Biology subjects

Williams, L.

Publications and source records attributed to Williams, L..

28 records · Page 2Linked to original sources

bioRxiv2022

The City Nature Challenge - A global citizen science phenomenon contributing to biodiversity knowledge and informing local government practices

The bioblitz phenomenon has recently branched into cities, presenting exciting opportunities for local governments to channel participants efforts toward local issues. The City Nature Challenge (CNC) is one such initiative that has been quickly uptaken by hundreds of municipalities worldwide. Despite high participation, we still lack a framework for evaluating how the CNC contributes to local biodiversity knowledge and to inform local government practices. Here, we develop such a tool and present a case study that illustrates its applicability. We demonstrate that the collected records contributed to a better understanding of contemporary, local biodiversity patterns and provided a more realistic representation of understudied groups such as insects and fungi. Importantly, we show that the CNC presented local governments with a cost-effective tool to make informed, evidence-based management and policy decisions, improve education and engagement programs, foster cross-council collaborations, and support a stronger sense of environmental stewardship within the local community.

scientific communication and education↗

bioRxiv2022

Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by PCM1. To study the requirement for centriolar satellites, we generated mice lacking PCM1. Pcm1-/- mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia and cerebellar hypoplasia, as well as variable expressivity of other ciliopathy features including cystic kidneys. Pcm1-/- multiciliated ependymal cells and PCM1-/- retinal pigmented epithelial 1 (RPE1) cells showed reduced ciliogenesis. PCM1-/- RPE1 cells displayed reduced docking of the mother centriole to the ciliary vesicle and removal of CP110 and CEP97 from the distal mother centriole, indicating compromized early ciliogenesis. We show these molecular cascades are maintained in vivo, and we suggest that the cellular threshold to trigger ciliogenesis varies between cell types. We propose that PCM1 and centriolar satellites facilitate efficient trafficking of proteins to and from centrioles, inducing the departure of CP110 and CEP97 to initiate ciliogenesis.

cell biology↗

bioRxiv2021

SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens

The baseline composition of T cells directly impacts later response to a pathogen, but the complexity of precursor states remains poorly defined. Here we examined the baseline state of SARS-CoV-2 specific T cells in unexposed individuals. SARS-CoV-2 specific CD4+ T cells were identified in pre-pandemic blood samples by class II peptide-MHC tetramer staining and enrichment. Our data revealed a substantial number of SARS-CoV-2 specific T cells that expressed memory phenotype markers, including memory cells with gut homing receptors. T cell clones generated from tetramer-labeled cells cross-reacted with bacterial peptides and responded to stool lysates in a MHC-dependent manner. Integrated phenotypic analyses revealed additional precursor diversity that included T cells with distinct polarized states and trafficking potential to other barrier tissues. Our findings illustrate a complex pre-existing memory pool poised for immunologic challenges and implicate non-infectious stimuli from commensal colonization as a factor that shapes pre-existing immunity. One Sentence SummaryPre-existing immunity to SARS-CoV-2 contains a complex pool of precursor lymphocytes that include differentiated cells with broad tissue tropism and the potential to cross-react with commensal antigens.

immunology↗

bioRxiv2021

Design considerations of a wearable electronic-skin for mental health and wellness: balancing biosignals and human factors

Chronic stress has been associated with a variety of pathophysiological risks including developing mental illness. Conversely, appropriate stress management, can be used to foster mental wellness proactively. Yet, there is no existing method that accurately and objectively monitors stress. With recent advances in electronic-skin (e-skin) and wearable technologies, it is possible to design devices that continuously measure physiological parameters linked to chronic stress and other mental health and wellness conditions. However, the design approach should be different from conventional wearables due to considerations like signal-to-noise ratio and the risk of stigmatization. Here, we present a multi-part study that combines user-centered design with engineering-centered data collection to inform future design efforts. To assess human factors, we conducted an n=24 participant design probe study that examined perceptions of an e-skin for mental health and wellness as well as preferred wear locations. We complement this with an n=10 and n=16 participant data collection study to measure physiological signals at several potential wear locations. By balancing human factors and biosignals, we conclude that the upper arm and forearm are optimal wear locations.

bioengineering↗

bioRxiv2020

The SEQC2 Epigenomics Quality Control (EpiQC) Study: Comprehensive Characterization of Epigenetic Methods, Reproducibility, and Quantification

