cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13365160.v1
title: Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling

description: Colon cancer is the commonest cancer worldwide. α-Hederin is a monodesmosidic triterpenoid saponin possessing diverse pharmacological activities. The running experiment was designed to test the chemopreventive activity of α-hederin when used as an adjuvant to carboplatin in an experimental model of mouse colon hyperplasia induced by 1,2-dimethylhydrazine (DMH). Fifty male Swiss albino mice were classified into five groups: group (I): saline group, group (II): DMH-induced colon hyperplasia control group, group (III): DMH + carboplatin (5 mg/kg) group, group (IV): DMH + α-hederin (80 mg/kg) group, and group (V): DMH + carboplatin (5 mg/kg)+α-hederin (80 mg/kg) group. Analyzing of colonic tissue indicated that the disease control group showed higher colon levels of phospho-PI3K to total-PI3K, phospho-AKT to total-AKT and cyclin D1 concurrent with lower phospho-JNK/total JNK ratio and caspase 3. However, treatment with α-hederin, in combination with carboplatin, favorably ameliorated phosphorylation of PI3K/AKT/JNK proteins, increased colon caspase 3 and downregulated cyclin D1. Microscopically, α-hederin, in combination with carboplatin, produced the most reduction in the histologic hyperplasia score, enhanced the goblet cell survival in periodic acid Schiff staining and reduced proliferation (Ki-67 immunostaining) in the current colon hyperplasia model. Collectively, the current study highlighted for the first time that using α-hederin as an adjuvant to carboplatin enhanced its chemopreventive activity, improved JNK signaling and increased apoptosis. Hence, further studies are warranted to test α-hederin as a promising candidate with chemotherapeutic agents in treating colon cancer.
DOI: 10.6084/m9.figshare.13365160
title: Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling

description: Colon cancer is the commonest cancer worldwide. α-Hederin is a monodesmosidic triterpenoid saponin possessing diverse pharmacological activities. The running experiment was designed to test the chemopreventive activity of α-hederin when used as an adjuvant to carboplatin in an experimental model of mouse colon hyperplasia induced by 1,2-dimethylhydrazine (DMH). Fifty male Swiss albino mice were classified into five groups: group (I): saline group, group (II): DMH-induced colon hyperplasia control group, group (III): DMH + carboplatin (5 mg/kg) group, group (IV): DMH + α-hederin (80 mg/kg) group, and group (V): DMH + carboplatin (5 mg/kg)+α-hederin (80 mg/kg) group. Analyzing of colonic tissue indicated that the disease control group showed higher colon levels of phospho-PI3K to total-PI3K, phospho-AKT to total-AKT and cyclin D1 concurrent with lower phospho-JNK/total JNK ratio and caspase 3. However, treatment with α-hederin, in combination with carboplatin, favorably ameliorated phosphorylation of PI3K/AKT/JNK proteins, increased colon caspase 3 and downregulated cyclin D1. Microscopically, α-hederin, in combination with carboplatin, produced the most reduction in the histologic hyperplasia score, enhanced the goblet cell survival in periodic acid Schiff staining and reduced proliferation (Ki-67 immunostaining) in the current colon hyperplasia model. Collectively, the current study highlighted for the first time that using α-hederin as an adjuvant to carboplatin enhanced its chemopreventive activity, improved JNK signaling and increased apoptosis. Hence, further studies are warranted to test α-hederin as a promising candidate with chemotherapeutic agents in treating colon cancer.
DOI: 10.6084/m9.figshare.12845213
title: Ready to go 3D? A semi-automated protocol for microwell spheroid arrays to increase scalability and throughput of 3D cell culture testing

