cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.25403/upresearchdata.21716900
title: Parentage analyses, selection of single nucleotide polymorphisms (SNPs) and design of panels for pedigree verification of the Bonsmara and Drakensberger cattle

description: The dataset was generated from the GeneSeek® Genomic Profiler (GGP) Bovine 150K BeadChip single nucleotide polymorphism (SNP) panel using 1 563 and 1 022 animals of the Bonsmara and Drakensberger, respectively. Data edits and calculations were all performed using the<em> R</em> software. After removing duplicate SNPs, those on the X, Y, and MT chromosomes, and those with unknown locations, a total of 119 375 autosomal SNPs based on the UMD3.1 bovine genome remained. Only animal genotypes with call rate more than 90% were considered for downstream analysis. The dataset only included 185 of the 200 parentage SNPs of the International Society for Animal Genetics (ISAG). The 185 SNPs were then evaluated for effectiveness in the Bonsmara and Drakensberger cattle populations. Results showed that the 185 ISAG were not sufficient for parentage testing in the two South African breeds. The primary dataset consisting of 119 375 number of SNPs was used to validate the parent-offspring relationships recorded in pedigree and to detect regions exhibiting hemizygous deletions. <br> Additional quality control edits applied to the 119 375 SNPs included the removal of genotypes with median GenCall (GC), GenTrain (GT) scores lower than 0.60 and 0.55, respectively. All SNPs that departed from Hardy–Weinberg equilibrium (p &lt; 0.001), with missing genotype rate of more than 5% and where the minor allele frequency (MAF) was &lt;0.05 across the populations were discarded. After edits, 2 585 animals (BON = 1 563 and DRB = 1 022) with 92 835 autosomal SNPs remained. This dataset was then used for parentage assignment and reconstruction of pedigree records using the gawk and <em>Hsphase</em> R package scripts, respectively. <br> Finally, the design of low-cost genotype parentage panels consisting of 200 SNPs per breed were selected from 78 286 SNP markers that had a GT score and GC score of 0.60&gt;= and 0.55&gt;=, respectively; a call rate of 0.99%&gt;=, MAF 0.05&gt;=, and those that had a HWE p-value &gt; 0.001. To minimize linkage disequilibrium (LD) among selected SNPs, the selected SNPs had to be at least 1 Mb apart and with a LogRRatio &gt; 0.001. <br>
DOI: 10.5281/zenodo.7550198
title: Dataset related to the article "Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation"

description: This record contains raw data related to the article "Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation" Rationale-Calcific aortic valve stenosis (CAVS) is a pathological condition of the aortic valve with a prevalence of 3% in the general population. It is characterized by massive rearrangement of the extracellular matrix, mostly due to the accumulation of fibro-calcific deposits driven by valve interstitial cells (VIC), and no pharmacological treatment is currently available. The aim of this study was to evaluate the effects of P2Y2 receptor (P2RY2) activation on fibro-calcific remodeling of CAVS. Methods-We employed human primary VICs isolated from CAVS leaflets treated with 2-thiouridine-5'-triphosphate (2ThioUTP, 10 µM), an agonist of P2RY2. The calcification was induced by inorganic phosphate (2 mM) and ascorbic acid (50 µg/mL) for 7 or 14 days, while the 2ThioUTP was administered starting from the seventh day. 2ThioUTP was chronically administered for 5 days to evaluate myofibroblastic activation. Results-P2RY2 activation, under continuous or interrupted pro-calcific stimuli, led to a significant inhibition of VIC calcification potential (<em>p</em> &lt; 0.01). Moreover, 2ThioUTP treatment was able to significantly reduce pro-fibrotic gene expression (<em>p</em> &lt; 0.05), as well as that of protein α-smooth muscle actin (<em>p</em> = 0.004). Conclusions-Our data suggest that P2RY2 activation should be further investigated as a pharmacological target for the prevention of CAVS progression, acting on both calcification and myofibroblastic activation.
description: This research was funded by Italian Ministry of Health funds (Ricerca Finalizzata: GR-2018-12366423; GR-2019-12370560) and by the Fondazione Gigi e Pupa Ferrari ONLUS (FPF-14).
DOI: 10.5281/zenodo.7550199
title: Dataset related to the article "Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation"

