cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123320
title: Supplementary Material for: Periventricular Demyelination and Axonal Pathology Is Associated with Subependymal Virus Spread in a Murine Model for Multiple Sclerosis

description: <b><i>Objectives:</i></b> Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelinating disorders, such as multiple sclerosis (MS). The aim of the present study was to identify topographical differences of TMEV spread and demyelination in the brain of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice. <b><i>Methods:</i></b> Demyelination was confirmed by Luxol fast blue and cresyl violet staining and axonal damage by neurofilament-specific and β-amyloid precursor protein-specific immunohistochemistry. Viral dissemination within the central nervous system (CNS) was quantified by immunohistochemistry and in situ hybridization. Further, the phenotype of infected cells was determined by confocal laser scanning microscopy. <b><i>Results:</i></b> An early transient infection of periventricular cells followed by demyelination and axonopathies around the fourth ventricle in SJL/J mice was noticed. Periventricular and brain stem demyelination was associated with a predominant infection of microglia/macrophages and oligodendrocytes. <b><i>Conclusions:</i></b> Summarized, the demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to injury and regenerative capacities of the brain in this MS model.
DOI: 10.6084/m9.figshare.5123323
title: Supplementary Material for: Association of the –1072G/A Polymorphism in the <b><i>LTC4S</i></b> Gene with Asthma in an Indian Population

description: <b><i>Background:</i></b> Atopic asthma, the most common chronic disease affecting children and young adults, is a complex disorder with variable phenotypes. Cysteine leukotrienes (Cys-LTs) are powerful bronchoconstrictors and play a critical role in airway inflammation and remodeling that are characteristic of asthma. <b><i>Objective:</i></b> To investigate the association of <i>ALOX5</i>, <i>LTC4S </i>and<i> CysLTR2 </i>gene polymorphisms with atopic asthma in an Indian population. <b><i>Methods:</i></b> A total of 19 single nucleotide polymorphisms (SNPs) within these genes were genotyped in a family-based cohort (n = 239) and a case-control cohort (139 cases and 194 controls) followed by association analyses. <b><i>Results:</i></b> We found a significant association of the –1072G/A (rs3776944) SNP with atopic asthma in the family-based association analysis (p = 0.0004). These results were also replicated in the case-control cohort (p = 0.009). The allele A was negatively associated with atopic asthma. We also noted a significant association in the two-locus (rs3776944G/A and rs730012A/C) haplotypic analysis of this gene both in the family-based (p = 0.03) and the case-control (p = 0.02) analyses. <b><i>Conclusion:</i></b> This study supports the role of the <i>LTC4S </i>gene polymorphism in genetic susceptibility to atopic asthma in an Indian population.
DOI: 10.6084/m9.figshare.5123326
title: Supplementary Material for: Lipopolysaccharide Neutralization by Antimicrobial Peptides: A Gambit in the Innate Host Defense Strategy

description: Antimicrobial peptides (AMPs) are nowadays understood as broad multifunctional tools of the innate immune system to fight microbial infections. In addition to its direct antimicrobial action, AMPs can modulate the host immune response by promoting or restraining the recruitment of cells and chemicals to the infection focus. Binding of AMPs to lipopolysaccharide is a critical step for both their antimicrobial action and their immunomodulatory properties. On the one hand, removal of Gram-negative bacteria by AMPs can be an effective strategy to prevent a worsened inflammatory response that may lead to septic shock. On the other hand, by neutralizing circulating endotoxins, AMPs can successfully reduce nitric oxide and tumor necrosis factor-α production, hence preventing severe tissue damage. Furthermore, AMPs can also interfere with the Toll-like receptor 4 recognition system, suppressing cytokine production and contributing to modulate the inflammatory response. Here, we review the immune system strategies devised by AMPs to avoid an exacerbated inflammatory response and thus prevent a fatal end to the host.
DOI: 10.6084/m9.figshare.5123317
title: Supplementary Material for: Reclassification of Giant Viruses Composing a Fourth Domain of Life in the New Order <b><i>Megavirales</i></b>

description: Interest in giant viruses has risen sharply since 2003, following the discovery of the Mimivirus and four other protist-infecting giant viruses that are linked to the nucleocytoplasmic large DNA viruses (NCLDVs). Despite considerable heterogeneity in hosts and genome sizes, the NCLDVs have been shown to be monophyletic based on analyses of their sequences and gene repertoires and recent studies have proposed that these viruses share a common ancient ancestor and compose a fourth domain of life. In addition, several characteristics of these giant viruses contradict or do not match the criteria used for the canonical definition of viruses, and the NCLDV denomination is not completely appropriate. We propose here to define a new viral order named <i>Megavirales</i>.
DOI: 10.6084/m9.figshare.5123320.v1
title: Supplementary Material for: Periventricular Demyelination and Axonal Pathology Is Associated with Subependymal Virus Spread in a Murine Model for Multiple Sclerosis

description: <b><i>Objectives:</i></b> Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelinating disorders, such as multiple sclerosis (MS). The aim of the present study was to identify topographical differences of TMEV spread and demyelination in the brain of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice. <b><i>Methods:</i></b> Demyelination was confirmed by Luxol fast blue and cresyl violet staining and axonal damage by neurofilament-specific and β-amyloid precursor protein-specific immunohistochemistry. Viral dissemination within the central nervous system (CNS) was quantified by immunohistochemistry and in situ hybridization. Further, the phenotype of infected cells was determined by confocal laser scanning microscopy. <b><i>Results:</i></b> An early transient infection of periventricular cells followed by demyelination and axonopathies around the fourth ventricle in SJL/J mice was noticed. Periventricular and brain stem demyelination was associated with a predominant infection of microglia/macrophages and oligodendrocytes. <b><i>Conclusions:</i></b> Summarized, the demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to injury and regenerative capacities of the brain in this MS model.
DOI: 10.6084/m9.figshare.5123323.v1
title: Supplementary Material for: Association of the –1072G/A Polymorphism in the <b><i>LTC4S</i></b> Gene with Asthma in an Indian Population

description: <b><i>Background:</i></b> Atopic asthma, the most common chronic disease affecting children and young adults, is a complex disorder with variable phenotypes. Cysteine leukotrienes (Cys-LTs) are powerful bronchoconstrictors and play a critical role in airway inflammation and remodeling that are characteristic of asthma. <b><i>Objective:</i></b> To investigate the association of <i>ALOX5</i>, <i>LTC4S </i>and<i> CysLTR2 </i>gene polymorphisms with atopic asthma in an Indian population. <b><i>Methods:</i></b> A total of 19 single nucleotide polymorphisms (SNPs) within these genes were genotyped in a family-based cohort (n = 239) and a case-control cohort (139 cases and 194 controls) followed by association analyses. <b><i>Results:</i></b> We found a significant association of the –1072G/A (rs3776944) SNP with atopic asthma in the family-based association analysis (p = 0.0004). These results were also replicated in the case-control cohort (p = 0.009). The allele A was negatively associated with atopic asthma. We also noted a significant association in the two-locus (rs3776944G/A and rs730012A/C) haplotypic analysis of this gene both in the family-based (p = 0.03) and the case-control (p = 0.02) analyses. <b><i>Conclusion:</i></b> This study supports the role of the <i>LTC4S </i>gene polymorphism in genetic susceptibility to atopic asthma in an Indian population.
DOI: 10.6084/m9.figshare.5123308
title: Supplementary Material for: Mutations in the Essential <i>Escherichia coli </i>Gene, <i>yqgF</i>, and Their Effects on Transcription

description: The <i>Escherichia coli</i> <i>yqgF</i> gene is highly conserved across a broad spectrum of bacterial genomes. The gene was first identified as being essential for cell growth during screening for targets for broad-spectrum antibiotics. YqgF is structurally similar to RuvC, a Holliday junction resolvase, but its function has not been established. This study describes the isolation of a temperature-sensitive <i>yqgF</i> mutant, the growth of which was inhibited by <i>rho</i> or <i>nusA</i> multicopy plasmids, indicating that YqgF is involved in transcription. Rho is a global transcription termination factor that acts at Rho-dependent terminator sites, which exist not only at the ends of genes but also within genes. The transcription of genes possessing intragenic, or upstream, Rho-dependent terminators was reduced in temperature-sensitive <i>yqgF</i> mutants. This transcription inhibition was sensitive to the Rho inhibitor, bicyclomycin. In addition, the transcription of mutant <i>tnaA</i> genes defective for upstream Rho-dependent termination was not significantly affected by the <i>yqgF</i> mutation. Taken together, these results suggest that YqgF is involved in anti-termination at Rho-dependent terminators in vivo.
DOI: 10.6084/m9.figshare.5123311
title: Supplementary Material for: On-Site Drugs of Abuse Urinary Screening Tests for the Management of Opiate-Addicted Patients: A Survey among French General Practitioners

