Search Results (395)

This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes. Full article

Ionotropic receptors (IRs) are a divergent subfamily of ionotropic glutamate receptors (iGluRs) that detect olfactory and environmental cues, influencing behaviors such as foraging and adaptation. To explore the evolution of IRs in relation to feeding ecology, we identified IRs and iGluRs from the genomes of four gastropods with distinct diets: Pomacea canaliculata (9 IRs/18 iGluRs), Bellamya purificata (10/22), Cipangopaludina chinensis (11/23), and Babylonia areolata (22/41). IRs were markedly expanded in B. areolata, suggesting lineage-specific diversification. Phylogenetic analysis grouped IRs and iGluRs into three clades, with IRs clustered with GluD, supporting early functional divergence following gene duplication. In all species, IR25b showed tandem duplication and played a central role in protein–protein interaction (PPI) networks. Most IRs were acidic, whereas IR-A and IR-C subgroups were basic, suggesting functional specialization among subfamilies. Structural analysis showed that IRs share conserved domains and motifs across species. Most IRs experienced purifying selection, while P. canaliculata showed relaxed constraints, suggesting weaker functional limitation. Collinearity analysis identified conserved genes, such as BarIR-A.6 and BarIR-D.1, across species. qPCR confirmed tissue-specific expression of IRs in multiple organs. Together, these results reveal the molecular features and evolutionary patterns of IRs in gastropods, highlighting their potential roles in olfaction and dietary adaptation. Full article

Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs—producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory–metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut–brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. Full article

To systematically investigate how the olfactory system of Bombus terrestris adapts to its social division of labor and reproductive strategies, this study integrated the micromorphology of antennal sensilla and the expression profiles of olfactory receptor (OR) genes from the heads of its three castes (workers, drones, and queens) for a multi-level analysis. Scanning electron microscopy (SEM) revealed that drones possess significantly longer chaetic sensilla (Sch), sensilla trichodea (Str A/B), and sensilla basiconica (Sba A), as well as larger-diameter sensilla coeloconica (Sco) compared to workers and queens, indicating structural and functional specialization for sensitive detection of single key signals (e.g., queen pheromones). In contrast, workers and queens exhibited a more complete composition of sensilla types and a higher sensilla distribution density, suggesting the construction of a perceptual system capable of processing multiple chemical signals simultaneously. RNA-seq combined with qRT-PCR confirmed the significant upregulation of seven OR genes (e.g., BterOR3, BterOR4) in drones, while workers showed upregulation of BterOR3/5/7 accompanied by enrichment of P450 detoxification pathways. Phylogenetic analysis suggested that BterOR5 serves as a conserved co-receptor, and some OR genes may originate from recent duplication events. In summary, distinct differences were observed in the morphological structure and molecular expression of the olfactory system among B. terrestris castes. Drones exhibited structural and gene expression features consistent with specialization in queen pheromone detection, while workers and queens demonstrated sensilla diversity and olfactory receptor expression patterns indicative of a broader response capacity to diverse chemical signals. These findings support the view that the olfactory system has undergone multi-level adaptive evolution driven by social division of labor and reproductive roles. Full article

Globally, Spodoptera frugiperda is a major threat to many important crops, including maize, rice, and cotton, causing significant economic damage. To control this invasive pest, environmentally friendly pest control techniques, including pheromone detection and identification of potential molecular targets to disrupt S. frugiperda mating communication, are needed. Female moths biosynthesize pheromones and emit them from the pheromone gland, which significantly depends on the intrinsic factors of the moth. Male S. frugiperda have a sophisticated olfactory circuit on their antennae that recognizes pheromone blends via olfactory receptor neurons (ORNs). With its potential to significantly modify the insect genome, CRISPR/Cas9 offers a revolutionary strategy to control this insect pest. The impairing physiological behaviors and disrupting the S. frugiperda volatile-sensing mechanism are the main potential applications of CRISPR/Ca9 explored in this review. Furthermore, the release of mutant S. frugiperda for their long-term persistence must be integral to the adoption of this technology. Looking forward, CRISPR/Cas9-based gene drive systems have the potential to synergistically target pheromone signaling pathways in S. frugiperda by disrupting pheromone receptors and key biosynthesis genes, thereby effectively blocking intraspecific communication and reproductive success. In conclusion, CRISPR/Cas9 provides an environmentally friendly and revolutionary platform for precise, targeted pest management in S. frugiperda. Full article

