Publications by authors named "K E Lawrence"

729 Publications

CHANGES IN THE LEVELS OF THEILERIA ORIENTALIS IKEDA TYPE INFECTION IN HAEMAPHYSALIS LONGICORNIS NYMPHS OVER A SIX-MONTH PERIOD.

J Parasitol 2021 Sep;107(5):710-716

School of Agriculture and Environment, Massey University, Palmerston North, 4442, New Zealand.

This study aimed to investigate whether the infection intensity of Theileria orientalis Ikeda type organisms within Haemaphysalis longicornis larvae and nymph stages fluctuated over 6 mo after feeding as larvae on infected calves in the field. Naïve larvae, hatched from eggs, were fed on infected calves for 5 days while contained within cotton socks glued over the calves' ears. Larvae were first sampled immediately post-feeding and then sampled every 3 wk for 23 wk in total, after molting to nymphs. All larvae and nymphs were tested for T. orientalis Ikeda organisms using quantitative PCR. The qPCR results showed that the infection intensity of Haemaphysalis longicornis larvae and nymphs was not constant over the sampling period, and after initially dropping after molting to nymphs, it then rose with fasting to a maximum at 17 and 23 wk post-feeding. The significant rise in T. orientalis Ikeda organisms observed at 23 wk postfeeding may explain why more severe clinical cases of bovine theileriosis in New Zealand are seen in the spring when nymphs are the predominant instar questing.
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http://dx.doi.org/10.1645/20-177DOI Listing
September 2021

Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.

Elife 2021 Sep 7;10. Epub 2021 Sep 7.

Harvard University, Cambridge, United States.

Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Here, we measure equilibrium dissociation constants of combinatorially complete mutational libraries for two naturally isolated influenza bnAbs (CR9114, 16 heavy-chain mutations; CR6261, 11 heavy-chain mutations), reconstructing all possible evolutionary intermediates back to the unmutated germline sequences. We find that these two libraries exhibit strikingly different patterns of breadth: while many variants of CR6261 display moderate affinity to diverse antigens, those of CR9114 display appreciable affinity only in specific, nested combinations. By examining the extensive pairwise and higher-order epistasis between mutations, we find key sites with strong synergistic interactions that are highly similar across antigens for CR6261 and different for CR9114. Together, these features of the binding affinity landscapes strongly favor sequential acquisition of affinity to diverse antigens for CR9114, while the acquisition of breadth to more similar antigens for CR6261 is less constrained. These results, if generalizable to other bnAbs, may explain the molecular basis for the widespread observation that sequential exposure favors greater breadth, and such mechanistic insight will be essential for predicting and eliciting broadly protective immune responses.
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http://dx.doi.org/10.7554/eLife.71393DOI Listing
September 2021

Vitamin D levels and mortality with SARS-COV-2 infection: a retrospective two-centre cohort study.

Postgrad Med J 2021 Sep 6. Epub 2021 Sep 6.

Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania.

Background: The role of vitamin D in increased mortality with SARS-COV-2 virus, namely, COVID-19, remains uncertain. We analysed all the patients who were treated as COVID-19-positive with or without a positive swab and were tested for vitamin D levels.

Methods: This was a retrospective, study involving 1226 patients swabbed for SARS-CoV-2 between the 10 February 2020 and 1 May 2020 at two hospitals of East Sussex Healthcare NHS Trust. Patients who were swab-positive for COVID-19 or treated as COVID-19-positive on clinical grounds even though swab results were negative were included in this study. We analysed the association of vitamin D levels and mortality, assessing linear and non-linear associations.

Results: A total of 1226 patients had SARS-CoV-2 RNA swabs in this period with age range from 1 year to 101 years. A cohort of 433 of these patients had swabs and recent vitamin D levels anytime in the previous 3 months. Mortality rates were not found to be associated with vitamin D levels (OR=1.04, 95% CI 0.96 to 1.12).

Conclusion: Our findings suggest similar mortality risk from COVID-19 irrespective of the levels of vitamin D. Larger prospective studies will be needed to confirm these findings.
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http://dx.doi.org/10.1136/postgradmedj-2021-140564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423517PMC
September 2021

Small intestinal levels of the branched short-chain fatty acid isovalerate are elevated during infection with and can promote helminth fecundity.

Infect Immun 2021 Aug 30:IAI0022521. Epub 2021 Aug 30.

Department of Biochemistry and Microbiology, Faculty of Science, University of Victoria, 3800 Finnerty Road, Victoria, BC, V8P 5C2, Canada.

is a helminth which naturally infects mice and is widely used as a laboratory model of chronic small intestinal helminth infection. While it is known that infection with alters the composition of the host's bacterial microbiota, the functional implications of this alteration are unclear. We investigated the impact of infection on short-chain fatty acid (SCFA) levels in the mouse intestine and sera. We found that helminth infection resulted in significantly upregulated levels of the branched SCFA isovaleric acid, exclusively in the proximal small intestine, which is the site of colonization. We next set out to test the hypothesis that elevating local levels of isovaleric acid was a strategy used by to promote its own fitness within the mammalian host. To test this, we supplemented the drinking water of mice with isovalerate during infection and examined whether this affected helminth fecundity or chronicity. We did not find that isovaleric acid supplementation affected helminth chronicity, however, we found that it did promote helminth fecundity, as measured by helminth egg output in the feces of mice. Through antibiotic-treatment of helminth-infected mice, we found that the bacterial microbiota was required in order to support elevated levels of isovaleric acid in the proximal small intestine during helminth infection. Overall, our data reveal that during infection there is a microbiota-dependent localized increase in the production of isovaleric acid in the proximal small intestine and this supports helminth fecundity in the murine host.
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http://dx.doi.org/10.1128/IAI.00225-21DOI Listing
August 2021

Conserved oligomeric Golgi (COG) complex genes functioning in defense are expressed in root cells undergoing a defense response to a pathogenic infection and exhibit regulation my MAPKs.

PLoS One 2021 26;16(8):e0256472. Epub 2021 Aug 26.

Department of Entomology and Plant Pathology, Auburn University, Auburn, AL, United States of America.

The conserved oligomeric Golgi (COG) complex maintains correct Golgi structure and function during retrograde trafficking. Glycine max has 2 paralogs of each COG gene, with one paralog of each gene family having a defense function to the parasitic nematode Heterodera glycines. Experiments presented here show G. max COG paralogs functioning in defense are expressed specifically in the root cells (syncytia) undergoing the defense response. The expressed defense COG gene COG7-2-b is an alternate splice variant, indicating specific COG variants are important to defense. Transcriptomic experiments examining RNA isolated from COG overexpressing and RNAi roots show some COG genes co-regulate the expression of other COG complex genes. Examining signaling events responsible for COG expression, transcriptomic experiments probing MAPK overexpressing roots show their expression influences the relative transcript abundance of COG genes as compared to controls. COG complex paralogs are shown to be found in plants that are agriculturally relevant on a world-wide scale including Manihot esculenta, Zea mays, Oryza sativa, Triticum aestivum, Hordeum vulgare, Sorghum bicolor, Brassica rapa, Elaes guineensis and Saccharum officinalis and in additional crops significant to U.S. agriculture including Beta vulgaris, Solanum tuberosum, Solanum lycopersicum and Gossypium hirsutum. The analyses provide basic information on COG complex biology, including the coregulation of some COG genes and that MAPKs functioning in defense influence their expression. Furthermore, it appears in G. max and likely other crops that some level of neofunctionalization of the duplicated genes is occurring. The analysis has identified important avenues for future research broadly in plants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256472PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389442PMC
August 2021
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