description: In France, opiate-addicted patients are mainly managed by general practitioners (GPs). Because on-site abuse drugs urinary screening tests (ODUTs) are now on the market, we investigated French GPs’ knowledge and practices concerning drug tests with a focus on ODUTs. We conducted a descriptive cross-sectional study in ambulatory practice. Postal questionnaires were sent to a random sample of GPs in the Midi-Pyrénées area of France in December 2009. Of the 482 GPs in the sample, 116 (24.1%) regularly treated opiate- addicted patients. Only 31 of them (26.7%) used drug tests and 4 of them (3.4%) performed ODUTs in their consultation rooms. Most of the GPs did not perform ODUTs because they were unaware of whether such tests were reliable or available. Many French GPs treating opiate-addicted patients regularly did not perform ODUTs and lacked knowledge of them.
DOI: 10.6084/m9.figshare.5123314
title: Supplementary Material for: Mitochondrial Inhibitor Models of Huntington’s Disease and Parkinson’s Disease Induce Zinc Accumulation and Are Attenuated by Inhibition of Zinc Neurotoxicity in vitro or in vivo

description: <b><i>Background:</i></b> Inhibition of mitochondrial function occurs in many neurodegenerative diseases, and inhibitors of mitochondrial complexes I and II are used to model them. The complex II inhibitor, 3-nitroproprionic acid (3-NPA), kills the striatal neurons susceptible in Huntington’s disease. The complex I inhibitor N-methyl-4-phenylpyridium (MPP<sup>+</sup>) and 6-hydroxydopamine (6-OHDA) are used to model Parkinson’s disease. Zinc (Zn<sup>2+)</sup> accumulates after 3-NPA, 6-OHDA and MPP<sup>+</sup> in situ or in vivo. <b><i>Objective:</i></b> We will investigate the role of Zn<sup>2+</sup> neurotoxicity in 3-NPA, 6-OHDA and MPP<sup>+</sup>. <b><i>Methods:</i></b> Murine striatal/midbrain tyrosine hydroxylase positive, or near-pure cortical neuronal cultures, or animals were exposed to 3-NPA or MPP<sup>+</sup> and 6-OHDA with or without neuroprotective compounds. Intracellular zinc ([Zn<sup>2+</sup>]<sub>i</sub>), nicotinamide adenine dinucleotide (NAD<sup>+</sup>), NADH, glycolytic intermediates and neurotoxicity were measured. <b><i>Results:</i></b> We showed that compounds or genetics which restore NAD<sup>+</sup> and attenuate Zn<sup>2+</sup> neurotoxicity (pyruvate, nicotinamide, NAD<sup>+</sup>, increased NAD<sup>+</sup> synthesis, sirtuin inhibition or Zn<sup>2+</sup> chelation) attenuated the neuronal death induced by these toxins. The increase in [Zn<sup>2+</sup>]<sub>i</sub> preceded a reduction in the NAD<sup>+</sup>/NADH ratio that caused a reversible glycolytic inhibition. Pyruvate, nicotinamide and NAD<sup>+</sup> reversed the reductions in the NAD<sup>+</sup>/NADH ratio, glycolysis and neuronal death after challenge with 3-NPA, 6-OHDA or MPP<sup>+</sup>, as was previously shown for exogenous Zn<sup>2+</sup>. To test efficacy in vivo, we injected 3-NPA into the striatum of rats and systemically into mice, with or without pyruvate. We observed early striatal Zn<sup>2+</sup> fluorescence, and pyruvate significantly attenuated the 3-NPA-induced lesion and restored behavioral scores. <b><i>Conclusions:</i></b> Together, these studies suggest that Zn<sup>2+</sup> accumulation caused by MPP<sup>+</sup> and 3-NPA is a novel preventable mechanism of the resultant neurotoxicity.
DOI: 10.6084/m9.figshare.5123302
title: Supplementary Material for: Phenotype-Genotype Correlations in Mouse Models of<b> </b>Amelogenesis Imperfecta<b> </b>Caused by<b><i> Amelx </i></b>and<b><i> Enam </i></b>Mutations

