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Journal of Neural Engineering Mar 2021. Accurate inference of functional connectivity is critical for understanding brain function. Previous methods have limited ability distinguishing between direct and...
. Accurate inference of functional connectivity is critical for understanding brain function. Previous methods have limited ability distinguishing between direct and indirect connections because of inadequate scaling with dimensionality. This poor scaling performance reduces the number of nodes that can be included in conditioning. Our goal was to provide a technique that scales better and thereby enables minimization of indirect connections.. Our major contribution is a powerful model-free framework, graphical directed information (GDI), that enables pairwise directed functional connections to be conditioned on the activity of substantially more nodes in a network, producing a more accurate graph of functional connectivity that reduces indirect connections. The key technology enabling this advancement is a recent advance in the estimation of mutual information (MI), which relies on multilayer perceptrons and exploiting an alternative representation of the Kullback-Leibler divergence definition of MI. Our second major contribution is the application of this technique to both discretely valued and continuously valued time series.. GDI correctly inferred the circuitry of arbitrary Gaussian, nonlinear, and conductance-based networks. Furthermore, GDI inferred many of the connections of a model of a central pattern generator circuit in, while also reducing many indirect connections.. GDI is a general and model-free technique that can be used on a variety of scales and data types to provide accurate direct connectivity graphs and addresses the critical issue of indirect connections in neural data analysis.
Topics: Brain; Magnetic Resonance Imaging; Models, Neurological; Nerve Net; Neural Networks, Computer
PubMed: 33684898
DOI: 10.1088/1741-2552/abecc6 -
Frontiers in Pharmacology 2023The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both...
The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc and Octopus, no precursor or receptors have been described in mollusc . Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for vasopressin-like peptide, which we named vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity.
PubMed: 37021048
DOI: 10.3389/fphar.2023.1132066 -
Journal of Natural Products Aug 2022New bromoditerpenes having an α-methylene carbonyl structure, azuriaplysins A () and B (), were isolated from the sea hare . Their relative stereostructures were... (Review)
Review
New bromoditerpenes having an α-methylene carbonyl structure, azuriaplysins A () and B (), were isolated from the sea hare . Their relative stereostructures were determined based on one- and two-dimensional NMR spectroscopic analysis. In addition, the absolute stereostructures were determined by the total synthesis of both enantiomers of azuriaplysins A () and B (), the key points of which were bromocyclization of farnesol and optical resolution of a key intermediate. Azuriaplysin B () and its enantiomer exhibited moderate cytotoxicity against HeLa S3 cells.
Topics: Animals; Aplysia; Hares; Magnetic Resonance Spectroscopy; Stereoisomerism
PubMed: 35834804
DOI: 10.1021/acs.jnatprod.2c00476 -
Journal of Proteome Research Oct 2023Protein database search engines are an integral component of mass spectrometry-based peptidomic analyses. Given the unique computational challenges of peptidomics, many...
Protein database search engines are an integral component of mass spectrometry-based peptidomic analyses. Given the unique computational challenges of peptidomics, many factors must be taken into consideration when optimizing search engine selection, as each platform has different algorithms by which tandem mass spectra are scored for subsequent peptide identifications. In this study, four different database search engines, PEAKS, MS-GF+, OMSSA, and X! Tandem, were compared with and peptidomics data sets, and various metrics were assessed such as the number of unique peptide and neuropeptide identifications, and peptide length distributions. Given the tested conditions, PEAKS was found to have the highest number of peptide and neuropeptide identifications out of the four search engines in both data sets. Furthermore, principal component analysis and multivariate logistic regression were employed to determine whether specific spectral features contribute to false C-terminal amidation assignments by each search engine. From this analysis, it was found that the primary features influencing incorrect peptide assignments were the precursor and fragment ion / errors. Finally, an assessment employing a mixed species protein database was performed to evaluate search engine precision and sensitivity when searched against an enlarged search space containing human proteins.
Topics: Humans; Animals; Rats; Search Engine; Peptides; Algorithms; Tandem Mass Spectrometry; Neuropeptides; Databases, Protein; Software
PubMed: 36809008
DOI: 10.1021/acs.jproteome.2c00307 -
The FEBS Journal Feb 2023So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an 'Unexpected expansion of the...
So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an 'Unexpected expansion of the voltage-gated proton channel family'. They searched for proton channel candidates and found three sequences in the genome of Aplysia californica (Ac), which were named AcHv1, AcHv2 and AcHv3. Based on electrophysiological experiments, AcHv1 and AcHv2 are voltage-gated channels. While AcHv1 behaves like Hv1 in other species, that is, it is voltage and pH-dependent, it can be inhibited by zinc and conducts protons outwardly, AcHv2 conducts protons inwards at symmetrical pH. AcHv3 constantly leaks protons, and its C-terminal part contains several cytoplasmic retention motifs. Through carefully designed and carried out electrophysiological experiments, Chaves et al. determined the biophysical parameters of all three proton channels, such as the voltage and the pH dependence, the threshold-voltage, the gating charge and the time constants of activation and inactivation. Comment on: https://doi.org/10.1111/febs.16617.
Topics: Protons; Ion Channel Gating; Ion Channels; Zinc
PubMed: 36315610
DOI: 10.1111/febs.16670 -
Journal of Molecular Neuroscience : MN Feb 2022Although Alzheimer's disease (AD) is the most common form of dementia in the United States, development of therapeutics has proven difficult. Invertebrate alternatives...
