Biology subjects

Yu, Y.

Publications and source records attributed to Yu, Y..

At least 289 records · Page 16Linked to original sources

bioRxiv2023

The conserved wobble uridine tRNA thiolase Ctu1 is required to sustain development and differentiation

Recent studies have revealed that tRNA modification is an important epigenetic mechanism involved in gene expression. Cytosolic thiouridylase (consisting of Ctu1 and Ctu2 subunit) are the enzyme complex which catalyze the thio-modification at the 34th wobble uridine of the anticodon of tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU. Besides introducing a thiol group at the C2 positions, those tRNAs were commonly modified with a methoxycarbonylmethyl at the C5 positions by Elongator and ALKBH8. tRNA-U34 modification, particularly the Elongator and ALKBH8, has been demonstrated to be involved in disease and development, however, the biological functional level of CTU in vertebrates remains elusive. Here, we found that in zebrafish, CTU may be an important regulatory factor in development and erythroid differentiation. By using morpholino targeting and knocking down CTU1, we observed that the loss of CTU1 led to impaired zebrafish larval development and blood vessel formation. Single-cell sequencing analysis showed that erythroid cell differentiation in the CTU1 knockdown group was blocked at an early stage, while the wild-type group exhibited mature erythroid cells. These findings suggest that CTU1 is involved in regulating erythrocyte development. These findings provide new insights into the biological function of CTU1.

developmental biology↗

bioRxiv2023

Brain-Age Prediction: Systematic Evaluation of Site Effects, and Sample Age Range and Size

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of site harmonization, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2,101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 years and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1,600 participants. These findings have been incorporated into CentileBrain [https://centilebrain.org/#/brainAGE2], an open-science, web-based platform for individualized neuroimaging metrics.

bioinformatics↗

bioRxiv2023

Exploring building blocks of cell organization by estimating network motifs using graph isomorphism network

The spatial arrangement of cells within tissues plays a pivotal role in shaping tissue functions. A critical spatial pattern is network motif as the building blocks of cell organization. Network motifs can be represented as recurring significant interconnections of cells with various types in a spatial cell-relation graph, i.e., enriched occurrences of isomorphic subgraphs in the graph, which is computationally infeasible to have an optimal solution with large-size (>3 nodes) subgraphs. We introduce Triangulation Network Motif Neural Network (TrimNN), a neural network-based approach designed to estimate the prevalence of network motifs of any size in a triangulated cell graph. TrimNN simplifies the intricate task of occurrence regression by decomposing it into several binary present/absent predictions on small graphs. TrimNN is trained using representative pairs of predefined subgraphs and triangulated cell graphs to estimate overrepresented network motifs. On typical spatial omics samples within thousands of cells in dozens of cell types, TrimNN robustly infers the presence of a large-size network motif in seconds. In a case study using STARmap Plus technologies, TrimNN identified several biological meaningful large-size network motifs significantly enriched in a mouse model of Alzheimers disease at different months of age. TrimNN provides an accurate, efficient, and robust approach for quantifying network motifs, which helps pave the way to disclose the biological mechanisms underlying cell organization in multicellular differentiation, development, and disease progression.

bioinformatics↗

bioRxiv2023

Excessive cortical beta oscillations are associated with slow-wave sleep dysfunction in mild parkinsonism

Increasing evidence associates slow-wave sleep (SWS) dysfunction with neurodegeneration. Using a within-subject design in the nonhuman primate model of Parkinsons disease (PD), we found that reduced SWS quantity in mild parkinsonism was accompanied by elevated beta and reduced delta power during SWS in the motor cortex. Our findings support excessive beta oscillations as a mechanism for SWS dysfunction and will inform development of neuromodulation therapies for enhancing SWS in PD.

neuroscience↗

bioRxiv2023

Cryo-EM structure of the Spo11 core complex bound to DNA

The DNA double-strand breaks that initiate meiotic recombination are formed by topoisomerase relative Spo11, supported by conserved auxiliary factors. Because high-resolution structural data are lacking, many questions remain about the architecture of Spo11 and its partners and how they engage with DNA. We report cryo-EM structures at up to 3.3 [A] resolution of DNA-bound core complexes of Saccharomyces cerevisiae Spo11 with Rec102, Rec104, and Ski8. In these structures, monomeric core complexes make extensive contacts with the DNA backbone and with the recessed 3-OH and first 5 overhanging nucleotide, definitively establishing the molecular determinants of DNA end-binding specificity and providing insight into DNA cleavage preferences in vivo. The structures of individual subunits and their interfaces, supported by functional data in yeast, provide insight into the role of metal ions in DNA binding and uncover unexpected structural variation in homologs of the Top6BL component of the core complex.

