Biology subjects

Young, M. R.

Publications and source records attributed to Young, M. R..

4 recordsLinked to original sources

bioRxiv2023

cGAS-activating lupus autoantibody for cancer immunotherapy

Cytoplasmic DNA triggers a cGAS-mediated signaling cascade that promotes an innate immune response and is potentially actionable in cancer immunotherapy. Here we show that a cytoplasmic-localizing lupus anti-DNA autoantibody activates cGAS and facilitates an immune-mediated prolongation of survival in orthotopic models of glioblastoma (GBM). Mechanistically, cellular penetration and blood-brain barrier crossing by the anti-DNA autoantibody is linked to nucleoside transport. Pulldown, knockdown, signaling, and cytotoxicity assays demonstrate autoantibody association with and activation of cGAS. In orthotopic GBM models, the autoantibody localizes to brain tumor, increases tumor CD8+ T cell content, and prolongs survival in immunocompetent but not immunodeficient mice. This work introduces the new concept of a cGAS-activating anti-DNA autoantibody, which impacts theories on mechanisms of autoimmunity and has translational applications in cancer immunotherapy.

immunology↗

bioRxiv2020

Caffeine Increases the Reinforcing Efficacy of Alcohol, an Effect that is Independent of Dopamine D2 Receptor Function

The rising popularity of alcohol mixed with energy drinks (AmEDs) has become a significant public health concern, with AmED users reporting higher levels of alcohol intake than non-AmED users. One mechanism proposed to explain heightened levels of alcohol intake in AmED users is that the high levels of caffeine found in energy drinks may increase the reinforcing properties of alcohol, an effect which may be dependent on interactions between adenosine signaling pathways and the dopamine D2 receptor. Therefore, the purpose of the current study was to confirm whether caffeine increases the reinforcing efficacy of alcohol using both fixed ratio (FR) and progressive ratio (PR) designs, and to investigate a potential role of the dopamine D2 receptor in caffeines reinforcement-enhancing effects. Male Long Evans rats were trained to self-administer a sweetened alcohol or sucrose solution on an FR2 schedule of reinforcement. Pretreatment with caffeine (5-10 mg/kg) significantly increased operant responding for the sweetened alcohol reinforcer, but not sucrose. PR tests of motivation for alcohol or sucrose likewise confirmed a caffeine-dependent increase in motivation for a sweetened alcohol solution, but not sucrose. However, the D2 receptor antagonist eticlopride did not block the reinforcementenhancing effects of caffeine using either an FR or PR schedule of reinforcement. Taken together, these results support the hypothesis that caffeine increases the reinforcing efficacy of alcohol, which may explain caffeine-induced increases in alcohol intake. However, the reinforcement-enhancing effects of caffeine appear to be independent of D2 receptor function.

animal behavior and cognition↗

bioRxiv2019

A reference library for the identification of Canadian invertebrates: 1.5 million DNA barcodes, voucher specimens, and genomic samples

The reliable taxonomic identification of organisms through DNA sequence data requires a well parameterized library of curated reference sequences. However, it is estimated that just 15% of described animal species are represented in public sequence repositories. To begin to address this deficiency, we provide DNA barcodes for 1,500,003 animal specimens collected from 23 terrestrial and aquatic ecozones at sites across Canada, a nation that comprises 7% of the planets land surface. In total, 14 phyla, 43 classes, 163 orders, 1123 families, 6186 genera, and 64,264 Barcode Index Numbers (BINs; a proxy for species) are represented. Species-level taxonomy was available for 38% of the specimens, but higher proportions were assigned to a genus (69.5%) and a family (99.9%). Voucher specimens and DNA extracts are archived at the Centre for Biodiversity Genomics where they are available for further research. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, and the Global Genome Biodiversity Network Data Portal.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC=\"FIGDIR/small/701805v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (17K):\norg.highwire.dtl.DTLVardef@5c6449org.highwire.dtl.DTLVardef@1bc0224org.highwire.dtl.DTLVardef@309dddorg.highwire.dtl.DTLVardef@1cc2cc8_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2017

Expedited Assessment of Terrestrial Arthropod Diversity by Coupling Malaise Traps with DNA Barcoding

O_LIMonitoring changes in terrestrial arthropod communities over space and time requires a dramatic increase in the speed and accuracy of processing samples that cannot be achieved with morphological approaches.\nC_LIO_LIThe combination of DNA barcoding and Malaise traps allows expedited, comprehensive inventories of species abundance whose cost will rapidly decline as high-throughput sequencing technologies advance.\nC_LIO_LIAside from detailing protocols from specimen sorting to data release, this paper describes their use in a survey of arthropod diversity in a national park that examined 20,000 specimens representing 2200 species.\nC_LIO_LIThese protocols can support arthropod monitoring programs at regional, national, and continental scales.\nC_LI

ecology↗