Biology subjects

Richards, E.

Publications and source records attributed to Richards, E..

12 recordsLinked to original sources

bioRxiv2026

Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model

Aquaporin 4 (AQP4) water channels are polarized to astrocytic endfeet at blood vessel interfaces, and lose polarity in vascular diseases, including stroke, chronic traumatic encephalopathy, and Alzheimers disease. AQP4 modulates water influx and efflux in the interstitial fluid, yet how AQP4 localization impacts cerebral amyloid angiopathy (CAA) remains poorly understood. Here we show that astrocytic end feet and AQP4 are displaced from amyloid-bearing vessels in a prion-CAA mouse model that expresses GPI-anchorless PrPC. Displacing AQP4 genetically through deleting alpha-syntrophin (Snta1-/-) led to a marked prolongation in survival, together with reduced microglial inflammation and C1q, in prion-CAA-affected mice. Additionally, synaptic structural proteins were better maintained. Finally, the level and distribution of prion aggregates were similar among the mice, indicating that prion conversion and spread was not affected. These results suggest that reducing AQP4 water channel function slows the decline in a vascular amyloid disease by reducing neuroinflammation.

neuroscience↗

bioRxiv2025

PrPC-induced signaling in human neurons activates phospholipase Cγ1 and an Arc/Arg3.1 response

Synaptic dysfunction and loss correlate with cognitive decline in neurodegenerative diseases, including Alzheimers disease (AD) and prion disease. Neuronal hyperexcitability occurs in the early stages of AD and experimental prion disease, prior to the onset of dementia, yet the underlying drivers are unclear. Here we identify an increase in the immediate early gene, Arc/Arg3.1, in the human prion disease-affected frontal cortex, suggestive of neuronal hyperactivity. To investigate early signaling events initiated by prion aggregates (PrPSc) in human neurons, we stimulated PrPC in human iPSC-derived excitatory neurons (iNs) with a known PrPSc-mimetic antibody (POM1), which recapitulated the Arc/Arg3.1 response within two hours. Proteomics, RNAseq, and a phosphokinase array in iNs revealed alterations in the EGF receptor and increased phosphorylated phospholipase C (PLC)-{gamma}1 (Y783), which was also observed in the cerebral cortex of prion-infected mice. Thus, PrPC ligands can induce a PLC-{gamma}1 intracellular signaling cascade together with an Arc response, suggestive of a neuronal activity response.

neuroscience↗

bioRxiv2021

Diversity begets diversity through shared adaptive genetic variation: discovery of a cryptic wide-mouthed scale-eater

Adaptive radiations involve astounding bursts of phenotypic, ecological, and species diversity. However, the microevolutionary processes that underlie the origins of these bursts are still poorly understood. We report the discovery of an intermediate wide-mouth scale-eating ecomorph in a sympatric radiation of Cyprinodon pupfishes, illuminating the transition from a widespread algae-eating generalist to a novel microendemic scale-eating specialist. We first show that this ecomorph occurs in sympatry with generalist C. variegatus and scale-eating specialist C. desquamator on San Salvador Island, Bahamas, but is genetically differentiated, morphologically distinct, and often consumes scales. We then compared the timing of selective sweeps on shared and unique adaptive variants in trophic specialists to characterize their adaptive walk. Shared adaptive regions swept first in both the specialist desquamator and the intermediate wide-mouth ecomorph, followed by unique sweeps of introgressed variation in wide-mouth and de novo variation in desquamator. The two scale-eating populations additionally shared 9% of their hard selective sweeps with molluscivores C. brontotheroides, despite no single common ancestor among specialists. Our work provides a new microevolutionary framework for investigating how major ecological transitions occur and illustrates how both shared and unique genetic variation can provide a bridge for multiple species to access novel ecological niches.

evolutionary biology↗

bioRxiv2021

Parallel genetic changes underlie integrated craniofacial traits in an adaptive radiation of trophic specialist pupfishes

