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Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

ABSTRACT: Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

PROVIDER: PRJNA1100974 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28706200_1.fastq.gz	Fastqsanger.gz
	SRR28706200_2.fastq.gz	Fastqsanger.gz
	SRR28706201_1.fastq.gz	Fastqsanger.gz
	SRR28706201_2.fastq.gz	Fastqsanger.gz
	SRR28706202_1.fastq.gz	Fastqsanger.gz

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Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

Project description:Current Multiple Sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail due to insufficient understanding of its underlying mechanisms. This study analyzes a clinically well-characterized MS autopsy cohort comparing selected individuals with opposite disease trajectories of slow versus rapid progression by extensive unbiased histology and spatial transcriptomics. It unveils a novel lesion type marked by an extensive myeloid cell rim with cellular and transcriptional signatures of inflammation, enhanced antigen presentation and lymphocyte activation that is strongly linked to rapid progression. Validation through an independent TSPO-PET study confirms the association between lesions with a broad myeloid cell rim and disease progression. These findings offer crucial insights into the mechanisms behind MS progression, identifying broad rim lesions as a biomarker for rapid disease progression and potentially guiding patient selection for future therapeutic trials targeting CNS intrinsic inflammation.

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Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis (part 2)

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Project description:Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis (part 2)

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Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis

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Project description:During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports microbial adaptation to alkaline pH. This cascading series of interacting proteins terminates in the proteolytic activation of the highly conserved Rim101/PacC protein, a transcription factor that mediates microbial responses that favor survival in neutral/alkaline pH growth conditions, including many mammalian tissues. We identified the putative Rim pathway proteins Rim101 and Rra1 in the human skin colonizing fungus Malassezia sympodialis. Targeted mutation of these proteins confirmed their role in M. sympodialis growth at higher pH. Additionally, comparative transcriptional analysis of the mutant strains compared to wild-type suggested mechanisms for fungal adaptation to alkaline conditions. These signaling proteins are required for optimal growth in a murine model of atopic dermatitis, a pathological condition associated with increased skin pH. Together these data elucidate both conserved and phylum-specific features of microbial adaptation to extracellular stresses.

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