Biology subjects

Simon, C.

Publications and source records attributed to Simon, C..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Effect of Methamphetamine on Ultraweak Photon Emission and Level of Reactive Oxygen Species in Male Rat Brain

All living cells, including neurons, generate ultra-weak photon emission (UPE) during biological activity, and in particular, in the brain, it has been shown that UPE is correlated with neuronal activity and associated metabolic processes. Various intracellular factors, as well as external factors, can reduce or increase the intensity of UPE. In this study, we have used Methamphetamine (METH) as one potentially effective external factor, which is a substance that has the property of stimulating the central nervous system. METH can impair mitochondrial function by causing toxicity via various pathways, including an increase in the number of mitochondria, hyperthermia, the increased metabolic activity of the brain, and the production of glutamate and excess calcium. In addition to mitochondrial dysfunction, METH alters cellular homeostasis, leading to cell damage and the production of excess ROS. The aim of this study is to measure and compare the UPE intensity and reactive oxygen species (ROS) levels of the prefrontal, motor, and visual cortex before and after METH administration. Twenty male rats were randomly assigned to two groups, the control, and METH groups. In the control group, 2 hours after injection of normal saline and without any intervention, and in the experimental group 2 hours after IP injection of 20 mg/kg METH, sections were prepared from three areas: prefrontal, motor, and V1-V2 cortex, which were used to evaluate the emission of UPE using a photomultiplier tube (PMT) device and to evaluate the amount of ROS. The results showed that the amount of ROS and UPE in the experimental group in all three areas significantly increased compared to the control group. So, METH increases UPE and ROS in the prefrontal, motor, and visual regions, and there is a direct relationship between UPE intensity and ROS production. Therefore, UPE can be used as a dynamic reading tool to monitor oxidative metabolism in physiological processes related to ROS. Also, the results of this experiment can support the hypothesis that the production of excess UPE may lead to the phenomenon of phosphene and visual hallucinations.

biophysics↗

bioRxiv2022

Network analysis of the human structural connectome including the brainstem: a new perspective on consciousness

The underlying anatomical structure is fundamental to the study of brain networks and is likely to play a key role in the generation of conscious experience. We conduct a computational and graph-theoretical study of the human structural connectome incorporating a variety of subcortical structures including the brainstem, which is typically not considered in similar studies. Our computational scheme involves the use of Python DIPY and Nibabel libraries to develop an averaged structural connectome comprised of 100 healthy adult subjects. We then compute degree, eigenvector, and betweenness centralities to identify several highly connected structures and find that the brainstem ranks highest across all examined metrics. Our results highlight the importance of including the brainstem in structural network analyses. We suggest that structural network-based methods can inform theories of consciousness, such as global workspace theory (GWT), integrated information theory (IIT), and the thalamocortical loop theory.

neuroscience↗

bioRxiv2022

Photons guided by axons may enable backpropagation-based learning in the brain

Despite great advances in explaining synaptic plasticity and neuron function, a complete understanding of the brains learning algorithms is still missing. Artificial neural networks provide a powerful learning paradigm through the backpropagation algorithm which modifies synaptic weights by using feedback connections. Backpropagation requires extensive communication of information back through the layers of a network. This has been argued to be biologically implausible and it is not clear whether backpropagation can be realized in the brain. Here we suggest that biophotons guided by axons provide a potential channel for backward transmission of information in the brain. Biophotons have been experimentally shown to be produced in the brain, yet their purpose is not understood. We propose that biophotons can propagate from each post-synaptic neuron to its pre-synaptic one to carry the required information backward. To reflect the stochastic character of biophoton emissions, our model includes the stochastic backward transmission of teaching signals. We demonstrate that a three-layered network of neurons can learn the MNIST handwritten digit classification task using our proposed backpropagation-like algorithm with stochastic photonic feedback. We model realistic restrictions and show that our system still learns the task for low rates of biophoton emission, information-limited (one bit per photon) backward transmission, and in the presence of noise photons. Our results suggest a new functionality for biophotons and provide an alternate mechanism for backward transmission in the brain.

biophysics↗

bioRxiv2021

Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis

Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of ROS production and the attenuation of adult hippocampal neurogenesis in a hypomagnetic field. The results of our calculations favor a singlet-born radical pair over a triplet-born radical pair. Our model predicts hypomagnetic field effects on the triplet/singlet yield of comparable strength as the effects observed in experimental studies on adult hippocampal neurogenesis. Our predictions are also in qualitative agreement with experimental results on superoxide concentration and other observed ROS effects. We also predict the effects of applied magnetic fields and oxygen isotopic substitution on adult hippocampal neurogenesis. Our findings strengthen the idea that nature might harness quantum resources in the context of the brain. Author summaryExposure to magnetic fields influences many neurobiological processes. The formation of new neurons (neurogenesis) in the hippocampal region of the adult brain plays a crucial role in learning and memory. It can be adversely affected by shielding the earths magnetic field, and this effect is intimately related to ROS concentration. In this study, we have developed a quantum mechanical model to explain this magnetic field dependence of adult hippocampal neurogenesis. Our model is also consistent with the observed ROS effects.

