bioRxiv Science⌕ Search

Biology subjects

Williamson, L.

Publications and source records attributed to Williamson, L..

9 recordsLinked to original sources

Design and Test Novel EEG Electrode Attachments for Type 4 Afro-textured Hairstyles

Black participants remain underrepresented in electroencephalography (EEG) research, partly because current EEG devices work poorly with dense, coily Type 4 Afro-textured hair. Research-grade EEG typically wires electrodes on a cap, and therefore the electrodes often fail to reach the scalp through dense, Afro-textured hair. Protocols that ask Black participants to unbraid or restyle protective hairstyles add burdens that discourage enrollment in research studies. To address this, we designed and tested 3D-printed attachments that fit onto an EEG electrode and anchored it directly in the hair, using the hairstyle itself as the mounting structure. We fabricated three design configurations for natural Afro-textured hair, cornrows/braids, and twists/microlocs. Seventeen healthy adults with Type 4a-4c hair used electrode attachments that matched their hairstyle. During a single visit, EEG was recorded with 16 conventional cap electrodes defined by the international 10-20 system and with 16 electrodes using novel electrode attachments anchored directly to their hair. Participants completed resting and walking trials with each system. Electrode-to-scalp distance and gel volume were measured during setup. Electrode disconnection, impedance, signal quality (i.e. peak alpha power and aperiodic (1/f) component), and comfort level were measured throughout the data collection. Compared with the conventional cap, the novel attachments reduced electrode-to-scalp distance, gel use, and impedance. Twenty percent of the conventional cap electrodes failed to connect to the scalp compared with 0.1% of novel electrodes. Impedance rose across trials for the conventional cap, whereas the novel attachments showed a smaller increase and maintained lower impedance throughout. Signal quality was significantly better using the novel attachments, while comfort level did not differ between systems. In conclusion, hair-anchored electrode attachment may present a feasible alternative to conventional cap-based EEG for people with Type 4 hair, yielding more usable channels and better signal quality, and supporting more inclusive EEG acquisition.

neuroscience↗

Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope

Optical clearing combined with light-sheet microscopy enables high-resolution imaging of extended tissue at scale. However, standard mesoSPIM systems are optimised for intact organs and are not suited to thin tissue slices. We present a no-shear imaging protocol using obliquely mounted samples held between refractive-index-matched slides in a 3D-printed frame. This enables mechanical de-skewing during acquisition, minimising post-processing requirements. We demonstrate feasibility in fluorescent bead phantoms and rabbit heart tissue, achieving a 4.8x reduction in processing time and a 1.5x improvement in axial resolution compared to the shear-method. The no-shear method extends mesoSPIMs utility to fragile, laterally extended tissue sections.

biophysics↗

Protein Coronas on Functionalized Nanoparticles Enable Quantitative and Precise Large-Scale Deep Plasma Proteomics

BackgroundThe wide dynamic range of circulating proteins coupled with the diversity of proteoforms present in plasma has historically impeded comprehensive and quantitative characterization of the plasma proteome at scale. Automated nanoparticle (NP) protein corona-based proteomics workflows can efficiently compress the dynamic range of protein abundances into a mass spectrometry (MS)-accessible detection range. This enhances the depth and scalability of quantitative MS-based methods, which can elucidate the molecular mechanisms of biological processes, discover new protein biomarkers, and improve comprehensiveness of MS-based diagnostics. MethodsInvestigating multi-species spike-in experiments and a cohort, we investigated fold-change accuracy, linearity, precision, and statistical power for the using the Proteograph Product Suite, a deep plasma proteomics workflow, in conjunction with multiple MS instruments. ResultsWe show that NP-based workflows enable accurate identification (false discovery rate of 1%) of more than 6,000 proteins from plasma (Orbitrap Astral) and, compared to a gold standard neat plasma workflow that is limited to the detection of hundreds of plasma proteins, facilitate quantification of more proteins with accurate fold-changes, high linearity, and precision. Furthermore, we demonstrate high statistical power for the discovery of biomarkers in small- and large-scale cohorts. ConclusionsThe automated NP workflow enables high-throughput, deep, and quantitative plasma proteomics investigation with sufficient power to discover new biomarker signatures with a peptide level resolution.

biochemistry↗

Flexible estimation of biodiversity with short-range multispectral imaging in a temperate grassland

O_LIImage sensing technologies are rapidly increasing the cost-effectiveness of biodiversity monitoring efforts. Species differences in the reflectance of electromagnetic radiation have recently been highlighted as a promising target to estimate plant biodiversity using multispectral image data. C_LIO_LIHowever, these efforts are currently hampered by logistical difficulties in broad-scale implementation and their use in characterizing biodiversity at different spatial scales. C_LIO_LIHere, we investigate the utility of multispectral imaging technology from commercially available unmanned aerial vehicles (UAVs, or drones) in estimating biodiversity metrics at short-range (<10 m image recording height) in a temperate calcareous grassland ecosystem in Oxfordshire, UK. We calculate a suite of moments (coefficient of variation, standard deviation, skew, kurtosis) for the distribution of radiance from multispectral images at five wavelength bands (Blue 450{+/-}16 nm; Green 560{+/-}16 nm; Red 650{+/-}16 nm; Red Edge 730{+/-}16 nm; Near Infrared 840{+/-}16 nm) and test their effectiveness at estimating ground-truthed biodiversity metrics from in-situ botanical surveys for 37 - 1 m x 1 m quadrats. C_LIO_LIWe find positive associations between the average coefficient of variation in spectral radiance and both the Shannon-Weiner and Simpsons biodiversity indices. Furthermore, we find that the average coefficient of variation in spectral radiance is consistent and highly repeatable, across sampling days and recording heights. Positive associations with biodiversity indices hold irrespective of the image recording height (2-8 m), but we report reductions in estimates of spectral diversity with increases to UAV recording height. UAV imaging reduced sampling time by 16-fold relative to in-situ botanical surveys. C_LIO_LISynthesis - We demonstrate the utility of multispectral radiance moments as an indicator of grassland biodiversity metrics at high spatial resolution using a widely available UAV monitoring system at a coarse spectral resolution. The use of UAV technology with multispectral sensors has far-reaching potential to provide cost-effective and high-resolution monitoring of biodiversity in complex environments. C_LI

