cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28531617.v2
title: Exploring the causal role of pathogen-derived antibodies in major urinary and kidney diseases: Insights from generalized summary data-based Mendelian randomization

description: Chronic kidney and urinary tract diseases, including glomerulonephritis, nephrotic syndrome, and chronic kidney disease (CKD), present significant global health challenges. Recent studies suggest a complex interplay between infectious pathogens and immune-mediated kidney damage. This study employs Generalized Summary data-based Mendelian Randomization (GSMR) to explore causal relationships between pathogen-derived antibodies and major urinary and kidney diseases.We conducted a two-sample MR analysis using summary statistics from large-scale Genome-Wide Association Studies (GWAS) to assess associations between 46 pathogen-specific antibodies and seven urinary system diseases. We utilized robust statistical methods, including inverse variance weighting, to ascertain causal effects while controlling for potential confounders.Significant associations were identified between several pathogen-specific antibodies and disease risk. Notably, Epstein-Barr virus (EBNA-1) antibody levels were inversely associated with glomerulonephritis and nephrotic syndrome, indicating a potential protective effect. Conversely, Anti-Merkel cell polyomavirus IgG seropositivity was linked to increased risks of CKD and glomerulonephritis. Additionally, immune-mediated mechanisms were highlighted, with certain antibodies exhibiting dual roles as risk factors or protective agents.This study underscores the complex role of pathogen antibodies in the pathogenesis of kidney and urinary tract diseases, revealing significant implications for future research and potential therapeutic strategies. The findings advocate for further investigation into specific pathogen interactions with the immune system, aiming to inform targeted interventions.
DOI: 10.15468/dl.8dyn5d
title: Occurrence Download

description: A dataset containing 916 species occurrences available in GBIF matching the query:
{
 "and" : [
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "TaxonKey is Calochortus lyallii"
 ]
}

 The dataset includes 916 records from 24 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0003551-260120142942310/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.28531617.v1
title: Exploring the causal role of pathogen-derived antibodies in Major urinary and kidney diseases: Insights from generalized summary Data-Based Mendelian Randomization

description: Chronic kidney and urinary tract diseases, including glomerulonephritis, nephrotic syndrome, and chronic kidney disease (CKD), present significant global health challenges. Recent studies suggest a complex interplay between infectious pathogens and immune-mediated kidney damage. This study employs Generalized Summary data-based Mendelian Randomization (GSMR) to explore causal relationships between pathogen-derived antibodies and major urinary and kidney diseases.We conducted a two-sample MR analysis using summary statistics from large-scale Genome-Wide Association Studies (GWAS) to assess associations between 46 pathogen-specific antibodies and seven urinary system diseases. We utilized robust statistical methods, including inverse variance weighting, to ascertain causal effects while controlling for potential confounders.Significant associations were identified between several pathogen-specific antibodies and disease risk. Notably, Epstein-Barr virus (EBNA-1) antibody levels were inversely associated with glomerulonephritis and nephrotic syndrome, indicating a potential protective effect. Conversely, Anti-Merkel cell polyomavirus IgG seropositivity was linked to increased risks of CKD and glomerulonephritis. Additionally, immune-mediated mechanisms were highlighted, with certain antibodies exhibiting dual roles as risk factors or protective agents.This study underscores the complex role of pathogen antibodies in the pathogenesis of kidney and urinary tract diseases, revealing significant implications for future research and potential therapeutic strategies. The findings advocate for further investigation into specific pathogen interactions with the immune system, aiming to inform targeted interventions.
DOI: 10.6084/m9.figshare.29240506
title: Involvement of a variant secretory protein in virulence of emerging <i>Cryptosporidium parvum</i> subtypes

