Propagation of Dental and Respiratory Cells and Organs in Microgravity

10.3791/62690 ◽  
2021 ◽  
Author(s):  
Mirali Pandya ◽  
Wei Ma ◽  
Huling Lyu ◽  
Xianghong Luan ◽  
Thomas G. H. Diekwisch
Keyword(s):  
Respiratory Cells

scholarly journals New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Bitam ◽  
Ahmad Elbahnsi ◽  
Geordie Creste ◽  
Iwona Pranke ◽  
Benoit Chevalier ◽  
...  
Keyword(s):  
Phosphinic Acid ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Transmembrane Conductance Regulator ◽  
Intracellular Loop ◽  
Respiratory Cells ◽  
Cftr Protein ◽  
Dynamics Simulations ◽  
And Function ◽  
Molecular Mode

AbstractC407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4–NBD1 interface.

scholarly journals Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mariana G. Ferrarini ◽  
Avantika Lal ◽  
Rita Rebollo ◽  
Andreas J. Gruber ◽  
Andrea Guarracino ◽  
...  
Keyword(s):  
Transposable Element ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Initiation Factor ◽  
Sequence Variant ◽  
The Novel ◽  
Sequencing Data ◽  
Genome Wide ◽  
Respiratory Cells ◽  
Nuclear Ribonucleoprotein

AbstractThe novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

Basal chloride currents in murine airway epithelial cells: modulation by CFTR

1998 ◽  
Vol 274 (4) ◽  
pp. C904-C913 ◽  
Author(s):  
R. Tarran ◽  
M. A. Gray ◽  
M. J. Evans ◽  
W. H. Colledge ◽  
R. Ratcliff ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Wild Type ◽  
Patch Clamp Technique ◽  
Chloride Currents ◽  
Cation Permeability ◽  
Current Voltage ◽  
Respiratory Cells

We have isolated ciliated respiratory cells from the nasal epithelium of wild-type and cystic fibrosis (CF) null mice and used the patch-clamp technique to investigate their basal conductances. Current-clamp experiments on unstimulated cells indicated the presence of K+ and Cl− conductances and, under certain conditions, a small Na+conductance. Voltage-clamp experiments revealed three distinct Cl− conductances. I tv-indep was time and voltage independent with a linear current-voltage ( I- V) plot; I v-actexhibited activation at potentials greater than ±50 mV, giving an S-shaped I- Vplot; and I hyp-act was activated by hyperpolarizing potentials and had an inwardly rectified I- Vplot. The current density sequence was I hyp-act = I v-act ≫ I tv-indep. These conductances had Cl−-to- N-methyl-d-glucamine cation permeability ratios of between 2.8 and 10.3 and were unaffected by tamoxifen, flufenamate, glibenclamide, DIDS, and 5-nitro-2-(3-phenylpropylamino) benzoic acid but were inhibited by Zn2+ and Gd3+. I tv-indep and I v-act were present in wild-type and CF cells at equal density and frequency. However, I hyp-actwas detected in only 3% of CF cells compared with 26% of wild-type cells, suggesting that this conductance may be modulated by cystic fibrosis transmembrane conductance regulator (CFTR).

scholarly journals The surface epithelium of teleostean fish gills. Cellular and junctional adaptations of the chloride cell in relation to salt adaptation.

1979 ◽  
Vol 80 (1) ◽  
pp. 96-117 ◽  
Author(s):  
C Sardet ◽  
M Pisam ◽  
J Maetz
Keyword(s):  
Salt Water ◽  
Freeze Fracture ◽  
Morphological Characteristics ◽  
Chloride Cell ◽  
Chloride Cells ◽  
Surface Epithelium ◽  
Salt Adaptation ◽  
Resistance Pathway ◽  
Shallow Junctions ◽  
Respiratory Cells

