cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120620
title: Supplementary Material for: M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

description: M1 protein contributes to Group A <i>Streptococcus</i> (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance to the human cathelicidin antimicrobial peptide LL-37, an important effector of bacterial killing within such phagocyte extracellular traps. Studies with purified recombinant protein fragments mapped the inhibition of cathelicidin killing to the M1 hypervariable N-terminal domain. A survey of GAS clinical isolates found that strains from patients with necrotizing fasciitis or toxic shock syndrome were significantly more likely to be resistant to cathelicidin than GAS M types not associated with invasive disease; M1 isolates were uniformly resistant. We conclude increased resistance to host cathelicidin and killing within phagocyte extracellular traps contribute to the propensity of M1 GAS strains to produce invasive infections.
DOI: 10.6084/m9.figshare.5120626.v1
title: Supplementary Material for: Mouse Neutrophil Extracellular Traps in Microbial Infections

description: Neutrophil extracellular traps (NETs) play an important role in innate immunity to microbial infections. NETs have been described in several species, but the molecular details of NET formation and their role in infection has not been addressed, partly because we lack optimal experimental models. Here we describe tools to investigate NET formation in neutrophils isolated from mice. Upon in vitro stimulation of wild-type mouse neutrophils with PMA, we analyzed 3 important steps in the process of NET formation: reactive oxygen species (ROS) production, NET cell death and NET release. As expected, neutrophils from NADPH oxidase-deficient mice failed to produce ROS and did not die nor release NETs upon stimulation. We found that neutrophils from several mouse strains produced NETs with different efficiency and that NET formation correlated with the amount of ROS produced. Activation with <i>Candida albicans</i> also resulted in ROS production and NET cell death. The hyphal form of this fungus induced NETs more effectively than the yeast form. With this work, we provide tools to study in vitro NET assembly in the mouse system.
DOI: 10.6084/m9.figshare.5120611
title: Supplementary Material for: MicroRNAs Expressed during Lung Cancer Development Are Expressed in Human Pseudoglandular Lung Embryogenesis

description: <i>Background/Aims:</i> MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17–92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics. <i>Methods:</i> RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR. <i>Results:</i> Members of the let-7 family were downregulated and members of the miR-17–92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008). <i>Conclusion:</i> Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.
DOI: 10.6084/m9.figshare.5120614
title: Supplementary Material for: Differential FGF Ligands and FGF Receptors Expression Pattern in Frontal and Parietal Calvarial Bones

description: The mammalian skull vault consists mainly of 5 flat bones, the paired frontals and parietals, and the unpaired interparietal. All of these bones are formed by intramembranous ossification within a layer of mesenchyme, the skeletogenic membrane, located between the dermal mesenchyme and the meninges surrounding the brain. While the frontal bones are of neural crest in origin, the parietal bones arise from mesoderm. The present study is a characterization of frontal and parietal bones at their molecular level, aiming to highlight distinct differences between the neural crest-derived frontal and mesodermal-derived parietal bone. We performed a detailed comparative gene expression profile of FGF ligands and their receptors known to play crucial role in skeletogenesis. This analysis revealed that a differential expression pattern of the major FGF osteogenic molecules and their receptors exists between the neural crest-derived frontal bone and the paraxial mesoderm-derived parietal bone. Particularly, the expression of ligands such as <i>Fgf-2, Fgf-9</i> and <i>Fgf-18</i> was upregulated in frontal bone on embryonic day 17.5, postnatal day 1 and postnatal day 60 mice. Frontal bone also elaborated higher levels of <i>Fgf receptor 1, 2</i> and <i>3</i> transcripts versus parietal bone. Taken together, these data suggest that the frontal bone is a domain with higher FGF-signaling competence than parietal bone.
DOI: 10.6084/m9.figshare.5120605
title: Supplementary Material for: Two populations of double minute chromosomes harbor distinct amplicons, the <i>MYC</i> locus at 8q24.2 and a 0.43-Mb region at 14q24.1, in the SW613-S human carcinoma cell line

