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Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses.

ABSTRACT: Macrophages initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed and thus, the type of response that ensues. Here, we examined how information about the stimulus is encoded in the dynamics of NFκB activity. We generated an mVenus-RelA reporter mouse line to enable high-throughput live-cell analysis of primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features-termed signaling codons-that convey stimulus information to the nucleus. In particular, oscillatory trajectories were a hallmark of responses to cytokine but not pathogen-derived stimuli. Single-cell imaging and RNA sequencing of macrophages from a mouse model of Sjögren's syndrome revealed inappropriate responses to stimuli, suggestive of confusion of two NFκB signaling codons. Thus, the dynamics of NFκB signaling classify immune threats through six signaling codons, and signal confusion based on defective codon deployment may underlie the etiology of some inflammatory diseases.

SUBMITTER: Adelaja A

PROVIDER: S-EPMC8184127 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses

Project description:Macrophages initiate inﬂammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed and thus, the type of response that ensues. Here, we examined how information about the stimulus is encoded in the dynamics of NFκB activity. We generated an mVenus-RelA reporter mouse line to enable high-throughput live-cell analysis of primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workﬂow identiﬁed six dynamical features—termed signaling codons—that convey stimulus information to the nucleus. In particular, oscillatory trajectories were a hallmark of responses to cytokine but not pathogen-derived stimuli. Single-cell imaging and RNA sequencing of macrophages from a mouse model of Sjögren’s syndrome revealed inappropriate responses to stimuli, suggestive of confusion of two NFκB signaling codons. Thus, the dynamics of NFκB signaling classify immune threats through six signaling codons, and signal confusion based on defective codon deployment may underlie the etiology of some inﬂammatory diseases.

2021-02-18 | GSE162992 | GEO

Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses

Project description:Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses

| PRJNA684151 | ENA

Neural network features distinguish chemosensory stimuli in Caenorhabditis elegans.

Project description:Nervous systems extract and process information from the environment to alter animal behavior and physiology. Despite progress in understanding how different stimuli are represented by changes in neuronal activity, less is known about how they affect broader neural network properties. We developed a framework for using graph-theoretic features of neural network activity to predict ecologically relevant stimulus properties, in particular stimulus identity. We used the transparent nematode, Caenorhabditis elegans, with its small nervous system to define neural network features associated with various chemosensory stimuli. We first immobilized animals using a microfluidic device and exposed their noses to chemical stimuli while monitoring changes in neural activity of more than 50 neurons in the head region. We found that graph-theoretic features, which capture patterns of interactions between neurons, are modulated by stimulus identity. Further, we show that a simple machine learning classifier trained using graph-theoretic features alone, or in combination with neural activity features, can accurately predict salt stimulus. Moreover, by focusing on putative causal interactions between neurons, the graph-theoretic features were almost twice as predictive as the neural activity features. These results reveal that stimulus identity modulates the broad, network-level organization of the nervous system, and that graph theory can be used to characterize these changes.

| S-EPMC8604368 | biostudies-literature

Flow stimuli reveal ecologically appropriate responses in mouse visual cortex.

Project description:Assessments of the mouse visual system based on spatial-frequency analysis imply that its visual capacity is low, with few neurons responding to spatial frequencies greater than 0.5 cycles per degree. However, visually mediated behaviors, such as prey capture, suggest that the mouse visual system is more precise. We introduce a stimulus class-visual flow patterns-that is more like what the mouse would encounter in the natural world than are sine-wave gratings but is more tractable for analysis than are natural images. We used 128-site silicon microelectrodes to measure the simultaneous responses of single neurons in the primary visual cortex (V1) of alert mice. While holding temporal-frequency content fixed, we explored a class of drifting patterns of black or white dots that have energy only at higher spatial frequencies. These flow stimuli evoke strong visually mediated responses well beyond those predicted by spatial-frequency analysis. Flow responses predominate in higher spatial-frequency ranges (0.15-1.6 cycles per degree), many are orientation or direction selective, and flow responses of many neurons depend strongly on sign of contrast. Many cells exhibit distributed responses across our stimulus ensemble. Together, these results challenge conventional linear approaches to visual processing and expand our understanding of the mouse's visual capacity to behaviorally relevant ranges.

| S-EPMC6217439 | biostudies-literature

Discrete Evaluative and Premotor Circuits Enable Vocal Learning in Songbirds.

