Biology subjects

Fischer, B.

Publications and source records attributed to Fischer, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Near-complete genomes for nine haplochromine cichlid fishes reveal a novel centromeric satellite structure organised around a pair of inverted elements

The haplochromine cichlid fishes of Lake Malawi form one of the most dramatic examples of recent rapid radiation in vertebrates. Here we describe nine new diploid telomere-to-telomere (T2T) genome sequences generated using ultra-long ONT reads, which include 78 ungapped chromosomes. We provide accurate annotations of transposable elements and tandem repeats, identify rDNA cluster regions and putative centromeres, and confirm previously reported large chromosomal inversions. The putative centromeres are primarily composed of satellite tandem arrays of previously reported 237 bp repeats, but notably on most chromosomes these are organised in a novel structure in which four blocks of satellites in alternating orientation are separated by an inverted pair of [~]15 kb sequences we term "centroids", which have similarity to a non-autonomous DNA transposable element and containing potential CENP-B binding boxes. The methylation dip region indicating the likely active centromere always lies between the centroids, whose separation is almost always around 200 kb (interquartile range 151-221kb). A structurally equivalent but non-homologous organisation is seen in the distantly related Etroplus cichlid genera from South Asia. By comparing these structures across chromosomes and species, we suggest how they may have evolved, and potentially how they could contribute to the rampant sympatric speciation seen in these species, based on meiotic drive and chromosome missegregation.

genomics↗

bioRxiv2026

Cephalo-pelvic covariation and sexual dimorphism are disrupted in hybrid mice: implications for the human obstetrical dilemma

Cephalo-pelvic disproportion in humans has traditionally been interpreted through the obstetrical dilemma framework, assuming a trade-off between bipedal locomotion and childbirth. However, cephalo-pelvic covariation and pelvic sexual dimorphism might be common adaptations to parturition among mammals. We use a controlled hybridization model in mice to test whether cephalo-pelvic covariation and pelvic sexual dimorphism are population-specific, genetically structured, and sensitive to hybridization. We analyzed skull-pelvis variation and covariation, as well as sexual dimorphism of pelvic morphology across four divergent wild-derived mouse strains and their hybrids. Hybridization induced consistent cranial and pelvic size enlargement. Females exhibited significant cephalo-pelvic shape covariation, characterized by an association between rounder, wider birth canals and larger neurocrania, consistent with functional integration under obstetric selection. Hybrids showed disrupted size covariation, increased pelvis shape variance, and reduced cephalo-pelvic integration. Pelvic sexual dimorphism was systematically reduced in hybrids. Cephalo-pelvic covariation and pelvic sexual dimorphism are not exclusive to bipedal or encephalized species. They likely reflect widespread selection on birth canal morphology in mammals and have a complex genetic basis sensitive to hybridization. These findings weaken a human-exclusive interpretation of the obstetrical dilemma and highlight genetic introgression as an understudied factor shaping cephalo-pelvic integration and disproportion risk in mammals, including humans.

evolutionary biology↗

bioRxiv2026

Genetic architecture of cichlid brain morphology

How evolutionary and developmental processes interact to determine axes of neural variation that produce behavioural diversity has been debated for many decades, with alternative hypotheses giving differential emphasis to functional coupling, which favours co-evolution, and developmental constraint, which enforces it. A critical omission is data on the genetic architecture of brain size and structure, which more closely illuminates the shared developmental dependencies between components of an integrated system. Here, we exploit ecological divergence between Astatotilapia calliptera and Aulonocara stuartgranti, two closely related cichlid species from Lake Malawi, to explore the genetic architecture of brain evolution. Using computer vision and machine learning techniques to extract volumetric data from micro-tomographic images, we first demonstrate significant divergence in brain composition between these species. Genomic and micro-tomographic imaging data from a population of hybrids generated between the two species were used to investigate genetic factors shaping this differentiation. We show that the majority of brain components are integrated phenotypically in hybrids, but genetic correlations between them are generally weaker. We further show that variation in multiple brain components is associated with variation in largely structure-specific quantitative trait loci, rather than determined by genetic factors with broad effects across the entire brain. These results suggest a genetic architecture that can facilitate modular changes in brain structure, and imply that individual components are independently evolvable.

