cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122963
title: Supplementary Material for: Neuroanatomical Correlates of Cognitive Performance in Late Life

description: <i>Background/Aim:</i> While a number of studies examined the neuroanatomical correlates of cognitive function in older adults, the results have been inconsistent. Examination of a large epidemiologically acquired sample with high-resolution magnetic resonance imaging has the potential to enhance the evidence in this field. <i>Methods:</i> The participants were 326 non-demented elderly adults undergoing a battery of neuropsychological tests and brain magnetic resonance imaging scans. Regression analyses were performed to examine the correlation between voxel-based grey matter (GM) volume and four cognitive domain scores. <i>Results:</i> Positive correlations were observed between specific GM volumes and cognitive domains, i.e. bilateral temporal lobes and hippocampi with language; bilateral temporal, parietal, and occipital lobes with processing speed; and bilateral frontal, temporal, parietal, and occipital lobes with executive function. The positive correlation between verbal memory performance and GM volume in the bilateral medial temporal lobes was not significant after correction for age. <i>Conclusion:</i> Our findings suggest that the location of GM correlates of cognitive tests is largely consistent with the conventional understanding of the neuroanatomical basis of cognition. However, the lack of hemispheric predominance in these GM correlates, and the extensively positive correlation between GM volume and cognitive performance, perhaps reflects the characteristics of the ageing brain.
DOI: 10.6084/m9.figshare.5122954
title: Supplementary Material for: Subsequent Risks of Parkinson Disease in Patients with Autoimmune and Related Disorders: A Nationwide Epidemiological Study from Sweden

description: <i>Objectives:</i> To investigate associations between autoimmune disorders and Parkinson disease (PD), and to study whether the risk is associated with follow-up time and age. <i>Methods:</i> Standardized incidence ratios (SIRs) were calculated for PD in patients with autoimmune disorders by comparing them to subjects without autoimmune disorders. <i>Results:</i> Among 310,522 patients with a total of 33 conditions of autoimmune disorders, 932 patients developed subsequent PD, giving an overall SIR of 1.33 and 1.19 for PD diagnosed later than 1 year after follow-up. Six types of autoimmune disorders showed an increased risk. These conditions included: amyotrophic lateral sclerosis, Graves’s disease/hyperthyroidism, Hashimoto’s disease/hypothyroidism, multiple sclerosis, pernicious anemia, and polymyalgia rheumatica. The risks depended on the age at hospitalization for PD. <i>Conclusions:</i> A 33% overall excess risk of PD was noted among patients with an autoimmune disorder; the risk was increased during the first 10 years of follow-up after hospitalization of autoimmune disorders.
DOI: 10.6084/m9.figshare.5122957
title: Supplementary Material for: FFSS – Fragebogen zur Erfassung funktioneller somatischer Syndrome

description: Medicine
DOI: 10.6084/m9.figshare.5122945
title: Supplementary Material for: Early Life Interventions to Prevent Allergy in the Offspring: The Role of Maternal Immunization and Postnatal Mucosal Allergen Exposure

description: <i>Background:</i> Childhood allergy is influenced by maternal factors and allergen exposure in early life, but the factors that determine the development of allergy and tolerance are unknown. Therefore, we compared the effects of two early life interventions, i.e. maternal allergen immunization and postnatal intranasal allergen exposure, as well as a combination of both treatments on allergic responses in the offspring. <i>Methods:</i> Female mice were immunized with ovalbumin (OVA) or vehicle during pregnancy. After birth, half the offspring from each group were exposed intranasally to low doses of OVA or vehicle weekly for 5 weeks before intraperitoneal immunization with OVA. <i>Results:</i> Maternal immunization reduced OVA-specific IgE and IgG1, but increased IgG2a and T<sub>H</sub>2 cytokine responses in the offspring after immunization. Postnatal intranasal OVA exposure similarly reduced both IgE and IgG1, but also spleen cell numbers and cytokine secretion. Following airway challenges of the offspring, IgE and airway inflammation were suppressed only by intranasal exposure, but not by maternal immunization, the effect of which also waned with age. Differential gene expression in the spleen of offspring supported that IgE suppression by the two interventions was caused by different mechanisms. Despite this, tolerance development after mucosal exposure was obtained in the offspring of immunized dams. <i>Conclusions:</i> The study suggests that prevention of allergy is possible if initiated in early life, and early mucosal allergen exposure may play a protective role independent of the maternal immune responses.
DOI: 10.6084/m9.figshare.5122948
title: Supplementary Material for: Endoplasmic Reticulum Stress Impairs Insulin Signaling through Mitochondrial Damage in SH-SY5Y Cells

