Biology subjects

Yu, Z.

Publications and source records attributed to Yu, Z..

At least 307 records · Page 17Linked to original sources

bioRxiv2020

The role of gene dosage in budding yeast centrosome scaling and spontaneous diploidization

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids rescues SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that acquisition of lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes. Author SummaryPloidy is the number of whole sets of chromosomes in a species. Most eukaryotes alternate between a diploid (two copy) and haploid (one copy) state during their life and sexual cycle. However, as part of normal human development, specific tissues increase their DNA content. This gain of entire sets of chromosomes is known as polyploidization, and it is observed in invertebrates, plants and fungi, as well. Polyploidy is thought to improve fitness under stressful conditions and promote evolutionary diversity, but how ploidy is determined is poorly understood. Here, we use budding yeast to investigate mechanisms underlying the ploidy of wild-type cells and specific mutants that affect the centrosome, a conserved structure involved in chromosome segregation during cell division. Our work suggests that different scaling relationships (allometry) between the genome and cellular structures underlies alterations in ploidy. Furthermore, mutations in cellular structures with incompatible allometric relationships with the genome may drive genomic changes such duplications, which are underly the evolution of many species including both yeasts and humans.

genetics↗

bioRxiv2020

Transport mechanism of the neuronal excitatory amino acid transporter

Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report Cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing for the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which conserved glutamate mediates proton symport.

biophysics↗

bioRxiv2020

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase

Asymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featuring in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.

cell biology↗

bioRxiv2020

Chemical probe-based Nanopore direct RNA sequencing method to selectively assess the pseudouridine and inosine modifications

Current methods to identify RNA modifications with short-read sequencing are laborious and direct RNA sequencing gets proclaimed as the viable alternative. Herein, we harness the selective reactivity of the acrylonitrile towards the Inosine (I) and pseudouridine ({Psi}) modifications and developed a chemical probe-based direct RNA sequencing method. We first demonstrated that the chemical probe-induced differential signature profile using nanopore sequencing could facilitate the selective assessment of I and{Psi} in the in vitro synthesized RNA. Furthermore, we verified the I and{Psi} modification with single-nucleotide resolution using RNA derived from mouse brain without the need for a null dataset using knockouts. Our chemical probe-based nanopore sequencing strategy can be extended to profile multiple RNA modifications on a single RNA and may facilitate the diagnosis of disease-associated epitranscriptome markers by generating a comparative dataset in clinical scenarios. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=39 SRC="FIGDIR/small/105338v3_ufig1.gif" ALT="Figure 1"> View larger version (10K): org.highwire.dtl.DTLVardef@137799aorg.highwire.dtl.DTLVardef@110764aorg.highwire.dtl.DTLVardef@1c61ddaorg.highwire.dtl.DTLVardef@1d1db4d_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2020

Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis

BackgroundThe natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA). MethodsHere we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. ResultsExpression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. ConclusionsThese results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

immunology↗

bioRxiv2020

DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients which is closely associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure or disseminated intravascular coagulation as the disease progresses, which can lead to death under such conditions. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patient serum, peripheral blood mononuclear cells (PBMCs) and macrophages, and further reveal that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor {kappa}B (NF-{kappa}B) signaling pathway. Additionally, NS1 inhibits TIMP-1 expression to facilitates the MMP-9 enzymatic activity which alters the adhesion and tight junctions and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with {beta}-catenin and Zona occludins protein-1/2 to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients. Author SummaryDENV is the most common mosquito-transmitted viral pathogen in humans. In general, DENV-infected patients are either asymptomatic or have flu-like symptoms with fever and rash. However, in severe cases of DENV infection, the disease may progress to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), the leading causes of morbidity and mortality in school-age children in tropical and subtropical regions. DENV-induced vascular leakage is characterized by enhanced vascular permeability without morphological damage to the capillary endothelium. We found that a distinct mechanism of DENV NS1 and MMP-9 cooperatively induce vascular leakage is the main reason leading to death in severe dengue patients. Also, NS1 recruits MMP-9 to degrade {beta}-catenin, ZO-1, ZO-2 to intervene endothelial hyperpermeability in human endothelial cells and mouse vascular. Finally, we reveal that DENV activating NF-{kappa}B signaling pathway induces MMP-9 expression, in patients, mice, PBMC and macrophages though the viral NS1 protein. This study would provide new in signs into the pathogenesis caused by DENV infection, and suggest that MMP-9 may acts as a drug target for the prevention and treatment of DENV-associated diseases.

