scholarly journals Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells

2015 ◽  
Vol 112 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Ellen F. Foxman ◽  
James A. Storer ◽  
Megan E. Fitzgerald ◽  
Bethany R. Wasik ◽  
Lin Hou ◽  
...  
Keyword(s):  
Viral Replication ◽  
Nasal Cavity ◽  
Common Cold ◽  
Defense Response ◽  
Type I ◽  
Antiviral Defense ◽  
Temperature Dependent ◽  
The Common ◽  
Dependent Growth ◽  
Airway Cells

Most isolates of human rhinovirus, the common cold virus, replicate more robustly at the cool temperatures found in the nasal cavity (33–35 °C) than at core body temperature (37 °C). To gain insight into the mechanism of temperature-dependent growth, we compared the transcriptional response of primary mouse airway epithelial cells infected with rhinovirus at 33 °C vs. 37 °C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited a striking enrichment in expression of antiviral defense response genes at 37 °C relative to 33 °C, which correlated with significantly higher expression levels of type I and type III IFN genes and IFN-stimulated genes (ISGs) at 37 °C. Temperature-dependent IFN induction in response to rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG-I–like receptors (RLRs). Stimulation of primary airway cells with the synthetic RLR ligand poly I:C led to greater IFN induction at 37 °C relative to 33 °C at early time points poststimulation and to a sustained increase in the induction of ISGs at 37 °C relative to 33 °C. Recombinant type I IFN also stimulated more robust induction of ISGs at 37 °C than at 33 °C. Genetic deficiency of MAVS or the type I IFN receptor in infected airway cells permitted higher levels of viral replication, particularly at 37 °C, and partially rescued the temperature-dependent growth phenotype. These findings demonstrate that in mouse airway cells, rhinovirus replicates preferentially at nasal cavity temperature due, in part, to a less efficient antiviral defense response of infected cells at cool temperature.

scholarly journals Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature

2016 ◽  
Vol 113 (30) ◽  
pp. 8496-8501 ◽  
Author(s):  
Ellen F. Foxman ◽  
James A. Storer ◽  
Kiran Vanaja ◽  
Andre Levchenko ◽  
Akiko Iwasaki
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Temperature Dependence ◽  
Host Cell ◽  
Common Cold ◽  
Virus Production ◽  
B Cell Lymphoma ◽  
Temperature Dependent ◽  
Innate Defense ◽  
The Common

Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33–35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 °C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells. During the single replication cycle, RV exhibited temperature-dependent replication in both cell types in the absence of IFN induction. At 37 °C, earlier signs of apoptosis in RV-infected cells were accompanied by reduced virus production. Furthermore, apoptosis of epithelial cells was enhanced at 37 °C in response to diverse stimuli. Dynamic mathematical modeling and B cell lymphoma 2 (BCL2) overexpression revealed that temperature-dependent host cell death could partially account for the temperature-dependent growth observed during RV amplification, but also suggested additional mechanisms of virus control. In search of a redundant antiviral pathway, we identified a role for the RNA-degrading enzyme RNAseL. Simultaneous antagonism of apoptosis and RNAseL increased viral replication and dramatically reduced temperature dependence. These findings reveal two IFN-independent mechanisms active in innate defense against RV, and demonstrate that even in the absence of IFNs, temperature-dependent RV amplification is largely a result of host cell antiviral restriction mechanisms operating more effectively at 37 °C than at 33 °C.

Targeting G-quadruplexes in the rhinovirus genome by Pyridostatin inhibits uncoating 3 and highlights a critical role for sodium ions.

2021 ◽  
Author(s):  
Antonio Real-Hohn ◽  
Martin Groznica ◽  
Georg Kontaxis ◽  
Rong Zhu ◽  
Otávio Chaves ◽  
...  
Keyword(s):  
Common Cold ◽  
Critical Role ◽  
Sodium Ions ◽  
Structural Elements ◽  
Temperature Dependent ◽  
Physiological Conditions ◽  
Metastable Structures ◽  
G Quadruplex ◽  
The Common ◽  
Secondary Structural Elements

