ALBERT

Description: Bentho-pelagic life cycles are the dominant reproductive strategy in marine invertebrates, providing great dispersal ability, access to different resources, and the opportunity to settle in suitable habitats upon the trigger of environmental cues at key developmental moments. However, free-dispersing larvae can be highly sensitive to environmental changes. Among these, the magnitude and the occurrence of elevated carbon dioxide (CO2) concentrations in oceanic habitats is predicted to exacerbate over the next decades, particularly in coastal areas, reaching levels beyond those historically experienced by most marine organisms. Here, we aimed to determine the sensitivity to elevated pCO2 of successive life stages of a marine invertebrate species with a bentho-pelagic life cycle, exposed continuously during its early ontogeny, whilst providing in-depth insights on their metabolic responses. We selected, as an ideal study species, the American lobster Homarus americanus, and investigated life history traits, whole-organism physiology, and metabolomic fingerprints from larval stage I to juvenile stage V exposed to different pCO2 levels. Current and future ocean acidification scenarios were tested, as well as extreme high pCO2/low pH conditions that are predicted to occur in coastal benthic habitats and with leakages from underwater carbon capture storage (CCS) sites. Larvae demonstrated greater tolerance to elevated pCO2, showing no significant changes in survival, developmental time, morphology, and mineralisation, although they underwent intense metabolomic reprogramming. Conversely, juveniles showed the inverse pattern, with a reduction in survival and an increase in development time at the highest pCO2 levels tested, with no indication of metabolomic reprogramming. Metabolomic sensitivity to elevated pCO2 increased until metamorphosis (between larval and juvenile stages) and decreased afterward, suggesting this transition as a metabolic keystone for marine invertebrates with complex life cycles.

Description: Background: Acute myeloid leukemia (AML) is a clinically heterogeneous group of cancers. While some patients respond well to chemotherapy, we describe here a subgroup with distinct molecular features that has very poor prognosis under chemotherapy. The classification of AML relies substantially on cytogenetics, but most cytogenetic abnormalities do not offer targets for development of targeted therapeutics. Therefore, it is important to create a detailed molecular characterization of the subgroup most in need of new targeted therapeutics.Methods: We used a multi-omics approach to identify a molecular subgroup with the worst response to chemotherapy, and to identify promising drug targets specifically for this AML subgroup.Results: Multi-omics clustering analysis resulted in three primary clusters among 166 AML adult cancer cases in TCGA data. One of these clusters, which we label as the high-risk molecular subgroup (HRMS), consisted of cases that responded very poorly to standard chemotherapy, with only about 10% survival to 2 years. The gene TP53 was mutated in most cases in this subgroup but not in all of them. The top six genes over-expressed in the HRMS subgroup included E2F4, CD34, CD109, MN1, MMLT3, and CD200. Multi-omics pathway analysis using RNA and CNA expression data identified in the HRMS subgroup over-activated pathways related to immune function, cell proliferation, and DNA damage.Conclusion: A distinct subgroup of AML patients are not successfully treated with chemotherapy, and urgently need targeted therapeutics based on the molecular features of this subgroup. Potential drug targets include over-expressed genes E2F4, and MN1, as well as mutations in TP53, and several over-activated molecular pathways.