Chemical Science Blog

Anthony White from the Department of Pathology, University of Melbourne and team have investigated the use of X-ray Fluorescence Microscopy to investigate subcellular biometal homeostasis in a mouse model of the childhood neurodegenerative disorder – Batten disease. This is a particularly nasty disease that causes progressive blindness and motor impairment leading to premature death. The team have previously highlighted the redistribution of brain zinc in diseased samples using subcellular fractionation techniques. However, the lack of a rapid, specific and sensitive technique to provide quantitative subcellular information in situ on biometal distributions is severely limiting the understanding of the effect that the changes in biometals distributions can have in neurodegenerative diseases.

Intracellular zinc and calcium distributions mapped by x-ray fluorescence microscopy.

In their Chemical Science paper the team have utilised the advances in data collection speed of X-ray fluorescence detectors to map the zinc and calcium distributions in a statistically relevant number of cells. Despite a lack of global changes in biometal levels this approach revealed the perturbed trafficking of zinc and the significantly altered subcellular calcium distributions. The restorative properties of a therapeutic zinc-complex were also shown using this technique.

Techniques and methodology reported in the Chemical Science paper can be applied to other neurodegenerative diseases and importantly can provide insights to the mechanism of action of novel therapeutics at the single cell level.

Read the Chem. Sci. paper in full today for free* and see if this technique could be applied to a disease you are studying!

X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder
A. Grubman, S.A. James, J. James, C. Duncan, I. Volitakis, J.L. Hickey, P.J. Crouch, P.S. Donnelly, K.M. Kanninen, J.R. Liddell, S.L. Cotman, M.D. de Jonge and A.R. White*
DOI: 10.1039/C4SC00316K

*Access is free until 20.06.14 through a registered RSC account – click here to register

We live in the technological age, surrounded by gadgets and gizmos with computer chips inside. They make our lives easier (mostly) and their speed just seems to keep increasing. But the computations only use binary code, zeros and ones and the speed at which they can be carried out will ultimately be limited by the size that the silicon circuits can be reduced to. What if computations could be done on a single molecule, which has been shown before, but also with the use of more than just two numbers? How about adding two and three to the available list of numbers? This is what Skrollan Stockinger and Oliver Trapp from the Ruprecht-Karls-Universitat Heidelberg detail in their recent Chemical Science paper.

They report a ternary/quaternary logic system based on a mixture of benzonitrile oxide with iron(III) ions and zinc ions which changes colour depending on the inputs. Using photographic recording and analysis of the Red/Green/Blue (RGB) values they can read out four different states: colourless, yellow, deep purple and a solution with precipitate present. This creates a system that gives the user a higher information processing density.

Two molecular logic systems with two independent input factors resulting in a continuous system and a system with a quaternary basis.

Does information processing really have to be restricted to zeros and ones? Using sodium thiocyanate ions rather than zinc ions the authors have created a continuous system. The sodium thiocynate creates a red complex and analysis of the RGB channels allow a range of concentrations to be detected which could be split up into any number of states for computation, rapidly increasing the information processing density. Therefore this continuous system could extend multi-valued logic beyond the ternary and quaternary systems described in the literature and the current paper.

Both systems show very good long-term stability and could find uses as a high potential storage medium with high data processing ability.

To find out the details of this work read the Chem. Sci. paper in full for free* today:

A Continuous and Multi Valued System as Molecular Answer for Data Processing and Data Storage

Skrollan Stockinger and Oliver Trapp

When most people read a book they don’t remember every word. They compress the story down to the main points and remember those. The reverse is also true – given a few facts most people can embellish a story to a suitably lengthy tale of adventure and mystery.

These data compression/decompression processes are called logic operations and are a central theme in information theory. They are also replicated in biological systems where scaffolding proteins within the regulatory cellular networks carry out the operations. However, there has been no synthetic DNA-based system that can carry out this data compression/decompression process, until now.

Logic circuit showing how 4 inputs (I) can be compressed to one output (S)

Itamar Willner from the Hebrew University of Jerusalem and colleagues have developed such a system based on Mg²⁺-dependent DNAzyme subunits. Unlike previous approaches where the demonstration is done using two inputs and one output the team have investigated enhanced multiplexing in the compression process with four inputs producing one output.

Additionally they have also demonstrated the expansion of a single input to produce two outputs. Having such systems based on nucleic acids also raises the possibility of resetting the computational module. This means you could reconfigure and change its operation in situ by the addition of suitable complementary nucleic acid strands.

This article details important advances in DNA based logic networking and raises the potential to compress information held within genes into a single output. It also raises challenges for the future that must be overcome before these synthetic biomolecular computational systems can control natural intracellular processes.

For more, read the Chemical Science Edge article in full:

DNAzyme-Based 2:1 and 4:1 Multiplexers and 1:2 Demultiplexer
Ron Orbach, Francoise Remacle, R. D. Levine and Itamar Willner*
Chem. Sci., 2013, Accepted Article
DOI: 10.1039/C3SC52752B

Iain Larmour is a guest web writer for Chemical Science. He has researched a wide variety of topics during his years in the lab including nanostructured surfaces for water repellency and developing nanoparticle systems for bioanalysis by surface enhanced optical spectroscopies. He currently works in science management with a focus on responses to climate change.  In his spare time he enjoys reading, photography, art and inventing.

Water is essential for life as we know it and we are all familiar with the sight of water in the atmosphere and on the surface of the earth.  But where is the water deep down, beyond the crust?

The mantle (the part of the earth between the crust and the core) is primarily composed of iron-bearing magnesium silicates which undergo a number of phase transitions with depth. At the transition between the upper and lower mantle, olivine transforms into wadsleyite and this mineral has received interest due to its potential for hosting hydrogen, which is termed water in the realm of the inner-Earth. If fully hydrated the amount of hydrogen potentially stored in this mineral is four times the amount present in the oceans and the atmosphere.

When a hydrogen atom is incorporated into the mineral it is balanced by the removal of a magnesium cation, this produces several possible locations for the incorporation of the hydrogen in the vacancy, as well as different possible ordering of the vacancy in the structure. To solve this complex problem Stephen Wimperis and Sharon Ashbrook have teamed up and used the developments of high-field NMR and sophisticated experimental methods to study the ‘difficult’ NMR nuclei of ²⁵Mg and ¹⁷O within hydrated wadsleyite. In addition to the experimental approach, they have also carried out extensive DFT calculations.

Anhydrous (left) and one of the hypothetical ordered structures for fully-hydrated wadsleyite (right).

Most of the hydrogen was found to be located on the O1 site with the substitution charge balanced by Mg3 cation vacancies. A smaller amount of hydrogen was also found to be present in slightly higher energy defect sites with different proton arrangements or centred at different cation vacancies.

This study demonstrates the benefits of using a combined computational and experimental approach to reveal the location of hydrogen within wadsleyite. The use of this multinuclear NMR approach can be used to investigate a wide range of other silicate phases which should lead to a better understanding of the locations and distribution of hydrogen in the Earth’s mantle.

For more, read this ‘HOT’ Chemical Science article in full:

Water in the Earth’s Mantle: A Solid-State NMR Study of Hydrous Wadsleyite

John M. Griffin, Andrew J. Berry, Daniel J. Frost, Stephen Wimperis and Sharon E. Ashbrook
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC21892A