Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P2 That Regulates Neuronal Excitability.

There is increasing evidence that the lysosome is involved in the pathogenesis of a variety of neurodegenerative disorders. Thus, mechanisms that link lysosome dysfunction to the disruption of neuronal homeostasis offer opportunities to understand the molecular underpinnings of neurodegeneration and potentially identify specific therapeutic targets. Here, using a monogenic neurodegenerative disorder, NPC1 disease, we demonstrate that reduced cholesterol efflux from lysosomes aberrantly modifies neuronal firing patterns. The molecular mechanism linking alterations in lysosomal cholesterol egress to intrinsic tuning of neuronal excitability is a transcriptionally mediated upregulation of the ABCA1 transporter, whose PtdIns(4,5)P2-floppase activity decreases plasma membrane PtdIns(4,5)P2. The consequence of reduced PtdIns(4,5)P2 is a parallel decrease in a key regulator of neuronal excitability, the voltage-gated KCNQ2/3 potassium channel, which leads to hyperexcitability in NPC1 disease neurons. Thus, cholesterol efflux from lysosomes regulates PtdIns(4,5)P2 to shape the electrical and functional identity of the plasma membrane of neurons in health and disease

Hydrogen vs. Battery in the long-term operation. A comparative between energy management strategies for hybrid renewable microgrids

The growth of the world’s energy demand over recent decades in relation to energy intensity and demography is clear. At the same time, the use of renewable energy sources is pursued to address decarbonization targets, but the stochasticity of renewable energy systems produces an increasing need for management systems to supply such energy volume while guaranteeing, at the same time, the security and reliability of the microgrids. Locally distributed energy storage systems (ESS) may provide the capacity to temporarily decouple production and demand. In this sense, the most implemented ESS in local energy districts are small–medium-scale electrochemical batteries. However, hydrogen systems are viable for storing larger energy quantities thanks to its intrinsic high mass-energy density. To match generation, demand and storage, energy management systems (EMSs) become crucial. This paper compares two strategies for an energy management system based on hydrogen-priority vs. battery-priority for the operation of a hybrid renewable microgrid. The overall performance of the two mentioned strategies is compared in the long-term operation via a set of evaluation parameters defined by the unmet load, storage efficiency, operating hours and cumulative energy. The results show that the hydrogen-priority strategy allows the microgrid to be led towards island operation because it saves a higher amount of energy, while the battery-priority strategy reduces the energy efficiency in the storage round trip. The main contribution of this work lies in the demonstration that conventional EMS for microgrids’ operation based on battery-priority strategy should turn into hydrogen-priority to keep the reliability and independence of the microgrid in the long-term operation

Stellar over-densities in the halo: the extent of the Virgo over-density

We map the three dimensional extent of the Virgo Over-density by combining distance information from RR Lyrae variables and projected spatial information from SEKBO (Keller et al. 2008) and Sloan Digital Sky Survey (SDSS) DR6 photometry. The Virgo Over-density is seen to comprise two filaments 14.5 x 3 degrees and 10 x 3 degrees and a circular structure 3 degrees in diameter. Together the three features span 38 degrees of right ascension and declinations of +2 to -15 degrees. RR Lyrae variables place the two filamentary features at heliocentric distances of 20 and 17 kpc respectively, with projected dimensions of 5 x 1 kpc and 3 x 1 kpc.Comment: 6 pages, 5 figures, MNRAS accepte

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation