Honestly it has never been made explicit.
My take is that Mako is upset that Yuri is no longer dependent on her. In addition Yuri's increasing eccentricity offends her sensibilities. Mako has been lashing out at Yoshida for similar reasons.
AI reference? I thought the story was supposed to be set in past like in 2010 or something. Anyway Nemo's mind is broken from exposing her bad side to her parent that she stopped caring any more.
I mean, how many manga have u read that have started in like say the 90s and are still going, but suddenly the characters go from flip phones to smart phones?