biochemistry↗

bioRxiv2023

Parabrachial Calca neurons drive nociplasticity

Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitter or directly stimulating them we demonstrate that activation of Calca neurons is both necessary for the manifestation of chronic pain after nerve ligation and is sufficient to drive nociplasticity in wild-type mice. Aversive stimuli such as exposure to nitroglycerin, cisplatin, or LiCl can drive nociplasticity in a Calca-neuron-dependent manner. Calcium fluorescence imaging reveals that nitroglycerin activates PBN Calca neurons and potentiates their responses to mechanical stimulation. The activity and excitability of Calca neurons increased for several days after aversive events, but prolonged nociplasticity likely occurs in downstream circuitry.

neuroscience↗

bioRxiv2023

A resource for probing influences of perinatal factors on neurodevelopment in 3-10-years-old Chinese children

Adverse perinatal factors can disrupt the normal development of the brain, with potential long-term impacts on childrens overall development. Currently, the neuropathological mechanisms by which these factors lead to various neurodevelopmental disorders (NDDs) remain largely unknown. An open resource that integrate perinatal factors with brain and mental health development is essential for investigating NDD-related aetiology. In this Data Descriptor, we introduce a multicentre database containing information on perinatal factors that influence childrens brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors associated with a high incidence of NDDs at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development among children aged 3-10 years are associated with perinatal factors. Ultimately, our goal was to develop an early prediction and screening model for NDDs that leverages normative data to facilitate NDD aetiology research. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD and present preliminary brain-mind associations.

neuroscience↗

bioRxiv2023

Substrate promiscuity of xenobiotic-transforming hydrolases from stream biofilms impacted by treated wastewater

Organic contaminants enter aquatic ecosystems from various sources, including wastewater treatment plant effluent. Freshwater biofilms play a major role in the removal of organic contaminants from receiving water bodies, but knowledge of the molecular mechanisms driving contaminant biotransformations in complex stream biofilm (periphyton) communities remains limited. Previously, we demonstrated that biofilms in experimental flume systems grown at higher ratios of treated wastewater (WW) to stream water displayed an increased biotransformation potential for a number of organic contaminants. We identified a positive correlation between WW percentage and biofilm biotransformation rates for the widely-used insect repellent, N,N-diethyl-meta-toluamide (DEET). Here, we conducted deep shotgun sequencing of flume biofilms and identified a positive correlation between WW percentage and metagenomic read abundances of DEET hydrolase (DH) homologs. To test the causality of this association, we constructed a targeted metagenomic library of DH homologs from flume biofilms. We screened our complete metagenomic library for activity with four different substrates and a subset thereof with 183 WW-related organic compounds. The majority of active hydrolases in our library preferred aliphatic and aromatic ester substrates while, remarkably, only a single reference enzyme was capable of DEET hydrolysis. Of the 626 total enzyme-substrate combinations tested, approximately 5% were active enzyme-substrate pairs. Metagenomic DH family homologs revealed a broad substrate promiscuity spanning 22 different compounds when summed across all enzymes tested. We biochemically characterized the most promiscuous and active enzymes identified based on metagenomic analysis from uncultivated Rhodospirillaceae and Planctomycetaceae. In addition to characterizing new DH family enzymes, we exemplified a framework for linking metagenome-guided hypothesis generation with experimental validation. Overall, this study expands the scope of known enzymatic contaminant biotransformations for metagenomic hydrolases from WW-receiving stream biofilm communities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/559296v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1b5cbaforg.highwire.dtl.DTLVardef@4f73f7org.highwire.dtl.DTLVardef@467d16org.highwire.dtl.DTLVardef@1be598d_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMetagenomic DEET hydrolase abundances higher in biofilms grown in treated wastewater. C_LIO_LIEleven out of 64 metagenomic hydrolases tested exhibited hydrolysis activity. C_LIO_LIRelated enzymes in a single family of DEET hydrolases biotransform 20+ contaminants. C_LIO_LIReference DEET hydrolase shows a substrate preference for benzamide moieties. C_LIO_LI True DEET hydrolases are in low abundance even in biofilms that degrade DEET. C_LI

biochemistry↗

bioRxiv2023

Visual feature tuning properties of short-latency stimulus-driven ocular position drift responses during gaze fixation