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and a global resource for epigenetics research from the FDAs Epigenomics Quality Control (EpiQC) Group. The study design leverages seven human cell lines that are designated as reference materials and publicly available from the National Institute of Standards and Technology (NIST) and Genome in a Bottle (GIAB) consortium. These samples were subject to a variety of genome-wide methylation interrogation approaches across six independent laboratories, with a primary focus was on 5-methylcytosine modifications. Each sample was processed in two or more technical replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), one enzymatic deamination method (EMseq), targeted methylation sequencing (Illumina Methyl Capture EPIC), and single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, BWAMeth, and GemBS), we found overall high concordance between assays (R=0.87-R0.93), differences in efficency of read mapping and CpG capture and coverage, and platform performance. The data provided herein can guide continued used of these reference materials in epigenomics assays, as well as provide best practices for epigenomics research and experimental design in future studies.

genomics↗

bioRxiv2020

The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation

Evidence strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain. SARS-CoV-2 enters cells via the S1 subunit of its spike protein, and S1 can be used as a proxy for the uptake patterns and mechanisms used by the whole virus; unlike studies based on productive infection, viral proteins can be used to precisely determine pharmacokinetics and biodistribution. Here, we found that radioiodinated S1 (I-S1) readily crossed the murine blood-brain barrier (BBB). I-S1 from two commercial sources crossed the BBB with unidirectional influx constants of 0.287 {+/-} 0.024 L/g-min and 0.294 {+/-} 0.032 L/g-min and was also taken up by lung, spleen, kidney, and liver. I-S1 was uniformly taken up by all regions of the brain and inflammation induced by lipopolysaccharide reduced uptake in the hippocampus and olfactory bulb. I-S1 crossed the BBB completely to enter the parenchymal brain space, with smaller amounts retained by brain endothelial cells and the luminal surface. Studies on the mechanisms of transport indicated that I-S1 crosses the BBB by the mechanism of adsorptive transcytosis and that the murine ACE2 receptor is involved in brain and lung uptake, but not that by kidney, liver, or spleen. I-S1 entered brain after intranasal administration at about 1/10th the amount found after intravenous administration and about 0.66% of the intranasal dose entered blood. ApoE isoform or sex did not affect whole brain uptake, but had variable effects on olfactory bulb, liver, spleen, and kidney uptakes. In summary, I-S1 readily crosses the murine BBB, entering all brain regions and the peripheral tissues studied, likely by the mechanism of adsorptive transcytosis. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗

bioRxiv2019

EM-seq: Detection of DNA Methylation at Single Base Resolution from Picograms of DNA

Bisulfite sequencing is widely used to detect 5mC and 5hmC at single base resolution. However, bisulfite treatment damages DNA resulting in fragmentation, loss of DNA and biased sequencing data. To overcome this, we developed Enzymatic Methyl-seq (EM-seq), an enzymatic based approach that uses as little as 100 pg of DNA. EM-seq outperformed bisulfite converted libraries in all metrics examined including coverage, duplication, sensitivity and nucleotide composition. EM-seq libraries displayed even GC distribution, improved correlation across input amounts as well as increased representation of genomic features. These data indicate that EM-seq is more accurate and reliable than whole genome bisulfite sequencing (WGBS).

genomics↗

bioRxiv2019

Neural correlates of the DMT experience as assessed via multivariate EEG

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience, and particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the relevant subjective experience and thus further our understanding of the neurobiological underpinnings of immersive states of consciousness.

neuroscience↗

bioRxiv2019

A universal scaling method for biodiversity-ecosystem functioning relationships

Global biodiversity is declining at rates faster than at any other point in human history. Experimental manipulations of biodiversity at small spatial scales have demonstrated that communities with fewer species consistently produce less biomass than higher diversity communities. However, understanding how the global extinction crisis is likely to impact global ecosystem functioning will require applying these local and largely experimental findings to natural systems at substantially larger spatial and temporal scales. Here we propose that we can use two simple macroecological patterns - the species area curve and the biomass-area curve - to upscale the species richness-biomass relationship. We demonstrate that at local spatial scales, each additional species will contribute more to biomass production with increasing area sampled because the species-area curve saturates and the biomass-area curve increases monotonically. We use species-area and biomass-area curves from a Minnesota grassland and a Panamanian tropical dry forest to examine the species richness - biomass relationship at three and ten sampling extents, respectively. In both datasets, the observed relationship between biodiversity and biomass production at every sampling extent was predicted from simple species-area and biomass-area relationships. These findings suggest that macroecological patterns like the species-area curve underpin the scaling of biodiversity-ecosystem functioning research and can be used to predict these relationships at the global scales where they are relevant for species loss.

ecology↗

bioRxiv2018

Reproductive longevity predicts mutation rates in primates

Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations1. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a by-product of their increased lifespan2,3. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from 6 multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 x 10-8 per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.

evolutionary biology↗