scholarly journals Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses

PLoS Biology ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. e3001065
Author(s):  
Vanessa Herder ◽  
Kieran Dee ◽  
Joanna K. Wojtus ◽  
Ilaria Epifano ◽  
Daniel Goldfarb ◽  
...  
Keyword(s):  
Elevated Temperature ◽  
Three Dimensional ◽  
International Health ◽  
Tissue Temperature ◽  
Host Responses ◽  
Microbial Infection ◽  
Health Crisis ◽  
Immune Defenses ◽  
Natural Tissue ◽  
Air Liquid Interface

The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air–liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.

scholarly journals Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of the induction of IFN-mediated innate immune defences

2020 ◽  
Author(s):  
Vanessa Herder ◽  
Kieran Dee ◽  
Joanna K. Wojtus ◽  
Daniel Goldfarb ◽  
Christoforos Rozario ◽  
...  
Keyword(s):  
Elevated Temperature ◽  
International Health ◽  
Tissue Temperature ◽  
Temperature Elevation ◽  
Microbial Infection ◽  
Health Crisis ◽  
Infection And Inflammation ◽  
Rna Accumulation ◽  
Natural Tissue ◽  
Immune Defences

AbstractThe pandemic spread of SARS-CoV-2, the etiological agent of COVID-19, represents a significant and ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection and inflammation that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 tropism and replication. Utilizing a 3D air-liquid interface (ALI) model that closely mimics the natural tissue physiology and cellular tropism of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. We show that temperature elevation induces wide-spread transcriptome changes that impact upon the regulation of multiple pathways, including epigenetic regulation and lncRNA expression, without disruption of general cellular transcription or the induction of interferon (IFN)-mediated antiviral immune defences. Respiratory tissue incubated at temperatures >37°C remained permissive to SARS-CoV-2 infection but severely restricted the initiation of viral transcription, leading to significantly reduced levels of intraepithelial viral RNA accumulation and apical shedding of infectious virus. To our knowledge, we present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication. Our data identify an important role for temperature elevation in the epithelial restriction of SARS-CoV-2 that occurs independently of the induction of canonical IFN-mediated antiviral immune defences and interferon-stimulated gene (ISG) expression.

scholarly journals Characterization of Polycaprolactone Nanohydroxyapatite Composites with Tunable Degradability Suitable for Indirect Printing

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 295
Author(s):  
Stephanie E. Doyle ◽  
Lauren Henry ◽  
Ellen McGennisken ◽  
Carmine Onofrillo ◽  
Claudia Di Bella ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Large Scale ◽  
Three Dimensional ◽  
Cell Number ◽  
Compressive Modulus ◽  
Degradation Rates ◽  
Scaffold Materials ◽  
Natural Tissue ◽  
Complete Regeneration

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.

scholarly journals An Immunoinformatics Approach for SARS-CoV-2 in Latam Populations and Multi-Epitope Vaccine Candidate Directed Towards the World’s Population

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 581
Author(s):  
Andrés Felipe Cuspoca ◽  
Laura Lorena Díaz ◽  
Alvaro Fernando Acosta ◽  
Marcela Katherine Peñaloza ◽  
Yardany Rafael Méndez ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Three Dimensional ◽  
Experimental Tests ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Histocompatibility Complex ◽  
Potential Vaccine ◽  
Lymphocyte Responses ◽  
Socioeconomic Consequences ◽  
Epitope Candidate

The coronavirus pandemic is a major public health crisis affecting global health systems with dire socioeconomic consequences, especially in vulnerable regions such as Latin America (LATAM). There is an urgent need for a vaccine to help control contagion, reduce mortality and alleviate social costs. In this study, we propose a rational multi-epitope candidate vaccine against SARS-CoV-2. Using bioinformatics, we constructed a library of potential vaccine peptides, based on the affinity of the most common major human histocompatibility complex (HLA) I and II molecules in the LATAM population to predict immunological complexes among antigenic, non-toxic and non-allergenic peptides extracted from the conserved regions of 92 proteomes. Although HLA-C, had the greatest antigenic peptide capacity from SARS-CoV-2, HLA-B and HLA-A, could be more relevant based on COVID-19 risk of infection in LATAM countries. We also used three-dimensional structures of SARS-CoV-2 proteins to identify potential regions for antibody production. The best HLA-I and II predictions (with increased coverage in common alleles and regions evoking B lymphocyte responses) were grouped into an optimized final multi-epitope construct containing the adjuvants Beta defensin-3, TpD, and PADRE, which are recognized for invoking a safe and specific immune response. Finally, we used Molecular Dynamics to identify the multi-epitope construct which may be a stable target for TLR-4/MD-2. This would prove to be safe and provide the physicochemical requirements for conducting experimental tests around the world.

