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McDermott, G.

Publications and source records attributed to McDermott, G..

7 recordsLinked to original sources

Genomic variation associated with endosymbiont shuffling and areal growth in the endangered elkhorn coral, Acropora palmata

Biodiversity losses continue to outpace traditional management, underscoring the need to understand adaptive capacity and the potential for interventions to increase fitness under climate change. We undertook a genome-wide association study on 156 Acropora palmata genets to investigate the genomic basis of areal growth, endosymbiont association, and thermal tolerance. Seven peaks on chromosomes 1, 3 and 14 were associated with endosymbiont shuffling and two peaks on chromosome 4 were associated with areal growth. As variants were located in non-coding regions we incorporated additional data from an independent field-transplant experiment to investigate their relationship with patterns of gene expression. Intersection of these datasets implicated melanocortin-like receptor activity and Ran GTPase activating protein 1 in endosymbiont composition and surface area growth, respectively. Results indicate that growth and endosymbiont associations may represent more viable intervention targets than temperature tolerance and highlight the need to better understand the role of non-coding variation in basic biology and development of restoration interventions.

genomics↗

High relatedness in sexually produced restoration cohorts of the endangered elkhorn coral, Acropora palmata

Climate change is driving the decline of coral populations around the world such that many are unlikely to recover without human intervention. Assisted sexual reproduction is one intervention proposed to enhance genetic diversity and support population recovery, yet its genetic outcomes remain poorly quantified. We evaluated genome-wide relatedness and genetic diversity in 168 restoration genets of the endangered Caribbean coral Acropora palmata, including 153 sexually produced offspring derived from multi-parent batch and biparental crosses. We detected high relatedness within multi-parent batch cross cohorts, with many genets comprising only one or a few full-sibling groups, indicating highly unequal parental contributions. Nucleotide diversity was lower in one batch cross cohort relative to founder populations, but the absolute difference was small and runs of homozygosity were relatively short indicating that inbreeding depression is not yet a concern. These patterns suggest that common larval propagation approaches can successfully generate large numbers of new genets but underscore the need to manage inbreeding risk, especially in small breeding stocks such as the Caribbean Acropora spp. Specifically, our results highlight the need for comprehensive genetic management to integrate assisted sexual reproduction into coral restoration, including parentage tracking, broodstock rotation, and relatedness-informed outplanting designs.

genomics↗

Ischemic stroke increases levels of the folate receptor and one-carbon enzymes in male and female brain tissue

Stroke is the second most common cause of death worldwide and predominantly affects individuals over 65 years old. Its prevalence is projected to increase in parallel with the aging global population. Nutrition is a modifiable risk factor for ischemic stroke. Folates, B-vitamins and choline play a central role in one-carbon metabolism (1C), which is a key metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, epigenetics, regulation of cell proliferation, and stress resistance. Our research group has previously shown that deficiencies in 1C lead to worsened stroke outcomes using preclinical models. However, the impact of ischemic stroke on 1C enzymes in affected brain tissue remains unknown. The objective of this study is to investigate whether ischemic stroke contributes to a change in the levels of 1C enzymes after ischemic stroke in male and female patients. Cortical brain tissue sections from ischemic stroke patients and controls were stained for enzymes involved in 1C. All tissue was co-stained with neuronal nuclei (NeuN) and DAPI (4',6-diamidino-2-phenylindole). The colocalization of all three markers was evaluated by two individuals who were blinded to the experimental groups. Ischemic stroke increased neuronal levels of the folate receptor and 1C enzymes, methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and serine hydroxy methyltransferase (SHMT). In male stroke brain tissue was observed to have increased levels of MTHFR, TS, and SHMT. Female brain tissue had increases in the folate receptor and TS. The results suggest that ischemic stroke leads to increased demand of 1C and that there are some differences between males and females. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/673861v1_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@18e7c60org.highwire.dtl.DTLVardef@187a339org.highwire.dtl.DTLVardef@1ed0568org.highwire.dtl.DTLVardef@1fdfe31_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

An ESCRT-dependent pathway of Nuclear and Cytoplasmic Spatial PQC is coordinated at Nuclear Vacuolar Junctions

Effective Protein Quality Control (PQC), essential for cellular health, relies on spatial sequestration of misfolded proteins into defined inclusions. Here we elucidate the coordination of nuclear and cytoplasmic spatial PQC. While cytoplasmic misfolded proteins concentrate in a cytoplasmic, perinuclear Juxta Nuclear Quality control compartment (JUNQ), nuclear misfolded proteins sequester into a perinucleolar IntraNuclear Quality control compartment (INQ). Particle tracking reveals the INQ and JUNQ converge to face each other across the nuclear envelope at a site proximal to the Nuclear-Vacuolar Junction (NVJ) marked by perinuclear ESCRT-II/-III protein Chm7. Strikingly, this ESCRT-dependent convergence facilitates VPS4-dependent vacuolar clearance of misfolded cytoplasmic and nuclear proteins, the latter entailing extrusion of nuclear INQ into the vacuole. We propose perinuclear ESCRT coordinates spatial PQC at nuclear-vacuolar contacts to facilitate vacuolar clearance of nuclear and cytoplasmic misfolded proteins.

biochemistry↗

Integrated systems biology and imaging of the smallest free-living eukaryote Ostreococcus tauri

Ostreococcus tauri is an ancient phototrophic microalgae that possesses favorable genetic and cellular characteristics for reductionist studies probing biosystem design and dynamics. Here multimodal bioimaging and multi-omics techniques were combined to interrogate O. tauri cellular changes in response to variations in bioavailable nitrogen and carbon ratios. Confocal microscopy, stimulated Raman scattering, and cryo-soft x-ray tomography revealed whole cell ultrastructural dynamics and composition while proteomic and lipidomic profiling captured changes at the molecular and macromolecular scale.\n\nDespite several energy dense long-chain triacylglycerol lipids showing more than 40-fold higher abundance under N deprivation, only a few proteins directly associated with lipid biogenesis showed significant expression changes. However, the entire pathway for starch granule biosynthesis was highly upregulated suggesting much of the cellular energy is preferentially directed towards starch over lipid accumulation. Additionally, three of the five most downregulated and five of the ten most upregulated proteins during severe nitrogen depletion were unnamed protein products that warrant additional biochemical analysis and functional annotation to control carbon transformation dynamics in this smallest eukaryote.

systems biology↗

PSF correction in soft x-ray tomography

In this manuscript, we introduce a linear approximation of the forward model of soft x-ray tomography (SXT), such that the reconstruction is solvable by standard iterative schemes. This linear model takes into account the three-dimensional point spread function (PSF) of the optical system, which consequently enhances the reconstruction data. The feasibility of the model is demonstrated on both simulated and experimental data, based on theoretically estimated and experimentally measured PSFs.

cell biology↗

Ostreococcus tauri is a high-lipid content green algae that extrudes clustered lipid droplets

Lipid droplet biogenesis, accumulation and secretion is an important field of research spanning biofuel feedstock production in algae and yeast to plant-microbe symbiosis or human metabolic disorders and other diseases. Here we evaluate the critical elements that influence lipid accumulation in the highly simplified and smallest known eukaryote Ostreococcus tauri and identify several conditions that satisfy its classification as an oleaginous green alga. In addition, these experiments revealed the release of excess lipids in pea-pod like structures where many dense lipid droplets are clustered in a linear fashion surrounded by an enveloping membrane which contrasts with known mechanisms from other eukaryotes. These results highlight the potential for Ostreococcus tauri to probe the evolution of lipid droplet dynamics as an emerging model organism with a compacted eukaryotic genome and also to impact lipid feedstock bioproduction applications either directly or using synthetic biology.\n\nOne Sentence SummaryThe smallest known eukaryote Ostreococcus tauri is oleaginous and sheds lipid droplets as pea-pod like membrane enclosed clusters.

cell biology↗