24 research outputs found
Highly sensitive quantitative PCR for the detection and differentiation of Pseudogymnoascus destructans and other Pseudogymnoascus species
White-nose syndrome is a fungal disease that has decimated bat populations across eastern North America. Identification of the etiologic agent, Pseudogymnoascus destructans (formerly Geomyces destructans), in environmental samples is essential to proposed management plans. A major challenge is the presence of closely related species, which are ubiquitous in many soils and cave sediments and often present in high abundance. We present a dual-probe real-time quantitative PCR assay capable of detecting and differentiating P. destructans from closely related fungi in environmental samples from North America. The assay, based on a single nucleotide polymorphism (SNP) specific to P. destructans, is capable of rapid low-level detection from various sampling media, including sediment, fecal samples, wing biopsy specimens, and skin swabs. This method is a highly sensitive, high-throughput method for identifying P. destructans, other Pseudogymnoascus spp., and Geomyces spp. in the environment, providing a fundamental component of research and risk assessment for addressing this disease, as well as other ecological and mycological work on related fungi
Using Mendelian randomisation to identify opportunities for type 2 diabetes prevention by repurposing medications used for lipid management
Background: Maintaining a healthy lifestyle to reduce type 2 diabetes (T2D) risk is challenging and additional strategies for T2D prevention are needed. We evaluated several lipid control medications as potential therapeutic options for T2D prevention using tissue-specific predicted gene expression summary statistics in a two-sample Mendelian randomisation (MR) design. Methods: Large-scale European genome-wide summary statistics for lipids and T2D were leveraged in our multi-stage analysis to estimate changes in either lipid levels or T2D risk driven by tissue-specific predicted gene expression. We incorporated tissue-specific predicted gene expression summary statistics to proxy therapeutic effects of three lipid control medications [i.e., statins, icosapent ethyl (IPE), and proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK-9i)] on T2D susceptibility using two-sample Mendelian randomisation (MR). Findings: IPE, as proxied via increased FADS1 expression, was predicted to lower triglycerides and was associated with a 53% reduced risk of T2D. Statins and PCSK-9i, as proxied by reduced HMGCR and PCSK9 expression, respectively, were predicted to lower LDL-C levels but were not associated with T2D susceptibility. Interpretation: Triglyceride lowering via IPE may reduce the risk of developing T2D in populations of European ancestry. However, experimental validation using animal models is needed to substantiate our results and to motivate randomized control trials (RCTs) for IPE as putative treatment for T2D prevention. Funding: Only summary statistics were used in this analysis. Funding information is detailed under Acknowledgments. © 2022Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Whole Genome Sequence analysis of apparent Treatment Resistant Hypertension Status in Participants From the Trans-Omics For Precision Medicine Program
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Development of novel YSTR assays for applicationi to genealogical research (lineage reconstruction)
P296: Leveraging electronic health records (EHR) to identify patients with rare disease: An atypical case of aromatic L-amino acid decarboxylase deficiency
Does fungicide run-off from citrus delay leaf litter decomposition?
