Reza, F. | Search bioRxiv

bioRxiv2022

An in situ quantitative map of initial human colorectal HIV transmission

The initial immune response to HIV is critical in determining transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. We combined RNAscope, cyclic-immunofluorescence and novel image analysis tools to quantify HIV transmission dynamics in intact human colorectal tissue. We mapped HIV enrichment to mucosal dendritic cells (DC) and submucosal macrophages, but not CD4+ T-cells, the primary targets of downstream infection. DCs appeared to funnel virus to lymphoid aggregates which acted as early sanctuaries of high viral titres whilst facilitating HIV passage to the submucosa. Finally, HIV entry induced rapid recruitment and clustering of target cells, facilitating DC and macrophage mediated HIV transfer and enhanced infection of CD4+ T-cells. These data demonstrate a rapid response to HIV structured to maximise the likelihood of mucosal infection, and provide a framework for in situ studies of host pathogen interactions and immune mediated pathologies. Highlights- in situ quantification of host cellular microenvironment response to pathogen invasion in human colorectal tissue. - HIV first localises to mucosal DCs and submucosal macrophages, but not CD4+ T cells. - Viral enrichment first occurs in lymphoid aggregates which is associated with passage into the submucosa. - Early localisation of HIV to CD4+ T cells is associated with interactions with DCs and macrophages. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/490175v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@ef8000org.highwire.dtl.DTLVardef@1bc8ed7org.highwire.dtl.DTLVardef@45ddbdorg.highwire.dtl.DTLVardef@e0a57c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Harmonized-Multinational qEEG Norms (HarMNqEEG)

This paper extends our frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. i) Create lifespan Hermitian Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control developmental equations for the mean and standard deviation of qEEG traditional and Hermitian Riemannian descriptive parameters were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. ii) We also show that the multinational harmonized Hermitian Riemannian norms produce z-scores with increased diagnostic accuracy to predict brain dysfunction at school-age produced by malnutrition only in the first year of life. We provide data and software for constructing norms. iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings. HighlightsO_LIWe create lifespan Hermitian Riemannian qEEG norms for cross-spectral tensors. C_LIO_LIThe norms are based on 9 countries, 12 devices, and 14 studies, with 1564 subjects. C_LIO_LIWe demonstrate qEEG "batch effects", providing harmonization methods to remove them. C_LIO_LIMultinational harmonized z-scores increase diagnostic accuracy of brain dysfunction. C_LIO_LIData and software are available for norm and individual z-scores calculation. C_LI

neuroscience↗