Conservation of magnetite biomineralization genes in all domains of life and implications for magnetic sensing

Animals use geomagnetic fields for navigational cues, yet the sensory mechanism underlying magnetic perception remains poorly understood. One idea is that geomagnetic fields are physically transduced by magnetite crystals contained inside specialized receptor cells, but evidence for intracellular, biogenic magnetite in eukaryotes is scant. Certain bacteria produce magnetite crystals inside intracellular compartments, representing the most ancient form of biomineralization known and having evolved prior to emergence of the crown group of eukaryotes, raising the question of whether magnetite biomineralization in eukaryotes and prokaryotes might share a common evolutionary history. Here, we discover that salmonid olfactory epithelium contains magnetite crystals arranged in compact clusters and determine that genes differentially expressed in magnetic olfactory cells, contrasted to nonmagnetic olfactory cells, share ancestry with an ancient prokaryote magnetite biomineralization system, consistent with exaptation for use in eukaryotic magnetoreception. We also show that 11 prokaryote biomineralization genes are universally present among a diverse set of eukaryote taxa and that nine of those genes are present within the Asgard clade of archaea Lokiarchaeota that affiliates with eukaryotes in phylogenomic analysis. Consistent with deep homology, we present an evolutionary genetics hypothesis for magnetite formation among eukaryotes to motivate convergent approaches for examining magnetite-based magnetoreception, molecular origins of matrix-associated biomineralization processes, and eukaryogenesis.

Morphology of the Human Olfactory Analyzer

The sense of smell provides people with valuable information about the biochemical environment and their own body. Olfactory disorders occur in pathologies of the nasal cavity, liver cirrhosis, psychological and endocrine diseases. Smell affects various psychological aspects of people's lives, forming positive and negative emotional memories associated with smells. With the dysfunction of the olfactory analyzer, a person will not do the analysis whether the food is good, will not be able to feel the presence of poisonous gases in the air, bad breath. This puts a person in an awkward position and increases the risk of social isolation. The purpose of the study was to highlight the components of the normal structure and functioning of the human olfactory analyzer. Identification of odors in the environment and from one's own body is provided by the olfactory analyzer. Primary odors as camphor, floral, fruity, spicy, tarry, burnt and putrid in different quantities form secondary odors. Aromas are composed of volatile molecules called odorants. The smallest amount of odorant that causes an odor sensation is called the odor threshold. In people with coronavirus disease the sense of smell temporarily disappears (anosmia); it is reduced (hyposmia) in liver cirrhosis and rhinitis, and in Alzheimer's disease and schizophrenia besides hyposmia there is olfactory hallucination (phantosmia). Olfactory dysfunction adversely affects children's cognitive abilities. Fragrances change emotions and behavior. Aromas are used to regulate the physical and psychological state of the patient. Volatile molecules of fragrances penetrate through the layer of mucus that covers the olfactory epithelium located in the olfactory region of the nasal mucosa. The olfactory epithelium consists of olfactory, supportive and basal epitheliocytes, as well as secretory cells of the olfactory glands. Olfactory cells are modified nerve cells that have a body, an axon, and a dendrite, which ends with a receptor in the form of olfactory cilia. Volatile molecules interact with the olfactory cilia and then with the receptor protein, which is located on the olfactory cell bodies. In humans, olfactory cells have 350 receptor proteins. One type of receptor can register molecules of several different odorants. Molecules of the same odorant can activate several different receptors simultaneously. The nerve impulse from the olfactory cells (bodies of I neurons) reaches the nerve cells (bodies of II neurons) of the olfactory bulbs via their central outgrowths (olfactory filaments). Axons of nerve cells of olfactory bulbs continue to bodies of III neurons, which are located in subcortical centers of the brain (almond-shaped body, nuclei of the transparent septum). In human, to analyze a particular odor, axons from bodies of III neurons continue to cortex, namely to the area of the uncus of the parahippocampal gyrus

Trypsin induces an aversive response in zebrafish by PAR2 activation in keratinocytes

Previously we have shown that trypsin, a protein typically involved in digestion, is released from gills of both fresh and saltwater fishes into surrounding water under stress or injury. We have also shown that each species produces trypsin with different specific activities. In this report, using zebrafish as a model, we identified that trypsin induces an aversive response in zebrafish larvae and adult zebrafish. Since Protease-Activated Receptor 2 (PAR2) responds to trypsin, we tested whether the aversive response is dependent on the activation of PAR2 located on the zebrafish skin cells. Zebrafish larvae treated separately with neomycin and zinc sulfate also showed aversive response indicating neuromast, and olfactory cells are not involved in this aversion. Cultured keratinocytes from zebrafish showed a response to trypsin. Zebrafish larvae subjected to knockdown of par2a also exhibited reduced escape response. Similarly, par2a-deficient mutant larvae displayed no response to trypsin. Since it has been shown that stress activates PAR2 and sends signals to the brain as shown by the increased c-fos expression, we tested c-fos expression in adult zebrafish brains after trypsin treatment of adults and found enhanced c-fos expression by qRT-PCR. Taken together, our results show that the trypsin activates PAR2 on keratinocytes signaling the brain, and this pathway of trypsin-induced escape response will provide a unique communication mechanism in zebrafish. Furthermore, since PAR2 activation also occurs in pain/pruritus sensing, this model might be useful in elucidating components of signaling pathways in pain/pruritus.

Olfactory entry promotes herpesvirus recombination

Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the immunity induced by their parents to reach higher loads. We tested this by co-infecting mice with attenuated mutants of Murid Herpesvirus-4 (MuHV-4). Infection by the natural olfactory route routinely allowed mutant viruses to reconstitute wild-type genotypes and reach normal viral loads. Lung co-infections rescued much less well. Attenuated murine cytomegalovirus mutants similarly showed recombinational rescue via the nose but not the lungs. These infections spread similarly, so route-specific rescue implied that recombination occurred close to the olfactory entry site. Rescue of replication-deficient MuHV-4 confirmed this, showing that coinfection occurred in the first encountered olfactory cells. This worked even with asynchronous inoculation, implying that a defective virus can wait here for later rescue. Virions entering the nose get caught on respiratory mucus, which the respiratory epithelial cilia push back towards the olfactory surface. Early infection was correspondingly focussed on the anterior olfactory edge. Thus, by concentrating incoming infection into a small area, olfactory entry seems to promote functionally significant recombination. Importance All organisms depend on genetic diversity to cope with environmental change. Small viruses rely on frequent point mutations. This is harder for herpesviruses because they have larger genomes. Recombination provides another means of genetic optimization. Human herpesviruses often co-infect, and they show evidence of past recombination, but whether this is rare and incidental or functionally important is unknown. We showed that herpesviruses entering mice via the natural olfactory route meet reliably enough for recombination routinely to repair crippling mutations and restore normal viral loads. It appeared to occur in the first encountered olfactory cells and reflected a concentration of infection at the anterior olfactory edge. Thus, natural host entry incorporates a significant capacity for herpesvirus recombination.

Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells

Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.

Functional Olfactory Neuroblastoma Inducing Symptomatic SIADH

Olfactory neuroblastoma (ONB) is a rare malignancy of the sinonasal cavity, originating from neuroepithelial olfactory cells. Olfactory neuroblastoma can be difficult to diagnose due to its anatomic position and variable symptomatic presentation, leading to diagnosis at a more advanced stage. Here, we present the case of a 35-year-old man with no previous medical history who had a bicycle accident secondary to syncope. He was found to be hyponatremic and suspected to have syndrome of inappropriate antidiuretic hormone secretion (SIADH). In the workup of SIADH, a brain magnetic resonance imaging revealed a mass in the left middle meatus. The lesion secreted inappropriate amounts of ADH, resulting in symptomatic paraneoplastic SIADH. This ultimately led to the early recognition and successful resection of this rare ONB. The patient has remained disease-free for over 5 years. This case is a fortunate example of a functional malignancy of the sinonasal tract that was discovered early and successfully treated as a result of symptomatic SIADH.

Compartmentalization of Photoreceptor Sensory Cilia

Functional compartmentalization of cells is a universal strategy for segregating processes that require specific components, undergo regulation by modulating concentrations of those components, or that would be detrimental to other processes. Primary cilia are hair-like organelles that project from the apical plasma membranes of epithelial cells where they serve as exclusive compartments for sensing physical and chemical signals in the environment. As such, molecules involved in signal transduction are enriched within cilia and regulating their ciliary concentrations allows adaptation to the environmental stimuli. The highly efficient organization of primary cilia has been co-opted by major sensory neurons, olfactory cells and the photoreceptor neurons that underlie vision. The mechanisms underlying compartmentalization of cilia are an area of intense current research. Recent findings have revealed similarities and differences in molecular mechanisms of ciliary protein enrichment and its regulation among primary cilia and sensory cilia. Here we discuss the physiological demands on photoreceptors that have driven their evolution into neurons that rely on a highly specialized cilium for signaling changes in light intensity. We explore what is known and what is not known about how that specialization appears to have driven unique mechanisms for photoreceptor protein and membrane compartmentalization.

The olfactory organ of schilbid catfish Eutropiichthys vacha (Hamilton, 1822): morphological and ultrastructural studies

Background A study of the olfactory organ structure in freshwater catfish, Eutropiichthys vacha, was carried out to explore the cellular constituents by aid of light as well as scanning and transmission electron microscopy. Results The paired elongated olfactory organs were situated on the dorsolateral facet of the head in the mold of simple pits. The olfactory organ was made up of a series of leaflets, the lamellae, which embedded into both sideways of slender central raphe, forming a rosette distinguished with sensory and nonsensory areas. The sensory receptor cells were present on sideward surface and linguiform process of olfactory lamella while the rest of the portion of the lamella was lined with nonsensory epithelium. Olfactory cells were characterized by their staining intensity, outline, surface features, and comprehensive morphology in the epithelium. The sensory mucosa was defined by the occurrence of three types of neuron: classic types bearing either cilia or numerous microvilli and third type having rod-shaped architecture. The nonsensory epithelium was composed of mucous cells, labyrinth cells, mast cells, and two types of supporting cells categorized as ciliated or nonciliated. Basal cells lie deep in the olfactory lining, near the central core. Conclusion The structural components of the olfactory apparatus crucial for olfaction were correlated with the behavioral activities of fish.

Anosmia: a missing link in the neuroimmunology of coronavirus disease 2019 (COVID-19)

Just before 2020 began, a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), brought for humans a potentially fatal disease known as coronavirus disease 2019 (COVID-19). The world has thoroughly been affected by COVID-19, while there has been little progress towards understanding the pathogenesis of COVID-19. Patients with a severe phenotype of disease and those who died from the disease have shown hyperinflammation and were more likely to develop neurological manifestations, linking the clinical disease with neuroimmunological features. Anosmia frequently occurs early in the course of COVID-19. The prevalence of anosmia would be influenced by self-diagnosis as well as self-misdiagnosis in patients with COVID-19. Despite this, the association between anosmia and COVID-19 has been a hope for research, aiming to understand the pathogenesis of COVID-19. Studies have suggested differently probable mechanisms for the development of anosmia in COVID-19, including olfactory cleft syndrome, postviral anosmia syndrome, cytokine storm, direct damage of olfactory sensory neurons, and impairment of the olfactory perception center in the brain. Thus, the observation of anosmia would direct us to find the pathogenesis of COVID-19 in the central nervous system, and this is consistent with numerous neurological manifestations related to COVID-19. Like other neurotropic viruses, SARS-CoV-2 might be able to enter the central nervous system via the olfactory epithelium and induce innate immune responses at the site of entry. Viral replication in the nonneural olfactory cells indirectly causes damage to the olfactory receptor nerves, and as a consequence, anosmia occurs. Further studies are required to investigate the neuroimmunology of COVID-19 in relation to anosmia.

Olfactory host entry supports herpesvirus recombination

Herpesvirus genomes record abundant recombination. Its impact on infection remains ill-defined. When co-infecting mice by the natural olfactory route, individually incapacitated Murid Herpesvirus-4 (MuHV-4) mutants routinely recombined to restore normal host colonization. Lung infection rescued much less well. Murine cytomegalovirus mutants deficient in salivary gland colonization also showed rescue via the nose but not the lungs. As nose and lung infections show similar spread, efficient recombination seemed specific to olfactory entry. Rescue of replication-deficient MuHV-4 implied co-infection of the first encountered cells, and this worked also with asynchronous inoculation, suggesting that latent virus could lie in wait for later reactivation. Inhaled MuHV-4 is commonly caught on respiratory mucus, which epithelial cilia push back towards the olfactory surface, and infection was correspondingly frequent at the anterior olfactory edge. Thus olfactory entry provides a general means for herpesviruses to meet.Author summaryInter-strain recombination allows viruses to optimise infection in diverse hosts. Many herpesviruses show past recombination. Yet they are ancient pathogens, so this past may be remote and recombination rare. Diverse herpesviruses enter new hosts via olfactory cells. We show that such entry routinely allows recombination between co-infecting virus strains, even when one strain cannot spread. Recombination was contrastingly rare after lung infection. Thus, entry via olfactory cells specifically supports frequent herpesvirus recombination.