OBJECTIVES: To investigate in silico the presence of nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human non-coding (nc)RNA genes.METHODS: The FASTA sequence (NC_045512.2) of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes was retrieved from NCBI.nlm.nih.gov/gene and the Ensembl.org library interrogated for any base-pair match with human ncRNA genes. SARS-CoV-2 gene-matched human ncRNAs were screened for functional activity using bioinformatic analysis. Finally, associations between identified ncRNAs and human diseases were searched in GWAS databases.RESULTS: A total of 252 matches were found between the nucleotide sequence of SARS-CoV-2 genes and human ncRNAs. With the exception of two small nuclear RNAs, all of them were long non-coding (lnc)RNAs expressed mainly in testis and central nervous system under physiological conditions. The percentage of alignment ranged from 91.30% to 100% with a mean nucleotide alignment length of 17.5 ± 2.4. Thirty-three (13.9%) of them contained predicted R-loop forming sequences, but none of these intersected the complementary sequences of SARS-CoV-2. However, in 31 cases matches fell on ncRNA regulatory sites, whose adjacent coding genes are mostly involved in cancer, immunological and neurological pathways. Similarly, several polymorphic variants of detected non-coding genes have been associated with neuropsychiatric and proliferative disorders.CONCLUSION: This pivotal in silico study shows that SARS-CoV-2 genes have Watson-Crick nucleotide complementarity to human ncRNA sequences, potentially disrupting ncRNA epigenetic control of target genes. It remains to be elucidated whether this could result in the development of human disease in the long term.
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNk4 ORF. The expression of IFNk4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNk4, which signals through the IFNkR1 and IL-10R2 receptor chains. Recombinant IFNk4 is antiviral against both HCV and coronaviruses at levels comparable to IFNk3. However, the secretion of IFNk4 is impaired compared to that of IFNk3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNk4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNk4 is strongly antiviral but a disadvantage during HCV infection. The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection
Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach.Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry.Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, andα-1-antiproteinase F.Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.
descriptionPublicationkeyboard_double_arrow_right Article 2021 Denmark American Society for Microbiology
Authors: Kamille Fogh; Jarl E. Strange; Bibi F. S. S. Scharff; Alexandra R. R. Eriksen; +30 Authors
Kamille Fogh; Jarl E. Strange; Bibi F. S. S. Scharff; Alexandra R. R. Eriksen; Rasmus B. Hasselbalch; Henning Bundgaard; Susanne D. Nielsen; Charlotte S. Jørgensen; Christian Erikstrup; Jakob Norsk; Pernille Brok Nielsen; Jonas H. Kristensen; Lars Østergaard; Svend Ellermann-Eriksen; Berit Andersen; Henrik Nielsen; Isik S. Johansen; Lothar Wiese; Lone Simonsen; Thea K. Fischer; Fredrik Folke; Freddy Lippert; Sisse R. Ostrowski; Thomas Benfield; Kåre Mølbak; Steen Ethelberg; Anders Koch; Ute Wolff Sönksen; Anne-Marie Vangsted; Tyra Grove Krause; Anders Fomsgaard; Henrik Ullum; Robert Skov; Kasper Iversen;
"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (age >15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by point-of care rapid test (POCT) distributed to participants' home addresses. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.
Association of Surgeons in Training Surgical Summit, online, 17 Oct 2020 - 17 Oct 2020 2021 Virtual Annual Meeting / Surgical Research Society, online, 24 Mar 2021 - 25 Mar 2021, National Research Collaborative Meeting, online, 10 Dec 2020 - 10 Dec 2020, Royal Australasian College of Surgeons Annual Academic Surgery Conference, online, 5 Nov 2020 - 5 Nov 2020; The British journal of surgery : BJS 108(12), 1448-1464 (2021). doi:10.1093/bjs/znab336 Published by Wiley, New York, NY [u.a.]
