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Zadeh-Haghighi, H.

Publications and source records attributed to Zadeh-Haghighi, H..

10 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↗

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↗

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↗

The Radical Pair Mechanism Cannot Explain Telecommunication Frequency Effects on Reactive Oxygen Species

In order to investigate whether the radical pair mechanism (RPM) can explain the effects of telecommunication frequency radiation on reactive oxygen species production, we modelled the effects of oscillating magnetic fields on radical pair systems. Our analysis indicates that the RPM cannot account for the biological effects observed under exposure to telecommunication frequencies due to negligible effects under low-amplitude conditions used in experimental setups. Observable effects on radical pairs at these frequencies would require hyperfine coupling constants that are precisely fine-tuned to large values that far exceed those naturally occurring within biological systems. We conclude that some other mechanism must be responsible for the effects of telecommunication frequency fields in biological systems.

biophysics↗

Radical pairs and superoxide amplification can explain magnetic field effects on planarian regeneration

Weak magnetic field exposure can affect many biological processes across a wide range of living organisms. Recently, it has been observed that weak magnetic fields can modulate reactive oxygen species (ROS) concentration, affecting regeneration in planaria. These effects show unusual nonlinear dependence on magnetic field strength, including a sign change. In another study by the same group, superoxide is identified as the particular ROS being modulated. We propose a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of superoxide production and its effect on planarian regeneration. The results of our calculations favor a triplet-born radical pair. Our yield calculations can reproduce the observed magnetic field dependence, including the sign change. Moreover, to explain the size of the effect on ROS concentration, we suggest a simple amplification model inspired by known biochemical mechanisms and lay out the conditions for such a model to work. Further, we also make empirical predictions concerning the hypomagnetic field effects on planarian regeneration.

biophysics↗

Radical Pair Model for Magnetic Field Effects on NMDA Receptor Activity

The N-methyl-D-aspartate receptor is a prominent player in brain development and functioning. Perturbations to its functioning through external stimuli like magnetic fields can potentially affect the brain in numerous ways. Various studies have shown that magnetic fields of varying strengths affect these receptors. We propose that the radical pair mechanism, a quantum mechanical process, could explain some of these field effects. Radicals of the form [RO* Mg(H2O)n+*], where R is a protein residue that can be Serine or Tyrosine, are considered for this study. The variation in the singlet fractional yield of the radical pairs, as a function of magnetic field strength, is calculated to understand how the magnetic field affects the products of the radical pair reactions. Based on the results, the radical pair mechanism is a likely candidate for explaining the magnetic field effects observed on the receptor activity. The model predicts changes in the behaviour of the system as magnetic field strength is varied and also predicts certain isotope effects. The results further suggest that similar effects on radical pairs could be a plausible explanation for various magnetic field effects within the brain.

biophysics↗

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↗

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↗

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↗

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↗