description: Several divergent <i>Cryptosporidium parvum</i> subtypes have emerged in people in recent years, but their infectivity, pathogenicity, and genetic characteristics are unclear. In the present study, IFN-γ knockout C57BL/6 (GKO) mice were infected with the novel IIoA15G1 and IIpA11 subtypes of <i>C. parvum</i> and the common IIaA17G2R1 subtype. The genomes of these isolates were sequenced and compared with each other. Further gene tagging and deletion were performed on the most polymorphic virulence-associated cgd8_5420 gene encoding a hypothetical protein using the CRISPR/Cas9 technology. IIpA11 and IIoA15G1 were highly infectious in GKO mice, with an ID<sub>50</sub> of 2.4 and 3.6 oocysts, respectively. The duration of oocyst shedding for IIpA11 (&gt;58.0 ± 1.4 d) and IIoA15G1 (&gt;57.5 ± 0.9 d) was significantly longer than for IIaA17G2R1 (5.5 ± 0.9 d; <i>p</i> &lt; 0.001). One of the mice infected with IIpA11 died on day 33 post infection. The genomes of IIaA17G2R1, IIoA15G1, and IIpA11 had 203, 46839, and 47,122 single nucleotide polymorphisms, respectively, compared to <i>C. parvum</i> IOWA II. In contrast, only 3,361 nucleotide differences were found between IIoA15G1 and IIpA11, with several genes encoding invasion-associated mucin glycoproteins and cgd8_5420 encoding a secretory protein being highly polymorphic. The latter is mainly expressed in trophozoites, merozoites, and macrogametes. Deletion of this gene reduced the intensity of IIpA11 infection and increased the survival of infected mice. Therefore, the emerging IIoA15G1 and IIpA11 subtypes have divergent genomes compared to common IIa subtypes and are highly infectious and pathogenic in GKO mice. Several secretory proteins, including a variant protein encoded by the subtelomeric cgd8_5420 gene, are associated with differences in virulence between the two subtypes.
DOI: 10.6084/m9.figshare.29240506.v1
title: Involvement of a variant secretory protein in virulence of emerging <i>Cryptosporidium parvum</i> subtypes

description: Several divergent <i>Cryptosporidium parvum</i> subtypes have emerged in people in recent years, but their infectivity, pathogenicity, and genetic characteristics are unclear. In the present study, IFN-γ knockout C57BL/6 (GKO) mice were infected with the novel IIoA15G1 and IIpA11 subtypes of <i>C. parvum</i> and the common IIaA17G2R1 subtype. The genomes of these isolates were sequenced and compared with each other. Further gene tagging and deletion were performed on the most polymorphic virulence-associated cgd8_5420 gene encoding a hypothetical protein using the CRISPR/Cas9 technology. IIpA11 and IIoA15G1 were highly infectious in GKO mice, with an ID<sub>50</sub> of 2.4 and 3.6 oocysts, respectively. The duration of oocyst shedding for IIpA11 (&gt;58.0 ± 1.4 d) and IIoA15G1 (&gt;57.5 ± 0.9 d) was significantly longer than for IIaA17G2R1 (5.5 ± 0.9 d; <i>p</i> &lt; 0.001). One of the mice infected with IIpA11 died on day 33 post infection. The genomes of IIaA17G2R1, IIoA15G1, and IIpA11 had 203, 46839, and 47,122 single nucleotide polymorphisms, respectively, compared to <i>C. parvum</i> IOWA II. In contrast, only 3,361 nucleotide differences were found between IIoA15G1 and IIpA11, with several genes encoding invasion-associated mucin glycoproteins and cgd8_5420 encoding a secretory protein being highly polymorphic. The latter is mainly expressed in trophozoites, merozoites, and macrogametes. Deletion of this gene reduced the intensity of IIpA11 infection and increased the survival of infected mice. Therefore, the emerging IIoA15G1 and IIpA11 subtypes have divergent genomes compared to common IIa subtypes and are highly infectious and pathogenic in GKO mice. Several secretory proteins, including a variant protein encoded by the subtelomeric cgd8_5420 gene, are associated with differences in virulence between the two subtypes.
DOI: 10.6084/m9.figshare.29575311
title: Comprehensive analysis of human keratinocyte interactions with <i>Candida albicans</i> and <i>Candida parapsilosis</i>

