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Electron spin relaxation is, on many occasions, considered an elephant in the room that challenges the idea of a radical-pair compass, a leading hypothesis for the navigation of migratory avian species. It has been widely recognized that an effective radical-pair magnetoreceptor requires a relaxation time that is long enough for an external magnetic field as weak as the geomagnetic field to significantly modify the coherent spin dynamics. However, previous studies proposed that certain spin relaxation, far quicker than the radical recombination reactions, could enhance, rather than degrade, the directional sensitivity of a radical-pair magnetoreceptor. Here, I investigate relaxation effects on the singlet–triplet interconversion of a model radical pair and find that the enhancement effect originates from population relaxation over a period of several microseconds as a result of efficient spin decoherence. Insights into the truncated spin systems shed light on the physics behind them. I further investigate the possibilities of such enhancement in cryptochrome-based magnetoreception, in which electron hopping takes place between tryptophan residues. [ABSTRACT FROM AUTHOR]

Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade. [ABSTRACT FROM AUTHOR]

Quantum biology is a modern field of research that aims to understand how quantum effects can affect the chemistry underlying various biological processes. This paper reviews several examples of biological processes where quantum effects might play a notable role. Initially, the photon capture mechanism present in vision is discussed, where the energy of the photon is used to cause conformational changes to chromophoric proteins. The second example elaborates the highly efficient energy transfer process present in photosynthesis and discusses, in particular, how the random quantum walk process may enhance the performance drastically. Subsequently, the vertebrate magnetoreception, and the possible associated role of the radical pair mechanism in the process is considered. The review concludes with the discussion of some speculative ideas of putative quantum effects arising in neural processes. [ABSTRACT FROM AUTHOR]

Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this ability in migratory birds to the photo-activation of the protein cryptochrome. Magnetic information is thought to induce structural changes in cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been the subject of previous all-atom molecular dynamics (MD) simulations, but insights were limited to short timescales and equilibrium structures. To address this, we developed a non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome’s photo-reduction over 20 replicates of 20 µs each. Our results revealed significant structural changes across the protein, with an overall time constant of 3 µs. The C-terminal (CT) region responded on a timescale of 4.7 µs, followed by the EEE-motif, while the phosphate binding loop (PBL) showed slower dynamics (9 µs). Network analysis highlighted direct pathways connecting the tryptophan tetrad to the CT, and distant pathways involving the EEE and PBL regions. The CT-dynamics are significantly impacted by a rearrangement of tryptophan residues in the central electron transfer chain. Our findings underscore the importance of considering longer timescales when studying cryptochrome magnetoreception and highlight the potential of non-equilibrium coarse-grained MD simulations as a powerful tool to unravel protein photoactivation reactions.

Abstract Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade.

In most avian retinas, double cones (consisting of a principal and accessory member) outnumber other photoreceptor types and have been associated with various functions, such as encoding luminance, sensing polarized light, and magnetoreception. However, their down-stream circuitry is poorly understood, particularly across bird species. Analysing species differences is important to understand changes in circuitry driven by ecological adaptations. We compare the ultrastructure of double cones and their postsynaptic bipolar cells between a night-migratory European robin and non-migratory chicken. We discover four previously unidentified bipolar cell types in the European robin retina, including midget-like bipolar cells mainly connected to one principal member. A downstream ganglion cell reveals a complete midget-like circuit similar to a circuit in the peripheral primate retina. Additionally, we identify a selective circuit transmitting information from a specific subset of accessory members. Our data highlight species-specific differences in double cone to bipolar cell connectivity, potentially reflecting ecological adaptations. Volume electron microscopy of retinas from two birds living in different habitats sheds light on species-specific wiring differences of double cone contacting bipolar cells and identifies principal and accessory member specific downstream circuits. [ABSTRACT FROM AUTHOR]

Migrating animals perform astonishing seasonal movements by orienting and navigating over thousands of kilometres with great precision. Many migratory species use cues from the sun, stars, landmarks, olfaction and the Earth's magnetic field for this task. Among vertebrates, songbirds are the most studied taxon in magnetic‐cue‐related research. Despite multiple studies, we still lack a clear understanding of when, where and how magnetic cues affect the decision‐making process of birds and hence, their realised migratory behaviour in the wild. This understanding is especially important to interpret the results of laboratory experiments in an ecologically appropriate way. In this review, we summarise the current findings about the role of magnetic cues for migratory decisions in songbirds. First, we review the methodological principles for orientation and navigation research, specifically by comparing experiments on caged birds with experiments on free‐flying birds. While cage experiments can show the sensory abilities of birds, studies with free‐flying birds can characterise the ecological roles of magnetic cues. Second, we review the migratory stages, from stopover to endurance flight, in which songbirds use magnetic cues for their migratory decisions and incorporate this into a novel conceptual framework. While we lack studies examining whether and when magnetic cues affect orientation or navigation decisions during flight, the role of magnetic cues during stopover is relatively well studied, but mostly in the laboratory. Notably, many such studies have produced contradictory results so that understanding the biological importance of magnetic cues for decisions in free‐flying songbirds is not straightforward. One potential explanation is that reproducibility of magnetic‐cue experiments is low, probably because variability in the behavioural responses of birds among experiments is high. We are convinced that parts of this variability can be explained by species‐specific and context‐dependent reactions of birds to the study conditions and by the bird's high flexibility in whether they include magnetic cues in a decision or not. Ultimately, this review should help researchers in the challenging field of magnetoreception to design experiments meticulously and interpret results of such studies carefully by considering the migration ecology of their focal species. [ABSTRACT FROM AUTHOR]

Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure produced greater enhancements in cell proliferation than light alone, yet the combined effects of magnetic fields and light were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields, and their combination, wherein statistical significance was only achieved by the combined COMS modality. By contrast, ATP production was most greatly enhanced by magnetic exposure in combination with light, indicating that mitochondrial respiratory efficiency was improved by the combination of magnetic fields plus light. Protein expression pertaining to cell proliferation was preferentially enhanced by the COMS modality, as were the protein levels of the TRPC1 cation channel that had been previously implicated as part of a calcium–mitochondrial signaling axis invoked by electromagnetic exposure and necessary for proliferation. These results indicate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. Aminoglycoside antibiotics (AGAs) have been previously shown to inhibit TRPC1-mediated magnetotransduction, whereas their influence over photomodulation has not been explored. Streptomycin applied during exposure to light, magnetic fields, or COMS reduced their respective proliferation enhancements, whereas streptomycin added after the exposure did not. Magnetic field exposure and the COMS modality were capable of partially overcoming the antagonism of proliferation produced by streptomycin treatment, whereas light alone was not. The antagonism of photon-electromagnetic effects by streptomycin implicates TRPC1-mediated calcium entry in both magnetotransduction and photomodulation. Avoiding the prophylactic use of AGAs during COMS therapy will be crucial for maintaining clinical efficacy and is a common concern in most other electromagnetic regenerative paradigms. [ABSTRACT FROM AUTHOR]

Magnetic sense, or termed magnetoreception, has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation. MagRs, highly conserved A-type iron-sulfur proteins, are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis. However, the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear. In this study, MagR sequences from 131 species, ranging from bacteria to humans, were selected for analysis, with 23 representative sequences covering species from prokaryotes to Mollusca, Arthropoda, Osteichthyes, Reptilia, Aves, and mammals chosen for protein expression and purification. Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution. Three types of MagRs were identified, each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability, indicating continuous expansion of the functional roles of MagRs during speciation and evolution. This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs. [ABSTRACT FROM AUTHOR]

The Earth’s abundance of iron has played a crucial role in both generating its geomagnetic field and contributing to the development of early life. In ancient oceans, iron ions, particularly around deep-sea hydrothermal vents, might have catalyzed the formation of macromolecules, leading to the emergence of life and the Last Universal Common Ancestor. Iron continued to influence catalysis, metabolism, and molecular evolution, resulting in the creation of magnetosome gene clusters in magnetotactic bacteria, which enabled these unicellular organisms to detect geomagnetic field. Although humans lack a clearly identified organ for geomagnetic sensing, many life forms have adapted to geomagnetic field—even in deep-sea environments—through mechanisms beyond the conventional five senses. Research indicates that zebrafish hindbrains are sensitive to magnetic fields, the semicircular canals of pigeons respond to weak potential changes through electromagnetic induction, and human brainwaves respond to magnetic fields in darkness. This suggests that the trigeminal brainstem nucleus and vestibular nuclei, which integrate multimodal magnetic information, might play a role in geomagnetic processing. From iron-based metabolic systems to magnetic sensing in neurons, the evolution of life reflects ongoing adaptation to geomagnetic field. However, since magnetite-activated, torque-based ion channels within cell membranes have not yet been identified, specialized sensory structures like the semicircular canals might still be necessary for detecting geomagnetic orientation. This mini-review explores the evolution of life from Earth’s formation to light-independent human magnetoreception, examining both the magnetite hypothesis and the electromagnetic induction hypothesis as potential mechanisms for human geomagnetic detection.

Quantum biology is a modern field of research that aims to understand how quantum effects can affect the chemistry underlying various biological processes. This paper reviews several examples of biological processes where quantum effects might play a notable role. Initially, the photon capture mechanism present in vision is discussed, where the energy of the photon is used to cause conformational changes to chromophoric proteins. The second example elaborates the highly efficient energy transfer process present in photosynthesis and discusses, in particular, how the random quantum walk process may enhance the performance drastically. Subsequently, the vertebrate magnetoreception, and the possible associated role of the radical pair mechanism in the process is considered. The review concludes with the discussion of some speculative ideas of putative quantum effects arising in neural processes.

The detection of magnetic fields by animals is known as magnetoreception. The ferromagnetic hypothesis explains magnetoreception assuming that magnetic nanoparticles are used as magnetic field transducers. Magnetite nanoparticles in the abdomen of Apis mellifera honeybees have been proposed in the literature as the magnetic field transducer. However, studies with ants and stingless bees have shown that the whole body of the insect contain magnetic material, and that the largest magnetization is in the antennae. The aim of the present study is to investigate the magnetization of all the body parts of honeybees as has been done with ants and stingless bees. To do that, the head without antennae, antennae, thorax, and abdomen obtained from Apis mellifera honeybees were analyzed using magnetometry and Ferromagnetic Resonance (FMR) techniques. The magnetometry and FMR measurements show the presence of magnetic material in all honeybee body parts. Our results present evidence of the presence of biomineralized magnetite nanoparticles in the honeybee abdomen and, for the first time, magnetite in the antennae. FMR measurements permit to identify the magnetite in the abdomen as biomineralized. As behavioral experiments reported in the literature have shown that the abdomen is involved in magnetoreception, new experimental approaches must be done to confirm or discard the involvement of the antennae in magnetoreception. [ABSTRACT FROM AUTHOR]

The Editors' and Readers' Choice Awards were established in 2022 to celebrate some of the outstanding articles published every year in the Journal of Comparative Physiology A. The recipients of the 2024 Editors' Choice Awards were selected based on votes cast by the Editorial Board on articles published in 2023. In the category Original Paper, this distinction goes to 'Views from 'crabworld': the spatial distribution of light in a tropical mudflat' by Jochen Zeil (J Comp Physiol A 209:859–876, 2023); and in the category Review Article to 'Olfactory navigation in arthropods' by Theresa J. Steele and colleagues (J Comp Physiol A 209:467–488, 2023). The winners of the 2024 Readers' Choice Awards were determined by the number of online accesses of articles published in 2022. In the category Original Paper, the winner is 'Broadband 75–85 MHz radiofrequency fields disrupt magnetic compass orientation in night‑migratory songbirds consistent with a flavin‑based radical pair magnetoreceptor' by Bo Leberecht and colleagues (J Comp Physiol A 208:97–106, 2022). In the category Review Article, the winner is 'Magnetic maps in animal navigation' by Kenneth J. Lohmann and colleagues (J Comp Physiol A 208:41–67, 2022), which already won the Editors' Choice Award in 2023. [ABSTRACT FROM AUTHOR]

