The article will start with the discovery of metallothioneins and definitions of the term with an account of the first 40 years of MT research culminating in the determination of three-dimensional (3D) structures of mammalian MTs. Seen with this perspective, the search for a function of an entire family of proteins turns out to be a quite educational lesson in the history of science. MT is emblematic of the difficulties faced when trying to define functions of proteins without known activities. Resolutions of conjectures had to await additional discoveries, especially insights into the molecular basis of how cellular metal metabolism is controlled. Trials and tribulations emerged from some assumptions in lieu of facts and from not interpreting chemistry in the context of biology. In a discussion of discoveries seriatim, the etymology of “metallothionein” and the epistemology of the field will foster an understanding of how our present ideas about metallothionein (MT) were shaped. It is crucial to start the narration with the early history to understand the facts and why and how contentions developed. Three human generations have witnessed the development of the field of metallothioneins. Recent advances in understanding the control of cellular zinc and copper homeostasis are the foundation for suggesting that mammalian metallothioneins provide a highly dynamic, regulated, and uniquely biological metal buffer to control the availability, fluctuations, and signaling transients of the most competitive Zn(II) and Cu(I) ions in cellular space and time. Many fundamental signal transduction pathways regulate the expression of the dozen of human metallothionein genes. Their coordination dynamics allows a vast conformational landscape for interactions with other proteins and ligands. The proteins, therefore, also exist in different redox states of the sulfur donor ligands. It endows the proteins with redox activity and a specific pH dependence of their metal affinities. The homoleptic thiolate coordination of mammalian metallothioneins is important for their molecular mechanism. They exist in multiple forms with different degrees of metalation and types of metal ions. The proteins need to be seen in their biological context, which limits and defines the chemistry possible. The terms metallothionein and thionein are ambiguous and insufficient to understand biological function. It challenges the dogma that the biologically relevant structure of the mammalian proteins is only the one determined by X-ray diffraction and NMR spectroscopy. This article guides through the history of investigations and resolves multiple contentions by providing new interpretations of the structure-stability-function relationship. I looked at the “config/terminal.ini” file as well as search the Registry (regedit) to see if I could circumvent the behaviour but could not find anything that could help me “fix” this.Īnyone have any idea how I could push into play the old behaviour and have everything where I want it to be (i.e.The functions, purposes, and roles of metallothioneins have been the subject of speculations since the discovery of the protein over 60 years ago. Now, with is this new build, even though I installed it under the above mentioned structure, it placed all my MT4 data under the Roaming User Profile (C: Drive), making it no longer portable, messing up my structure, backups & maintenance as well as affect the back-testing, since it is now slower because it is competing for hard-drive resources with the OS and other applications. This made it easy to maintain the data and quickly backup everything in one go as well as allow portability by just copying the structure to a USB Pen Drive and I was ready to use it on another PC.Īlso, since it was on a separate drive, my Strategy Tests did not weigh on the C: drive and affect the OS or other Applications running, making back-testing much faster. In previous builds, I had all my terminal installations, installed on my D: Drive under a directory tree structure organised by Broker, Live/Real and Account with hard-link junctions points for common areas such as experts, indicators, libraries, etc. Is there any way to make the latest build/release of MT4 portable?
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