Ocular position drifts during gaze fixation are generally considered to be random walks. However, we recently identified a short-latency ocular position drift response, of approximately 1 min arc amplitude, that is triggered within <100 ms by visual onsets. This systematic eye movement response is feature-tuned and seems to be coordinated with a simultaneous resetting of the saccadic system by visual stimuli. However, much remains to be learned about the drift response, especially for designing better-informed neurophysiological experiments unraveling its mechanistic substrates. Here we systematically tested multiple new feature tuning properties of drift responses. Using highly precise eye tracking in three male rhesus macaque monkeys, we found that drift responses still occur for tiny foveal visual stimuli. Moreover, the responses exhibit size tuning, scaling their amplitude as a function of stimulus size, and they also possess a monotonically increasing contrast sensitivity curve. Importantly, short-latency drift responses still occur for small peripheral visual targets, which additionally introduce spatially-directed modulations in drift trajectories towards the appearing peripheral stimuli. Drift responses also remain predominantly upward even for stimuli exclusively located in the lower visual field, and even when starting gaze position is upward. When we checked the timing of drift responses, we found that it was better synchronized to stimulus-induced saccadic inhibition timing than to stimulus onset. These results, along with a suppression of drift response amplitudes by peri-stimulus saccades, suggest that drift responses reflect the rapid impacts of short-latency and feature-tuned visual neural activity on final oculomotor control circuitry in the brain. SignificanceDuring gaze fixation, the eye drifts slowly in between microsaccades. While eye position drifts are generally considered to be random eye movements, we recently found that they are modulated with very short latencies by some stimulus onsets. Here we characterized the feature-tuning properties of such stimulus-driven drift responses. Our results demonstrate that drift eye movements are not random, and that visual stimuli can impact them in a manner similar to how such stimuli impact microsaccades.

neuroscience↗

bioRxiv2023

Structural insights into the orthosteric inhibition of P2X receptors by non-ATP-analog antagonists

P2X receptors are extracellular ATP-gated ion channels that form homo-or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. Here, we determined the cryo-EM structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5-phosphate derivatives, PPNDS and PPADS, at 3.3 and 3.6 [A] resolution, respectively, and performed structure-based mutational analysis by patch-clamp recording as well as MD simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo-and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes. Overall, our work provides structural insights into the orthosteric inhibition and subtype specificity of P2X receptors by the classical P2X antagonists, pyridoxal-5-phosphate derivatives, thereby facilitating the rational design of novel competitive antagonists for P2X receptors.

biophysics↗

bioRxiv2023

A cell-free transcription-translation pipeline for recreating methylation patterns boosts DNA transformation in bacteria

The bacterial world offers diverse strains for understanding medical and environmental processes and for engineering synthetic-biology chasses. However, genetically manipulating these strains has faced a long-standing bottleneck: how to efficiently transform DNA. Here we report IMPRINT, a generalized, rapid and scalable approach based on cell-free transcription-translation (TXTL) systems to overcome DNA restriction, a prominent barrier to transformation. IMPRINT utilizes TXTL to express DNA methyltransferases from the bacterial hosts restriction-modification systems. The expressed methyltransferases then methylate DNA in vitro to match the host DNAs methylation pattern, circumventing restriction and enhancing transformation. With IMPRINT, we efficiently multiplex methylation by diverse DNA methyltransferases and enhance plasmid transformation in gram-negative and gram-positive bacteria. We also developed a high-throughput pipeline that identifies the most consequential methyltransferases, and we apply IMPRINT to facilitate a library screen for translational rules in a hard-to-transform Bifidobacterium. Overall, IMPRINT can enhance DNA transformation, enabling use of increasingly sophisticated genetic manipulation tools across the bacterial world.

synthetic biology↗

bioRxiv2023

Overexpression of ZmSTOP1-A Enhances Aluminum Tolerance in Arabidopsis by Stimulating Organic Acid Secretion and Reactive Oxygen Species Scavenging

Aluminum (Al) toxicity and low pH are major factors limiting plant growth in acidic soils. Sensitive to Proton Rhizotoxicity 1 (STOP1) transcription factor respond to these stresses by regulating the expression of multiple Al- or low pH-responsive genes. ZmSTOP1-A, a STOP1-like protein from maize (Zea mays), was localized to the nucleus and had transactivation activity. ZmSTOP1-A was expressed moderately in both roots and shoots of maize seedlings, but was not induced by Al stress or low pH. Overexpression of ZmSTOP1-A in Arabidopsis Atstop1 mutant partially restored Al tolerance and completely low pH tolerance with respect to root growth. Regarding Al tolerance, ZmSTOP1-A/Atstop1 plants showed clear upregulation of organic acid transporter genes, and leading to increased organic acid secretion and reduced Al accumulation in roots. Besides, the antioxidant enzyme activity in roots and shoots of ZmSTOP1-A/Atstop1 plants was significantly enhanced, ultimately alleviating Al toxicity via scavenging reactive oxygen species. Similarly, ZmSTOP1-A could directly activate ZmMATE1 expression in maize, positively correlated with the number of Al-responsive GGNVS cis-element in the ZmMATE1 promoter. Our results revealed that ZmSTOP1-A antagonizes Al toxicity by enhancing organic acid secretion and reactive oxygen species scavenging in Arabidopsis, demonstrating that it is an important transcription factor conferring Al tolerance. Our findings help to comprehensively elucidate the role of STOP1-like transcript factor in enabling plants to detoxifying Al.