description: Mutations in human and in mouse orthologous genes <i>Amelx</i> and <i>Enam </i>result in a diverse range of enamel defects. In this study we aimed to investigate the phenotype-genotype correlation between the mutants and the wild-type controls in mouse models of amelogenesis imperfecta using novel measurement approaches. Ten hemi-mandibles and incisors were dissected from each group of <i>Amelx</i><sup>WT</sup>, <i>Amelx</i><sup>X/Y64H</sup>, <i>Amelx</i><sup>Y/Y64H</sup>, <i>Amelx</i><sup>Y64H/Y64H</sup>, and<i> Enam</i><sup>WT</sup>, <i>Enam</i><sup>Rgsc395</sup> heterozygous and <i>Enam</i><sup>Rgsc395</sup> homozygous mice. Their macro-morphology, colour and micro-topography were assessed using bespoke 2D and 3D image analysis systems and customized colour and whiteness algorithms. The novel methods identified significant differences (p ≤ 0.05) between the <i>Amelx</i> groups for mandible and incisor size and enamel colour and between the <i>Enam</i> groups for incisor size and enamel colour. The <i>Amelx</i><sup>WT</sup> mice had the largest mandibles and incisors, followed in descending order of size by the <i>Amelx</i><sup>X/Y64H</sup>, <i>Amelx</i><sup>Y/Y64H</sup> and <i>Amelx</i><sup>Y64H/Y64H</sup> mice. Within the <i>Enam</i> groups the <i>Enam</i><sup>WT</sup> incisors were largest and the <i>Enam</i><sup>Rgsc395</sup> heterozygous mice were smallest. The effect on tooth morphology was also reflected by the severity of the enamel defects in the colour and whiteness assessment. Amelogenin affected mandible morphology and incisor enamel formation, while enamelin only affected incisors, supporting the multifunctional role of amelogenin. The enamelin mutation was associated with earlier forming enamel defects. The study supported the critical involvement of amelogenin and enamelin in enamel mineralization.
DOI: 10.6084/m9.figshare.5123305
title: Supplementary Material for: Excision of Nonpalpable Breast Cancer with Indocyanine Green Fluorescence-Guided Occult Lesion Localization (IFOLL)

description: <i>Background: </i>Currently employed techniques for the localization of nonpalpable breast lesions suffer from various limitations. In this paper, we report on 2 patients in order to introduce an alternative technique, indocyanine green fluorescence-guided occult lesion localization (IFOLL), and determine its applicability for the surgical removal of this type of breast lesions. <i>Case Reports: </i>Preoperatively, one of the patients had a needle biopsyproven diagnosis of breast cancer, and the other one had suspicious findings for malignancy. Lesion localization was performed within 1 h before surgery under ultrasonography control by injecting 2 ml and 0.2 ml of indocyanine green into the lesion and its subcutaneous tissue projection, respectively. During surgery, the site of skin incision and the resection margins were identified by observing the area of indocyanine-derived fluorescence under the guidance of a near-infrared-sensitive camera. In both cases, the breast lesion was correctly localized, and the area of fluorescence corresponded well to the site of the lesions. Subsequent surgical excision was successful with no complications. On histopathologic examination, the surgical margins were found to be clear. <i>Conclusion: </i>IFOLL seems to be a technically applicable and clinically acceptable procedure for the removal of nonpalpable breast cancer.
DOI: 10.6084/m9.figshare.5123314.v1
title: Supplementary Material for: Mitochondrial Inhibitor Models of Huntington’s Disease and Parkinson’s Disease Induce Zinc Accumulation and Are Attenuated by Inhibition of Zinc Neurotoxicity in vitro or in vivo

