Brain energy metabolism: conserved functions of glycolytic glial cells

The discovery in mammals that axons are metabolically supported by myelinating glial cells explains why neurons can extend meters in length. In this issue, Volkenhoff et al. (2015) show that, in Drosophila, the transfer of lactate from the glial to the neuronal compartment is conserved in evolution, independent of body size

Monte Carlo Simulations of Globular Cluster Evolution - II. Mass Spectra, Stellar Evolution and Lifetimes in the Galaxy

We study the dynamical evolution of globular clusters using our new 2-D Monte Carlo code, and we calculate the lifetimes of clusters in the Galactic environment. We include the effects of a mass spectrum, mass loss in the Galactic tidal field, and stellar evolution. We consider initial King models containing N = 10^5 - 3x10^5 stars, and follow the evolution up to core collapse, or disruption, whichever occurs first. We find that the lifetimes of our models are significantly longer than those obtained using 1-D Fokker-Planck (F-P) methods. We also find that our results are in very good agreement with recent 2-D F-P calculations, for a wide range of initial conditions. Our results show that the direct mass loss due to stellar evolution can significantly accelerate the mass loss through the tidal boundary, causing most clusters with a low initial central concentration (Wo <~ 3) to disrupt quickly in the Galactic tidal field. Only clusters born with high initial central concentrations (Wo >~ 7) or steep initial mass functions are likely to survive to the present and undergo core collapse. We also study the orbital characteristics of escaping stars, and find that the velocity distribution of escaping stars in collapsing clusters looks significantly different from the distribution in disrupting clusters. We calculate the lifetime of a cluster on an eccentric orbit in the Galaxy, such that it fills its Roche lobe only at perigalacticon. We find that such an orbit can extend the lifetime by at most a factor of a few compared to a circular orbit in which the cluster fills its Roche lobe at all times.Comment: 32 pages, including 10 figures, to appear in ApJ, minor corrections onl

Fe I Oscillator Strengths for the Gaia-ESO Survey

The Gaia-ESO Public Spectroscopic Survey (GES) is conducting a large-scale study of multi-element chemical abundances of some 100 000 stars in the Milky Way with the ultimate aim of quantifying the formation history and evolution of young, mature and ancient Galactic populations. However, in preparing for the analysis of GES spectra, it has been noted that atomic oscillator strengths of important Fe I lines required to correctly model stellar line intensities are missing from the atomic database. Here, we present new experimental oscillator strengths derived from branching fractions and level lifetimes, for 142 transitions of Fe I between 3526 {\AA} and 10864 {\AA}, of which at least 38 are urgently needed by GES. We also assess the impact of these new data on solar spectral synthesis and demonstrate that for 36 lines that appear unblended in the Sun, Fe abundance measurements yield a small line-by-line scatter (0.08 dex) with a mean abundance of 7.44 dex in good agreement with recent publications.Comment: Accepted for publication in Mon. Not. R. Astron. So

Pathology of myelinated axons in the PLP-deficient mouse model of spastic paraplegia type 2 revealed by volume imaging using focused ion beam-scanning electron microscopy

Advances in electron microscopy including improved imaging techniques and state-of-the-art detectors facilitate imaging of larger tissue volumes with electron microscopic resolution. In combination with genetic tools for the generation of mouse mutants this allows assessing the three-dimensional (3D) characteristics of pathological features in disease models. Here we revisited the axonal pathology in the central nervous system of a mouse model of spastic paraplegia type 2, the Plp−/Y mouse. Although PLP is a bona fide myelin protein, the major hallmark of the disease in both SPG2 patients and mouse models are axonal swellings comprising accumulations of numerous organelles including mitochondria, gradually leading to irreversible axonal loss. To assess the number and morphology of axonal mitochondria and the overall myelin preservation we evaluated two sample preparation techniques, chemical fixation or high-pressure freezing and freeze substitution, with respect to the objective of 3D visualization. Both methods allowed visualizing distribution and morphological details of axonal mitochondria. In Plp−/Y mice the number of mitochondria is 2-fold increased along the entire axonal length. Mitochondria are also found in the excessive organelle accumulations within axonal swellings. In addition, organelle accumulations were detected within the myelin sheath and the inner tongue. We find that 3D electron microscopy is required for a comprehensive understanding of the size, content and frequency of axonal swel- lings, the hallmarks of axonal pathology

Maximum Valency Lattice Gas Models

We study lattice gas models with the imposition of a constraint on the maximum number of bonds (nearest neighbor interactions) that particles can participate in. The critical parameters, as well as the coexistence region are studied using the mean field approximation and the Bethe-Peierls approximation. We find that the reduction of the number of interactions suppresses the temperature-density region where the liquid and gas phases coexist. We confirm these results from simulations using the histogram reweighting method employing grand Canonical Monte Carlo simulations

Scaling of spontaneous rotation with temperature and plasma current in tokamaks

Using theoretical arguments, a simple scaling law for the size of the intrinsic rotation observed in tokamaks in the absence of momentum injection is found: the velocity generated in the core of a tokamak must be proportional to the ion temperature difference in the core divided by the plasma current, independent of the size of the device. The constant of proportionality is of the order of $10\,\mathrm{km \cdot s^{-1} \cdot MA \cdot keV^{-1}}$. When the intrinsic rotation profile is hollow, i.e. it is counter-current in the core of the tokamak and co-current in the edge, the scaling law presented in this Letter fits the data remarkably well for several tokamaks of vastly different size and heated by different mechanisms.Comment: 5 pages, 3 figure