Synergising International Public Health Law and International Disaster Law

2020 ◽  
pp. 1-11
Author(s):  
Pratik DIXIT
Keyword(s):  
Public Health ◽  
International Health ◽  
Health Law ◽  
Global Public Health ◽  
Public Health Law ◽  
Health Crisis ◽  
Response Strategies ◽  
Public Health Crisis ◽  
International Public Health ◽  
Health Regulations

There is no time more opportune to review the workings of the International Health Regulations (IHR) than the present COVID-19 crisis. This article analyses the theoretical and practical aspects of international public health law (IPHL), particularly the IHR, to argue that it is woefully unprepared to protect human rights in times of a global public health crisis. To rectify this, the article argues that the IHR should design effective risk reduction and response strategies by incorporating concepts from international disaster law (IDL). Along similar lines, this article suggests that IDL also has a lot to learn from IPHL in terms of greater internationalisation and institutionalisation. Institutionalisation of IDL on par with IPHL will provide it with greater legitimacy, transparency and accountability. This article argues that greater cross-pollination of ideas between IDL and IPHL is necessary in order to make these disciplines more relevant for the future.

scholarly journals The New Reality of Bangladesh: A Critical Analysis of New Normal Challenges and Opportunities

2020 ◽  
Vol 1 (2) ◽  
pp. 126-146
Author(s):  
Umme Sayeda
Keyword(s):  
Policy Development ◽  
Human Life ◽  
International Health ◽  
Analysis Tool ◽  
Governance System ◽  
Health Crisis ◽  
New Normal ◽  
Secondary Sources ◽  
Grounded Theory Method ◽  
Challenges And Opportunities

The post-COVID-19 new normal will arise as a game-changer in the policy-making of the world states. Accordingly, this article highlights the post-pandemic Bangladesh that should integrate biology affirmatively in the policy development procedures to reshape the new normal challenges as opportunities. The grounded theory method is adopted as a quantitative analysis tool relying on the secondary sources of data to portray the significance of biopolitics as political rationality in new norm Bangladesh. The researcher has used the neo-realism approach to develop the ‘Biopolitical Rationale Theory’, which uncovers how evolving neo-realist security demands the prioritization of biopolitics in every sphere of decision making for governing the post-pandemic new standard of existence. The 2020 corona outbreak proved that human life and the environment are the ultimate means of survival rather than the traditional security arrangements and extreme economic growth which are inhumane (rationality of death and militarization), unhygienic, and destructive to the environment (exploitation of nature is profitable). The article recommends some alternative new normal policies such as non-discriminative health policy, bordering in line with International Health Regulations (IHR), digitalization with better cybersecurity, virtualization of the tourist industry (application of Extended Reality), application of Career Resilience (CR), and Strategic Flexibility Analysis tools in the re-employment and career development, greening the economy, special arrangements for emergency health crisis and undertaking actions considering the environment as a remedy rather than a crisis. The review research concludes that the inclusion of biopolitics in the Bangladesh governance system can redesign the challenges of new normal as new opportunities. But the reshaping of such a new reality will itself prevail as a considerable challenge for Bangladesh.

Formulation of a Statistical Model of Heat Transfer in Perfused Tissue

1994 ◽  
Vol 116 (4) ◽  
pp. 521-527 ◽  
Author(s):  
J. W. Baish
Keyword(s):  
Heat Transfer ◽  
Heat Transport ◽  
Drug Transport ◽  
Transfer Problem ◽  
Three Dimensional ◽  
Tissue Temperature ◽  
Statistical Interpretation ◽  
Transfer Equations ◽  
Vascular Geometry ◽  
Steady State Heat