description: Endoplasmic reticulum (ER) and mitochondrial stress are considered causal factors that induce neurodegenerative diseases. However, the relationship between these stresses remains poorly understood. To investigate the molecular mechanism underlying crosstalk between the ER and mitochondria in neurodegeneration, we treated SH-SY5Y human neuroblastoma cells with thapsigargin and tunicamycin, two inducers of ER stress, and atrazine, a promoter of mitochondrial stress. Each pharmacological agent caused mitochondrial dysfunction, which was characterized by reduced intracellular ATP, mitochondrial membrane potential, and endogenous cellular respiration as well as an augmentation of oxidative stress. Oligonucleotide microarray analysis followed by semiquantitative RT-PCR validation assays revealed that thapsigargin and tunicamycin downregulated the expression of most mitochondria-related genes in a manner similar to that induced by atrazine. In contrast, atrazine did not alter the expression of markers of ER stress. Three-dimensional principal component analysis showed that the gene expression profile produced by atrazine treatment was distinct from that generated by ER stress. However, all three agents impaired insulin receptor substrate-1 and Akt phosphorylation in the insulin signaling pathway. Ectopic overexpression of mitochondrial transcription factor A reversed the effects of thapsigargin on mitochondria and Akt signaling. We conclude that ER stress induces neuronal cell death through common perturbation of mitochondrial function and Akt signaling.
DOI: 10.6084/m9.figshare.5122951
title: Supplementary Material for: Heat Shock Factor 1 Protects against Lung <i>Mycoplasma pneumoniae</i> Infection in Mice

description: Heat shock factor 1 (HSF1) is a transcriptional factor that controls the induction of heat shock proteins (e.g. HSP70) in response to stress. Bacterial infections contribute to the pathobiology of chronic lung diseases such as chronic obstructive pulmonary disease and asthma. Whether HSF1 is critical to lung bacterial infection remains unknown. This study is aimed at investigating the impact of HSF1 deficiency on lung <i>Mycoplasma pneumoniae</i> (Mp) infection and elucidating the underlying molecular mechanisms, such as Toll-like receptor 2 (TLR2) signaling. HSF1<sup>–/–</sup> and HSF1<sup>+/+</sup> mice were intranasally infected with Mp or saline and sacrificed 4, 24 and 72 h after treatment. HSF1<sup>–/–</sup> mice had a higher lung Mp load than HSF1<sup>+/+</sup> mice. Mp-induced lung TLR2, nuclear factor-ĸB and associated inflammation [e.g. keratinocyte-derived chemokine (KC), neutrophils and histopathology] were delayed in HSF1<sup>–/–</sup> mice as compared to HSF1<sup>+/+</sup> mice. HSP70 protein levels in bronchoalveolar lavage fluid of HSF1<sup>–/–</sup> mice were decreased. Furthermore, in response to Mp infection, HSF1<sup>–/–</sup> alveolar macrophages had less TLR2 mRNA expression and KC production than HSF1<sup>+/+</sup> counterparts. Nuclear factor-ĸB activity and KC production in HSF1<sup>–/–</sup> macrophages could be rescued by addition of exogenous HSP70 protein. These data suggest that HSF1 is necessary to initiate host defense against bacterial infection partly through promoting early TLR2 signaling activation.
DOI: 10.6084/m9.figshare.5122948.v1
title: Supplementary Material for: Endoplasmic Reticulum Stress Impairs Insulin Signaling through Mitochondrial Damage in SH-SY5Y Cells

