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Biology subjects

Simon, C.

Publications and source records attributed to Simon, C..

At least 19 recordsLinked to original sources

Magnetosensitivity of amphibian morphological pigmentation is light- and eye-dependent and consistent with the radical pair mechanism

Weak magnetic fields influence a wide range of biological processes, yet the underlying mechanisms are poorly understood. The radical pair mechanism (RPM), which involves quantum spin dynamics, is a leading hypothesis. Here we show that weak magnetic fields modulate morphological pigmentation--specifically, the number of perioptic melanophores-- in Xenopus laevis tadpoles in a field-strength-dependent manner. The response is light- and eye-dependent. The observed field-strength dependence is quantitatively consistent with a radical pair model. These properties are reminiscent of the light-dependent magnetoreception that is thought to operate in migratory birds, and establish amphibian pigmentation as a tractable vertebrate system for the study of radical-pair quantum biology. Significance statementWhether weak magnetic fields can influence vertebrate physiology through quantum spin dynamics has been difficult to test in a living animal. We show that weak magnetic fields alter the number of perioptic melanophores in Xenopus laevis tadpoles through a light- and eye-dependent mechanism whose field-strength dependence is quantitatively consistent with a radical-pair mechanism. Amphibian pigmentation thus offers a genetically tractable vertebrate system in which radical-pair quantum biology can be tested against whole-organism physiology.

biophysics↗

Full-thickness spatial transcriptomics of the human uterus reveals basalis niche architecture and regeneration gradients during menstrual breakdown

The human endometrium (uterine lining) undergoes cyclical breakdown and scarless regeneration during each menstrual cycle, representing an exceptional model of adult tissue renewal. Regeneration is driven primarily by progenitor cells retained within the deep, basalis compartment during menstruation, yet the full-depth spatiotemporal dynamics of this process have remained understudied due to anatomical and technical limitations. Here, we map spatial gene-expression gradients across the full thickness of the human endometrium, from the myometrial-endometrial boundary to the luminal surface, using high-resolution spatial transcriptomics integrated with single-cell transcriptomics. We profile more than ten million cells from biopsies, hysterectomy samples and menstrual fluid, enriching for the menstrual and proliferative phases, which are underrepresented in previous studies. We show that endometrial breakdown, regeneration and rapid luminal re-epithelialisation are concurrent rather than temporally separated, organised across distinct tissue compartments, revealing a mode of tissue renewal in which shedding and repair operate simultaneously. Continuous basalis-to-luminal transcriptional gradients link progenitor identity, niche signalling, and tissue remodelling, defining a coordinated regenerative axis spanning the full tissue depth. We resolve the basalis epithelial niche at unprecedented molecular resolution, identifying for the first time a discrete, predominantly quiescent progenitor-like epithelial subset and specialised supporting SFRP5+ fibroblasts, both characterised by WNT inhibition, alongside lymphoid aggregates, forming a multi-component architecture that persists after menopause, consistent with a long-lived regenerative reservoir. Together, these findings establish spatial transcriptional gradients as a central organising principle of endometrial renewal, providing a molecular framework for understanding disorders of menstruation, implantation failure, and impaired tissue repair.

cell biology↗

Revisiting claims of extracranial biophoton detection from the human brain

Ultraweak photon emission, also referred to as biological autoluminescence or biophoton emission, is the spontaneous emission of extremely low levels of light from a broad range of biological systems. Recent studies have reported that UPE measured extracranially can serve as a potential non-invasive biomarker of brain activity. Here, we show that this interpretation suffers from serious problems. We show that, when observed under properly dark conditions, the UPE from the head is much weaker than what is reported in certain papers on brain UPE from human heads. We also show that the large signals reported in these studies can be explained by background light contamination. Furthermore, photons with wavelengths < 600 nm are strongly attenuated by scalp and skull tissues, and longer wavelengths fall largely outside the effective spectral sensitivity of the photomultiplier tubes (PMTs) used. As a consequence, even if UPE from the head is detected under properly background-free conditions, it is likely to be dominated by emission from the scalp rather than from the brain, certainly as long as PMTs are used. Our results emphasize the importance of careful experimental design to make genuine progress on this important question.

biophysics↗

A chromosome-level, haplotype-resolved genome assembly for the barn owl, Tyto alba