Simple Summary: The Atlantic herring is one of many migratory fish that may use the geomagnetic field to navigate on its annual migration. The exact mechanism used for detecting the geomagnetic field in fish is still an open discussion, and the two main theories on magnetic sensing in animals are in the main focus: magnetite-based or radical pair-based. Here, we explore whether the cryptochrome 4 protein of fish would be able to carry out the necessary electron transfer activation to create a radical pair to be used for magnetic sensing. Marine fish migrate long distances up to hundreds or even thousands of kilometers for various reasons that include seasonal dependencies, feeding, or reproduction. The ability to perceive the geomagnetic field, called magnetoreception, is one of the many mechanisms allowing some fish to navigate reliably in the aquatic realm. While it is believed that the photoreceptor protein cryptochrome 4 (Cry4) is the key component for the radical pair-based magnetoreception mechanism in night migratory songbirds, the Cry4 mechanism in fish is still largely unexplored. The present study aims to investigate properties of the fish Cry4 protein in order to understand the potential involvement in a radical pair-based magnetoreception. Specifically, a computationally reconstructed atomistic model of Cry4 from the Atlantic herring (Clupea harengus) was studied employing classical molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) methods to investigate internal electron transfers and the radical pair formation. The QM/MM simulations reveal that electron transfers occur similarly to those found experimentally and computationally in Cry4 from European robin (Erithacus rubecula). It is therefore plausible that the investigated Atlantic herring Cry4 has the physical and chemical properties to form radical pairs that in turn could provide fish with a radical pair-based magnetic field compass sensor. [ABSTRACT FROM AUTHOR]

Magnetoreceptive biology as a field remains relatively obscure; compared with the breadth of species believed to sense magnetic fields, it remains under-studied. Here, we present grounds for the expansion of magnetoreception studies among teleosts. We begin with the electromagnetic perceptive gene (EPG) from Kryptopterus vitreolus and expand to identify 72 teleosts with homologous proteins containing a conserved three-phenylalanine (3F) motif. Phylogenetic analysis provides insight as to how EPG may have evolved over time and indicates that certain clades may have experienced a loss of function driven by different fitness pressures. One potential factor is water type with freshwater fish significantly more likely to possess the functional motif version (FFF), and saltwater fish to have the non-functional variant (FXF). It was also revealed that when the 3F motif from the homologue of Brachyhypopomus gauderio (B.g.) is inserted into EPG—EPG(B.g.)—the response (as indicated by increased intracellular calcium) is faster. This indicates that EPG has the potential to be engineered to improve upon its response and increase its utility to be used as a controller for specific outcomes.

Migratory birds possess remarkable accuracy in orientation and navigation, which involves various compass systems including the magnetic compass. Identifying the primary magnetosensor remains a fundamental open question. Cryptochromes (Cry) have been shown to be magnetically sensitive, and Cry4a from a migratory songbird seems to show enhanced magnetic sensitivity in vitro compared to Cry4a from resident species. We investigate Cry and their potential involvement in magnetoreception in a phylogenetic framework, integrating molecular evolutionary analyses with protein dynamics modelling. Our analysis is based on 363 bird genomes and identifies different selection regimes in passerines. We show that Cry4a is characterized by strong positive selection and high variability, typical characteristics of sensor proteins. We identify key sites that are likely to have facilitated the evolution of an optimized sensory protein for night-time orientation in songbirds. Additionally, we show that Cry4 was lost in hummingbirds, parrots and Tyranni (Suboscines), and thus identified a gene deletion, which might facilitate testing the function of Cry4a in birds. In contrast, the other avian Cry (Cry1 and Cry2) were highly conserved across all species, indicating basal, non-sensory functions. Our results support a specialization or functional differentiation of Cry4 in songbirds which could be magnetosensation. [ABSTRACT FROM AUTHOR]

Magnetotactic bacteria are microorganisms that produce intracellular magnetic nanoparticles organized in chains, conferring a magnetic moment to the bacterial body that allows it to swim following the geomagnetic field lines. Magnetotactic bacteria usually display two swimming polarities in environmental samples: the South-seeking (SS) polarity and the North-seeking (NS) polarity, characterized by the bacteria swimming antiparallel or parallel to the magnetic field lines, respectively. It has been observed that in the presence of inhomogeneous magnetic fields, NS magnetotactic bacteria can change their swimming polarity to SS or vice versa. The present study analyzes populations of NS cocci obtained from SS cocci isolated in the presence of a magnet. The aim was to study differences in the swimming characteristics and magnetic moment among both populations of cocci. For that, trajectories were recorded and the velocity and angle among the velocity and the applied magnetic field were calculated. In addition, micrographs from both SS and NS cocci were obtained and their magnetosomes were measured to analyze their length, width, aspect ratio and magnetic moment, to finally obtain the magnetic moment for each coccus. The results showed the following properties of NS relative to SS cocci: higher velocities, narrow bacterial magnetic moment distribution, higher dispersion in the distribution of angles among the velocity and the applied magnetic field and lower magnetic field sensibility. Those differences cannot be explained by the simple change in magnetic polarity of the magnetosome chain and can be related to the existence of an active magnetoreceptive process in magnetotactic bacteria. [ABSTRACT FROM AUTHOR]

