Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells

Background: Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human. Methodology/Principal Findings: Here we show that depletion of Tpr by RNA interference triggers G0–G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. We also found that Tpr depletion impairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In addition Tpr depletion impacts on level and function of the SUMO-protease SENP2 thus affecting SUMOylation regulation at the nuclear pore and overall SUMOylation in the cell. Conclusions: Our data for the first time provide evidence that a nuclear pore component plays a role in controlling cellular senescence. Our findings also point to new roles for Tpr in the regulation of SUMO-1 conjugation at the nuclear pore and directly confirm Tpr involvement in the nuclear export of NES-proteins

Goal Slippage: A Mechanism for Spontaneous Instrumental Helping in Infancy?

In recent years, developmental psychologists have increasingly been interested in various forms of prosocial behavior observed in infants and young children—in particular comforting, sharing, pointing to provide information, and spontaneous instrumental helping. We briefly review several models that have been proposed to explain the psychological mechanisms underpinning these behaviors. Focusing on spontaneous instrumental helping, we home in on models based upon what Paulus (Child Development Perspectives 8(2):77–81, 2014) has dubbed ‘goal-alignment’, i.e. the idea that the identification of an agent’s goal leads infants to take up that goal as their own. We identify a problem with the most well-known model based upon this idea, namely the ‘goal contagion’ model. The problem arises from the way in which the model specifies the content of the goal which is identified and taken up. We then propose an alternative way of specifying the content of the goal, and use this as a starting point for articulating an alternative model based upon the idea of alignment, namely the ‘goal slippage’ model. By elucidating the difference between goal contagion and goal slippage, we contribute to the articulation of experimental criteria for assessing whether and when the mechanisms specified by these two models are at work