microbiology↗

bioRxiv2020

Local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions, which could shed unique light on etiologic sharing and provide additional mechanistic insights into the genetic basis of complex traits compared to global genetic correlation. However, accurate estimation of local genetic correlation remains challenging, in part due to extensive linkage disequilibrium in local genomic regions and pervasive sample overlap across studies. We introduce SUPERGNOVA, a unified framework to estimate both global and local genetic correlations using summary statistics from genome-wide association studies. Through extensive simulations and analyses of 30 complex traits, we demonstrate that SUPERGNOVA substantially outperforms existing methods and identifies 150 trait pairs with significant local genetic correlations. In particular, we show that the positive, consistently-identified, yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically-distinct genetic signatures with bidirectional local genetic correlations. We believe that statistically-rigorous local genetic correlation analysis could accelerate progress in complex trait genetics research.

genetics↗

bioRxiv2020

Prediction of protein-protein interactions based on elastic net and deep forest

Prediction of protein-protein interactions (PPIs) helps to grasp molecular roots of disease. However, web-lab experiments to predict PPIs are limited and costly. Using machine-learning-based frameworks can not only automatically identify PPIs, but also provide new ideas for drug research and development from a promising alternative. We present a novel deep-forest-based method for PPIs prediction. First, pseudo amino acid composition (PAAC), autocorrelation descriptor (Auto), multivariate mutual information (MMI), composition-transition-distribution (CTD), and amino acid composition PSSM (AAC-PSSM), and dipeptide composition PSSM (DPC-PSSM) are adopted to extract and construct the pattern of PPIs. Secondly, elastic net is utilized to optimize the initial feature vectors and boost the predictive performance. Finally, GcForest-PPI model based on deep forest is built up. Benchmark experiments reveal that the accuracy values of Saccharomyces cerevisiae and Helicobacter pylori are 95.44% and 89.26%. We also apply GcForest-PPI on independent test sets and CD9-core network, crossover network, and cancer-specific network. The evaluation shows that GcForest-PPI can boost the prediction accuracy, complement experiments and improve drug discovery. The datasets and code of GcForest-PPI could be downloaded at https://github.com/QUST-AIBBDRC/GcForest-PPI/.

bioinformatics↗

bioRxiv2020

StackRAM: a cross-species method for identifying RNA N6-methyladenosine sites based on stacked ensemble

N6-methyladenosine is a prevalent RNA methylation modification, which plays an important role in various biological processes. Accurate identification of the m6A sites is fundamental to deeply understand the biological functions and mechanisms of the modification. However, the experimental methods for detecting m6A sites are usually time-consuming and expensive, and various computational methods have been developed to identify m6A sites in RNA. This paper proposes a novel cross-species computational method StackRAM using machine learning algorithms to identify the m6A sites in S. cerevisiaeH. sapiens and A. thaliana. First, the RNA sequences features are extracted through binary encoding, chemical property, nucleotide frequency, k-mer nucleotide frequency, pseudo dinucleotide composition, and position-specific trinucleotide propensity, and the initial feature set is obtained by feature fusion. Secondly, the Elastic Net is used for the first time to filter redundant and noisy information and retain important features for m6A sites classification. Finally, the base-classifiers output probabilities are combined with the optimal feature subset corresponding to the Elastic Net, and the combination feature input the second-stage meta-classifier SVM. The jackknife test on training dataset S. cerevisiae indicates that the prediction performance of StackRAM is superior to the current state-of-the-art methods. StackRAM prediction accuracy for independent test datasets H. sapiens and A. thaliana reach 92.30% and 87.06%, respectively. Therefore, StackRAM has development potential in cross-species prediction and can be a useful method for identifying m6A sites. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/StackRAM/.