description: This record contains raw data related to the article "Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation" Rationale-Calcific aortic valve stenosis (CAVS) is a pathological condition of the aortic valve with a prevalence of 3% in the general population. It is characterized by massive rearrangement of the extracellular matrix, mostly due to the accumulation of fibro-calcific deposits driven by valve interstitial cells (VIC), and no pharmacological treatment is currently available. The aim of this study was to evaluate the effects of P2Y2 receptor (P2RY2) activation on fibro-calcific remodeling of CAVS. Methods-We employed human primary VICs isolated from CAVS leaflets treated with 2-thiouridine-5'-triphosphate (2ThioUTP, 10 µM), an agonist of P2RY2. The calcification was induced by inorganic phosphate (2 mM) and ascorbic acid (50 µg/mL) for 7 or 14 days, while the 2ThioUTP was administered starting from the seventh day. 2ThioUTP was chronically administered for 5 days to evaluate myofibroblastic activation. Results-P2RY2 activation, under continuous or interrupted pro-calcific stimuli, led to a significant inhibition of VIC calcification potential (<em>p</em> &lt; 0.01). Moreover, 2ThioUTP treatment was able to significantly reduce pro-fibrotic gene expression (<em>p</em> &lt; 0.05), as well as that of protein α-smooth muscle actin (<em>p</em> = 0.004). Conclusions-Our data suggest that P2RY2 activation should be further investigated as a pharmacological target for the prevention of CAVS progression, acting on both calcification and myofibroblastic activation.
description: This research was funded by Italian Ministry of Health funds (Ricerca Finalizzata: GR-2018-12366423; GR-2019-12370560) and by the Fondazione Gigi e Pupa Ferrari ONLUS (FPF-14).
DOI: 10.5281/zenodo.7544682
title: Dataset related to the article " Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells"

description: This record contains raw data related to the article “Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca<sup>2+</sup> Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells" Abstract Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca<sup>2+</sup> release. NAADP-induced lysosomal Ca<sup>2+</sup> release may be amplified by the endoplasmic reticulum (ER) through the Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release (CICR) mechanism. NAADP-induced intracellular Ca<sup>2+</sup> signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca<sup>2+</sup> signal that was abolished by disrupting the lysosomal Ca<sup>2+</sup> store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca<sup>2+</sup> release resulted in the Ca<sup>2+</sup>-dependent recruitment of ER-embedded InsP<sub>3</sub>Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca<sup>2+</sup> to recruit ER-embedded InsP<sub>3</sub>Rs through CICR. NAADP-induced EL Ca<sup>2+</sup> mobilization via EL TPC was found to trigger the intracellular Ca<sup>2+</sup> signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca<sup>2+</sup> release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders.
description: Funding The authors gratefully acknowledge financial support from: Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018–2022)—Department of Biology and Biotechnology "L. Spallanzani," University of Pavia. Ricerca Corrente from Italian Ministry of Health to Centro Cardiologico Monzino IRCCS (2020, 2021). Fondazione di Comunità Milano e Fondo Fondazione Giacomo Ponzone (2021) to Angela Serena Maione.
DOI: 10.5281/zenodo.7544681
title: Dataset related to the article " Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells"

description: This record contains raw data related to the article “Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca<sup>2+</sup> Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells" Abstract Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca<sup>2+</sup> release. NAADP-induced lysosomal Ca<sup>2+</sup> release may be amplified by the endoplasmic reticulum (ER) through the Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release (CICR) mechanism. NAADP-induced intracellular Ca<sup>2+</sup> signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca<sup>2+</sup> signal that was abolished by disrupting the lysosomal Ca<sup>2+</sup> store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca<sup>2+</sup> release resulted in the Ca<sup>2+</sup>-dependent recruitment of ER-embedded InsP<sub>3</sub>Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca<sup>2+</sup> to recruit ER-embedded InsP<sub>3</sub>Rs through CICR. NAADP-induced EL Ca<sup>2+</sup> mobilization via EL TPC was found to trigger the intracellular Ca<sup>2+</sup> signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca<sup>2+</sup> release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders.
description: Funding The authors gratefully acknowledge financial support from: Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018–2022)—Department of Biology and Biotechnology "L. Spallanzani," University of Pavia. Ricerca Corrente from Italian Ministry of Health to Centro Cardiologico Monzino IRCCS (2020, 2021). Fondazione di Comunità Milano e Fondo Fondazione Giacomo Ponzone (2021) to Angela Serena Maione.
DOI: 10.6084/m9.figshare.21946367
title: chip.bam

description: example .bam format file from ChIP-seq data
DOI: 10.25430/researchdata.cab.unipd.it.00000802
title: Data related to eBiomedicine 2023 Article Number 104453 titled "Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice"

description: SUMMARY Background Keratitis ichthyosis deafness (KID) syndrome is a rare disorder caused by hemichannel (HC) activating gain-of-function mutations in the GJB2 gene encoding connexin (Cx) 26, for which there is no cure, or current treatments based upon the mechanism of disease causation. The recent development of specific monoclonal antibodies (mAbs) that block the acquired HC activity, and the availability of mouse models that replicate the skin pathology of KID syndrome, allow this deficiency to be directly addressed. In this study, we aimed to assess inhibition of mutant Cx HC activity with anti-HC monoclonal antibodies as therapeutic target in KID syndrome. Methods We used Adeno Associated Virus (AAV) mediated mAb gene transfer (AAVmAb) to treat the epidermal features of KID syndrome in a mouse model of the human disease with a well-characterized HC blocking antibody. Findings We demonstrate that in vivo AAVmAb treatment, via caudal vein injection of the mAb-encoding AAV vector, significantly reduced the size and thickness of KID lesions, in addition to blocking activity of mutant HCs in the epidermis in vivo. We also show that AAVmAb treatment eliminated abnormal keratinocyte proliferation and enlarged cell size, decreased apoptosis, and restored the normal distribution of keratin expression. Interpretation Our findings reinforce the critical role played by increased HC activity in the skin pathology associated with KID syndrome. They also underscore the clinical potential of anti-HC mAbs coupled with genetic based delivery systems for treating the underlying mechanistic basis of this disorder. Inhibition of HC activity is an ideal therapeutic target in KID syndrome, and the genetic delivery of mAbs targeted against mutant HCs could form the basis of new therapeutic interventions to treat this incurable disease. Funding Fondazione Telethon grant GGP19148 to FM; University of Padova grant Prot. BIRD187130 to FM; Foundation for Ichthyosis and Related Skin Types (FIRST) to TWW; National Institutes of Health grant EY 026911 to TWW.
DOI: 10.2908/t2020_rd310
title: Energy productivity
title: Productivité de l'énergie
title: Energieproduktivität

description: Der Indikator ergibt sich aus der Division des Bruttoinlandsprodukts (BIP) durch den Brutto verfügbare Energie für ein bestimmtes Kalenderjahr. Er misst die Produktivität des Energieverbrauchs und liefert ein Bild über den Grad der Abkopplung des Energieverbrauchs vom Wachstum des BIP. Für die Berechnung der Energieproduktivität nutzt Eurostat die BIP Daten entweder in der Einheit Million Euro in verketteten Volumen für das Berichtsjahr 2010 (zu den im Jahr 2010 geltenden Wechselkursen) oder in der Einheit Million Euro in Kaufkraftparitäten (KKP). Die Einheit Euro in verketteten Volumen erlaubt die Beobachtung von Trends in der Energieproduktivität über einen längeren Zeitraum in einer einzelnen geographischen Zone, wobei die Einheit KKP den Vergleich mehrerer Länder im gleichen Jahr möglich macht. Die Brutto verfügbare Energie errechnet sich als: Primärproduktion + Wiedergewinnung & wiederverwertete Produkte + Einfuhren - Ausfuhren + Bestandsveränderungen.
description: The indicator results from the division of the gross domestic product (GDP) by the gross available energy for a given calendar year. It measures the productivity of energy consumption and provides a picture of the degree of decoupling of energy use from growth in GDP. For the calculation of energy productivity Eurostat uses the GDP either in the unit of million euro in chain-linked volumes to the reference year 2010 (at 2010 exchange rates) or in the unit million purchasing power standards (PPS). The unit euro in chain linked volumes allows observing the energy productivity trends over time in a single geographic area, whereas the unit PPS allows comparison between countries for the same year. The gross available energy is calculated as: Primary production + Recovered & recycled products + Imports – Exports + Stock changes.
description: L’indicateur résulte de la division du produit intérieur brut (PIB) par l’énergie disponible brute pour une année civile donnée. Il mesure la productivité de la consommation d’énergie et fournit une indication du degré de découplage entre la consommation d’énergie et la croissance du PIB. Pour le calcul de la productivité énergétique Eurostat utilise le PIB soit dans l’unité de euros de volume chaînées pour l’année de référence 2010 (au taux de change de 2010) ou dans l’unité exprimé en millions de standard de pouvoir d’achat (SPA). L’unité euros en volumes chaînés permet d'observer les tendances de la productivité énergétique au fil du temps dans une seule zone géographique, tandis que l’unité SPA permet d’établir une comparaison entre les pays pour la même année. L'énergie disponible brute est calculée comme : Production primaire + Produits récupérés & recyclés + Importations - Exportations + Variation de stock.
DOI: 10.5281/zenodo.7544586
title: Dataset related to the article "Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide"

description: This record contains raw data related to the article "Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide" Abstract <strong>Background: </strong>Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca<sup>2+</sup>) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca<sup>2+</sup> oscillations and the Ca<sup>2+</sup> toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. <strong>Methods and results: </strong>ACM C-MSC show enhanced spontaneous Ca<sup>2+</sup> oscillations and concomitant increased Ca<sup>2+</sup>/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca<sup>2+</sup> Entry (SOCE), which leads to enhanced Ca<sup>2+</sup> release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca<sup>2+</sup> handling machinery or CaMKII activity, we demonstrated a causative link between Ca<sup>2+</sup> oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca<sup>2+</sup> signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca<sup>2+</sup> oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. <strong>Conclusions: </strong>Altogether, our results extend the knowledge of Ca<sup>2+</sup> dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.
description: Funding Ricerca Corrente from Italian Ministry of Health to Centro Cardiologico Monzino IRCCS (2020, 2021). Fondazione di Comunità Milano e Fondo Fondazione Giacomo Ponzone (2021) to Elena Sommariva and Angela Serena Maione.
DOI: 10.5281/zenodo.7544587
title: Dataset related to the article "Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide"

description: This record contains raw data related to the article "Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide" Abstract <strong>Background: </strong>Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca<sup>2+</sup>) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca<sup>2+</sup> oscillations and the Ca<sup>2+</sup> toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. <strong>Methods and results: </strong>ACM C-MSC show enhanced spontaneous Ca<sup>2+</sup> oscillations and concomitant increased Ca<sup>2+</sup>/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca<sup>2+</sup> Entry (SOCE), which leads to enhanced Ca<sup>2+</sup> release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca<sup>2+</sup> handling machinery or CaMKII activity, we demonstrated a causative link between Ca<sup>2+</sup> oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca<sup>2+</sup> signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca<sup>2+</sup> oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. <strong>Conclusions: </strong>Altogether, our results extend the knowledge of Ca<sup>2+</sup> dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.
description: Funding Ricerca Corrente from Italian Ministry of Health to Centro Cardiologico Monzino IRCCS (2020, 2021). Fondazione di Comunità Milano e Fondo Fondazione Giacomo Ponzone (2021) to Elena Sommariva and Angela Serena Maione.