cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120431.v1
title: Supplementary Material for: <i>LPA</i> and <i>PLG</i> Sequence Variation and Kringle IV-2 Copy Number in Two Populations

description: <i>Background/Aims:</i> Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic <i>LPA</i> kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations. <i>Methods:</i> To identify potential cis-acting factors, we re-sequenced the gene <i>LPA</i> for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen <i>(PLG)</i> and genotyped the kringle IV copy number variant in the same reference samples. <i>Results:</i> These data are the most comprehensive description of sequence variation in <i>LPA</i> and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of <i>LPA</i> sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within <i>PLG </i>are not in linkage disequilibrium with SNPs in <i>LPA</i>, and we show that kringle IV copy number variation is not in linkage disequilibrium with either <i>LPA</i> or <i>PLG</i> SNPs. <i>Conclusions:</i> Together, these data suggest that <i>LPA</i> SNPs could independently contribute to Lp(a) levels in the general population.
DOI: 10.6084/m9.figshare.5120434.v1
title: Supplementary Material for: Prothrombotic Gene Variation in Patients with Large and Small Vessel Disease

description: The classification of ischemic stroke into different subtypes is supported in genetic association studies. While several gene variants have been identified as being associated with ischemia subtypes, most studies have not been powered to study subtypes separately. We investigated 887 patients with nondisabling cerebral ischemia of arterial origin and classified ischemia as being caused by large or small vessel disease (LVD or SVD), primarily based on neuroimaging findings. In total, 621 patients had LVD and 266 SVD. The coagulation factor XIII subunit B gene (F13B) His95Arg variant was more common in patients with LVD (mean prevalence difference 9.9%; 95% CI 4.7–15). None of 21 other prothrombotic gene variants was associated with LVD or SVD. Many gene variants may not be specific for one subtype. We could not replicate the genetic associations identified in previous smaller previous studies. Thus claims about genetic associations with specific subtypes of ischemia should be interpreted with caution. The association between F13B His95Arg and LVD requires replication.
DOI: 10.6084/m9.figshare.5120422.v1
title: Supplementary Material for: Treatment of Painful Limbs/Moving Extremities with Botulinum Toxin Type A Injections

description: Medicine
DOI: 10.6084/m9.figshare.5120413
title: Supplementary Material for: Genome-Wide Analysis of Dietary Eicosapentaenoic Acid- and Oleic Acid-Induced Modulation of Colon Inflammation in Interleukin-10 Gene-Deficient Mice

description: <i>Background/Aims:</i> Dietary n–3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient <i>(Il10</i><sup>–/–</sup><i>)</i> mice. <i>Methods:</i> At 35 days of age, 12 weaned <i>Il10</i><sup>–/–</sup> and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n–3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. <i>Results:</i> In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed <i>Il10</i><sup>–/–</sup> compared to C57 mice. <i>Il10</i><sup>–/–</sup> mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in <i>Il10</i><sup>–/–</sup> mice. <i>Conclusions:</i> These data indicate that dietary EPA-induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the <i>Ppara</i> gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins.
DOI: 10.6084/m9.figshare.5120416
title: Supplementary Material for: Very-High-Frequency Ultrasound Corneal Imaging as a New Tool for Early Diagnosis of Ocular Surface Toxicity in Rabbits Treated with a Preserved Glaucoma Drug