description: High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level <i>MYC</i> amplification in the form of double minutes (DM<sup>+</sup> cells) and non tumorigenic cells exhibiting low-level <i>MYC</i> amplification in the form of homogeneously staining regions (DM<sup>–</sup> cells). Both cell types were studied at genomic and functional levels. The DM<sup>+</sup> cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the <i>PLEK2, PIGH, ARG2, VTI1B, RDH11</i><i>,</i> and <i>ZFYVE26</i> genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level <i>MYC</i> amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM <i>MYC</i> copies or after transfection of DM<sup>–</sup> cells with a <i>MYC</i> gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs.
DOI: 10.6084/m9.figshare.5120608
title: Supplementary Material for: Tube Is an IRAK-4 Homolog in a Toll Pathway Adapted for Development and Immunity

description: Acting through the Pelle and IRAK family of protein kinases, Toll receptors mediate innate immune responses in animals ranging from insects to humans. In flies, the Toll pathway also functions in patterning of the syncytial embryo and requires Tube, a <i>Drosophila</i>-specific adaptor protein lacking a catalytic domain. Here we provide evidence that the Tube, Pelle, and IRAK proteins originated from a common ancestral gene. Following gene duplication, IRAK-4, Tube-like kinases, and Tube diverged from IRAK-1, Pelle, and related kinases. Remarkably, the function of Tube and Pelle in <i>Drosophila</i> embryos can be reconstituted in a chimera modeled on the predicted progenitor gene. In addition, a divergent property of downstream transcription factors was correlated with developmental function. Together, these studies reveal previously unrecognized parallels in Toll signaling in fly and human innate immunity and shed light on the evolution of pathway organization and function.
DOI: 10.6084/m9.figshare.5120602
title: Supplementary Material for: <i>Sox100B</i>, a <i>Drosophila</i> Group E Sox-domain Gene, Is Required for Somatic Testis Differentiation

description: Sex determination mechanisms are thought to evolve rapidly and show little conservation among different animal species. For example, the critical gene on the Y chromosome, <i>SRY</i>, that determines sex in most mammals, is not found in other animals. However, a related Sox domain transcription factor, <i>SOX9</i>, is also required for testis development in mammals and exhibits male-specific gonad expression in other vertebrate species. Previously, we found that the <i>Drosophila</i> orthologue of <i>SOX9</i>, <i>Sox100B</i>, is expressed male-specifically during gonad development. We now investigate the function of <i>Sox100B</i> and find, strikingly, that <i>Sox100B</i> is essential for testis development in <i>Drosophila</i>. In <i>Sox100B</i> mutants, the adult testis is severely reduced and fails to interact with other parts of the reproductive tract, which are themselves unaffected. While a testis initially forms in <i>Sox100B</i> mutants, it fails to undergo proper morphogenesis during pupal stages, likely due to defects in the pigment cells. In contrast, no substantive defects are observed in ovary development in <i>Sox100B</i> mutant females. Thus, as is observed in mammals, a <i>Sox9</i> homolog is essential for sex-specific gonad development in <i>Drosophila</i>, suggesting that the molecular mechanisms regulating sexually dimorphic gonad development may be more conserved than previously suspected.
DOI: 10.6084/m9.figshare.5120605.v1
title: Supplementary Material for: Two populations of double minute chromosomes harbor distinct amplicons, the <i>MYC</i> locus at 8q24.2 and a 0.43-Mb region at 14q24.1, in the SW613-S human carcinoma cell line

description: High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level <i>MYC</i> amplification in the form of double minutes (DM<sup>+</sup> cells) and non tumorigenic cells exhibiting low-level <i>MYC</i> amplification in the form of homogeneously staining regions (DM<sup>–</sup> cells). Both cell types were studied at genomic and functional levels. The DM<sup>+</sup> cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the <i>PLEK2, PIGH, ARG2, VTI1B, RDH11</i><i>,</i> and <i>ZFYVE26</i> genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level <i>MYC</i> amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM <i>MYC</i> copies or after transfection of DM<sup>–</sup> cells with a <i>MYC</i> gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs.
DOI: 10.6084/m9.figshare.5120611.v1
title: Supplementary Material for: MicroRNAs Expressed during Lung Cancer Development Are Expressed in Human Pseudoglandular Lung Embryogenesis

