Enhancer of Zeste Homolog 2 (EZH2) Contributes to Rod Photoreceptor Death Process in Several Forms of Retinal Degeneration and Its Activity Can Serve as a Biomarker for Therapy Efficacy.

Inherited retinal dystrophies (IRD) are due to various gene mutations. Each mutated gene instigates a specific cell homeostasis disruption, leading to a modification in gene expression and retinal degeneration. We previously demonstrated that the polycomb-repressive complex-1 (PRC1) markedly contributes to the cell death process. To better understand these mechanisms, we herein study the role of PRC2, specifically EZH2, which often initiates the gene inhibition by PRC1. We observed that the epigenetic mark H3K27me3 generated by EZH2 was progressively and strongly expressed in some individual photoreceptors and that the H3K27me3-positive cell number increased before cell death. H3K27me3 accumulation occurs between early (accumulation of cGMP) and late (CDK4 expression) events of retinal degeneration. EZH2 hyperactivity was observed in four recessive and two dominant mouse models of retinal degeneration, as well as two dog models and one IRD patient. Acute pharmacological EZH2 inhibition by intravitreal injection decreased the appearance of H3K27me3 marks and the number of TUNEL-positive cells revealing that EZH2 contributes to the cell death process. Finally, we observed that the absence of the H3K27me3 mark is a biomarker of gene therapy treatment efficacy in XLRPA2 dog model. PRC2 and PRC1 are therefore important actors in the degenerative process of multiple forms of IRD

Phylogeny and biogeography of pholadid bivalve Barnea (Anchomasa) with considerations on the phylogeny of Pholadoidea

The paper examines the systematics, phylogeny and biogeographical history of Barnea (Anchomasa), which is one of the most abundant and diversified of modern pholadid bivalves. The range of morphology of its distinctive characters and comparisons with other pholadoidean taxa are described in detail. An extensive cladistic analysis based on morphological characters at genus and subgenus levels allowed the inclusion of B. (Anchomasa) into the phylogeny of Pholadoidea and the establishment of its most appropriate taxonomic position. The analysis confirms that Barnea s.s. and B. (Umitakea) are its closest relatives and that the morphological similarities to other taxa are mainly due to plesiomorphies. The fossil record and the data on the present 12day distribution contributed to trace the biogeographical history of B. (Anchomasa). The present 12day biogeography is marked by the disjunct distribution of species. Species are distributed mainly either along the Atlantic and Pacific coasts of the American continent (American group) or in the Indo 12West Pacific region (Indo 12West Pacific group). Both these groups have distinct morphological features and biogeographical structures. The fossil record and the known geodynamic scenario suggest a relationship of direct derivation between the Indo 12West Pacific group and a stock of north 12eastern Atlantic to Paratethyan species. This reflects a vicariant event related to the closure of the connection between western Tethys and the Indian Ocean in the middle Miocene. The American group presumably arose from the European stock during the Late Pliocene by dispersal towards the eastern coasts of North America and rapid southward diffusion. A relative differentiation within the American group is probably related to the last phases of emergence of the Panama Isthmus. The cladistic analysis also gives suggestions for the reconstruction of the phylogeny of the superfamily Pholadoidea. It confirms the interpretation of several characters sustained by previous authors. However, it also shows remarkable differences to the previous taxonomic arrangements. Pholadinae includes only taxa having the protoplax and it appears to be the sister 12group of a major clade composed mainly of two groups, namely Martesiinae\u2013Jouannetiinae and Xylophagainae\u2013Teredinidae. The Martesiinae are paraphyletic whereas the obligate wood 12boring Xylophagainae and Teredinidae form a well 12supported monophyletic group