Publications by authors named "Maneka A Perinpanayagam"

Background: Exercise prehabilitation is an evidence-based, safe, and effective method to increase quality of life, physical fitness and function, and post-surgical outcomes in solid organ transplant (SOT) patients. However, few prehabilitation programs for SOT patients exist in practice. Furthermore, there is a lack of multimodal prehabilitation programs that include behavior change support.

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The efficacy of the B cell-targeting drug rituximab (RTX) in childhood idiopathic nephrotic syndrome (INS) suggests that B cells may be implicated in disease pathogenesis. However, B cell characterization in children with INS remains limited. Here, using single-cell RNA sequencing, we demonstrate that a B cell transcriptional program poised for effector functions represents the major immune perturbation in blood samples from children with active INS.

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  • A study investigated the differences in corticosteroid dosage and duration of treatment for childhood nephrotic syndrome across 11 pediatric nephrology sites in Canada, highlighting the variability in treatment practices.
  • Data from 328 children revealed that the treatment dosage decreased as patients aged, and children of African and Indigenous background experienced longer treatment durations compared to White patients.
  • The findings suggest that the location of treatment contributes significantly to variations in corticosteroid prescription practices among pediatric nephrologists.
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  • Myristoylation is a modification of proteins that is important for cell signaling and targeting to membranes, and elevated levels of N-myristoyltransferase (NMT) in cancer cells make it a potential target for therapy.
  • Researchers found that the pan-NMT inhibitor PCLX-001 significantly affects hematological cancers, particularly B-cell lymphomas, by disrupting myristoylation and inhibiting survival signaling pathways.
  • PCLX-001 not only degrades Src family kinases but also leads to the degradation of other key cancer-promoting proteins, resulting in cancer cell death, and suggests it may serve as a new treatment option for lymphoma patients facing relapse.
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Background: To assess reasons for continuing practice variation in the management of childhood nephrotic syndrome despite expert reviews and guidelines, we are conducting a longitudinal cohort study in children with glucocorticoid sensitive nephrotic syndrome. Objectives of this mid-study report are to describe patient and physician recruitment characteristics, glucocorticoid prescriptions, use of second line agents, biopsy practices, and adherence to study protocol.

Methods: Children with new onset nephrotic syndrome and providers are being recruited from all 12 pediatric nephrology centres across Canada with > 2½ years follow-up.

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Background: GDC-0980 is a selective small molecule inhibitor of class I PI3K and mTOR pathway with a potent anti-proliferative activity.

Objective: We set out to evaluate the efficacy of GDC-0980, in pre-clinical studies, against pediatric leukemia cells.

Methods: The anti-neoplastic activity of GDC-0980 was evaluated in vitro using five different pediatric leukemia cells.

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  • * Researchers found that N-myristoyltransferases (NMTs) 1 and 2 are cleaved by caspases during apoptosis, impacting their localization and functionality, but their activity remains largely unaffected early on in the process.
  • * The interaction between caspases and NMTs could influence protein modifications during apoptosis, and diminished caspase activity in cancer cells may correlate with increased NMT levels, highlighting potential therapeutic targets in cancer treatment.
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  • * Researchers developed a plasmid reporter system (pTRAMPP) to find proteins that are myristoylated after translation, identifying seven such proteins, including known examples and new candidates linked to cell death and disease.
  • * A specific protein, ctPKCε, was found to be myristoylated post-translationally, leading to its membrane localization and enhanced signaling pathways that promote cell survival during apoptosis, suggesting an anti-apoptotic function.
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  • - The study introduces a new synthetic compound, omega-alkynyl-palmitate, which can be directly incorporated into specific proteins like GAPDH and certain Ras proteins, allowing for easier detection using click chemistry techniques.
  • - Researchers found that omega-alkynyl-palmitate preferentially labels certain Ras proteins (H- and N-Ras) over others (like K-Ras), revealing differing interactions with fatty acylation.
  • - Additionally, omega-alkynyl-myristate is successfully incorporated into myristoylated proteins, and the study demonstrates that these labeling methods can be applied in living cells and mice, promising advancements in the study of protein acylation.
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