Recent advances in long-read sequencing have enabled near telomere-to-telomere (T2T) assemblies across diverse taxa. However, avian genomes remain challenging due to numerous microchromosomes, small, typically < 20Mb, elements that are gene-, GC-, and repeat-rich. As a consequence, microchromosomes are often missing from genome assemblies. Here, we present a chromosome-level, haplotype-resolved genome assembly for the Western barn owl (Tyto alba). Using a trio-binning strategy with Illumina parental reads combined with PacBio HiFi and Oxford Nanopore Technologies data, we generated two phased contig sets. These were scaffolded into 40 linkage groups using a linkage map. Comparative analyses identified unplaced HiFi scaffolds corresponding to microchromosomes, which we integrated into six additional microchromosomes using long reads information. The two assemblies present 46 chromosomes, matching the karyotype of the species. They exhibit strong synteny between parental haplotypes, except for a [~]38 Mb complex region on chromosome 7 containing nested inversions. This high-quality reference provides the first haplotype-resolved and chromosome-level genome for Strigiformes, enabling fine-scale studies of structural variation and avian genome evolution.

genomics↗

Modeling human embryo adhesion using a microfluidic platform

Embryo adhesion represents the first step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We tested its function by introducing mouse and human blastocysts and showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage segregation. Moreover, human embryos secreted {beta}hCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity, and disorders affecting embryo-endometrium interactions. TeaserEndometrium-on-a-chip shows detailed human embryo adhesion dynamics.

molecular biology↗

The effect of age and sex on the rate of de novo mutations in barn owls

The rate of new mutations is the ultimate source of genetic variation, and thus, a fundamental quantity in evolution. Mutation rates vary across the tree of life, influenced by selection pressures and life-history traits. Within species, mutation rates and types show subtle differences between sexes as well as a positive association with parental age. Most of the direct estimates come from a few mammal species, often primates, and their generality has not been fully realised. Using 33 parent-offspring trios, we investigate the mutation rate in the barn owl (Tyto alba) and show that this species has a mutation rate of 5.6 x 10-9, matching rates of passerine species with a similar generation time of 2-3 years. Using different phasing methods we show that fathers pass on twice as many mutations as mothers and identify subtle differences in the sex-specific spectra of mutations. We also find that the number of mutations increases with paternal age, bringing direct evidence for germline senescence in birds. While across-species mutation rates and types appear conserved, the potential for within species variation due to age is substantial.

evolutionary biology↗

Phylogenomics and Fossilized Birth-Death Dating Reveals Gondawanan Origin and Extensive Post-Cretaceous Diversification of Worldwide Cicadidae.

The Cretaceous-Paleogene (K-Pg) mass extinction resulted in a massive turnover in biodiversity. The oldest fossils of the globally-distributed insect family Cicadidae date to the Paleocene, suggesting that this family diversified after the K-Pg boundary. We analyzed 490 nuclear Anchored Hybrid Enrichment loci as well as mitochondrial genomes for the Cicadidae, sampling all five subfamilies and 82% of tribes, using concatenated maximum-likelihood and multi-species coalescent approaches to resolve the phylogenetic relationships of Cicadidae subfamilies. We estimated divergence times of Cicadidae lineages using a fossilized birth-death model augmented into the multispecies coalescent with 44 fossil taxa. We estimated a Cretaceous origin for Cicadidae with four of the five subfamilies diversifying shortly after the K-Pg extinction event. Our fossilized birth-death tip-dating approach improved the precision of age estimates for many cicada clades compared to dates based on node-calibration from previous studies. Our results augment insight into how the K-Pg mass extinction shaped present-day diversity.

evolutionary biology↗

Benchmarking imputation accuracy in the presence or absence of a reference panel

Whole genome sequencing (WGS) of a large number of samples is costly. Solutions to reduce this cost include targeting a proportion of the genome (e.g. SNP arrays) or lowering the sequencing depth (low-coverage WGS, lcWGS) but both solutions suffer from either genotype missingness or uncertainty. Genomic imputation addresses this problem by inferring missing or uncertain genotypes using a collection of high quality genomic data (a reference panel). However, certain methods can impute a lcWGS dataset without a reference panel. Because the investment into generating a reference panel can be prohibitively expensive in non-model species, a benchmarking of the accuracy of these alternative methods of imputation can help inform study design. Here, we imputed a dataset of 2800 lcWGS in the presence and absence of a reference panel of 502 samples. We used 32 individuals sequenced at both high and low coverage to estimate the accuracy of each method and explored the limitations of lcWGS sample size and reference panel size. Although the best results were achieved with a large reference panel, using only a lcWGS dataset showed accurate imputation, when over 500 samples were used and we account for missing data and low frequency alleles. In addition, imputing with or without a reference panel gave similar results in a GWAS for a polygenic trait but required some quality control in the identification of homozygous-by-descent segments. Thus, while using a reference panel remains the ideal approach, imputation in suitably large lcWGS datasets can provide sufficient accuracy given proper quality control.

