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Mahon, C.

Publications and source records attributed to Mahon, C..

3 recordsLinked to original sources

Distinct Virome and Bacteriome Profiles of Term and Preterm Placentas from African, Asian and European Women

While the human placental microbiome has been extensively studied, information regarding the virome remains limited. The association between subclinical placental viral infections and spontaneous preterm birth (PTB) is poorly understood. Hence, we examined fresh placenta samples from women in the UK, Bangladesh, and South Africa to elucidate the virome profiles and association with spontaneous PTB. We employed shotgun metagenomics, real-time PCR, and Gram staining, complemented by bioinformatics, to detect both viruses and bacteria in the decidua and chorionic villous tissues. We did not identify any known pathogenic viruses in 236 placental samples, except for one preterm placenta from the Bangladeshi cohort, where human herpesvirus 6 was detected. The majority of the viruses were bacteriophages present at very low abundance and low frequencies across the three cohorts. Lambdavirus lambda was detected in 14% of UK and 11% of Bangladeshi samples but was absent in South African samples. Papiine betaherpesvirus 3 was identified in 62.5% of South African placentas. Punavirus (29.1%) and Streptococcus phages (16.67%) were also prevalent in South African samples. A variety of bacterial species including Moraxella osloensis, Delftia lacustris, Cutibacterium acnes, Escherichia coli and Staphylococcus epidermidis were detected in samples across the three cohorts in variable frequencies but without any notable tissue immune responses. None of the viruses or bacteria exhibited associations with PTB, except D. lacustris, which was significantly more abundant in preterm compared to term placentas in the Bangladeshi cohort. We conclude that the human placenta harbours a virome predominated by bacteriophages and that subclinical viral infection in spontaneous PTB is rare.

microbiology↗

Cellular heterogeneity in hypertrophic burn scars in response to carbon dioxide laser therapy

Fractional carbon dioxide (AFCO2) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO2 laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO2 laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1, POSTN, SPARC); whereas genes enriched in PR were related to enhanced immune responses (IL-12, MSTN, HLA-DQA). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO2, with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.

cell biology↗

Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier

Antisense oligonucleotides (ASO) are promising therapies for neurological disorders, though they are unable to cross the blood-brain barrier (BBB) and must be delivered directly to the central nervous system (CNS). Here, we use a human transferrin receptor (TfR)-binding molecule to transport ASO across the BBB in mice and non-human primates, termed oligonucleotide transport vehicle (OTV). Systemically delivered OTV drives significant, cumulative, and sustained knockdown of the ASO target across multiple CNS regions and all major cell types. Further, systemic OTV delivery enables more uniform ASO biodistribution and knockdown compared to two other clinically relevant ASO delivery routes: a standard, high affinity TfR antibody, or direct ASO delivery to the CSF. Together, our data support systemically delivered OTV as a potential therapeutic platform for neurological disorders. One-Sentence SummarySystemically dosed OTV delivered via TfR1 targeting shows widespread and cumulative target knockdown in the mouse and NHP CNS.

neuroscience↗