Possible positive autocrine feedback in the prereplicative phase of human fibroblasts

The growth of normal diploid fibroblasts is generally thought to be tightly controlled by exogenous growth factors such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). Subversion of a growth factor pathway at a regulatory point is considered to be a key event in neoplastic transformation and tumorigenesis. Thus, simian sarcoma virus has acquired the gene encoding the B-chain of PDGF and there is direct experimental proof that SSV-transformation is mediated by a PDGF-like growth factor. There is accumulating evidence that PDGF-like molecules are also synthesized and released by certain normal cells, suggesting an important role of cellularly produced PDGF in development and tissue regeneration. We now present evidence that a transient expression of the gene encoding the PDGF A-chain, and the synthesis and release of functional A-chain homodimers, is an early event in the prereplicative phase of normal human foreskin fibroblasts exposed to PDGF or EGF. Since these cells are PDGF-responsive, the results imply the existence of a positive autocrine signal that may serve as an amplifier of the mitogenic response under certain conditions.     

Summing up the noise in gene networks

Random fluctuations in genetic networks are inevitable as chemical reactions are probabilistic and many genes, RNAs and proteins are present in low numbers per cell. Such 'noise' affects all life processes and has recently been measured using green fluorescent protein (GFP). Two studies show that negative feedback suppresses noise, and three others identify the sources of noise in gene expression. Here I critically analyse these studies and present a simple equation that unifies and extends both the mathematical and biological perspectives.     

Evolutionary and functional perspectives of the major histocompatibility complex class I antigen-processing machinery

Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8+ T cells, providing the basis for immune recognition of pathogen-infected cells. Peptides generated mainly by proteasomes in the cytosol are transported into the lumen of the endoplasmic reticulum by transporters associated with antigen processing (TAP). The maturation of MHC class I molecules is controlled by a number of accessory proteins and chaperones that are to a varying degree dedicated to the assembly of MHC class I. Several newly characterised proteins have been demonstrated to play important roles in this process. This review focuses on the functional relationship and evolutionary history of the antigen-processing machinery (APM) components and MHC class I itself. These are of great interest for further elucidating the origin of the immune system and understanding the mechanisms of antigen presentation and immunology in general.