Accelerated Epigenetic Aging in Peripheral Blood does not Predict Dementia Risk.

BACKGROUND: There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. OBJECTIVE: This study aims to clarify whether epigenetic biomarkers of accelerated aging can predict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. METHODS: DNA methylation was measured in peripheral blood samples provided by 160 participants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic dementia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. RESULTS: There was no difference in age acceleration between dementia cases and controls. In males, only Hannum's intrinsic epigenetic age acceleration was increased in pre-symptomatic dementia cases compared to controls (Δ +1.8 years, p = 0.03). CONCLUSION: These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.

Oligomer-oligomer versus oligomer-monomer C(2)-C(2)' coupling reactions in polypyrrole growth.

The C(2)-C(2)' coupling reactions of oligopyrrole radical-cations of increasing length generated by electrochemical oxidation have been modeled by transition state calculations. The modeling approach takes into account solvent effects and (i) shows that the coupling distance in the transition state decreases with oligomer length, (ii) demonstrates that dimerization rates in the gas phase decrease with oligomer length but increase in water, (iii) suggests that in a less solvating medium the dimerization rates could be equivalent, (iv) indicates that in all solvents quaterpyrrole and sexipyrrole formation is faster through a coupling reaction between oligomer and monomer radical-cations than two oligomer radical-cations, and (v) suggests that for the formation of a long oligopyrrole from oligopyrrole-pyrrole reactions the mechanism might involve the coupling of the oligopyrrole dication with a non-oxidized pyrrole unit instead of the coupling of two radical-cations or that of the oligopyrrole dication with a pyrrole radical-cation.

Purification and characterization of an endoglucanase from Streptomyces lividans 66 and DNA sequence of the gene.

The endoglucanase isolated from culture filtrates of Streptomyces lividans IAF74 was shown to have an Mr of 46,000 and a pI of 3.3. The specific enzyme activity of 539 IU/mg, determined by the reducing assay method on carboxymethyl cellulose, is among the highest reported in the literature. The cellulase showed typical endo-type activity when reacting on oligocellodextrins. Optimal enzyme activity was obtained at 50 degrees C and pH 5.5. The kinetic constants for this endoglucanase, determined with carboxymethyl cellulose as the substrate, were a Vmax of 24.9 IU/mg of enzyme and a Km of 4.2 mg/ml. Activity was found against neither methylumbelliferyl- nor p-nitrophenyl-cellobiopyranoside nor with xylan. The DNA sequence contains one possible reading frame validated by the N terminus of the mature purified protein. However, neither ATG nor GTG starting codons were identified near the ribosome-binding site. A putative TTG codon was found as a good candidate for the start codon. Comparison of the primary amino acid sequence of the endoglucanase of S. lividans revealed that the N terminus contains a bacterial cellulose-binding domain. The catalytic domain at the C terminus showed similarity to endoglucanases from a Bacillus sp. Thus, the endoglucanase CelA belongs to family A of cellulases as described before (N. R. Gilkes, B. Henrissat, D. G. Kilburn, R. C. Miller, Jr., and R. A. J. Warren, Microbiol. Rev. 55:303-315, 1991.

Conducting-polymer electrochemical switching as an easy means for control of the molecular properties of grafted transition metal complexes.

Copper(II) 3',4'-bis(N,N'-oxamato)terthiophene has been synthesized and electropolymerized. The copper(II)-complex centers are not affected by the polymerization process, which involves coupling between Calpha carbon atoms of the terthiophene units and leads to a new conjugated polymer consisting of polythiophene chains bearing bis(oxamato)-Cu(II) groups regioregularly grafted onto the polymer backbone. The polymer is stable with respect to polythiophene electroactivity, and no demetallation or modification of the Cu oxidation state occurs over a large potential range. In this material, the two moieties exhibit direct electronic interaction, which makes it possible to use the conductive polymer backbone as a molecular wire or a nanocontact capable of inputting to the bis(oxamato)-Cu(II) groups through the polythiophene-switching reaction. FTIR, XPS, and XAS spectroscopies have been used to study the effect of the state of the conducting polymer upon the properties of the copper(II) center (electron density, ligand field strength, size of cavity, force constants of some bonds). These properties can be controlled to some extent by the potential applied to this device. From the point of view of the copper(II) center, this effect is similar to the grafting of substituents with various electronic properties.