Chemical-based interventions are mostly used to control insects that are harmful to human health and agriculture or that simply cause a nuisance. An overreliance on these insecticides however raises concerns for the environment, human health, and the development of resistance, not only in the target species. As such, there is a critical need for the development of novel nonchemical technologies to control insects. Electrocution traps using UV light as an attractant are one classical nonchemical approach to insect control but lack the specificity necessary to target only pest insects and to avoid harmless or beneficial species. Here we review the fundamental physics behind electric fields (EFs) and place them in context with electromagnetic fields more broadly. We then focus on how novel uses of strong EFs, some of which are being piloted in the field and laboratory, have the potential to repel, capture, or kill (electrocute) insects without the negative side effects of other classical approaches. As EF–insect science remains in its infancy, we provide recommendations for future areas of research in EF–insect science. [ABSTRACT FROM AUTHOR]

The ability to manipulate cellular function using an external stimulus is a powerful strategy for studying complex biological phenomena. One approach to modulate the function of the cellular environment is split proteins. In this method, a biologically active protein or an enzyme is fragmented so that it reassembles only upon a specific stimulus. Although many tools are available to induce these systems, nature has provided other mechanisms to expand the split protein toolbox. Here, we show a novel method for reconstituting split proteins using magnetic stimulation. We found that the electromagnetic perceptive gene (EPG) changes conformation due to magnetic field stimulation. By fusing split fragments of a certain protein to both termini of the EPG, the fragments can be reassembled into a functional protein under magnetic stimulation due to conformational change. We show this effect with three separate split proteins: NanoLuc, APEX2, and herpes simplex virus type-1 thymidine kinase. Our results show, for the first time, that reconstitution of split proteins can be achieved only with magnetic fields. We anticipate that this study will be a starting point for future magnetically inducible split protein designs for cellular perturbation and manipulation. With this technology, we can help expand the toolbox of the split protein platform and allow better elucidation of complex biological systems.

Simple Summary: The Earth's magnetic field is vital for life to exist. If the field becomes weaker, it's known as hypomagnetic conditions. Studying the impact of hypomagnetic conditions on living beings is significant for multiple reasons. Firstly, it helps us comprehend the biological consequences and learn more about how the magnetic field interacts with living organisms. Secondly, understanding the impact of hypomagnetic conditions on human health is important for preparing for extended space missions. This report outlines the influence of hypomagnetic conditions on various objects such as animals, humans, plants, bacteria, and individual molecules. It explains the effects at both a cellular and organismal level, and lists and characterizes the most likely mechanisms that account for biological responses to magnetic fields. Over the past century, scientists have gathered extensive data on the impacts of hypomagnetic conditions. We aimed to investigate the effect of experimental methods and type of exposure on the observed effects. Our findings indicate that hypomagnetic conditions primarily affect cellular processes such as gene expression and protein synthesis, as well as the functioning of the nervous system including neuron development and behavioral reactions. The geomagnetic field plays an important role in the existence of life on Earth. The study of the biological effects of (hypomagnetic conditions) HMC is an important task in magnetobiology. The fundamental importance is expanding and clarifying knowledge about the mechanisms of magnetic field interaction with living systems. The applied significance is improving the training of astronauts for long-term space expeditions. This review describes the effects of HMC on animals and plants, manifested at the cellular and organismal levels. General information is given about the probable mechanisms of HMC and geomagnetic field action on living systems. The main experimental approaches are described. We attempted to systematize quantitative data from various studies and identify general dependencies of the magnetobiology effects' value on HMC characteristics (induction, exposure duration) and the biological parameter under study. The most pronounced effects were found at the cellular level compared to the organismal level. Gene expression and protein activity appeared to be the most sensitive to HMC among the molecular cellular processes. The nervous system was found to be the most sensitive in the case of the organism level. The review may be of interest to biologists, physicians, physicists, and specialists in interdisciplinary fields. [ABSTRACT FROM AUTHOR]

Magnetoreception, the remarkable ability of organisms to perceive and respond to Earth's magnetic field, has captivated scientists for decades, particularly within the field of quantum biology. In the plant science, the exploration of the complicated interplay between quantum phenomena and classical biology in the context of plant magnetoreception has emerged as an attractive area of research. This comprehensive review investigates into three prominent theoretical models: the Radical Pair Mechanism (RPM), the Level Crossing Mechanism (LCM), and the Magnetite-based MagR theory in plants. While examining the advantages, limitations, and challenges associated with each model, this review places a particular weight on the RPM, highlighting its wellestablished role of cryptochromes and in-vivo experiments on light-independent plant magnetoreception. However, alternative mechanisms such as the LCM and the MagR theory are objectively presented as convincing perspectives that permit further investigation. To shed light on these theoretical frameworks, this review proposes experimental approaches including cutting-edge experimental techniques. By integrating these approaches, a comprehensive understanding of the complex mechanisms driving plant magnetoreception can be achieved, lending support to the fundamental principle in the RPM. In conclusion, this review provides a panoramic overview of plant magnetoreception, highlighting the exciting potential of quantum biology in unraveling the mysteries of magnetoreception. As researchers embark on this captivating scientific journey, the doors to decipher ing the diverse mechanisms of magnetoreception in plants stand wide open, offering a profound exploration of nature's adaptations to environmental cues. [ABSTRACT FROM AUTHOR]