evolutionary biology↗

bioRxiv2026

Treg-derived IκBζ promotes their conversion into Th2-like effectors and drives type 2 inflammation via BATF

Regulatory T cells (Treg cells) maintain peripheral immune tolerance but display considerable plasticity in peripheral tissues. The molecular mechanisms governing their function and plasticity, particularly under inflammatory conditions, remain poorly defined. Here, we identify the NF-{kappa}B-associated transcriptional cofactor I{kappa}B{zeta} as a critical regulator of Treg cell plasticity and function. Enforced expression of I{kappa}B{zeta} in Treg cells triggered the excessive expansion of functionally impaired Treg cells, resulting in lymphadenopathy, splenomegaly, and systemic type 2 inflammation, most prominently in the lung. Mechanistically, I{kappa}B{zeta} modified BATF expression and function, thereby driving the cell-intrinsic production of Th2-associated cytokines by Treg cells. Conversely, Treg-specific deletion of I{kappa}B{zeta} constrained IL-33-mediated expansion of tissue Treg cells and surprisingly attenuated type 2 inflammation. Thus, I{kappa}B{zeta} functions as a molecular switch that reprograms regulatory T cells into Th2-like Treg cells, thereby perturbing peripheral immune tolerance. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/707402v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1ef0b17org.highwire.dtl.DTLVardef@c12eaaorg.highwire.dtl.DTLVardef@decc86org.highwire.dtl.DTLVardef@1458767_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Ethics review for insect research in the UK: Patterns, drivers, and perceived impact on research quality and process

Research involving insects currently falls outside the scope of animal welfare legislation in the UK; however, many institutions in the UK require submission of procedures involving insects to their internal ethics review board. Here, we have surveyed UK institutions to assess what proportion require ethics applications for work with insects. Further, we surveyed entomologists working at UK institutions to understand when requirements first came about at their institution and (if applicable) their experiences with ethics review, including feedback received, resources used/desired, and their self-reported confidence in submitting applications. In addition, we assessed entomologists perception of the influence of ethics review on research quality and their general attitudes and values towards the ethical treatment of insects in research and the process of ethics review. Our data demonstrate that just over half of UK institutions (51.6%) require ethics review for research with insects starting in 2008 with a steady trend towards increasing institutional requirements over time. Entomologists currently submitting are largely confident in their applications (68.8%, confident) but the majority believed that resources like training on ethics in the insect context and greater research on insect welfare would be helpful. Entomologists largely believed that ethics applications had either a positive effect (44.6%) or no effect (39.6%) on research quality; early career entomologists were more likely to report a positive effect of ethics review on study quality. Qualitative responses suggest the entomological community has diverse values and attitudes towards the ethical treatment of insects in research.

zoology↗

bioRxiv2025

Development of an EPR-based methodology to study protein-lipid interaction

The interaction of protein with other biomolecules is central to all cellular processes. In particular, protein-lipid interactions play an essential role in regulating soluble and membrane protein function, structure, and dynamics. However, probing these interactions remains challenging due to the complexity and heterogeneity of membranes. Various methods have been developed to characterize protein-membrane interaction, each presenting advantages and limitations. This study presents a robust methodology based on continuous-wave Electron Paramagnetic Resonance (CW-EPR) spectroscopy to characterize protein-membrane interactions. We focused on the protein Tau, an intrinsically disordered protein associated with neurodegenerative diseases. We show that the interaction of labelled Tau with lipids gives rise to a very distinct lineshape, which can be used to quantify the fraction of bound protein. This allows to obtain the apparent binding mode and affinity through titration experiments. In addition, we show that a single measurement provides the absolute concentration of free and bound protein. We argue that this information, which is rarely obtained by other methods providing relative signals, is very useful for mechanistic studies. Furthermore, using mathematical modeling, we developed a minimal-data approach and demonstrated that a single EPR measurement can be used to derive binding constants. The approach is applied to the Taumembrane interaction occurring in different conditions affecting the binding behavior. The presented methodology is expected to be applicable to other proteins. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/672991v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@19cf0c5org.highwire.dtl.DTLVardef@833209org.highwire.dtl.DTLVardef@149fd8corg.highwire.dtl.DTLVardef@a4f50a_HPS_FORMAT_FIGEXP M_FIG C_FIG TOC Figure. Schematic representation of EPR-based analysis of Tau-membrane interactions using spin-labeled Tau and POPS vesicles

biophysics↗

bioRxiv2024

Introgression dynamics of sex-linked chromosomal inversions shape the Malawi cichlid adaptive radiation