neuroscience↗

bioRxiv2021

Radical pairs may play a role in microtubule reorganization

The exact mechanism behind general anesthesia remains an open question in neuroscience. It has been proposed that anesthetics selectively prevent consciousness and memory via acting on microtubules (MTs). It is known that the magnetic field modulates MT organization. A recent study shows that a radical pair model can explain the isotope effect in xenon-induced anesthesia and predicts magnetic field effects on anesthetic potency. Further, reactive oxygen species are also implicated in MT stability and anesthesia. Based on a simple radical pair mechanism model and a simple mathematical model of MT organization, we show that magnetic fields can modulate spin dynamics of naturally occurring radical pairs in MT. We show that the spin dynamics influence a rate in the reaction cycle, which translates into a change in the MT density. We can reproduce magnetic field effects on the MT concentration that have been observed. Our model also predicts additional effects at slightly higher fields. Our model further predicts that the effect of zinc on the MT density exhibits isotopic dependence. The findings of this work make a connection between microtubule-based and radical pair-based quantum theories of consciousness.

neuroscience↗

bioRxiv2021

Host-associated microbial diversity in New Zealand cicadas uncovers elevational structure and replacement of obligate bacterial endosymbionts by Ophiocordyceps fungal pathogens

Host-microbe interactions influence eukaryotic evolution, particularly in the sap-sucking insects that often rely on obligate microbial symbionts to provision deficient nutrients in their diets. Cicadas (Hemiptera: Auchenorrhyncha: Cicadidae) specialize on xylem fluid and derive many essential amino acids and vitamins from intracellular bacteria or fungi (Hodgkinia, Sulcia, and Ophiocordyceps) that are propagated via transmission from mothers to offspring. Despite the beneficial role of these symbionts in nutrient provisioning, they are generally not considered to function within the gut where microbiota may play an important dietary role during insect diversification. Here, we investigate the relative impact of host phylogeny and ecology on gut microbial diversity in cicadas by sequencing 16S ribosomal RNA gene amplicons from 197 wild-collected cicadas and new mitochondrial genomes across 38 New Zealand cicada species, including natural hybrids between one species pair. We find a lack of phylogenetic structure and hybrid effects but a significant role of elevation in explaining variation in gut microbiota. Additionally, we provide evidence of Hodgkinia loss with gains of Ophiocordyceps fungal pathogens in all New Zealand cicadas examined that suggests convergent domestications of fungal pathogens. This highlights the macroevolutionary instability of obligate symbiosis and the relative importance of ecology rather than phylogeny for structuring gut microbial diversity in cicadas. ImportanceAn unresolved question in evolutionary biology is how beneficial associations between eukaryotes and microbes impact macroevolutionary patterns. We report substantial data from natural populations that suggest the absence of macroevolutionary impacts from gut microbiota in cicadas. Instead, gut microbial diversity is better explained by elevational variation across an island landscape. Cicadas, like many insects, have obligate nutritional associations with bacteria housed in organs outside of the gut, but we show that these associations seem also to be unstable at macroevolutionary scales. We report evidence for unexpected and widespread replacement of obligate bacteria by a domesticated and formerly pathogenic Ophiocordyceps fungus representing an evolutionarily convergent pattern across the cicada phylogeny.

evolutionary biology↗

bioRxiv2021

Radical pairs can explain magnetic field and lithium effects on the circadian clock

AO_SCPLOWBSTRACTC_SCPLOWDrosophilas circadian clock can be perturbed by magnetic fields, as well as by lithium administration. Cryptochromes are critical for the circadian clock. Further, the radical pairs in cryptochrome also can explain magnetoreception in animals. Based on a simple radical pair mechanism model of the animal magnetic compass, we show that both magnetic fields and lithium can influence the spin dynamics of the naturally occurring radical pairs and hence modulate the circadian clocks rhythms. Using a simple chemical oscillator model for the circadian clock, we show that the spin dynamics influence a rate in the chemical oscillator model, which translates into a change in the circadian period. Our model can reproduce the results of two independent experiments, magnetic fields and lithium effects on the circadian clock. Our model predicts that stronger magnetic fields would shorten the clocks period. We also predict that lithium influences the clock in an isotope-dependent manner. Furthermore, our model also predicts that magnetic fields and hyperfine interactions modulate oxidative stress. The findings of this work suggest that quantum nature and entanglement of radical pairs might play roles in the brain, as another piece of evidence in addition to recent results on xenon anesthesia and lithium effects on hyperactivity.

