Biology subjects

McCormack, A.

Publications and source records attributed to McCormack, A..

3 recordsLinked to original sources

bioRxiv2026

Biomineralization from platelet δ-granules as the origin of cardiovascular calcification in humans and other animals.

Cardiovascular calcification is present in practically all cardiac diseases, which are the top killers in the world today1, and is particularly associated with atherosclerosis2, aortic stenosis3 and rheumatic fever4. If not the direct cause of death, calcification contributes considerably to complications that can lead to heart failure5. Nonetheless, the origins and mechanisms of cardiovascular calcification are still strongly debated3,6-12. Just over a decade ago, it has been reported that nano and micron-sized calcified spherical particles, formed from a single crystal of magnesium-containing calcium phosphate, were the first calcified structure that could be detected in cardiovascular tissue13. These particles were found even before any sign of cardiac disease was present and were present in all stages of cardiac diseases13. The ubiquity of these particles suggests their importance for the origins and development of cardiovascular calcific diseases. Here, we show that these particles originate from platelet {delta}-granules and are present in mammals, birds and lizards. Based on our results, we suggest a new mechanism for the origins of these particles, complementing existing models of cardiovascular calcification7,14, and bringing a new, early, and hitherto unaccounted key event in the process of cardiovascular calcification. This new mechanism model, along with a better understanding of the early stages of cardiovascular calcification, could open the path for the development of pharmacological prevention and treatment solutions for several cardiac diseases.

pathology↗

bioRxiv2023

Plasmacytoid dendritic cells (pDCs) display surface but not membrane-bound IgE across a broad range of total serum IgE levels

IntroductionPlasmacytoid dendritic cells (pDCs) are unique antigen presenting cells that may be implicated in allergic disease because they bind IgE on their surface and modulate important Th1/Th2 cytokine responses. While conducting in vitro experiments using excess omalizumab to capture IgE, we discovered that this immunoglobulin is not readily removed from pDC to the same extent observed for basophils suggesting that a portion of the IgE on pDC is membrane bound. MethodsBasophils and pDC were prepared from leukopacks using established protocols. In order to isolate PBMCs, blood was also drawn from consenting donors with a wide range in total serum IgE levels. B cells and pDCs were identified by flow cytometry by gating on CD19/CD27 and BDCA2/CD123, respectively. Quilizumab, a mouse anti-human monoclonal IgG1 antibody with specificity only for membrane-bound IgE, was used to detect this molecule in both cell types. ResultsWhen used in vitro at 1.5 mg/ml, omalizumab removed [~]80-90% of the IgE expressed by basophils. In contrast, IgE expression decreased only 30-40% on pDC treated likewise. Upon analyzing pDC for membrane-bound IgE, there was no significant difference in number of target-bound cells and mean fluorescence between the mouse isotype control and quilizumab among pDCs (P = 0.125, 0.165). However, the ratio of the proportion of target-bound CD19+27+ B cells compared to other cells was 32:1 for isotype (P < 0.001) and 54:1 for quilizumab (P = 0.015). ConclusionOverall, this study demonstrates that while pDCs express significant levels of Fc{varepsilon}RI that binds IgE to the surface, there is no appreciable amount of membrane-bound IgE noted. The reason for omalizumabs poor ability to remove IgE from pDCs remains unknown.

immunology↗

bioRxiv2020

A novel fluorescence and DNA combination for complex, long-term marking of mosquitoes

BackgroundCurrent mark release recapture methodologies are limited in their ability to address complex problems in vector biology, such as studying multiple groups overlapping in space and time. Additionally, limited mark retention, reduced post-marking survival, and the large effort in marking, collection and recapture, all complicate effective insect tracking. MethodWe have developed and evaluated a marking method using a fluorescent dye (Smartwater(R)) combined with synthetic DNA tags to informatively and efficiently mark adult mosquitoes using an airbrush pump and nebulizer. Using handheld UV flashlights, the fluorescent marking enabled quick and simple initial detection of recaptures in a simple, field-ready, and non-destructive approach that when combined with a simple, extraction-free PCR on individual mosquito legs provides potentially unlimited marking information. ResultsThis marking, first tested in the laboratory with Anopheles gambiae s.l. mosquitoes, did not affect survival (median ages 24-28 days, p-adj > 0.25), oviposition (median eggs/female of 28.8, 32.5, 33.3 for water, green, red dyes, respectively, p-adj > 0.44), or Plasmodium competence (mean oocysts 5.56 to 10.6, p-adj > 0.95). DNA and fluorescence had 100% retention up to 3 weeks (longest time point tested) with high intensity, indicating marks would persist longer. ConclusionsWe describe a novel, simple, no/low-impact, and long-lasting marking method that allows separation of multiple insect subpopulations by combining unlimited length and sequence variation in the synthetic DNA tags. This method can be readily deployed in the field for marking multiple groups of mosquitoes or other insects.

ecology↗