cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12852027.v1
title: Attenuation of <i>Pseudomonas aeruginosa</i> infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis

description: is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistance mechanisms that make treatment a significant challenge and new therapeutic interventions are needed. Type III secretion inhibitors have been studied as an alternative or in accompaniment to traditional antibiotics to inhibit virulence of bacteria. In this study, INP0341, a T3SS inhibitor, inhibited cytotoxicity by <i>P. aeruginosa</i> toward human corneal epithelial cells (HCEC) at 100 μM without affecting bacterial growth in the liquid media. An increased expression of antimicrobial peptides and reactive oxygen species generation was also observed in cells exposed to <i>P. aeruginosa</i> in the presence of INP0341. Furthermore, INP0341 efficiently attenuated corneal infection by <i>P. aeruginosa</i> in an experimental model of murine keratitis as evident from corneal opacity, clinical score and bacterial load. Thus, INP0341 appears to be a promising candidate to treat corneal infection caused by <i>P. aeruginosa</i> and can be further considered as an alternative therapeutic intervention.
DOI: 10.6084/m9.figshare.13488231.v1
title: Tissue specific diversification, virulence and immune response to <i>Mycobacterium bovis</i> BCG in a patient with an IFN-γ R1 deficiency

description: <b>Summary</b>: We characterized <i>Mycobacterium bovis</i> BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. <b>Background</b>: We report a case of a patient with partial recessive IFNγR1 deficiency who developed disseminated BCG infection after neonatal vaccination (BCG-vaccine). Distinct <i>M. bovis</i> BCG-vaccine derived clinical strains were recovered from the patient’s lungs and brain. <b>Methods</b>: BCG strains were phenotypically (growth, antibiotic susceptibility, lipid) and genetically (whole genome sequencing) characterized. Mycobacteria cell infection models were used to assess apoptosis, necrosis, cytokine release, autophagy, and JAK-STAT signaling. <b>Results</b>: Clinical isolates BCG-brain and BCG-lung showed distinct Rv0667 <i>rpoB</i> mutations conferring high- and low-level rifampin resistance; the latter displayed clofazimine resistance through Rv0678 gene (MarR-like transcriptional regulator) mutations. BCG-brain and BCG-lung showed mutations in <i>fadA2, fadE5, and mymA</i> operon genes, respectively. Lipid profiles revealed reduced levels of PDIM in BCG-brain and BCG-lung and increased TAGs and Mycolic acid components in BCG-lung, compared to parent BCG-vaccine. <i>In vitro</i> infected cells showed that the BCG-lung induced a higher cytokine release, necrosis, and cell-associated bacterial load effect when compared to BCG-brain; conversely, both strains inhibited apoptosis and altered JAK-STAT signaling. <b>Conclusions</b>: During a chronic-disseminated BCG infection, BCG strains can evolve independently at different sites likely due to particular microenvironment features leading to differential antibiotic resistance, virulence traits resulting in dissimilar responses in different host tissues.
DOI: 10.6084/m9.figshare.13053352.v1
title: Transcriptomic analyses reveal comprehensive responses of insect hemocytes to mycopathogen Beauveria bassiana, and fungal virulence-related cell wall protein assists pathogen to evade host cellular defense

description: Entomopathogenic fungi naturally infect insect hosts in environment. Fungal invasion and host immune defense are still in the progress of co-evolution. In this study, entomopathogenic fungus <i>Beauveria bassiana</i> and lepidopteran insect <i>Galleria mellonella</i> were used to investigate host cellular immunity and fungal strategy to evade host defense. First of all, genome-wide expression revealed the transcriptomic responses of hemocytes to insect mycopathogen, which dynamically varied during infection process. Enrichment analysis indicated that differentially expressed genes were primarily involved in metabolism, cellular process and immune system. Notably, cellular response involved a series of hydrolytic enzyme and antimicrobial peptide genes which were sorted together in clustering analysis. In <i>B. bassiana</i>, a cell-wall protein gene (<i>BbCwp</i>) contributes to fungal development in host hemocoel and virulence. RT-qPCR analyses indicated that infection by Δ<i>BbCwp</i> mutant strain caused the up-regulated expression of a series of immunity-related genes, including β-1, 3-glucan recognition protein, hydrolytic enzyme and antimicrobial peptide genes. Disruption of <i>BbCwp</i> resulted in a significant change in conidial lectin-binding feature and the enhanced encapsulation by the host hemocytes. After being treated with hydrolytic enzymes, Δ<i>BbCwp</i> mutant displayed a significantly enhanced sensitivity to osmotic and oxidative stresses. In conclusion, fungal invasion initiates comprehensive physiological responses in the host hemocytes. For mycopathogen, cell-wall protein plays an important role in fungal evasion of immunity defense and colonization in host. Our studies provide an initial framework for exploring more mechanistic details about the fungus–host interaction.
DOI: 10.6084/m9.figshare.12319658.v1
title: Host surface ectonucleotidase-CD73 and the opportunistic pathogen, <i>Porphyromonas gingivalis</i>, cross-modulation underlies a new homeostatic mechanism for chronic bacterial survival in human epithelial cells

