Phosphorylation of the Leukemic Oncoprotein EVI1 on Serine 196 Modulates DNA Binding, Transcriptional Repression and Transforming Ability

The EVI1 (ecotropic viral integration site 1) gene at 3q26 codes for a transcriptional regulator with an essential role in haematopoiesis. Overexpression of EVI1 in acute myeloid leukaemia (AML) is frequently associated with 3q26 rearrangements and confers extremely poor prognosis. EVI1 mediates transcriptional regulation, signalling, and epigenetic modifications by interacting with DNA, proteins and protein complexes. To explore to what extent protein phosphorylation impacts on EVI1 functions, we analysed endogenous EVI1 protein from a high EVI1 expressing Fanconi anaemia (FA) derived AML cell line. Mass spectrometric analysis of immunoprecipitated EVI1 revealed phosphorylation at serine 196 (S196) in the sixth zinc finger of the N-terminal zinc finger domain. Mutated EVI1 with an aspartate substitution at serine 196 (S196D), which mimics serine phosphorylation of this site, exhibited reduced DNA-binding and transcriptional repression from a gene promotor selectively targeted by the N-terminal zinc finger domain. Forced expression of the S196D mutant significantly reduced EVI1 mediated transformation of Rat1 fibroblasts. While EVI1-mediated serial replating of murine haematopoietic progenitors was maintained by EVI1-S196D, this was associated with significantly higher Evi1-trancript levels compared with WT-EVI1 or EVI1-S196A, mimicking S196 non-phosphorylated EVI1. These data suggest that EVI1 function is modulated by phosphorylation of the first zinc finger domain

Too much or not enough? Planning electric vehicle charging infrastructure: A review of modeling options

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A herpetotheriid marsupial from the Oligocene of Bugti Hills, Balochistan, Pakistan

International audienceDidelphimorph marsupials were widely distributed in Asia during the Cenozoic, but their occurrence in the Indian subcontinent has not so far been demonstrated. Here, we describe a new herpetotheriid marsupial Asiddidelphis akbar-bugtii sp. nov. from the early Oligocene Bugti Member of the Chitarwata Formation, Bugti Hills, Pakistan. The discovery of the herpetotheriids in the Oligocene of Pakistan represents the most southern occurrence of the family, which was thought to have occurred only to the north of the Alpine-Himalayan Suture. Our data suggest that episodic faunal exchanges occurred between the Asian mainland and the Indian subcontinent during the late Paleogene, and that the southern Asian faunas were not as completely isolated by the Himalayan chain as formerly believed

A Multilingual Semantic Similarity-Based Approach for Question-Answering Systems

International audienceQuestion-answering systems face a challenge related to the process of deciding automatically about the veracity of a given answer. This issue is particularly problematic when handling open-ended questions. In this paper, we propose a multilingual semantic similarity-based approach to estimate the similarity score between the user’s answer and the right one saved in the data tier. This approach is mainly based on semantic information notably the synonymy relationships between words and syntactico-semantic information especially semantic class and thematic role. It supports three languages: English, French and Arabic. Our approach is applied to a multilingual ontology-based question-answering training for Alzheimer’s disease patients. The performance of the pro- posed approach was confirmed through experiments on 20 patients that promising capabilities in identifying literal and some types of intelligent similarity