Chromosomal inversions contribute to adaptive speciation by linking co-adapted alleles. Querying 1,375 genomes of the species-rich Malawi cichlid fish radiation, we discovered five large inversions segregating in the benthic subradiation that each suppress recombination over more than half a chromosome. Two inversions were transferred from deepwater pelagic Diplotaxodon via admixture, while the others established early in the deep benthic clade. Introgression of haplotypes from lineages inside and outside the Malawi radiation coincided with bursts of species diversification. Inversions show evidence for transient sex linkage and a striking excess of protein changing substitutions points towards selection on neuro-sensory, physiological and reproductive genes. We conclude that repeated interplay between depth adaptation and sex-specific selection on large inversions has been central to the evolution of this iconic system.

evolutionary biology↗

bioRxiv2024

A pangenomic perspective of the Lake Malawi cichlid radiation reveals extensive structural variation driven by transposable elements

The East African Rift Lakes, namely Lake Malawi, Victoria, and Tanganyika, host a remarkable diversity of cichlid fishes, representing one of natures most striking vertebrate radiations. Despite rich phenotypic diversity, single nucleotide polymorphism (SNP)-based sequencing studies have revealed little sequence divergence between cichlids, with 0.1 to 0.25% pairwise divergence within Lake Malawi. These studies were based on aligning short reads to a single linear reference genome, which ignores the contribution of larger scale structural variants (SVs). To complement existing SNP-based studies, we adopted a pangenomic approach by constructing a multiassembly graph of haplochromine cichlids in Lake Malawi. We produced six new long read genome assemblies, alongside two publicly available ones, to span most of the major eco-morphological clades in the lake. This approach not only identifies longer SVs, but also visually represents complex and nested variation. Strikingly, the SV landscape is dominated by large insertions, many exclusive to individual assemblies. From a pangenomic perspective, we observed an exceptional amount of extra sequence, totaling up to 33.1% additional bases with respect to a single cichlid genome. Approximately 4.73 to 9.86% of the cichlid assemblies were estimated to be interspecies structural variation, suggesting substantial genomic diversity underappreciated in previous SNP-based studies. While coding regions remain highly conserved, our analysis uncovers a significant contribution of SVs from transposable element (TE) insertions, especially DNA, LINE, and LTR transposons. These findings underscore the intricate interplay of evolutionary forces shaping cichlid genome diversity, including both small nucleotide mutations and large TE-derived sequence alterations.

evolutionary biology↗

bioRxiv2023

Developmental plasticity and variability in the formation of egg-spots, a pigmentation ornament in the cichlid Astatotilapia calliptera

Vertebrate pigmentation patterns are highly diverse, yet we have a limited understanding of how evolutionary changes to genetic, cellular, and developmental mechanisms generate variation. To address this, we examine the formation of a sexually-selected male ornament exhibiting inter- and intra-specific variation, the egg-spot pattern, consisting of circular yellow-orange markings on the male anal fins of haplochromine cichlid fishes. We focus on Astatotilapia calliptera, the ancestor-type species of the Malawi cichlid adaptive radiation of over 850 species. We identify a key role for iridophores in initialising egg-spot aggregations composed of iridophore-xanthophore associations. Despite adult sexual dimorphism, aggregations initially form in both males and females, with development only diverging between the sexes at later stages. Unexpectedly, we found that the timing of egg-spot initialisation is plastic. The earlier individuals establish their own territory the earlier the aggregations form, with iridophores being the cell type that responds to social conditions. Furthermore, we observe apparent competitive interactions between adjacent egg-spot aggregations, which strongly suggests that egg-spot patterning results mostly from cell-autonomous cellular interactions. Together, these results demonstrate that A. calliptera egg-spot development is an exciting model for investigating pigment pattern formation at the cellular level in a system with developmental plasticity, sexual dimorphism, and intra-specific variation. As A. calliptera represents the ancestral bauplan for egg-spots, these findings provide a baseline for informed comparisons across the incredibly diverse Malawi cichlid radiation.

