1,721,228 research outputs found
Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing
Full text linkX-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. To address these challenges, we here design and implement a novel integrated and high throughput XPCT imaging and analysis workflow for 3D histology, pathohistology and drug testing. Our approach uses semi-automated data acquisition, reconstruction and statistical quantification. We demonstrate its capability for the example of lung pathohistology in Covid-19. Using a small animal model, different Covid-19 drug candidates are administered after infection and tested in view of restoration of the physiological cytoarchitecture, specifically the alveolar morphology. To this end, we then use morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing quantitative insights into the pathological progression and partial recovery due to drug treatment. Finally, we stress that the XPCT image chain implemented here only used synchrotron radiation for validation, while the data used for analysis was recorded with laboratory µCT radiation, more easily accessible for pre-clinical research
Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing
Full text linkX-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory μCT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment
3D imaging of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography enables drug testing
Full text linkX-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. To address these challenges, we here design and implement a novel integrated and high throughput XPCT imaging and analysis workflow for 3D histology, pathohistology and drug testing. Our approach uses semi-automated data acquisition, reconstruction and statistical quantification. We demonstrate its capability for the example of lung pathohistology in Covid-19. Using a small animal model, different Covid-19 drug candidates are administered after infection and tested in view of restoration of the physiological cytoarchitecture, specifically the alveolar morphology. To this end, we then use morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing quantitative insights into the pathological progression and partial recovery due to drug treatment. Finally, we stress that the XPCT image chain implemented here only used synchrotron radiation for validation, while the data used for analysis was recorded with laboratory CT radiation, more easily accessible for pre-clinical research
Health Triad Comprising People, Animals and the Environment of Nipah virus Infection in South and South-East Asia Region, and all of its interactions
No full textZombie-Hirsch erlegt und gegessen: Zwei Jäger sterben – zuvor auffällige Symptome
No full textAustin – Immer wieder werden Hirsche in den USA und Kanada mit der tödlichen Nervenkrankheit „Chronic Wasting Disease“ (CWD) infiziert. Bereits im Jahr 2019 kämpfte der US-Bundesstaat Nevada gegen die Ausbreitung des sogenannten „Zombie-Erregers“, indem sie um Mithilfe beim Aufspüren von erkrankten Tieren baten. Nun schlagen Experten Alarm, weil das „Zombie-Wild-Syndrom“ zwei Jägern das Leben kostete. Zuvor hatten sie verseuchtes Fleisch von einem Hirsch gegessen
Nipah-Virus in Indien : Vorsichtige Einschätzung der Pandemierisiken
No full textDurch das Nipah-Virus sind in Indien bisher zwei Menschen gestorben und weitere Personen unter Beobachtung, so Anne Balkema-Buschmann, Leiterin des Nationalen Referenzlabors für Nipah-Viren am Friedrich-Loeffler-Institut. Sie beschreibt die Risiken
Some hamsters are extremely susceptible to COVID-19: Low doses make the animals sick and rapid tests can sometimes detect the infection
No full textGolden Syrian hamsters are highly susceptible to the coronavirus that causes COVID-19, a new study shows. While the species is popular among pet owners, the results, posted April 20 at bioRxiv, are not cause for panic, says Anne Balkema-Buschmann, a veterinarian at the Friedrich-Loeffler-Institut in Riems, Germany. “The message of this paper is not that hamsters are ticking time bombs that can’t be kept in households any longer.” But pinpointing just how sensitive the animals are to SARS-CoV-2 can help researchers fine-tune experiments that use hamsters to test potential treatments for COVID-19