description: Cell surface nucleotide-metabolizing enzyme, ectonucleotidase-CD73, has emerged as a central component of the cellular homeostatic-machinery that counterbalances the danger-molecule (extracellular-ATP)-driven proinflammatory response in immune cells. While the importance of CD73 in microbial host fitness and symbiosis is gradually being unraveled, there remains a significant gap in knowledge of CD73 and its putative role in epithelial cells. Here, we depict a novel host-pathogen adaptation mechanism where CD73 takes a center role in the intracellular persistence of <i>Porphyromonas gingivalis</i>, a major colonizer of oral mucosa, using human primary gingival epithelial cell (GEC) system. Temporal analyses revealed, upon invasion into the GECs, <i>P. gingivalis</i> can significantly elevate the host-surface CD73 activity and expression. The enhanced and active CD73 significantly increases <i>P. gingivalis</i> intracellular growth in the presence of substrate-AMP and simultaneously acts as a negative regulator of reactive oxygen species (ROS) generation upon eATP treatment. The inhibition of CD73 by siRNA or by a specific inhibitor markedly increases ROS production. Moreover, CD73 and <i>P. gingivalis</i> cross-signaling significantly modulates pro-inflammatory interleukin-6 (IL-6) in the GECs. Conversely, exogenous treatment of the infected GECs with IL-6 suppresses the intracellular bacteria via amplified ROS generation. However, the decreased bacterial levels can be restored by overexpressing functionally active CD73. Together, these findings illuminate how the local extracellular-purine-metabolism, in which CD73 serves as a core molecular switch, can alter intracellular microbial colonization resistance. Further, host-adaptive pathogens such as <i>P. gingivalis</i> can target host ectonucleotidases to disarm specific innate defenses for successful intracellular persistence in mucosal epithelia.
DOI: 10.6084/m9.figshare.12864242.v1
title: Tobacco Hornworm (<i>Manduca sexta</i>) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

description: The two leading yeast pathogens of humans, <i>Candida albicans</i> and <i>Cryptococcus neoformans</i>, cause systemic infections in &gt;1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth <i>Manduca sexta</i> as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including <i>C. albicans, C. neoformans, C. auris</i>, and <i>C. glabrata</i>. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s feces and hemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease and to facilitate host tissue-specific expression analyses. <i>M. sexta</i> caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.
DOI: 10.6084/m9.figshare.12851937.v1
title: IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

description: Epithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HGSOC). The SRC kinase is a key driver of cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation of AJ proteins. Here, we show that the IGF2 mRNA-binding protein 1 (IGF2BP1) is up-regulated in mesenchymal-like HGSOC and promotes SRC activation by a previously unknown protein-ligand-induced, but RNA-independent mechanism. IGF2BP1-driven invasive growth of ovarian cancer cells essentially relies on the SRC-dependent disassembly of AJs. Concomitantly, IGF2BP1 enhances ERK2 expression in an RNA-binding dependent manner. Together this reveals a post-transcriptional mechanism of interconnected stimulation of SRC/ERK signalling in ovarian cancer cells. The IGF2BP1-SRC/ERK2 axis is targetable by the SRC-inhibitor saracatinib and MEK-inhibitor selumetinib. However, due to IGF2BP1-directed stimulation, only combinatorial treatment effectively overcomes the IGF2BP1-promoted invasive growth in 3D culture conditions as well as intraperitoneal mouse models. In conclusion, we reveal an unexpected role of IGF2BP1 in enhancing SRC/MAPK-driven invasive growth of ovarian cancer cells. This provides a rationale for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HGSOC.
DOI: 10.6084/m9.figshare.14681418.v3
title: miRNA exosomes in patientes with ICAD -5.xlsx

description: miRNA in Intracranial AtherosclerosisData Availability Access PolicyThe deidentified miRNA data is available to all investigators that provide theinvestigators with a request and have a plan for a research project in which theinformation collected could be used. Please be aware that the paper originally publishedfrom this data needs to be cited for any additional use.Please include the following information in an email to the corresponding author (Dr.<br>
DOI: 10.6084/m9.figshare.14675595
title: Drone Photographs from the Upper Impoundment 2019-8-14 Flight Date (Dover, NH, USA)

description: These are the raw drone aerial images taken of the upper impoundment area on August 14, 2019 for the Evans et al. Sawyer Mill dam removal study. Alexandra Evans, a certified FAA Part 107 remote pilot, served as the remote pilot in command for the flight mission and was accompanied by a spotter.<br>A DJI Phantom 3 Professional drone was used to take the images, equipped with its original RGB camera and a polarizing filter. Please see the referenced automated flight paths for details on altitude, image overlap, etc. The flight paths were executed using the Litchi flight app.<br>These materials were made using resources from an NSF EPSCoR funded project “RII Track-2 FEC: Strengthening the scientific basis for decision-making about dams: Multi-scale, coupled-systems research on ecological, social, and economic trade-offs” (a.k.a. "Future of Dams"). Support for this project is provided by the National Science Foundation’s Research Infrastructure Improvement NSF #IIA-1539071. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
DOI: 10.6084/m9.figshare.13029039.v12
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i><sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i><sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i><sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i><sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i><sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.14681418
title: miRNA exosomes in patientes with ICAD -5.xlsx