Leaf litter is a major inoculum source for citrus diseases such citrus black spot caused by Phyllosticta citricarpa, and greasy spot caused by Mycosphaerella citri. In order to reduce this inoculum source, the efficacy of urea, dolomitic lime, a commercial compost accelerator, and an organic mulch, was assessed for enhanced leaf decomposition and reduction in sporocarps. However, due to the potential for run-off from high volume fungicide applications to disrupt leaf decomposition and microbial antagonism, the amendments were compared with and without simulated fungicide run-off. Mature green leaves of Citrus sinensis were removed from trees and placed inside mesh bags before being pinned to the orchard floor. The amendments were applied, and then simulated run-off from a typical citrus black spot fungicide program (copper, mancozeb, azoxystrobin) was applied. Leaf degradation was assessed every 2-3 weeks by visual ratings and dry weight. No direct effects on sporocarps could be observed due to insufficient infection. The results showed that the organic mulch was the most effective at enhancing decomposition, while there was significantly (P < 0.05) less decomposition in the presence of fungicide run-off
Identification of resistance to citrus black spot using a novel in-field inoculation assay
Citrus black spot is an important fungal disease of citrus resulting in fruit drop and rind blemish in tropical and subtropical production areas. The disease is incited by the fungus Phyllosticta citricarpa (McAlpine) van der Aa (synonym: Guignardia citricarpa Kiely), with control currently relying on the application of fungicides. Because the presence and expression of resistance is poorly understood, we sought to develop a method for inoculating fruit in the field that gives reproducible symptoms of citrus black spot consistent with natural field infection. We subsequently validated this method by screening 49 citrus accessions and characterized their qualitative expression of citrus black spot symptoms. Challenge inoculations were undertaken with a known isolate of P. citricarpa, and control fruit were inoculated with water or the endophyte P. paracapitalensis Guarnaccia & Crous. Our results showed that all mandarin, sweet orange, lemon and papeda types were susceptible; pummelo, lime, and sour orange types expressed immunity; while various hybrids were susceptible, resistant and immune. Hybrid progeny from crosses using pummelo [Citrus maxima (Burm.) Merr.] as a parent showed preliminary evidence of segregation for citrus black spot immunity. The implications of these results to achieve genetic improvement for citrus black spot resistance in citrus breeding programs are discussed
Uncovering the Origins of Autophagosomes: How Cells Recycle Waste
Autophagy is molecular machinery for “self-digestion” in cells. It is a highly conserved process for cell survival in response to stressors such as starvation, growth factor deprivation, and pathogen infection. Autophagy is a unique membrane trafficking process whereby double-layered membranes are formed to engulf parts of the cytoplasm for degradation. The origin of the autophagosome membrane and how its formation is initiated remain open questions after more than 50 years of investigation, and it is still not well understood how the membranes grow and expand to form the autophagosome. A number of lipids have been identified in the autophagosome membrane, including phosphoinositides and phosphatidylethanolamines. However, the complete lipid composition of autophagosome precursors and of completed autophagosomes is not known. This knowledge gap hinders the in-depth understanding of the role of lipids in autophagy. The objective of the proposed project is to elucidate lipid composition of autophagosomes. In this project, HeLa-Difluo™ hLC3 cells, a commercially available autophagy reporter cell line, were cultured to 80% confluency and treated with rapamycin to stimulate autophagy. Autophagosome membranes were isolated via immunoprecipitation using an anti-GFP antibody immunocomplex bound to magnetic beads. Lipid components from the isolated membrane were extracted and analyzed by MALDI. The results of this project contribute to the complete elucidation of lipid composition of the autophagosome membrane and the role of lipids in autophagy
Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition
International audienceObjectives: This study postulated that antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibition may mitigate vascular endothelial growth factor inhibitor (VEGFi)-mediated increases in blood pressure more effectively than other antihypertensive medications in patients receiving VEGFi therapy.Background: VEGFi therapy is commonly used in the treatment of cancer. One common side effect of VEGFi therapy is elevated blood pressure. Evidence suggests that the RAAS may be involved in VEGFi-mediated increases in blood pressure.Methods: This retrospective cohort analysis was performed using a de-identified version of the electronic health record at Vanderbilt University Medical Center in Nashville, Tennessee. Subjects with cancer who were exposed to VEGFi therapy were identified, and blood pressure and medication data were extracted. Changes in mean systolic and diastolic blood pressure in response to VEGFi therapy in patients receiving RAAS inhibitor (RAASi) therapy before VEGFi initiation were compared with changes in mean systolic and diastolic blood pressure in patients not receiving RAASi therapy before VEGFi initiation.Results: Mean systolic and diastolic blood pressure rose in both groups after VEGFi use; however, patients who had RAASi therapy before VEGFi initiation had a significantly lower increase in systolic blood pressure as compared with patients with no RAASi therapy (2.46 mm Hg [95% confidence interval: 0.7 to 4.2] compared with 4.56 mm Hg [95% confidence interval: 3.5 to 5.6], respectively; p = 0.034).Conclusions: In a real-world clinical population, RAASi therapy before VEGFi initiation may ameliorate VEGFi-mediated increases in blood pressure. Randomized clinical trials are needed to further our understanding of the role of RAASi therapy in VEGFi-mediated increases in blood pressure. (J Am Coll Cardiol CardioOnc 2019;1:14-23)