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Zhang, D.

Publications and source records attributed to Zhang, D..

At least 325 records · Page 18Linked to original sources

Hepatic Deletion of X-box Binding Protein 1 in Farnesoid X Receptor Null Mice Leads to Enhanced Liver Injury

Background & AimsFarnesoid X receptor (FXR) regulates bile acid metabolism and FXR null (Fxr-/-) mice have elevated bile acid levels and progressive liver injury. The inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) pathway is a protective pathway of the unfolded protein response (UPR) that is activated in response to ER stress. In this study we sought to determine the role of the UPR in Fxr-/- mice. Approach & ResultsWe examined hepatic UPR gene and protein expression in 10- and 24-week-old wild type (WT) and Fxr-/- mice. Hepatic XBP1 and other UPR pathways were activated in 24-week-old Fxr-/- mice, but not WT mice. To further determine the role of the liver UPR activation in Fxr-/- mice, we generated mice with FXR and liver-specific XBP1 double knockout (DKO, Fxr-/-Xbp1LKO) and Fxr-/- Xbp1fl/fl single knockout (SKO) mice and characterized their phenotypes at different ages. DKO mice demonstrated enhanced liver injury, apoptosis and fibrosis compared with SKO mice. RNA-seq revealed increased gene expression in apoptosis, inflammation and cell proliferation pathways in DKO mice. The proapoptotic C/EBP-homologous protein (CHOP) pathway was activated in DKO mice. At age 60 weeks, all DKO mice and no SKO mice spontaneously developed liver tumors. ConclusionsThe hepatic XBP1 pathway is activated in older Fxr-/- mice and has a protective role. The potential interaction between XBP1 and FXR signaling may be important in modulating the hepatocellular cholestatic stress responses.

molecular biology↗

A cooperative switch within the KaiC hexamer revealed by cryo-EM

The circadian clock of cyanobacteria is based on an approximately 24h rhythm in the phosphorylation level of KaiC, a hexameric ATPase. This oscillation can be reconstituted in vitro by incubating three proteins together with ATP. Like all chemical oscillators, this system must include a nonlinear, or switch-like, feedback loop, whose nature has been unclear. Here, by using single particle cryo-EM at near-atomic resolution we identified two major conformational states of KaiC subunits, denoted as the exposed state and the buried state, which may provide a structural basis of how the KaiC hexamer changes its conformation during the (day-night) phosphorylation-dephosphorylation cycle. We classify the abundance and pattern of exposed and buried states within hexamers for more than 160,000 KaiC particles. The statistics of the spatial arrangement of the two states in hexamers can be quantitatively fit by a simple statistical physics model with an interaction energy between neighboring subunits and a local field that depends on phosphorylation state. Our study shows that phosphorylation shifts the probability of each conformation and reveals that there is substantial cooperativity between neighboring subunits, which can allow a KaiC hexamer to respond in an ultrasensitive, switch-like manner to changes in the phosphorylation level.

biophysics↗

CRISPR-Detector: Fast and Accurate Detection, Visualization, and Annotation of Genome Wide Mutations Induced by Gene Editing Events

The leading edge of genome editing, driven by CRISPR/Cas technology, is revolutionizing biotechnologies. In pace with the burst of novel genome editing methods, bioinformatic tools to monitor the on/off-target events need to be more evolved as well. Existing tools suffer from limitations in speed and scalability, and they especially struggle with whole genome sequencing (WGS) data analysis which has the potential to detect off-target mutations at a genome-wide level via an unbiased manner. Here, we introduce our CRISPR-detector tool, which is a web-hosted or locally deployable pipeline with five key innovations: 1) optimized scalability allowing for WGS data analysis beyond BED (Browser Extensible Data) file-defined regions; 2) improved accuracy benefiting from haplotype-based variant calling to handle sequencing errors; 3) treated and control sample co-analysis to remove background variants existing prior to genome editing; 4) integrated structural variation (SV) calling; and 5) functional and clinical annotation of editing-induced mutations.

bioinformatics↗

Nuclear Receptor 5A2 Regulation of Agrp underlies Olanzapine-induced Hyperphagia

Summary/AbstractAntipsychotic (AP) drugs are highly efficacious treatments for psychiatric disorders, but a serious side effect of their use is excessive weight gain and subsequent development of metabolic disease. Increased food intake is the underlying driver of AP-induced weight gain, although the underlying mechanisms remain unknown. In previous studies, we identified hypothalamic genes whose expression level was altered following APs-induced hyperphagia. Among these genes, the orexigenic peptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) were two of the most significantly upregulated genes by APs. NR5a2 is broadly expressed throughout the body, but little is known about its role in the brain. In this study, we investigated the role of hypothalamic NR5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, OLZ treatment resulted in a dose-dependent increase in gene expression of NR5a2 and Agrp. In mice, administration of a specific Nr5a2 inhibitor decreased olanzapine-induced hyperphagia and weight gain, while knockdown of Nr5a2 in the arcuate nucleus (ARC) partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation-PCR studies showed for the first time that NR5a2 directly binds to the Agrp promoter region. In addition, in situ hybridization studies confirm that NR5a2 and Agrp are co-localized in a subset of cells in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake and these findings can be used to inform future clinical development of APs that do not activate hyperphagia and weight gain.

