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Current Biology : CB Dec 2023Insects and mammals have independently evolved odorant receptor genes that are arranged in large genomic tandem arrays. In mammals, each olfactory sensory neuron chooses...
Insects and mammals have independently evolved odorant receptor genes that are arranged in large genomic tandem arrays. In mammals, each olfactory sensory neuron chooses to express a single receptor in a stochastic process that includes substantial chromatin rearrangements. Here, we show that ants, which have the largest odorant receptor repertoires among insects, employ a different mechanism to regulate gene expression from tandem arrays. Using single-nucleus RNA sequencing, we found that ant olfactory sensory neurons choose different transcription start sites along an array but then produce mRNA from many downstream genes. This can result in transcripts from dozens of receptors being present in a single nucleus. Such rampant receptor co-expression at first seems difficult to reconcile with the narrow tuning of the ant olfactory system. However, RNA fluorescence in situ hybridization showed that only mRNA from the most upstream transcribed odorant receptor seems to reach the cytoplasm where it can be translated into protein, whereas mRNA from downstream receptors gets sequestered in the nucleus. This implies that, despite the extensive co-expression of odorant receptor genes, each olfactory sensory neuron ultimately only produces one or very few functional receptors. Evolution has thus found different molecular solutions in insects and mammals to the convergent challenge of selecting small subsets of receptors from large odorant receptor repertoires.
Topics: Animals; Receptors, Odorant; Ants; In Situ Hybridization, Fluorescence; Olfactory Receptor Neurons; Mammals; RNA, Messenger
PubMed: 38070504
DOI: 10.1016/j.cub.2023.11.025 -
Scientific Reports Dec 2023Agriculturally important crop plants emit a multitude of volatile organic compounds (VOCs), which are excellent indicators of their health status and their interactions...
High-throughput ligand profile characterization in novel cell lines expressing seven heterologous insect olfactory receptors for the detection of volatile plant biomarkers.
Agriculturally important crop plants emit a multitude of volatile organic compounds (VOCs), which are excellent indicators of their health status and their interactions with pathogens and pests. In this study, we have developed a novel cellular olfactory panel for detecting fungal pathogen-related VOCs we had identified in the field, as well as during controlled inoculations of several crop plants. The olfactory panel consists of seven stable HEK293 cell lines each expressing a functional Drosophila olfactory receptor as a biosensing element along with GCaMP6, a fluorescent calcium indicator protein. An automated 384-well microplate reader was used to characterize the olfactory receptor cell lines for their sensitivity to reference VOCs. Subsequently, we profiled a set of 66 VOCs on all cell lines, covering a concentration range from 1 to 100 μM. Results showed that 49 VOCs (74.2%) elicited a response in at least one olfactory receptor cell line. Some VOCs activated the cell lines even at nanomolar (ppb) concentrations. The interaction profiles obtained here will support the development of biosensors for agricultural applications. Additionally, the olfactory receptor proteins can be purified from these cell lines with sufficient yields for further processing, such as structure determination or integration with sensor devices.
Topics: Humans; Animals; Olfactory Receptor Neurons; Receptors, Odorant; Ligands; HEK293 Cells; Insecta; Drosophila; Volatile Organic Compounds; Biomarkers
PubMed: 38066004
DOI: 10.1038/s41598-023-47455-4 -
PloS One 2023This paper presents an electronic nose system inspired by the biological olfactory system. When comparing the human olfactory system to that of a dog, it's worth noting...
This paper presents an electronic nose system inspired by the biological olfactory system. When comparing the human olfactory system to that of a dog, it's worth noting that dogs have 30 times more olfactory receptors and three times as many types of olfactory receptors. This implies that the number of olfactory receptors could be a more important parameter for classifying chemical compounds than the number of receptor types. Instead of using expensive precision sensors, the proposed electronic nose system relies on numerous low-cost homogeneous and heterogeneous sensors with poor cross-interference characteristics due to their low gas selectivity. Even if the same type of sensor shows a slightly different output for the same chemical compound, this variation becomes a unique signal for the target gas being measured. The electronic nose system comprises 30 sensors, the e-nose had 6 differing sensors with 5 replicates of each type. The characteristics of the electronic nose system are evaluated using three different volatile alcoholic compounds, more than 99% of which are the same. Liquid samples are supplied to the sensor chamber for 60 seconds using an air bubbler, followed by a 60-second cleaning of the chamber. Sensor signals are acquired at a sampling rate of 100 Hz. In this experimental study, the effects of data preprocessing methods and the number of sensors of the same type are investigated. By increasing the number of sensors of the same type, classification accuracy exceeds 99%, regardless of the deep learning model. The proposed electronic nose system, based on low-cost sensors, demonstrates similar results to commercial expensive electronic nose systems.