description: <b><i>Background:</i></b> Inhibition of mitochondrial function occurs in many neurodegenerative diseases, and inhibitors of mitochondrial complexes I and II are used to model them. The complex II inhibitor, 3-nitroproprionic acid (3-NPA), kills the striatal neurons susceptible in Huntington’s disease. The complex I inhibitor N-methyl-4-phenylpyridium (MPP<sup>+</sup>) and 6-hydroxydopamine (6-OHDA) are used to model Parkinson’s disease. Zinc (Zn<sup>2+)</sup> accumulates after 3-NPA, 6-OHDA and MPP<sup>+</sup> in situ or in vivo. <b><i>Objective:</i></b> We will investigate the role of Zn<sup>2+</sup> neurotoxicity in 3-NPA, 6-OHDA and MPP<sup>+</sup>. <b><i>Methods:</i></b> Murine striatal/midbrain tyrosine hydroxylase positive, or near-pure cortical neuronal cultures, or animals were exposed to 3-NPA or MPP<sup>+</sup> and 6-OHDA with or without neuroprotective compounds. Intracellular zinc ([Zn<sup>2+</sup>]<sub>i</sub>), nicotinamide adenine dinucleotide (NAD<sup>+</sup>), NADH, glycolytic intermediates and neurotoxicity were measured. <b><i>Results:</i></b> We showed that compounds or genetics which restore NAD<sup>+</sup> and attenuate Zn<sup>2+</sup> neurotoxicity (pyruvate, nicotinamide, NAD<sup>+</sup>, increased NAD<sup>+</sup> synthesis, sirtuin inhibition or Zn<sup>2+</sup> chelation) attenuated the neuronal death induced by these toxins. The increase in [Zn<sup>2+</sup>]<sub>i</sub> preceded a reduction in the NAD<sup>+</sup>/NADH ratio that caused a reversible glycolytic inhibition. Pyruvate, nicotinamide and NAD<sup>+</sup> reversed the reductions in the NAD<sup>+</sup>/NADH ratio, glycolysis and neuronal death after challenge with 3-NPA, 6-OHDA or MPP<sup>+</sup>, as was previously shown for exogenous Zn<sup>2+</sup>. To test efficacy in vivo, we injected 3-NPA into the striatum of rats and systemically into mice, with or without pyruvate. We observed early striatal Zn<sup>2+</sup> fluorescence, and pyruvate significantly attenuated the 3-NPA-induced lesion and restored behavioral scores. <b><i>Conclusions:</i></b> Together, these studies suggest that Zn<sup>2+</sup> accumulation caused by MPP<sup>+</sup> and 3-NPA is a novel preventable mechanism of the resultant neurotoxicity.
DOI: 10.6084/m9.figshare.5123299
title: Supplementary Material for: Family History Tools in Primary Care: Does One Size Fit All?

description: Family health history (FHH) has potential value in many health care settings. This review discusses the potential uses of FHH information in primary care and the need for tools to be designed accordingly. We developed a framework in which the attributes of FHH tools are mapped against these different purposes. It contains 7 attributes mapped against 5 purposes. In considering different FHH tool purposes, it is apparent that different attributes become more or less important, and that tools for different purposes require different implementation and evaluation strategies. The context in which a tool is used is also relevant to its effectiveness. For FHH tools, it is unlikely that ‘one size fits all’, although appreciation of different purposes, users and contexts should facilitate the development of different applications from single FHH platforms.
DOI: 10.6084/m9.figshare.5123296
title: Supplementary Material for: Involvement of Can f 5 in a Case of Human Seminal Plasma Allergy

description: <b><i>Background:</i></b> The existence of IgE binding to dog dander extract without IgE antibodies against the described dog allergens (Can f 1, 2, 3 and 4) implies the presence of other dog allergens yet to be identified. Recently, an IgE-binding protein was isolated from dog urine and identified as prostatic kallikrein; it has been named Can f 5. Cross-reactivity between a dog dander allergen and human prostate-specific antigen (PSA) has been described. The aim of this study was to identify the dog dander allergen that presents cross-reactivity with PSA and demonstrate its clinical relevance in our patient with human seminal plasma allergy. <b><i>Methods:</i></b> SDS-PAGE immunoblotting and inhibition tests were performed. Mass spectrometry was carried out to identify the protein involved in the allergy reactions. <b><i>Results:</i></b> SDS-PAGE immunoblotting-inhibition with an IgE-binding protein from dog prostatic secretion showed total IgE binding inhibition to a 28-kDa IgE-reactive band identified as PSA. The electroeluted protein from dog prostatic secretion was identified by mass spectrometry as Can f 5. IgE immunoblotting of human seminal plasma incubated with the serum of the patient revealed two IgE-binding bands (28 and 32.7 kDa). Both SDS-PAGE immunoblotting inhibition assays, with human seminal plasma or purified PSA in solid phase, showed complete IgE binding inhibition when the serum of the anaphylactic patient was preincubated with dog dander extract or recombinant Can f 5. <b><i>Conclusions:</i></b> The dog dander allergen that shows cross-reactivity with human PSA has been characterized and turns out to be the recently described Can f 5. We demonstrated the clinical relevance of this cross-reactivity in a patient.