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  1. Artikel ; Online: Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract.

    Gartner, Matthew J / Lee, Leo Yi Yang / Mordant, Francesca L / Suryadinata, Randy / Chen, Joseph / Robinson, Philip / Polo, Jose M / Subbarao, Kanta

    Med (New York, N.Y.)

    2023  Band 4, Heft 12, Seite(n) 944–955.e7

    Abstract: Background: The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and became the globally dominant variant by January 2022. Authentic virus and pseudovirus systems have shown Omicron spike has an increased dependence on the endosomal pathway for ... ...

    Abstract Background: The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and became the globally dominant variant by January 2022. Authentic virus and pseudovirus systems have shown Omicron spike has an increased dependence on the endosomal pathway for entry.
    Methods: We investigated the entry mechanisms of Omicron, Delta, and ancestral viruses in cell models that represent different parts of the human respiratory tract, including nasal epithelial cells (hNECs), large-airway epithelial cells (LAECs), small-airway epithelial cells, and embryonic stem cell-derived type II alveolar cells.
    Findings: Omicron had an early replication advantage in LAECs, while Delta grew to higher titers in all cells. Omicron maintained dependence on serine proteases for entry in all culture systems. While serine protease inhibition with camostat was less robust for Omicron in hNECs, endosomal entry was not enhanced.
    Conclusions: Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract.
    Funding: This work was supported by The Medical Research Future Fund (MRF9200007; K.S., J.M.P.) and the DHHS Victorian State Government grant (Victorian State Government; DJPR/COVID-19; K.S, J.M.P.). K.S. is supported by a National Health and Medical Research Council of Australia Investigator grant (APP1177174).
    Mesh-Begriff(e) Humans ; Serine Proteases/genetics ; SARS-CoV-2/genetics ; COVID-19/epidemiology ; Serine Endopeptidases/genetics ; Respiratory System
    Chemische Substanzen Serine Proteases (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Sprache Englisch
    Erscheinungsdatum 2023-09-27
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2023.08.006
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: A Review of DNA Vaccines Against Influenza.

    Lee, Leo Yi Yang / Izzard, Leonard / Hurt, Aeron C

    Frontiers in immunology

    2018  Band 9, Seite(n) 1568

    Abstract: The challenges of effective vaccination against influenza are gaining more mainstream attention, as recent influenza seasons have reported low efficacy in annual vaccination programs worldwide. Combined with the potential emergence of novel influenza ... ...

    Abstract The challenges of effective vaccination against influenza are gaining more mainstream attention, as recent influenza seasons have reported low efficacy in annual vaccination programs worldwide. Combined with the potential emergence of novel influenza viruses resulting in a pandemic, the need for effective alternatives to egg-produced conventional vaccines has been made increasingly clear. DNA vaccines against influenza have been in development since the 1990s, but the initial excitement over success in murine model trials has been tempered by comparatively poor performance in larger animal models. In the intervening years, much progress has been made to refine the DNA vaccine platform-the rational design of antigens and expression vectors, the development of novel vaccine adjuvants, and the employment of innovative gene delivery methods. This review discusses how these advances have been applied in recent efforts to develop an effective influenza DNA vaccine.
    Sprache Englisch
    Erscheinungsdatum 2018
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.01568
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Author Correction: Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses.

    McMillan, Christopher L D / Cheung, Stacey T M / Modhiran, Naphak / Barnes, James / Amarilla, Alberto A / Bielefeldt-Ohmann, Helle / Lee, Leo Yi Yang / Guilfoyle, Kate / van Amerongen, Geert / Stittelaar, Koert / Jakob, Virginie / Lebas, Celia / Reading, Patrick / Short, Kirsty R / Young, Paul R / Watterson, Daniel / Chappell, Keith J

    NPJ vaccines

    2022  Band 7, Heft 1, Seite(n) 3

    Sprache Englisch
    Erscheinungsdatum 2022-01-05
    Erscheinungsland England
    Dokumenttyp Published Erratum
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-021-00428-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells.

    Lee, Leo Yi Yang / Suryadinata, Randy / McCafferty, Conor / Ignjatovic, Vera / Purcell, Damian F J / Robinson, Phil / Morton, Craig J / Parker, Michael W / Anderson, Gary P / Monagle, Paul / Subbarao, Kanta / Neil, Jessica A

    Viruses

    2022  Band 14, Heft 12

    Abstract: SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants ... ...

    Abstract SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.
    Mesh-Begriff(e) Humans ; COVID-19 ; Epithelial Cells/virology ; Heparin/pharmacology ; Pandemics ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Replication/drug effects
    Chemische Substanzen Heparin (9005-49-6) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2022-11-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14122620
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Portosystemic Shunt in Pediatric Living Donor Liver Transplant.