Abstract The ~ 2.4 µm long rhinovirus ss(+)RNA genome consists of roughly 7,200 nucleotides. It is tightly folded to fit into the ~ 22 nm diameter void in the protein capsid. In addition to previously predicted secondary structural elements in the RNA, using the QGRS mapper, we revealed the presence of multiple quadruplex forming G-rich sequences (QGRS) in the RV-A, B, and C clades, with four of them being exquisitely conserved. The biophysical analyses of ribooligonucleotides corresponding to selected QGRS demonstrate G-quadruplex (GQ) formation in each instance and resulted in discovering another example of an unconventional, two-layer zero-nucleotide loop RNA GQ stable at physiological conditions. By exploiting the temperature-dependent viral breathing to allow diffusion of small compounds into the virion, we demonstrate that the GQ-binding compounds PhenDC3 and pyridostatin (PDS) uniquely interfere with viral uncoating. Remarkably, this inhibition was entirely prevented in the presence of K+ but not Na+, despite the higher GQ stabilising effect of K+. Based on virus thermostability studies combined with ultrastructural imaging of isolated viral RNA, we propose a mechanism where Na+ keeps the encapsidated genome loose, allowing its penetration by PDS to promote the transition of QGRS sequestered in alternative metastable structures into GQs. The resulting conformational change then materialises in a severely compromised RNA release from the proteinaceous shell. Targeting extracellularly circulating RVs with GQ-stabilisers might thus become a novel way of combating the common cold.

scholarly journals Targeting G-quadruplexes in the rhinovirus genome by Pyridostatin inhibits uncoating and highlights a critical role for sodium ions.

2021 ◽  
Author(s):  
Antonio Real-Hohn ◽  
Martin Groznica ◽  
Georg Kontaxis ◽  
Rong Zhu ◽  
Otávio Chaves ◽  
...  
Keyword(s):  
Common Cold ◽  
Critical Role ◽  
Sodium Ions ◽  
Structural Elements ◽  
Temperature Dependent ◽  
Physiological Conditions ◽  
Metastable Structures ◽  
G Quadruplex ◽  
The Common ◽  
Secondary Structural Elements

Abstract The ~ 2.4 µm long rhinovirus ss(+)RNA genome consists of roughly 7,200 nucleotides. It is tightly folded to fit into the ~ 22 nm diameter void in the protein capsid. In addition to previously predicted secondary structural elements in the RNA, using the QGRS mapper, we revealed the presence of multiple quadruplex forming G-rich sequences (QGRS) in the RV-A, B, and C clades, with four of them being exquisitely conserved. The biophysical analyses of ribooligonucleotides corresponding to selected QGRS demonstrate G-quadruplex (GQ) formation in each instance and resulted in discovering another example of an unconventional, two-layer zero-nucleotide loop RNA GQ stable at physiological conditions. By exploiting the temperature-dependent viral breathing to allow diffusion of small compounds into the virion, we demonstrate that the GQ-binding compounds PhenDC3 and pyridostatin (PDS) uniquely interfere with viral uncoating. Remarkably, this inhibition was entirely prevented in the presence of K+ but not Na+, despite the higher GQ stabilising effect of K+. Based on virus thermostability studies combined with ultrastructural imaging of isolated viral RNA, we propose a mechanism where Na+ keeps the encapsidated genome loose, allowing its penetration by PDS to promote the transition of QGRS sequestered in alternative metastable structures into GQs. The resulting conformational change then materialises in a severely compromised RNA release from the proteinaceous shell. Targeting extracellularly circulating RVs with GQ-stabilisers might thus become a novel way of combating the common cold.

scholarly journals Temperature-Dependent Growth of 36 Inner Nanotubes inside Nickelocene, Cobaltocene and Ferrocene-Filled Single-Walled Carbon Nanotubes

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2984
Author(s):  
Marianna V. Kharlamova ◽  
Christian Kramberger
Keyword(s):  
Carbon Nanotubes ◽  
Single Walled Carbon Nanotubes ◽  
Metal Catalyst ◽  
Temperature Dependent ◽  
Single Walled Carbon ◽  
Catalyst Type ◽  
The Common ◽  
Effects Of Temperature ◽  
Dependent Growth ◽  
Walled Carbon Nanotubes

We have investigated the effects of temperature, diameter and metal catalyst type on the growth of inner nanotubes inside metallocene-filled single-walled carbon nanotubes (SWCNTs). The effects on the yield of different chiralities of inner nanotubes were scrutinized by multifrequency Raman spectroscopy. The investigated diameters range from ~0.7 to 1.3 nm and comprise 36 distinct chiralities. For all three investigated metals (Ni, Co, Fe), there is a linear correlation of growth temperature with nanotube diameter. The common slope for these metals is found to be 40.5 °C/Å. The temperature difference between the largest and the smallest diameter tubes amounts to ~230 °C for all three precursors. The growth temperatures are offset by 34 °C from Ni to Co and another 28 °C from Co to Fe. The quantified correlations of temperature, diameter and metal catalyst type provide the basis for engineering the diameter-specific growth of nanotubes.