Although Alzheimer's disease (AD) is the most common form of dementia in the United States, development of therapeutics has proven difficult. Invertebrate alternatives to current mammalian AD models have been successfully employed to study the etiology of the molecular hallmarks of AD. The marine snail Aplysia californica offers a unique and underutilized system in which to study the physiological, behavioral, and molecular impacts of AD. Mapping of the Aplysia proteome to humans and cross-referencing with two databases of genes of interest in AD research identified 898 potential orthologs of interest in Aplysia. Included among these orthologs were alpha, beta and gamma secretases, amyloid-beta, and tau. Comparison of age-associated differential expression in Aplysia sensory neurons with that of late-onset AD in the frontal lobe identified 59 ortholog with concordant differential expression across data sets. The 21 concordantly upregulated genes suggested increased cellular stress and protein dyshomeostasis. The 47 concordantly downregulated genes included important components of diverse neuronal processes, including energy metabolism, mitochondrial homeostasis, synaptic signaling, Ca regulation, and cellular cargo transport. Compromised functions in these processes are known hallmarks of both human aging and AD, the ramifications of which are suggested to underpin cognitive declines in aging and neurodegenerative disease.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Aplysia; Humans; Mammals; Neurodegenerative Diseases; Neurons; tau Proteins
PubMed: 34664226
DOI: 10.1007/s12031-021-01918-3 -
ELife Nov 2020Sea slugs increase the longevity of the chloroplasts they steal from algae by limiting the harmful side-effects of photosynthesis.
Sea slugs increase the longevity of the chloroplasts they steal from algae by limiting the harmful side-effects of photosynthesis.
Topics: Animals; Aplysia; Chloroplasts; Gastropoda; Photosynthesis; Theft
PubMed: 33215989
DOI: 10.7554/eLife.64057 -
Journal of Visualized Experiments : JoVE Jun 2022The nematode Caenorhabditis elegans is an attractive model organism to study learning and memory at molecular and cellular levels because of the simplicity of its...
The nematode Caenorhabditis elegans is an attractive model organism to study learning and memory at molecular and cellular levels because of the simplicity of its nervous system, whose chemical and electrical wiring diagrams were completely reconstructed from serial electron micrographs of thin sections. Here, we describe detailed protocols for the conditioning of C. elegans by massed and spaced training for the formation of short-term memory (STM) and long-term memory (LTM), respectively. By pairing 1-propanol and hydrochloric acid as conditioned and unconditioned stimuli, respectively, C. elegans was successfully trained to form aversive associative STM and LTM. While naïve animals were attracted to 1-propanol, the trained animals were no longer or very weakly attracted to 1-propanol. Like in other organisms such as Aplysia and Drosophila, "learning and memory genes" play essential roles in memory formation. Particularly, NMDA-type glutamate receptors, expressed in only six pairs of interneurons in C. elegans, are required for the formation of both STM and LTM, possibly as a coincidence factor. Therefore, the memory trace may reside among the interneurons.
Topics: 1-Propanol; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Conditioning, Classical; Memory, Long-Term; Memory, Short-Term; Receptors, N-Methyl-D-Aspartate
PubMed: 35816003
DOI: 10.3791/64137 -
Nature Methods Oct 2021Peptidergic dense-core vesicles are involved in packaging and releasing neuropeptides and peptide hormones-critical processes underlying brain, endocrine and exocrine...
Peptidergic dense-core vesicles are involved in packaging and releasing neuropeptides and peptide hormones-critical processes underlying brain, endocrine and exocrine function. Yet, the heterogeneity within these organelles, even for morphologically defined vesicle types, is not well characterized because of their small volumes. We present image-guided, high-throughput mass spectrometry-based protocols to chemically profile large populations of both dense-core vesicles and lucent vesicles for their lipid and peptide contents, allowing observation of the chemical heterogeneity within and between these two vesicle populations. The proteolytic processing products of four prohormones are observed within the dense-core vesicles, and the mass spectral features corresponding to the specific peptide products suggest three distinct dense-core vesicle populations. Notable differences in the lipid mass range are observed between the dense-core and lucent vesicles. These single-organelle mass spectrometry approaches are adaptable to characterize a range of subcellular structures.
Topics: Animals; Aplysia; High-Throughput Screening Assays; Machine Learning; Organelles; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34594032
DOI: 10.1038/s41592-021-01277-2 -
Biomolecules Jun 2023With a single gene encoding H1 channel, proton channel diversity is particularly low in mammals compared to other members of the superfamily of voltage-gated ion... (Review)
Review
With a single gene encoding H1 channel, proton channel diversity is particularly low in mammals compared to other members of the superfamily of voltage-gated ion channels. Nonetheless, mammalian H1 channels are expressed in many different tissues and cell types where they exert various functions. In the first part of this review, we regard novel aspects of the functional expression of H1 channels in mammals by differentially comparing their involvement in (1) close conjunction with the NADPH oxidase complex responsible for the respiratory burst of phagocytes, and (2) in respiratory burst independent functions such as pH homeostasis or acid extrusion. In the second part, we dissect expression of H channels within the eukaryotic tree of life, revealing the immense diversity of the channel in other phylae, such as mollusks or dinoflagellates, where several genes encoding H channels can be found within a single species. In the last part, a comprehensive overview of the biophysical properties of a set of twenty different H channels characterized electrophysiologically, from Mammalia to unicellular protists, is given.
Topics: Animals; Protons; Ion Channels; Cell Membrane; Respiratory Burst; Eukaryota; Mammals
PubMed: 37509071
DOI: 10.3390/biom13071035