Microglia morphotyping in the adult mouse CNS using hierarchical clustering on principal components reveals regional heterogeneity but no sexual dimorphism

Microglia are the resident macrophages of the central nervous system (CNS) and play a pivotal role in immune surveillance and CNS homeostasis. Morphological transitions in microglia are indicative for local changes in the CNS microenvironment and serve as a proxy for the detection of alterations in the CNS, both in health and disease. Current strategies to ‘measure’ microglia combine advanced morphometrics with clustering approaches to identify and categorize microglia morphologies. However, these studies are labor intensive and clustering approaches are often subject to relevant feature selection bias. Here, we provide a morphometrics pipeline with user-friendly computational tools for image segmentation, automated feature extraction and morphological categorization of microglia by means of hierarchical clustering on principal components (HCPC) without the need for feature inclusion criteria. With this pipeline we provide new and detailed insights in the distribution of microglia morphotypes across sixteen CNS regions along the rostro-caudal axis of the adult C57BL/6J mouse CNS. Although regional variations in microglia morphologies were evident, we found no evidence for male–female dimorphism at any CNS region investigated, indicating that - by and large - microglia in adult male and female mice are morphometrically indistinguishable. Taken together, our newly developed pipeline provides valuable tools for objective and unbiased identification and categorization of microglia morphotypes and can be applied to any CNS (disease) model.</p

Theorem on the Distribution of Short-Time Particle Displacements with Physical Applications

The distribution of the initial short-time displacements of particles is considered for a class of classical systems under rather general conditions on the dynamics and with Gaussian initial velocity distributions, while the positions could have an arbitrary distribution. This class of systems contains canonical equilibrium of a Hamiltonian system as a special case. We prove that for this class of systems the nth order cumulants of the initial short-time displacements behave as the 2n-th power of time for all n>2, rather than exhibiting an nth power scaling. This has direct applications to the initial short-time behavior of the Van Hove self-correlation function, to its non-equilibrium generalizations the Green's functions for mass transport, and to the non-Gaussian parameters used in supercooled liquids and glasses.Comment: A less ambiguous mathematical notation for cumulants was adopted and several passages were reformulated and clarified. 40 pages, 1 figure. Accepted by J. Stat. Phy

Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement

The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutiveErcc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects ofErcc1-deficiency on microglia are unclear. In this study,Ercc1was specifically deleted from Cx3cr1-expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2-12 months afterErcc1deletion. Larger and more ramified microglia were observed followingErcc1deletion both in vivo and in organotypic hippocampal slice cultures.Ercc1-deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased.Ercc1-deficient microglia were gradually replaced by nondeficient microglia carrying a functionalErcc1allele. In contrast to constitutiveErcc1-deficient mice, microglia-specific deletion ofErcc1did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested thatErcc1deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile.</p

Density fluctuations and single-particle dynamics in liquid lithium

The single-particle and collective dynamical properties of liquid lithium have been evaluated at several thermodynamic states near the triple point. This is performed within the framework of mode-coupling theory, using a self-consistent scheme which, starting from the known static structure of the liquid, allows the theoretical calculation of several dynamical properties. Special attention is devoted to several aspects of the single-particle dynamics, which are discussed as a function of the thermodynamic state. The results are compared with those of Molecular Dynamics simulations and other theoretical approaches.Comment: 31 pages (in preprint format), 14 figures. Submitted to Phys. Rev.

Systematic review of the effectiveness of innovative, gamified interventions for cognitive training in paediatric acquired brain injury

Effectiveness of innovative, gamified interventions (i.e., Augmented Reality, Computer-Based Cognitive Retraining [CBCR], and Virtual Reality [VR] in conjunction with a Serious Game) for cognitive training in paediatric ABI was evaluated. Studies were identified on PsycINFO, PubMed and Scopus; last searched 4 January 2022. Eligibility criteria were participants diagnosed with ABI and aged ≤ 18 years, experimental intervention to train cognition, cognition assessed pre- and post-intervention at: (1) The level of function, or (2) The level of activity, and written in English. ROB 2 and ROBINS-I were utilised to assess risk of bias. Extracted study characteristics were methods, participants, interventions, outcomes, and results. Seven studies were included, comprising six CBCR studies and one VR study, with 182 participants. Following CBCR: (1) Improvements were observed in several cognitive functions, but there was inconsistent evidence; (2) Improvements were reported in attention and executive functions (EF) at home and at school. Following VR: (1) Improvements were observed in attention and EF; (2) Not evaluated. Due to the small number of included studies with (relatively) small and heterogeneous samples, only a cautious interpretation of the evidence was provided. There is a need for carefully designed studies with more attention to inter-individual differences and generalisation to daily life

