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Biology subjects

Wing, E.

Publications and source records attributed to Wing, E..

3 recordsLinked to original sources

A comprehensive analysis of rheumatoid arthritis B cells reveals the importance of CD11c+ve double-negative-2 B cells as the major synovial plasma cell precursor.

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of targeted therapies. Here, we combine flow cytometry of circulating B cells with single-cell RNA and paired repertoire sequencing of over 27,000 synovial B cells from patients with established RA. Twelve B cell clusters were identified including previously recognised subsets, and a novel cluster that strongly expressed heat shock proteins. All lineages identified by trajectory analysis contribute to the DN2 B cell population, which is the major precursor to synovial ASCs. This was further supported by B cell receptor (BCR) lineage analysis, which revealed clonal relationships between DN2 cells and ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium.

immunology↗

Visual and semantic representations predict subsequent memory in perceptual and conceptual memory tests

It is generally assumed that the encoding of a single event generates multiple memory representations, which contribute differently to subsequent episodic memory. We used fMRI and representational similarity analysis (RSA) to examine how visual and semantic representations predicted subsequent memory for single item encoding (e.g., seeing an orange). Three levels of visual representations corresponding to early, middle, and late visual processing stages were based on a deep neural network. Three levels of semantic representations were based on normative Observed ("is round"), Taxonomic ("is a fruit"), and Encyclopedic features ("is sweet"). We identified brain regions where each representation type predicted later Perceptual Memory, Conceptual Memory, or both (General Memory). Participants encoded objects during fMRI, and then completed both a word-based conceptual and picture-based perceptual memory test. Visual representations predicted subsequent Perceptual Memory in visual cortices, but also facilitated Conceptual and General Memory in more anterior regions. Semantic representations, in turn, predicted Perceptual Memory in visual cortex, Conceptual Memory in the perirhinal and inferior prefrontal cortex, and General Memory in the angular gyrus. These results suggest that the contribution of visual and semantic representations to subsequent memory effects depends on a complex interaction between representation, test type, and storage location.

neuroscience↗

Excitatory TMS Boosts Memory Representations

Brain stimulation technologies have seen increasing application in basic science investigations, specifically towards the goal of improving memory functioning. However, proposals concerning the neural mechanisms underlying cognitive enhancement often rely on simplified notions of excitation and, most applications examining the effects of transcranial magnetic stimulation (TMS) on functional neuroimaging measures have been limited to univariate analyses of brain activity. We present here analyses using representational similarity analysis (RSA) and encoding-retrieval similarity (ERS) analysis in order to quantify the effect of TMS on memory representations. To test whether an increase in local excitability in PFC can have measurable influences on upstream representations in earlier temporal memory regions, we compared 1Hz and 5Hz stimulation to the left dorsolateral PFC. We found that 10 minutes of 5Hz rTMS, relative to 1Hz, had multiple effects on neural representations: 1) greater RSA during both encoding and retrieval, 2) greater ERS across all items, and, critically, 3) increasing ERS in MTL with increasing univariate activity in DLPFC, and greater functional connectivity for hits than misses between these regions. These results provide the first evidence of rTMS enhancing semantic representations and strengthen the idea that rTMS may affect the reinstatement of previously experienced events in upstream regions.

neuroscience↗