developmental biology↗

bioRxiv2022

Nanobody CDR3 mimetics enhance SOS1-catalyzed nucleotide exchange on RAS

RAS proteins control various intracellular signaling networks. Mutations at specific locations were shown to stabilize their active GTP-bound state, which is associated with the development of multiple cancers. An attractive approach to modulate RAS signaling is through its regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1). With the recent discovery of Nanobody14, which potently enhances SOS1-catalyzed nucleotide exchange on RAS, we explored the feasibility of developing peptide mimetics by structurally mimicking the complementarity-determining region 3 (CDR3). Guided by a biochemical GEF assay and X-ray co-crystal structures, successive rounds of optimization and gradual conformational rigidification led to CDR3 mimetics showing half of the maximal activation potential of the native nanobody. Altogether, this study provides the first proof-of-concept that peptides able to functionally modulate a protein-protein interaction can be obtained by structural mimicry of a nanobody paratope.

bioengineering↗

bioRxiv2022

ChILL & DisCO to discover competitive, connective and allosteric Nanobodies that modulate the SOS1-RAS protein-protein interactions and tune the nucleotide exchange rate

Protein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce novel and broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse Nanobodies that either stabilize or disrupt PPIs in a single experiment. We applied ChILL and DisCO to identify competitive, connective or fully allosteric Nanobodies that inhibit or facilitate the formation of the SOS1*RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro and RAS signalling in cellulo. One of these connective Nanobodies fills a cavity that was previously identified as the binding pocket for a series of therapeutic lead compounds. The long complementarity-determining region (CDR3) that penetrates this binding pocket serves as an innovative pharmacophore for extending the repertoire of potential leads.

bioengineering↗

bioRxiv2022

A novel model of multicellular communication through extracellular matrix microstructure

Extracellular matrix (ECM) is a key component of the cellular microenvironment and critical in multiple disease and developmental processes. Representing ECM and cell-ECM interactions is a challenging multiscale problem as they span molecular-level details to tissue-level dynamics. While several computational frameworks exist for ECM modeling, they often focus on very detailed modeling of individual ECM fibers or represent only a single aspect of the ECM. Using the PhysiCell agent-based modeling platform, we developed a framework of intermediate detail with the ability to capture bidirectional cell-ECM interactions. We represent a small region of ECM, an ECM element, with three variables describing its local microstructure: anisotropy, density, and overall fiber orientation. To spatially model the ECM, we use an array of ECM elements. Cells remodel local ECM microstructure and in turn, local microstructure impacts cellular motility. We demonstrate the utility of this framework and reusability of its core cell-ECM interaction model through examples in cellular invasion, wound healing, basement membrane degradation, and leader-follower collective migration. Despite the relative simplicity of the framework, it is able to capture a broad range of cell-ECM interactions of interest to the modeling community. Furthermore, variables representing the ECM microstructure are accessible through simple programming interfaces. This allows them to impact cell behaviors, such as proliferation and death, without requiring custom code for each interaction, particularly through PhysiCells modeling grammar, enabling rapid modeling of a diverse range of cell-matrix biology. We make this framework available as a free and open source software package at https://github.com/PhysiCell-Models/collective-invasion.

systems biology↗

bioRxiv2022

From Pigs to Silkworms: Cognition and Welfare across 10 Farmed Taxa

Billions of animals across many taxa are extensively farmed, with critical impacts on animal welfare. Societal efforts to reduce animal suffering lack rigorous and systematic approaches that facilitate maximising welfare improvements, such as informed funding allocation decisions. We present a multi-measure, cross-taxa framework for modelling differences in pain, suffering, and related cognition to assess whether certain animals have larger welfare ranges (how well or badly animals can fare). Measures include behavioural flexibility, cognitive sophistication, and general learning. We evaluated 90 empirically detectable proxies for cognition and welfare range (henceforth proxies) in pigs, chickens, carp, salmon, octopus, shrimp, crabs, crayfish, bees, and silkworms. We grouped a subset of proxies into: A) 10 ideal proxies and B) 10 less ideal proxies but with sufficient data for interspecies comparisons. We graded the strength of evidence per proxy across taxa, and constructed a cognition and welfare range profile, with overall judgement scores (ranging from likely no/low confidence to yes/very high confidence). We discuss the implications of comparisons and highlight key avenues for future research. This work is timely, given recent indications of significant political will towards reducing animal suffering, such as the inclusion of cephalopods and decapods in the Animal Welfare (Sentience) Bill following a UK government-commissioned research review. Given the novelty and robustness of our review, we believe it sets a new standard for investigating interspecies comparisons of cognition and welfare ranges and helps inform future research. This should help streamline funding allocations and improve the welfare of millions of farmed animals. Graphical/ Visual Abstract and Caption O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY Cognition and welfare in farmed animals - from pigs to silkworms (Free stock images: http://www.pixabay.com) C_FIG_DISPLAY