genomics↗

Genomic bases of short-term evolution in the wild revealed by long-term monitoring and population-scale sequencing

Understanding how wild populations adapt to rapid environmental change requires linking phenotypic evolution to its genomic basis over contemporary timescales. This remains challenging because genetic and environmental effects are often intertwined. Here, we leverage a 30-year study of Swiss barn owls (Tyto alba) to explore this process. During this period, owls have evolved darker plumage and increased spottiness, two melanin-based traits associated with fitness. Whole-genome sequencing of 3,102 individuals reveals that these traits are largely controlled by few loci of major effect with partially overlapping architectures. Temporal allele frequency analyses show subtle but consistent shifts at these loci. Simulations indicate that genetic drift alone cannot explain these changes, whereas models incorporating selection do. Our findings demonstrate that selection on a small number of loci can drive rapid phenotypic evolution in the wild. This work underscores the adaptive potential of natural populations and the value of long-term genomic monitoring under accelerating climate change.

evolutionary biology↗

Growth effects and the underlying genetic architecture of inbreeding depression in a wild raptor

1Despite its potentially devastating effects, the prevalence and underlying mechanisms of inbreeding depression in wild populations are still relatively under-explored. Here, we use whole-genome sequence data from >3,000 wild barn owls from Switzerland to investigate the presence, severity, and genetic architecture of inbreeding depression in three morphological traits. Using a combination of linear models (accounting for age) and non-linear models (to measure growth effects) we clearly show inbreeding depression is present in this population. Moreover, by breaking-down the timing of the effects we also have a better ability to detect inbreeding depression, as in some traits we find that it manifests during juvenile growth, and in others during adulthood. To our knowledge this is the first study to show direct evidence for inbreeding depression during the crucial early life weight gain period in a wild animal. We further show that certain trait-specific patterns may reflect differences in environmental influences across life stages, as we find that heritability is often lower before adulthood. We also use two classes of genomic inbreeding coefficients: FROH and FUniW, and while the directionality of effects is equivalent, the strength of evidence regarding the presence of inbreeding depression differs depending on the coefficient used. This discrepancy might give some insight into the frequency distribution of responsible variants, as each coefficient weights variants differently based on their population frequencies. Finally, an assessment of local genomic inbreeding effects highlights a handful of regions with significantly deleterious effects, alongside many regions with a smaller contribution to the observed inbreeding depression. Overall, we provide a comprehensive overview of the effects of inbreeding in this wild population, highlighting the dynamic interplay between environmental influences and the selection pressure against inbred individuals.

evolutionary biology↗

Single-Cell Profiling Reveals Altered Endometrial Cellular Features Across the Menstrual Cycle in Endometriosis Patients

Endometriosis is a chronic, estrogen-dependent condition affecting over 190 million women globally, characterized by the ectopic presence of endometrial-like tissue that leads to inflammation, pain, and infertility. Despite its prevalence, the pathogenesis of endometriosis remains poorly understood. Here, we present a comprehensive single-cell transcriptomic atlas comprising 228,000 cells derived from 43 eutopic endometrial biopsies from patients with endometriosis, fibroid controls and healthy controls, sampled across the menstrual cycle. This analysis reveals previously uncharacterized subpopulations of endometrial fibroblasts and epithelial cells undergoing epithelial-mesenchymal transition, alongside disrupted immune cell communication networks. Comparative gene expression profiling implicates oxidative stress, aberrant cell migration, and dysregulated apoptosis as central features of the disease state. These findings suggest that endometriosis alters eutopic endometrial homeostasis, with potential consequences for fertility, regeneration, and disease progression. Our dataset provides a valuable resource for biomarker discovery and identifies candidate therapeutic targets aimed at restoring endometrial function and alleviating symptoms in affected individuals.

bioinformatics↗

Magnetic Field-dependent Isotope Effect Supports Radical Pair Mechanism in Tubulin Polymerization

