Publications by authors named "J Alvin"

Article Synopsis
  • Pathological mutations in the Trk-fused gene (TFG) are linked to neurodegenerative diseases, particularly hereditary spastic paraplegia (HSP), causing lower limb issues.* -
  • Researchers used X-ray crystallography and cryo-electron microscopy to reveal how TFG forms octameric ring complexes, crucial for its function.* -
  • Mutations from HSP patients disrupt the stability of these complexes, leading to neurodegenerative effects, but different mutations have varying impacts, indicating multiple mechanisms of disease progression.*
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Article Synopsis
  • Inherited motor neuron diseases (MND) like hereditary spastic paraplegias (HSP) involve the death or dysfunction of nerve cells that control muscle activity, but genetic variants may also affect other supportive cells.
  • Researchers used a rat model with a specific TFG mutation that mimics human HSP symptoms, such as motor deficits and spasticity, to investigate the source of axonopathy in the corticospinal tract.
  • Results showed that introducing the normal TFG gene into specific neurons significantly improved motor function, while targeting supportive glial cells did not yield similar benefits, highlighting the importance of neuron-focused therapies for TFG-related HSP.
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Molecular pathways that intrinsically regulate neuronal maintenance are poorly understood, but rare pathogenic mutations that underlie neurodegenerative disease can offer important insights into the mechanisms that facilitate lifelong neuronal function. Here, we leverage a rat model to demonstrate directly that the TFG p.R106C variant implicated previously in complicated forms of hereditary spastic paraplegia (HSP) underlies progressive spastic paraparesis with accompanying ventriculomegaly and thinning of the corpus callosum, consistent with disease phenotypes identified in adolescent patients.

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Background: The "Assay for Transposase Accessible Chromatin sequencing" (ATAC-seq) is an efficient and easy to implement protocol to measure chromatin accessibility that has been widely used in multiple applications studying gene regulation. While several modifications or variants of the protocol have been published since it was first described, there has not yet been an extensive evaluation of the effects of specific protocol choices head-to-head in a consistent experimental setting. In this study, we tested multiple protocol options for major ATAC-seq components (including three reaction buffers, two reaction temperatures, two enzyme sources, and the use of either native or fixed nuclei) in a well-characterized cell line.

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Transition metals are necessary cofactors and structural elements in living systems. Exposure to high concentrations of biologically important transition metals, such as zinc and copper, results in cell toxicity. At the infection site, the immune system deploys metal sorbent proteins (e.

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