cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.34943/c12cc0f2-4e19-40ce-b133-6ff098f1d032
title: Baynes Sound Oxygen Sensor Deployed 2022-07-20

description: The Sea-Bird SBE 63 Dissolved Oxygen Sensor 632516 was deployed on 2022-07-20 at Baynes Sound. Baynes Sound is located between Denman Island and Vancouver Island. This device is a Oxygen Sensor. Oxygen sensors measure dissolved oxygen concentration in seawater. It was deployed on a fixed platform. Data from this deployment were archived and made available through Ocean Networks Canada's Oceans 3.0 digital infrastructure, with quality assurance and derived data products following established practices.
DOI: 10.34943/f0fe3033-5f25-4d8f-876b-a87a56f02e55
title: Baynes Sound Conductivity Temperature Depth Deployed 2022-07-20

description: The Sea-Bird SeaCAT SBE19plus V2 5270 was deployed on 2022-07-20 at Baynes Sound. Baynes Sound is located between Denman Island and Vancouver Island. This device is a Conductivity Temperature Depth. Conductivity Temperature Depth (CTD) is an instrument package that contains sensors for measuring the conductivity, temperature, and pressure of seawater. Salinity, sound velocity, depth and density are variables that can be derived from sensor measurements. CTDs can carry additional instruments and sensors such as oxygen sensors, turbidity sensors and fluorometers. It was deployed on a fixed platform. Data from this deployment were archived and made available through Ocean Networks Canada's Oceans 3.0 digital infrastructure, with quality assurance and derived data products following established practices.
DOI: 10.6084/m9.figshare.15124078
title: Novel murine models for studying Cache Valley virus pathogenesis and <i>in utero</i> transmission

description: Cache Valley virus (CVV) is a prevalent emerging pathogen of significant importance to agricultural and human health in North America. Emergence in livestock can result in substantial agroeconomic losses resulting from the severe embryonic lethality associated with infection during pregnancy. Although CVV pathogenesis has been well described in ruminants, small animal models are still unavailable, which limits our ability to study its pathogenesis and perform preclinical testing of therapeutics. Herein, we explored CVV pathogenesis, tissue tropism, and disease outcomes in a variety of murine models, including immune -competent and -compromised animals. Our results show that development of CVV disease in mice is dependent on innate immune responses, and type I interferon signalling is essential for preventing infection in mice. IFN-αβR<sup>-/-</sup> mice infected with CVV present with significant disease and lethal infections, with minimal differences in age-dependent pathogenesis, suggesting this model is appropriate for pathogenesis-related, and short- and long-term therapeutic studies. We also developed a novel CVV <i>in utero</i> transmission model that showed high rates of transmission, spontaneous abortions, and congenital malformations during infection. CVV infection presents a wide tissue tropism, with significant amplification in liver, spleen, and placenta tissues. Immune-competent mice are generally resistant to infection, and only show disease in an age dependent manner. Given the high seropositivity rates in regions of North America, and the continuing geographic expansion of competent mosquito vectors, the risk of epidemic and epizootic emergence of CVV is high, and interventions are needed for this important pathogen.
DOI: 10.6084/m9.figshare.15124078.v2
title: Novel murine models for studying Cache Valley virus pathogenesis and <i>in utero</i> transmission