animal behavior and cognition↗

bioRxiv2021

Loss of hepatic Lgr4 and Lgr5 promotes nonalcoholic fatty liver disease

Background & AimsThe Rspo-Lgr4/5-Znrf3/Rnf43 module is a master regulator of hepatic Wnt/{beta}-catenin signaling and metabolic zonation, but its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. We studied whether liver-specific loss of the Wnt/{beta}-catenin modulators Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 4/5 (Lgr4/5) promotes nonalcoholic fatty liver disease (NAFLD). MethodsMice with liver-specific deletion of both receptors Lgr4/5 (Lgr4/5dLKO) were fed with normal diet (ND) or high fat diet (HFD). Livers of these mice were analyzed for lipid and fibrotic content by tissue staining and immunohistochemistry (IHC), and lipoproteins, inflammation and liver enzyme markers were measured in blood. Mechanistic insights into hepatic lipid accumulation were obtained by using ex vivo primary hepatocyte cultures derived from the Lgr4/5dLKO mice. Lipid analysis of mouse livers was performed by mass spectrometry (MS)-based untargeted lipidomic analysis. ResultsWe demonstrated that liver-specific ablation of Lgr4/5-mediated Wnt signaling resulted in hepatic steatosis, impaired bile acid (BA) secretion and predisposition to liver fibrosis. Under HFD conditions, we observed progressive intrahepatic fat accumulation, developing into macro-vesicular steatosis. Serum lipoprotein levels in HFD-fed Lgr4/5dLKO mice were decreased, rather than increased, suggesting that accumulation of fat in the liver was due to impaired lipid secretion by hepatocytes. Our lipidome analysis revealed a severe alteration of several lipid species in livers of Lgr4/5dLKO mice, including triacylglycerol estolides (TG-EST), a storage form of bioactive free fatty acid (FA) esters of hydroxy FAs (FAHFAs). ConclusionsLoss of hepatic Wnt/{beta}-catenin activity by Lgr4/5 deletion led to deregulation of lipoprotein pathways, loss of BA secretion, intrinsic alterations of lipid homeostasis and the onset of NAFLD. Lay summaryThe Wnt/{beta}-catenin pathway plays an important role during development and tissue homeostasis. Loss of Wnt/{beta}-catenin activity in mouse liver leads to loss of liver zonation, but the impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. We show that livers of mice developed steatosis upon deletion of the positive pathway regulators Lgr4/5. Livers of knock-out (KO) mice exhibited altered lipid composition due to impaired lipid secretion. Furthermore, livers of these mice developed a nonalcoholic steatohepatitis (NASH)-like phenotype and fibrotic features derived from activated hepatic stellate cells. Our data demonstrate a protective role of Wnt/{beta}-catenin pathway activity towards the development of NAFLD. HighlightsO_LIAbrogation of hepatic Wnt/{beta}-catenin activity and liver zonation upon Lgr4/5 deletion in mice led to hepatic steatosis. C_LIO_LILiver fat accumulation was caused by impaired lipid secretion from hepatocytes. C_LIO_LISteatotic livers contained increased levels of diverse lipid species, including polyunsaturated fatty acids and triglycerol-estolides. C_LIO_LIThese data confirmed that a decrease in Wnt/{beta}-catenin signaling led to the development of nonalcoholic fatty liver disease (NAFLD) in mice. C_LI

physiology↗

bioRxiv2021

Differential use of multiple genetic sex determination systems in divergent ecomorphs of an African crater lake cichlid

