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Biology subjects

McLaughlin, D.

Publications and source records attributed to McLaughlin, D..

3 recordsLinked to original sources

Domesticated pennycress is a self-pollinated crop

CoverCress is a new winter annual oilseed crop developed from field pennycress within the past 20 years. Field pennycress is commonly considered to be self-pollinated but little basic research has been published and there is some misalignment of conclusions. Our experience working with pennycress plant growth in greenhouse and field conditions over the past 13 years suggests that outcrossing is uncommon. We conducted lab, greenhouse, and field experiments to strengthen the body of work. Pollen viability kinetics analysis showed that longevity of pollen viability is negatively impacted by increasing temperatures and by direct exposure to light. Samples treated at 4C declined to 50% viability in 12 hours while it took just 2.5 hrs at 37C, and 1.6 hrs in full sunlight on a cool early April day. Cross-pollination was absent among greenhouse-grown plants flowering inside an agitated plastic pollen-containment covering. Across greenhouse tests, high rates of cross-pollination occurred only in an emasculation treatment that rendered flowers male sterile and opened the pistil to cross-fertilization. Field trials designed to measure pollen flow distance using a trackable fae1 knockout reporter gene failed to show detectable movement of pollen under field conditions in two locations. This data strongly suggests that domesticated field pennycress may be considered a self-pollinated crop and managed as such.

plant biology↗

Mitofusin agonists enhances long-term engraftment and potency of cultured hematopoietic stem cells

Umbilical cord blood (CBU) is a valuable source of hematopoietic stem cells (HSCs) due to lower incidence of graft-versus-host disease. However, limited HSC counts restrict use in adults, necessitating improved methods for ex vivo expansion and improved HSC function. Mitofusin 2 (MFN2), a mitochondrial membrane fusion protein, is necessary for preserving HSC function and mitofusin agonists have been characterized. We report ex vivo culture of CBU HSCs with mitofusin agonists (MAs) enhances long-term repopulating activity by over five-fold in both primary and secondary transplantation assays without changes of total nucleated cells or phenotypic HSCs. Mechanistically, MA-treated HSCs show suppressed protein synthesis, increased autophagic flux, and elevated lysosomal mass. Transcriptomic analysis implicates downregulation of MTOR signaling, and immunoprecipitation studies suggest MFN2 interacts with MTOR. These data support a model in which fusion-competent MFN2 sequesters MTOR, promoting a catabolic state that preserves HSC potency. Our findings suggest a novel MFN2-MTOR regulatory axis that enhances the function of human HSCs cultured ex vivo for potential therapeutic application.

cell biology↗

Comprehensive Analysis of Regenerative and Transformed Liver Reveals Distinct, Early Metabolic Alterations in Cancer

Alterations in cellular metabolism represent an important response to proliferative signals in both normal and transformed tissues. The benign proliferative process of liver regeneration after partial hepatectomy offers insight into homeostatic mechanisms to control liver mass, which are disrupted in liver disease induced by viral factors, alcohol, or associated with obesity. Moreover, successful targeting of cancer depends on the identification of genes and pathways that are selectively activated in the transformed state. Here, we present a differential transcriptomic and metabolomic analysis of benign proliferative and transformed liver, including associated plasma metabolite and lipid species. Using partial hepatectomy-induced liver regeneration and diethylnitrosamine (DEN) induced carcinogenesis, we identify and analyze alterations specific to multiple regenerative and transformed tissue states. Transcriptomics and LC/MS based metabolite profiling reveal fatty acid import and storage are specifically rewired during liver regeneration in a time dependent manner, a phenomenon not observed in liver tumors. In contrast, liver tumors exhibit preferential activation of numerous metabolic pathways, including glycolysis, serine biosynthesis, and polyamine metabolism. Alterations in serine metabolism occur at the earliest detectable stages in tumorigenesis and promote survival upon serine restriction. These data demonstrate that transformation-induced alterations in metabolism are distinct from those observed in normal regenerative cell division, which may be used to identify transformation-specific liabilities.

cancer biology↗