Topics: Animals; Humans; Dogs; Electronic Nose; Receptors, Odorant; Olfactory Receptor Neurons
PubMed: 38064527
DOI: 10.1371/journal.pone.0295703 -
Proceedings of the National Academy of... Dec 2023
Topics: Animals; Drosophila; Drosophila melanogaster; Olfactory Receptor Neurons; Neuronal Plasticity
PubMed: 38048452
DOI: 10.1073/pnas.2315790120 -
Insect Biochemistry and Molecular... Jan 2024In insect antenna, following the activation of olfactory sensory neurons, odorant molecules are inactivated by enzymes in the sensillum lymph. How the inactivation...
In insect antenna, following the activation of olfactory sensory neurons, odorant molecules are inactivated by enzymes in the sensillum lymph. How the inactivation products are cleared from the sensillum lymph is presently unknown. Here we studied the role of support cells (SCs) and the so-called sensory neuron membrane protein 2 (SNMP2), a member of the CD36 family of lipid transporters abundantly expressed in SCs, in sensillum lymph clearance processes in the moths Heliothis virescens and Bombyx mori. In these species, the sex pheromone components are inactivated to long-chain fatty acids. To approach a role of SNMP2 in the removal of such inactivation products, we analyzed the uptake of a fluorescent long-chain fatty acid analog into a newly generated HvirSNMP2-expressing cell line. We found an increased uptake of the analog into SNMP2-cells compared to control cells, which could be blocked by the CD36 protein inhibitor, SSO. Furthermore, analyses of sensilla from antenna treated with the fatty acid analog indicated that SNMP2-expressing SCs are able to take up fatty acids from the sensillum lymph. In addition, sensilla from SSO-pretreated antenna of B. mori showed reduced removal of the fluorescent analog from the sensillum lymph. Finally, we revealed that SSO pretreatment of male silkmoth antenna significantly prolonged the duration of the female pheromone-induced wing-fluttering behavior, possibly as a result of impaired lymph clearance processes. Together our findings in H. virescens and B. mori support a pivotal role of olfactory SCs in sensillum lymph maintenance processes and suggest an integral role of SNMP2 in the removal of lipophilic "waste products" such as fatty acids resulting from sex pheromone inactivation.
Topics: Male; Female; Animals; Moths; Sensilla; Pheromones; Sex Attractants; Membrane Proteins; Insect Proteins; Bombyx; Sensory Receptor Cells; Olfactory Receptor Neurons; Fatty Acids
PubMed: 38043913
DOI: 10.1016/j.ibmb.2023.104046 -
Ear, Nose, & Throat Journal Nov 2023To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce... (Review)
Review
To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce cross-sectional, high-resolution images of biologic tissues, for evaluating the sinonasal mucosa in patients. Original articles utilizing OCT to image the sinonasal mucosa in patients were identified from the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases using the search phrase: "Optical Coherence Tomography" AND (sinonasal OR intranasal OR sinus OR nose OR sinusitis OR rhinitis OR olfactory). Strength of evidence, quality of evidence, and risk of bias were measured using validated scales. Study results were qualitatively assessed. Out of 1662 original records identified through database searching, 9 studies were included in the systematic review. Levels of evidence ranged from III to IV and quality of evidence ranged from moderate to very low. Endoscopic OCT systems as well as OCT systems integrated with surgical microscopes were described in the literature. Applications of OCT for imaging the sinonasal mucosa included identifying morphological patterns unique to individual diseases, detecting mucosal structural changes after medical therapies and procedures, and evaluating mucociliary clearance. Most studies investigating OCT imaging of the sinonasal mucosa featured small sample sizes and lacked control groups. While OCT imaging could be a useful adjunct for diagnosing sinonasal disorders and monitoring response to treatment in the future, additional high-quality studies are necessary to determine if the use of OCT imaging can lead to improved diagnostic accuracy and health outcomes for patients with sinonasal pathologies.