bioinformatics↗

bioRxiv2020

Neuron-glia Integrity: Functional Assessment, Molecular Underpinnings, and Implication for Higher Brain Functions

We developed a theory of neuron-glia integrity to underline the fact that neurons and glia cells work together in the central nervous system. Here we substantiated this theory and exemplified the implication of intact neuron-glia integrity for higher brain functions. An animal model of maternal separation with early weaning (MSEW) was applied to neonatal rats to mimic early life neglect and abuse in humans. Behavioral performance of rats was evaluated at adulthood, followed by functional assessments of neuron-glia integrity in living rats, and the demonstration of molecular underpinnings of impaired neuron-glia integrity in MSEW rats. MSEW rats showed higher levels of anxiety and explorative activity, higher glutamate level, but lower GABA level in PFC and hippocampus. MSEW procedure down-regulated protein levels of GLT-1 and ATP-, but up-regulated GAD65 and GS, while had no effects on GLAST and PAG. Moreover, it reduced the fractional anisotropy values in various brain regions, in addition to increasing NAA levels. Concurrently, MSEW led to hypomyelination in PFC as evidenced by relevant cellular and molecular changes.

neuroscience↗

bioRxiv2020

Efferent Synaptic Transmission at the Vestibular Type II Hair Cell Synapse

In the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via non-quantal transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents. Here, we aimed at characterizing the synaptic efferent inputs to type II HCs using electrical and optogenetic stimulation of efferent fibers combined with in vitro whole-cell patch clamp recording from type II HCs in the rodent vestibular crista. Properties of efferent synaptic currents in type II HCs were similar to those found in cochlear hair cells and mediated by activation of 9/10 nicotinic acetylcholine receptors (AChRs) and SK potassium channels. While efferents showed a low probability of release at low frequencies of stimulation, repetitive stimulation resulted in facilitation and increased probability of release. Notably, the membrane potential of type II HCs measured during optogenetic stimulation of efferents showed a strong hyperpolarization even in response to single pulses and was further enhanced by repetitive stimulation. Such efferent-mediated inhibition of type II HCs can provide a mechanism to adjust the contribution of signals from type I and type II HCs to vestibular nerve fibers. As a result, the relative input of type I hair cells to vestibular afferents will be strengthened, emphasizing the phasic properties of the incoming signal that are transmitted via fast non-quantal transmission. New and NoteworthyType II vestibular hair cells (HCs) receive inputs from efferent fibers originating in the brainstem. We used in vitro optogenetic and electrical stimulation of efferent fibers to study their synaptic inputs to type II HCs. Efferent inputs inhibited type II HCs, similar to cochlear efferent effects. We propose that efferent inputs adjust the contribution of signals from type I and type II HCs that report different components of the incoming signal to vestibular nerve fibers.

neuroscience↗

bioRxiv2020

A Method for Large Scale Implantation of 3D Microdevice Ensembles into Brain and Soft Tissue

Wireless networks of implantable electronic sensors and actuators on the microscale (sub-mm) are being explored for monitoring and modulation of physiological activity for medical diagnostics and therapeutic purposes. Beyond the requirement of integrating multiple electronic or chemical functions within small device volumes, a key challenge is the development of high-throughput methods for implantation of large numbers of microdevices into soft tissues with minimal damage. To that end, we have developed a method for high-throughput implantation of ∼100-200 μm size devices which are here simulated by proxy microparticle ensembles. While generally applicable to subdermal tissue, our main focus and experimental testbed is the implantation of microparticles into the brain. The method deploys a scalable delivery tool composed of a 2-dimensional array of polyethylene glycol tipped microneedles which confine the microparticle payloads. Upon dissolution of the bioresorbable polyethylene glycol, the supporting array structure is retrieved and the microparticles remain embedded in the tissue, distributed spatially and geometrically according to the design of the microfabricated delivery tool. We first evaluated the method in an agarose testbed in terms of spatial precision and throughput for up to 1000 passive spherical and planar microparticles acting as proxy devices. We then performed the same evaluations of particles implanted into the rat cortex under acute conditions and assessed the tissue injury produced by our method of implantation under chronic conditions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2020