description: <i>Aim:</i> To evaluate very-high-frequency (VHF) ultrasound imaging as a new method to detect and quantify early corneal epithelium changes induced by chronic exposure to a benzalkonium-chloride-containing antiglaucoma drug. <i>Methods:</i> Timolol preserved with 0.01% benzalkonium chloride solution was applied b.i.d. in 1 eye of 10 rabbits for 56 days. Unpreserved timolol solution was used as control. Ocular surface changes were assessed weekly combining clinical examinations, in vivo 60-MHz ultrasound imaging and ex vivo histological analysis. <i>Results:</i> VHF ultrasound imaging allowed quantitative measurement of corneal epithelium thickness and qualitative imaging of toxic epithelial damage. It revealed significantly decreased epithelial thickness in vivo as early as the 21st day of treatment (40.75 ± 1.72 µm at D0 vs. 39 ± 2 at D21, vs. 31.9 ± 2.98 at D56; p = 0.017 and p = 0.005, respectively). The first clinical changes appeared from the 42nd day of treatment (conjunctival redness, conjunctival staining and corneal staining; D56 compared to D0: p = 0.005, 0.01 and 0.004, respectively) and then correlated with VHF ultrasound data. Epithelial thickness measured with VHF ultrasound was correlated with histological epithelial pachymetry (p &lt; 0.001) and with the corneal damage score assessed with scanning electron microscopy (p = 0.038). <i>Conclusion:</i> VHF ultrasound imaging provided an early in vivo diagnosis of corneal epithelium pathology induced by chronic exposure to a preserved glaucoma drug, before the first clinical evidence of ocular toxicity. It could be a new reproducible method to detect the toxicity of glaucoma medication so that therapy can then be adapted.
DOI: 10.6084/m9.figshare.5120419
title: Supplementary Material for: Lifestyle and Memory in the Elderly

description: <i>Background:</i> Healthy lifestyle has been associated with a decreased risk of developing cardiovascular disease, but its relationship with memory functions is still inconclusive. This study aims to analyze the association between a composite lifestyle index and memory performance. <i>Methods:</i> In this cross-sectional survey, 198 healthy individuals (aged 65–84 years) underwent tests of verbal episodic memory. A composite lifestyle index was calculated that included the following lifestyle dimensions: physical exercise, dietary habits, BMI, smoking and alcohol consumption. The healthiest behavior was defined as: a BMI &lt;22; a diet high in fruits, vegetables, wholemeal/low-fat foods and unsaturated fatty acids; energy expenditure through physical activity &gt;13,000 kcal/week; a history of never smoking; an alcohol consumption of 4–10 drinks per week. <i>Results:</i> Linear regression analysis revealed that a high lifestyle index score was associated with a better memory score (after adjusting for age, sex, education and blood pressure). The composite index had a stronger relationship with memory scores than single factors. <i>Conclusions:</i> This cross-sectional study revealed that a healthy lifestyle, assessed by a simple composite index, is related to better memory performance in healthy elderly individuals. Our findings point to the importance of a comprehensive modulation of lifestyle factors when finding ways to preserve memory functions in the elderly.
DOI: 10.6084/m9.figshare.5120407
title: Supplementary Material for: Mutations in the <i>RSPO1</i> Coding Region Are Not the Main Cause of Canine <i>SRY</i>-Negative XX Sex Reversal in Several Breeds

description: This report details a case of <i>SRY</i>-negative XX sex reversal in a mixed breed dog and surveys affected dogs of several breeds for mutations in <i>RSPO1</i> coding regions. Genomic DNA from the mixed breed case was evaluated for mutations in candidate genes. Sequencing identified a homozygous G to A transition in <i>RSPO1</i> exon 4 that changes a highly conserved amino acid codon in the thrombospondin domain. The possibility that this was a single nucleotide polymorphism (SNP) could not be excluded by genotyping family members. Therefore, the coding region of <i>RSPO1</i> was sequenced in a survey of affected dogs, which identified a T to C transition (exon 3) in some, the above G to A transition (exon 4) in others, and no change in the remaining affected dogs. Genotypes at these base pair positions were not uniquely associated with the affected phenotype in any breed, indicating the identified transitions are most likely SNPs, not causative mutations for this canine disorder. However, the possibility that polymorphisms play a modifier role, such as changing threshold or severity of phenotypic expression in a mixed breed dog, cannot be excluded. This study emphasizes the importance of canine pedigree, breed, and population studies in evaluating candidate mutations.
DOI: 10.6084/m9.figshare.5120410
title: Supplementary Material for: ‘Speech-Smile’, ‘Speech-Laugh’, ‘Laughter’ and Their Sequencing in Dialogic Interaction

