Publications by authors named "Alex W Joyce"

Article Synopsis
  • Schizophrenia involves significant brain function changes, with insulin signaling pathways, especially AKT, playing a key role in its development.
  • This study found increased mRNA levels of AKT1-3 in neurons from schizophrenia patients, while total AKT protein levels remained unchanged or lower, indicating a potential disconnect between gene expression and protein presence.
  • The research also revealed sex-specific differences in AKT activity, additional changes in related signaling components, and heightened expression of the glucose metabolism regulator FOXO1, suggesting potential compensatory mechanisms in response to insulin signaling issues.
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Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia.

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Due to their oftentimes ambiguous nature, phosphopeptide positional isomers can present challenges in bottom-up mass spectrometry-based workflows as search engine scores alone are often not enough to confidently distinguish them. Additional scoring algorithms can remedy this by providing confidence metrics in addition to these search results, reducing ambiguity. Here we describe challenges to interpreting phosphoproteomics data and review several different approaches to determine sites of phosphorylation for both data-dependent and data-independent acquisition-based workflows.

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Biological regulatory networks are dynamic, intertwined, and complex systems making them challenging to study. While quantitative measurements of transcripts and proteins are key to investigate the state of a biological system, they do not inform the "active" state of regulatory networks. In consideration of that fact, "functional" proteomics assessments are needed to decipher active regulatory processes.

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