Hypothetical types of biochemistry

Summary

Hypothetical types of biochemistry are forms of biochemistry agreed to be scientifically viable but not proven to exist at this time. The kinds of living organisms currently known on Earth all use carbon compounds for basic structural and metabolic functions, water as a solvent, and DNA or RNA to define and control their form. If life exists on other planets or moons it may be chemically similar, though it is also possible that there are organisms with quite different chemistries – for instance, involving other classes of carbon compounds, compounds of another element, or another solvent in place of water. The possibility of life-forms being based on "alternative" biochemistries is the topic of an ongoing scientific discussion, informed by what is known about extraterrestrial environments and about the chemical behaviour of various elements and compounds. It is of interest in synthetic biology and is also a common subject in science fiction. The element silicon has been

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A Model of Synaptic Reconsolidation

Wulfram Gerstner, David Barak Kastner, Tilo Schwalger, Lorric Ziegler

Reconsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of synaptic consolidation to capture hippocampal slice experiments that have been interpreted as reconsolidation at the synaptic level. The model implements reconsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which synaptic reconsolidation does or does not occur, often referred to as the boundary conditions of reconsolidation. We find that our computational model of synaptic reconsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of synaptic reconsolidation.

Frontiers Research Foundation2016

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Previous retrosynthetic and isotope-labeling studies have indicated that biosynthesis of the iron guanylylpyridinol (FeGP) cofactor of [Fe]-hydrogenase requires a methyltransferase. This hypothetical enzyme covalently attaches the methyl group at the 3-position of the pyridinol ring. We describe the identification of HcgC, a gene product of the hcgA-G cluster responsible for FeGP cofactor biosynthesis. It acts as an S-adenosylmethionine (SAM)-dependent methyltransferase, based on the crystal structures of HcgC and the HcgC/SAM and HcgC/S-adenosylhomocysteine (SAH) complexes. The pyridinol substrate, 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol, was predicted based on properties of the conserved binding pocket and substrate docking simulations. For verification, the assumed substrate was synthesized and used in a kinetic assay. Mass spectrometry and NMR analysis revealed 6-carboxymethyl-3,5-dimethyl-4-hydroxy-2-pyridinol as the reaction product, which confirmed the function of HcgC.

Wiley-Blackwell2016

Photobleaching Kinetics and Time-Integrated Emission of Fluorescent Probes in Cellular Membranes

Daniel Sage

Since the pioneering work of Hirschfeld, it is known that time-integrated emission (TiEm) of a fluorophore is independent of fluorescence quantum yield and illumination intensity. Practical implementation of this important result for determining exact probe distribution in living cells is often hampered by the presence of autofluorescence. Using kinetic modelling of photobleaching combined with pixel-wise bleach rate fitting of decay models with an updated plugin to the ImageJ program, it is shown that the TiEm of a fluorophore in living cells can be determined exactly from the product of bleaching amplitude and time constant. This applies to mono-exponential bleaching from the first excited singlet and/or triplet state and to multi-exponential combinations of such processes. The TiEm can be used to correct for illumination shading and background autofluorescence without the need for fluorescent test layers or separate imaging of non-stained cells. We apply the method to simulated images and to images of cells, whose membranes were labelled with fluorescent sterols and sphingolipids. Our bleaching model can be extended to include a probability density function (PDF) of intrinsic bleach rate constants with a memory kernel. This approach results in a time-dependent bleach rate coefficient and is exemplified for fluorescent sterols in restricted intracellular environments, like lipid droplets. We show that for small deviations from the classical exponential bleaching, the TiEm of decay functions with rate coefficients remains largely independent of fluorescence lifetime and illumination, and thereby represents a faithful measure of probe distribution.

Mdpi Ag2014