Mitohormesis is a process whereby mitochondrial stress responses, mediated by reactive oxygen species (ROS), act cumulatively to either instill survival adaptations (low ROS levels) or to produce cell damage (high ROS levels). The mitohormetic nature of extremely low-frequency electromagnetic field (ELF-EMF) exposure thus makes it susceptible to extraneous influences that also impinge on mitochondrial ROS production and contribute to the collective response. Consequently, magnetic stimulation paradigms are prone to experimental variability depending on diverse circumstances. The failure, or inability, to control for these factors has contributed to the existing discrepancies between published reports and in the interpretations made from the results generated therein. Confounding environmental factors include ambient magnetic fields, temperature, the mechanical environment, and the conventional use of aminoglycoside antibiotics. Biological factors include cell type and seeding density as well as the developmental, inflammatory, or senescence statuses of cells that depend on the prior handling of the experimental sample. Technological aspects include magnetic field directionality, uniformity, amplitude, and duration of exposure. All these factors will exhibit manifestations at the level of ROS production that will culminate as a unified cellular response in conjunction with magnetic exposure. Fortunately, many of these factors are under the control of the experimenter. This review will focus on delineating areas requiring technical and biological harmonization to assist in the designing of therapeutic strategies with more clearly defined and better predicted outcomes and to improve the mechanistic interpretation of the generated data, rather than on precise applications. This review will also explore the underlying mechanistic similarities between magnetic field exposure and other forms of biophysical stimuli, such as mechanical stimuli, that mutually induce elevations in intracellular calcium and ROS as a prerequisite for biological outcome. These forms of biophysical stimuli commonly invoke the activity of transient receptor potential cation channel classes, such as TRPC1. [ABSTRACT FROM AUTHOR]

We show that the stochastic Schrödinger equation (SSE) provides an ideal way to simulate the quantum mechanical spin dynamics of radical pairs. Electron spin relaxation effects arising from fluctuations in the spin Hamiltonian are straightforward to include in this approach, and their treatment can be combined with a highly efficient stochastic evaluation of the trace over nuclear spin states that is required to compute experimental observables. These features are illustrated in example applications to a flavin–tryptophan radical pair of interest in avian magnetoreception and to a problem involving spin-selective radical pair recombination along a molecular wire. In the first of these examples, the SSE is shown to be both more efficient and more widely applicable than a recent stochastic implementation of the Lindblad equation, which only provides a valid treatment of relaxation in the extreme-narrowing limit. In the second, the exact SSE results are used to assess the accuracy of a recently proposed combination of Nakajima–Zwanzig theory for the spin relaxation and Schulten–Wolynes theory for the spin dynamics, which is applicable to radical pairs with many more nuclear spins. We also analyze the efficiency of trace sampling in some detail, highlighting the particular advantages of sampling with SU(N) coherent states. [ABSTRACT FROM AUTHOR]

The mechanism of the magnetic compass sense of migratory songbirds is thought to involve magnetically sensitive chemical reactions of light-induced radical pairs in cryptochrome proteins located in the birds' eyes. However, it is not yet clear whether this mechanism would be sensitive enough to form the basis of a viable compass. In the present work, we report spin dynamics simulations of models of cryptochrome-based radical pairs to assess whether accumulation of nuclear spin polarization in multiple photocycles could lead to significant enhancements in the sensitivity with which the proteins respond to the direction of the geomagnetic field. Although buildup of nuclear polarization appears to offer sensitivity advantages in the more idealized model systems studied, we find that these enhancements do not carry over to conditions that more closely resemble the situation thought to exist in vivo. On the basis of these simulations, we conclude that buildup of nuclear polarization seems unlikely to be a source of significant improvements in the performance of cryptochrome-based radical pair magnetoreceptors. [ABSTRACT FROM AUTHOR]

Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure produced greater enhancements in cell proliferation than light alone, yet the combined effects of magnetic fields and light were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields, and their combination, wherein statistical significance was only achieved by the combined COMS modality. By contrast, ATP production was most greatly enhanced by magnetic exposure in combination with light, indicating that mitochondrial respiratory efficiency was improved by the combination of magnetic fields plus light. Protein expression pertaining to cell proliferation was preferentially enhanced by the COMS modality, as were the protein levels of the TRPC1 cation channel that had been previously implicated as part of a calcium–mitochondrial signaling axis invoked by electromagnetic exposure and necessary for proliferation. These results indicate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. Aminoglycoside antibiotics (AGAs) have been previously shown to inhibit TRPC1-mediated magnetotransduction, whereas their influence over photomodulation has not been explored. Streptomycin applied during exposure to light, magnetic fields, or COMS reduced their respective proliferation enhancements, whereas streptomycin added after the exposure did not. Magnetic field exposure and the COMS modality were capable of partially overcoming the antagonism of proliferation produced by streptomycin treatment, whereas light alone was not. The antagonism of photon-electromagnetic effects by streptomycin implicates TRPC1-mediated calcium entry in both magnetotransduction and photomodulation. Avoiding the prophylactic use of AGAs during COMS therapy will be crucial for maintaining clinical efficacy and is a common concern in most other electromagnetic regenerative paradigms.

Marine fish migrate long distances up to hundreds or even thousands of kilometers for various reasons that include seasonal dependencies, feeding, or reproduction. The ability to perceive the geomagnetic field, called magnetoreception, is one of the many mechanisms allowing some fish to navigate reliably in the aquatic realm. While it is believed that the photoreceptor protein cryptochrome 4 (Cry4) is the key component for the radical pair-based magnetoreception mechanism in night migratory songbirds, the Cry4 mechanism in fish is still largely unexplored. The present study aims to investigate properties of the fish Cry4 protein in order to understand the potential involvement in a radical pair-based magnetoreception. Specifically, a computationally reconstructed atomistic model of Cry4 from the Atlantic herring (Clupea harengus) was studied employing classical molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) methods to investigate internal electron transfers and the radical pair formation. The QM/MM simulations reveal that electron transfers occur similarly to those found experimentally and computationally in Cry4 from European robin (Erithacus rubecula). It is therefore plausible that the investigated Atlantic herring Cry4 has the physical and chemical properties to form radical pairs that in turn could provide fish with a radical pair-based magnetic field compass sensor.