African cichlid fishes not only exhibit remarkably high rates of speciation but also have some of the fastest evolving sex determination systems in vertebrates. However, little is known empirically in cichlids about the genetic mechanisms generating new sex-determining variants, what forces dictate their fate, the demographic scales at which they evolve, and whether they are related to speciation. To address these questions, we looked for sex-associated loci in full genome data from 647 individuals of Astatotilapia calliptera from Lake Masoko, a small isolated crater lake in Tanzania, which contains two distinct ecomorphs of the species. We identified three separate XY systems on recombining chromosomes. Two Y alleles derive from mutations that increase expression of the gonadal soma-derived factor gene (gsdf) on chromosome 7; the first is a tandem duplication of the entire gene observed throughout much of the Lake Malawi haplochromine cichlid radiation to which A. calliptera belongs, and the second is a 5 kb insertion directly upstream of gsdf. Both the latter variant and another 700 bp insertion on chromosome 19 responsible for the third Y allele arose from transposable element insertions. Males belonging to the Masoko deep-water benthic ecomorph are determined exclusively by the gsdf duplication, whereas all three Y alleles are used in the Masoko littoral ecomorph, in which they appear to act antagonistically among males with different amounts of benthic admixture. This antagonism in the face of ongoing admixture may be important for sustaining multifactorial sex determination in Lake Masoko. In addition to identifying the molecular basis of three coexisting sex determining alleles, these results demonstrate that genetic interactions between Y alleles and genetic background can potentially affect fitness and adaptive evolution.

evolutionary biology↗

bioRxiv2021

Epigenetic Divergence during Early Stages of Speciation in an African Crater Lake Cichlid Fish

Epigenetic variation can alter transcription and promote phenotypic divergence between populations facing different environmental challenges. Here we assess the epigenetic basis of diversification during the early stages of speciation. We focus on the extent and functional relevance of DNA methylome divergence between two Astatotilapia calliptera ecomorphs in crater Lake Masoko, southern Tanzania. We report extensive genome-wide methylome divergence between populations linked to key biological processes, including transcriptional activity of ecologically-relevant genes. These include genes involved in steroid metabolism, haemoglobin composition and erythropoiesis, consistent with divergent habitat occupancy of the ecomorphs. Using a common garden experiment, we found that global methylation profiles are rapidly remodelled across generations, but ecomorph-specific differences can be inherited. Collectively, our study suggests an epigenetic contribution to early stages of vertebrate speciation. One sentence summaryInheritance and plasticity of epigenetic divergence characterise early stages of speciation in an incipient cichlid species of an African crater lake.

genomics↗

bioRxiv2021

Phospholipidosis is a shared mechanism underlying the in vitro antiviral activity of many repurposed drugs against SARS-CoV-2

Repurposing drugs as treatments for COVID-19 has drawn much attention. A common strategy has been to screen for established drugs, typically developed for other indications, that are antiviral in cells or organisms. Intriguingly, most of the drugs that have emerged from these campaigns, though diverse in structure, share a common physical property: cationic amphiphilicity. Provoked by the similarity of these repurposed drugs to those inducing phospholipidosis, a well-known drug side effect, we investigated phospholipidosis as a mechanism for antiviral activity. We tested 23 cationic amphiphilic drugs--including those from phenotypic screens and others that we ourselves had found--for induction of phospholipidosis in cell culture. We found that most of the repurposed drugs, which included hydroxychloroquine, azithromycin, amiodarone, and four others that have already progressed to clinical trials, induced phospholipidosis in the same concentration range as their antiviral activity; indeed, there was a strong monotonic correlation between antiviral efficacy and the magnitude of the phospholipidosis. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the gross physical properties of drugs, and does not reflect specific target-based activities, rather it may be considered a confound in early drug discovery. Understanding its role in infection, and detecting its effects rapidly, will allow the community to better distinguish between drugs and lead compounds that more directly impact COVID-19 from the large proportion of molecules that manifest this confounding effect, saving much time, effort and cost. One Sentence SummaryDrug-induced phospholipidosis is a single mechanism that may explain the in vitro efficacy of a wide-variety of therapeutics repurposed for COVID-19.

pharmacology and toxicology↗

bioRxiv2020

Monkey V1 epidural field potentials provide significant information about stimulus location, size, shape, and color.

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey significant and reliable information about constituent features of activating stimuli.

neuroscience↗