Prevalence and correlates of frailty among older adults: findings from the German health interview and examination survey

Background: Despite having the third highest proportion of people aged 60 years and older in the world, Germany has been recently reported as having the lowest prevalence of frailty of 15 European countries. The objective of the study is to describe the prevalence of frailty in a large nationwide population-based sample and examine associations with sociodemographic, social support and health characteristics. Methods: We performed a cross-sectional analysis of the first wave of the German Health Interview and Examination Survey for Adults (DEGS1) conducted 2008–2011. Participants were 1843 community-dwelling people aged 65–79 years. Frailty and pre-frailty were defined, according to modified Fried criteria, as 3 and more or 1–2 respectively, of the following: exhaustion, low weight, low physical activity, low walking speed and low grip strength. The Oslo-3 item Social Support Scale (OSS-3) was used. Patient Health Questionnaire (PHQ-9) measured depressive symptoms and the Digit Symbol Substitution Test (DSST) measured cognition. Associations between participants’ characteristics and frailty status were examined using unadjusted and adjusted multinomial logistic regression models estimating relative risk ratios (RRR) of frailty and pre-frailty. Results: The prevalence of frailty among women was 2.8% (CI 1.8-4.3) and pre-frailty 40.4% (CI 36.3-44.7) and among men was 2.3% (CI 1.3-4.1) and 36.9% (CI 32.7-41.3) respectively. Independent determinants of frailty, from unadjusted models, included older age, low socioeconomic status, poor social support, lower cognitive function and a history of falls. In adjusted models current depressive symptoms (RRR 12.86, CI 4.47-37.03), polypharmacy (RRR 7.78, CI 2.92-20.72) and poor hearing (RRR 5.38, CI 2.17-13.35) were statistically significantly associated with frailty. Conclusions: Frailty prevalence is relatively low among community-dwelling older adults in Germany. Modifiable characteristics like low physical activity provide relevant targets for individual and population-level frailty detection and intervention strategies

Diffusivity and configurational entropy maxima in short range attractive colloids

We study tagged particle diffusion at large packing fractions, for a model of particles interacting with a generalized Lennard-Jones 2n-n potential, with large n. The resulting short-range potential mimics interactions in colloidal systems. In agreement with previous calculations for short-range potential, we observe a diffusivity maximum as a function of temperature. By studying the temperature dependence of the configurational entropy -- which we evaluate with two different methods -- we show that a configurational entropy maximum is observed at a temperature close to that of the diffusivity maximum. Our findings suggest a relationbetween dynamics and number of distinct states for short-range potentials.Comment: 4 pages, 3 figures, submited to Physical Review Lette

Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene

Mutations in the X-linked Plp gene lead to dysmyelinating phenotypes and oligodendrocyte cell death. Here, we exploit the X inactivation phenomenon to show that a hierarchy exists in the influence of different mutant Plp alleles on oligodendrocyte survival. We used compound heterozygote mice to study the long-term fate of oligodendrocytes expressing either the jimpy or rumpshaker allele against a background of cells expressing a Plp-null allele. Although mutant and null oligodendrocytes were generated in equal numbers, the proportion expressing the mutant allele subsequently declined, but whereas those expressing the rumpshaker allele formed a reduced but stable population, the number of jimpy cells fell progressively. The age of decline in the jimpy cells in different regions of the CNS correlated with the temporal sequence of myelination. In compound heterozygotes expressing rumpshaker and jimpy alleles, oligodendrocytes expressing the former predominated and were more abundant than when the rumpshaker and null alleles were in competition. Thus, oligodendrocyte survival is not determined solely by cell intrinsic factors, such as the conformation of the misfolded PLP, but is influenced by neighboring cells, possibly competing for cell survival factors

Stage-specific control of oligodendrocyte survival and morphogenesis by TDP-43

Generation of oligodendrocytes in the adult brain enables both adaptive changes in neural circuits and regeneration of myelin sheaths destroyed by injury, disease, and normal aging. This transformation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes requires processing of distinct mRNAs at different stages of cell maturation. Although mislocal- ization and aggregation of the RNA-binding protein, TDP-43, occur in both neurons and glia in neurodegenerative diseases, the consequences of TDP-43 loss within different stages of the oligo- dendrocyte lineage are not well understood. By performing stage-specific genetic inactivation of Tardbp in vivo, we show that oligodendrocyte lineage cells are differentially sensitive to loss of TDP- 43. While OPCs depend on TDP-43 for survival, with conditional deletion resulting in cascading cell loss followed by rapid regeneration to restore their density, oligodendrocytes become less sensitive to TDP-43 depletion as they mature. Deletion of TDP-43 early in the maturation process led to even- tual oligodendrocyte degeneration, seizures, and premature lethality, while oligodendrocytes that experienced late deletion survived and mice exhibited a normal lifespan. At both stages, TDP-43- deficient oligodendrocytes formed fewer and thinner myelin sheaths and extended new processes that inappropriately wrapped neuronal somata and blood vessels. Transcriptional analysis revealed that in the absence of TDP-43, key proteins involved in oligodendrocyte maturation and myelination were misspliced, leading to aberrant incorporation of cryptic exons. Inducible deletion of TDP-43 from oligodendrocytes in the adult central nervous system (CNS) induced the same progressive morphological changes and mice acquired profound hindlimb weakness, suggesting that loss of TDP-43 function in oligodendrocytes may contribute to neuronal dysfunction in neurodegenerative disease