Publications by authors named "M J Wakelam"

Article Synopsis
  • Scientists from 34 labs in 19 countries worked together to measure certain fats (ceramides) in human blood using special techniques.
  • They used both standard methods and their own methods to get very accurate and consistent results.
  • The study helps improve future medical tests and treatments by providing reliable information about these fats in blood samples.
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Phospholipase D (PLD) hydrolyses phosphatidylcholine (PtdCho) to produce free choline and the critically important lipid signaling molecule phosphatidic acid (PtdOH). Since the initial discovery of PLD activities in plants and bacteria, PLDs have been identified in a diverse range of organisms spanning the taxa. While widespread interest in these proteins grew following the discovery of mammalian isoforms, research into the PLDs of non-mammalian organisms has revealed a fascinating array of functions ranging from roles in microbial pathogenesis, to the stress responses of plants and the developmental patterning of flies.

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Rationale: The present work shows comprehensive chromatographic methods and MS conditions that have been developed based on the chemical properties of each lipid subclass to detect low-abundance molecular species. This study shows that the developed methods can detect low- and/or very-low-abundant lipids like phosphatidic acid (PA) in the glycerophospholipid (GP) method; dihydroceramide (dhCer) and dihydrosphingosine/sphinganine (dhSPB) in the sphingolipid (SP) method; and lysophosphatidic acid (LPA), LPI, LPG and sphingosine-1-phosphate (SPBP) in the lysolipid method.

Methods: An optimised method for the extraction of lysolipids in plasma is used in addition to Folch extraction.

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Article Synopsis
  • Peroxisome biogenesis disorders caused by gene mutations can lead to severe symptoms, including hearing impairment and early childhood death.
  • A study on mice with these mutations showed normal hearing development at first, but they later experienced increasing hearing loss linked to issues in synapses beneath inner ear hair cells.
  • The research indicated that local expression of certain genes in the cochlea is crucial for normal hearing and identified a reduction in plasmalogens in the inner ear, mirroring findings in humans with similar disorders.
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The identification of effective pharmacological tools for Alzheimer's disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming.

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