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Frontiers in Behavioral Neuroscience 2022Learning to identify and predict threats is a basic skill that allows animals to avoid harm. Studies in invertebrates like , and have revealed that the basic mechanisms... (Review)
Review
Learning to identify and predict threats is a basic skill that allows animals to avoid harm. Studies in invertebrates like , and have revealed that the basic mechanisms of learning and memory are conserved. We will summarize these studies and highlight the common pathways and mechanisms in invertebrate fear-associated behavioral changes. Fear conditioning studies utilizing electric shock in and have demonstrated that serotonin or dopamine are typically involved in relaying aversive stimuli, leading to changes in intracellular calcium levels and increased presynaptic neurotransmitter release and short-term changes in behavior. Long-term changes in behavior typically require multiple, spaced trials, and involve changes in gene expression. studies have demonstrated these basic aversive learning principles as well; however, fear conditioning has yet to be explicitly demonstrated in this model due to stimulus choice. Because predator-prey relationships can be used to study learned fear in a naturalistic context, this review also summarizes what is known about predator-induced behaviors in these three organisms, and their potential applications for future investigations into fear conditioning.
PubMed: 36439964
DOI: 10.3389/fnbeh.2022.1008818 -
Cold Spring Harbor Perspectives in... Dec 2019When protein/peptides aggregate, they usually form the amyloid state consisting of cross β-sheet structure built by repetitively stacked β-strands forming long... (Review)
Review
When protein/peptides aggregate, they usually form the amyloid state consisting of cross β-sheet structure built by repetitively stacked β-strands forming long fibrils. Amyloids are usually associated with disease including Alzheimer's. However, amyloid has many useful features. It efficiently transforms protein from the soluble to the insoluble state in an essentially two-state process, while its repetitive structure provides high stability and a robust prion-like replication mechanism. Accordingly, amyloid is used by nature in multifaceted and ingenious ways of life, ranging from bacteria and fungi to mammals. These include (1) Structure: Templating for small chemical molecules (Pmel17), biofilm formation in bacteria (curli), assisting aerial hyphae formation in streptomycetes (chaplins) or monolayer formation at a surface (hydrophobins). (2) Reservoirs: A storage state for peptide/proteins to protect them from their surroundings or vice versa (storage of peptide hormones in mammalian secretory granules or major basic protein in eosinophils). (3) Information carriers: The fungal immune system (HET-s prion in , yeast prions) or long-term memory (e.g., mnemons in yeast, cytoplasmic polyadenylation element-binding protein in aplysia). Aggregation is also used to (4) "suppress" the function of the soluble protein (e.g., Cdc19 in yeast stress granules), or (5) "signaling" through formation of oligomers (e.g., HET-s prion, necroptosis-related proteins RIP1/RIP3). This review summarizes current knowledge on functional amyloids with a focus on the amyloid systems curli in bacteria, HET-s prion in , and peptide hormone storage in mammals together with an attempt to highlight differences between functional and disease-associated amyloids.
Topics: Amyloid; Bacteria; Fungi; Structure-Activity Relationship
PubMed: 31088827
DOI: 10.1101/cshperspect.a033860 -
JACC. Cardiovascular Interventions Dec 2021
Topics: Heart Ventricles; Humans; Shock, Cardiogenic; Treatment Outcome
PubMed: 34949395
DOI: 10.1016/j.jcin.2021.10.012 -
Trends in Neurosciences Mar 2023Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons... (Review)
Review
Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal groups as a physiological response that can increase survival long after bodily injury, using both highly conserved and divergent underlying mechanisms.
Topics: Humans; Animals; Nociceptors; Sensory Receptor Cells; Neuralgia; Adaptation, Physiological
PubMed: 36610893
DOI: 10.1016/j.tins.2022.12.007 -
Neuropharmacology Nov 2021Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the... (Review)
Review
Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.
Topics: Animals; Biological Evolution; Glutamic Acid; Receptors, Glutamate; Signal Transduction; Synapses
PubMed: 34343611
DOI: 10.1016/j.neuropharm.2021.108740 -
Proceedings of the National Academy of... Sep 2021Habituation and sensitization (nonassociative learning) are among the most fundamental forms of learning and memory behavior present in organisms that enable adaptation...
Habituation and sensitization (nonassociative learning) are among the most fundamental forms of learning and memory behavior present in organisms that enable adaptation and learning in dynamic environments. Emulating such features of intelligence found in nature in the solid state can serve as inspiration for algorithmic simulations in artificial neural networks and potential use in neuromorphic computing. Here, we demonstrate nonassociative learning with a prototypical Mott insulator, nickel oxide (NiO), under a variety of external stimuli at and above room temperature. Similar to biological species such as , habituation and sensitization of NiO possess time-dependent plasticity relying on both strength and time interval between stimuli. A combination of experimental approaches and first-principles calculations reveals that such learning behavior of NiO results from dynamic modulation of its defect and electronic structure. An artificial neural network model inspired by such nonassociative learning is simulated to show advantages for an unsupervised clustering task in accuracy and reducing catastrophic interference, which could help mitigate the stability-plasticity dilemma. Mott insulators can therefore serve as building blocks to examine learning behavior noted in biology and inspire new learning algorithms for artificial intelligence.