description: Laughing is examined auditorily and acoustico-graphically, on the basis of exemplary speech data from spontaneous German dialogues, as pulmonic air stream modulation for communicative functions, paying attention to fine phonetic detail in interactional context. These phonetic case descriptions of laughing phenomena in speaker interaction in a small corpus have as their goal to create an awareness of the phonetic and functional parameters that need to be considered in the future acquisition, acoustic analysis and statistical evaluation of large spontaneous databases.
DOI: 10.6084/m9.figshare.5120407.v1
title: Supplementary Material for: Mutations in the <i>RSPO1</i> Coding Region Are Not the Main Cause of Canine <i>SRY</i>-Negative XX Sex Reversal in Several Breeds

description: This report details a case of <i>SRY</i>-negative XX sex reversal in a mixed breed dog and surveys affected dogs of several breeds for mutations in <i>RSPO1</i> coding regions. Genomic DNA from the mixed breed case was evaluated for mutations in candidate genes. Sequencing identified a homozygous G to A transition in <i>RSPO1</i> exon 4 that changes a highly conserved amino acid codon in the thrombospondin domain. The possibility that this was a single nucleotide polymorphism (SNP) could not be excluded by genotyping family members. Therefore, the coding region of <i>RSPO1</i> was sequenced in a survey of affected dogs, which identified a T to C transition (exon 3) in some, the above G to A transition (exon 4) in others, and no change in the remaining affected dogs. Genotypes at these base pair positions were not uniquely associated with the affected phenotype in any breed, indicating the identified transitions are most likely SNPs, not causative mutations for this canine disorder. However, the possibility that polymorphisms play a modifier role, such as changing threshold or severity of phenotypic expression in a mixed breed dog, cannot be excluded. This study emphasizes the importance of canine pedigree, breed, and population studies in evaluating candidate mutations.
DOI: 10.6084/m9.figshare.5120410.v1
title: Supplementary Material for: ‘Speech-Smile’, ‘Speech-Laugh’, ‘Laughter’ and Their Sequencing in Dialogic Interaction

description: Laughing is examined auditorily and acoustico-graphically, on the basis of exemplary speech data from spontaneous German dialogues, as pulmonic air stream modulation for communicative functions, paying attention to fine phonetic detail in interactional context. These phonetic case descriptions of laughing phenomena in speaker interaction in a small corpus have as their goal to create an awareness of the phonetic and functional parameters that need to be considered in the future acquisition, acoustic analysis and statistical evaluation of large spontaneous databases.
DOI: 10.6084/m9.figshare.5120413.v1
title: Supplementary Material for: Genome-Wide Analysis of Dietary Eicosapentaenoic Acid- and Oleic Acid-Induced Modulation of Colon Inflammation in Interleukin-10 Gene-Deficient Mice

description: <i>Background/Aims:</i> Dietary n–3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient <i>(Il10</i><sup>–/–</sup><i>)</i> mice. <i>Methods:</i> At 35 days of age, 12 weaned <i>Il10</i><sup>–/–</sup> and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n–3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. <i>Results:</i> In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed <i>Il10</i><sup>–/–</sup> compared to C57 mice. <i>Il10</i><sup>–/–</sup> mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in <i>Il10</i><sup>–/–</sup> mice. <i>Conclusions:</i> These data indicate that dietary EPA-induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the <i>Ppara</i> gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins.
DOI: 10.6084/m9.figshare.5120416.v1
title: Supplementary Material for: Very-High-Frequency Ultrasound Corneal Imaging as a New Tool for Early Diagnosis of Ocular Surface Toxicity in Rabbits Treated with a Preserved Glaucoma Drug

