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Sam (Radnor) is a struggling writer who has trouble with long-term relationships; one day while on the subway, he meets Rasheen (Michael Algieri), a young boy who has been abandoned by his parents. Sam takes the boy in, which gives him a preview of parenthood but also proves to be more complicated than he expected. Sam is infatuated with Mississippi (Kate Mara), a bartender with a dream of making it as a musician; tired of one-night stands, she agrees to move in with Sam for a few days to see how she feels about a ‘real’ relationship, but Rasheen’s presence makes things awkward. Another of Sam’s sometime girlfriends is Annie (Malin Akerman), who suffers from a rare medical condition that prevents her from having any hair. Though she’s beautiful, Annie’s lack of hair has caused her to have a dire self-image and she jumps from one relationship to another with a handful of men, some of whom treat her poorly. And Mary Catherine (Zoe Kazan) and Charlie (Pablo Schreiber) are a couple whose relationship is teetering on the brink as he considers a lucrative job offer in Los Angeles while she refuses to budge.
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