Dynamical Properties and Plasmon Dispersion of a Weakly Degenerate Correlated One-Component Plasma

Classical Molecular Dynamics (MD) simulations for a one-component plasma (OCP) are presented. Quantum effects are included in the form of the Kelbg potential. Results for the dynamical structure factor are compared with the Vlasov and RPA (random phase approximation) theories. The influence of the coupling parameter $\Gamma$, degeneracy parameter $\rho \Lambda^3$ and the form of the pair interaction on the optical plasmon dispersion is investigated. An improved analytical approximation for the dispersion of Langmuir waves is presented.Comment: 23 pages, includes 7 ps/eps-figures and 2 table

Systematic review of the effectiveness of innovative, gamified interventions for cognitive training in paediatric acquired brain injury

Effectiveness of innovative, gamified interventions (i.e., Augmented Reality, Computer-Based Cognitive Retraining [CBCR], and Virtual Reality [VR] in conjunction with a Serious Game) for cognitive training in paediatric ABI was evaluated. Studies were identified on PsycINFO, PubMed and Scopus; last searched 4 January 2022. Eligibility criteria were participants diagnosed with ABI and aged ≤ 18 years, experimental intervention to train cognition, cognition assessed pre- and post-intervention at: (1) The level of function, or (2) The level of activity, and written in English. ROB 2 and ROBINS-I were utilised to assess risk of bias. Extracted study characteristics were methods, participants, interventions, outcomes, and results. Seven studies were included, comprising six CBCR studies and one VR study, with 182 participants. Following CBCR: (1) Improvements were observed in several cognitive functions, but there was inconsistent evidence; (2) Improvements were reported in attention and executive functions (EF) at home and at school. Following VR: (1) Improvements were observed in attention and EF; (2) Not evaluated. Due to the small number of included studies with (relatively) small and heterogeneous samples, only a cautious interpretation of the evidence was provided. There is a need for carefully designed studies with more attention to inter-individual differences and generalisation to daily life

Predicting mental imagery based BCI performance from personality, cognitive profile and neurophysiological patterns

Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy— EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants’ BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants’ performance with a mean error of less than 3 points. This study determined how users’ profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user

Statistical Mechanics of Vacancy and Interstitial Strings in Hexagonal Columnar Crystals

Columnar crystals contain defects in the form of vacancy/interstitial loops or strings of vacancies and interstitials bounded by column ``heads'' and ``tails''. These defect strings are oriented by the columnar lattice and can change size and shape by movement of the ends and forming kinks along the length. Hence an analysis in terms of directed living polymers is appropriate to study their size and shape distribution, volume fraction, etc. If the entropy of transverse fluctuations overcomes the string line tension in the crystalline phase, a string proliferation transition occurs, leading to a supersolid phase. We estimate the wandering entropy and examine the behaviour in the transition regime. We also calculate numerically the line tension of various species of vacancies and interstitials in a triangular lattice for power-law potentials as well as for a modified Bessel function interaction between columns as occurs in the case of flux lines in type-II superconductors or long polyelectrolytes in an ionic solution. We find that the centered interstitial is the lowest energy defect for a very wide range of interactions; the symmetric vacancy is preferred only for extremely short interaction ranges.Comment: 22 pages (revtex), 15 figures (encapsulated postscript

Harmonic Solid Theory of Photoluminescence in the High Field Two-Dimensional Wigner Crystal

Motivated by recent experiments on radiative recombination of two-dimensional electrons in acceptor doped GaAs-AlGaAs heterojunctions as well as the success of a harmonic solid model in describing tunneling between two-dimensional electron systems, we calculate within the harmonic approximation and the time dependent perturbation theory the line shape of the photoluminescence spectrum corresponding to the recombination of an electron with a hole bound to an acceptor atom. The recombination process is modeled as a sudden perturbation of the Hamiltonian for the in-plane degrees of freedom of the electron. We include in the perturbation, in addition to changes in the equilibrium positions of electrons, changes in the curvatures of the harmonically approximated potential. The computed spectra have line shapes similar to that seen in a recent experiment. The spectral width, however, is roughly a factor of 3 smaller than that seen in experiment if one assumes a perfect Wigner crystal for the initial state state of the system, whereas a simple random disorder model yields a width a factor of 3 too large. We speculate on the possible mechanisms that may lead to better quantitative agreement with experiment.Comment: 22 pages, RevTex, 8 figures. Submitted to the Physical Review