    Lim, Wei-Xiong / Lin, An-Ni / Cheng, Yu-Fan / Lee, Sieh-Yang / Hsu, Hsien-Wen / Chen, Chao-Long / Chang, Wan-Ching / Yu, Chun-Yen / Tsang, Leo Leung-Chit / Chuang, Yi-Hsuan / Ou, Hsin-You

    Transplantation proceedings

    2022  Band 54, Heft 2, Seite(n) 403–405

    Abstract: Background: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients.: Methods: Retrospective review of 121 pediatric patients who underwent LDLT between ... ...

    Abstract Background: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients.
    Methods: Retrospective review of 121 pediatric patients who underwent LDLT between May 1994 and December 2015 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and postoperative computed tomography images of the liver were reviewed, and portal vein complications were assessed.
    Results: Ninety-seven pediatric patients were included in the study, and 70 had portosystemic shunts before transplant. Thirty-three patients have portal systemic shunt (PSS) 6 months after transplant (mean [SD] shunt size, 4.59 [1.98] mm). Thirty-seven patients' portosystemic shunts closed spontaneously (mean [SD] shunt size, 3.14 [1.06] mm). Smaller PSSs tend to close spontaneously with a cutoff point of 3.35 mm by receiver operating characteristic curve (P = .01). Patients with PSS have more portal vein complications than those without PSS (44.3% vs 11.1%, P = .02). Among PSS recipients, patients with portal vein complications tend to have larger PSS size (mean [SD], 4.14 [1.96] mm vs 3.59 [1.48] mm), although the difference is not statistically significant (P = .19).
    Conclusions: In pediatric patients, preoperative portosystemic shunts are significantly correlated with portal venous complications, some of which require minimal interventions after LDLT with good outcomes. Shunts larger than 3.35 mm tend to persist after transplant with increased portal venous complications.
    Mesh-Begriff(e) Child ; Humans ; Liver Transplantation ; Living Donors ; Portal Vein/diagnostic imaging ; Portal Vein/surgery ; Portasystemic Shunt, Surgical/adverse effects ; Portasystemic Shunt, Surgical/methods ; Portasystemic Shunt, Transjugular Intrahepatic ; Retrospective Studies
    Sprache Englisch
    Erscheinungsdatum 2022-01-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 82046-5
    ISSN 1873-2623 ; 0041-1345
    ISSN (online) 1873-2623
    ISSN 0041-1345
    DOI 10.1016/j.transproceed.2021.09.072
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

    Rudraraju, Rajeev / Gartner, Matthew J / Neil, Jessica A / Stout, Elizabeth S / Chen, Joseph / Needham, Elise J / See, Michael / Mackenzie-Kludas, Charley / Yang Lee, Leo Yi / Wang, Mingyang / Pointer, Hayley / Karavendzas, Kathy / Abu-Bonsrah, Dad / Drew, Damien / Yang Sun, Yu Bo / Tan, Jia Ping / Sun, Guizhi / Salavaty, Adrian / Charitakis, Natalie /
    Nim, Hieu T / Currie, Peter D / Tham, Wai-Hong / Porrello, Enzo / Polo, Jose M / Humphrey, Sean J / Ramialison, Mirana / Elliott, David A / Subbarao, Kanta

    Stem cell reports

    2023  Band 18, Heft 6, Seite(n) 1308–1324

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.
    Mesh-Begriff(e) Humans ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Stem Cells ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Lung
    Chemische Substanzen Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Antiviral Agents
    Sprache Englisch
    Erscheinungsdatum 2023-06-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2023.05.007
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: Characterization of Low-Loss Dielectric Materials for High-Speed and High-Frequency Applications.

    Lee, Tzu-Nien / Lau, John-H / Ko, Cheng-Ta / Xia, Tim / Lin, Eagle / Yang, Kai-Ming / Lin, Puru-Bruce / Peng, Chia-Yu / Chang, Leo / Chen, Jia-Shiang / Fang, Yi-Hsiu / Liao, Li-Yueh / Charn, Edward / Wang, Jason / Tseng, Tzyy-Jang

    Materials (Basel, Switzerland)

    2022  Band 15, Heft 7

    Abstract: In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed ... ...