description: Cache Valley virus (CVV) is a prevalent emerging pathogen of significant importance to agricultural and human health in North America. Emergence in livestock can result in substantial agroeconomic losses resulting from the severe embryonic lethality associated with infection during pregnancy. Although CVV pathogenesis has been well described in ruminants, small animal models are still unavailable, which limits our ability to study its pathogenesis and perform preclinical testing of therapeutics. Herein, we explored CVV pathogenesis, tissue tropism, and disease outcomes in a variety of murine models, including immune -competent and -compromised animals. Our results show that development of CVV disease in mice is dependent on innate immune responses, and type I interferon signalling is essential for preventing infection in mice. IFN-αβR<sup>-/-</sup> mice infected with CVV present with significant disease and lethal infections, with minimal differences in age-dependent pathogenesis, suggesting this model is appropriate for pathogenesis-related, and short- and long-term therapeutic studies. We also developed a novel CVV <i>in utero</i> transmission model that showed high rates of transmission, spontaneous abortions, and congenital malformations during infection. CVV infection presents a wide tissue tropism, with significant amplification in liver, spleen, and placenta tissues. Immune-competent mice are generally resistant to infection, and only show disease in an age dependent manner. Given the high seropositivity rates in regions of North America, and the continuing geographic expansion of competent mosquito vectors, the risk of epidemic and epizootic emergence of CVV is high, and interventions are needed for this important pathogen.
DOI: 10.6084/m9.figshare.14480996.v1
title: A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity

description: African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 &gt; 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2–8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.
DOI: 10.6084/m9.figshare.13736502
title: Human pathogenic <i>Mycobacterium kansasii</i> (former subtype I) with zoonotic potential isolated from a diseased indoor pet cat, Japan

description: Nontuberculous mycobacterial (NTM) infections in humans have increased in prevalence in recent decades. <i>Mycobacterium kansasii</i> is one of the most prevalent human pathogenic NTM species worldwide<i>.</i> Herein, we report the first isolation of <i>M. kansasii</i> from an indoor domestic cat in Japan. Comparative genome sequence analysis of the feline isolate showed this pathogen is genetically identical to human pathogenic <i>M. kansasii</i>. This finding suggests that <i>M. kansasii</i> has a potential risk of zoonoses and requires the “One Health” approach to control NTM infection.
DOI: 10.6084/m9.figshare.14480996
title: A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity

description: African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 &gt; 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2–8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.
DOI: 10.6084/m9.figshare.13736502.v1
title: Human pathogenic <i>Mycobacterium kansasii</i> (former subtype I) with zoonotic potential isolated from a diseased indoor pet cat, Japan

description: Nontuberculous mycobacterial (NTM) infections in humans have increased in prevalence in recent decades. <i>Mycobacterium kansasii</i> is one of the most prevalent human pathogenic NTM species worldwide<i>.</i> Herein, we report the first isolation of <i>M. kansasii</i> from an indoor domestic cat in Japan. Comparative genome sequence analysis of the feline isolate showed this pathogen is genetically identical to human pathogenic <i>M. kansasii</i>. This finding suggests that <i>M. kansasii</i> has a potential risk of zoonoses and requires the “One Health” approach to control NTM infection.
DOI: 10.6084/m9.figshare.14694950.v1
title: Blood virosphere in febrile Tanzanian children

description: Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (&lt;5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT02225769.
DOI: 10.6084/m9.figshare.14694950
title: Blood virosphere in febrile Tanzanian children

description: Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (&lt;5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT02225769.
DOI: 10.6084/m9.figshare.14339382
title: Pathogenic assessment of avian influenza viruses in migratory birds

description: Several subtypes of avian influenza (AI) viruses have caused human infections in recent years; however, there is a severe knowledge gap regarding the capacity of wild bird viruses to infect mammals. To assess the risk of mammalian infection by AI viruses from their natural reservoirs, a panel of isolates from 34 wild birds was examined in animal models. All selected AI virus subtypes were found to predominantly possess Eurasian lineage, although reassortment with North American lineage AI viruses was also noted in some isolates. When used to infect chickens, 20 AI isolates could be recovered from oropharyngeal swabs at 5 days post-infection (dpi) without causing significant morbidity. Similarly, mild to no observable disease was observed in mice infected with these viruses although the majority replicated efficiently in murine lungs. As expected, wild bird AI isolates were found to recognize avian-like receptors, while a few strains also exhibited detectable human-like receptor binding. Selected strains were further tested in ferrets, and 15 out of 20 were found to shed the virus in the upper respiratory tract until 5 dpi. Overall, we demonstrate that a diversity of low-pathogenic AI viruses carried by wild migratory birds have the capacity to infect land-based poultry and mammalian hosts while causing minimal signs of clinical disease. This study reiterates that there is a significant capacity for interspecies transmission of AI viruses harboured by wild aquatic birds. Thus, these viruses pose a significant threat to human health underscoring the need for continued surveillance.
DOI: 10.6084/m9.figshare.14339382.v1
title: Pathogenic assessment of avian influenza viruses in migratory birds