A new model of steady-state heat transport in perfused tissue is presented. The key elements of the model are as follows: (1) a physiologically-based algorithm for simulating the geometry of a realistic vascular tree containing all thermally significant vessels in a tissue; (2) a means of solving the conjugate heat transfer problem of convection by the blood coupled to three-dimensional conduction in the extravascular tissue, and (3) a statistical interpretation of the calculated temperature field. This formulation is radically different from the widely used Pennes and Weinbaum-Jiji bio-heat transfer equations that predict a loosely defined local average tissue temperature from a local perfusion rate and a minimal representation of the vascular geometry. Instead, a probability density function for the tissue temperature is predicted, which carries information on the most probable temperature at a point and uncertainty in that temperature due to the proximity of thermally significant blood vessels. A sample implementation illustrates the dependence of the temperature distribution on the flow rate of the blood and the vascular geometry. The results show that the Pennes formulation of the bio-heat transfer equation accurately predicts the mean tissue temperature except when the arteries and veins are in closely spaced pairs. The model is useful for fundamental studies of tissue heat transport, and should extend readily to other forms of tissue transport including oxygen, nutrient, and drug transport.

scholarly journals An In Vitro Lung System to Assess the Proinflammatory Hazard of Carbon Nanotube Aerosols

2020 ◽  
Vol 21 (15) ◽  
pp. 5335
Author(s):  
Hana Barosova ◽  
Bedia Begum Karakocak ◽  
Dedy Septiadi ◽  
Alke Petri-Fink ◽  
Vicki Stone ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Three Dimensional ◽  
Adverse Outcomes ◽  
Alveolar Epithelial Cells ◽  
Proinflammatory Response ◽  
Multiwalled Carbon ◽  
Alveolar Epithelial ◽  
Culture Model ◽  
Air Liquid Interface

In vitro three-dimensional (3D) lung cell models have been thoroughly investigated in recent years and provide a reliable tool to assess the hazard associated with nanomaterials (NMs) released into the air. In this study, a 3D lung co-culture model was optimized to assess the hazard potential of multiwalled carbon nanotubes (MWCNTs), which is known to provoke inflammation and fibrosis, critical adverse outcomes linked to acute and prolonged NM exposure. The lung co-cultures were exposed to MWCNTs at the air-liquid interface (ALI) using the VITROCELL® Cloud system while considering realistic occupational exposure doses. The co-culture model was composed of three human cell lines: alveolar epithelial cells (A549), fibroblasts (MRC-5), and macrophages (differentiated THP-1). The model was exposed to two types of MWCNTs (Mitsui-7 and Nanocyl) at different concentrations (2–10 μg/cm2) to assess the proinflammatory as well as the profibrotic responses after acute (24 h, one exposure) and prolonged (96 h, repeated exposures) exposure cycles. The results showed that acute or prolonged exposure to different concentrations of the tested MWCNTs did not induce cytotoxicity or apparent profibrotic response; however, suggested the onset of proinflammatory response.

Three-Dimensional Numerical Analysis for Bolted Flange Joints Considering Effect of Creep

2018 ◽  
Author(s):  
Lewen Bi ◽  
Lanzhu Zhang
Keyword(s):  
High Temperature ◽  
Elevated Temperature ◽  
Numerical Analysis ◽  
Yield Strength ◽  
Room Temperature ◽  
Three Dimensional ◽  
Short Term ◽  
Flange Connection ◽  
Petroleum Chemical ◽  
Bolted Flange

Bolted flange joints are widely used in petroleum, chemical, nuclear and power industries, etc. With more and more devices are used at high temperature, the performance of flange connections becomes more complex, especially with creep of different components in flange connection. At elevated temperature, with the loss of bolt force and gasket force due to creep, the joints are prone to leak. Based on this, this paper analyzed the relaxation of bolt force at elevated temperature due to creep of bolt, flange and gasket separately and simultaneously. Besides, the influence of different initial installation stress of bolts was also studied. The results showed bolted flange joints relaxed due to gasket creep during early short term service. However, contribution of bolt and flange creep became more and more significant with the extension of time. With considering the creep of bolt, flange and gasket simultaneously, 50% to 60% of the bolt material yield strength at room temperature was recommended as the bolt initial installation stress for the joint case studied in this paper.

scholarly journals A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance

2016 ◽  
Vol 2 (3) ◽  
pp. e1501462 ◽  
Author(s):  
Cameron A. McConkey ◽  
Elizabeth Delorme-Axford ◽  
Cheryl A. Nickerson ◽  
Kwang Sik Kim ◽  
Yoel Sadovsky ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Maternal Blood ◽  
Microbial Infection ◽  
Microbial Resistance ◽  
Fetal Protection ◽  
Multinucleated Cells ◽  
Culture Model ◽  
Microbial Infections ◽  
Cells Cultured

In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)–based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance.

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