description: 3-dimensional (3D) cell cultures are being increasingly recognized as physiologically more relevant <i>in vitro</i> models than traditional monolayer cultures, because they better mimic <i>in vivo</i>-like microenvironment, cell-cell and cell-extracellular matrix interactions. Nevertheless, the broader use of 3D models might be limited by requirements for special consumables, equipment, or skills for 3D cell cultures, and by their limited throughput and scalability. In this study, we optimized and adapted a commercially available agarose-micromolding technique to produce scaffold-free spheroid cultures. Brightfield microscopy was used for routine nondestructive and noninvasive evaluation of spheroid formation and growth. The workflow is compatible with manual, as well as high speed automated microscopic image acquisition, and it is supplemented with an in-house developed macro ‘Spheroid_Finder’ for open source software Fiji to facilitate rapid automated image analysis. This protocol was used to characterize and quantify spheroid formation and growth of two different hepatic cell lines, hTERT immortalized, but non-cancerous, adult human liver stem cell line HL1-hT1, and human hepatocellular carcinoma cell line HepG2, as well as their responses to a model antiproliferative and cytotoxic agent, 5-fluorouracil. The complete protocol provides a simple and ready-to-use solution to initiate scaffold-free spheroid cultures in any laboratory with standard equipment for mammalian <i>in vitro</i> cell culture work. Thus, it allows to increase throughput and scale of spheroid culture experiments, which can be greatly utilized in different areas of biomedical, pharmaceutical and toxicological research.
DOI: 10.6084/m9.figshare.12845213.v2
title: Ready to go 3D? A semi-automated protocol for microwell spheroid arrays to increase scalability and throughput of 3D cell culture testing

description: 3-dimensional (3D) cell cultures are being increasingly recognized as physiologically more relevant <i>in vitro</i> models than traditional monolayer cultures, because they better mimic <i>in vivo</i>-like microenvironment, cell-cell and cell-extracellular matrix interactions. Nevertheless, the broader use of 3D models might be limited by requirements for special consumables, equipment, or skills for 3D cell cultures, and by their limited throughput and scalability. In this study, we optimized and adapted a commercially available agarose-micromolding technique to produce scaffold-free spheroid cultures. Brightfield microscopy was used for routine nondestructive and noninvasive evaluation of spheroid formation and growth. The workflow is compatible with manual, as well as high speed automated microscopic image acquisition, and it is supplemented with an in-house developed macro ‘Spheroid_Finder’ for open source software Fiji to facilitate rapid automated image analysis. This protocol was used to characterize and quantify spheroid formation and growth of two different hepatic cell lines, hTERT immortalized, but non-cancerous, adult human liver stem cell line HL1-hT1, and human hepatocellular carcinoma cell line HepG2, as well as their responses to a model antiproliferative and cytotoxic agent, 5-fluorouracil. The complete protocol provides a simple and ready-to-use solution to initiate scaffold-free spheroid cultures in any laboratory with standard equipment for mammalian <i>in vitro</i> cell culture work. Thus, it allows to increase throughput and scale of spheroid culture experiments, which can be greatly utilized in different areas of biomedical, pharmaceutical and toxicological research.
DOI: 10.6084/m9.figshare.12845207.v2
title: ‘Ideal correlations’ for the predictive toxicity to <i>Tetrahymena pyriformis</i>

description: Predictive models for toxicity to <i>Tetrahymena pyriformis</i> are an important component of natural sciences. The present study aims to build up a predictive model for the endpoint using the so-called index of ideality of correlation (<i>IIC</i>). Besides, the comparison of the predictive potential of these models with the predictive potential of models suggested in the literature is the task of the present study. The Monte Carlo technique is a tool to build up the predictive model applied in this study. The molecular structure is represented via a simplified molecular input-line entry system (SMILES). The <i>IIC</i> is a statistical characteristic sensitive to both the correlation coefficient and mean absolute error. Applying of the <i>IIC</i> to build up quantitative structure–activity relationships (QSARs) for the toxicity to <i>Tetrahymena pyriformis</i> improves the predictive potential of those models for random splits into the training set and the validation set. The calculation was carried out with CORAL software (http://www.insilico.eu/coral). The statistical quality of the suggested models is incredibly good for the external validation set, but the statistical quality of the models for the training set is modest. This is the paradox of ideal correlation, which is obtained with applying the <i>IIC.</i> The Monte Carlo technique is a convenient and reliable way to build up a predictive model for toxicity to <i>Tetrahymena pyriformis</i>. The <i>IIC</i> is a useful statistical criterion for building up predictive models as well as for the assessment of their statistical quality.
DOI: 10.6084/m9.figshare.12845207
title: ‘Ideal correlations’ for the predictive toxicity to <i>Tetrahymena pyriformis</i>