description: Several subtypes of avian influenza (AI) viruses have caused human infections in recent years; however, there is a severe knowledge gap regarding the capacity of wild bird viruses to infect mammals. To assess the risk of mammalian infection by AI viruses from their natural reservoirs, a panel of isolates from 34 wild birds was examined in animal models. All selected AI virus subtypes were found to predominantly possess Eurasian lineage, although reassortment with North American lineage AI viruses was also noted in some isolates. When used to infect chickens, 20 AI isolates could be recovered from oropharyngeal swabs at 5 days post-infection (dpi) without causing significant morbidity. Similarly, mild to no observable disease was observed in mice infected with these viruses although the majority replicated efficiently in murine lungs. As expected, wild bird AI isolates were found to recognize avian-like receptors, while a few strains also exhibited detectable human-like receptor binding. Selected strains were further tested in ferrets, and 15 out of 20 were found to shed the virus in the upper respiratory tract until 5 dpi. Overall, we demonstrate that a diversity of low-pathogenic AI viruses carried by wild migratory birds have the capacity to infect land-based poultry and mammalian hosts while causing minimal signs of clinical disease. This study reiterates that there is a significant capacity for interspecies transmission of AI viruses harboured by wild aquatic birds. Thus, these viruses pose a significant threat to human health underscoring the need for continued surveillance.
DOI: 10.6084/m9.figshare.14112530
title: Amoebae can promote the survival of <i>Francisella</i> species in the aquatic environment

description: <i>Francisella tularensis</i>, a tier 1 select agent, is the causative bacterium of tularemia, a zoonosis with a large animal reservoir. However, <i>F. tularensis</i>, like many other <i>Francisella</i> species, is assumed to have an aquatic reservoir. The mechanisms of <i>Francisella</i> species persistence in surface water remain poorly characterized. In this study, we deeply investigated the long-term interactions of the tularemia agent <i>F. tularensis</i> subsp. <i>holarctica</i>, <i>F. novicida</i> or <i>F. philomiragia</i> with amoebae of the <i>Acanthamoeba</i> species. In amoeba plate screening tests, all the <i>Francisella</i> species tested resisted the attack by amoebae. In <i>in vitro</i> infection models, intra-amoebic growth of <i>Francisella</i> varied according to the involved bacterial species and strains, but also the amoeba culture medium used. In co-culture models, the amoebae favoured <i>Francisella</i> survival over 16 days, which was likely dependent on direct contact between bacteria and amoebae for <i>F. novicida</i> and on amoeba-excreted compounds for <i>F. novicida</i> and for <i>F. tularensis</i>. In a spring water co-culture model, amoebae again enhanced <i>F. novicida</i> survival and preserved bacterial morphology. Overall, our results demonstrate that amoebae likely promote <i>Francisella</i> survival in aquatic environments, including the tularemia agent <i>F. tularensis</i>. However, bacteria-amoebae interactions are complex and depend on the <i>Francisella</i> species considered.
DOI: 10.6084/m9.figshare.14112530.v1
title: Amoebae can promote the survival of <i>Francisella</i> species in the aquatic environment