description: In recent years, microbiome studies have revealed that <i>Candida</i> species are common colonizers of the human skin. The distribution of species, however, varies greatly. Although <i>C. parapsilosis</i> is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding <i>C. albicans</i> that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - <i>Candida</i> interactions. To study species-specific host responses, we examined internalization, cytokine and metabolic responses in different keratinocytes (HaCaT, HPV-KER) along with host cell damage following fungal stimuli. To rigorously examine yeast-keratinocyte interactions, we applied two distinct isolates of both <i>C. albicans</i> (SC5314, WO-1) and <i>C. parapsilosis</i> (GA1, CLIB214). Comparison of the two fungi’s virulence revealed that while <i>C. albicans</i> effectively adheres to human keratinocytes and causes subsequent damage, <i>C. parapsilosis</i> is unable to establish lasting physical contact and causes less harm. In terms of keratinocyte response, both cell lines showed significantly enhanced cellular (internalization), humoral (IL-6, IL-8) and metabolic responses (2-ketoglutaric acid, citric acid, threorine, hypotaurine) to <i>C. albicans</i> strains, while those towards <i>C. parapsilosis</i> remained relatively low or similar to the control condition. Under certain conditions strain preference was also detected. Of the two cell lines, HPV-KER was more sensitive, as besides interspecies differences, intraspecies differences were also measurable. These results suggest that <i>C. albicans</i> triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like <i>C. parapsilosis</i>. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.
DOI: 10.6084/m9.figshare.29575311.v2
title: Comprehensive analysis of human keratinocyte interactions with <i>Candida albicans</i> and <i>Candida parapsilosis</i>

description: In recent years, microbiome studies have revealed that <i>Candida</i> species are common colonizers of the human skin. The distribution of species, however, varies greatly. Although <i>C. parapsilosis</i> is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding <i>C. albicans</i> that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - <i>Candida</i> interactions. To study species-specific host responses, we examined internalization, cytokine and metabolic responses in different keratinocytes (HaCaT, HPV-KER) along with host cell damage following fungal stimuli. To rigorously examine yeast-keratinocyte interactions, we applied two distinct isolates of both <i>C. albicans</i> (SC5314, WO-1) and <i>C. parapsilosis</i> (GA1, CLIB214). Comparison of the two fungi’s virulence revealed that while <i>C. albicans</i> effectively adheres to human keratinocytes and causes subsequent damage, <i>C. parapsilosis</i> is unable to establish lasting physical contact and causes less harm. In terms of keratinocyte response, both cell lines showed significantly enhanced cellular (internalization), humoral (IL-6, IL-8) and metabolic responses (2-ketoglutaric acid, citric acid, threorine, hypotaurine) to <i>C. albicans</i> strains, while those towards <i>C. parapsilosis</i> remained relatively low or similar to the control condition. Under certain conditions strain preference was also detected. Of the two cell lines, HPV-KER was more sensitive, as besides interspecies differences, intraspecies differences were also measurable. These results suggest that <i>C. albicans</i> triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like <i>C. parapsilosis</i>. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.
DOI: 10.6084/m9.figshare.29062737
title: Tamdy virus pathogenesis in immunocompetent and immunocompromised mouse models

