Enhanced axonal response of mitochondria to demyelination offers neuroprotection:implications for multiple sclerosis

Axonal loss is the key pathological substrate of neurological disability in demyelinating disorders, including multiple sclerosis (MS). However, the consequences of demyelination on neuronal and axonal biology are poorly understood. The abundance of mitochondria in demyelinated axons in MS raises the possibility that increased mitochondrial content serves as a compensatory response to demyelination. Here, we show that upon demyelination mitochondria move from the neuronal cell body to the demyelinated axon, increasing axonal mitochondrial content, which we term the axonal response of mitochondria to demyelination (ARMD). However, following demyelination axons degenerate before the homeostatic ARMD reaches its peak. Enhancement of ARMD, by targeting mitochondrial biogenesis and mitochondrial transport from the cell body to axon, protects acutely demyelinated axons from degeneration. To determine the relevance of ARMD to disease state, we examined MS autopsy tissue and found a positive correlation between mitochondrial content in demyelinated dorsal column axons and cytochromecoxidase (complex IV) deficiency in dorsal root ganglia (DRG) neuronal cell bodies. We experimentally demyelinated DRG neuron-specific complex IV deficient mice, as established disease models do not recapitulate complex IV deficiency in neurons,and found that these mice are able to demonstrate ARMD, despite the mitochondrial perturbation.Enhancement of mitochondrial dynamics in complex IV deficient neurons protects the axon upon demyelination. Consequently, increased mobilisation of mitochondria from the neuronal cell body to the axon is a novel neuroprotective strategy for the vulnerable, acutely demyelinated axon. We propose that promoting ARMD is likely to be a crucial preceding step for implementing potential regenerative strategies for demyelinating disorders.</p

Multiwavelength campaign on Mrk 509: Reverberation of the Fe Kalpha line

We report on a detailed study of the Fe K emission/absorption complex in the nearby, bright Seyfert 1 galaxy Mrk 509. The study is part of an extensive XMM-Newton monitoring consisting of 10 pointings (~60 ks each) about once every four days, and includes also a reanalysis of previous XMM-Newton and Chandra observations. Mrk 509 shows a clear (EW=58 eV) neutral Fe Kalpha emission line that can be decomposed into a narrow (sigma=0.027 keV) component (found in the Chandra HETG data) plus a resolved (sigma=0.22 keV) component. We find the first successful measurement of a linear correlation between the intensity of the resolved line component and the 3-10 keV flux variations on time-scales of years down to a few days. The Fe Kalpha reverberates the hard X-ray continuum without any measurable lag, suggesting that the region producing the resolved Fe Kalpha component is located within a few light days-week (r<~10^3 rg) from the Black Hole (BH). The lack of a redshifted wing in the line poses a lower limit of >40 rg for its distance from the BH. The Fe Kalpha could thus be emitted from the inner regions of the BLR, i.e. within the ~80 light days indicated by the Hbeta line measurements. In addition to these two neutral Fe Kalpha components, we confirm the detection of weak (EW~8-20 eV) ionised Fe K emission. This ionised line can be modeled with either a blend of two narrow FeXXV and FeXXVI emission lines or with a single relativistic line produced, in an ionised disc, down to a few rg from the BH. Finally, we observe a weakening/disappearing of the medium and high velocity high ionisation Fe K wind features found in previous XMM-Newton observations. This campaign has made possible the first reverberation measurement of the resolved component of the Fe Kalpha line, from which we can infer a location for the bulk of its emission at a distance of r~40-1000 rg from the BH.Comment: Accepted for publication in A&

Enhanced axonal response of mitochondria to demyelination offers neuroprotection:implications for multiple sclerosis

Axonal loss is the key pathological substrate of neurological disability in demyelinating disorders, including multiple sclerosis (MS). However, the consequences of demyelination on neuronal and axonal biology are poorly understood. The abundance of mitochondria in demyelinated axons in MS raises the possibility that increased mitochondrial content serves as a compensatory response to demyelination. Here, we show that upon demyelination mitochondria move from the neuronal cell body to the demyelinated axon, increasing axonal mitochondrial content, which we term the axonal response of mitochondria to demyelination (ARMD). However, following demyelination axons degenerate before the homeostatic ARMD reaches its peak. Enhancement of ARMD, by targeting mitochondrial biogenesis and mitochondrial transport from the cell body to axon, protects acutely demyelinated axons from degeneration. To determine the relevance of ARMD to disease state, we examined MS autopsy tissue and found a positive correlation between mitochondrial content in demyelinated dorsal column axons and cytochrome c oxidase (complex IV) deficiency in dorsal root ganglia (DRG) neuronal cell bodies. We experimentally demyelinated DRG neuron-specific complex IV deficient mice, as established disease models do not recapitulate complex IV deficiency in neurons, and found that these mice are able to demonstrate ARMD, despite the mitochondrial perturbation. Enhancement of mitochondrial dynamics in complex IV deficient neurons protects the axon upon demyelination. Consequently, increased mobilisation of mitochondria from the neuronal cell body to the axon is a novel neuroprotective strategy for the vulnerable, acutely demyelinated axon. We propose that promoting ARMD is likely to be a crucial preceding step for implementing potential regenerative strategies for demyelinating disorders.</p

Benchmark systems for small signal stability analysis and control

This report documents the work of the IEEE PES Task Force (TF) on Benchmark Systems for Stability Controls. The following sections present the objectives of the TF, the guidelines used to select the benchmarks, a brief description of each benchmark system so the reader can select the most suitable system for the intended application, the input data and results for each benchmark system, and a set of conclusions

Microgrid Stability Definitions, Analysis, and Examples

This document is a summary of a report prepared by the IEEE PES Task Force (TF) on Microgrid Stability Definitions, Analysis, and Modeling \cite{task}, which defines concepts and identifies relevant issues related to stability in microgrids. In this paper, definitions and classification of microgrid stability are presented and discussed, considering pertinent microgrid features such as voltage-frequency dependency, unbalancing, low inertia, and generation intermittency. A few examples are also presented, highlighting some of the stability classes defined in the paper. Further examples, along with discussions on microgrid components modeling and stability analysis tools can be found in the TF report