description: Endoplasmic reticulum (ER) and mitochondrial stress are considered causal factors that induce neurodegenerative diseases. However, the relationship between these stresses remains poorly understood. To investigate the molecular mechanism underlying crosstalk between the ER and mitochondria in neurodegeneration, we treated SH-SY5Y human neuroblastoma cells with thapsigargin and tunicamycin, two inducers of ER stress, and atrazine, a promoter of mitochondrial stress. Each pharmacological agent caused mitochondrial dysfunction, which was characterized by reduced intracellular ATP, mitochondrial membrane potential, and endogenous cellular respiration as well as an augmentation of oxidative stress. Oligonucleotide microarray analysis followed by semiquantitative RT-PCR validation assays revealed that thapsigargin and tunicamycin downregulated the expression of most mitochondria-related genes in a manner similar to that induced by atrazine. In contrast, atrazine did not alter the expression of markers of ER stress. Three-dimensional principal component analysis showed that the gene expression profile produced by atrazine treatment was distinct from that generated by ER stress. However, all three agents impaired insulin receptor substrate-1 and Akt phosphorylation in the insulin signaling pathway. Ectopic overexpression of mitochondrial transcription factor A reversed the effects of thapsigargin on mitochondria and Akt signaling. We conclude that ER stress induces neuronal cell death through common perturbation of mitochondrial function and Akt signaling.
DOI: 10.6084/m9.figshare.5122942
title: Supplementary Material for: Increased Expression of Nox1 in Neointimal Smooth Muscle Cells Promotes Activation of Matrix Metalloproteinase-9

description: <i>Objective:</i> Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). <i>Methods and Results:</i> Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. <i>Conclusions:</i> Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.
DOI: 10.6084/m9.figshare.5122945.v1
title: Supplementary Material for: Early Life Interventions to Prevent Allergy in the Offspring: The Role of Maternal Immunization and Postnatal Mucosal Allergen Exposure

description: <i>Background:</i> Childhood allergy is influenced by maternal factors and allergen exposure in early life, but the factors that determine the development of allergy and tolerance are unknown. Therefore, we compared the effects of two early life interventions, i.e. maternal allergen immunization and postnatal intranasal allergen exposure, as well as a combination of both treatments on allergic responses in the offspring. <i>Methods:</i> Female mice were immunized with ovalbumin (OVA) or vehicle during pregnancy. After birth, half the offspring from each group were exposed intranasally to low doses of OVA or vehicle weekly for 5 weeks before intraperitoneal immunization with OVA. <i>Results:</i> Maternal immunization reduced OVA-specific IgE and IgG1, but increased IgG2a and T<sub>H</sub>2 cytokine responses in the offspring after immunization. Postnatal intranasal OVA exposure similarly reduced both IgE and IgG1, but also spleen cell numbers and cytokine secretion. Following airway challenges of the offspring, IgE and airway inflammation were suppressed only by intranasal exposure, but not by maternal immunization, the effect of which also waned with age. Differential gene expression in the spleen of offspring supported that IgE suppression by the two interventions was caused by different mechanisms. Despite this, tolerance development after mucosal exposure was obtained in the offspring of immunized dams. <i>Conclusions:</i> The study suggests that prevention of allergy is possible if initiated in early life, and early mucosal allergen exposure may play a protective role independent of the maternal immune responses.
DOI: 10.6084/m9.figshare.5122957.v1
title: Supplementary Material for: FFSS – Fragebogen zur Erfassung funktioneller somatischer Syndrome

description: Medicine
DOI: 10.6084/m9.figshare.5122933
title: Supplementary Material for: A Generalized Sequential Bonferroni Procedure Using Smoothed Weights for Genome-Wide Association Studies Incorporating Information on Hardy-Weinberg Disequilibrium among Cases

