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Aging Cell Jun 2024The molecular mechanisms underlying age-related declines in learning and long-term memory are still not fully understood. To address this gap, our study focused on...
The molecular mechanisms underlying age-related declines in learning and long-term memory are still not fully understood. To address this gap, our study focused on investigating the transcriptional landscape of a singularly identified motor neuron L7 in Aplysia, which is pivotal in a specific type of nonassociative learning known as sensitization of the siphon-withdraw reflex. Employing total RNAseq analysis on a single isolated L7 motor neuron after short-term or long-term sensitization (LTS) training of Aplysia at 8, 10, and 12 months (representing mature, late mature, and senescent stages), we uncovered aberrant changes in transcriptional plasticity during the aging process. Our findings specifically highlight changes in the expression of messenger RNAs (mRNAs) that encode transcription factors, translation regulators, RNA methylation participants, and contributors to cytoskeletal rearrangements during learning and long noncoding RNAs (lncRNAs). Furthermore, our comparative gene expression analysis identified distinct transcriptional alterations in two other neurons, namely the motor neuron L11 and the giant cholinergic neuron R2, whose roles in LTS are not yet fully elucidated. Taken together, our analyses underscore cell type-specific impairments in the expression of key components related to learning and memory within the transcriptome as organisms age, shedding light on the complex molecular mechanisms driving cognitive decline during aging.
PubMed: 38924663
DOI: 10.1111/acel.14228 -
Biological Cybernetics Jun 2024The coordination of complex behavior requires knowledge of both neural dynamics and the mechanics of the periphery. The feeding system of Aplysia californica is an...
The coordination of complex behavior requires knowledge of both neural dynamics and the mechanics of the periphery. The feeding system of Aplysia californica is an excellent model for investigating questions in soft body systems' neuromechanics because of its experimental tractability. Prior work has attempted to elucidate the mechanical properties of the periphery by using a Hill-type muscle model to characterize the force generation capabilities of the key protractor muscle responsible for moving Aplysia's grasper anteriorly, the I2 muscle. However, the I1/I3 muscle, which is the main driver of retractions of Aplysia's grasper, has not been characterized. Because of the importance of the musculature's properties in generating functional behavior, understanding the properties of muscles like the I1/I3 complex may help to create more realistic simulations of the feeding behavior of Aplysia, which can aid in greater understanding of the neuromechanics of soft-bodied systems. To bridge this gap, in this work, the I1/I3 muscle complex was characterized using force-frequency, length-tension, and force-velocity experiments and showed that a Hill-type model can accurately predict its force-generation properties. Furthermore, the muscle's peak isometric force and stiffness were found to exceed those of the I2 muscle, and these results were analyzed in the context of prior studies on the I1/I3 complex's kinematics in vivo.
PubMed: 38922432
DOI: 10.1007/s00422-024-00990-3 -
Developmental and Comparative Immunology Jun 2024The California sea hare (Aplysia californica) is a model for age associated cognitive decline. Recent researched identified a novel nidovirus, Aplysia Abyssovirus 1,...
The California sea hare (Aplysia californica) is a model for age associated cognitive decline. Recent researched identified a novel nidovirus, Aplysia Abyssovirus 1, with broad tropism enriched in the Aplysia nervous system. This virus is ubiquitous in wild and maricultured, young and old animals without obvious pathology. Here we re-evaluated gene expression data from several previous studies to investigate differential expression in the nervous system and gill in response to virus and aging as well as the mutational spectrum observed in the viral sequences obtained from these datasets. Viral load and age were highly correlated, indicating persistent infection. Upregulated genes in response to virus were enriched for immune genes and signatures of ER and proteostatic stress, while downregulated genes were enriched for mitochondrial metabolism. Differential expression with respect to age suggested increased iron accumulation and decreased glycolysis, fatty acid metabolism, and proteasome function. Interaction of gene expression trends associated with viral infection and aging suggest that viral infection likely plays a role in aging in the Aplysia nervous system. Mutation analysis of viral RNA identified signatures suggesting ADAR and AID/APOBEC like deaminase act as part of Aplysia anti-viral defense.
PubMed: 38885747
DOI: 10.1016/j.dci.2024.105211 -
The Journal of Comparative Neurology Jun 2024Gastropod molluscs such as Aplysia, Lymnaea, and Tritonia have been important for determining fundamental rules of motor control, learning, and memory because of their...
Gastropod molluscs such as Aplysia, Lymnaea, and Tritonia have been important for determining fundamental rules of motor control, learning, and memory because of their large, individually identifiable neurons. Yet only a small number of gastropod neurons have known molecular markers, limiting the ability to establish brain-wide structure-function relations. Here we combine high-throughput, single-cell RNA sequencing with in situ hybridization chain reaction in the nudibranch Berghia stephanieae to identify and visualize the expression of markers for cell types. Broad neuronal classes were characterized by genes associated with neurotransmitters, like acetylcholine, glutamate, serotonin, and GABA, as well as neuropeptides. These classes were subdivided by other genes including transcriptional regulators and unannotated genes. Marker genes expressed by neurons and glia formed discrete, previously unrecognized regions within and between ganglia. This study provides the foundation for understanding the fundamental cellular organization of gastropod nervous systems.
Topics: Animals; Gastropoda; Ganglia, Invertebrate; Neurons; Head; Gene Expression
PubMed: 38852042
DOI: 10.1002/cne.25628 -
Journal of Agricultural and Food... Jun 2024Structure-activity relationships of diazinoyl nicotinic insecticides (diazinoyl isomers and 5- or 6-substituted pyrazin-2-oyl analogues) are considered in terms of...
Structure-activity relationships of diazinoyl nicotinic insecticides (diazinoyl isomers and 5- or 6-substituted pyrazin-2-oyl analogues) are considered in terms of affinity to the insect nicotinic acetylcholine receptor (nAChR) and insecticidal activity against the imidacloprid-resistant brown planthopper. Among the test compounds, 3-(6-chloropyridin-3-ylmethyl)-2-(pyrazinoyl)iminothiazoline shows the highest potency in nAChR affinity and insecticidal activity. acetylcholine binding protein (AChBP) mutants (Y55W + Q57R and Y55W + Q57T) are utilized to compare molecular recognition of nicotinic insecticides with diverse pharmacophores. -nitro- or -cyanoimine imidacloprid or acetamiprid, respectively, exhibits a high affinity to these AChBP mutants at a similar potency level. Intriguingly, the pyrazin-2-oyl analogue has a higher affinity to AChBP Y55W + Q57R than that to Y55W + Q57T, thereby indicating that pyrazine nitrogen atoms contact Arg57 guanidinium and Trp55 indole NH. Furthermore, nicotine prefers AChBP Y55W + Q57T over Y55W + Q57R, conceivably suggesting that the protonated nicotine is repulsed by Arg57 guanidinium, consistent with its inferior potency to insect nAChR.
Topics: Animals; Insecticides; Receptors, Nicotinic; Hemiptera; Structure-Activity Relationship; Insect Proteins; Neonicotinoids; Nitro Compounds; Aplysia; Nicotine
PubMed: 38814790
DOI: 10.1021/acs.jafc.4c01499 -
ACS Chemical Neuroscience Jun 2024Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channel receptors that contribute to cognition, memory, and motor control in many organisms....
Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channel receptors that contribute to cognition, memory, and motor control in many organisms. The pharmacological targeting of these receptors, using small molecules or peptides, presents an important strategy for the development of drugs that can treat important human diseases, including neurodegenerative disorders. The acetylcholine binding protein (Ac-AChBP) is a structural surrogate of the nAChR with high homology to the extracellular ligand binding domain of homopentameric nAChRs. In this study, we optimized protein-painting-based mass spectrometry to identify regions of interaction between the Ac-AChBP and several nAChR ligands. Using molecular dyes that adhere to the surface of a solubilized Ac-AChBP complex, we identified amino acid residues that constitute a contact site within the Ac-AChBP for α-bungarotoxin, choline, nicotine, and amyloid-β 1-42. By integrating innovation in protein painting mass spectrometry with computational structural modeling, we present a new experimental tool for analyzing protein interactions of the nAChR.
Topics: Animals; Aplysia; Receptors, Nicotinic; Mass Spectrometry; Binding Sites; Protein Binding; Carrier Proteins; Bungarotoxins; Acetylcholine; Amyloid beta-Peptides; Models, Molecular
PubMed: 38804618
DOI: 10.1021/acschemneuro.4c00149 -
Biological Cybernetics May 2024Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of...
Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding.
PubMed: 38769189
DOI: 10.1007/s00422-024-00991-2 -
ACS Biomaterials Science & Engineering Jun 2024In recent years, a novel treatment method for cancer has emerged, which is based on the starvation of tumors of amino acids like arginine. The deprivation of arginine in...
