Targeting vasoactive peptides for managing calcific aortic valve disease

Calcific aortic valve disease (CAVD) represents a spectrum of disease spanning from milder degrees of calcification of valve leaflets, i.e., aortic sclerosis, to severe calcification i.e., aortic stenosis (AS) with hemodynamic instability. The prevalence of CAVD is increasing rapidly due to the aging of the population, being up to 2.8% among patients over 75 years of age. Even without significant aortic valve stenosis, aortic sclerosis is associated with a 50% increased risk of myocardial infarction and death from cardiovascular causes. To date, there is no pharmacological treatment available to reverse or hinder the progression of CAVD. So far, the cholesterol-lowering therapies (statins) and renin-angiotensin system (RAS) blocking drugs have been the major pharmacological agents investigated for treatment of CAVD. Especially angiotensin receptor blockers (ARB)s and angiotensin convertase enzyme inhibitors (ACEI)s, have been under active investigation in clinical trials, but have proven to be unsuccessful in slowing the progression of CAVD. Several studies have suggested that other vasoactive hormones, including endothelin and apelin systems are also associated with development of AS. In the present review, we discuss the role of vasoactive factors in the pathogenesis of CAVD as novel pharmacological targets for the treatment of aortic valve calcification.Peer reviewe

RNA-Seq Reveals Acute Manganese Exposure Increases Endoplasmic Reticulum Related and Lipocalin mRNAs in Caenorhabditis elegans

Manganese (Mn) is an essential nutrient; nonetheless, excessive amounts can accumulate in brain tissues causing manganism, a severe neurological condition. Previous studies have suggested oxidative stress, mitochondria dysfunction, and impaired metabolism pathways as routes for Mn toxicity. Here, we used the nematode Caenorhabditis elegans to analyze gene expression changes after acute Mn exposure using RNA-Seq. L1 stage animals were exposed to 50 mM MnCl2 for 30 min and analyzed at L4. We identified 746 up- and 1828 downregulated genes (FDR corrected p < 0.05; two-fold change) that included endoplasmic reticulum related abu and fkb family genes, as well as six of seven lipocalin-related (lpr) family members. These were also verified by qRT-PCR. RNA interference of lpr-5 showed a dramatic increase in whole body vulnerability to Mn exposure. Our studies demonstrate that Mn exposure alters gene transcriptional levels in different cell stress pathways that may ultimately contribute to its toxic effects

Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans

Methylmercury (MeHg) is a persistent environmental and dietary contaminant that causes serious adverse developmental and physiologic effects at multiple cellular levels. In order to understand more fully the consequences of MeHg exposure at the molecular level, we profiled gene and miRNA transcripts from the model organism Caenorhabditis elegans. Animals were exposed to MeHg (10µM) from embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the Illumina platform revealed 541 genes up- and 261 genes down-regulated at a cutoff of 2-fold change and false discovery rate-corrected significance q < 0.05. Among the up-regulated genes were those previously shown to increase under oxidative stress conditions including hsp-16.11 (2.5-fold), gst-35 (10.1-fold), and fmo-2(58.5-fold). In addition, we observed up-regulation of 6 out of 7 lipocalin related (lpr) family genes and down regulation of 7 out of 15 activated in blocked unfolded protein response (abu) genes. Gene Ontology enrichment analysis highlighted the effect of genes related to development and organism growth. miRNA-seq analysis revealed 6–8 fold down regulation of mir-37-3p, mir-41-5p, mir-70-3p, and mir-75-3p. Our results demonstrate the effects of MeHg on specific transcripts encoding proteins in oxidative stress responses and in ER stress pathways. Pending confirmation of these transcript changes at protein levels, their association and dissocation characteristics with interaction partners, and integration of these signals, these findings indicate broad and dynamic mechanisms by which MeHg exerts its harmful effects

Paljasjyväisen kauran korjuu ja käsittely vaatii tarkkuutta

Liite 2.4.2001Siementen alhainen korjuukosteus on oleellinen tekijä pyrittäessä saamaan hyvin itävää ja laadukasta paljasjyväistä kauraa. Puimurin säädöillä pystytään vähentämään itävyysvaurioita, eivätkä ne enää lisäänny kuivauksessa, vaikka käsiteltävä materiaali olisi kosteaakin.vokKV

Neurofibromatosis Type 1 Gene Mutation Analysis Using Sequence Capture and High-throughput Sequencing

Peer reviewe

Calibration of RADMON radiation monitor onboard Aalto-1 CubeSat

RADMON is a small radiation monitor designed and assembled by students of University of Turku and University of Helsinki. It is flown on-board Aalto-1, a 3-unit CubeSat in low Earth orbit at about 500 km altitude. The detector unit of the instrument consists of two detectors, a Si solid-state detector and a CsI(Tl) scintillator, and utilizes the ΔE-E technique to determine the total energy and species of each particle hitting the detector. We present the results of the on-ground and in-flight calibration campaigns of the instrument, as well as the characterization of its response through extensive simulations within the Geant4 framework. The overall energy calibration margin achieved is about 5%. The full instrument response to protons and electrons is presented and the issue of proton contamination of the electron channels is quantified and discussed.RADMON is a small radiation monitor designed and assembled by students of University of Turku and University of Helsinki. It is flown on-board Aalto-1, a 3-unit CubeSat in low Earth orbit at about 500 km altitude. The detector unit of the instrument consists of two detectors, a Si solid-state detector and a CsI(Tl) scintillator, and utilizes the Delta E-E technique to determine the total energy and species of each particle hitting the detector. We present the results of the on-ground and in-flight calibration campaigns of the instrument, as well as the characterization of its response through extensive simulations within the Geant4 framework. The overall energy calibration margin achieved is about 5%. The full instrument response to protons and electrons is presented and the issue of proton contamination of the electron channels is quantified and discussed. (C) 2019 COSPAR. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Radiation monitor RADMON aboard Aalto-1 CubeSat : First results