description: miRNA in Intracranial AtherosclerosisData Availability Access PolicyThe deidentified miRNA data is available to all investigators that provide theinvestigators with a request and have a plan for a research project in which theinformation collected could be used. Please be aware that the paper originally publishedfrom this data needs to be cited for any additional use.<br>Please include the following information in an email to the corresponding author (Dr.Nestor Gonzalez. Email: nestor.gonzalez@cshs.org) in order to access the data.- General purpose of the proposed study.- Detailed description of how the data will be used.- Institutional approval for used of data shared.- Source of funding.<br>
DOI: 10.6084/m9.figshare.14681418.v4
title: miRNA exosomes in patientes with ICAD -5.xlsx

description: miRNA in Intracranial AtherosclerosisData Availability Access PolicyThe deidentified miRNA data is available to all investigators that provide theinvestigators with a request and have a plan for a research project in which theinformation collected could be used. Please be aware that the paper originally publishedfrom this data needs to be cited for any additional use.Please include the following information in an email to the corresponding author (Dr.<br>
DOI: 10.6084/m9.figshare.14675604.v1
title: Drone Photographs from the Vegetation Area 2020-8-6 Flight Date (Dover, NH, USA)

description: These are the raw drone aerial images taken of the vegetation area on August 6, 2020 for the Evans et al. Sawyer Mill dam removal study. Alexandra Evans, a certified FAA Part 107 remote pilot, served as the remote pilot in command for the flight mission and was accompanied by a spotter.<br>A DJI Phantom 3 Professional drone was used to take the images, equipped with its original RGB camera and a polarizing filter. Please see the referenced automated flight paths for details on altitude, image overlap, etc. The flight paths were executed using the Litchi flight app.<br>These materials were made using resources from an NSF EPSCoR funded project “RII Track-2 FEC: Strengthening the scientific basis for decision-making about dams: Multi-scale, coupled-systems research on ecological, social, and economic trade-offs” (a.k.a. "Future of Dams"). Support for this project is provided by the National Science Foundation’s Research Infrastructure Improvement NSF #IIA-1539071. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
DOI: 10.6084/m9.figshare.14675595.v1
title: Drone Photographs from the Upper Impoundment 2019-8-14 Flight Date (Dover, NH, USA)

description: These are the raw drone aerial images taken of the upper impoundment area on August 14, 2019 for the Evans et al. Sawyer Mill dam removal study. Alexandra Evans, a certified FAA Part 107 remote pilot, served as the remote pilot in command for the flight mission and was accompanied by a spotter.<br>A DJI Phantom 3 Professional drone was used to take the images, equipped with its original RGB camera and a polarizing filter. Please see the referenced automated flight paths for details on altitude, image overlap, etc. The flight paths were executed using the Litchi flight app.<br>These materials were made using resources from an NSF EPSCoR funded project “RII Track-2 FEC: Strengthening the scientific basis for decision-making about dams: Multi-scale, coupled-systems research on ecological, social, and economic trade-offs” (a.k.a. "Future of Dams"). Support for this project is provided by the National Science Foundation’s Research Infrastructure Improvement NSF #IIA-1539071. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
DOI: 10.6084/m9.figshare.13029039.v13
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i> <sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i> <sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i> <sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i> <sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i> <sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.14681442
title: testmodel.bin

description: Model for tokenclassification after being trained on custom data. Extracts role, employer, medium from post quote sentences
DOI: 10.6084/m9.figshare.7937387.v1
title: Cumulative acquisition of pathogenicity islands has shaped virulence potential and contributed to the emergence of LEE-negative Shiga toxin-producing <i>Escherichia coli</i> strains

description: Shiga toxin-producing <i>Escherichia coli</i> (STEC) are foodborne pathogens causing severe gastroenteritis, which may lead to hemolytic uremic syndrome. The Locus of Enterocyte Effacement (LEE), a Pathogenicity Island (PAI), is a major determinant of intestinal epithelium attachment of a group of STEC strains; however, the virulence repertoire of STEC strains lacking LEE, has not been fully characterized. The incidence of LEE-negative STEC strains has increased in several countries, highlighting the relevance of their study. In order to gain insights into the basis for the emergence of LEE-negative STEC strains, we performed a large-scale genomic analysis of 367 strains isolated worldwide from humans, animals, food and the environment. We identified uncharacterized genomic islands, including two PAIs and one Integrative Conjugative Element. Additionally, the Locus of Adhesion and Autoaggregation (LAA) was the most prevalent PAI among LEE-negative strains and we found that it contributes to colonization of the mice intestine. Our comprehensive and rigorous comparative genomic and phylogenetic analyses suggest that the accumulative acquisition of PAIs has played an important, but currently unappreciated role, in the evolution of virulence in these strains. This study provides new knowledge on the pathogenicity of LEE-negative STEC strains and identifies molecular markers for their epidemiological surveillance.