Many factors such as divergence time, shared standing genetic variation, frequency of introgression, and mutation rates can influence the likelihood of whether populations adapt to similar environments via parallel or non-parallel genetic changes. However, the frequency of parallel vs non-parallel genetic changes resulting in parallel phenotypic evolution is still unknown. In this study, we used a QTL mapping approach to investigate the genetic basis of highly divergent craniofacial traits between scale- and snail-eating trophic specialist species across similar hypersaline lake environments in an adaptive radiation of pupfishes endemic to San Salvador Island, Bahamas. We raised F2 intercrosses of scale- and snail-eaters from two different lake populations of sympatric specialists, estimated linkage maps, scanned for significant QTL for 30 skeletal and craniofacial traits, and compared the location of QTL between lakes to quantify parallel and non-parallel genetic changes. We found strong support for parallel genetic changes in both lakes for five traits in which we detected a significant QTL in at least one lake. However, many of these shared QTL affected different, but highly correlated craniofacial traits in each lake, suggesting that pleiotropy and trait integration should not be neglected when estimating rates of parallel evolution. We further observed a 23-52% increase in adaptive introgression within shared QTL, suggesting that introgression may be important for parallel evolution. Overall, our results suggest that the same genomic regions contribute to parallel integrated craniofacial phenotypes across lakes. We also highlight the need for more expansive searches for shared QTL when testing for parallel evolution.

evolutionary biology↗

bioRxiv2021

Adaptive introgression and de novo mutations increase access to novel fitness peaks on the fitness landscape during a vertebrate adaptive radiation

Estimating the complex relationship between fitness and genotype or phenotype (i.e. the adaptive landscape) is one of the central goals of evolutionary biology. However, adaptive walks connecting genotypes to organismal fitness, speciation, and novel ecological niches are still poorly understood and processes for surmounting fitness valleys remain controversial. One outstanding system for addressing these connections is a recent adaptive radiation of ecologically and morphologically novel pupfishes (a generalist, molluscivore, and scale-eater) endemic to San Salvador Island, Bahamas. We leveraged whole-genome sequencing of 139 hybrids from two independent field fitness experiments to identify the genomic basis of fitness, estimate genotypic fitness networks, and measure the accessibility of adaptive walks on the fitness landscape. We identified 132 SNPs that were significantly associated with fitness in field enclosures. Six out of the 13 regions most strongly associated with fitness contained differentially expressed genes and fixed SNPs between trophic specialists; one gene (mettl21e) was also misexpressed in lab-reared hybrids, suggesting a potential intrinsic genetic incompatibility. We then constructed genotypic fitness networks from adaptive alleles and show that scale-eating specialists are the most isolated of the three species on these networks. Intriguingly, introgressed and de novo variants reduced fitness landscape ruggedness as compared to standing variation, increasing the accessibility of genotypic fitness paths from generalist to specialists. Our results suggest that adaptive introgression and de novo mutations alter the shape of the fitness landscape, providing key connections in adaptive walks circumventing fitness valleys and triggering the evolution of novelty during adaptive radiation.

evolutionary biology↗

bioRxiv2021

How many replicates to accurately estimate fish biodiversity using environmental DNA on coral reefs?

Quantifying the diversity of species in rich tropical marine environments remains challenging. Environmental DNA (eDNA) metabarcoding is a promising tool to face this challenge through the filtering, amplification, and sequencing of DNA traces from water samples. However, the reliability of biodiversity detection from eDNA samples can be low in marine environments because eDNA density is low and certainly patchy in this vast, heterogenous and dynamic environment. So, the number of sampling replicates and filtered volume necessary to obtain accurate estimates of biodiversity in rich tropical marine environments using eDNA metabarcoding is still unknown. Here, we used a paired sampling design of 30L per replicate on 68 reef transects from 8 sites in three tropical regions and identified fish Molecular Taxonomic Units (MOTUs) using a 12S marker. We quantified local biodiversity variation as MOTU richness, compositional turnover and compositional nestedness between replicated pairs of seawater samples. We report strong turnover of MOTUs between replicated pairs of samples undertaken in the same location, time, and conditions. Paired samples contained non-overlapping assemblages rather than subsets of one-another. As a result, localised diversity accumulation curves showed that even 6 replicates (180L) in the same location underestimated local diversity (for an area <1km). However, sampling of regional diversity using [~]25 replicates in variable locations (often covering 10s of km) achieved saturation of biodiversity accumulation curves. Our results demonstrate high variability of diversity estimates perhaps arising from heterogeneous and local distribution of eDNA distribution in seawater or highly skewed frequencies of eDNA traces. This high compositional variability has consequences for using eDNA to monitor temporal and spatial biodiversity changes of local assemblages. Future biomonitoring efforts could be strongly undermined by a high level of false-negative detections under low replication protocols. We reveal the need to increase replicates or increase sampled water volume to better inform management of marine biodiversity using eDNA.