Supplementary dataset to publication: Approaching the complexity of Crimean-Congo hemorrhagic fever virus serology: a study in swine
No full text<p>For the detection of anti-CCHFV antibodies in swine, we established a swine-specific in-house ELISA, indirect immunofluorescence assay and a virus neutralization test. Uploaded data contains sample performance in each test. Samples used in this study include swine serum samples from Germany and Spain.</p>
Experimentelle Untersuchungen an Fledermäusen als potenzielles Reservoir von Ebolaviren
Full text linkWenige Studien haben erste Hinweise darauf geliefert, dass die insektivore Fledermausart Mops condylurus ein natürliches Reservoir von Ebolaviren sein könnte. Im Rahmen dieser Doktorarbeit wurden weitere Hinweise gesucht, um die Bedeutung dieser Fledermausart als Reservoirwirt für Ebolaviren besser beurteilen zu können. Dafür wurden die Expressionslevel des Membranproteins Niemann-Pick C1 (NPC1), welches essentiell für den Eintritt von Ebolaviren in ihre Wirtszellen ist, in vitro durch konfokale Mikroskopie und Durchflusszytometrie charakterisiert. In dieser Arbeit generierte Primärzellkulturen aus 12 verschiedenen Organen von M. condylurus zeigten für die meisten Primärzellen deutlich niedrigere Expressionslevel als Kontrollzellen von Mensch, Affe oder einer europäischen Fledermaus. Die untersuchte Replikationskinetik von Ebola virus (EBOV) zeigte in allen Primärzellen von M. condylurus niedrigere Replikationsraten, die meistens mit den niedrigen NPC1 Rezeptor-Expressionsleveln korrelierten. Geringere Mengen von NPC1 könnten in vivo zur Virusreplikation auf niedrigerem Niveau beitragen. Desweiteren zeigten alle Primärzellen von M. condylurus eine hohe Toleranz gegenüber EBOV ohne Zelltot. Eine beobachtete Persistenz in Lungenprimärzellen könnte die intrinsische Fähigkeit widerspiegeln, dass Ebolaviren auch in vivo in dieser Fledermausart persistieren könnten. Mit den geringeren NPC1-Rezeptor-Expressionsleveln, der geringeren Virusreplikation, der hohen Toleranz gegenüber EBOV und der Etablierung von persistenten Infektionen in Primärzellen von M. condylurus wurden in vitro zusätzliche Hinweise gewonnen, die die Wahrscheinlichkeit dieser Fledermausspezies als ein mögliches natürliches Reservoir von Ebolaviren erhöht. Ergebnisse von zusätzlichen Temperaturversuchen lassen vermuten, dass die Heterothermie der Fledermäuse einen Schlüsselfaktor für die Toleranz von Ebolaviren in vivo darstellen und darüber hinaus an der Balance zwischen Viruskontrolle und Virusvermehrung beteiligt sein könnte.Few studies provide first evidence that Mops condylurus, an insectivorous microbat, could be a natural reservoir for ebolaviruses. The aim of this thesis was to investigate indicators to determine the potential role of this bat species in the ecology of ebolaviruses. Therefore, the expression levels of the membrane protein Niemann-Pick C1 (NPC1), essential for the entry of ebolaviruses into their host cells, were characterized in vitro by confocal microscopy and flow cytometry. Our generated primary cell cultures from 12 different organs from M. condylurus showed significantly lower expression levels in most primary cells compared to control cells from human, monkey or a European bat. In most cases, lower Ebola virus (EBOV) replication rates in primary cells from M. condylurus, determined by RT-qPCR, correlated to lower NPC1 receptor expression levels. Low NPC1 receptor expression levels may contribute to decreased virus replication rates also in vivo. Additionally, all primary cells were highly tolerant to EBOV infections without cell death. The observed establishment of persistent EBOV infections in lung primary cells from M. condylurus may reflect the intrinsic ability to persist in vivo in this bat species. With lower NPC1 receptor expression levels, lower virus replication rates, high tolerance to EBOV infections and establishment of persistent infections in primary cells from M. condylurus, the in vitro experiments provided further evidence that this bat species is a potential reservoir of ebolaviruses. Results from additional temperature experiments suggest, that heterothermy of M. condylurus could be a key factor for tolerance to EBOV infections in vivo and be involved in balancing the level of virus replication
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