COVID-19 is a new zoonotic disease caused by the SARS-CoV-2 virus. Since its emergence in Wuhan City, China, the virus has rapidly spread across the globe causing calamitous health, economic and societal consequences. It causes disproportionately severe disease in the elderly and those with co-morbidities, such as hypertension and diabetes. There is currently no proven treatment for COVID-19 and a safe and effective vaccine is at least a year away. The virus gains access to the respiratory epithelium through cell surface angiotensin converting enzyme 2 (ACE2). The receptor binding domain (RBD) of the virus is unlikely to mutate without loss of pathogenicity and thus represents an attractive target for antiviral treatment. Inhaled modified recombinant human ACE2, may bind SARS-CoV-2 and mitigate lung damage. This decoy strategy is unlikely to provoke an adverse immune response and may reduce morbidity and mortality in high-risk groups.
Click to increase image sizeClick to decrease image size Declaration of InterestsThe SARS-CoV-2 T cell assay is not under consideration by LabPLUS, Auckland Hospital. The NZACE2-Pātari project has not received funding for human studies at this time and is undergoing in vitro testing against variants of concern. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed and would be pleased to share their protocols gratis.Editor disclosuresThe editor that approved this manuscript for publication has no relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper is not funded.
Economically important milk production traits including milk volume, milk fat and protein yield vary considerably across dairy goats in New Zealand. A significant portion of the variation is attributable to genetic variation. Discovery of genetic markers linked to milk production traits can be utilised to drive selection of high-performance animals. A previously reported genome wide association study across dairy goats in New Zealand identified a quantitative trait locus (QTL) located on chromosome 19. The most significantly associated single nucleotide polymorphism (SNP) marker for this locus is located at position 26,610,610 (SNP marker rs268292132). This locus is associated with multiple milk production traits including fat, protein and volume. The predicted effect of selection for the beneficial haplotype would result in an average production increase of 2.2 kg fat, 1.9 kg protein and 73.6 kg milk yield. An outstanding question was whether selection for the beneficial allele would co-select for any negative pleiotropic effects. An adverse relationship between milk production and udder health traits has been reported at this locus. Therefore, a genome wide association study was undertaken looking for loci associated with udder traits.The QTL and production associated marker rs268292132 was identified in this study to also be associated with several goat udder traits including udder depth (UD), fore udder attachment (FUA) and rear udder attachment (RUA). Our study replicates the negative relationship between production and udder traits with the high production allele at position 19:26,610,610 (SNP marker rs268292132) associated with an adverse change in UD, FUA and RUA.Our study has confirmed the negative relationship between udder traits and production traits in the NZ goat population. We have found that the frequency of the high production allele is relatively high in the NZ goat population, indicating that its effect on udder conformation is not significantly detrimental on animal health. It will however be important to monitor udder conformation as the chromosome 19 locus is progressively implemented for marker assisted selection. It will also be of interest to determine if the gene underlying the production QTL has a direct effect on mammary gland morphology or whether the changes observed are a consequence of the increased milk volume.
Summary The differentiation of myeloid cells into macrophages and granulocytes is accompanied by marked changes in adhesive phenotype. Here we seek to understand the regulation of expression and functionality of the VLA‐4 (α4βl). LPAM‐I (α4β7) and HML‐I (αEβ7) integrins on monocytes/macrophages and granulocytes, given that these integrins including LFA‐I (αLβ2) mediate the entry, retention and signalling events of pathogenic leucocytes within chronically inflamed tissues. Phorbol ester‐induced monocytic differentiation of the promyelocyte cell line HL60 led to increases in the steady‐state levels of β2 and β7 mRNA transcripts, requiring a period of 10 and 24 h. respectively, of de novo protein synthesis. There was a parallel de now expression of LPAM‐1 on the cell surface, despite the fact that a4 mRNA transcripts were rapidly down regulated. At 72 h. HML‐1 was not coexpressed with LPAM‐1 on HL60 cells, although it was weakly expressed on peripheral blood monocytes/macrophages after a prolonged period of in vitro culture. Retinoic acidinduced granulocytic differentiation of HL60 cells led to the appearance of low levels of LPAM‐1 at the cell surface. LPAM‐1 was not found expressed on peripheral blood neutrophils, raising the possibility that it is transiently expressed during granulocyte differentiation. In accord with the above findings, differentiated monocytes and HL60 cells bound to recombinant MAdCAM‐1 in an α4‐ and β7‐integrin‐dependent fashion, whereas a population of undifferentiated HL60 cells and Mn ++ ‐activated monocytes bound in an α4‐integrindependent β7‐integrin‐independent manner via VLA‐4 expressed abundantly at all stages of differentiation. Four h after attachment, some of these VLA‐4 + LPAM‐1 ‐ HL60 cells could be seen to start spreading. These findings suggest that MAdCAM‐l can bind to VLA‐4 when LPAM‐1 is absent, and thus has the potential to recruit both VLA‐4‐bearing monocytes and VLA‐4 + LPAM‐1 + macrophages into chronically inflamed tissues.
Milkfat composition influences the nutritional value and manufacturing characteristics of milk. This research studied the influence of: 1) stage of lactation on the concentration of unsaturated fatty acids (UFA) in milkfat of Holstein-Friesian, Jersey and Crossbred cows, 2) segregation of cows according to their UFA concentration in milkfat. The concentration of UFA in milkfat was predicted with a calibration equation using Fourier transform infrared spectroscopy. The data (21,757 test-day records) were analysed using a mixed model with a third-order orthogonal polynomial. In the three breeds studied, after early lactation the concentration of UFA in milkfat decreased steadily as the lactation progressed, but in Holstein-Friesian cows it increased slightly at the end of lactation. Throughout lactation, Holstein-Friesian cows produced milkfat with a higher concentration of UFA than Jersey and Crossbred cows. In each herd, cows were split into a high and a low group according to the average UFA concentration of the herd. The high UFA group had higher (P <0.001) milk yield, but lower (P <0.001) yields and concentrations of fat and protein than the low UFA group. This study indicates that concentration of UFA in milkfat is affected by breed and stage of lactation in New Zealand dairy cattle.
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