description: <i>Background/Objectives:</i> For genome-wide association studies (GWAS) with case-control designs, one of the most widely used association tests is the Cochran-Armitage (CA) trend test assuming an additive mode of inheritance. The CA trend test often has higher power than other association tests under additive and multiplicative disease models. However, it can have very low power under a recessive disease model in GWAS. Although tests (such as MAX3) robust to different genetic models have been developed, they often have relatively lower power than the CA trend test under additive and multiplicative models. The goal of this study is to propose an efficient method that not only has higher power than the CA trend test under dominant and recessive models but also maintains the power of the CA trend test under additive and multiplicative models. <i>Methods:</i> We employed the generalized sequential Bonferroni (GSB) procedure of Holm to incorporate information from a Hardy-Weinberg disequilibrium (HWD) test into the CA trend test based on estimating weights from the p values of the HWD test. We proposed to smooth the weights to reduce possible noise. <i>Results and Conclusions:</i> Results from extensive simulation studies showed that the proposed GSB procedure can achieve the goal described above.
DOI: 10.6084/m9.figshare.5122936
title: Supplementary Material for: The Antimicrobial Peptide hLF1–11 Drives Monocyte-Dendritic Cell Differentiation toward Dendritic Cells That Promote Antifungal Responses and Enhance Th17 Polarization

description: The hLF1–11 peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo, enhances the inflammatory response of monocytes and directs monocyte-macrophage differentiation toward cells with enhanced antimicrobial properties. In this study, we investigated the effects of hLF1–11 on human monocyte-dendritic cell (DC) differentiation and subsequent T cell activation. Results revealed that – compared to control (peptide-incubated) DCs – hLF1–11-differentiated DCs displayed enhanced expression of HLA class II antigens and dectin-1, and increased phagocytosis of <i>Candida albicans</i>. In addition, hLF1–11-differentiated DCs produced enhanced amounts of reactive oxygen species, IL-6 and IL-10, but not IL-12p40 and TNF-α, upon stimulation with <i>C. albicans</i>. Moreover, 6-day-cultured hLF1–11-differentiated DCs and control (peptide-incubated) DCs that had been stimulated with a Th17-inducing mix of antigens (including <i>C. albicans</i>) for 24 h were cocultured with autologous CD4+ T cells for 72 h and then the levels of IL-10, IL-17 and IFN-γ production and the percentage of cytokine-producing T cells were assessed. The results revealed that the hLF1–11-differentiated DCs induced an enhanced IL-17, but reduced IFN-γ, production by T cells as compared to control (peptide-incubated) DCs. Collectively, the hLF1–11 peptide drives monocyte-DC differentiation toward DCs that promote antifungal responses and enhance Th17 polarization.
DOI: 10.6084/m9.figshare.5122939
title: Supplementary Material for: Factors Associated with Insulin Resistance among Children and Adolescents Perinatally Infected with HIV-1 in the Pediatric HIV/AIDS Cohort Study

description: <i>Background/Aims:</i> Because of prior inconsistent findings, we studied a large cohort of HIV-infected children to determine: (1) prevalence of insulin resistance (IR); (2) anthropometric and clinical correlates of IR, and (3) concomitant abnormalities of glucose tolerance. <i>Methods:</i> The study population consisted of 451 children from the Pediatric HIV/AIDS Cohort Study. The outcome of interest was HOMA-IR. Covariates included demographic, metabolic, growth, body composition, HIV laboratory tests, and treatment characteristics. Children meeting triggers for IR underwent oral glucose tolerance tests and hemoglobin A1c (HbA1c) measurements. <i>Results:</i> Among 402 children with glucose and insulin measurements, 15.2% had IR of whom 79% were pubertal. IR was associated with higher alanine aminotransferase, body mass index, and nadir CD4%, Tanner stage 5, and ever having received amprenavir. Of those with IR, three had impaired fasting glucose (IFG), three impaired glucose tolerance (IGT), one IFG and IGT, none diabetic glucose tolerance, and three HbA1c between 6.1 and 6.5%. <i>Conclusion:</i> In our cohort of HIV-infected adolescents, we observed a 15.2% prevalence of IR more closely linked to obesity than any other variable. This finding mirrors the high prevalence of obesity-mediated IR in American youth. However, associations with CD4 count and use of protease inhibitors may indicate some effect of HIV and/or its treatment.
DOI: 10.6084/m9.figshare.5122930
title: Supplementary Material for: Differentiation of Multipotent Adult Germline Stem Cells Derived from Mouse Testis into Functional Endothelial Cells

