oxygen consumption from ATP production

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition. Interestingly this sensitivity was unrelated to canonical functions of PLK1 in mediating G2-M cell cycle transition. Instead, a whole-genome CRISPR screen revealed PLK1 inhibitor sensitivity in ARID1A deficient cells to be dependent on the mitochondrial translation machinery. We find that ARID1A knocked-out (KO) cells have an unusual mitochondrial phenotype with aberrant biogenesis, increased oxygen consumption/ expression of oxidative phosphorylation genes, but without increased ATP production. Using expansion microscopy and biochemical fractionation, we see that a subset of PLK1 localizes to the mitochondria in interphase cells. Inhibition of PLK1 in ARID1A KO cells further uncouples oxygen consumption from ATP production, with subsequent membrane depolarization and apoptosis. Knockdown of a key subunit of the mitochondrial ribosome reverses PLK1-inhibitor induced apoptosis in ARID1A deficient cells, confirming specificity of the phenotype. Together, these findings highlight a novel interphase role for PLK1 in maintaining mitochondrial fitness under metabolic stress, and a strategy for therapeutic use of PLK1 inhibitors. To translate these findings, we describe a quantitative microscopy assay for assessment of ARID1A protein loss, which could offer a novel patient selection strategy for the clinical development of PLK1 inhibitors in cancer. Statement of significanceCurrently, no predictive biomarkers have been identified for PLK1 inhibitors in cancer treatment. We show that ARID1A loss sensitizes cells to PLK1 inhibitors through a previously unrecognized vulnerability in mitochondrial oxygen metabolism.

cancer biology↗

bioRxiv2020

PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism

PD-1 signalling downregulates the T cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Drp1-dependent mitochondrial fission plays a crucial role to sustain T cell motility, proliferation, survival and glycolytic engagement and, interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here we show that the signature of PD-1pos CD8+ T cells infiltrating MC38-derived murine tumor mass is having downregulated Drp1 activity and more fused mitochondria, compared to PD-1neg counterparts. Also, PD-1pos lymphocytic elements infiltrating human colon cancer rarely express active Drp1. Mechanistically, PD-1 signalling directly prevents mitochondria fragmentation following T cell stimulation by downregulating Drp1 phosphorylation on Ser616, via regulation of the ERK1/2 and mTOR pathways. In addition, downregulation of Drp1 activity in tumor-infiltrating PD-1pos CD8+ T cells seems to be a mechanism exploited by PD-1 signalling to reduce motility and proliferation of these cells. Overall, our data indicate that the modulation of Drp1 activity in tumor-infiltrating T cells may become a valuable target to ameliorate the anti-cancer immune response in future immunotherapy approaches.

immunology↗