Importance: The coronavirus disease 2019 (COVID-19) was the third leading cause of mortality in the United States for three years in a row. The genetic contributions to disease severity remain unclear and many previously identified single nucleotide polymorphisms (SNPs) have not been replicated nor linked with functional significance. Objective: To identify SNPs associated with mortality among hospitalized COVID-19 patients supplemented by expression quantitative trait loci (eQTL) evidence to infer plausible functional mechanisms related to COVID-19 severity. Design: A quality-controlled genome-wide association study (GWAS) supported by robust gene-level omnibus kernel association tests (SKAT-O), functional prediction, and eQTL analyses of the top GWAS signal. Setting: Massachusetts General Hospital (MGH). Participants: 370 adult ICU patients with SARS-CoV-2 infection and acute hypoxemic respiratory failure and floor patients with mild hypoxemia managed with supplemental oxygen consecutively admitted to MGH between March and June 2020 (Surge 1), and January and March 2021 (Surge 2) with baseline clinical characteristics and demographics collected. Exposures: Low-pass genotyped SNPs from whole blood and aggregated SNP-sets of potential disease susceptibility loci with $\pm$500 kb flanking regions. Main Outcomes & Measures: Genome-wide individual SNP associations and SNP-set associations with mortality outcomes from 370 severe COVID-19 cases. Results: After LD pruning (<0.8) and false discovery rate adjustment (<0.05), we identified rs7420371 G>A of the receptor transporter protein 5 (RTP5) gene as the top independent signal significantly associated with 30- and 60-day mortality among severe COVID-19 patients (OR, 2.32; 95% CI, 1.59–3.39; p = 4.92 × 10⁻⁹ and OR, 2.06; 95% CI, 1.43–2.97; p = 5.43 × 10⁻⁸, respectively). SKAT-O analyses on the RTP5 SNP-set showed associations with both mortality outcomes (p = 5.90 × 10⁻⁵ and 6.17 × 10⁻⁵, respectively). eQTL analysis showed rs7420371 A allele significantly upregulated the mRNA expression of RTP5 in 266 cerebellum tissues, in 277 cerebellar hemisphere tissues, and in 270 cerebral cortex samples. Conclusions & Relevance: We discovered a novel, independent, and potentially functional SNP RTP5 rs7420371 G>A to be significantly associated with COVID-19 mortality. The A allele is significantly associated with elevated mRNA expression of RTP5 in the brain, an important protein coding gene that modulates olfactory binding and taste perceptions in response to SARS-CoV-2 infection. Full article

The development of human-robot interfaces that support daily social interaction requires biomimetic innovation inspired by the sensory receptors of the five human senses (tactile, olfactory, gustatory, auditory, and visual) and employing soft materials to enable natural multimodal sensing. The receptors have a structure formulated by variegated shapes; therefore, the morphological mimicry of the structure is critical. We proposed a spring-like structure which morphologically mimics the roll-type structure of the Meissner corpuscle, whose haptic performance in various dynamic motions has been demonstrated in another study. This study demonstrated the gustatory performance by using the roll-type Meissner corpuscle. The gustatory iontronic mechanism was analyzed using electrochemical impedance spectroscopy with an inductance-capacitance-resistance meter to determine the equivalent electric circuit and current-voltage characteristics with a potentiostat, in relation to the hydrogen concentration (pH) and the oxidation-reduction potential. In addition, thermo-sensitivity and tactile responses to shearing and contact were evaluated, since gustation on the tongue operates under thermal and concave-convex body conditions. Based on the established properties, the roll-type Meissner corpuscle sensor enables the iontronic behavior to provide versatile multimodal sensitivity among the five senses. The different condition of the application of the electric field in the production of two-types of A and B Meissner corpuscle sensors induces distinctive features, which include tactility for the dynamic motions (for type A) or gustation (for type B). Full article

The mechanism by which odorants are recognized by olfactory receptors remains primarily unresolved. While charge transport is believed to play a significant role, its precise nature is still unclear. Here, we present a novel perspective by exploring the interplay between the intrinsic energy scales of odorant molecules and the gap states that facilitate intermolecular charge transport. We find that odorants act as weak tunneling conductors mainly because of the limited magnitude of electronic coupling between frontier molecular levels. This behavior is further connected to electron–phonon interaction and reorganization energy, suggesting that physically meaningful values for the latter parameter emerge only in the deep off-resonant tunneling regime. These findings complement the swipe card model of olfaction, in which an odorant needs both the right shape to bind to a receptor and the correct vibrational frequency to trigger signal transduction. Moreover, they reveal that the underlying mechanisms are much more complex than previously assumed. Full article

