Biologically Plausible Models of Neurite Outgrowth

The growth of a neuronal dendritic tree depends on the neuron’s internal state and the environment within which it is situated. Different types of neuron develop dendritic trees with specific characteristics, such as the average number of terminal branches and the average length of terminal and intermediate segments. A key aspect of the growth process is the construction of the microtubule cytoskeleton within the dendritic tree. Neurite elongation requires assembly of microtubules from free tubulin at the growth cone. The stability of microtubule bundles is an important factor in determining how likely it is for a growth cone to split to form new daughter branches. Microtubule assembly rates and bundle stability are controlled by microtubule-associated proteins, principally MAP2 in dendrites. Extending previous work (Hely et al, J. Theor. Biol. 210:375-384, 2001) I have developed a mathematical model of neurite outgrowth in which elongation and branching rates are determined by the phosphorylation state of MAP2 at the tips of each terminal branch. Tubulin and MAP2 are produced in the cell body and transported along the neurite by a combination of diffusion and active transport. Microtubule (dis)assembly at neurite tips is a function of tubulin concentration. The rate of assembly depends on the amount of unphosphorylated MAP2 bound to the microtubules and linking them together. Phosphorylation of MAP2 destroys its linking capability and destabilises the microtubule bundles. Each terminal has a probability of branching that depends on the phosphorylation of MAP2 which, in turn, is a function of calcium concentration. Results from this model show that changes in the (de)phosphorylation rates of MAP2 affect the topology of the final dendritic tree. Higher phosphorylation promotes branching and results in trees with many short terminal branches and relatively long intermediate segments. Reducing phosphorylation promotes elongation and inhibits branching

Coronal density structure and its role in wave damping in loops

This project has received funding from the Science and Technology Facilities Council (UK) and the European Research Council (ERC) under the European Unionʼs Horizon 2020 research and innovation program (grant agreement No 647214). The research leading to these results has also received funding from the European Commission Seventh Framework Programme (FP7/2007-2013) under the grant agreement SOLSPANET (project No. 269299, www.solspanet.eu/about).It has long been established that gradients in the Alfvén speed, and in particular the plasma density, are an essential part of the damping of waves in the magnetically closed solar corona by mechanisms such as resonant absorption and phase mixing. While models of wave damping often assume a fixed density gradient, in this paper the self-consistency of such calculations is assessed by examining the temporal evolution of the coronal density. It is shown conceptually that for some coronal structures, density gradients can evolve in a way that the wave-damping processes are inhibited. For the case of phase mixing we argue that (a) wave heating cannot sustain the assumed density structure and (b) inclusion of feedback of the heating on the density gradient can lead to a highly structured density, although on long timescales. In addition, transport coefficients well in excess of classical are required to maintain the observed coronal density. Hence, the heating of closed coronal structures by global oscillations may face problems arising from the assumption of a fixed density gradient, and the rapid damping of oscillations may have to be accompanied by a separate (non-wave-based) heating mechanism to sustain the required density structuring.Publisher PDFPeer reviewe

Mutations underlying Episodic Ataxia type-1 antagonize Kv1.1 RNA editing

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 41095, doi:10.1038/srep41095.Adenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele. Editing of transcripts encoding mutant channels affects numerous biophysical properties including channel opening, closing, and inactivation. Thus EA1 symptoms could be influenced not only by the direct effects of the mutations on channel properties, but also by their influence on RNA editing. These studies provide the first evidence that mutations associated with human genetic disorders can affect cis-regulatory elements to alter RNA editing.This work was supported by the Vanderbilt Molecular Endocrinology Training Program (T32DK007563; E.A.F.K.), a Ruth L. Kirschstein National Research Service Award (F31NS087911; E.A.F.K), a Vanderbilt Dissertation Enhancement Grant (E.A.F.K.), and the Vanderbilt Joel G. Hardman Chair in Pharmacology (R.B.E). Additional support for J.J.C.R. included NINDS (R0111223855, R01NS64259) and the Cystic Fibrosis Foundation Therapeutics (Rosent14XXO). Infrastructural support for J.J.C.R. was provided by NIGMS (P20GM103642), NIMH (G12-MD007600), and NSF (DBI 0115825, DBI 1337284)

