Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-κB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-κBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-κB and NF-κB-dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-κB activation was blunted in RAGE-null (RAGE -/-) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE -/-mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE-NF-κB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.

Enantiomeric esterifications and transesterifications catalyzed by hydrolytic enzymes in nonaqueous media, pioneered by our group and others, are emerging as a method of choice for facile kinetic resolution of racemic alcohols, acids, and other derivatives.' In organic solvents, it is also well established that hydrolases can catalyze the reactions of aminolysis, thiotransesterification, and oximolysis in addition to the aforementioned reactions.' Based on these knowledges, it occurred to us that the kinetic resolution of racemic amines, thiols, and oximes might be possible by the same strategy. In this paper, we wish to report the first successful enzymatic resolution of racemic amines.'Our first choice of enzyme was lipases, which are successfully used for the resolution of alcohols.' In order to find the enzyme for an enantioselective amidation reaction, we examined 15 commercially available lipases4 as a catalyst for the reaction between trifluoroethyl butyrate and the enantiomers of a-methylbenzylamine' in anhydrous n-octane.6 Among them, lipases from Candida cylindracea, Pseudomonas sp., Mucor sp., porcine pancreas, and Chromobacterium viscosum exhibited significant catalytic activity. However, the ratios of the initial rates for S and R isomers (VJV,) were 0.88,0.94, 1.0, 1.5, and 0.66, respectively, and no lipase tested showed substantial enantioselectivity.Protease subtilisin Carlsberg is known to catalyze the amide (peptide) bond formation between carboxylic acid esters and amines in anhydrous organic solvents.' Moreover, a recent study of our group unveiled that the enantioselectivity of this enzyme is greatly affected by the hydrophobicity of the reaction medium.' Encouraged by these findings, we used subtilisin as a catalyst for the aforementioned reaction and examined the dependency of the selectivity factor (VJ V,) on the solvent. As seen in

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Perovskite-type oxides are highly flexible materials that show properties that are beneficial for application in reverse water-gas shift processes (rWGS). Due to their stable nature, the ability to incorporate catalytically active dopants in their lattice structure, and the corresponding feature of nanoparticle exsolution, they are promising candidates for a materials design approach. On an industrial level, the rWGS has proven to be an excellent choice for the efficient utilisation of CO2 as an abundant and renewable carbon source, reflected by the current research on novel and improved catalyst materials. In the current study, a correlation between rWGS reaction environments (CO2 to H2 ratios and temperature), surface morphology, and catalytic activity of three perovskite catalysts (Nd0.6Ca0.4Fe0.9Co0.1O3-δ, Nd0.6Ca0.4Fe0.97Co0.03O3-δ, and Nd0.6Ca0.4Fe0.97Ni0.03O3-δ) is investigated, combining catalytic measurements with SEM and NAP-XPS. The materials were found to react dynamically to the conditions showing both activation due to in situ nanoparticle exsolution and deactivation via CaCO3 formation. This phenomenon could be influenced by choice of material and conditions: less reductive conditions (larger CO2 to H2 or lower temperature) lead to smaller exsolved particles and reduced carbonate formation. However, the B-site doping was also important; only with 10% Co-doping, a predominant activation could be achieved.

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