description: Tamdy virus (TAMV) is one of the zoonotic tick-borne bunyaviruses that have emerged as global public health threats in recent decades. To date, however, TAMV pathogenesis remains poorly understood. In the present study, we have established different mouse infection models to enable investigation of TAMV pathogenesis. Adult BALB/c mice did not exhibit obvious clinical symptoms or signs post-TAMV infection. In contrast, adult type I interferon receptor knockout (IFNAR<sup>−/−</sup>) A129 mice were found to be susceptible to high-doses of TAMV (6 × 10<sup>2</sup> and 6 × 10<sup>4</sup> FFU) and all developed severe clinical symptoms and signs, including weight loss and immobility, and reached the euthanasia criteria at 4/5-day post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the high-dose infected adult A129 mice, with the highest viral loads in the liver (approximately 10<sup>8.3</sup> copies/μL). Pathological examination also revealed severe liver damage in the high-dose infected A129 mice. In addition, the titres of TAMV-specific IgM and IgG antibodies increased rapidly 4–5 dpi. Analysis of cytokine and chemokine expression changes demonstrated that type I IFN may play an important role in the host defence against viral infection by enhancing IL-10 production. Gene ontology and KEGG analyses showed that liver injury may be associated with virus-induced expression of inflammatory cytokines and chemokines. Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which will facilitate the development of TAMV-specific antivirals and vaccines.
DOI: 10.6084/m9.figshare.29062737.v1
title: Tamdy virus pathogenesis in immunocompetent and immunocompromised mouse models

description: Tamdy virus (TAMV) is one of the zoonotic tick-borne bunyaviruses that have emerged as global public health threats in recent decades. To date, however, TAMV pathogenesis remains poorly understood. In the present study, we have established different mouse infection models to enable investigation of TAMV pathogenesis. Adult BALB/c mice did not exhibit obvious clinical symptoms or signs post-TAMV infection. In contrast, adult type I interferon receptor knockout (IFNAR<sup>−/−</sup>) A129 mice were found to be susceptible to high-doses of TAMV (6 × 10<sup>2</sup> and 6 × 10<sup>4</sup> FFU) and all developed severe clinical symptoms and signs, including weight loss and immobility, and reached the euthanasia criteria at 4/5-day post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the high-dose infected adult A129 mice, with the highest viral loads in the liver (approximately 10<sup>8.3</sup> copies/μL). Pathological examination also revealed severe liver damage in the high-dose infected A129 mice. In addition, the titres of TAMV-specific IgM and IgG antibodies increased rapidly 4–5 dpi. Analysis of cytokine and chemokine expression changes demonstrated that type I IFN may play an important role in the host defence against viral infection by enhancing IL-10 production. Gene ontology and KEGG analyses showed that liver injury may be associated with virus-induced expression of inflammatory cytokines and chemokines. Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which will facilitate the development of TAMV-specific antivirals and vaccines.
DOI: 10.6084/m9.figshare.29575311.v1
title: Comprehensive analysis of human keratinocyte interactions with <i>Candida albicans</i> and <i>Candida parapsilosis</i>

description: In recent years, microbiome studies revealed that <i>Candida</i> species are common colonisers of the human skin. The distribution of species however varies greatly. Although <i>C. parapsilosis</i> is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding <i>C. albicans</i>, that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - <i>Candida</i> interactions. To study species-specific host responses, we examined internalization, cytokine and metabolic responses in different keratinocytes (HaCaT, HPV-KER) along with host cell damage following fungal stimuli. To rigorously examine yeast-keratinocyte interactions, we applied two distinct isolates of both <i>C. albicans</i> (SC5314, WO-1) and <i>C. parapsilosis</i> (GA1, CLIB214). Comparison of the two fungi’s virulence revealed that while <i>C. albicans</i> effectively adheres to human keratinocytes and causes subsequent damage, <i>C. parapsilosis</i> is unable to establish lasting physical contact and causes less harm. In terms of keratinocyte response, both cell lines showed significantly enhanced cellular (internalization), humoral (IL-6, IL-8) and metabolic responses (2-ketoglutaric acid, citric acid, threorine, hypotaurine) to <i>C. albicans</i> strains, while those towards <i>C. parapsilosis</i> remained relatively low or similar to the control condition. Under certain conditions strain preference was also detected. Of the two cell lines, HPV-KER was more sensitive, as besides interspecies differences, intraspecies differences were also measurable. These results suggest that <i>C. albicans</i> triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like <i>C. parapsilosis</i>. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.
DOI: 10.6084/m9.figshare.30128121
title: Tilmicosin inhibits the infections of currently prevalent porcine reproductive and respiratory syndrome viruses via the downregulation of CD163 expression