description: <i>Aim:</i> To evaluate very-high-frequency (VHF) ultrasound imaging as a new method to detect and quantify early corneal epithelium changes induced by chronic exposure to a benzalkonium-chloride-containing antiglaucoma drug. <i>Methods:</i> Timolol preserved with 0.01% benzalkonium chloride solution was applied b.i.d. in 1 eye of 10 rabbits for 56 days. Unpreserved timolol solution was used as control. Ocular surface changes were assessed weekly combining clinical examinations, in vivo 60-MHz ultrasound imaging and ex vivo histological analysis. <i>Results:</i> VHF ultrasound imaging allowed quantitative measurement of corneal epithelium thickness and qualitative imaging of toxic epithelial damage. It revealed significantly decreased epithelial thickness in vivo as early as the 21st day of treatment (40.75 ± 1.72 µm at D0 vs. 39 ± 2 at D21, vs. 31.9 ± 2.98 at D56; p = 0.017 and p = 0.005, respectively). The first clinical changes appeared from the 42nd day of treatment (conjunctival redness, conjunctival staining and corneal staining; D56 compared to D0: p = 0.005, 0.01 and 0.004, respectively) and then correlated with VHF ultrasound data. Epithelial thickness measured with VHF ultrasound was correlated with histological epithelial pachymetry (p &lt; 0.001) and with the corneal damage score assessed with scanning electron microscopy (p = 0.038). <i>Conclusion:</i> VHF ultrasound imaging provided an early in vivo diagnosis of corneal epithelium pathology induced by chronic exposure to a preserved glaucoma drug, before the first clinical evidence of ocular toxicity. It could be a new reproducible method to detect the toxicity of glaucoma medication so that therapy can then be adapted.
DOI: 10.6084/m9.figshare.5120392
title: Supplementary Material for: Granule Formation in NGF-Cultured Mast Cells Is Associated with Expressions of Pyruvate Kinase Type M2 and Annexin I Proteins

description: <i>Background:</i> Nerve growth factor (NGF) is a potent mediator, which regulates characteristics of mast cells, but its biological function is not well characterized. This study aimed to screen proteins associated with the maturation of human mast cells-1 (HMC-1) or mouse bone marrow-derived mast cells (BMMCs) cultured with NGF, and to examine the functions of proteins involved. <i>Methods:</i> NGF (10 ng/ml) was added to cell culture medium every other day for 10 days for HMC-1 or twice a week for 5 weeks for BMMCs. Granule formation was determined by electron microscopy or May-Grünwald-Giemsa staining, TNF-α by ELISA, expressions of various proteins by two-dimensional gel electrophoresis (2-DE), siRNA transfection by Lipofectamine 2000, and the expressions of pyruvate kinase and annexin I by immunoblotting. <i>Results:</i> After NGF treatment, granule formation and total amounts of granular mediator, TNF-α increased in both mast cells. This TNF-α was released by calcium ionophore or by antigen/antibody reaction. Expressions of pyruvate kinase and annexin I obtained by 2-DE were confirmed by immunoblotting and siRNA-transfected HMC-1 cells. Expressions of proteins, granule formation and TNF-α content were blocked by both the TrkA inhibitor, K252a, and the ERK inhibitor, PD98059, but not by the PI3 kinase inhibitors, LY294002 and wortmannin. <i>Conclusion:</i> These data suggest that pyruvate kinase and annexin I expressed by NGF contribute to granule formation containing TNF-α as well as other mediators in mast cells, which play a major role in allergic diseases via a TrkA/ERK pathway.
DOI: 10.6084/m9.figshare.5120401
title: Supplementary Material for: <i>DNAI1</i> Mutations Explain Only 2% of Primary Ciliary Dykinesia

description: <i>Background:</i> Primary ciliary dyskinesia (PCD) is a rare recessive hereditary disorder characterized by dysmotility to immotility of ciliated and flagellated structures. Its main symptoms are respiratory, caused by defective ciliary beating in the epithelium of the upper airways (nose, bronchi and paranasal sinuses). Impairing the drainage of inhaled microorganisms and particles leads to recurrent infections and pulmonary complications. To date, 5 genes encoding 3 dynein protein arm subunits <i>(DNAI1</i>, <i>DNAH5</i> and <i>DNAH11)</i>, the kinase <i>TXNDC3</i> and the X-linked <i>RPGR</i> have been found to be mutated in PCD. <i>Objectives:</i> We proposed to determine the impact of the <i>DNAI1</i> gene on a cohort of unrelated PCD patients (n = 104) recruited without any phenotypic preselection. <i>Methods:</i> We used denaturing high-performance liquid chromatography and sequencing to screen for mutations in the coding and splicing site sequences of the gene <i>DNAI1</i>. <i>Results:</i> Three mutations were identified: a novel missense variant (p.Glu174Lys) was found in 1 patient and 2 previously reported variants were identified (p.Trp568Ser in 1 patient and IVS1+2_3insT in 3 patients). Overall, mutations on both alleles of gene <i>DNAI1</i> were identified in only 2% of our clinically heterogeneous cohort of patients. <i>Conclusion:</i> We conclude that <i>DNAI1</i> gene mutation is not a common cause of PCD, and that major or several additional disease gene(s) still remain to be identified before a sensitive molecular diagnostic test can be developed for PCD.
DOI: 10.6084/m9.figshare.5120404
title: Supplementary Material for: Recruitment and in situ Renewal Regulate Rapid Accumulation of CD11c+ Cells in the Lung following Intranasal Superantigen Challenge