The Radiation Monitor (RADMON) on-board Aalto-1 CubeSat is an energetic particle detector that fulfills the requirements of small size, low power consumption and low budget. Aalto-1 was launched on 23 June 2017 to a sun-synchronous polar orbit with 97.4° inclination and an average altitude of somewhat above 500 km. RADMON has been measuring integral particle intensities from October 2017 to May 2018 with electron energies starting at low-MeV and protons from 10 MeV upwards. In this paper, we present first electron and proton intensity maps obtained over the mission period. In addition, the response of RADMON measurements to magnetospheric dynamics are analyzed, and the electron observations are compared with corresponding measurements by the PROBA-V/EPT mission. Finally, we describe the RADMON data set, which is made publicly available.The Radiation Monitor (RADMON) on-board Aalto-1 CubeSat is an energetic particle detector that fulfills the requirements of small size, low power consumption and low budget. Aalto-1 was launched on 23 June 2017 to a sun-synchronous polar orbit with 97.4 degrees inclination and an average altitude of somewhat above 500 km. RADMON has been measuring integral particle intensities from October 2017 to May 2018 with electron energies starting at low-MeV and protons from 10 MeV upwards. In this paper, we present first electron and proton intensity maps obtained over the mission period. In addition, the response of RADMON measurements to magnetospheric dynamics are analyzed, and the electron observations are compared with corresponding measurements by the PROBA-V/EPT mission. Finally, we describe the RADMON data set, which is made publicly available. (C) 2019 COSPAR. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Particle telescope aboard FORESAIL-1 : Simulated performance

The Particle Telescope (PATE) of FORESAIL-1 mission is described. FORESAIL-1 is a CubeSat mission to polar Low Earth Orbit. Its scientific objectives are to characterize electron precipitation from the radiation belts and to observe energetic neutral atoms (ENAs) originating from the Sun during the strongest solar flares. For that purpose, the 3-unit CubeSat carries a particle telescope that measures energetic electrons in the nominal energy range of 80–800 keV in seven energy channels and energetic protons at 0.3–10 MeV in ten channels. In addition, particles penetrating the whole telescope at higher energies will be measured in three channels: one >800 keV electron channel, two integral proton channels at >10 MeV energies. The instrument contains two telescopes at right angles to each other, one measuring along the spin axis of the spacecraft and one perpendicular to it. During a spin period (nominally 15 s), the rotating telescope will, thus, deliver angular distributions of protons and electrons, at 11.25-degree clock-angle resolution, which enables one to accurately determine the pitch-angle distribution and separate the trapped and precipitating particles. During the last part of the mission, the rotation axis will be accurately pointed toward the Sun, enabling the measurement of the energetic hydrogen from that direction. Using the geomagnetic field as a filter and comparing the rates observed by the two telescopes, the instrument can observe the solar ENA flux for events similar to the only one so far observed in December 2006. We present the Geant4-simulated energy and angular response functions of the telescope and assess its sensitivity showing that they are adequate to address the scientific objectives of the mission.The Particle Telescope (PATE) of FORESAIL-1 mission is described. FORESAIL-1 is a CubeSat mission to polar Low Earth Orbit. Its scientific objectives are to characterize electron precipitation from the radiation belts and to observe energetic neutral atoms (ENAs) originating from the Sun during the strongest solar flares. For that purpose, the 3-unit CubeSat carries a particle telescope that measures energetic electrons in the nominal energy range of 80-800 keV in seven energy channels and energetic protons at 0.3-10 MeV in ten channels. In addition, particles penetrating the whole telescope at higher energies will be measured in three channels: one >800 keV electron channel, two integral proton channels at >10 MeV energies. The instrument contains two telescopes at right angles to each other, one measuring along the spin axis of the spacecraft and one perpendicular to it. During a spin period (nominally 15 s), the rotating telescope will, thus, deliver angular distributions of protons and electrons, at 11.25-degree clock-angle resolution, which enables one to accurately determine the pitch-angle distribution and separate the trapped and precipitating particles. During the last part of the mission, the rotation axis will be accurately pointed toward the Sun, enabling the measurement of the energetic hydrogen from that direction. Using the geomagnetic field as a filter and comparing the rates observed by the two telescopes, the instrument can observe the solar ENA flux for events similar to the only one so far observed in December 2006. We present the Geant4-simulated energy and angular response functions of the telescope and assess its sensitivity showing that they are adequate to address the scientific objectives of the mission. (C) 2019 COSPAR. Published by Elsevier Ltd. All rights reserved.Peer reviewe