Publications by authors named "M H Hastings"
Article Synopsis
- There is a significant need for new treatments targeting diseases caused by premature termination codons (PTCs), which lead to faulty proteins.
- Splice-switching antisense oligonucleotides (ASOs) can help by inducing exon skipping, effectively removing PTCs from mRNA and potentially restoring protein function if the remaining exons are in the correct reading frame.
- The research focuses on the cystic fibrosis transmembrane regulator (CFTR) gene, demonstrating that ASOs can restore CFTR function in airway cells from individuals with PTC-causing mutations, showing the potential for ASO therapies across similar multi-exon genes.
Article Synopsis
- IgA vasculitis (IgAV) is a pediatric disease characterized by skin and systemic symptoms, and researchers conducted comprehensive studies involving genome, transcriptome, and proteome analyses on a large cohort of IgAV patients and controls to better understand the disease mechanisms.* -
- Significant associations were found with specific genetic risk factors, including two novel non-HLA loci linked to IgA receptor functioning, which may contribute to disease development through altered immune responses.* -
- Systems biology approaches helped identify key regulatory networks and master regulators in myeloid cells, along with 21 genetic loci that overlap with IgA nephropathy, suggesting shared pathways in these related conditions.*
The biological clock of the suprachiasmatic nucleus (SCN) orchestrates circadian (approximately daily) rhythms of behaviour and physiology that underpin health. SCN cell-autonomous time-keeping revolves around a transcriptional/translational feedback loop (TTFL) within which PERIOD (PER1,2) and CRYPTOCHROME (CRY1,2) proteins heterodimerise and suppress trans-activation of their encoding genes (Per1,2; Cry1,2). To explore its contribution to SCN time-keeping, we used adeno-associated virus-mediated translational switching to express PER2 (tsPER2) in organotypic SCN slices carrying bioluminescent TTFL circadian reporters.
View Article and Find Full Text PDFInflammation has an essential role in healing. However, over-active inflammation disrupts normal cellular functions and can be life-threatening when not resolved. The NLRP3 inflammasome, a component of the innate immune system, is an intracellular multiprotein complex that senses stress-associated signals, and, for this reason is a promising therapeutic target for treating unresolved, pathogenic inflammation.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric-blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs.
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