The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma half-life by an FcRn-driven cellular recycling mechanism, investigated using a wild type (WT) albumin sequence and sequence engineered with null FcRn binding (NB). Binding of rHA-ACE2 fusions to SARS-CoV-2 spike protein subdomain 1 (S1) was demonstrated (WT-ACE2 KD = 32.8 nM and NB-ACE2 KD = 31.7 nM) using Bio-Layer Interferometry and dose-dependent in vitro inhibition of host cell infection of pseudotyped viruses displaying surface SARS-CoV-2 spike (S) protein. FcRn-mediated in vitro recycling was translated to a five times greater plasma half-life of WT-ACE2 (t½ β = 13.5 h) than soluble ACE2 (t½ β = 2.8 h) in humanised FcRn/albumin double transgenic mice. The rHA-ACE2-based SARS-CoV-2 decoy system exhibiting FcRn-driven circulatory half-life extension introduced in this work offers the potential to expand and improve the anti-COVID-19 anti-viral drug armoury. Statement of significance: The COVID-19 pandemic has highlighted the need for rapid development of efficient antiviral therapeutics to combat SARS-CoV-2 and new mutants to lower morbidity and mortality in severe cases, and for people that are unable to receive a vaccine. Here we report a therapeutic albumin ACE2 fusion protein (rHA-ACE2), that can bind SARS-CoV-2 S protein decorated virus-like particles to inhibit viral infection, and exhibits extended in vivo half-life compared to ACE2 alone. Employing ACE2 as a binding decoy for the virus is expected to efficiently inhibit all SARS-CoV-2 mutants as they all rely on binding with endogenous ACE2 for viral cell entry and, therefore, rHA-ACE2 constitutes a versatile addition to the therapeutic arsenal for combatting COVID-19.
<b><i>Background:</i></b> The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. <b><i>Objectives:</i></b> To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. <b><i>Methods:</i></b> Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. <b><i>Results:</i></b> Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4<sup>+</sup> T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). <b><i>Conclusions:</i></b> Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.
descriptionPublicationkeyboard_double_arrow_right Book 2021 Denmark English Aarhus University
Authors: Jensby, Anne; Mogensen, Oliver Bendix Gammeljord; Svejvig, Per;
Jensby, Anne; Mogensen, Oliver Bendix Gammeljord; Svejvig, Per;
The purpose of this report is to outline the evaluation and comparison approach and the knowledge obtained through a detailed data collection process, in order to examine the implementation and application of the Half Double Methodology (HDM) at Forsvarsministeriets Material- og Indkøbsstyrelse (FMI), as well as compare and contrast pilot and reference projects. State-owned FMI is the Danish Ministry of Defence Acquisition and Logistics Organization (English abbreviation: DALO), and thus a unit under the Ministry of Defence and the Danish public sector. It is likely that the Half Double Methodology has had a positive impact on FMI and their team collaboration. The procurement process is faster, which especially is evident in pilot case 3, but also the initial versions of pilot case 1 and 2. However, here, the cases were subject to external conditions which increased the duration. FMI experiences satisfaction from stakeholders involved in the procurement. This satisfaction is also present in most of the team members engaging with the methodology. Hence overall, integrating the Half Double Methodology in FMI’s team collaboration is perceived as a success in FMI and continues to be applied. However, there is still room for improvements in the procurement process and team configuration. This relates to the application of HDM, but also other constraints in FMI, which is related to a lack of resources to develop interdisciplinary teams, as well as challenges from covid-19 restrictions. The purpose of this report is to outline the evaluation and comparison approach and the knowledge obtained through a detailed data collection process, in order to examine the implementation and application of the Half Double Methodology (HDM) at Forsvarsministeriets Material- og Indkøbsstyrelse (FMI), as well as compare and contrast pilot and reference projects. State-owned FMI is the Danish Ministry of Defence Acquisition and Logistics Organization (English abbreviation: DALO), and thus a unit under the Ministry of Defence and the Danish public sector. It is likely that the Half Double Methodology has had a positive impact on FMI and their team collaboration. The procurement process is faster, which especially is evident in pilot case 3, but also the initial versions of pilot case 1 and 2. However, here, the cases were subject to external conditions which increased the duration. FMI experiences satisfaction from stakeholders involved in the procurement. This satisfaction is also present in most of the team members engaging with the methodology. Hence overall, integrating the Half Double Methodology in FMI’s team collaboration is perceived as a success in FMI and continues to be applied. However, there is still room for improvements in the procurement process and team configuration. This relates to the application of HDM, but also other constraints in FMI, which is related to a lack of resources to develop interdisciplinary teams, as well as challenges from covid-19 restrictions.
