8 research outputs found
Quantitative modelling of amino acid transport and homeostasis in mammalian cells
Homeostasis is one of the fundamental concepts in physiology. Despite remarkable progress in our molecular understanding of amino acid transport, metabolism and signaling, it remains unclear by what mechanisms cytosolic amino acid concentrations are maintained. We propose that amino acid transporters are the primary determinants of intracellular amino acid levels. We show that a cellâs endowment with amino acid transporters can be deconvoluted experimentally and used this data to computationally simulate amino acid translocation across the plasma membrane. Transport simulation generates cytosolic amino acid concentrations that are close to those observed in vitro. Perturbations of the system are replicated in silico and can be applied to systems where only transcriptomic data are available. This work explains amino acid homeostasis at the systems-level, through a combination of secondary active transporters, functionally acting as loaders, harmonizers and controller transporters to generate a stable equilibrium of all amino acid concentrations
Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques
SARS-CoV-2 mainly transmits via respiratory droplets. Here Deng et al. show that SARS-CoV-2 can infect rhesus macaques via ocular conjunctival inoculation
Ageârelated rhesus macaque models of COVIDâ19
BACKGROUND:
Since December 2019, an outbreak of the Corona Virus disease 2019 (COVIDâ19) caused by severe acute respiratory syndrome coronavirus (SARSâCoVâ2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARSâCoVâ2 was a need to explore the possible ageârelated phenomena with nonâhuman primate models.
METHODS:
Three 3â5 years old and two 15 years old rhesus macaques were intratracheally infected with SARSâCoVâ2, and then analyzed by clinical signs, viral replication, chest Xâray, histopathological changes and immune response.
RESULTS:
Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARSâCoVâ2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages.
CONCLUSION:
SARSâCoVâ2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARSâCoVâ2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARSâCoVâ2 infection