ecology↗

Protective transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates

Breast milk secretory IgA antibodies provide a first line of defense against enteric infections. Despite this and an effective vaccine, human rotaviruses (RVs) remain the leading cause of severe infectious diarrhea in children in low- and middle-income countries (LMIC) where vaccine efficacy is lower than that of developed nations. Therapeutic strategies that deliver potently neutralizing antibodies into milk could provide protection against enteric pathogens such as RVs. We developed a murine model of maternal protective-transfer using systemic administration of a dimeric IgA (dIgA) monoclonal antibody. We confirmed that systemically-administered dIgA passively transferred into milk and stomach of suckling pups in a dose-dependent manner. We then demonstrated that systemic administration of an engineered potent RV-neutralizing dIgA (mAb41) in lactating dams protected suckling pups from RV-induced diarrhea. This maternal protective-transfer immunization platform could be an effective strategy to improve infant mortality against enteric infections, particularly in LMIC with high rates of breastfeeding. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/461116v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1af34dcorg.highwire.dtl.DTLVardef@1b78cb2org.highwire.dtl.DTLVardef@1760a62org.highwire.dtl.DTLVardef@a3cea2_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Ploidetect enables pan-cancer analysis of the causes and impacts of chromosomal instability

Cancers routinely exhibit chromosomal instability that results in copy number variants (CNVs), namely changes in the abundance of genomic material. Unfortunately, the detection of these variants in cancer genomes is difficult. We present Ploidetect, a software package that effectively identifies CNVs within whole-genome sequenced tumors. Ploidetect utilizes a coarse-to-fine segmentation approach which yields highly contiguous segments while allowing for focal CNVs to be detected with high sensitivity. We benchmark Ploidetect against popular CNV tools using synthetic data, cell line data, and real-world metastatic tumor data, and find an improvement in sensitivity and accuracy while maintaining low levels of oversegmentation. We show that the improved CNV sensitivity enables Ploidetect to recover recurrent homozygous deletions and genes associated with chromosomal instability in a multi-cancer cohort of 687 patients. Using highly contiguous CNV calls afforded by Ploidetect, we also demonstrate the use of segment N50 as a novel metric for the measurement of chromosomal instability within tumor biopsies. We propose that increasingly accurate determination of CNVs is critical for their productive study in cancer, and our work demonstrates advances made possible by progress in this regard.

cancer biology↗

A Platform for Oncogenomic Reporting and Interpretation

Manual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we created the Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework created to facilitate the interpretation and reporting of somatic variants in cancer. PORI is unique in its integration of reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents one of the first open-source platform alternatives to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 TCGA tumours to the graph knowledge base, revealing that 88.2% have at least one potentially targetable alteration, and making available reports describing select individual samples.

bioinformatics↗

A polyglutamine domain is required for de novo CIZ1 assembly formation at the inactive X chromosome

CIP1-interacting zinc finger protein 1 (CIZ1) forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner. Here we address the requirements for assembly formation, and show that CIZ1 interacts directly with Xist via two independent domains in its N- and C-terminus. Interaction with Xist repeat E, assembly at Xi in cells, and the complexity of self-assemblies formed in vitro, are all modulated by alternatively-spliced exons that include two glutamine-rich prion-like domains (PLD1 and PLD2), both conditionally excluded from the N-terminal domain. Exclusion of PLD1 alone is sufficient to abrogate de novo establishment of new CIZ1 assemblies and Xi territories enriched for H3K27me3 in CIZ1-null fibroblasts. Together the data suggest that PLD1-driven CIZ1 assemblies form at Xi, are nucleated by interaction with Xist and amplified by multivalent interaction with RNA, so implicating a polyglutamine tract in the maintenance of epigenetic state.

cell biology↗

The ash dieback invasion of Europe was founded by two individuals from a native population with huge adaptive potential

Accelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback is one such pathogen, moving across continents and hosts from Asian to European ash. Most European common ash (Fraxinus excelsior) trees are highly susceptible to H. fraxineus although a small minority (~5%) evidently have partial resistance to dieback. We have assembled and annotated a draft of the H. fraxineus genome which approaches chromosome scale. Pathogen genetic diversity across Europe, and in Japan, reveals a tight bottleneck into Europe, though a signal of adaptive diversity remains in key host interaction genes (effectors). We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the 'shadow' of a large source population and subsequent introduction would greatly increase adaptive potential and the pathogen's threat. Thus, EU wide biological security measures remain an important part of the strategy to manage this disease.

genomics↗