Genetic modifiers ameliorate endocytic and neuromuscular defects in a model of spinal muscular atrophy

© 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Background: Understanding the genetic modifiers of neurodegenerative diseases can provide insight into the mechanisms underlying these disorders. Here, we examine the relationship between the motor neuron disease spinal muscular atrophy (SMA), which is caused by reduced levels of the survival of motor neuron (SMN) protein, and the actin-bundling protein Plastin 3 (PLS3). Increased PLS3 levels suppress symptoms in a subset of SMA patients and ameliorate defects in SMA disease models, but the functional connection between PLS3 and SMN is poorly understood.Results: We provide immunohistochemical and biochemical evidence for large protein complexes localized in vertebrate motor neuron processes that contain PLS3, SMN and members of the hnRNP F/H family of proteins. Using a Caenorhabditis elegans (C. elegans) SMA model, we determine that overexpression of PLS3 or loss of the C. elegans hnRNP F/H ortholog SYM-2 enhances endocytic function and ameliorates neuromuscular defects caused by decreased SMN-1 levels. Furthermore, either increasing PLS3 or decreasing SYM-2 levels suppresses defects in a C. elegans ALS model.Conclusions: We propose that hnRNP F/H act in the same protein complex as PLS3 and SMN and that the function of this complex is critical for endocytic pathways, suggesting that hnRNP F/H proteins could be potential targets for therapy development.Peer reviewe

How to achieve a 100% RES electricity supply for Portugal?

Portugal is a country with an energy system highly dependent on oil and gas imports. Imports of oil and gas accounted for 85% of the country's requirements in 2005 and 86% in 2006. Meanwhile, the share of renewable energy sources (RES) in the total primary energy consumption was only 14% in 2006. When focusing only on electricity production, the situation is somewhat better. The share of RES in gross electricity production varies between 20% and 35% and is dependent on the hydropower production in wet and dry years. This paper presents, on a national scale, Portugal's energy system planning and technical solutions for achieving 100% RES electricity production. Planning was based on hourly energy balance and use of H2RES software. The H2RES model provides the ability to integrate various types of storages into energy systems in order to increase penetration of the intermittent renewable energy sources or to achieve a 100% renewable island, region or country. The paper also represents a stepping-stone for studies offering wider possibilities in matching and satisfying electricity supply in Portugal with potential renewable energy sources. Special attention has been given to intermittent sources such as wind, solar and ocean waves that can be coupled to appropriate energy storage systems charged with surplus amounts of produced electricity. The storage systems also decrease installed power requirements for generating units. Consequently, these storages will assist in avoiding unnecessary rejection of renewable potential and reaching a sufficient security of energy supply.Renewable energy H2RES Sustainable energy planning Energy storage 100% Renewable systems Portugal

RenewIslands methodology for sustainable energy and resource planning for islands

With respect to energy supply, most of the islands depend on importation, mainly from oil and its related products, and others are dependant on weak electricity grid connexions with mainland. Scarce resources are used inefficiently, supplying end-use energy and other life-supporting commodities, like power, heat, cold, transport fuel, water, waste treatment and waste water treatment. It is possible to integrate various flows and decrease the energy intensity, although the task is situation dependant and involves a large number of different systems. RenewIslands methodology for the assessment of alternative scenarios for energy and resource planning is presented here, and applied to several islands. The methodology helps in choosing energy and resource flows integration, based on the island needs, its resources, and the applicable technologies.H2RES RenewIslands methodology Energy storage Islands Hydrogen

Feed-in tariffs for promotion of energy storage technologies

Faster market integration of new energy technologies can be achieved by use of proper support mechanisms that will create favourable market conditions for such technologies. The best examples of support mechanisms presented in the last two decades have been the various schemes for the promotion of renewable energy sources (RES). In the EU, the most successful supporting schemes are feed-in tariffs which have significantly increased utilisation of renewable energy sources in Germany, Spain, Portugal, Denmark and many other EU countries. Despite the successful feed-in tariffs for RES promotion, in many cases RES penetration is limited by power system requirements linked to the intermittency of RES sources and technical capabilities of grids. These problems can be solved by implementation of energy storage technologies like reversible or pumped hydro, hydrogen, batteries or any other technology that can be used for balancing or dump load. In this paper, feed-in tariffs for various energy storage technologies are discussed along with a proposal for their application in more appropriate regions. After successful application on islands and outermost regions, energy storage tariffs should be also applied in mainland power systems. Increased use of energy storage could optimise existing assets on the market.Feed-in tariffs Energy storage Renewable energy sources

Fourier Transform Infrared Spectroscopy Reveals Molecular Changes in Blood Vessels of Rats Treated with Pentadecapeptide BPC 157

Recently, it was found that when confronted with major vessel occlusion and vascular failure, stable gastric pentadecapeptide BPC 157 therapy might rapidly functionally improve minor vessels to take over the function of disabled major vessels, reorganize blood flow, and compensate failed vessel function. We focused on the BPC 157 therapy effect obtained by giving 10 ng/kg ip to rats 5 min before sacrifice on the rat thoracic aorta, which we assessed with Fourier transform infrared spectroscopy (FTIR) 90 min thereafter. We applied a principal component analysis (PCA). The PCA model showed, with a clear distinction being mostly due to the PC1 score, differences between the spectra of BPC 157- and saline-treated rats. The comparison of the averaged spectra of these two groups with their differential spectrum and PC loadings allowed us to identify the parts of the FTIR spectra that contributed the most to the spectral separation of the two observed groups. The PC1 loadings and the differential spectrum showed that the main bands affecting the separation were the amid I band around 1650 cm−1, the amid II band around 1540 cm−1, and the vibrational band around 1744 cm−1. Fitting the spectral range between 1450 and 1800 cm−1 showed changes in protein conformation and confirmed the appearance of the vibrational band at 1744 cm−1. Controls had a substantially more intense vibrational band at 1744 cm−1. These spectral results showed the cells from saline-treated (control) rats to be in the early stage of cell death, while the samples from BPC 157-rats were protected. Thus, BPC 157 therapy changed the lipid contents and protein secondary structure conformation, with a rapid effect on vessels, within a short time upon application