The parent?infant dyad and the construction of the subjective self

Developmental psychology and psychopathology has in the past been more concerned with the quality of self-representation than with the development of the subjective agency which underpins our experience of feeling, thought and action, a key function of mentalisation. This review begins by contrasting a Cartesian view of pre-wired introspective subjectivity with a constructionist model based on the assumption of an innate contingency detector which orients the infant towards aspects of the social world that react congruently and in a specifically cued informative manner that expresses and facilitates the assimilation of cultural knowledge. Research on the neural mechanisms associated with mentalisation and social influences on its development are reviewed. It is suggested that the infant focuses on the attachment figure as a source of reliable information about the world. The construction of the sense of a subjective self is then an aspect of acquiring knowledge about the world through the caregiver's pedagogical communicative displays which in this context focuses on the child's thoughts and feelings. We argue that a number of possible mechanisms, including complementary activation of attachment and mentalisation, the disruptive effect of maltreatment on parent-child communication, the biobehavioural overlap of cues for learning and cues for attachment, may have a role in ensuring that the quality of relationship with the caregiver influences the development of the child's experience of thoughts and feelings

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a de-regulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells