How Should We Treat Meningeal Melanocytoma? A Retrospective Analysis of Potential Treatment Strategies

Background: Meningeal melanocytomas (MM) are rare primary melanocytic tumors of the leptomeninges with an incidence of 1:10,000,000. Until now, there has been only sparse information about this tumor entity. Here, we provide a meta-analysis of all cases published in the English language since 1972. Methods: A literature review was performed using PubMed and Web of Science. All published cases were evaluated for location, sex, age, therapeutic approach, and outcome. In total, we included 201 patient cases in our meta–analysis. Results: The majority of MM was diagnosed more frequently in men between the third and fifth decade of life. Surgery is the preferred therapeutic approach, and total resection is associated with the best outcome. Patients with partial resection or tumor recurrence benefit from adjuvant radiotherapy, whereas chemo- or immunotherapies do not improve the disease course. Malignant transformation was described in 18 patients. Of these, 11 patients developed metastasis. Conclusions: We present the first retrospective meta-analysis of all MM cases published in the English language, including an evaluation of different treatment strategies allowing us to suggest a novel treatment guideline highlighting the importance of total resection for recurrence–free survival and characterizing those cases which benefit from adjuvant radiotherapy

NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation

Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expression levels of the translation initiation factor Eif4a2 and its premature termination codon-encoding isoform (Eif4a2(PTC)). NMD deficiency leads to translation of the truncated eIF4A2(PTC) protein. eIF4A2(PTC) elicits increased mTORC1 activity and translation rates and causes differentiation delays. This establishes a previously unknown feedback loop between NMD and translation initiation. Furthermore, our results show a clear hierarchy in the severity of target deregulation and differentiation phenotypes between NMD effector KOs (Smg5 KO > Smg6 KO > Smg7 KO), which highlights heterodimer-independent functions for SMG5 and SMG7. Together, our findings expose an intricate link between mRNA homeostasis and mTORC1 activity that must be maintained for normal dynamics of cell state transitions

Evolution and history of grapevine (Vitis vinifera) under domestication: new morphometric perspectives to understand seed domestication syndrome and reveal origins of ancient European cultivars

International audienceBackground and Aims In spite of the abundance of archaeological, bio-archaeological, historical and genetic data, the origins, historical biogeography, identity of ancient grapevine cultivars and mechanisms of domestication are still largely unknown. Here, analysis of variation in seed morphology aims to provide accurate criteria for the discrimination between wild grapes and modern cultivars and to understand changes in functional traits in relation to the domestication process. This approach is also used to quantify the phenotypic diversity in the wild and cultivated compartments and to provide a starting point for comparing well-preserved archaeological material, in order to elucidate the history of grapevine varieties. Methods Geometrical analysis (elliptic Fourier transform method) was applied to grapevine seed outlines from modern wild individuals, cultivars and well-preserved archaeological material from southern France, dating back to the first to second centuries. Key Results and Conclusions Significant relationships between seed shape and taxonomic status, geographical origin (country or region) of accessions and parentage of varieties are highlighted, as previously noted based on genetic approaches. The combination of the analysis of modern reference material and well-preserved archaeological seeds provides original data about the history of ancient cultivated forms, sonic of them morphologically close to the current 'Clairette' and 'Mondeuse blanche' cultivars. Archaeobiological records seem to confirm the complexity of human contact, exchanges and migrations which spread grapevine cultivation in Europe and in Mediterranean areas, and argue in favour of the existence of local domestication in the Languedoc (southern France) region during Antiquity