description: <i>Background/Aims:</i> MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17–92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics. <i>Methods:</i> RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR. <i>Results:</i> Members of the let-7 family were downregulated and members of the miR-17–92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008). <i>Conclusion:</i> Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.
DOI: 10.6084/m9.figshare.5120596
title: Supplementary Material for: Reducing the Global Genomic Inequity Gap: Development of an African Genome Project

description: Medicine
DOI: 10.6084/m9.figshare.5120599
title: Supplementary Material for: Plant Polyphenol Intake Alters Gene Expression in Canine Leukocytes

description: <i>Background/Aims:</i> Polyphenol compounds may explain most of the health-related beneficial effects of plants and vegetables, mainly through their antioxidant properties. The aim of the study was to assess the main changes on leukocyte gene expression of dogs caused by intake of three natural polyphenol-rich extracts and to compare them with caloric restriction. <i>Methods:</i> 20 female dogs were divided into 5 groups: control fed ad libitum (C), caloric-restricted to 30% less than control (CR), and 3 groups fed ad libitum supplemented with citrus extract (CE), green tea extract (GTE) or grape seed extract (GSE). Leukocytes gene expression was analyzed in a specially designed microarray. <i>Results:</i> CE treatment mainly downregulated genes related to inflammative (IL-8, VLA-4) and cytotoxic response (GRP 58) as well as proliferation of leukocytes. GTE induced gene expression related to leukocyte proliferation and signaling (GNAQ, PKC-B). GSE upregulated some of the genes increased by CE treatment. CR downregulated genes related with energy metabolism (ATP5A1, COX7C) and inflammatory markers (VLA-4). <i>Conclusion:</i> A chronic ingestion of citric, grape seed and green tea polyphenols is able to modulate canine leukocyte functions through changes in gene expression. CE ingestion reduces expression of some genes also diminished by a 30% caloric restriction.
DOI: 10.6084/m9.figshare.5120602.v1
title: Supplementary Material for: <i>Sox100B</i>, a <i>Drosophila</i> Group E Sox-domain Gene, Is Required for Somatic Testis Differentiation

description: Sex determination mechanisms are thought to evolve rapidly and show little conservation among different animal species. For example, the critical gene on the Y chromosome, <i>SRY</i>, that determines sex in most mammals, is not found in other animals. However, a related Sox domain transcription factor, <i>SOX9</i>, is also required for testis development in mammals and exhibits male-specific gonad expression in other vertebrate species. Previously, we found that the <i>Drosophila</i> orthologue of <i>SOX9</i>, <i>Sox100B</i>, is expressed male-specifically during gonad development. We now investigate the function of <i>Sox100B</i> and find, strikingly, that <i>Sox100B</i> is essential for testis development in <i>Drosophila</i>. In <i>Sox100B</i> mutants, the adult testis is severely reduced and fails to interact with other parts of the reproductive tract, which are themselves unaffected. While a testis initially forms in <i>Sox100B</i> mutants, it fails to undergo proper morphogenesis during pupal stages, likely due to defects in the pigment cells. In contrast, no substantive defects are observed in ovary development in <i>Sox100B</i> mutant females. Thus, as is observed in mammals, a <i>Sox9</i> homolog is essential for sex-specific gonad development in <i>Drosophila</i>, suggesting that the molecular mechanisms regulating sexually dimorphic gonad development may be more conserved than previously suspected.
DOI: 10.6084/m9.figshare.5120590
title: Supplementary Material for: Variance Components Linkage Analysis with Repeated Measurements