Studies at the cellular and molecular level of magnetoreception—sensing and responding to magnetic fields—are a relatively new research area. It appears that different mechanisms of magnetoreception in animals evolved from different origins, and, therefore, many questions about its mechanisms remain left open. Here we present new information regarding the Electromagnetic Perceptive Gene (EPG) from Kryptopterus vitreolus that may serve as part of the foundation to understanding and applying magnetoreception. Using HaloTag coupled with fluorescent ligands and phosphatidylinositol specific phospholipase C we show that EPG is associated with the membrane via glycosylphosphatidylinositol anchor. EPG's function of increasing intracellular calcium was also used to generate an assay using GCaMP6m to observe the function of EPG and to compare its function with that of homologous proteins. It was also revealed that EPG relies on a motif of three phenylalanine residues to function—stably swapping these residues using site directed mutagenesis resulted in a loss of function in EPG. This information not only expands upon our current understanding of magnetoreception but may provide a foundation and template to continue characterizing and discovering more within the emerging field.

Cryptochromes are flavoproteins related to photolyases that are widespread throughout the plant and animal kingdom. They govern blue light-dependent growth in plants, control circadian rhythms in a light-dependent manner in invertebrates, and play a central part in the circadian clock in vertebrates. In addition, cryptochromes might function as receptors that allow animals to sense the Earth's magnetic field. As cryptochromes are also present in mammals including humans, the possibility of a magnetosensitive protein is exciting. Here we attempt to provide a concise overview of cryptochromes in mammals. We briefly review their canonical role in the circadian rhythm from the molecular level to physiology, behaviour and diseases. We then discuss their disputed light sensitivity and proposed role in the magnetic sense in mammals, providing three mechanistic hypotheses. Specifically, mammalian cryptochromes could form light-induced radical pairs in particular cellular milieus, act as magnetoreceptors in darkness, or as secondary players in a magnetoreception signalling cascade. Future research can test these hypotheses to investigate if the role of mammalian cryptochromes extends beyond the circadian clock. [ABSTRACT FROM AUTHOR]

In this special issue of articles from leading neuroethologists—all of whom gave outstanding presentations within the Presidential Symposium of the 2022 International Congress of Neuroethology held in Lisbon, Portugal—we learn about the role of cryptochrome molecules in the magnetic sense of animals, how honeybees construct their honeycombs, why fish eyes are built the way they are in species from different depths, how archerfish intercept their newly downed prey with a swift muscular curving of the body (known as a C-start) and how birds process optic flow information to control flight. Each contribution showcases how nervous systems have evolved to control behaviour, the raison d'être of neuroethology. [ABSTRACT FROM AUTHOR]

Migratory animals can detect and use the Earth's magnetic field for orientation and navigation, sometimes over distances spanning thousands of kilometers. How they do so remains, however, one of the greatest mysteries in all sensory biology. Here, the author reviews the progress made to understand the molecular bases of the animal magnetic sense focusing on insect species, the only species in which genetic studies have so far been possible. The central hypothesis in the field posits that magnetically sensitive radical pairs formed by photoexcitation of cryptochrome proteins are key to animal magnetoreception. The author provides an overview of our current state of knowledge for the involvement of insect light-sensitive type I and light-insensitive type II cryptochromes in this enigmatic sense, and highlights some of the unanswered questions to gain a comprehensive understanding of magnetoreception at the organismal level. [ABSTRACT FROM AUTHOR]

The detection of the geomagnetic field by animals to use as a cue in homing and migration is known as magnetoreception. The ferromagnetic hypothesis explains magnetoreception assuming that magnetic nanoparticles in cellular structures are used as magnetic field transducers. Considering magnetoreception in social insects, the most studied has been the honeybee Apis mellifera and only in two wasp species (Vespa orientalis and Polybia paulista) have been shown a magnetosensitive behavior. In the present report the body parts (abdomen, head and antennae) of Polistes versicolor and Polybia paulista wasps were studied aiming to find biomineralized magnetic nanoparticles, using magnetometry measurements and ferromagnetic resonance spectroscopy. The magnetometry measurements show the presence of magnetic nanoparticles in all body parts, being characterized as mixtures of superparamagnetic, single domain and pseudo-single domain nanoparticles. From the ferromagnetic resonance spectra were obtained the asymmetry ratio A and the effective g factor geff, and those parameters are consistent with the presence of biomineralized magnetic nanoparticles in both wasps. In the case of Polybia paulista, the magnetic nanoparticles can be associated with some sort of magnetosensor once this wasp is magnetosensitive. For Polistes versicolor, the results indicate that this wasp can be magnetosensitive as Polybia paulista once their magnetic nanoparticles are biomineralized in the body. Behavioral studies with Polistes versicolor wasps deserve to be performed. [ABSTRACT FROM AUTHOR]

Night-migratory songbirds have a light-dependent magnetic compass sense, the mecha- nism of which is thought to depend on the photochemical formation of radical pairs in cryptochrome (Cry) proteins located in the retina. The finding that weak radiofrequency (RF) electromagnetic fields can prevent birds from orienting in the Earth’s magnetic field has been regarded as a diagnostic test for this mechanism and as a potential source of information on the identities of the radicals. The maximum frequency that could cause such disorientation has been predicted to lie between 120 and 220 MHz for a flavin–tryptophan radical pair in Cry. Here we show that the magnetic orientation capabilities of Eurasian blackcaps (Sylvia atricapilla) are not affected by RF noise in the frequency bands 140 to 150 MHz and 235 to 245 MHz. From a consideration of its internal magnetic interactions, we argue that RF field effects on a flavin-containing radical- pair sensor should be approximately independent of frequency up to 116 MHz and that birds’ sensitivity to RF disorientation should fall by about two orders of mag- nitude when the frequency exceeds 116 MHz. Taken together with our earlier finding that 75 to 85 MHz RF fields disrupt the magnetic orientation of blackcaps, these results provide compelling evidence that the magnetic compass of migratory birds operates by a radical pair mechanism. [ABSTRACT FROM AUTHOR]

