cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126623
title: Supplementary Material for: Association of Leptin Gene -2548 G/A Polymorphism with Obesity: A Meta-Analysis

description: <b><i>Background:</i></b> A common single-nucleotide polymorphism identified in the 5′-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis. <b><i>Methods:</i></b> Medline, Embase and ISI Web of Science databases were searched to identify relevant studies. Meta-analysis of the total and subgroup populations was conducted using allelic, additive, dominant and recessive models, and odds ratios and their 95% confidence intervals were calculated in a fixed-effect model if no heterogeneity (evaluated as I<sup>2</sup> statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by ethnicity. Meta-regression and the HETRED analysis were used to explore the potential sources of between-study heterogeneity. Egger's test and influence analysis were conducted to evaluate the publication bias and study power, respectively. <b><i>Results:</i></b> The final selection enrolled 9 studies, including 2,988 subjects (1,372 obese subjects and 1,616 controls). No significant association was identified between the LEP -2548 G/A polymorphism and obesity for all genetic models in the overall population and Caucasians. We found a significant association with allelic, additive and dominant models for subjects of mixed race from South America. Notwithstanding, this significance should be treated cautiously for it is based on a rather small sample (788 involved subjects). <b><i>Conclusions:</i></b> In total, the combined analysis of data from current and published studies suggested that the LEP -2548 G/A polymorphism does not contribute to the development of obesity, despite the fact that a significant association exists in a small subgroup from South America. Further studies are needed to elucidate the relationship.
DOI: 10.6084/m9.figshare.5126617
title: Supplementary Material for: Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model

description: Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases.
DOI: 10.6084/m9.figshare.5126623.v1
title: Supplementary Material for: Association of Leptin Gene -2548 G/A Polymorphism with Obesity: A Meta-Analysis

description: <b><i>Background:</i></b> A common single-nucleotide polymorphism identified in the 5′-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis. <b><i>Methods:</i></b> Medline, Embase and ISI Web of Science databases were searched to identify relevant studies. Meta-analysis of the total and subgroup populations was conducted using allelic, additive, dominant and recessive models, and odds ratios and their 95% confidence intervals were calculated in a fixed-effect model if no heterogeneity (evaluated as I<sup>2</sup> statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by ethnicity. Meta-regression and the HETRED analysis were used to explore the potential sources of between-study heterogeneity. Egger's test and influence analysis were conducted to evaluate the publication bias and study power, respectively. <b><i>Results:</i></b> The final selection enrolled 9 studies, including 2,988 subjects (1,372 obese subjects and 1,616 controls). No significant association was identified between the LEP -2548 G/A polymorphism and obesity for all genetic models in the overall population and Caucasians. We found a significant association with allelic, additive and dominant models for subjects of mixed race from South America. Notwithstanding, this significance should be treated cautiously for it is based on a rather small sample (788 involved subjects). <b><i>Conclusions:</i></b> In total, the combined analysis of data from current and published studies suggested that the LEP -2548 G/A polymorphism does not contribute to the development of obesity, despite the fact that a significant association exists in a small subgroup from South America. Further studies are needed to elucidate the relationship.
DOI: 10.6084/m9.figshare.5126629
title: Supplementary Material for: Frugivory and Seed Dispersal Patterns of the Red-Ruffed Lemur, <b><i>Varecia rubra,</i></b> at a Forest Restoration Site in Masoala National Park, Madagascar

description: Frugivorous primates can play a critical role in the regeneration of degraded habitats by dispersing seeds of their food plants. We studied the diet and seed dispersal patterns of 3 groups of habituated red-ruffed lemurs <i>(Varecia rubra)</i> in a rain forest restoration site in Masoala National Park, Madagascar, to assess the species' seed dispersal effectiveness. Fruits accounted for 61% of the diet, with an average foraging time of 10 min per fruit patch per day. Seeds from 75% of the consumed fruit species were recovered in the collected <i>V. rubra </i>feces. We traced the potential parent plants of 20 dispersed-seed species to calculate a gut passage range (63-423 min; mean = 225, n = 35). The median seed dispersal distance from the potential parent plant was 48 m (mean = 83 m, range 0-568 m, n = 194). The home ranges of 2 of the 3 groups overlapped with the regenerating forest parcels. Although 92% of fecal samples with seeds were dispersed into the undisturbed forest, <i>V. rubra</i> fed on the fruits of the non-native pioneer shrub <i>Clidemia hirta,</i> while also dispersing native and non-native seed species into the regenerating forest parcels.
DOI: 10.6084/m9.figshare.5126611
title: Supplementary Material for: <b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

