The Nuclear Factor of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is a Repressor of Chondrogenesis

Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor

Hyperproliferation and Dysregulation ofIL-4 Expression in NF-ATp-Deficient Mice

AbstractNF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM–CSF, and TNFα was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFNγ were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.BDY

A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

A quantitative description of the transition between intuitive altruism and rational deliberation in iterated Prisoner's Dilemma experiments

What is intuitive: pro-social or anti-social behaviour? To answer this fundamental question, recent studies analyse decision times in game theory experiments under the assumption that intuitive decisions are fast and that deliberation is slow. These analyses keep track of the average time taken to make decisions under different conditions. Lacking any knowledge of the underlying dynamics, such simplistic approach might however lead to erroneous interpretations. Here we model the cognitive basis of strategic cooperative decision making using the Drift Diffusion Model to discern between deliberation and intuition and describe the evolution of the decision making in iterated Prisoner's Dilemma experiments. We find that, although initially people's intuitive decision is to cooperate, rational deliberation quickly becomes dominant over an initial intuitive bias towards cooperation, which is fostered by positive interactions as much as frustrated by a negative one. However, this initial pro-social tendency is resilient, as after a pause it resets to the same initial value. These results illustrate the new insight that can be achieved thanks to a quantitative modelling of human behavior