neuroscience↗

bioRxiv2021

Mapping lignification dynamics with a combination of chemistry, data segmentation and ratiometric analysis

This article describes a new methodology for detailed mapping of the lignification capacity of plant cell walls that we have called "REPRISAL" for REPorter Ratiometrics Integrating Segmentation for Analyzing Lignification. REPRISAL consists of the combination of three separate approaches. In the first approach, H*, G* and S* monolignol chemical reporters, corresponding to p-coumaryl alcohol, coniferyl alcohol and sinapyl alcohol, are used to label the growing lignin polymer in a fluorescent triple labelling strategy based on the sequential use of 3 main bioorthogonal chemical reactions. In the second step, an automatic parametric and/or artificial intelligence (AI) segmentation algorithm is developed that assigns fluorescent image pixels to 3 distinct cell wall zones corresponding to cell corners (CC), compound middle lamella (CML) and secondary cell walls (SCW). The last step corresponds to the exploitation of a ratiometric approach enabling statistical analyses of differences in monolignol reporter distribution (ratiometric method 1) and proportions (ratiometric method 2) within the different cell wall zones. In order to demonstrate the potential of REPRISAL for investigating lignin formation we firstly describe its use to map developmentally-related changes in the lignification capacity of WT Arabidopsis interfascicular fiber cells. We then show how it can be used to reveal subtle phenotypical differences in lignification by analyzing the Arabidopsis prx64 peroxidase mutant and provide further evidence for the implication of the AtPRX64 protein in floral stem lignification. Finally, we demonstrate the general applicability of REPRISAL by using it to map lignification capacity in poplar, flax and maize.

plant biology↗

bioRxiv2021

Entangled radicals may explain lithium effects on hyperactivity

It is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithiums effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brains cognitive processes.

neuroscience↗

bioRxiv2020

Single-cell RNA Expression of SARS-CoV-2 Cell Entry Factors in Human Endometrium during Preconception

We investigated potential SARS-CoV-2 tropism in human endometrium by single-cell RNA-sequencing of viral entry-associated genes in healthy women. Percentages of endometrial cells expressing ACE2, TMPRSS2, CTSB, or CTSL were <2%, 12%, 80%, and 80%, respectively, with 0.7% of cells expressing all four genes. Our findings imply low efficiency of SARS-CoV-2 infection in the endometrium before embryo implantation, providing information to assess preconception risk in asymptomatic carriers.

cell biology↗

bioRxiv2020

Could radical pairs play a role in xenon-induced general anesthesia?

Understanding the mechanisms underlying anesthesia would be a key step towards understanding consciousness. The process of xenon-induced general anesthesia has been shown to involve electron transfer, and the potency of xenon as a general anesthetic exhibits isotopic dependence. We propose that these observations can be explained by a mechanism in which the xenon nuclear spin influences the recombination dynamics of a naturally occurring radical pair of electrons. We develop a simple model inspired by the body of work on the radical-pair mechanism in cryptochrome in the context of avian magnetoreception, and we show that our model can reproduce the observed isotopic dependence of the general anesthetic potency of xenon in mice. Our results are consistent with the idea that radical pairs of electrons with entangled spins could be important for consciousness.

biophysics↗

bioRxiv2020

DNA Methylation Repels Binding of HIF Transcription Factors to Maintain Tumour Immunotolerance

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSHypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia. ResultsHere, we report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines. Based on in silico structural modelling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid-down by the differential expression and binding of other transcription factors under normoxia control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumours with high immune checkpoint expression, but not in tumours with low immune checkpoint expression, where they would compromise tumour immunotolerance. In a low-immunogenic tumour model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumour growth. ConclusionsOur data elucidate the mechanism underlying cell-type specific responses to hypoxia, and suggest DNA methylation and hypoxia to underlie tumour immunotolerance.

genomics↗

bioRxiv2019

The human α-defensin-derived peptide HD5(1-9) inhibits cellular attachment and entry of human cytomegalovirus.

