Temporal Progression Patterns of Brain Atrophy in Corticobasal Syndrome and Progressive Supranuclear Palsy Revealed by Subtype and Stage Inference (SuStaIn)

Differentiating corticobasal degeneration presenting with corticobasal syndrome (CBD-CBS) from progressive supranuclear palsy with Richardson's syndrome (PSP-RS), particularly in early stages, is often challenging because the neurodegenerative conditions closely overlap in terms of clinical presentation and pathology. Although volumetry using brain magnetic resonance imaging (MRI) has been studied in patients with CBS and PSP-RS, studies assessing the progression of brain atrophy are limited. Therefore, we aimed to reveal the difference in the temporal progression patterns of brain atrophy between patients with CBS and those with PSP-RS purely based on cross-sectional data using Subtype and Stage Inference (SuStaIn)—a novel, unsupervised machine learning technique that integrates clustering and disease progression modeling. We applied SuStaIn to the cross-sectional regional brain volumes of 25 patients with CBS, 39 patients with typical PSP-RS, and 50 healthy controls to estimate the two disease subtypes and trajectories of CBS and PSP-RS, which have distinct atrophy patterns. The progression model and classification accuracy of CBS and PSP-RS were compared with those of previous studies to evaluate the performance of SuStaIn. SuStaIn identified distinct temporal progression patterns of brain atrophy for CBS and PSP-RS, which were largely consistent with previous evidence, with high reproducibility (99.7%) under cross-validation. We classified these diseases with high accuracy (0.875) and sensitivity (0.680 and 1.000, respectively) based on cross-sectional structural brain MRI data; the accuracy was higher than that reported in previous studies. Moreover, SuStaIn stage correctly reflected disease severity without the label of disease stage, such as disease duration. Furthermore, SuStaIn also showed the genialized performance of differentiation and reflection for CBS and PSP-RS. Thus, SuStaIn has potential for improving our understanding of disease mechanisms, accurately stratifying patients, and providing prognoses for patients with CBS and PSP-RS

Microscopic Surface Structure of Liquid Alkali Metals

We report an x-ray scattering study of the microscopic structure of the surface of a liquid alkali metal. The bulk liquid structure factor of the eutectic K67Na33 alloy is characteristic of an ideal mixture, and so shares the properties of an elemental liquid alkali metal. Analysis of off-specular diffuse scattering and specular x-ray reflectivity shows that the surface roughness of the K-Na alloy follows simple capillary wave behavior with a surface structure factor indicative of surface induced layering. Comparison of thelow-angle tail of the K67Na33 surface structure factor with the one measured for liquid Ga and In previously suggests that layering is less pronounced in alkali metals. Controlled exposure of the liquid to H2 and O2 gas does not affect the surface structure, indicating that oxide and hydride are not stable at the liquid surface under these experimental conditions.Comment: 12 pages, 3 figures, published in Phys. Rev.

Microscopic dynamics in liquid metals: the experimental point of view

The experimental results relevant for the understanding of the microscopic dynamics in liquid metals are reviewed, with special regards to the ones achieved in the last two decades. Inelastic Neutron Scattering played a major role since the development of neutron facilities in the sixties. The last ten years, however, saw the development of third generation radiation sources, which opened the possibility of performing Inelastic Scattering with X rays, thus disclosing previously unaccessible energy-momentum regions. The purely coherent response of X rays, moreover, combined with the mixed coherent/incoherent response typical of neutron scattering, provides enormous potentialities to disentangle aspects related to the collectivity of motion from the single particle dynamics. If the last twenty years saw major experimental developments, on the theoretical side fresh ideas came up to the side of the most traditional and established theories. Beside the raw experimental results, therefore, we review models and theoretical approaches for the description of microscopic dynamics over different length-scales, from the hydrodynamic region down to the single particle regime, walking the perilous and sometimes uncharted path of the generalized hydrodynamics extension. Approaches peculiar of conductive systems, based on the ionic plasma theory, are also considered, as well as kinetic and mode coupling theory applied to hard sphere systems, which turn out to mimic with remarkable detail the atomic dynamics of liquid metals. Finally, cutting edges issues and open problems, such as the ultimate origin of the anomalous acoustic dispersion or the relevance of transport properties of a conductive systems in ruling the ionic dynamic structure factor are discussed.Comment: 53 pages, 41 figures, to appear in "The Review of Modern Physics". Tentatively scheduled for July issu

Aggregatibacter actinomycetemcomitans Omp29 Is Associated with Bacterial Entry to Gingival Epithelial Cells by F-Actin Rearrangement

