ORCID Profile
0000-0002-5654-5662
Current Organisation
INIA
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Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1038/S41467-021-21389-9
Abstract: A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory s les revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/AN14137
Abstract: Conventional shearing of sheep is labour-intensive, expensive and presents significant occupational health and safety risks. The only alternative at present is based on injection of epidermal growth factor, which severs the fibre at the follicle level. This technology cannot be used in pregnant animals and requires application of a net to retain the severed fleece. An alternative is to create a weakened zone within the wool staple, which would be sufficiently strong to retain the fleece on the sheep while a protective covering regrows, but sufficiently weak as to allow painless and automated removal of the fleece. We demonstrate that this approach is possible using mixtures of amino acids lacking lysine and methionine. Initially we demonstrate the relationships between staple strength, a subjective ‘harvestability’ score and a subjective ‘pain’ score, using fleeces from animals treated with varying levels of cortisol to create a wide range of strengths of wool attachment. We assigned a score to the ease with which we could manually break the staples, and also to the animal’s response to breaking the staples still attached to the skin. The relationships between these variables indicated that a staple was considered harvestable and could be removed with minimal skin flinch response at a staple strength of ~10–13 N/kTex. Staples within this range were then produced by intravenous infusion of mixtures of amino acids lacking in lysine and methionine for a 5-day period. The weak point was uniformly created across the entire fleece and when a prototype roller-pin device was applied to the weakened wool, it uniformly broke the fleece of the three sheep tested. The mode of action of the amino acid treatment on wool growth was studied. There was no effect of unbalanced amino acids on the rate of follicle bulb cell ision, the number of active wool follicles, or the length of the keratinisation zone in the wool follicle. Fibre diameter was reduced by ~4 microns by treatment, and intrinsic fibre strength (strength relative to cross-sectional area of the wool fibres), was reduced by ~50%. Results of these trials are encouraging but further work is required to develop a practical, on-farm method of altering systemic amino acid supply and to design an automated, high-throughput system of severing the weakened wool.
Publisher: MDPI AG
Date: 27-10-2016
DOI: 10.3390/V8110277
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1038/S41586-021-03767-X
Abstract: The genetic make-up of an in idual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Peru
No related grants have been discovered for Graciela Isabel García Dorival.