molecular biology↗

bioRxiv2023

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86

The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86s NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86s transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86s infectivity.

immunology↗

bioRxiv2023

Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 enhances antibody evasion and ACE2 binding

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade Class 1 NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.

immunology↗

bioRxiv2023

Mesoscale functional architecture in medial posterior parietal cortex

The posterior parietal cortex (PPC) in mice has various functions including multisensory integration1-3, vision-guided behaviors4-6, working memory7-13, and posture control14,15. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope16. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

neuroscience↗

bioRxiv2023

Identification and functional analysis of extrachromosomal circular DNA in plasma extracellular vesicles of liver failure patients

Withdrawal statementThe authors have withdrawn their manuscript owing to having identified certain issues with the current representation of the data in the manuscript after performing further analyses of the bioinformatics data from their eccDNA sequencing results. Therefore, the authors do not wish this work to be cited as reference for the project. A revised and corrected version will be submitted in the future. If you have any questions, please contact the corresponding authors.

genomics↗

bioRxiv2023

NUCLEOPORIN1 mediates proteasome-based degradation of ABI5 to regulate Arabidopsis seed germination

NUCLEOPORIN1 (NUP1), a member of the Nuclear Pore Complex (NPC), is located on the inner side of the nuclear membrane. It is highly expressed in seeds; however, its role in seeds including germination has not been explored yet. Here, we identified an abscisic acid (ABA) hypersensitive phenotype of nup1 during germination. ABA treatment drastically changes the expression pattern of thousands of genes in nup1, including the major transcription factors (TFs) involved in germination, ABI3, ABI4, and ABI5. Double mutant analysis of NUP1 and these ABA-related genes showed that mutations in ABI5 can rescue the phenotype of nup1, suggesting that NUP1 acts upstream of ABI5 to regulate seed germination. ABI5, a key negative regulator of germination, is abundant in dry seeds and rapidly degrades during germination. However, its spatiotemporal regulation and interaction with other molecular players during degradation remained to be fully elucidated. We found that NUP1 is physically associated with ABI5 and the 26S proteasome. Mutation in NUP1 delayed ABI5 degradation through its post-translational retention in nucleolus under abiotic stress. Taken together, our findings suggest that NUP1 anchors the proteasome to NPC and modulates seed germination through proteasome-mediated degradation of ABI5 in the vicinity of NPC in the nucleoplasm.

plant biology↗

bioRxiv2023

A dynamic model of neurovascular coupling network accounting for capillary K+-sensing vasomotion

Neurovascular coupling (NVC) is a fundamental unit that elucidates the regulation of vascular activity by neuronal electrical activity, ensuring adequate blood flow to the brains active regions and optimizing neural function. In this article, we propose a comprehensive dynamic model of a neural vascular coupling network that integrates the capillary K+ sensing mechanism and its impact on vascular motion. Our computational framework incorporates the dynamics of neurons, astrocytes, and smooth muscle cells at the cellular level. By integrating recent experimental findings, we have successfully demonstrated the ability of capillary endothelial cells to detect localized fluctuations in extracellular potassium (K+) concentration via the Kir2.1 channel situated on their membranes. Subsequently, these cells transmit this signal to smooth muscle cells, initiating the release of vasoactive substances and thereby facilitating vascular movement. This sequence of events serves as the fundamental basis of our model. Furthermore, the simulation we provide supports the inclusion of a temperature term in our model, enabling accurate replication of experimental observations: variations in neuronal electrical activity resulting from an increase in temperature and subsequent vasoconstriction. In conclusion, our dynamic model presents a valuable tool for investigating the mechanisms underlying neurovascular coupling and the role of capillary K+ sensing in regulating vascular activity. It enhances our understanding of brain function and offers insights for developing therapeutic interventions for neurovascular diseases. Author summaryIt is widely accepted that neuronal activity induces vasodilation, resulting in increased blood flow, while vascular activity provides energy supply to the nervous system. The role of astrocytes in these processes has been extensively studied, revealing their dual involvement in neuronal firing and facilitation of energy delivery to the nervous system through blood vessels. As cellular mediators of bidirectional processes, astrocytes play a crucial role in promoting neurovascular coupling, leading to the formation of neurovascular coupling units. Building upon existing experimental observations and previous theoretical reports, the present study successfully replicates the phenomenon of vasodilation caused by an increase in potassium ion concentration in the perivascular space, as well as vasoconstriction resulting from elevated potassium ion concentration. A new neuron-astrocyte-endothelial-smooth muscle cell coupling network model, incorporating temperature considerations, was constructed to achieve these outcomes. Additionally, by manipulating temperature, the experimental observation of neuronal vasoconstriction during febrile seizures was successfully reproduced. These results highlight the significance of the neurovascular coupling unit as the fundamental entity for investigating the functions and mechanisms of the nervous system and brain.

neuroscience↗