Interventional Thermal Injury of the Arterial Wall: Unfolding of von Willebrand Factor and Its Increased Binding to Collagen after 55° C Heating

1996 ◽  
Vol 75 (03) ◽  
pp. 515-519 ◽  
Author(s):  
Mark J Post ◽  
Anke N de Graaf-Bos ◽  
George Posthuma ◽  
Philip G de Groot ◽  
Jan J Sixma ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Conformational Changes ◽  
Arterial Wall ◽  
Platelet Adhesion ◽  
Type I ◽  
Temperature Dependent ◽  
Collagen Types ◽  
Electron Microscopic ◽  
Von Willebrand ◽  
Willebrand Factor

Summary Purpose. Thermal angioplasty alters the thrombogenicity of the arterial wall. In previous studies, platelet adhesion was found to increase after heating human subendothelium to 55° C and decrease after heating to 90° C. In the present electron microscopic study, the mechanism of this temperature-dependent platelet adhesion to the heated arterial wall is elucidated by investigating temperature-dependent conformational changes of von Willebrand factor (vWF) and collagen types I and III and the binding of vWF to heated collagen. Methods. Purified vWF and/or collagen was applied to electron microscopic grids and heated by floating on a salt-solution of 37° C, 55° C or 90° C for 15 s. After incubation with a polyclonal antibody against vWF and incubation with protein A/gold, the grids were examined by electron microscopy. Results. At 37° C, vWF was coiled. At 55° C, vWF unfolded, whereas heating at 90° C caused a reduction in antigenicity. Collagen fibers heated to 37° C were 60.3 ± 3.1 nm wide. Heating to 55° C resulted in the unwinding of the fibers, increasing the width to 87.5 ± 8.2 nm (p < 0.01). Heating to 90° C resulted in denatured fibers with an enlarged width of 85.1 ± 6.1 nm (p < 0.05). Heating of collagen to 55° C resulted in an increased vWF binding as compared to collagen heated to 37° C or to 90° C. Incubation of collagen with vWF, prior to heating, resulted in a vWF binding after heating to 55° C that was similar to the 37° C binding and a decreased binding after 90° C. Conclusions. After 55° C heating, the von Willebrand factor molecule unfolds and collagen types I and III exhibit an increased adhesiveness for von Willebrand factor. Heating to 90° C denatures von Willebrand factor and collagen. The conformation changes of von Willebrand factor and its altered binding to collagen type I and III may explain the increased and decreased platelet adhesion to subendothelium after 55° C and 90° C heating, respectively.

The concept of motivation for effective credit risk management

2020 ◽  
Vol 26 (11) ◽  
pp. 2567-2593
Author(s):  
M.V. Pomazanov
Keyword(s):  
Risk Management ◽  
Economic Modeling ◽  
Type I ◽  
Credit Risk Management ◽  
Curve Modeling ◽  
Business Functions ◽  
The Common ◽  
Lending Decisions ◽  
The One

Subject. The study addresses the improvement of risk management efficiency and the quality of lending decisions made by banks. Objectives. The aim is to present the bank management with a fair algorithm for risk management motivation on the one hand, and the credit management (business) on the other hand. Within the framework of the common goal to maximize risk-adjusted income from loans, this algorithm will provide guidelines for ‘risk management’ and ‘business’ functions on how to improve individual and overall efficiency. Methods. The study employs the discriminant analysis, type I and II errors, Lorentz curve modeling, statistical analysis, economic modeling. Results. The paper offers a mechanism for assessing the quality of risk management decisions as opposed to (or in support of) decisions of the lending business when approving transactions. The mechanism rests on the approach of stating type I and II errors and the corresponding classical metric of the Gini coefficient. On the ‘business’ side, the mechanism monitors the improvement or deterioration of the indicator of changes in losses in comparison with the market average. Conclusions. The study substantiates the stimulating ‘rules of the game’ between the ‘business’ and ‘risk management’ to improve the efficiency of the entire business, to optimize interactions within the framework of internal competition. It presents mathematical tools to calculate corresponding indicators of the efficiency of internally competing entities.

Current updates on COVID-19 - A review

2020 ◽  
Vol 10 (1) ◽  
pp. 1-8
Author(s):  
Ghotekar D S ◽  
Vishal N Kushare ◽  
Sagar V Ghotekar
Keyword(s):  
World Health Organization ◽  
Common Cold ◽  
Respiratory Diseases ◽  
Gastrointestinal Diseases ◽  
Hubei Province ◽  
World Health ◽  
The World ◽  
The Common ◽  
Novel Coronavirus ◽  
Health Organization

Coronaviruses are a family of viruses that cause illness such as respiratory diseases or gastrointestinal diseases. Respiratory diseases can range from the common cold to more severe diseases. A novel coronavirus outbreak was first documented in Wuhan, Hubei Province, China in December 2019. The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) a pandemic. A global coordinated effort is needed to stop the further spread of the virus. A novel coronavirus (nCoV) is a new strain that has not been identified in humans previously. Once scientists determine exactly what coronavirus it is, they give it a name (as in the case of COVID-19, the virus causing it is SARS-CoV-2).

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