description: <i>Porphyromonas gingivalis</i> is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-interleukin (IL)-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of <i>P. gingivalis</i> fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with <i>P. gingivalis</i> (381) or isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K<sup>+</sup> efflux and Ca<sup>2+</sup>-independent phospholipase A<sub>2</sub> activity. Accordingly, non-fimbriated <i>P. gingivalis</i> failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, <i>P. gingivalis</i>-driven stimulation of IL-1β was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of <i>P. gingivalis</i> stimulation, which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a marked focus formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by <i>P. gingivalis </i>fimbriae in a P2X7-dependent manner.
DOI: 10.6084/m9.figshare.5126614
title: Supplementary Material for: Oligophrenin-1 Is Associated with Cell Adhesion and Migration in Prostate Cancer

description: <b><i>Objective:</i></b> We performed <i>Escherichia coli</i> ampicillin secretion trap (CAST) analysis in prostate cancer (PCa) to identify novel biomarkers. We show here that <i>OPHN1</i>, which encodes oligophrenin-1 protein, is upregulated in PCa. <i>OPHN1</i> was first determined to be one of the genes associated with X-linked mental retardation; however, neither the gene's function nor the link between its expression and survival of patients has been investigated. <b><i>Methods:</i></b> We investigate the expression of oligophrenin-1 in 141 PCa tissue samples by immunohistochemistry and perform functional analysis using RNA interference. <b><i>Results:</i></b> Immunohistochemical analysis of oligophrenin-1 demonstrated that 60 (43%) PCa cases were positive for oligophrenin-1. Positive oligophrenin-1 expression was significantly correlated with a high Gleason score (p = 0.0198). Furthermore, patients with oligophrenin-1-positive PCa had a worse biochemical recurrence-free survival rate than patients with oligophrenin-1-negative PCa (p = 0.0079). Cell adhesion to fibronectin was significantly reduced in <i>OPHN1</i> small interfering (si)RNA-transfected LNCaP and PC3 cells in comparison to negative-control siRNA-transfected cells. Knockdown of <i>OPHN1</i> reduced the expression of <i>ITGA5 </i>and stress fiber formation in LNCaP and PC3 cells. <b><i>Conclusion:</i></b> These results suggest that oligophrenin-1 is involved in tumor progression in PCa.
DOI: 10.6084/m9.figshare.5126617.v1
title: Supplementary Material for: Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model

description: Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases.
DOI: 10.6084/m9.figshare.5126629.v1
title: Supplementary Material for: Frugivory and Seed Dispersal Patterns of the Red-Ruffed Lemur, <b><i>Varecia rubra,</i></b> at a Forest Restoration Site in Masoala National Park, Madagascar

description: Frugivorous primates can play a critical role in the regeneration of degraded habitats by dispersing seeds of their food plants. We studied the diet and seed dispersal patterns of 3 groups of habituated red-ruffed lemurs <i>(Varecia rubra)</i> in a rain forest restoration site in Masoala National Park, Madagascar, to assess the species' seed dispersal effectiveness. Fruits accounted for 61% of the diet, with an average foraging time of 10 min per fruit patch per day. Seeds from 75% of the consumed fruit species were recovered in the collected <i>V. rubra </i>feces. We traced the potential parent plants of 20 dispersed-seed species to calculate a gut passage range (63-423 min; mean = 225, n = 35). The median seed dispersal distance from the potential parent plant was 48 m (mean = 83 m, range 0-568 m, n = 194). The home ranges of 2 of the 3 groups overlapped with the regenerating forest parcels. Although 92% of fecal samples with seeds were dispersed into the undisturbed forest, <i>V. rubra</i> fed on the fruits of the non-native pioneer shrub <i>Clidemia hirta,</i> while also dispersing native and non-native seed species into the regenerating forest parcels.
DOI: 10.6084/m9.figshare.5126608
title: Supplementary Material for: Two Adjustment Strategies for Imputation across Genotyping Arrays