Many organisms can sense and respond to magnetic fields (MFs), with migratory species in particular utilizing geomagnetic field information for long-distance migration. Cryptochrome proteins (Crys) along with a highly conserved Iron-sulfur cluster assembly protein (i.e., MagR) have garnered significant attention for their involvement in magnetoresponse (including magnetoreception). However, in vivo investigations of potential transcriptional crosstalk between Crys and MagR genes have been limited. The brown planthopper, Nilaparvata lugens, is a major migratory pest insect and an emerging model for studying MF intensity-related magnetoresponse. Here, we explored in vivo transcriptional crosstalk between Crys (Cry1 and Cry2) and MagR in N. lugens. The expression of Crys and MagR were found to be sensitive to MF intensity changes as small as several micro-teslas. Knocking down MagR expression led to a significant downregulation of Cry1, but not Cry2. The knockdown of either Cry1 or Cry2 individually did not significantly affect MagR expression. However, their double knockdown resulted in significant upregulation of MagR. Our findings clearly indicate transcriptional crosstalk between MagR and Crys known to be involved in magnetoresponse. This work advances the understanding of magnetoresponse signaling and represents a key initial step towards elucidating the functional consequences of these novel in vivo interactions. [ABSTRACT FROM AUTHOR]

The samples of leaves and roots of Nicotiana tabacum, the stems and tubers of Solanum tuberosum and the stems of pea Pisum sativum were examined by scanning probe microscopy in atomic force and magnetic force modes after cultivation without and with addition of magnetite nanoparticles in soil. Chains of both biogenic and anthropogenic magnetic nanoparticles are detected in the wall of the phloem sieve tubes i.e., the vascular tissue of plants. Such a localization of biogenic magnetic nanoparticles supports the idea that the chains of magnetic nanoparticles in different organs of plants have common metabolic functions. Stray gradient magnetic fields about several thousand Oe, which are created by chains of both biogenic and anthropogenic magnetic nanoparticles, can significantly affect the metabolic processes through the influence on mass transfer of vesicles, granules, organelles and other components. In view of the results of this investigation, both BMNs and anthropogenic magnetite nanoparticles chains can significantly affect the processes of mass transfer of vesicles, organelles, structural elements of the membrane and others components because they create stray magnetic fields and gradient magnetic forces. [ABSTRACT FROM AUTHOR]

A popular hypothesis ascribes magnetoreception to a magnetosensitive recombination reaction of a pair of radicals in the protein cryptochrome. Many theoretical studies of this model have ignored inter-radical interactions, particularly the electron–electron dipolar (EED) coupling, which have a detrimental effect on the magnetosensitivity. Here, we set out to elucidate if a radical pair allowed to undergo internal motion can yield enhanced magneto-sensitivity. Our model considers the effects of diffusive motion of one radical partner along a one-dimensional reaction coordinate. Such dynamics could, in principle, be realized either via actual diffusion of a mobile radical through a protein channel or via bound radical pairs subjected to protein structural rearrangements and fluctuations. We demonstrate that the suppressive effect of the EED interactions can be alleviated in these scenarios as a result of the quantum Zeno effect and intermittent reduction of the EED coupling during the radical's diffusive excursions. Our results highlight the importance of the dynamic environment entwined with the radical pair and ensuing magnetosensitivity under strong EED coupling, where it had not previously been anticipated, and demonstrate that a triplet-born radical pair can develop superior sensitivity over a singlet-born one. [ABSTRACT FROM AUTHOR]

This short review reports the surprising phenomenon of nuclear hyperpolarization occurring in chemical reactions, which is called CIDNP (chemically induced dynamic nuclear polarization) or photo-CIDNP if the chemical reaction is light-driven. The phenomenon occurs in both liquid and solid-state, and electron transfer systems, often carrying flavins as electron acceptors, are involved. Here, we explain the physical and chemical properties of flavins, their occurrence in spin-correlated radical pairs (SCRP) and the possible involvement of flavin-carrying SCRPs in animal magneto-reception at earth's magnetic field. [ABSTRACT FROM AUTHOR]

The continuously changing magnetic field of the Earth and its constant influence on the vital activity of all living organisms makes studies of magnetobiological effects important and in demand. The effects of weak magnetic fields, especially weak static magnetic fields, on living objects remains inappropriately understudied. The biological effects of weak magnetic fields result from chemical processes involving radicals, radical ions, and paramagnetic particles. As attenuation of the magnetic field is a stress factor for the body and given that the nervous system performs the most important regulatory functions in forming the body's stress response, this review addresses the influences of weak static magnetic fields on the functioning of the nervous system. Our own and published data are summarized; these indicate that weak static magnetic fields affect key biological processes, such as gene expression, cell proliferation and differentiation, and apoptosis, as well as behavior. Special attention is paid to the therapeutic potential of weak magnetic fields for clinical use in neurological pathologies. [ABSTRACT FROM AUTHOR]

The advances in biological magnetoreception and microelectronics have promoted the vigorous development of interactive electronic devices capable of noncontact interaction and control via magnetic fields. Here, a magnetosensory power device (MPD) that integrates a magnetic film ((Fe90Co10)78Si12B10) unit into a cantilever‐structured AlGaN/GaN‐based high‐electron‐mobility‐transistor is presented. The MPD is capable to not only sense external magnetic field, but also control device output power with the emulation of magnetoreception. Specifically, the device can achieve significant control of output power density (18.04 to 18.94 W mm−2) quasi‐linearly with magnetic field stimuli (0–400 mT) at a gate bias of −5 V. In addition, the maximum output power density of the MPD can reach 85.8 W mm−2 when a gate bias of 1 V is applied. The simulation and experimental results show that MPD has excellent orientation and magnetic field sensing functions under 0–400 mT magnetic fields. With the intelligent capabilities of magnetic sense and output power control, such interactive electronic devices will have broad application prospects in the fields of artificial intelligence, advanced robotics, and human‐machine interfaces. [ABSTRACT FROM AUTHOR]

