Brain age as a surrogate marker for cognitive performance in multiple sclerosis

Background: Data from neuro-imaging techniques allow us to estimate a brain's age. Brain age is easily interpretable as "how old the brain looks", and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility by investigating the relationship between brain age and cognitive performance in multiple sclerosis (MS). Methods: A linear regression model was trained to predict age from brain MRI volumetric features and sex in a healthy control dataset (HC_train, n=1673). This model was used to predict brain age in two test sets: HC_test (n=50) and MS_test (n=201). Brain-Predicted Age Difference (BPAD) was calculated as BPAD=brain age minus chronological age. Cognitive performance was assessed by the Symbol Digit Modalities Test (SDMT). Results: Brain age was significantly related to SDMT scores in the MS_test dataset (r=-0.46, p<.001), and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r=-0.24, p<.001) and a significant weight (-0.25, p=0.002) in a multivariate regression equation with age. Conclusions: Brain age is a candidate biomarker for cognitive dysfunction in MS and an easy to grasp metric for brain health

Characterization of a protein serine kinase from yeast plasma membrane.

A casein kinase activity, which copurifies with the H+-ATPase activity during isolation of plasma membranes Saccharomyces cerevisiae and during centrifugation of the solubilized membrane extract through a sucrose gradient, is separated from the Mr = 100,000 ATPase catalytic polypeptide by subsequent DEAE-cellulose chromatography. The purified casein kinase activity exhibits a low Km of 12 microM MgATP, is maximally stimulated by 6 mM free Mg2+, and is 50% inhibited by 300 microM Zn2+, by 7.5 micrograms of heparin/ml, and by 300 microM orthovanadate. It phosphorylates only seryl residues. The purified casein kinase contains two polypeptides of Mr = 45,000 and 39,000 which yield antibodies which do not cross-react to each other. The two polypeptides seem to originate from a precursor of Mr = 85,000 which is detected by both antibodies in partly purified fractions. In the absence of casein, a zinc and heparin-sensitive phosphorylation of the ATPase polypeptide is observed in partly purified ATPase fractions, and a peptide of similar mobility is phosphorylated, among others, in isolated plasma membranes. The purified ATPase activity is markedly inhibited by incubation in the presence of acid phosphatase. In agreement with a recent report that the purified active ATPase molecule is largely phosphorylated (Yanagita, Y., Abdel-Ghany, M., Raden, D., Nelson, N., and Racker, E. (1987) Proc. Natl. Acad. Sci. U. S. A. 894, 925-929) this data suggests that dephosphorylation leads to deactivation of ATPase activity

General Strategy for the Design of DNA Coding Sequences Applied to Nanoparticle Assembly

International audienceThe DNA-directed assembly of nano-objects has been the subject of many recent studies as a means to construct advanced nanomaterial architectures. Although much experimental in silico work has been presented and discussed, there has been no in-depth consideration of the proper design of single-strand sticky termination of DNA sequences, noted as ssST, which is important in avoiding self-folding within one DNA strand, unwanted strand-to-strand interaction, and mismatching. In this work, a new comprehensive and computationally efficient optimization algorithm is presented for the construction of all possible DNA sequences that specifically prevents these issues. This optimization procedure is also effective when a spacer section is used, typically repeated sequences of thymine or adenine placed between the ssST and the nano-object, to address the most conventional experimental protocols. We systematically discuss the fundamental statistics of DNA sequences considering complementarities limited to two (or three) adjacent pairs to avoid self-folding and hybridization of identical strands due to unwanted complements and mismatching. The optimized DNA sequences can reach maximum lengths of 9 to 34 bases depending on the level of applied constraints. The thermodynamic properties of the allowed sequences are used to develop a ranking for each design. For instance, we show that the maximum melting temperature saturates with 14 bases under typical solvation and concentration conditions. Thus, DNA ssST with optimized sequences are developed for segments ranging from 4 to 40 bases, providing a very useful guide for all technological protocols. An experimental test is presented and discussed using the aggregation of Al and CuO nanoparticles and is shown to validate and illustrate the importance of the proposed DNA coding sequence optimization. ■ INTRODUCTION The interest in DNA nanotechnology to program the assembly of nanoparticles into macroscopic nanocomposites emerged in the 1990s. 1,2 Undoubtedly, the controlled interplay of DNA complementary and noncomplementary strands made DNA nanotechnologies one of the most powerful bottom-up approaches to building hierarchical architectures of nano-objects (noble metals, semiconductors, oxides, and polymers) leading to an almost infinite variety of high-performance programmable DNA/nanoparticles hybrid materials. One mainstream DNA-based assembly approach consists of directing the assembly of colloids of interest, mostly gold nanoparticles, by taking advantage of the thiol/metal chemistry 3 to covalently attach DNA strands to nanoparticle surfaces. Other chemical alternatives have also been investigated , such as antigen/antibody-like binding. 4,5 Since the seminal work by Alavisatos and Mirkin 1,2 on gold nanoparticles, many DNA/nanoparticle assembly processes have been reported, notably by varying the DNA length and processing conditions and with a consideration of other materials for applications in catalytics, 6 spectroscopy, 7−10 optical devices

The role of hippocampal theta oscillations in working memory impairment in multiple sclerosis

Working memory (WM) problems are frequently present in people with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a visual‐verbal 2‐back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event‐related fields and theta (4–8 Hz) and alpha (8–13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = .014). This theta power increase value correlated negatively with reaction time on the task in MS (r = −.32, p = .029). Evidence was provided that this relationship could not be explained by a ‘common cause’ confounding relationship with MS‐related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS

Micromachined accelerometers with sub-µg/ Hz noise floor: A review

This paper reviews√ the research and development of micromachined accelerometers with a noise floor lower than 1 µg/ Hz. Firstly, the basic working principle of micromachined accelerometers is introduced. Then, different methods of reducing the noise floor of micromachined accelerometers√ are analyzed. Different types of micromachined accelerometers with a noise floor below 1 µg/ Hz are discussed. Such sensors can mainly be categorized into: (i) micromachined accelerometers with a low spring constant; (ii) with a large proof mass; (iii) with a high quality factor; (iv) with a low noise interface circuit; (v) with sensing schemes leading to a high scale factor. Finally, the characteristics of various micromachined accelerometers and their trends are discussed and investigated. © 2020 by the authors. Licensee MDPI, Basel, Switzerland