description: <i>Francisella tularensis</i>, a tier 1 select agent, is the causative bacterium of tularemia, a zoonosis with a large animal reservoir. However, <i>F. tularensis</i>, like many other <i>Francisella</i> species, is assumed to have an aquatic reservoir. The mechanisms of <i>Francisella</i> species persistence in surface water remain poorly characterized. In this study, we deeply investigated the long-term interactions of the tularemia agent <i>F. tularensis</i> subsp. <i>holarctica</i>, <i>F. novicida</i> or <i>F. philomiragia</i> with amoebae of the <i>Acanthamoeba</i> species. In amoeba plate screening tests, all the <i>Francisella</i> species tested resisted the attack by amoebae. In <i>in vitro</i> infection models, intra-amoebic growth of <i>Francisella</i> varied according to the involved bacterial species and strains, but also the amoeba culture medium used. In co-culture models, the amoebae favoured <i>Francisella</i> survival over 16 days, which was likely dependent on direct contact between bacteria and amoebae for <i>F. novicida</i> and on amoeba-excreted compounds for <i>F. novicida</i> and for <i>F. tularensis</i>. In a spring water co-culture model, amoebae again enhanced <i>F. novicida</i> survival and preserved bacterial morphology. Overall, our results demonstrate that amoebae likely promote <i>Francisella</i> survival in aquatic environments, including the tularemia agent <i>F. tularensis</i>. However, bacteria-amoebae interactions are complex and depend on the <i>Francisella</i> species considered.
DOI: 10.6084/m9.figshare.17081902
title: Skin models for cutaneous melioidosis reveal <i>Burkholderia</i> infection dynamics at wound’s edge with inflammasome activation, keratinocyte extrusion and epidermal detachment

description: Melioidosis is a serious infectious disease endemic in Southeast Asia, Northern Australia and has been increasingly reported in other tropical and subtropical regions in the world. Percutaneous inoculation through cuts and wounds on the skin is one of the major modes of natural transmission. Despite cuts in skin being a major route of entry, very little is known about how the causative bacterium <i>Burkholderia pseudomallei</i> initiates an infection at the skin and the disease manifestation at the skin known as cutaneous melioidosis. One key issue is the lack of suitable and relevant infection models. Employing an <i>in vitro</i> 2D keratinocyte cell culture, a 3D skin equivalent fibroblast-keratinocyte co-culture and <i>ex vivo</i> organ culture from human skin, we developed infection models utilizing surrogate model organism <i>Burkholderia thailandensis</i> to investigate <i>Burkholderia</i>-skin interactions. Collectively, these models show that the bacterial infection was largely limited at the wound’s edge. Infection impedes wound closure, triggers inflammasome activation and cellular extrusion in the keratinocytes as a potential way to control bacterial infectious load at the skin. However, extensive infection over time could result in the epidermal layer being sloughed off, potentially contributing to formation of skin lesions.
DOI: 10.6084/m9.figshare.17081902.v3
title: Skin models for cutaneous melioidosis reveal <i>Burkholderia</i> infection dynamics at wound’s edge with inflammasome activation, keratinocyte extrusion and epidermal detachment

description: Melioidosis is a serious infectious disease endemic in Southeast Asia, Northern Australia and has been increasingly reported in other tropical and subtropical regions in the world. Percutaneous inoculation through cuts and wounds on the skin is one of the major modes of natural transmission. Despite cuts in skin being a major route of entry, very little is known about how the causative bacterium <i>Burkholderia pseudomallei</i> initiates an infection at the skin and the disease manifestation at the skin known as cutaneous melioidosis. One key issue is the lack of suitable and relevant infection models. Employing an <i>in vitro</i> 2D keratinocyte cell culture, a 3D skin equivalent fibroblast-keratinocyte co-culture and <i>ex vivo</i> organ culture from human skin, we developed infection models utilizing surrogate model organism <i>Burkholderia thailandensis</i> to investigate <i>Burkholderia</i>-skin interactions. Collectively, these models show that the bacterial infection was largely limited at the wound’s edge. Infection impedes wound closure, triggers inflammasome activation and cellular extrusion in the keratinocytes as a potential way to control bacterial infectious load at the skin. However, extensive infection over time could result in the epidermal layer being sloughed off, potentially contributing to formation of skin lesions.