description: Predictive models for toxicity to <i>Tetrahymena pyriformis</i> are an important component of natural sciences. The present study aims to build up a predictive model for the endpoint using the so-called index of ideality of correlation (<i>IIC</i>). Besides, the comparison of the predictive potential of these models with the predictive potential of models suggested in the literature is the task of the present study. The Monte Carlo technique is a tool to build up the predictive model applied in this study. The molecular structure is represented via a simplified molecular input-line entry system (SMILES). The <i>IIC</i> is a statistical characteristic sensitive to both the correlation coefficient and mean absolute error. Applying of the <i>IIC</i> to build up quantitative structure–activity relationships (QSARs) for the toxicity to <i>Tetrahymena pyriformis</i> improves the predictive potential of those models for random splits into the training set and the validation set. The calculation was carried out with CORAL software (http://www.insilico.eu/coral). The statistical quality of the suggested models is incredibly good for the external validation set, but the statistical quality of the models for the training set is modest. This is the paradox of ideal correlation, which is obtained with applying the <i>IIC.</i> The Monte Carlo technique is a convenient and reliable way to build up a predictive model for toxicity to <i>Tetrahymena pyriformis</i>. The <i>IIC</i> is a useful statistical criterion for building up predictive models as well as for the assessment of their statistical quality.
DOI: 10.6084/m9.figshare.13713080.v1
title: Using mechanistic information to support evidence integration and synthesis: a case study with inhaled formaldehyde and leukemia

description: Formaldehyde is one of the most comprehensively studied chemicals, with over 30 years of research focused on understanding the development of cancer following inhalation. The causal conclusions regarding the potential for leukemia are largely based on the epidemiological literature, with little consideration of cancer bioassays, dosimetry studies, and mechanistic research, which challenge the biological plausibility of the disease. Recent reanalyzes of the epidemiological literature have also raised significant questions related to the purported associations between formaldehyde and leukemia. Because of this, considerable scientific debate and uncertainty remain on whether there is a causal association between formaldehyde inhalation exposure and leukemia. Further complexity in evaluating this association is related to the endogenous production of formaldehyde. Multiple modes of action (MOA) have been postulated for the development of leukemia following formaldehyde inhalation that includes unsupported hypotheses of direct or indirect toxicity to the target cell population. Herein, the available evidence relevant to evaluating the postulated MOAs for leukemia following formaldehyde inhalation exposure is organized in the IPCS MOA Framework. The integration of all the available evidence clearly highlights the limited amount of data that support any of the postulated MOAs and demonstrates a significant amount of research supporting the null hypothesis that there is no causal association between formaldehyde inhalation exposure and leukemia. These analyses result in a lack of confidence in any of the postulated MOAs, increasing confidence in the conclusion that there is a lack of biological plausibility for a causal association between formaldehyde inhalation exposure and leukemia.
DOI: 10.6084/m9.figshare.13713080
title: Using mechanistic information to support evidence integration and synthesis: a case study with inhaled formaldehyde and leukemia

description: Formaldehyde is one of the most comprehensively studied chemicals, with over 30 years of research focused on understanding the development of cancer following inhalation. The causal conclusions regarding the potential for leukemia are largely based on the epidemiological literature, with little consideration of cancer bioassays, dosimetry studies, and mechanistic research, which challenge the biological plausibility of the disease. Recent reanalyzes of the epidemiological literature have also raised significant questions related to the purported associations between formaldehyde and leukemia. Because of this, considerable scientific debate and uncertainty remain on whether there is a causal association between formaldehyde inhalation exposure and leukemia. Further complexity in evaluating this association is related to the endogenous production of formaldehyde. Multiple modes of action (MOA) have been postulated for the development of leukemia following formaldehyde inhalation that includes unsupported hypotheses of direct or indirect toxicity to the target cell population. Herein, the available evidence relevant to evaluating the postulated MOAs for leukemia following formaldehyde inhalation exposure is organized in the IPCS MOA Framework. The integration of all the available evidence clearly highlights the limited amount of data that support any of the postulated MOAs and demonstrates a significant amount of research supporting the null hypothesis that there is no causal association between formaldehyde inhalation exposure and leukemia. These analyses result in a lack of confidence in any of the postulated MOAs, increasing confidence in the conclusion that there is a lack of biological plausibility for a causal association between formaldehyde inhalation exposure and leukemia.
DOI: 10.5517/ccdc.csd.cc25x2gn
title: CCDC 2022981: Experimental Crystal Structure Determination

description: Related Article: Xiao‐Han Yang, Shao‐Bin Dou, Qian Zhang, Rui‐Lian Yang, Zhuo Liu, Gao‐Nan Li, Zhi‐Gang Niu|2021|Z.Anorg.Allg.Chem.|647|1038|doi:10.1002/zaac.202000298
DOI: 10.5517/ccdc.csd.cc25xgyj
title: CCDC 2023368: Experimental Crystal Structure Determination