description: Genotype imputation is a powerful approach in genome-wide association studies (GWAS) because it can provide higher resolution for associated regions and facilitate meta-analysis. However, bias can exist if different genotyping arrays are used and are unbalanced for case versus control subjects. The intersection imputation strategy [imputation based on single nucleotide polymorphisms (SNPs) available on all arrays] is a valid strategy that eliminates the bias caused by unbalanced genotyping, but achieved at the expense of reduced statistical power. In order to improve power in this situation, we introduce two new strategies: the replacement strategy based on the imputation quality score (IQS) ≥0.9 and the correction strategy. The IQS is a score that we have previously introduced based on Cohen's kappa of rater agreement. The replacement strategy with IQS ≥0.9 is a hybrid approach that utilizes measured genotypes for SNPs available on one or more of all arrays whenever the SNP has a high imputation quality (defined by IQS ≥0.9). The correction strategy combines measured genotypes as well as imputed and corrected genotype dosages for SNPs available on one or more of all arrays. The correction strategy yields a valid statistical test, while the replacement strategy with IQS ≥0.9 eliminates most spurious associations. Both strategies maintain statistical power.
DOI: 10.6084/m9.figshare.5126602
title: Supplementary Material for: A Serine Protease Homolog Negatively Regulates TEP1 Consumption in Systemic Infections of the Malaria Vector Anopheles gambiae

description: Clip domain serine protease homologs are widely distributed in insect genomes and play important roles in regulating insect immune responses, yet their exact functions remain poorly understood. Here, we show that CLIPA2, a clip domain serine protease homolog of <i>Anopheles gambiae</i>, regulates the consumption of the mosquito complement-like protein TEP1 during systemic bacterial infections. We provide evidence that CLIPA2 localizes to microbial surfaces in a TEP1-dependent manner whereby it negatively regulates the activity of a putative TEP1 convertase, which converts the full-length TEP1-F form into active TEP1<sub>cut</sub>. CLIPA2 silencing triggers an exacerbated TEP1-mediated response that significantly enhances mosquito resistance to infections with a broad class of microorganisms including <i>Plasmodium berghei</i>, <i>Escherichia coli</i> and the entomopathogenic fungus <i>Beauveria bassiana</i>. We also provide further evidence for the existence of a functional link between TEP1 and activation of hemolymph prophenoloxidase during systemic infections. Interestingly, the enhanced TEP1-mediated immune response in <i>CLIPA2</i> knockdown mosquitoes correlated with a significant reduction in fecundity, corroborating the existence of a trade-off between immunity and reproduction. In sum, CLIPA2 is an integral regulatory component of the mosquito complement-like pathway which functions to prevent an overwhelming response by the host in response to systemic infections.
DOI: 10.6084/m9.figshare.5126605
title: Supplementary Material for: A Common Copy Number Variation Polymorphism in the <b><i>CNTNAP2</i></b> Gene: Sexual Dimorphism in Association with Healthy Aging and Disease

description: <b><i>Background:</i></b> New therapeutic targets are needed to fight aging-related diseases and increase life span. A new female-specific association with diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the <i>CNTNAP4 </i>gene from the neurexin superfamily. <b><i>Objective:</i></b> We asked whether there are CNVs that are associated with aging phenotypes within other genes from the neurexin superfamily and whether this association is sex specific. <b><i>Methods:</i></b> Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR assays. <b><i>Results:</i></b> A case/control study, in which a group of 81- to 90-year-old community-dwelling Caucasians with no chronic diseases (case) was compared to a similar control group of 65- to 75-year-olds, revealed a negative association with healthy aging for the ins allele of common esv11910 CNV in the <i>CNTNAP2 </i>gene (n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95% CI: 0.42-1.57, p = 0.625 for females). This male-specific association was validated in a study of an independent group of 76- to 80-year-olds. To look for a corresponding positive association of the allele with aging-related diseases, two case subgroups of 81- to 90-year-olds, one composed of individuals with cognitive impairment and the other with various diseases not directly related to the nervous system, such as cardiovascular diseases, etc., were compared to a healthy control subgroup of the same age. A positive male-specific association was found for both cases (OR = 2.75, p = 0.008 for association with cognitive impairment, and OR = 3.18, p = 0.002 for other diseases combined). <b><i>Conclusions:</i></b> A new male-specific association with aging is reported for a CNV in the <i>CNTNAP2 </i>gene. The polymorphism might be useful for diagnosing individual genetic predispositions to healthy aging versus aging complicated by chronic diseases.
DOI: 10.6084/m9.figshare.5126611.v1
title: Supplementary Material for: <b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

