Negatively charged macromolecules or polyanions, including nucleic acids [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], phospholipids [21], [22], [23], [24] and glycosaminoglycans (GAGs) have been implicated as facilitating cofactors in the conversion of PrPC to PrPSc and thereby in the transmission and pathogenesis of prion disease.
Activation of the sympathetic nervous system (SNS) and the hypothalamic pituitary adrenal (HPA) axis was implicated as facilitating cancer progression, as were pro-inflammatory factors and prostaglandins [3], [14], [17], [18].
By extension, the psychologists who are members of the association are implicated as well.
It has been implicated as an oncogene to facilitate cell growth and survival.
TNF α has been implicated as a key molecule to facilitate insulin-mediated glucose uptake at peripheral tissues [ 33] and the increased expression of TNF- α– 4 e)) could however be partly responsible for the marked increase in macrophage infiltration– 4 e)) and IL-6 expression that we have observed from the Mutant pancreas– 4(i)).
The complement anaphylatoxins have been implicated as tumor-elaborated signals that facilitate both the formation of this altered microenvironment and suppression of infiltrating immune cells 5. Much of the attention directed toward complement in cancer has centered on membrane complement regulatory proteins (mCRPs), which represent another mechanism of tumor immune evasion.
Recently, aquaporins have been implicated as key in freeze tolerance, perhaps by facilitating osmotic equilibration of cells during the freezing process [7], [8].
Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization.
Sterols facilitate normal membrane function by controlling their fluidity, but they have also been implicated as ligands for nuclear receptors directly affecting transcription and signal transduction pathways [ 51].
Ca2+ influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of oxidative stress.
ATP8A1/ATPase II facilitates ATP-dependent transport of phosphatidylserine (PS) across vesicle membranes in vitro and has been implicated as the "flippase" that maintains PS asymmetry in the plasma membrane [40], [41].