Weak magnetic fields and isotopes have been shown to influence biological processes; however, the underlying mechanisms remain poorly understood, particularly because the corresponding interaction energies are far below thermal energies, making classical explanations challenging or impossible. Microtubules, dynamic cytoskeletal fibers, offer an ideal system to test weak magnetic field effects due to their self-assembling capabilities, sensitivity to magnetic fields, and their central role in cellular processes. In this study, we use a combination of experiments and simulations to explore how nuclear spin dynamics affect microtubule polymerization by examining interactions between magnesium isotope substitution and weak magnetic fields. Our experiments reveal an isotope-dependent effect, which can be explained via a radical pair mechanism, explicitly arising from nuclear spin properties rather than isotopic mass differences. This nuclear spin-driven isotope effect is notably enhanced under an applied weak magnetic field of approximately 3 mT. Our theoretical model based on radical pairs achieves quantitative agreement with our experimental observations. These results establish a direct connection between quantum spin dynamics and microtubule assembly, providing new insights into how weak magnetic fields influence cellular and biomolecular functions.

biophysics↗

Untangling a History of Hybridization: A Comparison of Phylogenetic Network Methods in Reconstructing Reticulate Evolution in New Zealand Cicadas

Rapid species radiations make hybridization among species more likely. Detecting and reconstructing hybridization is therefore critical for understanding species relationships in many cases. We explored the relative performace of two phylogenetic network methods, SNaQ and PhyNEST, in evaluating the likelihood of proposed past hybridization hypotheses. We used a phylogenomic dataset of over 500 nuclear AHE genes along with mitochondrial genomes to investigate hybridization in a radiation of New Zealand cicada genera Kikihia and Maoricicada. We generated hypotheses for the existence of hybridization events based on patterns of mito-nuclear discordance and hybrid mating signals observed in a previous study. We used the D-statistic to test for the signal from hypothesized hybridization and compared SNaQ and PhyNEST results in reconstructing our hypothesized hybridization events. We found that New Zealand cicadas have an extensive history of reticulate evolution matching predictions based on patterns of mito-nuclear discordance. We also found differences in the biological plausibility of networks inferred between the two network programs, and suggest areas of improvement for network method developers.

evolutionary biology↗

Nanotribology of Viruses Reveals Their Adhesion Strength and Modality of Motion on Surfaces

We studied the friction dynamics of icosahedral viruses adsorbed to solid surfaces to probe their adhesion. Using the lateral torsion of cantilevers in atomic force microscopy to move individual capsids in a liquid environment, we found that the virions tend to roll rather than slide on the surface. In contrast, rigid, ligand-stabilized gold nanoparticles are more likely to combine rolling with sliding under the same conditions. The experiments indicate that the force required to drag the viruses on the surface is four times less than that of AuNPs, while the lateral force work needed to induce virus movement was [~] 104 kT, ten times less than that of the rigid gold nanoparticles. These results go beyond the paradigm that adhesion of nanoparticles is mainly governed by geometrical factors, such as size and area of contact, highlighting the need to amend modeling approaches to account for mechanically-compliant tribological response of biologically derived nanoparticles.

biophysics↗

Verification of radical pair mechanism predictions for weak magnetic field effects on superoxide in planarians

Superoxide concentration and tissue regeneration in planarians exhibit a complex non-monotonic dependence on the strength of an applied weak magnetic field. While this is difficult to understand based on classical physics, a recently proposed quantum model based on a flavinsuperoxide radical pair mechanism could replicate the previously observed superoxide concentrations. However, this model also predicts increased superoxide concentrations for both lower and higher fields. This seemed to conflict with earlier experimental observations on blastema sizes, which were correlated with superoxide in the previously observed regime but were known not to follow the predicted trends for lower and higher fields. Motivated by this apparent contradiction, we here directly experimentally tested the predictions of the quantum model for superoxide for lower and higher fields. To our own surprise, our experiments confirmed the predictions of the radical pair model for superoxide, and incorporating interactions with multiple nuclei further improved the models agreement with the experimental data. While open questions remain regarding the exact relationship between blastema sizes and superoxide, which is revealed to be more complex than previously observed, and the detailed properties of the underlying radical pair, our results significantly support a quantum biological explanation for the observed magnetic field effects.

biophysics↗

Imaging Ultraweak Photon Emission from Living and Dead Mice and from Plants under Stress