Molecular goniometers for single-particle cryo-EM of DNA-binding proteins

Correct reconstruction of macromolecular structure by cryo-electron microscopy relies on accurate determination of the orientation of single-particle images. For small (<100 kDa) DNA-binding proteins, obtaining particle images with sufficiently asymmetric features to correctly guide alignment is challenging. DNA nanotechnology was conceived as a potential tool for building host nanostructures to prescribe the locations and orientations of docked proteins. We used DNA origami to construct molecular goniometers--instruments to precisely orient objects--to dock a DNA-binding protein on a double-helix stage that has user-programmable tilt and rotation angles. Each protein orientation maps to a distinct barcode pattern specifying particle classification and angle assignment. We used goniometers to obtain a 6.5 [A] structure of BurrH, an 82-kDa DNA-binding protein whose helical pseudosymmetry prevents accurate image orientation using classical cryo-EM. Our approach should be adaptable for other DNA-binding proteins, and a wide variety of other small proteins, by fusing DNA binding domains to them.

biophysics↗

bioRxiv2020

The CEPR2-mediated phosphorylation of NRT1.2 mainly regulates ABA import in Arabidopsis

Abscisic acid (ABA) transport plays important role in systematic plant responses to environmental factors. Here, we showed that C-terminally encoded peptide receptor 2 (CEPR2) directly interacted with the ABA transporter NRT1.2. Using transgenic seedlings, we demonstrated that NRT1.2 positively regulated the ABA response, and that CEPR2 acted on NRT1.2 epistatically and negatively. Under normal conditions, CEPR2 phosphorylated NRT1.2 at least at serine 292 to promote the degradation of NRT1.2. However, ABA and serine 292 nonphospharylation strongly inhibited the degradation of NRT1.2, indicating that ABA-inhibited the phosphorylation of NRT1.2. Transport assays in yeast and Xenopus oocytes showed that nonphosphorylated NRT1.2 had high levels of ABA-import activity, but phosphorylated NRT1.2 did not import ABA. Analyses of complement nrt1.2 mutants by mimicking nonphospharylated and phospharylated NRT1.2 confirmed that nonphospharylated NRT1.2S292A had high stability and ABA import activity in planta. Further experiments indicated that NRT1.2 was degraded via the 26S proteasome and vacuolar degradation pathways. UBC32, UBC33, and UBC34 interacted with, and mediated the ubiquitination of NRT1.2. UBC32, UBC33, and UBC34 acted on NRT1.2 epistatically and negatively in planta. Thus, our results suggested the existence of novel plant mechanisms regulating NRT1.2 stability and ABA import activity in response to environmental conditions.

molecular biology↗

bioRxiv2020

Agewise mapping of genomic oxidative DNA modification demonstrates oxidative-driven reprogramming of pro-longevity genes

The accumulation of unrepaired oxidatively damaged DNA can influence both the rate of ageing and life expectancy of an organism. Mapping oxidative DNA damage sites at whole-genome scale will help us to recognize the damage-prone sequence and genomic feature information, which is fundamental for ageing research. Here, we developed an algorithm to map the whole-genome oxidative DNA damage at single-base resolution using Single-Molecule Real-Time (SMRT) sequencing technology. We sequenced the genomic oxidative DNA damage landscape of C. elegans at different age periods to decipher the potential impact of genomic DNA oxidation on physiological ageing. We observed an age-specific pattern of oxidative modification in terms of motifs, chromosomal distribution, and genomic features. Integrating with RNA-Seq data, we demonstrated that oxidative modification in promoter regions was negatively associated with the expression of pro-longevity genes, denoting that oxidative modification in pro-longevity genes may exert epigenetic potential and thus affect lifespan determination. Together, our study opens up a new field for exploration of "oxigenetics," that focuses on the mechanisms of redox-mediated ageing. SummaryO_LIWe developed an algorithm to map the oxidative DNA damage at single-base resolution. C_LIO_LIOxidative DNA damage landscape in C. elegans illustrated an age-specific pattern in terms of motifs, chromosomal distribution, and genomic features. C_LIO_LIOxidative modification in older worms occurred higher frequency at the sex chromosome, with the preference for promoter and exon regions. C_LIO_LIOxidative modification in promoter regions of pro-longevity genes was negatively associated with their expression, suggesting the oxidative-driven transcript reprogramming of pro-longevity genes in physiological ageing. C_LI