description: Related Article: Dan Qin, Hai-Liang Pei, Chong-An Chen, Guo-Yu Yang|2021|Inorg.Chem.|60|6576|doi:10.1021/acs.inorgchem.1c00384
DOI: 10.5517/ccdc.csd.cc25xh2p
title: CCDC 2023372: Experimental Crystal Structure Determination

description: Related Article: Dan Qin, Hai-Liang Pei, Chong-An Chen, Guo-Yu Yang|2021|Inorg.Chem.|60|6576|doi:10.1021/acs.inorgchem.1c00384
DOI: 10.5517/ccdc.csd.ccr7201
title: CCDC 691982: Experimental Crystal Structure Determination

description: Related Article: Konstantin Karaghiosoff, Thomas M. Klapötke, Thomas Kunz, Peter Mayer, Wolfgang Beck|2021|Z.Anorg.Allg.Chem.|647|943|doi:10.1002/zaac.202000445
DOI: 10.5517/ccdc.csd.ccr7212
title: CCDC 691983: Experimental Crystal Structure Determination

description: Related Article: Konstantin Karaghiosoff, Thomas M. Klapötke, Thomas Kunz, Peter Mayer, Wolfgang Beck|2021|Z.Anorg.Allg.Chem.|647|943|doi:10.1002/zaac.202000445
DOI: 10.5517/ccdc.csd.ccr7223
title: CCDC 691984: Experimental Crystal Structure Determination

description: Related Article: Konstantin Karaghiosoff, Thomas M. Klapötke, Thomas Kunz, Peter Mayer, Wolfgang Beck|2021|Z.Anorg.Allg.Chem.|647|943|doi:10.1002/zaac.202000445
DOI: 10.5517/ccdc.csd.ccr7234
title: CCDC 691985: Experimental Crystal Structure Determination

description: Related Article: Konstantin Karaghiosoff, Thomas M. Klapötke, Thomas Kunz, Peter Mayer, Wolfgang Beck|2021|Z.Anorg.Allg.Chem.|647|943|doi:10.1002/zaac.202000445
DOI: 10.5517/ccdc.csd.cc26py3z
title: CCDC 2046871: Experimental Crystal Structure Determination

description: Related Article: Pierre Milcendeau, Zhenhao Zhang, Nicolas Glinsky-Olivier, Elsa van Elslande, Xavier Guinchard|2021|J.Org.Chem.|86|6406|doi:10.1021/acs.joc.1c00270
DOI: 10.5517/ccdc.csd.cc272tcj
title: CCDC 2058287: Experimental Crystal Structure Determination

description: Related Article: Hong Zhang, Alexander J. E. Novak, Cooper S. Jamieson, Xiao-Song Xue, Shuming Chen, Dirk Trauner, K. N. Houk|2021|J.Am.Chem.Soc.|143|6601|doi:10.1021/jacs.1c01856
DOI: 10.6084/m9.figshare.3761562.v1863
title: Online Labour Index: Measuring the Online Gig Economy for Policy and Research

description: Data repository for the data underlying the Online Labour Index. See http://ilabour.oii.ox.ac.uk online-labour-index/ for details.
DOI: 10.5519/qd.g1hqy5vv
title: Query on the Natural History Museum Data Portal (data.nhm.ac.uk) (8681 records)
DOI: 10.6084/m9.figshare.12601402
title: Diversifying selection detected in only a minority of xenobiotic-metabolizing <i>CYP1-3</i> genes among primate species

description: 1. Primates exhibit a high degree of among-species dietary diversity, which likely exposes them to varying levels of xenobiotic compounds. Here, we examined the evolution of primate <i>CYP1-3</i> gene families, and we classified the 15 <i>CYP1-3</i> gene subfamilies as either xenobiotic-metabolizing (XM) or endogenous-metabolizing (EM) based on sources in the P450 literature. 2. We predicted that XM P450s would show (1) greater variability in gene-copy number and (2) more evidence of diversifying selection and, especially on codons that encode the substrate-recognition sites (SRSs) for the final enzymes. 3. Counter to our first prediction, EM and XM P450s showed similar levels of variation in gene-copy number. We did find, however, that four XM P450 subfamilies (<i>CYP2C, CYP2D, CYP2E,</i> and <i>CYP3A</i>) showed evidence of diversifying selection while no EM subfamilies demonstrated any consistent signal of diversifying selection. Of these four, <i>CYP2C, CYP2D,</i> and <i>CYP3A</i> showed significant links between SRSs and diversifying selection. 4. These results reveal an amount of evolutionary dynamism that would not be expected when viewing P450 subfamilies along a simple binary EM/XM spectrum. We recommend that comparative studies of cytochrome P450 evolution should focus on the <i>CYP2C, CYP2D, CYP2E,</i> and <i>CYP3A</i> subfamilies.
DOI: 10.6084/m9.figshare.12601402.v1
title: Diversifying selection detected in only a minority of xenobiotic-metabolizing <i>CYP1-3</i> genes among primate species