PubMed: 38032064
DOI: 10.1177/01455613231214622 -
Frontiers in Oncology 2023Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB...
BACKGROUND
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.
METHODS
Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.
RESULTS
Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.
CONCLUSION
This study presents data on the genomic and immune landscape of ONB cases in China. and were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.
IMPLICATIONS FOR PRACTICE
In this study, the most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.
PubMed: 38023213
DOI: 10.3389/fonc.2023.1226494 -
Vaccines Nov 2023Polymyxin B (PMB) is an antibiotic that exhibits mucosal adjuvanticity for ovalbumin (OVA), which enhances the immune response in the mucosal compartments of mice....
Polymyxin B (PMB) is an antibiotic that exhibits mucosal adjuvanticity for ovalbumin (OVA), which enhances the immune response in the mucosal compartments of mice. Frequent breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicate that the IgA antibody levels elicited by the mRNA vaccines in the mucosal tissues were insufficient for the prophylaxis of this infection. It remains unknown whether PMB exhibits mucosal adjuvanticity for antigens other than OVA. This study investigated the adjuvanticity of PMB for the virus proteins, hemagglutinin (HA) of influenza A virus, and the S1 subunit and S protein of SARS-CoV-2. BALB/c mice immunized either intranasally or subcutaneously with these antigens alone or in combination with PMB were examined, and the antigen-specific antibodies were quantified. PMB substantially increased the production of antigen-specific IgA antibodies in mucosal secretions and IgG antibodies in plasma, indicating its adjuvanticity for both HA and S proteins. This study also revealed that the PMB-virus antigen complex diameter is crucial for the induction of mucosal immunity. No detrimental effects were observed on the nasal mucosa or olfactory bulb. These findings highlight the potential of PMB as a safe candidate for intranasal vaccination to induce mucosal IgA antibodies for prophylaxis against mucosally transmitted infections.
PubMed: 38006059
DOI: 10.3390/vaccines11111727 -
Pharmaceutics Oct 2023Intranasal administration has attracted attention as a means of delivering drugs because it bypasses the blood-brain barrier. However, conventional intranasal...
Intranasal administration has attracted attention as a means of delivering drugs because it bypasses the blood-brain barrier. However, conventional intranasal administration of drug solutions to mice using the micropipette method (MP method) is complicated and time-consuming because it requires small doses to be administered under inhalation anesthesia. This study evaluated the effectiveness of a novel intranasal administration method using Micro FPS™, a novel micro-spraying device (the MSD method). The MSD method allowed more reliable administration of the solution to the nasal mucosa than the MP method did. The transfer of inulin, a model water-soluble macromolecule compound, to the olfactory bulb and brain (cerebrum, cerebellum, brainstem, and striatum) was similar with the two methods. It also allowed the drug to be administered in a shorter time. These results suggest that the MSD method is simpler and more rapid than the MP method for intranasal administration of drugs to mice and achieves comparable delivery of inulin to the olfactory bulb and brain. Therefore, the Micro FPS™ device is a potentially useful tool for intranasal drug administration to rodents and could facilitate the development of intranasal formulations, contributing to drug development for central nervous system diseases.
PubMed: 38004533
DOI: 10.3390/pharmaceutics15112553 -
Biomolecules Oct 2023Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might... (Review)
Review
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an-at least partial-role in its pathogenesis. In recent years, emerging research has explored the possible involvement of external, invading pathogens in starting or accelerating the neuroinflammatory processes in AD. In this narrative review, we advance the hypothesis that neuroinflammation in AD might be partially caused by viral, bacterial, and fungal pathogens entering the brain through the nose and the olfactory system. The olfactory system represents a plausible route for pathogen entry, given its direct anatomical connection to the brain and its involvement in the early stages of AD. We discuss the potential mechanisms through which pathogens may exploit the olfactory pathway to initiate neuroinflammation, one of them being accidental exposure of the olfactory mucosa to hands contaminated with soil and feces when picking one's nose.
Topics: Humans; Alzheimer Disease; Neuroinflammatory Diseases; Brain; Amyloidogenic Proteins
PubMed: 38002250
DOI: 10.3390/biom13111568