The vomeronasal system (VNS) is directly linked to the various behavior and ecology of all animal species, and understanding it might help to prevent deer damage. We therefore histochemically analyzed the accessory olfactory bulb (AOB) and the vomeronasal organ (VNO) that, respectively, function as a primary integrative center and a peripheral receptor organ, in Hokkaido sika deer (Cervus nippon ssp. yesoensis). The AOB consisted of the vomeronasal nerve, glomerular, plexiform, and granule cell layers. We found that G protein α subunit i2 (Gαi2) and o (Gαo) that are, respectively, coupled with vomeronasal receptor type 1 and 2 families were strongly and weakly expressed in the glomerular layer, respectively. These properties of the AOB of sika deer were similar to those of other artiodactyl species, including wapiti. We then explored the sika deer VNO using 21 lectins that bind to each glycan structure. Although various cell types in the VNO had unique lectin binding profiles, all 21 lectins bound to the free border of the sensory epithelium, suggesting that various glycoconjugates are involved in pheromone detection in sika deer via the VNO. Furthermore, the reactivity of some lectins in the sensory epithelium and vomeronasal gland differed from those of roe deer and wapiti. Our findings suggest that the composition of glycoconjugates in the VNO differs among deer species. Full article

Olfactory perception depends on soluble proteins in the perireceptor environment that support odorant transport, mucosal protection, and tissue homeostasis. In insects, odorant-binding proteins (OBPs) in the sensillum lymph are indispensable for odor detection, whereas in humans the indispensability of OBPs (OBP2A/2B) remains unclear because they are inconsistently detected in nasal mucus. Consequently, it remains unclear whether other soluble proteins compensate for this function or how they contribute to odorant processing and signal transmission within the olfactory mucus. Accumulating evidence indicates that OBP-like lipocalins (LCN1, LCN2, LCN15) and apolipoprotein D, together with bactericidal/permeability-increasing (BPI)-fold proteins, act as major mediators of odorant solubilization, antimicrobial defense, oxidative stress regulation, and extracellular matrix (ECM) remodeling. Alterations in those proteins and ECM organization are linked to idiopathic and age-related smell loss, chronic rhinosinusitis, and neurodegenerative disorders, underscoring their broad relevance at the interface of chemosensation, mucosal defense, and brain health. Major unresolved issues include the functional indispensability of human OBPs, the receptor-specific contributions of OBP-like proteins, and the mechanistic relationships linking olfactory proteome remodeling, sensory signaling, and disease progression. This review provides an integrative overview of structural and mechanistic insights, highlights current controversies, and proposes future research directions, including receptor–protein mapping, integrated structural–functional studies, structural–functional analysis of OBP–ECM networks, and clinical validation of OBP-related biomarkers. Full article

The RNAs present in spermatozoa play a crucial role in reproduction and embryonic development. They represent a promising diagnostic tool for assessing male infertility. However, their extraction is challenging due to their low concentration and highly condensed chromatin structure, as well as the presence of numerous cellular contaminants. These challenges vary across species and require the development of an optimized and reliable isolation method to obtain high-quality RNAs, which is essential for further molecular analyses regarding the roles played by these RNAs. This study evaluated two RNA extraction methods for spermatozoa in humans and other mammals (dogs, stallions, and bulls): a standard method using the NucleoSpin RNA^® II kit (Macherey-Nagel) and an optimized method that combined this kit with dithiothreitol and TRIzol™ pretreatment. In addition, the samples underwent pre-purification to eliminate somatic cells. The optimized method produced a significantly higher total RNA yield along with better purity, which was confirmed by the absence of the 18S and 28S ribosomal RNA peaks, indicating the absence of somatic cell contamination. Additionally, RT-PCR was performed to validate the presence of sperm-specific markers. The quality of the extracted RNAs was assessed by sequencing the mRNA encoding the human olfactory receptor OR1D2 and observing the resulting band on an agarose slab gel with a size corresponding to its entire open reading frame. By addressing long-standing challenges in sperm RNA isolation, our method provides an easy and standardized technique for research in reproductive biology and for advancing our understanding of paternal contributions to transgenerational inheritance. Full article