description: <i>Background:</i> When subjects are measured multiple times, linkage analysis needs to appropriately model these repeated measures. A number of methods have been proposed to model repeated measures in linkage analysis. Here, we focus on assessing the impact of repeated measures on the power and cost of a linkage study. <i>Methods:</i> We describe three alternative extensions of the variance components approach to accommodate repeated measures in a quantitative trait linkage study. We explicitly relate power and cost through the number of measures for different designs. Based on these models, we derive general formulas for optimal number of repeated measures for a given power or cost and use analytical calculations and simulations to compare power for different numbers of repeated measures across several scenarios. We give rigorous proof for the results under the balanced design. <i>Results:</i> Repeated measures substantially improve power and the proportional increase in LOD score depends mostly on measurement error and total heritability but not much on marker map, the number of alleles per marker or family structure. When measurement error takes up 20% of the trait variability and 4 measures/subject are taken, the proportional increase in LOD score ranges from 38% for traits with heritability of ~20% to 63% for traits with heritability of ~80%. An R package is provided to determine optimal number of repeated measures for given measurement error and cost. Variance component and regression based implementations of our methods are included in the MERLIN package to facilitate their use in practical studies.
DOI: 10.6084/m9.figshare.5120599.v1
title: Supplementary Material for: Plant Polyphenol Intake Alters Gene Expression in Canine Leukocytes

description: <i>Background/Aims:</i> Polyphenol compounds may explain most of the health-related beneficial effects of plants and vegetables, mainly through their antioxidant properties. The aim of the study was to assess the main changes on leukocyte gene expression of dogs caused by intake of three natural polyphenol-rich extracts and to compare them with caloric restriction. <i>Methods:</i> 20 female dogs were divided into 5 groups: control fed ad libitum (C), caloric-restricted to 30% less than control (CR), and 3 groups fed ad libitum supplemented with citrus extract (CE), green tea extract (GTE) or grape seed extract (GSE). Leukocytes gene expression was analyzed in a specially designed microarray. <i>Results:</i> CE treatment mainly downregulated genes related to inflammative (IL-8, VLA-4) and cytotoxic response (GRP 58) as well as proliferation of leukocytes. GTE induced gene expression related to leukocyte proliferation and signaling (GNAQ, PKC-B). GSE upregulated some of the genes increased by CE treatment. CR downregulated genes related with energy metabolism (ATP5A1, COX7C) and inflammatory markers (VLA-4). <i>Conclusion:</i> A chronic ingestion of citric, grape seed and green tea polyphenols is able to modulate canine leukocyte functions through changes in gene expression. CE ingestion reduces expression of some genes also diminished by a 30% caloric restriction.
DOI: 10.6084/m9.figshare.5120587
title: Supplementary Material for: Antioxidants and Other Micronutrients in Complementary Oncology

description: Many patients being treated for cancer use micronutrient supplements, with the intention to complement their cancer treatment or help them cope with the therapy- and disease-associated side effects. The majority are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants are added to conventional cytotoxic therapies. However, it is imperative that physicians explore the use of antioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative as well as potentially beneficial effects.
DOI: 10.6084/m9.figshare.5120590.v1
title: Supplementary Material for: Variance Components Linkage Analysis with Repeated Measurements

description: <i>Background:</i> When subjects are measured multiple times, linkage analysis needs to appropriately model these repeated measures. A number of methods have been proposed to model repeated measures in linkage analysis. Here, we focus on assessing the impact of repeated measures on the power and cost of a linkage study. <i>Methods:</i> We describe three alternative extensions of the variance components approach to accommodate repeated measures in a quantitative trait linkage study. We explicitly relate power and cost through the number of measures for different designs. Based on these models, we derive general formulas for optimal number of repeated measures for a given power or cost and use analytical calculations and simulations to compare power for different numbers of repeated measures across several scenarios. We give rigorous proof for the results under the balanced design. <i>Results:</i> Repeated measures substantially improve power and the proportional increase in LOD score depends mostly on measurement error and total heritability but not much on marker map, the number of alleles per marker or family structure. When measurement error takes up 20% of the trait variability and 4 measures/subject are taken, the proportional increase in LOD score ranges from 38% for traits with heritability of ~20% to 63% for traits with heritability of ~80%. An R package is provided to determine optimal number of repeated measures for given measurement error and cost. Variance component and regression based implementations of our methods are included in the MERLIN package to facilitate their use in practical studies.