Search

Despite initial high response rates to first-line EGFR TKI, all non-small-cell lung cancer (NSCLC) with EGFR-activating mutation will ultimately develop resistance to treatment. Identification of resistance mechanisms is critical to adapt treatment and improve patient outcomes. Here, we show that a PPP3CB transcript that encodes full-length catalytic subunit 2B of calcineurin accumulates in EGFR-mutant NSCLC cells with acquired resistance against different EGFR TKIs and in post-progression biopsies of NSCLC patients treated with EGFR TKIs. Neutralization of PPP3CB by siRNA or inactivation of calcineurin by cyclosporin A induces apoptosis in resistant cells treated with EGFR TKIs. Mechanistically, EGFR TKIs increase the cytosolic level of calcium and trigger activation of a calcineurin/MEK/ERK pathway that prevents apoptosis. Combining EGFR, calcineurin, and MEK inhibitors overcomes resistance to EGFR TKI in both in vitro and in vivo models. Our results identify PPP3CB overexpression as a new mechanism of acquired resistance to EGFR TKIs, and provide a promising therapeutic approach for NSCLC patients that progress under TKI treatment., (© 2024 Gazzeri et al.)

Lactation is the most energy-demanding event in mammals' reproduction. In pinnipeds, females are the only food providers to the young and have developed numerous behavioral and physiological lactation strategies, from capital-breeding to income-breeding. Lactating females' fine-scale foraging strategy, and precise understanding of how females supplement their pup's needs as well as their own are important to understand the species' ecology and energetic balance. Polar pinnipeds, inhabiting extreme environments, are sensitive to climate change and variability, understanding their constraints and foraging strategy during lactation is therefore important. In 2019, three sonar tags were deployed on lactating Weddell seals in Terre Adélie (East Antarctica) for 7 days, to study fine-scale predator-prey interactions. Feeding activity was mostly benthic, reduced, central-placed, and spatially limited. Females spent most of their time hauled-out. A total of 331 prey capture attempts (PrCAs) were recorded using triaxial acceleration data, with 125 prey identified on echograms (5 cm, acoustic size). All PrCAs occurred on the seafloor, shallower than usual records (mean depth of 88 m, vs 280 m after their molt). We also found that they only fed in three of the five identified dive shapes, during the ascent or throughout the dive. Half of the prey were reactive to the seal's approach, either leaving the seafloor, or escaping just above the seafloor, suggesting that the seals hunt by chasing them from the seabed. Seals continuously scanned the area during the approach phase, evoking opportunistic foraging. Our results provide additional evidence that Weddell seal forage during lactation, displaying a mix of capital-breeding and income-breeding strategies during this period of physiological stress. This work sheds light on previously unexplored aspects of their foraging behavior, such as shallow water environments, targeting benthic prey, generally focusing on single prey rather than schools, and evidence of visual scanning through observed head movements., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Predicting species survival in the face of climate change requires understanding the drivers that influence their distribution. Emperor penguins ( Aptenodytes forsteri ) incubate and rear chicks on landfast sea ice, whose extent, dynamics, and quality are expected to vary substantially due to climate change. Until recently, this species' continent-wide observations were scarce, and knowledge on their distribution and habitat limited. Advances in satellite imagery now allow their observation and characterization of habitats across Antarctica at high resolution. Using circumpolar high-resolution satellite images, unique fast ice metrics, and geographic and biological factors, we identified diverse penguin habitats across the continent, with no significant difference between areas with penguins or not. There is a clear geographic partitioning of colonies with respect to their defining habitat characteristics, indicating possible behavioral plasticity among different metapopulations. This coincides with geographic structures found in previous genetic studies. Given projections of quasi-extinction for this species in 2100, this study provides essential information for conservation measures.

Plastic garbage patches at the ocean surface are symptomatic of a wider pollution affecting the whole marine environment. Sinking of plastic debris increasingly appears to be an important process in the global fate of plastic in the ocean. However, there is insufficient knowledge about the processes affecting plastic distributions and degradation and how this influences the release of additives under varying environmental conditions, especially in deep-sea environments. Here we show that in abiotic conditions increasing hydrostatic pressure inhibits the leaching of the heaviest organic additives such as tris(2-ethylhexyl) phosphate and diisononyl phthalate from polyethylene and polyvinylchloride materials, whereas deep-sea and surface marine prokaryotes promote the release of all targeted additives (phthalates, bisphenols, organophosphate esters). This study provides empirical evidences for more efficient additive release at the ocean surface than in deep seawater, where the major plastic burden is supposed to transit through before reaching the sediment compartment., (© 2021. The Author(s).)

Phytoplankton is a key component in marine ecosystems. It is responsible for most of the marine primary production, particularly in eutrophic lagoons, where it frequently blooms. Because they are very sensitive to their environment, the dynamics of these microbial communities has to be observed over different time scales, however, assessment of short term variability is often out of reach of traditional monitoring methods. To overcome these limitations, we set up a Cytosense automated flow cytometer (Cytobuoy b.v.), designed for high frequency monitoring of phytoplankton composition, abundance, cell size, and pigment content, in one of the largest Mediterranean lagoons, the Berre lagoon (South-Eastern France). During October 2011, it recorded the cell optical properties of 12 groups of pico-, nano-, and microphytoplankton. Daily variations in the cluster optical properties were consistent with individual changes observed using microscopic imaging, during the cell cycle. We therefore used an adaptation of the size-structured matrix population model, developed by Sosik et al. (2003) to process the single cell analysis of the clusters and estimate the division rates of 2 dinoflagellate populations before, during, and after a strong wind event. The increase in the estimated in situ daily cluster growth rates suggest that physiological changes in the cells can prevail over the response of abundance.

Bacterial bioluminescence is commonly found in the deep sea and depends on environmental conditions. Photobacterium phosphoreum ANT-2200 has been isolated from the NW Mediterranean Sea at 2200-m depth (in situ temperature of 13°C) close to the ANTARES neutrino telescope. The effects of hydrostatic pressure on its growth and luminescence have been investigated under controlled laboratory conditions, using a specifically developed high-pressure bioluminescence system. The growth rate and the maximum population density of the strain were determined at different temperatures (from 4 to 37°C) and pressures (from 0.1 to 40 MPa), using the logistic model to define these two growth parameters. Indeed, using the growth rate only, no optimal temperature and pressure could be determined. However, when both growth rate and maximum population density were jointly taken into account, a cross coefficient was calculated. By this way, the optimum growth conditions for P. phosphoreum ANT-2200 were found to be 30°C and, 10 MPa defining this strain as mesophile and moderately piezophile. Moreover, the ratio of unsaturated vs. saturated cellular fatty acids was found higher at 22 MPa, in agreement with previously described piezophile strains. P. phosphoreum ANT-2200 also appeared to respond to high pressure by forming cell aggregates. Its maximum population density was 1.2 times higher, with a similar growth rate, than at 0.1 MPa. Strain ANT-2200 grown at 22 MPa produced 3 times more bioluminescence. The proposed approach, mimicking, as close as possible, the in situ conditions, could help studying deep-sea bacterial bioluminescence and validating hypotheses concerning its role into the carbon cycle in the deep ocean.