Human cytomegalovirus (HCMV) infection causes severe illness in newborns and immunocompromised patients. Since treatment options are limited there is an unmet need for new therapeutic approaches. Defensins are cationic peptides, produced by various human tissues, which serve as antimicrobial effectors of the immune system. Furthermore, some defensins are proteolytically cleaved, resulting in the generation of smaller fragments with increased activity. Together, this led us to hypothesize that defensin-derived peptides are natural human inhibitors of virus infection with low toxicity. We screened several human defensin HNP4- and HD5-derived peptides and found HD5(1-9) to be antiviral without toxicity at high concentrations. HD5(1-9) inhibited HCMV cellular attachment and thereby entry and was active against primary as well as a multiresistant HCMV isolate. Moreover, cysteine and arginine residues were identified to mediate the antiviral activity of HD5(1-9). Altogether, defensin-derived peptides, in particular HD5(1-9), qualify as promising candidates for further development as a novel class of HCMV entry inhibitors.\n\nAUTHOR SUMMARYDefensins are peptides produced by various human organs which take part in the natural defense against pathogens. Recently, it has been shown that defensins are further cleaved to smaller peptides that have high intrinsic anti-microbial activity. We here challenged the hypothesis that these peptides might have antiviral activity, and due to their presumably natural occurrence, low toxicity. Indeed, we found one peptide fragment that turned out to block the attachment of the human cytomegalovirus (HCMV) to cells. Furthermore, this peptide did not show toxicity in various cellular assays or impede the embryonic development of zebrafish at the concentrations used to block HCMV. This is important, since HCMV is one of the most important viral congenital infections. Altogether, our results hold promise for the development of a new class of antivirals against HCMV.

microbiology↗

bioRxiv2019

Actin shells control buckling and wrinkling of biomembranes

Global changes of cell shape under mechanical or osmotic external stresses are mostly controlled by the mechanics of the cortical actin cytoskeleton underlying the cell membrane. Some aspects of this process can be recapitulated in vitro on reconstituted actin-and-membrane systems. In this paper, we investigate how the mechanical properties of a branched actin network shell, polymerized at the surface of a liposome, control membrane shape when the volume is reduced. We observe a variety of membrane shapes depending on the actin thickness. Thin shells undergo buckling, characterized by a cup-shape deformation of the membrane that coincides with the one of the actin network. Thick shells produce membrane wrinkles, but do not deform their outer layer. For intermediate micrometerthick shells, wrinkling of the membrane is observed, and the actin layer is slightly deformed. Confronting our experimental results with a theoretical description, we determine the transition between buckling and wrinkling depending on the thickness of the actin shell and the size of the liposome. We thus unveil the generic mechanism by which biomembranes are able to accommodate their shape against mechanical compression, through thickness adaptation of their cortical cytoskeleton.

biophysics↗

bioRxiv2019

Actin modulates shape and mechanics of tubular membranes

The actin cytoskeleton shapes cells and also organizes internal membranous compartments. In particular, it interacts with membranes in intracellular transport of material in mammalian cells, yeast or plant cells. Tubular membrane intermediates, pulled along microtubule tracks, are involved during these processes, and destabilize into vesicles. While the role of actin in this destabilization process is still debated, literature also provide examples of membranous structures stabilization by actin. To directly address this apparent contradiction, we mimic the geometry of tubular intermediates with preformed membrane tubes. The growth of an actin sleeve at the tube surface is monitored spatio-temporally. Depending on network cohesiveness, actin is able to stabilize, or maintain membrane tubes under pulling. Indeed, on a single tube, thicker portions correlate with the presence of actin. Such structures relax over several minutes, and may provide enough time and curvature geometries for other proteins to act on tube stability.

biophysics↗

bioRxiv2019

Achronopresence: how temporal visuotactile and visuomotor mismatches modulate embodiment

The loss of body ownership, the feeling that your body and its limbs no longer belong to you, presents a severe clinical condition that has proven difficult to study directly. We here propose a novel paradigm using mixed reality to interfere with natural embodiment using temporally conflicting sensory signals from the own hand. In Experiment 1 we investigated how such a mismatch affects phenomenological and physiological aspects of embodiment, and identified its most important dimensions using a principle component analysis. The results suggest that such a mismatch induces a strong reduction in embodiment accompanied by an increase in feelings of disownership and deafference, which was, however, not reflected in physiological changes. In Experiment 2 we refined the paradigm to measure perceptual thresholds for temporal mismatches and compared how different multimodal, mismatching information alters the sense of embodiment. The results showed that while visual delay decreased embodiment both while actively moving and during passive touch, the effect was stronger for the former. Our results extend previous findings as they demonstrate that a sense of disembodiment can be induced through controlled multimodal mismatches about ones own body and more so during active movement as compared to passive touch. Based on the ecologically more valid protocol we propose here, we argue that such a sense of disembodiment may fundamentally differ from disownership sensations as discussed in the rubber hand illusion literature, and emphasize its clinical relevance. This might importantly advance the current debate on the relative contribution of different modalities to our sense of body and its plasticity.