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E. coli OmpA, in promoting bacterial entry into gingival epithelial cells. To accomplish this, Omp29 expression vector was incorporated in an OmpA-deficient mutant of E. coli. Omp29+/OmpA− E. coli demonstrated 22-fold higher entry into human gingival epithelial line cells (OBA9) than Omp29−/OmpA− E. coli. While the entry of Aa and Omp29+/OmpA− E. coli into OBA9 cells were inhibited by anti-Omp29 antibody, their adherence to OBA9 cells was not inhibited. Stimulation of OBA9 cells with purified Omp29 increased the phosphorylation of focal adhesion kinase (FAK), a pivotal cell-signaling molecule that can up-regulate actin rearrangement. Furthermore, Omp29 increased the formation of F-actin in OBA9 cells. The internalization of Omp29-coated beads and the entry of Aa into OBA9 were partially inhibited by treatment with PI3-kinase inhibitor (Wortmannin) and Rho GTPases inhibitor (EDIN), both known to convey FAK-signaling to actin-rearrangement. These results suggest that Omp29 is associated with the entry of Aa into gingival epithelial cells by up-regulating F-actin rearrangement via the FAK signaling pathway

A Histone-Like Protein of Mycobacteria Possesses Ferritin Superfamily Protein-Like Activity and Protects against DNA Damage by Fenton Reaction

Iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the Fenton reaction. In addition, ferric ion shows low solubility under physiological conditions. To overcome these obstacles living organisms possess Ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. These proteins minimize hydroxyl radical formation by ferroxidase activity that converts Fe2+ into Fe3+ and sequesters iron by storing it as a mineral inside a protein cage. In this study, we discovered that mycobacterial DNA-binding protein 1 (MDP1), a histone-like protein, has similar activity to ferritin superfamily proteins. MDP1 prevented the Fenton reaction and protects DNA by the ferroxidase activity. The Km values of the ferroxidase activity by MDP1 of Mycobacterium bovis bacillus Calmette-Guérin (BCG-3007c), Mycobacterium tuberculosis (Rv2986c), and Mycobacterium leprae (ML1683; ML-LBP) were 0.292, 0.252, and 0.129 mM, respectively. Furthermore, one MDP1 molecule directly captured 81.4±19.1 iron atoms, suggesting the role of this protein in iron storage. This study describes for the first time a ferroxidase-iron storage protein outside of the ferritin superfamily proteins and the protective role of this bacterial protein from DNA damage

Optimised Motion Tracking for Positron Emission Tomography Studies of Brain Function in Awake Rats

Positron emission tomography (PET) is a non-invasive molecular imaging technique using positron-emitting radioisotopes to study functional processes within the body. High resolution PET scanners designed for imaging rodents and non-human primates are now commonplace in preclinical research. Brain imaging in this context, with motion compensation, can potentially enhance the usefulness of PET by avoiding confounds due to anaesthetic drugs and enabling freely moving animals to be imaged during normal and evoked behaviours. Due to the frequent and rapid motion exhibited by alert, awake animals, optimal motion correction requires frequently sampled pose information and precise synchronisation of these data with events in the PET coincidence data stream. Motion measurements should also be as accurate as possible to avoid degrading the excellent spatial resolution provided by state-of-the-art scanners. Here we describe and validate methods for optimised motion tracking suited to the correction of motion in awake rats. A hardware based synchronisation approach is used to achieve temporal alignment of tracker and scanner data to within 10 ms. We explored the impact of motion tracker synchronisation error, pose sampling rate, rate of motion, and marker size on motion correction accuracy. With accurate synchronisation (<100 ms error), a sampling rate of >20 Hz, and a small head marker suitable for awake animal studies, excellent motion correction results were obtained in phantom studies with a variety of continuous motion patterns, including realistic rat motion (<5% bias in mean concentration). Feasibility of the approach was also demonstrated in an awake rat study. We conclude that motion tracking parameters needed for effective motion correction in preclinical brain imaging of awake rats are achievable in the laboratory setting. This could broaden the scope of animal experiments currently possible with PET

Phenylpropanoid Glycoside Analogues: Enzymatic Synthesis, Antioxidant Activity and Theoretical Study of Their Free Radical Scavenger Mechanism

Phenylpropanoid glycosides (PPGs) are natural compounds present in several medicinal plants that have high antioxidant power and diverse biological activities. Because of their low content in plants (less than 5% w/w), several chemical synthetic routes to produce PPGs have been developed, but their synthesis is a time consuming process and the achieved yields are often low. In this study, an alternative and efficient two-step biosynthetic route to obtain natural PPG analogues is reported for the first time. Two galactosides were initially synthesized from vanillyl alcohol and homovanillyl alcohol by a transgalactosylation reaction catalyzed by Kluyveromyces lactis β-galactosidase in saturated lactose solutions with a 30%–35% yield. To synthesize PPGs, the galactoconjugates were esterified with saturated and unsaturated hydroxycinnamic acid derivatives using Candida antarctica Lipase B (CaL-B) as a biocatalyst with 40%–60% yields. The scavenging ability of the phenolic raw materials, intermediates and PPGs was evaluated by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) method. It was found that the biosynthesized PPGs had higher scavenging abilities when compared to ascorbic acid, the reference compound, while their antioxidant activities were found similar to that of natural PPGs. Moreover, density functional theory (DFT) calculations were used to determine that the PPGs antioxidant mechanism proceeds through a sequential proton loss single electron transfer (SPLET). The enzymatic process reported in this study is an efficient and versatile route to obtain PPGs from different phenylpropanoid acids, sugars and phenolic alcohols