Artiklen undersøger universitetsadjunkter og postdocs inden for det teknisk-naturvidenskabelige områdes ændrede holdning til teknologi i undervisningen, der er med sandsynlighed kan tilskrives coronapandemien. Ved hjælp af en multivariatanalyse baseret på fire enslydende spørgeskemaundersøgelser blandt samtlige teknisk-naturvidenskabelige deltagerne (N=66) i Aarhus Universitets adjunktpædagogikum umiddelbart ét år før og ét år efter pandemiens udbrud, identificeres der fire temaer af signifikante ændringer i deltagernes holdning til teknologi i undervisningen. Undersøgelsen viser en generelt og signifikant øget, positiv holdning til teknologi i undervisningen og interesse i de elementer, der omhandler pædagogiske metoder og modeller, teknologiens potentiale og rolle samt brugen af videokonference og video. Endvidere er der en signifikant øget interesse i vidensdeling med kolleger og pædagogisk support. Ingen negative holdningsændringer blev identificeret. Undersøgelsen peger således på et stort aktuelt potentiale for undervisningsudvikling og pædagogisk kompetenceudvikling i brug af teknologi på universiteterne, da de holdningsmæssige barrierer blandt undervisere, der før blev anset for vanskelige at overkomme, måske er ved at nedbrydes. The article investigates university science assistant professors and postdocs change of attitude towards technology in teaching and learning that is most likely attributed to the Covid-19 pandemic. Using a multivariate analysis based on identical surveys pre and post the outbreak among all assistant professors and postdocs enrolled in the required teacher professional development programme (N = 66) at Aarhus University, four statistically significant themes of change of attitude towards educational technology are identified. The changes are: an increased interest in pedagogical methods and models for technology in teaching and learning, an increased interest in the educational potential and role of the technology, an increased interest in video conference and video, andan increased interest in knowledge sharing and pedagogical support on technology. No adverse changes are identified. Consequently, the investigation identifies a considerable topical potential to overcome the difficult barriers associated with educators’ attitudes towards technology in teaching and learning and the potential for educational and professional development on educational technology.
The recently emerged coronavirus disease (COVID-19), which has been characterised as a pandemic by the World Health Organization (WHO), is impacting all parts of human society including agriculture, manufacturing, and tertiary sectors involving all service provision industries. This paper aims to give an overview of potential host reservoirs that could cause pandemic outbreak caused by zoonotic transmission. Amongst all, continues surveillance in slaughterhouse for possible pathogens transmission is needed to prevent next pandemic outbreak. This paper also summary the potential threats of pandemic to agriculture and aquaculture sector that control almost the total food supply chain and market. The history lesson from the past, emerging and reemerging infectious disease including the Severe Acute Respiratory Syndrome (SARS) in 2002, Influenza A H1N1 (swine flu) in 2009, Middle East Respiratory Syndrome (MERS) in 2012 and the recent COVID-19 should give us some clue to improve especially the governance to be more ready for next coming pandemic. Highlights • Urbanization promotes the occurrence of zoonotic diseases transmission. • The outbreak of COVID19 affected the global food supply chain. • In preparedness to prevent pandemic outbreak, the continues surveillance of food safety is obligated.