Cell culture models for SARS-CoV-2 infectivity and systemic complications

COVID-19 was declared by WHO as a pandemic since March 2020. The vaccination program has been implemented worldwide. Specific antiviral drugs such as remdesivir, molnupiravir and ritonavir-based nirmatrelvir were effective against SARS-CoV-2 infection. However, the new SARS-CoV-2 variants have been elevated due to viral mutation causing vaccine resistance and rapid spreading. Long-term COVID-19 complications have been life-threatening in some recovery cases. To overcome viral adaptation, cell culture model is essential to comprehend SARS-CoV-2 infection, pathophysiology, complications, and drug target alterations. The classical 2D culture cell was frequency used for viral propagation and high-throughput screening. Modern 3D culture has recapitulated key cellular and molecular events of tissue physiology. Here, we reviewed the cell lines, 3D culture, organoid and relevant models for the aforementioned applications

The formation of opal in marine reptile bones and wood

This item is only available electronically.The age of precious opal and the mechanisms that result in formation as opposed to the ubiquitous common opal are poorly understood. Until now, there has been no research on the replacement of biominerals in vertebrate bones by opal. As the microtexture, mineralogy and chemistry of bones are well-known, they provide a unique opportunity to study the mechanism of precious opal deposition. In this article chemical and textural features of Andamooka opalised plesiosaur bones were compared with those in non-opalised ichthyosaur bones from Moon Plain and a recent dolphin bone. Opalised wood samples from Nevada and White Cliffs were also studied to compare with bone opalisation and different depositional environments (sedimentary vs volcanogenic). The cellular form of a continuous irregular framework of silica was retained in the wood samples. The mineralogy of the wood samples reflects their depositional environment, where opal-CT and opal-C is dominant in volcanic deposits (Nevada) and opal-A in sedimentary deposits (White Cliffs). Comparison of the Nevada wood to Post-Archean average shale (PAAS) shows that it is rich in most trace elements with the exception of Y and U. The high amount of trace elements is a reflection of its volcanic origin. In contrast, the opalised wood from White Cliffs is depleted in most trace elements with the exception of Co. Cracks were observed in both the opalised wood and bone samples which allowed the void space required to form precious opal. The opalised wood from White Cliffs and the opalised plesiosaur bones from Andamooka are chemically very similar and reflect similar compositions for the opalising fluids. The Haversian system was preserved in the non-opalised ichthyosaur bone but not in the opalised bones. The ichthyosaur bone is comprised mostly of carbonate-hydroxylapatite but in the opalised bones the major mineral is quartz. Modern dolphin bone consists of bioapatite with water and organic material: its trace element composition is broadly similar to the ichthyosaur bone from Moon Plain but is richer in Sr, Zn and Co. When normalized to PAAS, the ichthyosaur bone is depleted in all trace elements with the exception of Sr, which is likely a product of the carbonate-rich mineralogy. Like the ichthyosaur bones, the opalised bones are also depleted in trace elements, with the exception of Co and Zn. There is no evidence of remnant bioapatite in the opalised bone, a finding consistent with the chemical analyses that show only trace amounts of Ca and no P. The level of microstructural preservation in the opalised bone suggests that opalisation is not a closely coupled dissolution-reprecipitation reaction and that there was a fluid filled space between the reaction fronts which allowed the opal silica spheres to form and settle within a comparatively small space (100 µm). An alternative interpretation is that the fibrous quartz filled the osteon canals before opalisation and that the bioapatite was then dissolved away leaving a hollow cast that filled slowly with opal.Thesis (B.Sc.(Hons)) -- University of Adelaide, School of Physical Sciences, 200

The formation of precious opal: Clues from the opalization of bone

Copyright © 2008 Mineralogical Association of CanadaThe composition and microstructure of opalized saurian bones (Plesiosaur) from Andamooka, South Australia, have been analyzed and compared to saurian bones that have been partially replaced by magnesian calcite from the same geological formation, north of Coober Pedy, South Australia. Powder X-ray-diffraction analyses show that the opalized bones are composed of opal-AG and quartz. Major- and minor-element XRF analyses show that they are essentially pure SiO₂ (88.59 to 92.69 wt%), with minor amounts of Al₂O₃ (2.02 to 4.41 wt%) and H₂O (3.36 to 4.23 wt%). No traces of biogenic apatite remain after opalization. The opal is depleted in all trace elements relative to PAAS. During the formation of the opal, the coarser details of the bone microstructure have been preserved down to the level of the individual osteons (scale of around 100 μm), but the central canals and the boundary area have been enlarged and filled with chalcedony, which postdates opal formation. These chemical and microstructural features are consistent with the opalization process being a secondary replacement after partial replacement of the bone by magnesian calcite. They are also consistent with the opal forming first as a gel in the small cavities left by the osteons, and the individual opal spheres growing as they settle within the gel. Changes in the viscosity of the gel provide a ready explanation for the occurrence of color and potch banding in opals. The indication that opalization is a secondary process after calcification on the Australian opal fields is consistent with a Tertiary age for formation.Benjamath Pewkliang, Allan Pring and Joël Brugge

Suite de la defense de l'Esprit des loix, ou Examen de la replique du gazetier ecclesiastique a la Defense de l'Esprit des loix

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Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy.

Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confounds their utility. We have recently developed an immortalized hepatocyte-like cell line (imHC) from human mesenchymal stem cells, and tested it for use as a substitute model for hepatotropic infectious diseases. With a special interest in liver pathogenesis of viral infection, herein we determined the suitability of imHC as a host cell target for dengue virus (DENV) and as a model for anti-viral drug testing. We characterized the kinetics of DENV production, cellular responses to DENV infection (apoptosis, cytokine production and lipid droplet metabolism), and examined anti-viral drug effects in imHC cells with comparisons to the commonly used hepatoma cell lines (HepG2 and Huh-7) and PHHs. Our results showed that imHC cells had higher efficiencies in DENV replication and NS1 secretion as compared to HepG2 and Huh-7 cells. The kinetics of DENV infection in imHC cells showed a slower rate of apoptosis than the hepatoma cell lines and a certain similarity of cytokine profiles to PHHs. In imHC, DENV-induced alterations in levels of lipid droplets and triacylglycerols, a major component of lipid droplets, were more apparent than in hepatoma cell lines, suggesting active lipid metabolism in imHC. Significantly, responses to drugs with DENV inhibitory effects were greater in imHC cells than in HepG2 and Huh-7 cells. In conclusion, our findings suggest superior suitability of imHC as a new hepatocyte model for studying mechanisms underlying viral pathogenesis, liver diseases and drug effects