From prokaryotes to higher vertebrates. orientation. navigation. and/or homing are important aspects of survival. Organisms in all major taxonomic groups have exhibited behavioral responses to magnetic fields, and study results suggest that even snakes have a map and compass sense involved in navigation and orientation within the local environment demonstrated by their ability to navigate home. While the mechanism for magnetoreception is debated, it may involve abundant intl·acellular magnetic particles such as iron that are associated with a mechanosensitive membrane receptor capable of converting mechanical signals into electrical signals usable by the nervous system. Our goal was to use local, wild-caught invasive pythons to test the hypothesis that the snake 1-etina contains a mechanosensitive transient receptor potential protein (TRPVI) that potentially colocalizes with the iron storage protein fet-ritin. Fixed Burmese python eyes were thinly sliced and used with immunohistochemistry and fluorescence microscopy to evaluate TRPV1 and ferritin presence and distribution. In our preliminary assessments, we observed TRI)Vl labeling distributed throughout most retinai cell layers. Analysis of ferritin is also discussed, as it is reportedly widely and unevenly distributed throughout the retina. where it functions in DNA repair and maintenance of phototransduction coinponents. These results can advance knowledge regarding these invasive, apex predators. their spatial orientation abilities, capacity for geographic expansion and opportunities for management. while also enhancing understanding of the potentially primal sensory modality of magnetoreception. [ABSTRACT FROM AUTHOR]

Abstract The advances in biological magnetoreception and microelectronics have promoted the vigorous development of interactive electronic devices capable of noncontact interaction and control via magnetic fields. Here, a magnetosensory power device (MPD) that integrates a magnetic film ((Fe90Co10)78Si12B10) unit into a cantilever‐structured AlGaN/GaN‐based high‐electron‐mobility‐transistor is presented. The MPD is capable to not only sense external magnetic field, but also control device output power with the emulation of magnetoreception. Specifically, the device can achieve significant control of output power density (18.04 to 18.94 W mm−2) quasi‐linearly with magnetic field stimuli (0–400 mT) at a gate bias of −5 V. In addition, the maximum output power density of the MPD can reach 85.8 W mm−2 when a gate bias of 1 V is applied. The simulation and experimental results show that MPD has excellent orientation and magnetic field sensing functions under 0–400 mT magnetic fields. With the intelligent capabilities of magnetic sense and output power control, such interactive electronic devices will have broad application prospects in the fields of artificial intelligence, advanced robotics, and human‐machine interfaces.

The possibility of realization of magnetoreception in vertebrates with chains of magnetite nanocrystals (magnetosomes) attached to hair cells of the inner ear is evaluated. To this end, statistical mechanics is applied to analyze fluctuations of stereocilia bundles. Correlation functions of fluctuations of the bundle position and of the number of open mechanoreceptor channels are derived. The sensitivity threshold of the hair cell to applied forces is calculated. Its comparison with the force couple exerted by the magnetosome in the geomagnetic field suggests that a compass magnetoreceptor can be realized with ~ 100 specifically adapted hair cells. To the opposite, no viable magnetic map receptor is possible within this system. [ABSTRACT FROM AUTHOR]

Magnetoreception is a key element in the sensory repertoire of many organisms, and it has been shown to play a particular role in animal navigation. While the first data to demonstrate a magnetic compass in songbirds through behavioural measures were presented decades ago, studies of behaviour are still the main source of information in learning about the magnetic senses. The behavioural evidence is, however, scattered with sometimes contradictory results. Partly, this is a consequence of a wide spectrum of methods used across multiple research groups studying different model organisms. This has limited the ability of researchers to pin down exactly how and why animals use the Earth's magnetic field. Here, we lay out how a range of methods for testing behaviour spanning from field observations to laboratory manipulations can be used to test for a magnetic sense in animals. To this end, we discuss the principal limitations of behavioural testing in telling us how animals sense the magnetic field, and we argue that behaviour must go hand in hand with other fields to advance our understanding of the magnetic sense. [ABSTRACT FROM AUTHOR]

Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single‐cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species‐specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale. [ABSTRACT FROM AUTHOR]

Virtual magnetic displacements are used to examine the magnetoreceptive ability of animals by changing the local magnetic field to emulate one that exists elsewhere. This technique can be used to test whether animals use a magnetic map. The viability of a magnetic map is dependant upon which magnetic parameters an animal's coordinate system is composed of, and how sensitive they are to those parameters. Previous research has not considered the degree to which sensitivity can change an animal's impression of where a virtual magnetic displacement is located. We re-assessed all published studies that use virtual magnetic displacements assuming the highest likely level of sensitivity to magnetic parameters in animals. The vast majority are susceptible to the existence of alternate possible virtual locations. In some cases, this can cause results to become ambiguous. We present a tool for visualising all possible virtual magnetic displacement alternative locations (ViMDAL) and propose changes to how further research on animal magnetoreception is conducted and reported. A tool for visualising virtual magnetic displacement locations (ViMDAL) is used to analyse existing data on virtual magnetic displacements in animals. This shows the existence of alternate possible virtual locations that may confound existing research. [ABSTRACT FROM AUTHOR]

The synthesis of flavin‐indole conjugates with a trans‐1,4‐diaminocyclohexane and a 2,6‐diaminodecahydronaphthalene linker is reported. Both compounds should serve as artificial model compounds for natural cryptochrome. It is assumed that cryptochrome photoreceptor proteins located in the retina show a light‐dependent quantum effect which enables migratory birds to perceive the Earth's magnetic field and is thus used for navigation. Both model compounds were prepared by stepwise reductive aminations of indole carbaldehyde and a flavin‐substituted acetaldehyde with the appropriate diamine linkers. The hitherto unknown 2,6‐diaminodecahydronaphthalene was prepared in four steps from 2,6‐dihydroxynaphthalene as the achiral (meso) ax,ax,trans‐diastereoisomer. The configuration of this key intermediate as well as synthetic precursors has been established by a series of X‐ray single crystal analyses. [ABSTRACT FROM AUTHOR]