Publications by authors named "M F O'Donohue"
The identification of pathways that control elimination of protein inclusions is essential to understand the cellular response to proteotoxicity, particularly in the nuclear compartment, for which our knowledge is limited. We report that stress-induced nuclear inclusions related to the nucleolus are eliminated upon stress alleviation during the recovery period. This process is independent of autophagy/lysosome and CRM1-mediated nuclear export pathways, but strictly depends on the ubiquitin-activating E1 enzyme, UBA1, and on nuclear proteasomes that are recruited into the formed inclusions.
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- - Diamond-Blackfan anemia syndrome (DBA) is caused by mutations in over 20 ribosomal protein genes, and this study specifically investigates the role of RPL17, which encodes a large ribosomal subunit protein.
- - Patients with RPL17 mutations exhibited typical DBA symptoms and erythroid proliferation defects, with further experiments showing that these mutations are pathogenic and lead to anemia in model organisms.
- - The research found that RPL17 variants result in defects in ribosomal RNA maturation and suggest that DBA primarily stems from insufficient ribosome production rather than changes in ribosome structure, as indicated by altered translation profiles in cell lines.
The endogenous cannabinoid (ECB) system is a small molecule lipid signalling system that is involved in stress response activation and is associated with PTSD, but it is unclear whether salivary ECBs are part of the sympathetic nervous system response to stress. We conducted an adapted trauma film paradigm, where participants completed a cold pressor test (or control) while watching a 10-minute trauma film. We also collected saliva and hair samples and tested them for ECBs, cortisol, and salivary alpha amylase (sAA).
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- - Diamond-Blackfan anemia (DBA) is the first ribosomopathy identified in humans, characterized by a specific type of anemia caused by issues in red blood cell development and ribosomal protein deficiencies affecting 24 different genes.
- - Around 50% of DBA cases also present with various physical malformations, and the condition is linked to malfunctioning ribosomal RNA maturation, which contributes to ineffective blood cell production.
- - The complexity of DBA symptoms arises from multiple mechanisms, including defects in gene translation, chaperone deficits, free heme toxicity, and p53 activation, leading to a wide range of clinical presentations even among family members.
Transferrin, a central player in iron transport, has been recognized not only for its role in binding iron but also for its interaction with other metals, including titanium. This study employs solid-state nanopores to investigate the binding of titanium ions [Ti(IV)] to transferrin in a single-molecule and label-free manner. We demonstrate the novel application of solid-state nanopores for single-molecule discrimination between apo-transferrin (metal-free) and Ti(IV)-transferrin.
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