genetics↗

bioRxiv2020

Validity of Two-Dimensional Static Footprint in Medial Longitudinal Arch Evaluation and the Characteristics of Athletes' Footprints

BackgroundWe aimed to explore the validity of two-dimensional static footprint analysis in medial longitudinal arch evaluation as well as the characteristics of athletes footprints to provide a basis for the evaluation and selection of athletes. MethodsExperiment One: Twenty-nine high level athletes (runners and jumpers) and forty normal college students were selected. Based on the X-ray photos taken of the medial foot, we measured the calcaneal inclination angle, the calcaneal-first metatarsal angle and the ratio of height to length of the medial longitudinal arch. We collected indicators of two-dimensional static footprints. Experiment Two: 106 high level athletes (runners and jumpers) and 104 normal college students were selected. We also collected indicators of two-dimensional static footprints. ResultsThe average measuring the Interclass Correlation Efficient (ICC) of calcaneal inclination angle, calcaneal-first metatarsal angle, the ratio of height to length of the medial longitudinal arch, the width of ball, arch and heel, the length of footprint and each toe, Chippaux-Smirak Index (CSI) and Staheli Index (SAI) were higher than 0.800. Regardless of athletes or college students, male or female, the correlation between CSI, SAI and calcaneal inclination angle, calcaneal-first metatarsal angle, the ratio of height to length of the medial longitudinal arch was statistically significant (P<0.05). College students CSI of the right foot is significantly higher than that of the left foot regardless of gender (P<0.05). ConclusionsWe prove the qualification of CSI and SAI in medial longitudinal arch evaluation and explain that the relative height of medial longitudinal arch is an important indicator in track and field.

genetics↗

bioRxiv2020

Non-invasive, Real-time Detection of Vascular Disorders in Mice using Bright SWIR-emitting Gold Nanoclusters and Monte Carlo Image Analysis

We present here a new approach for non-invasive high resolution whole-body vascular imaging in depth by combining water-soluble and bright SWIR-emitting gold nanoclusters revealing an anisotropic surface charge with Monte Carlo image processing of the images. We applied and validated this approach to quantify vessel complexity in transgenic mice presenting vascular disorders.

bioengineering↗

bioRxiv2020

Opposing neural signals of CaV1-encoded peptides are tuned by C-terminus mediated inhibition

L-type calcium (CaV1) channels regulate gene expressions via the cascade of excitation-transcription coupling, or directly as standalone CCAT (Calcium Channel Associated Transcriptional-regulator) peptides encoding distal carboxyl-terminus (DCT) of CaV1, both evidenced in dendritogenesis signaling in neurons. We here discover that DCT peptides opposedly mediate these two sets of transcription signals, all tunable in accordance to C-terminus mediated inhibition (CMI) of Ca2+/CaV1 influx. By electrophysiology, neurite morphology, and FRET 2-hybrid binding analyses, we systematically examined native and derived DCT peptides across CaV1, unveiling that the overall balance between cytosolic inhibition versus nuclear facilitation is spatially and temporally tuned by CMI of each DCT variant. Our findings not only resolve several controversies existing to DCT variants, but also propose a de novo scheme of CaV1-centric gene regulation: two concurrent routes of transcription signals initiated from either membrane CaV1 channels or nuclear CaV1-encoded peptides are subject to autonomous feedback tuning by peptide/channel interactions.

neuroscience↗