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Hay Mele, B.

Publications and source records attributed to Hay Mele, B..

3 recordsLinked to original sources

Particle-based representation of phytoplankton modulates emergent coexistence and biogeography in a model ocean

Phytoplankton communities sustain the marine food web through primary productivity. These communities sustain a high diversity of species, all of which must draw from the same finite nutrient supply. The mechanisms driving phytoplankton biogeography and succession, as well as those enabling high diversity, remain incompletely understood. Here, we compare emerging patterns of biogeography, richness, and diversity in a size-structured phytoplankton community as it is advected and diffused within an idealized North Atlantic double-gyre circulation, using both Eulerian and Lagrangian (particle-based) modeling (PBM) frameworks. When a sufficient number of particles is modeled, the PBM, which resolves mortality at the particle level, produces stronger seasonal variability in biomass in the northern gyre and less stable and higher biomass in the southern gyre, while reproducing large-scale chlorophyll patterns observed by satellite. These contrasting dynamics are accompanied by distinct regional diversity patterns: local richness and diversity are generally higher in the PBM than in the Eulerian model in the northern gyre, with differences depending on the mortality threshold, whereas in the oligotrophic southern gyre, PBM local richness increases with particle number, while Eulerian richness is more sensitive to the mortality threshold. The PBM also produces a dynamic and emergent biogeographical structure that is more robust to the mortality threshold than the Eulerian model. Finally, Lagrangian variability in environmental conditions experienced by particles shows a stronger impact compared to the local Eulerian variability in the Northern gyre and stresses variable sensitivity to environmental histories. Together, these results suggest that the discrete representation of biomass fundamentally alters mortality, biogeography, and emergent coexistence patterns in model plankton ecosystems.

ecology↗

Identification of genetic and non-genetic modifiers of genomic imprinting through whole genome screening in humans

Genomic imprinting is required for normal development, and abnormal methylation of differentially methylated regions (iDMRs) controlling the parent of origin-dependent expression of the imprinted genes has been found in constitutional disorders affecting growth, metabolism, neurobehavior, and in cancer. In most of these cases the cause of the imprinting abnormalities is unknown. Also, these studies have generally been performed on a limited number of CpGs, and a systematic investigation of iDMR methylation in the general population is lacking. By analysing the iDMRs in a large number of peripheral blood DNA methylation array datasets of unaffected individuals and patients with rare disorders, we determined the most common iDMR methylation profiles and identified many genetic and non-genetic factors contributing to their variability. We found that methylation variability is not homogeneous within the iDMRs and that the CpGs closer to the ZFP57 binding sites are less susceptible to methylation changes. We demonstrated the methylation polymorphism of three iDMRs and the atypical behaviour of several others, and reported the association of 25 disease- and 47 non-disease-complex traits, including blood cell type composition, as well as 15 mendelian or chromosomal disorders, with iDMR methylation changes in blood DNA. These findings identify several genetic and non-genetic factors associated with genomic imprinting maintenance in humans, which may have a role in the aetiology of the diseases associated with imprinting abnormalities and have clear implications in molecular diagnostics.

genetics↗

A maternal-effect Padi6 variant results in abnormal nuclear localization of DNMT1 and failure of epigenetic reprogramming and zygotic genome activation in mouse embryos

PADI6 belongs to the multi-protein sub-cortical maternal complex (SCMC) that is present specifically in mammalian oocytes and early embryos. Maternal inactivation of SCMC genes generally results in early embryo lethality. In humans, variants in a subset of SCMC genes have been found in the healthy mothers of children affected by genomic imprinting disorders and characterized by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. To address this issue, we generated a mouse line carrying a Padi6 missense variant that had been identified in the mother of two sisters affected by Beckwith-Wiedemann syndrome and MLID. We found that if homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell DNA methylation and RNA analyses demonstrated genomic hypermethylation, down-regulation of zygotic genome activation (ZGA) genes and up-regulation of maternal decay genes in 2-cell embryos from homozygous females. In addition, immunofluorescence analysis showed abnormal localization of DNMT1 and UHRF1 in mutant oocytes and zygotes. Taken together, this study demonstrates that PADI6 controls the subcellular localization of DNMT1 that is necessary for pre-implantation epigenetic reprogramming and ZGA.

genomics↗