Biomimetic olfactory and taste biosensors replicate human sensory functions by coupling selective biological recognition elements (such as receptors, binding proteins, or synthetic mimics) with highly sensitive transducers (including electrochemical, transistor, optical, and mechanical types). This review summarizes recent progress in olfactory and taste biosensors focusing on three key areas: (i) materials and device design, (ii) artificial intelligence (AI) and data fusion for real-time decision-making, and (iii) pathways for practical application, including hybrid platforms, Internet of Things (IoT) connectivity, and regulatory considerations. We provide a comparative analysis of smell and taste sensing methods, emphasizing cases where integrating both modalities enhances sensitivity, selectivity, detection limits, and reliability in complex environments like food, environmental monitoring, healthcare, and security. Ongoing challenges are addressed with emerging solutions such as antifouling/self-healing interfaces, modular cartridges, machine learning (ML)-assisted calibration, and manufacturing-friendly approaches using scalable microfabrication and sustainable materials. The review concludes with a practical roadmap advocating for the joint development of receptors, materials, and algorithms; establishment of open standards for long-term stability; implementation of explainable/edge AI with privacy-focused analytics; and proactive collaboration with regulatory bodies. Collectively, these strategies aim to advance biomimetic smell and taste biosensors from experimental prototypes to dependable, commercially viable tools for continuous chemical sensing in real-world applications. Full article

Odorant receptors (ORs) in Drosophila melanogaster represent important proteins of the insect’s olfactory system, enabling the detection of environmental cues such as food sources, host plants, and mating signals. Their modulation by natural ligands offers a sustainable strategy for pest management, particularly through the use of bioactive compounds obtained from agricultural crop and food production residues (ACFPR). In this study, as a model we employed the AlphaFold-predicted structure of the odorant receptor Q9W1P8 for structure-based virtual screening. Molecular docking was carried out using GNINA, a deep learning-enhanced docking tool. Screening of 164 ACFPR-derived compounds from different sources revealed several strong binders, including α-tomatine, peonidin 3-rutinoside, and cinnamtannin B1. Predicted binding modes support the role of plant-derived molecules as candidate modulators of insect olfactory receptors. These findings highlight the utility of integrating AlphaFold models with advanced docking platforms to support the development of sustainable pest management strategies. Full article

Bactrocera dorsalis Hendel is a devastating invasive pest that costs billions of dollars in agricultural losses worldwide. Current control strategies rely heavily on male-specific attractants such as methyl eugenol, which are less effective against females, underscoring the need for female-targeted control approaches. Here, we investigated the molecular mechanisms underlying female attraction to cis-linalool oxide by functionally characterizing the odorant receptor OR45a, identifying it as a molecular target for female-oriented pest management. We conducted spatiotemporal expression analysis of OR45a in response to cis-linalool oxide, followed by RNAi and behavioral assays. Phylogenetic analysis of OR45a orthologs from 10 Dipteran species, combined with structural topology prediction and solvent-accessible surface area (ASA) analysis, helped identify functional domains and residues. Site-directed mutagenesis and two-electrode voltage clamp (TEVC) recordings validated receptor–ligand interactions. Results showed that OR45a was specifically upregulated in antennae, with peak expression at 10 days post-eclosion, coinciding with oviposition periods. RNAi significantly reduced OR45a transcript levels and female behavioral responses to cis-linalool oxide. Phylogenetic analysis showed that OR45a is highly conserved within Tephritidae but diverges from Drosophilidae, with closest similarity to Anastrepha ludens, indicating ecological specialization. Structural modeling predicted a canonical seven-transmembrane architecture with three extracellular loops forming the ligand-binding pocket. Among five key residues identified, Leu122 and Ile146 were essential for ligand recognition, while Tyr107 contributed to protein stability. These findings reveal a female-specific odorant receptor mechanism in B. dorsalis and provide molecular targets for OR45a-based attractants, addressing a critical gap in female-focused pest management. Full article

Anastatus orientalis, a prominent egg parasitoid of Lycorma delicatula, demonstrates considerable potential for biological control. A. orientalis is dependent on host volatiles to identify and locate appropriate hosts for reproduction, with its olfactory system playing a vital role in volatile detection. There is little known about the chemosensory genes in A. orientalis. Therefore, here, we conducted a transcriptome analysis of the males and females from A. orientalis. Overall, 24 odorant binding proteins (OBPs), 4 chemosensory proteins (CSPs), 26 odorant receptors (ORs), 3 gustatory receptors (GRs), 3 ionotropic receptors (IRs), and 2 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. The values for fragments per kilobase per million (FPKM) indicated that the chemosensory protein gene families in A. orientalis exhibit different expression levels in male and female adults, with some genes showing significant differences and displaying sex-biased expression. Furthermore, RACE technology, phylogenetic analysis, and expression analysis were used to investigate the role that AoOBP8 plays in olfaction in A. orientalis. AoOBP8 was highly expressed in females and the heads of adults, indicating that the gene has a crucial role to play in the search for hosts and in oviposition in female adults, while the head is crucial in recognizing chemical information. These results contribute to a deeper understanding of the functions of chemosensory protein gene families in A. orientalis and offer a reference for developing biocontrol methods for forestry pests. Full article