Nutritional Status of Children with Attention Deficit Hyperactivity Disorder: A Pilot Study

Objectives. This is a pilot study of the dietary intake and nutrient status of children with Attention Deficit Hyperactivity Disorder (ADHD). Method. Nutritional assessment of 43 children aged 6–12 with ADHD was performed using a 3-day food record, 24-hour recall, and serum assessors. Results. Macronutrient intake and consumption of Low-Nutrient Foods were comparable to population norms; however, 66% were found to be deficient in zinc and 23% in copper. Conclusions. This pilot study reports the food intake and nutrient status of children with ADHD and shows a predisposition for low zinc and copper status in ADHD

Biodiversity characterisation and hydrodynamic consequences of marine fouling communities on submerged marine structures in the Orkney Islands Archipelago, Scotland, UK.

As part of ongoing commitments to produce electricity from renewable energy sources in Scotland, Orkney waters have been targeted for potential large-scale deployment of wave and tidal energy converting devices. Orkney has a well-developed infrastructure supporting the marine energy industry; recently enhanced by the construction of additional piers. A major concern to marine industries is biofouling on submerged structures, including energy converters and measurement instrumentation. In this study, the marine energy infrastructure and instrumentation were surveyed to characterise the biofouling. Fouling communities varied between deployment habitats; key species were identified allowing recommendations for scheduling device maintenance and preventing spread of invasive organisms. A method to measure the impact of biofouling on hydrodynamic response is described and applied to data from a wave-monitoring buoy deployed at a test site in Orkney. The results are discussed in relation to the accuracy of the measurement resources for power generation. Further applications are suggested for future testing in other scenarios, including tidal energy

Biodiversity characterisation and hydrodynamic consequences of marine fouling communities on submerged marine structures in the Orkney Islands Archipelago, Scotland, UK.

<p>As part of ongoing commitments to produce electricity from renewable energy sources in Scotland, Orkney waters have been targeted for potential large-scale deployment of wave and tidal energy converting devices. Orkney has a well-developed infrastructure supporting the marine energy industry; recently enhanced by the construction of additional piers. A major concern to marine industries is biofouling on submerged structures, including energy converters and measurement instrumentation. In this study, the marine energy infrastructure and instrumentation were surveyed to characterise the biofouling. Fouling communities varied between deployment habitats; key species were identified allowing recommendations for scheduling device maintenance and preventing spread of invasive organisms. A method to measure the impact of biofouling on hydrodynamic response is described and applied to data from a wave-monitoring buoy deployed at a test site in Orkney. The results are discussed in relation to the accuracy of the measurement resources for power generation. Further applications are suggested for future testing in other scenarios, including tidal energy.</p

Identifying environmental and management factors that may be associated with the quality of life of kennelled dogs (Canis familiaris)