description: <i>Background:</i><i> Staphylococcus</i><i>aureus</i>, a primary source of bacterial superantigen, is known to colonize the human respiratory tract and has been implicated in airway inflammation. The potential pathological effect of staphylococcal enterotoxins on the respiratory tract necessitates a detailed understanding of how they regulate innate immune cells, particularly CD11c-expressing dendritic cells (DCs). <i>Methods:</i> C57BL/6 mice were challenged intranasally with staphylococcal enterotoxin A (SEA) and at indicated time points lung tissue was perfused, digested and analyzed for CD11c+ expressing cells. <i>Results:</i> The pulmonary CD11c+ cells can be divided into two major populations based on their MHC II expression. One day following intranasal SEA challenge, there was rapid accumulation of CD11c+ cells expressing medium to high levels of MHC II. The peak accumulation of CD11c+ MHC II– population was observed 2 days after SEA challenge; however, careful examination of this cell population revealed that they were heterogeneous, being comprised of cells bearing CD3, CD19, NK1.1 and F4/80 along with varying levels of CD11c. Nevertheless, there was a 2-fold increase of CD11c+ MHC II– (CD3– CD19– NK1.1– F4/80–) cells in the lungs. <i>Conclusion:</i> The mechanism of increase in the CD11c+ MHC II– immune progenitor population was mainly due to cellular division rather than migration from blood to lung. In contrast, the early and rapid accumulation of CD11c+ MHC II<sup>hi</sup> cells, conventionally known as DCs, in the lung on day 1 was mostly due to migration from blood. Thus this study examines the pulmonary innate immune response to a powerful immune stimulus.
DOI: 10.6084/m9.figshare.5120395
title: Supplementary Material for: Chemokine MIP-2/CXCL2, Acting on CXCR2, Induces Motor Neuron Death in Primary Cultures

description: <i>Objectives:</i> Chemokines are implicated in many diseases of the central nervous system (CNS). Although their primary role is to induce inflammation through the recruitment of leukocytes by their chemotactic activity, they may also have direct effects on neuronal cells. We evaluated the expression of CXCR1 and CXCR2 and investigated the effect of CXCR2 activation by the agonist MIP-2 (CXCL2) on primary cultured motor neurons. To specifically assess the role of CXCR2 in the neurotoxicity induced by MIP-2, we used the CXCR1/2 inhibitor reparixin and studied the effect of the chemokine on motor neuron cultures from CXCR2-deficient mice. <i>Methods:</i> Primary motor neurons prepared from rat or mouse embryos were treated with MIP-2 and reparixin. Motor neuron viability and receptor expression were assessed by immunocytochemical techniques. <i>Results:</i> Rat primary motor neurons expressed CXCR2 receptors and recombinant rat MIP-2 induced dose-dependent neurotoxicity. This neurotoxicity was counteracted by reparixin, a specific CXCR1/2 inhibitor, and was not observed in motor neurons from CXCR2-deficient mice. <i>Conclusions:</i> CXCR2 activation might directly contribute to motor neuron degeneration. Thus, chemokines acting on CXCR2, including IL-8, may have direct pathogenic effects in CNS diseases, independent of the induction of leukocyte migration.