Project description:Virtuosic motor performance requires the ability to evaluate and modify individual gestures within a complex motor sequence. Where and how the evaluative and premotor circuits operate within the brain to enable such temporally precise learning is poorly understood. Songbirds can learn to modify individual syllables within their complex vocal sequences, providing a system for elucidating the underlying evaluative and premotor circuits. We combined behavioral and optogenetic methods to identify 2 afferents to the ventral tegmental area (VTA) that serve evaluative roles in syllable-specific learning and to establish that downstream cortico-basal ganglia circuits serve a learning role that is only premotor. Furthermore, song performance-contingent optogenetic stimulation of either VTA afferent was sufficient to drive syllable-specific learning, and these learning effects were of opposite valence. Finally, functional, anatomical, and molecular studies support the idea that these evaluative afferents bidirectionally modulate VTA dopamine neurons to enable temporally precise vocal learning.

| S-EPMC6842112 | biostudies-literature

Retrospective Attention Gates Discrete Conscious Access to Past Sensory Stimuli.

Project description:Cueing attention after the disappearance of visual stimuli biases which items will be remembered best. This observation has historically been attributed to the influence of attention on memory as opposed to subjective visual experience. We recently challenged this view by showing that cueing attention after the stimulus can improve the perception of a single Gabor patch at threshold levels of contrast. Here, we test whether this retro-perception actually increases the frequency of consciously perceiving the stimulus, or simply allows for a more precise recall of its features. We used retro-cues in an orientation-matching task and performed mixture-model analysis to independently estimate the proportion of guesses and the precision of non-guess responses. We find that the improvements in performance conferred by retrospective attention are overwhelmingly determined by a reduction in the proportion of guesses, providing strong evidence that attracting attention to the target's location after its disappearance increases the likelihood of perceiving it consciously.

| S-EPMC4749386 | biostudies-literature

Predominance of six different hexanucleotide recoding signals 3' of read-through stop codons.

Project description:Redefinition of UAG, UAA and UGA to specify a standard amino acid occurs in response to recoding signals present in a minority of mRNAs. This 'read-through' is in competition with termination and is utilized for gene expression. One of the recoding signals known to stimulate read-through is a hexanucleotide sequence of the form CARYYA 3' adjacent to the stop codon. The present work finds that of the 91 unique viral sequences annotated as read-through, 90% had one of six of the 64 possible codons immediately 3' of the read-through stop codon. The relative efficiency of these read-through contexts in mammalian tissue culture cells has been determined using a dual luciferase fusion reporter. The relative importance of the identity of several individual nucleotides in the different hexanucleotides is complex.

| S-EPMC113845 | biostudies-literature

Six penA Codons Accurately and Reliably Predict Cefixime-Decreased Susceptibility in Neisseria gonorrhoeae.

Project description: Not available

| S-EPMC8202096 | biostudies-literature

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly.

Project description:Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ~80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices.

| S-EPMC4547892 | biostudies-literature

Culturally Appropriate Stimuli for Cognitive Neuropsychology-Based Treatment "Intensive Language Action Therapy (ILAT)".

Project description:ContextA standardized set of picture stimuli for neuro-language disorder has been long overdue.AimsTo develop a standardized set of 303 pictures for use in experiments of Intensive Language Action Therapy (ILAT).Methods and materialSeveral sources with standardized picture stimuli having culturally unbiased features were studied. Among those studies two prime sources (1) Snodgrass & Vanderwart (1980), 127 (89+37) items and (2) Neininger & Pulvermuller (2002), 147 (89+56) items were used extensively. Out of 303 stimuli, 89 items were common to both principle sources. An Indian study by George & Mathuranath (2007) has also been taken as an additional source. Line drawing stimuli were standardized on four variables of central relevance to memory and cognitive processing: name agreement, image agreement, familiarity, and visual complexity.Statistical analysis usedAll measures related to 303 concepts i.e. % correct, H statistics, familiarity, image agreement and visual complexity were analysed descriptively.ResultsLow mean and positive skew on H statistics and visual complexity show that many concepts had a high name agreement (13 concepts have H values of .0, and 55 have H values of 0.68 or below, where 0.68 represents consensus among all but few of the subjects on a picture's name) and were visually simple line drawings. The intercorrelations among the four measures were low, suggesting that they are indices of different attributes of the pictures.ConclusionsUsage of appropriate items/stimuli has immense potential to influence aphasia therapy outcome. This set of pictures and its normative variable has enhanced the ILAT outcome. It could be generalised for other aphasia therapy too to understand its efficacy.

| S-EPMC7731687 | biostudies-literature

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