In recent years, a novel treatment method for cancer has emerged, which is based on the starvation of tumors of amino acids like arginine. The deprivation of arginine in serum is based on enzymatic degradation and can be realized by arginine deaminases like the l-amino acid oxidase found in the ink toxin of the sea hare . Previously isolated from the ink, the l-amino acid oxidase was described to oxidate the essential amino acids l-lysine and l-arginine to their corresponding deaminated alpha-keto acids. Here, we present the recombinant production and functionalization of the amino acid oxidase ink toxin (APIT). PEGylated APIT (APIT-PEG) increased the blood circulation time. APIT-PEG treatment of patient-derived xenografted mice shows a significant dose-dependent reduction of tumor growth over time mediated by amino acid starvation of the tumor. Treatment of mice with APIT-PEG, which led to deprivation of arginine, was well tolerated.
Topics: Animals; Arginine; Lysine; Polyethylene Glycols; Humans; Aplysia; Mice; Xenograft Model Antitumor Assays; Marine Toxins; Recombinant Proteins; L-Amino Acid Oxidase; Female; Cell Line, Tumor
PubMed: 38722049
DOI: 10.1021/acsbiomaterials.4c00473 -
Highly stretchable and customizable microneedle electrode arrays for intramuscular electromyography.Science Advances May 2024Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable...
Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable bioelectronics. These 3D microelectrode arrays can penetrate and conform to dynamically deforming tissues, thereby facilitating targeted sensing and stimulation of interior regions in a minimally invasive manner. However, fabricating custom stretchable 3D microelectrode arrays presents material integration and patterning challenges. In this study, we present the design, fabrication, and applications of stretchable microneedle electrode arrays (SMNEAs) for sensing local intramuscular electromyography signals ex vivo. We use a unique hybrid fabrication scheme based on laser micromachining, microfabrication, and transfer printing to enable scalable fabrication of individually addressable SMNEA with high device stretchability (60 to 90%). The electrode geometries and recording regions, impedance, array layout, and length distribution are highly customizable. We demonstrate the use of SMNEAs as bioelectronic interfaces in recording intramuscular electromyography from various muscle groups in the buccal mass of .
Topics: Electromyography; Needles; Microelectrodes; Animals; Equipment Design; Electrodes; Muscle, Skeletal; Humans
PubMed: 38691612
DOI: 10.1126/sciadv.adn7202 -
Scandinavian Journal of Pain Jan 2024Although the relationship between traumatic experiences (TEs) and psychosomatic manifestations (pain, somatization, somatosensory amplification [SSA], and alexithymia)...
OBJECTIVES
Although the relationship between traumatic experiences (TEs) and psychosomatic manifestations (pain, somatization, somatosensory amplification [SSA], and alexithymia) has been widely described, very few studies have investigated how these variables correlate with each other and with a history of TEs. The aim of this study was to investigate whether and how current psychosomatic manifestations are correlated with major and minor adult- and childhood TEs.
METHODS
One hundred and forty-six patients (91 with pain) from the Pisa Gift Institute for Integrative Medicine Psychosomatics Lab., Italy, were assessed for pain, history of TEs (divided into major and minor based on whether or not they meet the DSM-5 Criterion A for post-traumatic stress disorder), alexithymia, somatization, and SSA.
RESULTS
TEs were positively correlated with age, the sensorial dimension and intensity of pain, somatization, psychopathology index, SSA, and alexithymia. Using the somatization score (controlled for age) as a covariate, the previous correlations between psychosomatic dimensions and TEs lost their statistical significance: SSA (total TEs: from = 0.30, = 0.000 to = -0.04, = 0.652); alexithymia (total TEs: from = 0.28, = 0.001 to = 0.04, = 0.663); sensorial dimension of pain (total TEs: from = 0.30, = 0.015 to = 0.12, = 0.373); and pain intensity (total TEs: from = 0.38, = 0.004 to = -0.15, = 0.317). Interestingly, the tendency to report more intense pain was mainly predicted by minor TEs in childhood ( = 0.28; = 0.030).
CONCLUSIONS
The number of lifetime TEs is positively correlated with the sensorial dimension and intensity of pain but not its affective and cognitive dimensions. However, the former relationship depends on the presence of somatization. The intensity of pain is associated with minor rather than major TEs, especially when they occur in childhood.
Topics: Humans; Male; Female; Affective Symptoms; Adult; Middle Aged; Somatoform Disorders; Psychophysiologic Disorders; Pain; Stress Disorders, Post-Traumatic; Young Adult; Aged; Italy
PubMed: 38661113
DOI: 10.1515/sjpain-2023-0102