    Abstract In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed on the sample preparation, data collection, and the comparison with the data sheet values provided from vendors. A coplanar waveguide with ground (CPWG) test vehicle with one of these raw dielectric materials (vendor 1) is designed (through Polar and simulation) and fabricated. The impedance of the test vehicle is measured by TDR (time-domain reflectometer), and the effective Dk of the test vehicle is calculated by the real cross-section of the metal line width, spacing, and thickness of the test vehicle and a closed-form equation. In parallel, the insertion loss and return loss are measured with the VNA (vector network analyzer) of the test vehicle. Finally, the measurement and simulation results are correlated. Some recommendations on the low-loss dielectric materials of the Dk and Df are also provided.
    Sprache Englisch
    Erscheinungsdatum 2022-03-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2487261-1
    ISSN 1996-1944
    ISSN 1996-1944
    DOI 10.3390/ma15072396
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: A novel and highly divergent Canine Distemper Virus lineage causing distemper in ferrets in Australia

    George, Ankita M. / Wille, Michelle / Wang, Jianning / Anderson, Keith / Cohen, Shari / Moselen, Jean / Yang Lee, Leo Yi / Suen, Willy W. / Bingham, John / Dalziel, Antonia E. / Whitney, Paul / Stannard, Harry / Hurt, Aeron C. / Williams, David T. / Deng, Yi-Mo / Barr, Ian G.

    Virology. 2022 Sept. 04,

    2022  

    Abstract: Canine distemper virus (CDV) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of CDV. While the CDV ...

    Abstract Canine distemper virus (CDV) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of CDV. While the CDV strain caused mainly mild symptoms in ferrets, histopathology results presented a typical profile of distemper pathology, with multi-system virus replication. Through the development of a discriminatory PCR, paired with full genome sequencing, we revealed that the outbreak was caused by a novel lineage of CDV. The novel CDV lineage was highly divergent, with less than 93% similarity across the H gene to other described lineages, including the vaccine strain, and diverged approximately 140–400 years ago. Enhanced surveillance to determine the prevalence of CDV in ferrets, dogs and other at-risk species is critical to better understand the presence and diversity of CDV in Australia currently.
    Schlagwörter Canine morbillivirus ; animals ; distemper ; genes ; histopathology ; monitoring ; vaccines ; virus replication ; Australia
    Sprache Englisch
    Erscheinungsverlauf 2022-0904
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    Anmerkung Pre-press version
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2022.09.001
    Datenquelle NAL Katalog (AGRICOLA)

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  9. Artikel ; Online: Robustness of the Ferret Model for Influenza Risk Assessment Studies: a Cross-Laboratory Exercise.

    Belser, Jessica A / Lau, Eric H Y / Barclay, Wendy / Barr, Ian G / Chen, Hualan / Fouchier, Ron A M / Hatta, Masato / Herfst, Sander / Kawaoka, Yoshihiro / Lakdawala, Seema S / Lee, Leo Yi Yang / Neumann, Gabriele / Peiris, Malik / Perez, Daniel R / Russell, Charles / Subbarao, Kanta / Sutton, Troy C / Webby, Richard J / Yang, Huanliang /
    Yen, Hui-Ling

    mBio

    2022  Band 13, Heft 4, Seite(n) e0117422

    Abstract: Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information ... ...

    Abstract Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.
    Mesh-Begriff(e) Animals ; Ferrets ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; Laboratories ; Lung ; Orthomyxoviridae Infections ; Risk Assessment
    Sprache Englisch
    Erscheinungsdatum 2022-07-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01174-22
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Efficacy of a patient isolation hood in reducing exposure to airborne infectious virus in a simulated healthcare setting

    Lee, Leo Yi Yang / Landry, Shane A / Jamriska, Milan / Subedi, Dinesh / Joosten, Simon A / Barr, Jeremy J / Brown, Reece / Kevin, Kevin / Schofield, Robyn / Monty, Jason / Subbarao, Kanta / McGain, Forbes

    medRxiv

    Abstract: Background: Healthcare workers treating patients with SARS-CoV-2 are at risk of infection from patient-emitted virus-laden aerosols. We quantified the reduction of airborne infectious virus in a simulated hospital room when a ventilated patient isolation ...

    Abstract Background: Healthcare workers treating patients with SARS-CoV-2 are at risk of infection from patient-emitted virus-laden aerosols. We quantified the reduction of airborne infectious virus in a simulated hospital room when a ventilated patient isolation (McMonty) hood was in use. Methods: We nebulised 10<sup>9</sup> plaque forming units (PFU) of bacteriophage PhiX174 virus into a 35.1m<sup>3</sup> room with a hood active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The particle number concentration (PNC) was monitored continuously using an optical particle sizer. Results: Median airborne viral concentration in the room reached 1.41 x 10<sup>5</sup> PFU.m<sup>-3</sup> with the hood inactive. Using the active hood as source containment reduced infectious virus concentration by 374-fold in air samples. This was associated with a 109-fold reduction in total airborne particle number escape rate. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. Conclusions: The isolation hood significantly reduced airborne infectious virus exposure in a simulated hospital room. Our findings support the use of the hood to limit exposure of healthcare workers to airborne virus in clinical environments.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2022-07-29
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2022.07.24.22277784
    Datenquelle COVID19

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