Publications by authors named "Sean M Flynn"

Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the possible involvement of other epigenomic features such as G-quadruplex DNA secondary structures (G4s). To bridge this gap, we introduce ViCAR (viewpoint HiCAR), for the direct antibody-based capture of chromatin interactions at folded G4s.

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G-quadruplexes (G4s) are four-stranded DNA secondary structures that occur in the human genome and play key roles in transcription, replication, and genome stability. G4-specific molecular probes are of vital importance to elucidate the structure and function of G4s. The scFv antibody BG4 has been a widely used G4 probe but has various limitations, including relatively poor in vitro expression and the inability to be expressed intracellularly to interrogate G4s in live cells.

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The establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation.

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Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C.

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Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C.

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Article Synopsis
  • Neuroblastoma is the most common solid tumor in children and causes 15% of pediatric cancer deaths, highlighting the need for improved therapies!
  • RXDX-105, a small molecule inhibitor targeting RET and BRAF kinases, significantly reduces neuroblastoma cell growth and enhances cell death!
  • When combined with 13-cis-retinoic acid, RXDX-105 shows even greater effectiveness, indicating its potential as a promising treatment for high-risk and relapsed neuroblastoma in children!
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Background And Objectives: Carnoy's fixation and compression represents a novel technique to enhance lymph node evaluation and accuracy of staging after colorectal cancer resection.

Methods: This study was performed in all adults undergoing colorectal cancer operations by Kaiser Permanente surgeons at two separate facilities. Patients were assigned to either location based upon surgeon and patient availability.

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