Various species of teleostean fishes were adapted to fresh or salt water and their gill surface epithelium was examined using several techniques of electron microscopy. In both fresh and salt water the branchial epithelium is mostly covered by flat respiratory cells. They are characterized by unusual outer membrane fracture faces containing intramembranous particles and pits in various stages of ordered aggregation. Freeze fracture studies showed that the tight junctions between respiratory cells are made of several interconnecting strands, probably representing high resistance junctions. The organization of intramembranous elements and the morphological characteristics of the junctions do not vary in relation to the external salinity. Towards the base of the secondary gill lamellae, the layer of respiratory cells is interrupted by mitochondria-rich cells ("chloride cells"), also linked to respiratory cells by multistranded junctions. There is a fundamental reorganization of the chloride cells associated with salt water adaptation. In salt water young adjacent chloride cells send interdigitations into preexisting chloride cells. The apex of the seawater chloride cell is therefore part of a mosaic of sister cells linked to surrounding respiratory cells by multistranded junctions. The chloride cells are linked to each other by shallow junctions made of only one strand and permeable to lanthanum. It is therefore suggested that salt water adaptation triggers a cellular reorganization of the epithelium in such a way that leaky junctions (a low resistance pathway) appear at the apex of the chloride cells. Chloride cells are characterized by an extensive tubular reticulum which is an extension of the basolateral plasma membrane. It is made of repeating units and is the site of numerous ion pumps. The presence of shallow junctions in sea water-adapted fish makes it possible for the reticulum to contact the external milieu. In contrast in the freshwater-adapted fish the chloride cell's tubular reticulum is separated by deep apical junctions from the external environment. Based on these observations we discuss how solutes could transfer across the epithelium.

scholarly journals Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation

2021 ◽  
Vol 118 (47) ◽  
pp. e2109905118
Author(s):  
Liping Zhang ◽  
Matthew Mann ◽  
Zulfeqhar A. Syed ◽  
Hayley M. Reynolds ◽  
E. Tian ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Protein S ◽  
Viral Infectivity ◽  
The Novel ◽  
Furin Cleavage ◽  
Global Pandemic ◽  
Furin Cleavage Site ◽  
Respiratory Cells ◽  
Syncytia Formation

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells. Here, we show that O-glycosylation near the furin cleavage site is mediated by members of the GALNT enzyme family, resulting in decreased furin cleavage and decreased syncytia formation. Moreover, we show that O-glycosylation is dependent on the novel proline at position 681 (P681). Mutations of P681 seen in the highly transmissible alpha and delta variants abrogate O-glycosylation, increase furin cleavage, and increase syncytia formation. Finally, we show that GALNT family members capable of glycosylating S are expressed in human respiratory cells that are targets for SARS-CoV-2 infection. Our results suggest that host O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the role of the P681 mutations found in the highly transmissible alpha and delta variants.

scholarly journals ICAM-1 induction in respiratory cells exposed to a replication-deficient recombinant adenovirus in vitro and in vivo

Gene Therapy ◽  
1998 ◽  
Vol 5 (1) ◽  
pp. 131-136 ◽  
Author(s):  
E Nicolis ◽  
A Tamanini ◽  
P Melotti ◽  
R Rolfini ◽  
G Berton ◽  
...  
Keyword(s):  
Recombinant Adenovirus ◽  
Respiratory Cells

Ion exchanges through respiratory and chloride cells in freshwater- and seawater-adapted teleosteans

1980 ◽  
Vol 238 (3) ◽  
pp. R260-R268 ◽  
Author(s):  
J. P. Girard ◽  
P. Payan
Keyword(s):  
Chloride Cells ◽  
Acid Base Balance ◽  
Acid Base ◽  
Seawater Adaptation ◽  
Exchange Diffusion ◽  
Adrenergic Control ◽  
Base Balance ◽  
Respiratory Cells ◽  
Functional Advantage ◽  
External Salinity

The present study discusses the respective roles of the chloride and respiratory cells in branchial ion exchange in freshwater- and seawater-adapted teleosts. In the gill, two distinct epithelia are defined according to their blood irrigation and cellular characteristics: the primary lamellar epithelium containing mostly chloride cells is functionally connected to the venous compartment; the secondary lamellar epithelium consisting of respiratory cells is irrigated by the arterioarterial circulation. The fundamental reorganization occurring in the chloride cells during adaptation to seawater consists of the appearance of leaky ultrastructure related to an increase in the ionic and nonelectrolyte permeabilities of the primary lamellar epithelium. The physiological functions of respiration, excretion, and the maintenance of acid-base balance occur through the secondary lamellar epithelium both in freshwater and seawater fish. The increase of the exchange diffusion across the secondary lamellar epithelium on seawater adaptation is directly related to the increase in the external salinity. The study of adrenergic control in the teleost gill emphasizes the functional advantage to the fish during adaptation to seawater of the anatomic separation of the osmoregulatory primary lamellar epithelium.

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