description: Porcine reproductive and respiratory syndrome virus (PRRSV) has a disastrous impact on the global swine industry. Even though PRRS commercial vaccines can provide homologous protection, broadly effective anti-PRRSV strategies are still in urgent need. Tilmicosin is a semi-synthetic macrolide antibiotic that was noticed to have anti-PRRSV capacity in the field. However, the antiviral activities of tilmicosin against currently prevalent PRRSV isolates have not been systematically evaluated. More importantly, the anti-PRRSV mechanisms of tilmicosin are not clarified. In this study, <i>in vitro</i> experiments showed that tilmicosin dose-dependently inhibits the replications of prevalent PRRSV (NADC34-like PRRSV-2, NADC30-like PRRSV-2, HP-PRRSV-2, and PRRSV-1) isolates in different target cells (PAMs and Marc-145). <i>In vivo</i> studies supported that tilmicosin inhibits NADC34-like PRRSV-2 replication and reduces pathogenic lesions in weaned piglets. Remarkably, the transcriptomic analysis provided the first clue that PRRSV key receptor CD163 was significantly downregulated by tilmicosin, which was further confirmed by qPCR and WB detections. In addition, anti-inflammatory factors (such as IL-10) were downregulated, while pro-inflammatory factors (such as IL-1β) were upregulated after tilmicosin treatment. Flow cytometric analysis indicated that anti-inflammatory may reverse the downregulation effect of tilmicosin on CD163, while pro-inflammatory mediators can enhance the downregulation effect of tilmicosin on CD163, which leads to increased and decreased replication of PRRSV, respectively. These findings demonstrate that tilmicosin can inhibit PRRSV replication via the reduction of CD163 expression, which provides new insights into anti-PRRSV mechanisms of tilmicosin.
DOI: 10.6084/m9.figshare.30128121.v1
title: Tilmicosin inhibits the infections of currently prevalent porcine reproductive and respiratory syndrome viruses via the downregulation of CD163 expression

description: Porcine reproductive and respiratory syndrome virus (PRRSV) has a disastrous impact on the global swine industry. Even though PRRS commercial vaccines can provide homologous protection, broadly effective anti-PRRSV strategies are still in urgent need. Tilmicosin is a semi-synthetic macrolide antibiotic that was noticed to have anti-PRRSV capacity in the field. However, the antiviral activities of tilmicosin against currently prevalent PRRSV isolates have not been systematically evaluated. More importantly, the anti-PRRSV mechanisms of tilmicosin are not clarified. In this study, <i>in vitro</i> experiments showed that tilmicosin dose-dependently inhibits the replications of prevalent PRRSV (NADC34-like PRRSV-2, NADC30-like PRRSV-2, HP-PRRSV-2, and PRRSV-1) isolates in different target cells (PAMs and Marc-145). <i>In vivo</i> studies supported that tilmicosin inhibits NADC34-like PRRSV-2 replication and reduces pathogenic lesions in weaned piglets. Remarkably, the transcriptomic analysis provided the first clue that PRRSV key receptor CD163 was significantly downregulated by tilmicosin, which was further confirmed by qPCR and WB detections. In addition, anti-inflammatory factors (such as IL-10) were downregulated, while pro-inflammatory factors (such as IL-1β) were upregulated after tilmicosin treatment. Flow cytometric analysis indicated that anti-inflammatory may reverse the downregulation effect of tilmicosin on CD163, while pro-inflammatory mediators can enhance the downregulation effect of tilmicosin on CD163, which leads to increased and decreased replication of PRRSV, respectively. These findings demonstrate that tilmicosin can inhibit PRRSV replication via the reduction of CD163 expression, which provides new insights into anti-PRRSV mechanisms of tilmicosin.