The phenomenon of biological ultraweak photon emission (UPE), that is, extremely low-intensity emission (10 - 103 photons/cm2/sec) in the spectral range of 200 - 1000 nm, has been observed in all living systems that have been examined. Here we report experiments that exemplify the ability of novel imaging systems to detect variations in UPE for a set of physiologically important scenarios. We use EMCCD and CCD cameras to capture single visible-wavelength photons with low noise and quantum efficiencies higher than 90%. Our investigation reveals significant contrast between the UPE from live vs. dead mice. In plants we observed that an increase in temperature and injuries both caused an increase in UPE intensity. Moreover, chemical treatments modified the UPE emission characteristics of plants, particularly the application of an anesthetic (benzocaine) to injury, which showed the highest emission among the compounds tested. As a result, UPE imaging provides the possibility of non-invasive label-free imaging of vitality in animals and the responses of plants to stress.

biophysics↗

The Impact of Ketamine and Thiopental Anesthesia onUltraweak Photon Emission and Oxidative-Nitrosative Stress in Rat Brains

Anesthetics such as ketamine and thiopental, commonly used for inducing unconsciousness, have distinct effects on neuronal activity, metabolism, and cardiovascular and respiratory systems. Ketamine increases heart rate and blood pressure while preserving respiratory function, whereas thiopental decreases both and can cause respiratory depression. This study investigates the impact of ketamine (100 mg/kg) and thiopental (45 mg/kg) on ultraweak photon emission (UPE), oxidative-nitrosative stress, and antioxidant capacity in isolated rat brains. To our knowledge, no previous study has investigated and compared UPE in the presence and absence of anesthesia. Here, we compare the effects of ketamine and thiopental anesthetics with each other and with a non-anesthetized control group. Ketamine increased UPE, lipid peroxidation, and antioxidant enzyme activity while reducing thiol levels. Conversely, thiopental decreased UPE, oxidative markers, and antioxidant enzyme activity, while increasing thiol levels. UPE was negatively correlated with thiol levels and positively correlated with oxidative stress markers. These findings suggest that the contrasting effects of ketamine and thiopental on UPE are linked to their differing impacts on brain oxidative stress and antioxidant capacity. This research suggests a potential method to monitor brain oxidative stress via UPE during anesthesia, and opens up new ways for understanding and managing anesthetic effects. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/609284v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@13459d7org.highwire.dtl.DTLVardef@1f64a77org.highwire.dtl.DTLVardef@92d5e4org.highwire.dtl.DTLVardef@189b37_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation

HighlightsO_LICircadian pigmentation of tadpoles in vivo is mainly driven by melatonin C_LIO_LILight and melatonin differentially regulate proliferation C_LIO_LIMelatonin mimics the expression of circadian core genes in the dark phase C_LIO_LIDeregulation of the circadian rhythm inhibits melanin synthesis C_LI Circadian regulation of skin pigmentation is essential for thermoregulation, UV protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells. We studied light/dark cycles and melatonin coordination in melanin synthesis and cell proliferation of Xenopus laevis melanophores. In vivo, tadpole pigmentation shows robust circadian regulation mainly hormone-driven, in that isolated melanophores respond strongly to melatonin but only slightly to light. Melanophore proliferation is faster in the dark and slower with melatonin compared to a 12/12 light/dark cycle. Expression of circadian core genes (clock, bmal1, per1, per2, per3, cry1, cry2, and cry4) in melatonin-treated cells during the light phase mimics dark phase expression. Individual Cry overexpression did not affect melanisation or cell proliferation, likely due to functional redundancy. Melanin synthesis was inhibited by circadian cycle deregulation through: a) pharmacological inhibition of Cry1 and Cry2 degradation with KL001, b) continuous light or dark conditions, and c) melatonin treatment. Our findings suggest that circadian cycle regulation, rather than proliferative capacity, alters melanisation of melanophores. SignificanceCircadian rhythms are a highly conserved phenomenon in nature. In vertebrates, the modification of skin pigmentation and epidermal cell renewal in response to the environmental light-dark cycle are crucial physiological adaptations that serve various purposes, including thermoregulation, reducing ultraviolet damage, and regulating skin stem cell proliferation. Our observations indicate that, in vivo, the circadian regulation of skin pigmentation is more influenced by cycling-melatonin levels than light/dark. The deregulation of the circadian cell cycle through various mechanisms all inhibited melanisation while cell proliferation was increased or reduced, suggesting that proliferation and melanisation are mechanistically dissociated responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/604624v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@9787deorg.highwire.dtl.DTLVardef@59022corg.highwire.dtl.DTLVardef@19dd46eorg.highwire.dtl.DTLVardef@e58fec_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

physiology↗