description: Pluripotent stem cells hold great promise for the treatment of cardiovascular disease. We previously described multipotent adult germline stem cells (maGSCs) from mouse testis with differentiation potential similar to embryonic stem cells. The aim of this work was to differentiate maGSCs into functional endothelial cells and to study their potential for vasculogenesis. MaGSCs were cocultivated with OP9 stromal cells to induce differentiation into cardiovascular progenitors, i.e. fetal liver kinase 1-positive (Flk-1<sup>+</sup>) cells. Five days later, Flk-1<sup>+</sup> cells were separated using fluorescence-activated cell sorting, followed by cultivation on collagen type IV under endothelial differentiation conditions. At different time points, maGSC-derived endothelial-like cells were characterized using RT-PCR, flow cytometry, immunofluorescence and functional assays. Cultivation of Flk-1<sup>+</sup> cells resulted in the progressive upregulation of endothelial cell markers, including VE-cadherin, von Willebrand factor and endothelial nitric oxide synthase. Moreover, Flk-1<sup>+</sup> maGSC-derived endothelial-like cells were able to branch and form networks in vitro and promoted functional blood vessel formation in vivo. Importantly, Flk-1<sup>+</sup> cells retained their potential to proliferate and could be continuously expanded, while the ability of contact inhibition was preserved. Thus, maGSCs may provide a useful source of endothelial-like cells to study the basic mechanisms of vasculogenesis or endothelial differentiation.
DOI: 10.6084/m9.figshare.5122939.v1
title: Supplementary Material for: Factors Associated with Insulin Resistance among Children and Adolescents Perinatally Infected with HIV-1 in the Pediatric HIV/AIDS Cohort Study

description: <i>Background/Aims:</i> Because of prior inconsistent findings, we studied a large cohort of HIV-infected children to determine: (1) prevalence of insulin resistance (IR); (2) anthropometric and clinical correlates of IR, and (3) concomitant abnormalities of glucose tolerance. <i>Methods:</i> The study population consisted of 451 children from the Pediatric HIV/AIDS Cohort Study. The outcome of interest was HOMA-IR. Covariates included demographic, metabolic, growth, body composition, HIV laboratory tests, and treatment characteristics. Children meeting triggers for IR underwent oral glucose tolerance tests and hemoglobin A1c (HbA1c) measurements. <i>Results:</i> Among 402 children with glucose and insulin measurements, 15.2% had IR of whom 79% were pubertal. IR was associated with higher alanine aminotransferase, body mass index, and nadir CD4%, Tanner stage 5, and ever having received amprenavir. Of those with IR, three had impaired fasting glucose (IFG), three impaired glucose tolerance (IGT), one IFG and IGT, none diabetic glucose tolerance, and three HbA1c between 6.1 and 6.5%. <i>Conclusion:</i> In our cohort of HIV-infected adolescents, we observed a 15.2% prevalence of IR more closely linked to obesity than any other variable. This finding mirrors the high prevalence of obesity-mediated IR in American youth. However, associations with CD4 count and use of protease inhibitors may indicate some effect of HIV and/or its treatment.
DOI: 10.6084/m9.figshare.5122942.v1
title: Supplementary Material for: Increased Expression of Nox1 in Neointimal Smooth Muscle Cells Promotes Activation of Matrix Metalloproteinase-9

description: <i>Objective:</i> Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). <i>Methods and Results:</i> Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. <i>Conclusions:</i> Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.