description: 1. Primates exhibit a high degree of among-species dietary diversity, which likely exposes them to varying levels of xenobiotic compounds. Here, we examined the evolution of primate <i>CYP1-3</i> gene families, and we classified the 15 <i>CYP1-3</i> gene subfamilies as either xenobiotic-metabolizing (XM) or endogenous-metabolizing (EM) based on sources in the P450 literature. 2. We predicted that XM P450s would show (1) greater variability in gene-copy number and (2) more evidence of diversifying selection and, especially on codons that encode the substrate-recognition sites (SRSs) for the final enzymes. 3. Counter to our first prediction, EM and XM P450s showed similar levels of variation in gene-copy number. We did find, however, that four XM P450 subfamilies (<i>CYP2C, CYP2D, CYP2E,</i> and <i>CYP3A</i>) showed evidence of diversifying selection while no EM subfamilies demonstrated any consistent signal of diversifying selection. Of these four, <i>CYP2C, CYP2D,</i> and <i>CYP3A</i> showed significant links between SRSs and diversifying selection. 4. These results reveal an amount of evolutionary dynamism that would not be expected when viewing P450 subfamilies along a simple binary EM/XM spectrum. We recommend that comparative studies of cytochrome P450 evolution should focus on the <i>CYP2C, CYP2D, CYP2E,</i> and <i>CYP3A</i> subfamilies.
DOI: 10.6084/m9.figshare.7886671
title: Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes

description: Rett syndrome (RTT) is a rare disorder causing severe intellectual and physical disability. The cause is a mutation in the gene coding for the methyl-CpG binding protein 2 (MECP2), a multifunctional regulator protein. Purpose of the study was integration and investigation of multiple gene expression profiles in human cells with impaired <i>MECP2</i> gene to obtain a robust, data-driven insight in molecular disease mechanisms. Information about changed gene expression was extracted from five previously published studies, integrated and the resulting differentially expressed genes were analysed using overrepresentation analysis of biological pathways and gene ontology, and network analysis. We identified a set of genes, which are significantly changed not in all but several transcriptomics datasets and were not mentioned in the context of RTT before. We found that these genes are involved in several processes and molecular pathways known to be affected in RTT. Integrating transcription factors we identified a possible link how MECP2 regulates cytoskeleton organisation via MEF2C and CAPG. Integrative analysis of omics data and prior knowledge databases is a powerful approach to identify links between mutation and phenotype especially in rare disease research where little data is available.
DOI: 10.6084/m9.figshare.7547249
title: A positive association between a polymorphism in the <i>HTR2B</i> gene and cocaine-crack in a French Afro-Caribbean population

description: Cocaine dependence has a strong heritability component. The aim of this study was to investigate the putative association between the serotonin 2B receptor gene (<i>HTR2B</i>), crack use disorders and impulsivity. A French Afro-Caribbean male population of patients with crack use disorders (<i>n</i> = 80) was compared to healthy Afro-Caribbean male controls (<i>n</i> = 60). Comorbid ADHD and impulsivity were assessed. Five single nucleotide polymorphisms (SNPs) in the <i>HTR2B</i> gene were selected: rs643700, rs6736017, rs1549339, rs17586428 and rs3806545. These SNPs were chosen to include most of the linkage disequilibrium blocks in the <i>HTR2B</i> gene. The French translation of the Barratt Impulsivity Scale BIS-11 was used to evaluate impulsivity. Comorbid ADHD was diagnosed using the Wender Utah Rating Scale-25 item for Attention Deficit-Hyperactivity Disorder. We have observed a positive association between the rs6736017 polymorphism and crack use disorders in a French Afro-Caribbean male population. In our population, the risk effect of <i>HTR2B</i> rs6736017 appeared to be specific to individuals with crack use disorders rather than being driven by impulsivity or ADHD alone.