Sarm1 Deletion, but Not WldS, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy

Studies with the WldS mutant mouse have shown that axon and synapse pathology in several models of neurodegenerative diseases are mechanistically related to injury-induced axon degeneration (Wallerian degeneration). Crucially, an absence of SARM1 delays Wallerian degeneration as robustly as WldS, but their relative capacities to confer long-term protection against related, non-injury axonopathy and/or synaptopathy have not been directly compared. Whilst Sarm1 deletion or WldS can each rescue perinatal lethality and widespread Wallerian-like axonopathy in young NMNAT2-deficient mice, we now report that an absence of SARM1 enables these mice to survive into old age with no overt phenotype whereas those rescued by WldS invariantly develop a progressive neuromuscular defect in their hindlimbs from around 3 months of age. We therefore propose Sarm1 deletion as a more reliable tool than WldS for investigating Wallerian-like mechanisms in disease models and suggest that SARM1 blockade may have greater therapeutic potential than WLDS-related strategies.This work was funded by an Institute Strategic Programme grant from the Biotechnology and Biological Sciences Research Council, Medical Research Council grants MR/N004582/1 and MR/M024075/1, and Motor Neurone Disease Association (MNDA) grant 838-791

Understanding the dispersion and assembly of bacterial cellulose in organic solvents

The constituent nanofibrils of bacterial cellulose are of interest to many researchers because of their purity and excellent mechanical properties. Mechanisms to disrupt the network structure of bacterial cellulose (BC) to isolate bacterial cellulose nanofibrils (BCN) are limited. This work focuses on liquid-phase dispersions of BCN in a range of organic solvents. It builds on work to disperse similarly intractable nanomaterials, such as single-walled carbon nanotubes, where optimum dispersion is seen for solvents whose surface energies are close to the surface energy of the nanomaterial; bacterial cellulose is shown to disperse in a similar fashion. Inverse gas chromatography was used to determine the surface energy of bacterial cellulose, under relevant conditions, by quantifying the surface heterogeneity of the material as a function of coverage. Films of pure BCN were prepared from dispersions in a range of solvents; the extent of BCN exfoliation is shown to have a strong effect on the mechanical properties of BC films and to fit models based on the volumetric density of nanofibril junctions. Such control offers new routes to producing robust cellulose films of bacterial cellulose nanofibrils

Materials science: Carbon sheet solutions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62936/1/442254a.pd

Tuneable photoconductivity and mobility enhancement in printed MoS 2 /graphene composites

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this record.With the aim of increasing carrier mobility in nanosheet-network devices, we have investigated MoS2–graphene composites as active regions in printed photodetectors. Combining liquid exfoliation and inkjet-printing, we fabricated all-printed photodetectors with graphene electrodes and MoS2–graphene composite channels with various graphene mass fractions (0  ≤  M f  ≤  16 wt%). The increase in channel dark conductivity with M f was consistent with percolation theory for composites below the percolation threshold. While the photoconductivity increased with graphene content, it did so more slowly than the dark conductivity, such that the fractional photoconductivity decayed rapidly with increasing M f. We propose that both mobility and dark carrier density increase with graphene content according to percolation-like scaling laws, while photo-induced carrier density is essentially independent of graphene loading. This leads to percolation-like scaling laws for both photoconductivity and fractional photoconductivity—in excellent agreement with the data. These results imply that channel mobility and carrier density increase up to 100-fold with the addition of 16 wt% graphene.We acknowledge the Science Foundation Ireland (SFI/12/RC/2278), the European Commission (n° 696656, Graphene Flagship) and the European Research Council (FUTURE-PRINT)

Controlling the Optical Properties of a Conjugated Co-polymer through Variation of Backbone Isomerism and the Introduction of Carbon Nanotubes

The need to control the formation of weakly emitting species in polymers such as aggregates and excimers, which are normally detrimental to device performance, is illustrated for the example of the polymer poly(m-phenylenevinylene-co-2,5-dioctyloxy-p-phenylenevinylene), using the model compound, 2,5-dioctyloxy-p-distyrylbenzene as a comparison. Two different methods, namely a Homer-Emmons polycondensation in dimethylformamide (DMF) and a Wittig polycondensation in dry toluene, have been used during synthesis resulting in a polymer with a predominantly trans-vinylene backbone and a polymer with a predominantly cis-vinylene backbone, respectively. Photoluminescence and absorption spectroscopy indicate that the polymer forms aggregate species in solution with spectra that are distinctly red-shifted from those associated with the intra-chain exciton. Concentration dependent optical studies were used to probe the evolution of aggregation in solution for both polymers. The results indicate that inter-chain coupling in the predominantly cis-polymer is prominent at lower concentrations than in the case of the trans-counterpart. These results are supported by pico-second pump and probe transient absorption measurements where, in dilute solutions, the polymer in a cis-configuration exhibits highly complex excited state dynamics, whereas the polymer in a trans-configuration behaves similarly to the model compound. It is proposed therefore that the degree of backbone isomerism has a profound impact on the morphology of the polymeric solid and control over it is a route towards optimising the performance of the material in thin film form. Another method to inhibit inter-chain effects using multi walled carbon nanotubes (MWNT) as nano-spacers in the polymer solutions is proposed. By comparison to spectroscopic analysis, aggregation effects are shown to be reduced by the introduction of nanotubes. Electron microscopy and computer simulation suggest a well-defined interaction between the polymer backbone and the lattice of the nanotube

Guidance for Evidence-Informed Policies about Health Systems: Linking Guidance Development to Policy Development

In the second paper in a three-part series on health systems guidance, John Lavis and colleagues explore the challenge of linking guidance development and policy development at global and national levels

Direct exfoliation and dispersion of two-dimensional materials in pure water via temperature control

The high-volume synthesis of two-dimensional (2D) materials in the form of platelets is desirable for various applications. While water is considered an ideal dispersion medium, due to its abundance and low cost, the hydrophobicity of platelet surfaces has prohibited its widespread use. Here we exfoliate 2D materials directly in pure water without using any chemicals or surfactants. In order to exfoliate and disperse the materials in water, we elevate the temperature of the sonication bath, and introduce energy via the dissipation of sonic waves. Storage stability greater than one month is achieved through the maintenance of high temperatures, and through atomic and molecular level simulations, we further discover that good solubility in water is maintained due to the presence of platelet surface charges as a result of edge functionalization or intrinsic polarity. Finally, we demonstrate inkjet printing on hard and flexible substrates as a potential application of water-dispersed 2D materials.close1