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

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

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

Using the theoretical domains framework to inform strategies to support dietitians undertaking body composition assessments in routine clinical care

BACKGROUND: Malnutrition, sarcopenia and cachexia are clinical wasting syndromes characterised by muscle loss. Systematic monitoring by body composition assessment (BCA) is recommended for the diagnosis, treatment and monitoring of the syndrome(s). This study investigated practices, competency, and attitudes of Australian dietitians regarding BCA, to inform a local implementation process. METHODS: Applying the Action cycle in the Knowledge to Action framework, surveys were distributed to the 26 dietitians of an 800-bed tertiary hospital. The survey assessed barriers and enablers to performing routine BCA in clinical care. Results were categorised using the Theoretical Domains Framework (TDF) and suitable interventions mapped using the Behaviour Change Wheel. RESULTS: Twenty-two dietitians (84.6%) completed the survey. Barriers to BCA were identified in all TDF domains, particularly in Knowledge, Skills, Social/professional role and identity, Beliefs about capabilities, and Environmental context and resources. Enablers existed in domains of: Skills; Beliefs about consequences; Goals; Environmental context and resources; Social influences; Intentions; Optimism; Reinforcement. CONCLUSIONS: This study showed that hospital dietitians experience individual, team, and organisational barriers to adopt BCAs in clinical practice. We were able to formulate targeted implementation strategies to overcome these barriers to assist BCA adoption into routine practice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-021-06375-7

Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states.

Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons