cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.7093721
title: The isotopic evolution of the Kohistan Ladakh arc from subduction initiation to continent arc collision

description: Data and Concordia plots of data samples.
DOI: 10.6084/m9.figshare.7093718
title: The isotopic evolution of the Kohistan Ladakh arc from subduction initiation to continent arc collision

description: Data and Concordia plots of data samples.
DOI: 10.6084/m9.figshare.7093715
title: The isotopic evolution of the Kohistan Ladakh arc from subduction initiation to continent arc collision

description: Data and Concordia plots of data samples.
DOI: 10.6084/m9.figshare.7093652
title: Supplementary Material for: Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures

description: <b><i>Background/Aims:</i></b> Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been clarified. This study aimed to explore the effect and mechanism of gentiopicroside in cholestasis induced by alpha-naphthylisothiocyanate. <b><i>Methods:</i></b> We performed isobaric tags for relative and absolute quantification-based quantitative proteomics and metabolomics using liquid chromatography quadruple time-of-fight mass spectrometry and identified the expression of 73 metabolites and 84 proteins associated with cholestasis-related dysfunctions in the metabolism of bile acids, fatty acids, and glycerophospholipids. <b><i>Results:</i></b> Integrated analyses of proteomic and metabonomic studies showed altered pathways in cholestasis-induced liver injury involving increased activity of farnesoid X receptor/retinoid X receptor, bile acid biosynthesis, and peroxisome proliferator-activated receptor-α/retinoid X receptor-α. Gentiopicroside could reverse these metabolite, protein, and blood biochemical indices, as well as alleviate liver damage. The progressive changes in the proteins and genes may be correlated with cholestasis and were confirmed by western blot and quantitative realtime polymerase chain reaction. <b><i>Conclusion:</i></b> Gentiopicroside could be used to protect the liver in the presence of cholestasis.
DOI: 10.6084/m9.figshare.7093652.v1
title: Supplementary Material for: Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures

description: <b><i>Background/Aims:</i></b> Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been clarified. This study aimed to explore the effect and mechanism of gentiopicroside in cholestasis induced by alpha-naphthylisothiocyanate. <b><i>Methods:</i></b> We performed isobaric tags for relative and absolute quantification-based quantitative proteomics and metabolomics using liquid chromatography quadruple time-of-fight mass spectrometry and identified the expression of 73 metabolites and 84 proteins associated with cholestasis-related dysfunctions in the metabolism of bile acids, fatty acids, and glycerophospholipids. <b><i>Results:</i></b> Integrated analyses of proteomic and metabonomic studies showed altered pathways in cholestasis-induced liver injury involving increased activity of farnesoid X receptor/retinoid X receptor, bile acid biosynthesis, and peroxisome proliferator-activated receptor-α/retinoid X receptor-α. Gentiopicroside could reverse these metabolite, protein, and blood biochemical indices, as well as alleviate liver damage. The progressive changes in the proteins and genes may be correlated with cholestasis and were confirmed by western blot and quantitative realtime polymerase chain reaction. <b><i>Conclusion:</i></b> Gentiopicroside could be used to protect the liver in the presence of cholestasis.
DOI: 10.6084/m9.figshare.7093643
title: Data Set 3.xlsx

description: Collection of 5 Italian and 21 Spanish subjects with a LHON-causing mutation in heteroplasmy and 90 control subjects.
DOI: 10.6084/m9.figshare.7093646
title: Arlequin input file

description: Microsatellite data input file for Arlequin (Fst, AMOVA, Mantel Test)
DOI: 10.6084/m9.figshare.7093640
title: S wave attenuation at Imperial College site in UK

description: Porosity 1: 0.6Porosity 2: 0.3Porosity 3: 0.076
DOI: 10.6084/m9.figshare.7093640.v1
title: S wave attenuation at Imperial College site in UK

description: Porosity 1: 0.6Porosity 2: 0.3Porosity 3: 0.076
DOI: 10.6084/m9.figshare.7093625
title: Understanding edge angle variability and morpho-functional design of Late Middle Palaeolithic Keilmesser assemblages

description: <b>Understanding edge angle variability and morpho-functional design of Late Middle Palaeolithic Keilmesser assemblages </b> The Late Middle Palaeolithic <i>‘Keilmessergruppen’<i> (KMG) assemblages of Central and Eastern Europe are characterised by asymmetrically backed tools. Most of these items are bifacially worked, produced in a highly standardised mode and display characteristic wedge-(‘Keil’)-shaped sections. Due to their single working edge these tools have been interpreted as knives. In Keilmesser, long reduction sequences have repeatedly been documented (Jöris 2006), allowing for detailed morpho-technological reconstructions of their use-life histories, including repetitive phases of production, usage, re-sharpening and re-use. </i></i><i><i> </i></i> Due to the aforementioned characteristics, Keilmesser provide a unique archive for tracing certain features of late Neanderthal behaviour. These may range from understanding tool dedication, function and its underlying design and production concept, learning strategies, technical innovations, the transmission of ideas and knowledge to the formation of late Neanderthal regional traditions. At some KMG sites, Keilmesser frequently display the application of tranchet blows that sharpens the working edge at the tip of the tool through removing the lateral edge. The use of this method (within KMG contexts called <i>‘Prądnik method’<i>) reflects intentional design and puts special emphasize on the edge angle near the tool-tip. This observation implies a certain hierarchization of different parts of the working edge within the same tools that might be related to its use-life. Various interpretations consider the application of this method as e.g. tool-finishing or as maintenance, sharpening or optimization of an existing working edge. Nevertheless, which effect it has remains so far speculative. </i></i><i><i> </i></i> In order to address these aspects, here we apply a particular methodology, which includes - among others - 3D scanning to acquire the measurements and for morphometric analyses (Grosman <i>et al.<i> 2008). To obtain a more distinct picture of the working edge a sample of Keilmesser made of silicified schist is used as a case study. Our study aims at an improved understanding of how the working edge of a Keilmesser was actually designed and which effects specific edge angles might have had. Targeted objective and quantitative use-wear analyses (Marreiros <i>et al.<i> 2015) on the material will supplement this study. </i></i></i></i><i><i><i> </i></i></i> By including controlled experiments, 3D morphometric data analysis as well as macro and micro use-wear analysis, this approach will provide new data that aim to test the given interpretations of these asymmetrically backed tools from the Late Middle Palaeolithic. Hence, this research will contribute to a more holistic understanding of the concepts underlying tool design, function and its realisation.
DOI: 10.6084/m9.figshare.7093619
title: Data Set 2.xlsx

description: Collection of 52 Spanish subjects with a LHON-causing mutation in homoplasmy and 28 control subjects.<br>
DOI: 10.6084/m9.figshare.7093595
title: Grouplens Datasets (ml-1m, ml-100K, and hetrec2011-movielens-2k-v2)

description: GroupLens is a research lab in the Department of Computer Science and Engineering at the University of Minnesota, Twin Cities specializing in recommender systems, online communities, mobile and ubiquitous technologies, digital libraries, and local geographic information systems.
DOI: 10.6084/m9.figshare.7093595.v1
title: Grouplens Datasets (ml-1m, ml-100K, and hetrec2011-movielens-2k-v2)

description: GroupLens is a research lab in the Department of Computer Science and Engineering at the University of Minnesota, Twin Cities specializing in recommender systems, online communities, mobile and ubiquitous technologies, digital libraries, and local geographic information systems.
DOI: 10.6084/m9.figshare.7093580
title: Supplementary Material for: Administration of Thyrotropin-Releasing Hormone in the Hypothalamic Paraventricular Nucleus of Male Rats Mimics the Metabolic Cold Defense Response

description: <b><i>Background:</i></b> Cold exposure increases thyrotropin-releasing hormone (TRH) expression primarily in the hypothalamic paraventricular nucleus (PVN). The PVN is a well-known hypothalamic hub in the control of energy metabolism. TRH terminals and receptors are found on PVN neurons. We hypothesized that TRH release in the PVN plays an important role in the control of thermogenesis and energy mobilization during cold exposure. <b><i>Methods:</i></b> Male Wistar rats were exposed to a cold environment (4°C) or TRH retrodialysis in the PVN for 2 h. We compared the effects of cold exposure and TRH administration in the PVN on plasma glucose, corticosterone, and thyroid hormone concentrations, body temperature, locomotor activity, as well as metabolic gene expression in the liver and brown adipose tissue. <b><i>Results:</i></b> Cold exposure increased body temperature, locomotor activity, and plasma corticosterone concentrations, but blood glucose concentrations were similar to that of room temperature control animals. TRH administration in the PVN also promptly increased body temperature, locomotor activity and plasma corticosterone concentrations. However, TRH administration in the PVN markedly increased blood glucose concentrations and endogenous glucose production (EGP) compared to saline controls. Selective hepatic sympathetic or parasympathetic denervation reduced the TRH-induced increase in glucose concentrations and EGP. Gene expression data indicated increased gluconeogenesis in liver and lipolysis in brown adipose tissue, both after cold exposure and TRH administration. <b><i>Conclusions:</i></b> We conclude that TRH administration in the rat PVN largely mimics the metabolic and behavioral changes induced by cold exposure indicating a potential link between TRH release in the PVN and cold defense.
DOI: 10.6084/m9.figshare.7093562
title: Supplementary Material for: Chronic Maternal Hyperoxygenation and Effect on Cerebral and Placental Vasoregulation and Neurodevelopment in Fetuses with Left Heart Hypoplasia

description: <b><i>Introduction:</i></b> In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls. <b><i>Material and Methods:</i></b> Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks’ gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared. <b><i>Results:</i></b> There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (<i>z</i>-score change –0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, <i>p</i> = 0.02). At 6 months postnatal age, the mean head circumference <i>z</i>-score in the CMH group was smaller than that of controls (–0.20 ± 0.58 vs. +0.85 ± 1.11, <i>p</i> = 0.048). There were no differences in neurodevelopmental testing at 6 and 12 months. <b><i>Discussion:</i></b> In this pilot study, relatively diminished fetal BPD growth and smaller infant head circumference <i>z</i>-scores at 6 months were noted with in utero CMH exposure.
DOI: 10.6084/m9.figshare.7093556
title: Target-based drug discovery through inversion of quantitative structure-drug-property relationships and molecular simulation: CA IX-sulphonamide complexes

description: In this work, a target-based drug screening method is proposed exploiting the synergy effect of ligand-based and structure-based computer-assisted drug design. The new method provides great flexibility in drug design and drug candidates with considerably lower risk in an efficient manner. As a model system, 45 sulphonamides (33 training, 12 testing ligands) in complex with carbonic anhydrase IX were used for development of quantitative structure-activity-lipophilicity (property)-relationships (QSPRs). For each ligand, nearly 5,000 molecular descriptors were calculated, while lipophilicity (log<i>k</i><sub>w</sub>) and inhibitory activity (log<i>K</i><sub>i</sub>) were used as drug properties. Genetic algorithm-partial least squares (GA-PLS) provided a QSPR model with high prediction capability employing only seven molecular descriptors. As a proof-of-concept, optimal drug structure was obtained by inverting the model with respect to reference drug properties. 3509 ligands were ranked accordingly. Top 10 ligands were further validated through molecular docking. Large-scale MD simulations were performed to test the stability of structures of selected ligands obtained through docking complemented with biophysical experiments.
DOI: 10.6084/m9.figshare.7093559
title: Data Set 1.xlsx

description: Collection of clinical and molecular data of 46 Italian subjects with a LHON-causing mutation in homoplasmy and 90 control subjects.<br>
DOI: 10.6084/m9.figshare.7093556.v1
title: Target-based drug discovery through inversion of quantitative structure-drug-property relationships and molecular simulation: CA IX-sulphonamide complexes

description: In this work, a target-based drug screening method is proposed exploiting the synergy effect of ligand-based and structure-based computer-assisted drug design. The new method provides great flexibility in drug design and drug candidates with considerably lower risk in an efficient manner. As a model system, 45 sulphonamides (33 training, 12 testing ligands) in complex with carbonic anhydrase IX were used for development of quantitative structure-activity-lipophilicity (property)-relationships (QSPRs). For each ligand, nearly 5,000 molecular descriptors were calculated, while lipophilicity (log<i>k</i><sub>w</sub>) and inhibitory activity (log<i>K</i><sub>i</sub>) were used as drug properties. Genetic algorithm-partial least squares (GA-PLS) provided a QSPR model with high prediction capability employing only seven molecular descriptors. As a proof-of-concept, optimal drug structure was obtained by inverting the model with respect to reference drug properties. 3509 ligands were ranked accordingly. Top 10 ligands were further validated through molecular docking. Large-scale MD simulations were performed to test the stability of structures of selected ligands obtained through docking complemented with biophysical experiments.
DOI: 10.6084/m9.figshare.7093526
title: Supplementary Material for: <b><i>In Silico</i></b> Identification and <b><i>in Vitro</i></b> Analysis of B and T-Cell Epitopes of the Black Turtle Bean (<b><i>Phaseolus Vulgaris L</i></b>.) Lectin

description: <b><i>Background/Aims:</i></b> The incidence of lectin allergic disease is increasing in recent decades, and definitive treatment is still lacking. Identification of B and T-cell epitopes of allergen will be useful in understanding the allergen antibody responses as well as aiding in the development of new diagnostics and therapy regimens for lectin poisoning. In the current study, we mainly addressed these questions. <b><i>Methods:</i></b> Three-dimensional structure of the lectin from black turtle bean (<i>Phaseolus vulgaris L.</i>) was modeled using the structural template of Phytohemagglutinin from <i>P. vulgaris</i> (PHA-E, PDB ID: 3wcs.1.A) with high identity. The B and T-cell epitopes were screened and identified by immunoinformatics and subsequently validated by ELISA, lymphocyte proliferation and cytokine profile analyses. <b><i>Results:</i></b> Seven potential B-cell epitopes (B1 to B7) were identified by sequence and structure based methods, while three T-cell epitopes (T1 to T3) were identified by the predictions of binding score and inhibitory concentration. The epitope peptides were synthesized. Significant IgE binding capability was found in B-cell epitopes (B2, B5, B6 and B7) and T2 (a cryptic B-cell epitope). T1 and T2 induced significant lymphoproliferation, and the release of IL-4 and IL-5 cytokine confirmed the validity of T-cell epitope prediction. Abundant hydrophobic amino acids were found in B-cell epitope and T-cell epitope regions by amino acid analysis. Positively charged amino acids, such as His residue, might be more favored for B-cell epitope. <b><i>Conclusion:</i></b> The present approach can be applied for the identification of epitopes in novel allergen proteins and thus for designing diagnostics and therapies in lectin allergy.
DOI: 10.6084/m9.figshare.7093463
title: Characterization of multi-locus imprinting disturbances and underlying genetic defects in patients with chromosome 11p15.5 related imprinting disorders

description: The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in <i>NLRP2</i>, affecting ADP binding and protein activity, and one in <i>ZFP42</i>, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. <i>In silico</i> protein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of <i>ZFP42</i> variants in MLID development and confirmed <i>NLRP2</i> as causative locus in BWS-MLID.
DOI: 10.6084/m9.figshare.7093472
title: <i>Streptococcus suis</i> synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

description: <i>Streptococcus suis</i> is a major porcine bacterial pathogen and emerging zoonotic agent. <i>S. suis</i> 5ʹ-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions <i>in vitro</i> and it is an important virulence factor. Here, we show that <i>S. suis</i> 5ʹ-nucleotidase not only enables producing 2ʹ-deoxyadenosine from 2ʹ-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis <i>in vitro</i>, but also synthesizes both 2ʹ-deoxyadenosine and adenosine in mouse blood <i>in vivo</i> by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2ʹ-deoxyadenosine by 5ʹ-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The <i>in vivo</i> infection experiment showed that 2ʹ-deoxyadenosine synthesized by 5ʹ-nucleotidase caused monocytopenia in mouse blood. The <i>in vivo</i> transcriptome analysis in mouse blood showed the inhibitory effect of 5ʹ-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that <i>S. suis</i> synthesizes 2ʹ-deoxyadenosine and adenosine by 5ʹ-nucleotidase to dampen host immune responses, which represents a new mechanism of <i>S. suis</i> pathogenesis.
DOI: 10.6084/m9.figshare.7093472.v1
title: <i>Streptococcus suis</i> synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

description: <i>Streptococcus suis</i> is a major porcine bacterial pathogen and emerging zoonotic agent. <i>S. suis</i> 5ʹ-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions <i>in vitro</i> and it is an important virulence factor. Here, we show that <i>S. suis</i> 5ʹ-nucleotidase not only enables producing 2ʹ-deoxyadenosine from 2ʹ-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis <i>in vitro</i>, but also synthesizes both 2ʹ-deoxyadenosine and adenosine in mouse blood <i>in vivo</i> by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2ʹ-deoxyadenosine by 5ʹ-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The <i>in vivo</i> infection experiment showed that 2ʹ-deoxyadenosine synthesized by 5ʹ-nucleotidase caused monocytopenia in mouse blood. The <i>in vivo</i> transcriptome analysis in mouse blood showed the inhibitory effect of 5ʹ-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that <i>S. suis</i> synthesizes 2ʹ-deoxyadenosine and adenosine by 5ʹ-nucleotidase to dampen host immune responses, which represents a new mechanism of <i>S. suis</i> pathogenesis.