ecology↗

bioRxiv2019

BlobToolKit Interactive quality assessment of genome assemblies

Reconstruction of target genomes from sequence data produced by instruments that are agnostic as to the species-of-origin may be confounded by contaminant DNA. Whether introduced during sample processing or through co-extraction alongside the target DNA, if insufficient care is taken during the assembly process, the final assembled genome may be a mixture of data from several species. Such assemblies can confound sequence-based biological inference and, when deposited in public databases, may be included in downstream analyses by users unaware of underlying problems. We present BlobToolKit, a software suite to aid researchers in identifying and isolating non-target data in draft and publicly available genome assemblies. BlobToolKit can be used to process assembly, read and analysis files for fully reproducible interactive exploration in the browser-based Viewer. BlobToolKit can be used during assembly to filter non-target DNA, helping researchers produce assemblies with high biological credibility. We have been running an automated BlobToolKit pipeline on eukaryotic assemblies publicly available in the International Nucleotide Sequence Data Collaboration and are making the results available through a public instance of the Viewer at https://blobtoolkit.genomehubs.org/view. We aim to complete analysis of all publicly available genomes and then maintain currency with the flow of new genomes. We have worked to embed these views into the presentation of genome assemblies at the European Nucleotide Archive, providing an indication of assembly quality alongside the public record with links out to allow full exploration in the Viewer.

bioinformatics↗

bioRxiv2019

In-field whole plant maize architecture characterized by Latent Space Phenotyping

Collecting useful, interpretable, and biologically relevant phenotypes in a resource-efficient manner is a bottleneck to plant breeding, genetic mapping, and genomic prediction. Autonomous and affordable sub-canopy rovers are an efficient and scalable way to generate sensor-based datasets of in-field crop plants. Rovers equipped with light detection and ranging (LiDar) can produce three-dimensional reconstructions of entire hybrid maize fields. In this study, we collected 2,103 LiDar scans of hybrid maize field plots and extracted phenotypic data from them by Latent Space Phenotyping (LSP). We performed LSP by two methods, principal component analysis (PCA) and a convolutional autoencoder, to extract meaningful, quantitative Latent Space Phenotypes (LSPs) describing whole-plant architecture and biomass distribution. The LSPs had heritabilities of up to 0.44, similar to some manually measured traits, indicating they can be selected on or genetically mapped. Manually measured traits can be successfully predicted by using LSPs as explanatory variables in partial least squares regression, indicating the LSPs contain biologically relevant information about plant architecture. These techniques can be used to assess crop architecture at a reduced cost and in an automated fashion for breeding, research, or extension purposes, as well as to create or inform crop growth models.

plant biology↗

bioRxiv2019

Marketplace Shrimp Mislabeling in North Carolina

Seafood mislabeling occurs in a wide range of seafood products worldwide, resulting in public distrust, economic fraud, and health risks for consumers. We quantified the extent of shrimp mislabeling in coastal and inland North Carolina. We used standard DNA barcoding procedures to determine the species identity of 106 shrimp sold by 60 vendors across North Carolina as \"local\" shrimp. Thirty-four percent of the purchased shrimp was mislabeled, and surprisingly the percentage did not differ significantly between coastal and inland counties. Roughly one third of product incorrectly marketed as \"local\" was in fact whiteleg shrimp: an imported, and very likely farmed, species from the eastern Pacific (and not found in North Carolina waters). In addition to the negative ecosystem consequences of shrimp farming (e.g., the loss of mangroves forests and the coastal buffering they provide) and seafood importation, North Carolina fishers--as with local fishers elsewhere--are negatively impacted when vendors label farmed, frozen, and imported shrimp as local, fresh, and wild-caught.