neuroscience↗

bioRxiv2019

A biochemical mechanism for time-encoding memory formation within individual synapses of Purkinje cells

Within the classical eye-blink conditioning, Purkinje cells within the cerebellum are known to suppress their tonic firing rates for a well defined time period in response to the conditional stimulus after training. The temporal profile of the drop in tonic firing rate, i.e., the onset and the duration, depend upon the time interval between the onsets of the training conditional and unconditional stimulus. Direct stimulation of parallel fibers and climbing fiber by electrodes was found to be sufficient to reproduce the same characteristic drop in the firing rate of the Purkinje cell. In addition, the specific metabotropic glutamate-based receptor type 7 (mGluR7), which resides on the Purkinje cell synapses, was found responsible for the initiation of the response, suggesting an intrinsic mechanism within the Purkinje cell for the temporal learning. In an attempt to look for a mechanism for time-encoding memory formation within individual Purkinje cells, we propose a biochemical mechanism based on recent experimental findings. The proposed model tries to answer key aspects of the \"Coding problem\" of Neuroscience by focussing on the Purkinje cells ability to encode time intervals through training. According to the proposed mechanism, the time memory is encoded within the dynamics of a set of proteins -- mGluR7, G-protein, G-protein coupled Inward Rectifier Potassium ion channel, Protein Kinase A and Protein Phosphatase 1 -- which self-organize themselves into a protein complex. The intrinsic dynamics of these protein complexes can differ and thus can encode different time durations. Based on their amount and their collective dynamics within individual synapses, the Purkinje cell is able to suppress its own tonic firing rate for a specific time interval. The time memory is encoded within the effective rate constants of the biochemical reactions and altering these rates constants means storing a different time memory. The proposed mechanism is verified by a simplified mathematical model and corresponding dynamical simulations of the involved biomolecules, yielding testable experimental predictions.\n\nAuthor summaryHebbian plasticity is a widely accepted form of learning that can encode memories in our brain. Spike-timing dependent plasticity resulting in Long-term Potentiation or Depression of synapses has become the default mechanistic explanation behind memory formation within a neuronal population. However, recent experiments of conditional eyeblink response in Purkinje cells have challenged this point of view by showing that these mechanisms alone cannot account for time memory formation in the Purkinje cell. To explain the underlying mechanism behind this novel synaptic plasticity, we introduce a biochemical mechanism based on protein interactions occurring within a single synapse. These protein interactions and the associated effective rate constants are sufficient to encode time delays by auto-induced inhibition on a single excitatory synapse, suggesting that synapses are capable of storing more information than previously thought.

neuroscience↗

bioRxiv2019

Expression of glucocorticoid and mineralocorticoid receptor genes co-vary with a stress-related colour signal in barn owls

Glucocorticoid hormones are important intermediates between an organism and its environment. They enable an organism to adjust its behavioural and physiological processes in response to environmental changes by binding to mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) expressed in many tissues, including the integument. The regulation of glucocorticoids covaries with melanin-based colouration in numerous species, an association that might result from the melanocortin system and evolve within a signalling context. Most studies have focused on the circulating levels of glucocorticoids disregarding the receptors that mediate their action and could partly account for the covariation between the regulation of stress and melanin-based coloration. We investigated the association between melanin-based coloration and the gene expression levels of GR and MR but also of the melanocortin system and melanogenesis in the growing feathers of nestling barn owls (Tyto alba). We also considered the expression of genes related to the melanocortin system and melanogenesis to better understand the origin of the link between the expression of receptors to which corticosterone binds and melanin-based coloration. Nestling barn owls displaying larger black feather spots expressed GR and MR at lower levels than did smaller-spotted individuals. Because the expression of the GR and MR genes was positively, rather than negatively, correlated with the expression of melanogenic genes, we suggest that the link between melanin-based coloration, GR and MR is not directly associated to melanogenesis. The finding that the expression of GR and MR was positively associated with the expression of the PCSK2 gene (encoding the protein convertase responsible for post-translational modification of the proopiomelanocortin hormone) suggests that the melanocortin system may be implicated in the establishment of the covariation between melanism and the expression of receptors to which glucocorticoids bind. Together with previous studies, our results suggest that coloration is not only related to the production of glucocorticoids but also to the sensitivity of the integument to glucocorticoids.

physiology↗