586 research outputs found
SARS-CoV-2 ORF8 accessory protein is a virulence factor
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) 6, 7a, or 7b individually did not significantly impact viral pathogenicity in humanized K18-hACE2 transgenic mice. In contrast, the deletion of ORF8 partially attenuated SARS-CoV-2, resulting in reduced lung pathology and 40% less mortality, indicating that ORF8 is a critical determinant of SARS-CoV-2 pathogenesis. Attenuation of SARS-CoV-2-∆8 was not associated with a significant decrease in replication either in the lungs of mice or in organoid-derived human airway cells. An increase in the interferon signaling at early times post-infection (1 dpi) in the lungs of mice and a decrease in the pro-inflammatory and interferon response at late times post-infection, both in the lungs of mice (6 dpi) and in organoid-derived human airway cells [72 hours post-infection (hpi)], were observed. The early, but not prolonged, interferon response along with the lower inflammatory response could explain the partial attenuation of SARS-CoV-∆8. The presence of ORF8 in SARS-CoV-2 was associated with an increase in the number of macrophages in the lungs of mice. In addition, the supernatant of SARS-CoV-2-WT (wild-type)-infected organoid-derived cells enhanced the activation of macrophages as compared to SARS-CoV-2-∆8-infected cells. These results show that ORF8 is a virulence factor involved in inflammation that could be targeted in COVID-19 therapies. IMPORTANCE The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.</p
SARS-CoV-2 ORF8 accessory protein is a virulence factor
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) 6, 7a, or 7b individually did not significantly impact viral pathogenicity in humanized K18-hACE2 transgenic mice. In contrast, the deletion of ORF8 partially attenuated SARS-CoV-2, resulting in reduced lung pathology and 40% less mortality, indicating that ORF8 is a critical determinant of SARS-CoV-2 pathogenesis. Attenuation of SARS-CoV-2-∆8 was not associated with a significant decrease in replication either in the lungs of mice or in organoid-derived human airway cells. An increase in the interferon signaling at early times post-infection (1 dpi) in the lungs of mice and a decrease in the pro-inflammatory and interferon response at late times post-infection, both in the lungs of mice (6 dpi) and in organoid-derived human airway cells [72 hours post-infection (hpi)], were observed. The early, but not prolonged, interferon response along with the lower inflammatory response could explain the partial attenuation of SARS-CoV-∆8. The presence of ORF8 in SARS-CoV-2 was associated with an increase in the number of macrophages in the lungs of mice. In addition, the supernatant of SARS-CoV-2-WT (wild-type)-infected organoid-derived cells enhanced the activation of macrophages as compared to SARS-CoV-2-∆8-infected cells. These results show that ORF8 is a virulence factor involved in inflammation that could be targeted in COVID-19 therapies. IMPORTANCE The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.</p
Stability of trapped Bose-Einstein condensates
In three-dimensional trapped Bose-Einstein condensate (BEC), described by the
time-dependent Gross-Pitaevskii-Ginzburg equation, we study the effect of
initial conditions on stability using a Gaussian variational approach and exact
numerical simulations. We also discuss the validity of the criterion for
stability suggested by Vakhitov and Kolokolov. The maximum initial chirp
(initial focusing defocusing of cloud) that can lead a stable condensate to
collapse even before the number of atoms reaches its critical limit is obtained
for several specific cases. When we consider two- and three-body nonlinear
terms, with negative cubic and positive quintic terms, we have the conditions
for the existence of two phases in the condensate. In this case, the magnitude
of the oscillations between the two phases are studied considering sufficient
large initial chirps. The occurrence of collapse in a BEC with repulsive
two-body interaction is also shown to be possible.Comment: 15 pages, 11 figure
Short-Wave Excitations in Non-Local Gross-Pitaevskii Model
It is shown, that a non-local form of the Gross-Pitaevskii equation allows to
describe not only the long-wave excitations, but also the short-wave ones in
the systems with Bose-condensate. At given parameter values, the excitation
spectrum mimics the Landau spectrum of quasi-particle excitations in superfluid
Helium with roton minimum. The excitation wavelength, at which the roton
minimum exists, is close to the inter-particle interaction range. It is shown,
that the existence domain of the spectrum with a roton minimum is reduced, if
one accounts for an inter-particle attraction.Comment: 5 pages, 5 figures, UJP style; presented at Bogolyubov Kyiv
Conference "Modern Problems of Theoretical and Mathematical Physics",
September 15-18, 200
Exact results on the dynamics of multi-component Bose-Einstein condensate
We study the time-evolution of the two dimensional multi-component
Bose-Einstein condensate in an external harmonic trap with arbitrary
time-dependent frequency. We show analytically that the time-evolution of the
total mean-square radius of the wave-packet is determined in terms of the same
solvable equation as in the case of a single-component condensate. The dynamics
of the total mean-square radius is also the same for the rotating as well as
the non-rotating multi-component condensate. We determine the criteria for the
collapse of the condensate at a finite time. Generalizing our previous work on
a single-component condensate, we show explosion-implosion duality in the
multi-component condensate.Comment: Two-column 6 pages, RevTeX, no figures(v1); Added an important
reference, version to appear in Physical Review A (v2
Evaluation of turbulent dissipation rate retrievals from Doppler Cloud Radar
Turbulent dissipation rate retrievals from cloud radar Doppler velocity measurements are evaluated using independent, in situ observations in Arctic stratocumulus clouds. In situ validation data sets of dissipation rate are derived using sonic anemometer measurements from a tethered balloon and high frequency pressure variation observations from a research aircraft, both flown in proximity to stationary, ground-based radars. Modest biases are found among the data sets in particularly low- or high-turbulence regimes, but in general the radar-retrieved values correspond well with the in situ measurements. Root mean square differences are typically a factor of 4-6 relative to any given magnitude of dissipation rate. These differences are no larger than those found when comparing dissipation rates computed from tetheredballoon and meteorological tower-mounted sonic anemometer measurements made at spatial distances of a few hundred meters. Temporal lag analyses suggest that approximately half of the observed differences are due to spatial sampling considerations, such that the anticipated radar-based retrieval uncertainty is on the order of a factor of 2-3. Moreover, radar retrievals are clearly able to capture the vertical dissipation rate structure observed by the in situ sensors, while offering substantially more information on the time variability of turbulence profiles. Together these evaluations indicate that radar-based retrievals can, at a minimum, be used to determine the vertical structure of turbulence in Arctic stratocumulus clouds
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