ecology↗

bioRxiv2018

New criteria for sympatric speciation in the genomic era

Sympatric speciation illustrates how natural and sexual selection may create new species in isolation without geographic barriers. However, recent genomic reanalyses of classic examples of sympatric speciation have revealed complex histories of secondary gene flow. Thus, there is a need to revisit how to connect the diverse theoretical models of sympatric speciation and their predictions to empirical case studies in the face of widespread gene flow. We summarize theoretical differences between sympatric speciation and speciation-with-gene-flow models and propose genomic analyses for distinguishing which models apply to case studies based on the timing and function of adaptive introgression. Investigating whether secondary gene flow contributed to reproductive isolation is necessary to test whether predictions of theory are ultimately borne out in nature.

evolutionary biology↗

bioRxiv2017

Don’t throw out the sympatric species with the crater lake water: fine-scale investigation of introgression provides weak support for functional role of secondary gene flow in one of the clearest examples of sympatric speciation

Genomic data has revealed complex histories of colonization and repeated gene flow previously unrecognized in some of the most celebrated examples of sympatric speciation and radiation. However, much of the evidence for secondary gene flow into these radiations comes from genome-wide tests, which tells us little about how gene flow potentially influenced sympatric diversification. Here we investigated whole genomes of Barombi Mbo crater lake cichlids for fine-scale patterns of introgression between species with neighboring riverine cichlid populations. We did find evidence of secondary gene flow into the radiation scattered across < 0.24% of the genome; however, the functional and genetic diversity in these regions paint no clear picture of how that variation could have contributed to the ecological and morphological diversity found in the lake. Our results suggest that either variation in novel genetic pathways introduced during secondary gene flow contributed to the radiation, or that secondary gene flow was predominantly neutral with respect to the diversification processes. We also found evidence for differential assortment of ancestral polymorphism found in riverine populations between sympatric sister species, suggesting the presence of a hybrid swarm in the past. While the history of gene flow and colonization appears to be more complicated than once thought, the lack of compelling evidence for secondary gene flow influencing diversification suggests that we should not yet rule out one of the most celebrated examples of sympatric speciation in nature.

evolutionary biology↗

bioRxiv2017

A Possible Role Of Microglia In Zika Virus Infection Of The Fetal Human Brain

Maternal Zika virus (ZIKV) infection during pregnancy is increasingly recognized as the cause of an epidemic of microcephaly and other neurological anomalies in human fetuses. However, it remains unclear how ZIKV gains access to the highly vulnerable population of neural progenitors of the fetal central nervous system (CNS), and which cell types of the CNS may serve as viral reservoirs. To model viral interaction with cells of the fetal CNS in vitro, we investigated the tropism of ZIKV for different iPS-derived human cells, with a particular focus on microglia-like cells derived from human pluripotent stem cells. We show that ZIKV infected isogenic neural progenitors, astrocytes and microglia-like cells, but was only cytotoxic to neural progenitors. Infected glial cells propagated the virus and maintained viral load over time, leading to viral spread to susceptible cells. ZIKV-infected microglia, when co-cultured with pre-established neural spheroids, invaded the tissue and initiated neural infection. Since microglia derive from primitive macrophages originating in anatomical proximity to the maternal vasculature of the placenta, we propose that they may act in vivo as a viral reservoir for ZIKV and, owing to their natural ability to traverse the embryo, can establish infection of the fetal brain. Infection of immature neural stem cells by invading microglia may occur in the early stages of pregnancy, before vascular circulation is established. Our data are also consistent with the virus affecting the integrity of the blood-brain barrier (BBB), which may allow infection of the brain at later stages.

neuroscience↗