Topics: Algorithms; Animals; Aplysia; Artificial Intelligence; Electrons; Insulator Elements; Models, Neurological; Neural Networks, Computer; Neuronal Plasticity; Nickel; Synapses
PubMed: 34531299
DOI: 10.1073/pnas.2017239118 -
Molecules (Basel, Switzerland) Feb 2020Invertebrates are an important source of structurally-diverse and biologically-active halogenated metabolites. The sea hare Rang has long been known to possess... (Review)
Review
Invertebrates are an important source of structurally-diverse and biologically-active halogenated metabolites. The sea hare Rang has long been known to possess halogenated metabolites of dietary origin that are used as a self-defense mechanism. The compounds from Rang are comprised mainly of terpenoids and small percentages of C-15 acetogenins, indoles, macrolides, sterols and alkaloids with potent cytotoxic, anti-microbial and anti-inflammatory properties. For decades the metabolites discovered have been investigated for their medical and pharmaceutical applications, so much so that the ecological role of the metabolites has been overlooked. The interaction between Rang and its diet that is comprised of seaweed can provide information into the distribution and diversity of the seaweed, the application of bioaccumulated secondary metabolites as part of its defense mechanism and the potential roles of these metabolites for adaptation in the marine environment. This paper compiles the diversity of halogenated secondary metabolites documented from Rang.
Topics: Acetogenins; Alkaloids; Animals; Aplysia; Halogenation; Indoles; Macrolides; Seaweed; Sterols
PubMed: 32070000
DOI: 10.3390/molecules25040815 -
Nature Chemical Biology Oct 2023Phe-Met-Arg-Phe-amide (FMRFamide)-activated sodium channels (FaNaCs) are a family of channels activated by the neuropeptide FMRFamide, and, to date, the underlying...
Phe-Met-Arg-Phe-amide (FMRFamide)-activated sodium channels (FaNaCs) are a family of channels activated by the neuropeptide FMRFamide, and, to date, the underlying ligand gating mechanism remains unknown. Here we present the high-resolution cryo-electron microscopy structures of Aplysia californica FaNaC in both apo and FMRFamide-bound states. AcFaNaC forms a chalice-shaped trimer and possesses several notable features, including two FaNaC-specific insertion regions, a distinct finger domain and non-domain-swapped transmembrane helix 2 in the transmembrane domain (TMD). One FMRFamide binds to each subunit in a cleft located in the top-most region of the extracellular domain, with participation of residues from the neighboring subunit. Bound FMRFamide adopts an extended conformation. FMRFamide binds tightly to A. californica FaNaC in an N terminus-in manner, which causes collapse of the binding cleft and induces large local conformational rearrangements. Such conformational changes are propagated downward toward the TMD via the palm domain, possibly resulting in outward movement of the TMD and dilation of the ion conduction pore.
Topics: FMRFamide; Cryoelectron Microscopy; Ion Channel Gating; Neuropeptides; Sodium Channels
PubMed: 37550431
DOI: 10.1038/s41589-023-01401-7 -
Journal of Biotechnology Nov 2022Simultaneous coexpression of multiple proteins is essential for biotechnology and synthetic biology. Currently, the most popular polyprotein coexpression system utilizes...
Simultaneous coexpression of multiple proteins is essential for biotechnology and synthetic biology. Currently, the most popular polyprotein coexpression system utilizes the foot-and-mouth disease virus (FMDV) 2A peptide that mediates translational ribosome-skipping events. However, due to unfavorable consumer acceptance of transgenic products containing animal-virus sequences, novel non-viral 2A-like peptides from purple sea urchin (Strongylcentrotus purpuratus) and California sea slug (Aplysia californica) were investigated for polyprotein coexpression in this study. We demonstrated that these non-viral 2A sequences functioned similarly to their viral counterpart in polyprotein processing, in both plant and mammalian cells, and were successfully used to express a functional recombinant antibody. The new non-viral 2A-like sequences offer an alternative tool for engineering multigenic traits or production of protein complexes as biomedicine via coexpression of protein subunits.
Topics: Animals; Foot-and-Mouth Disease Virus; Mammals; Peptides; Polyproteins; Protein Subunits; Viral Proteins
PubMed: 35995093
DOI: 10.1016/j.jbiotec.2022.08.014 -
Small GTPases 2021Since the discovery by Madaule and Axel in 1985 of the first Ras homologue (Rho) protein in and its human orthologue RhoB, membership in the Rho GTPase family has grown... (Review)
Review
Since the discovery by Madaule and Axel in 1985 of the first Ras homologue (Rho) protein in and its human orthologue RhoB, membership in the Rho GTPase family has grown to 20 proteins, with representatives in all eukaryotic species. These GTPases are molecular switches that cycle between active (GTP bound) and inactivate (GDP bound) states. The exchange of GDP for GTP on Rho GTPases is facilitated by guanine exchange factors (GEFs). Approximately 80 Rho GEFs have been identified to date, and only a few GEFs associate with microtubules. The guanine nucleotide exchange factor H1, GEF-H1, is a unique GEF that associates with microtubules and is regulated by the polymerization state of microtubule networks. This review summarizes the regulation and functions of GEF-H1 and discusses the roles of GEF-H1 in human diseases.
Topics: Animals; Disease; Gene Expression Regulation; Humans; Microtubules; Rho Guanine Nucleotide Exchange Factors
PubMed: 33126816
DOI: 10.1080/21541248.2020.1840889