description: <i>Porphyromonas gingivalis</i> is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-interleukin (IL)-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of <i>P. gingivalis</i> fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with <i>P. gingivalis</i> (381) or isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K<sup>+</sup> efflux and Ca<sup>2+</sup>-independent phospholipase A<sub>2</sub> activity. Accordingly, non-fimbriated <i>P. gingivalis</i> failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, <i>P. gingivalis</i>-driven stimulation of IL-1β was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of <i>P. gingivalis</i> stimulation, which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a marked focus formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by <i>P. gingivalis </i>fimbriae in a P2X7-dependent manner.
DOI: 10.6084/m9.figshare.5126608.v1
title: Supplementary Material for: Two Adjustment Strategies for Imputation across Genotyping Arrays

description: Genotype imputation is a powerful approach in genome-wide association studies (GWAS) because it can provide higher resolution for associated regions and facilitate meta-analysis. However, bias can exist if different genotyping arrays are used and are unbalanced for case versus control subjects. The intersection imputation strategy [imputation based on single nucleotide polymorphisms (SNPs) available on all arrays] is a valid strategy that eliminates the bias caused by unbalanced genotyping, but achieved at the expense of reduced statistical power. In order to improve power in this situation, we introduce two new strategies: the replacement strategy based on the imputation quality score (IQS) ≥0.9 and the correction strategy. The IQS is a score that we have previously introduced based on Cohen's kappa of rater agreement. The replacement strategy with IQS ≥0.9 is a hybrid approach that utilizes measured genotypes for SNPs available on one or more of all arrays whenever the SNP has a high imputation quality (defined by IQS ≥0.9). The correction strategy combines measured genotypes as well as imputed and corrected genotype dosages for SNPs available on one or more of all arrays. The correction strategy yields a valid statistical test, while the replacement strategy with IQS ≥0.9 eliminates most spurious associations. Both strategies maintain statistical power.
DOI: 10.6084/m9.figshare.5126593
title: Supplementary Material for: Anterior Temporal Atrophy and Posterior Progression in Patients with Parkinson's Disease

description: <b><i>Background:</i></b> Parkinson's disease (PD) is characterized by specific motor and nonmotor impairments. This suggests that PD is characterized by disease-specific regional cortical atrophy. Given the change of symptoms over time, a concurrent increase in regional atrophy may further be assumed to reflect the dynamic process of disease progression. <b><i>Methods:</i></b> In this study we retrospectively collected T1-weighted MRI scans from previous studies performed in our center, enabling the comparison of gray matter atrophy in 77 PD patients with 87 controls using voxel-based morphometry (VBM). This large VBM analysis provided the opportunity to investigate cortical atrophy in relation with disease progression. <b><i>Results:</i></b> We found significant PD-related reductions of gray matter density bilaterally in the anterior temporal cortex, the left inferior frontal and left extrastriate visual cortex, independent from normal aging. The anterior temporal cortex did not show major progression, whereas particularly the posterior parts of the lateral temporal cortex and adjacent extrastriate visual cortex occurred at a later stage of disease. <b><i>Conclusions:</i></b> Temporal pole atrophy as an early sign of PD is consistent with the PD pathology classification of Braak. The initial anterior temporal atrophy with spread to occipitotemporal and posterior parietal regions may subserve ‘emotion-based' sensorimotor transformations and deficits in the visual domain, respectively, which may be regarded as premotor symptoms.