Abstract This paper describes the use of a validated quality of life assessment tool (described elsewhere) to identify environmental and management factors that may affect quality of life in dogs kennelled in rehoming centres. Dogs were allocated to one of four treatment groups, all of which had a positive (0.0 - 1.0) average quality of life score: long stay dogs with an enriched routine had a mean score of 0.477; long stay dogs with a standard routine had a mean score of 0.453; newly admitted dogs with an enriched routine had a mean score of 0.399; and newly admitted dogs with a standard routine had a mean score of 0.362. Only 2 of the dogs had a negative score (-1.0 - 0.0). Thirteen rehoming centre managers completed a questionnaire relating to the kennel environment and management practices of their rehoming centres. The environmental and management factors� associations with quality of life scores, collected from 202 dogs from the 13 rehoming centres using this scoring system, were analysed as fixed factors in a linear mixed-effect model, with rehoming centre fitted as a random factor, and a multiple linear regression model. There was a statistically significant association between quality of life scores and rehoming centre (H(12)&#xa0;=&#xa0;54.153, p &lt;0.001), however, the fitted linear mixed-effect model did not improve upon the null model and therefore cannot be used to explain the 29 variance in quality of life scores attributed to rehoming centre. The multiple linear regression model explained 42 of the variation in quality of life scores (F(10,131)&#xa0;=&#xa0;9.318, p&#xa0;&lt;&#xa0;0.001): the provision of bunk beds increased quality of life scores by 0.3 (t&#xa0;=&#xa0;3.476, p&#xa0;&lt;&#xa0;0.001); provision of 30&#xa0;minutes or more of staff or volunteer interaction increased scores by 0.26 (t&#xa0;=&#xa0;-2.551, p&#xa0;=&#xa0;0.012); grooming dogs decreased scores by 0.404 (t&#xa0;=&#xa0;3.326, p&#xa0;=&#xa0;0.001); exercising dogs more than once a day decreased scores by 0.173 (t&#xa0;=&#xa0;-3.644, p&#xa0;=&#xa0;&lt;0.001), whereas exercising dogs for 30&#xa0;minutes or more increased quality of life scores by 0.213 (t&#xa0;=&#xa0;-2.374, p&#xa0;=&#xa0;0.019) and the provision of less common types of exercise increased scores by 0.504 (t&#xa0;=&#xa0;5.120, p&#xa0;&lt;&#xa0;0.001); training dogs for 30&#xa0;minutes or more every day increased scores by 0.688 (t&#xa0;=&#xa0;3.040, p&#xa0;=&#xa0;0.003) and training dogs less than daily decreased scores by 0.393 (t&#xa0;=&#xa0;-4.245, p&#xa0;&lt;&#xa0;0.001); feeding a diet of dry and wet food compared to dry food alone decreased scores by 0.08 (t&#xa0;=&#xa0;-2.331, p&#xa0;=&#xa0;0.021); and a quiet environment increased scores by 0.275 (t&#xa0;=&#xa0;-3.459, p&#xa0;&lt;&#xa0;0.001). These results suggest that environmental design and kennel management have an impact on the quality of life of kennelled dogs and should be considered carefully in decision-making processes. However, further study may be required as grooming and exercising dogs more than once per day decreased quality of life scores, which are not obviously intuitive results

Stochastic Continuous Time Neurite Branching Models with Tree and Segment Dependent Rates

In this paper we introduce a continuous time stochastic neurite branching model closely related to the discrete time stochastic BES-model. The discrete time BES-model is underlying current attempts to simulate cortical development, but is difficult to analyze. The new continuous time formulation facilitates analytical treatment thus allowing us to examine the structure of the model more closely. We derive explicit expressions for the time dependent probabilities p(\gamma, t) for finding a tree \gamma at time t, valid for arbitrary continuous time branching models with tree and segment dependent branching rates. We show, for the specific case of the continuous time BES-model, that as expected from our model formulation, the sums needed to evaluate expectation values of functions of the terminal segment number \mu(f(n),t) do not depend on the distribution of the total branching probability over the terminal segments. In addition, we derive a system of differential equations for the probabilities p(n,t) of finding n terminal segments at time t. For the continuous BES-model, this system of differential equations gives direct numerical access to functions only depending on the number of terminal segments, and we use this to evaluate the development of the mean and standard deviation of the number of terminal segments at a time t. For comparison we discuss two cases where mean and variance of the number of terminal segments are exactly solvable. Then we discuss the numerical evaluation of the S-dependence of the solutions for the continuous time BES-model. The numerical results show clearly that higher S values, i.e. values such that more proximal terminal segments have higher branching rates than more distal terminal segments, lead to more symmetrical trees as measured by three tree symmetry indicators.Comment: 41 pages, 2 figures, revised structure and text improvement