physiology↗

Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Glial cells play a crucial role in regulating physiological and pathological functions, such as sensation, infections, acute injuries, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS) and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Despite the understanding of glial subtypes and functional heterogeneity in animal models achieved by single-cell or single-nucleus RNA sequencing, no research has investigated the transcriptomic profiles of glial cells in the human PNS and spinal cord. Here, we used high-throughput single-nucleus RNA sequencing to map the cellular and molecular heterogeneity of SGCs in the human dorsal root ganglion (DRG) and astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these human findings with those from mice. Additionally, the expression profiles of risk genes of common DRG and spinal cord diseases in glial cells were compared between humans and mice. As a result, little SGCs heterogeneity was found in both human and mouse DRG. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were respectively divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into six, five, and six distinct transcriptomic subclusters, respectively. The comparative results revealed substantial heterogeneity in all glial cells between humans and mice. Notably, we also identified transcriptomic heterogeneity in several classical genes and risk genes for neurological disorders across humans and mice. Together, the present data comprehensively profiled glial cell heterogeneity and provides a powerful resource for investigating the cellular basis of glial-related physiological and pathological conditions in peripheral somatosensory system.

neuroscience↗

Staphylococcus aureus nt5 gene contributes to bacterial infection ability to form kidney abscess

Staphylococcus aureus (S. aureus) is a commonly conditional infection pathogen, in which several key virulence genes are responsible for bacterial infection ability. The S. aureus nt5 gene, encoding 5-nucleotidase, mediates bacterial nucleic acid pathway, yet it is nearly unknown of nt5 function for staphylococcal infection ability. Herein we have constructed S. aureus mutant with the gene nt5C166T silence (S. aureus {Delta}nt5) by a CRISPR RNA-guided base editing system to investigate bacterial infection ability in vitro and in vivo. As expected, several nt5-related genes are disturbed in S. aureus {Delta}nt5, in which gene transcription level of py is decreased compared with the wild-type S. aureus. Bacterial gene nt5 is downregulated and py/adk are upregulated when S. aureus is exposed to antibiotics daptomycin, which indicates nt5-mediated nucleic acid pathway is interfered upon with daptomycin treatment. Furthermore, the mutant {Delta}nt5 displays about a 40-fold reduction of bacterial loading in mouse kidney on a mouse sepsis model, and the infection ability of {Delta}nt5 is reduced than the wild-type bacteria. The gene nt5 contributes to S. aureus-infected abscess formation in mouse kidney, and the silence of nt5 gene promotes phagocytosis of S. aureus by mouse and human immunocytes. In general, our findings reveal nt5 silence impedes bacterial loading in kidney to form abscess but enhances S. aureus to be phagocytosed by host cell immune system in vitro and in vivo, which indicates that nt5 gene plays an important role in bacterial infection and immune evasion.

immunology↗

SdiA, a Quorum Sensing Transcriptional Regulator, Enhanced the Drug Resistance of Cronobacter sakazakiiand Suppressed its Motility, Adhesion and Biofilm Formation

Cronobacter sakazakii is a common foodborne pathogen, and the mortality rate of its infection is as high as 40-80%. Quorum sensing is a regulation system of bacterial density-dependent multigene expression and is an important regulatory mechanism involved in adhesion, biofilm formation and virulence. C. sakazakii contains a QS signal molecular receiver, which is the LuxR receptor homolog SdiA, but its regulatory mechanism in C. sakazakii QS has not been defined. Here, we further determined the effect of SdiA on the QS system of C. sakazakii. The SdiA gene in C. sakazakii was knocked out by gene editing technology, and the biological characteristics of the {Delta}sdiA gene deletion strain of C. sakazakii were studied, followed by transcriptome analysis to elucidate its effects. The results suggested that SdiA enhanced the drug resistance of C. sakazakii but diminished its motility, adhesion and biofilm formation ability and had no effect on its growth. Transcriptome analysis showed that the deletion of the SdiA gene upregulated the expression levels of D-galactose operon genes (including dgoR, dgoK, dgoA, dgoD and dgoT) and flagella-related genes (FliA and FliC) in C. sakazakii and downregulated the expression levels of related genes in the type VI secretion system (VasK gene was downregulated by 1.53-fold) and ABC transport system (downregulated by 1.5-fold), indicating that SdiA was related to the physiological metabolism of C. sakazakii. The results of this study may be useful for clarifying the pathogenic mechanism of C. sakazakii and provide a theoretical basis for controlling bacterial infection. IMPORTANCECronobacter sakazakii, as an emerging opportunistic foodborne pathogen, was associated with sepsis, meningitis and necrotizing enterocolitis in neonates and infants, with a mortality rate of 40-80%. Quorum sensing plays an important regulatory role in the pathogenicity of C. sakazakii. Nevertheless, the regulatory mechanism of QS in C. sakazakii remains unknown. Here, we studied the QS transcriptional regulator SdiA of C. sakazakii. We revealed the regulatory mechanisms of SdiA in C. sakazakii cell adhesion, motility, biofilm formation and drug resistance. It was helpful to further explore the function of the SdiA gene, revealing the pathogenic mechanism of C. sakazakii. It will also provide a new target for therapeutic interventions targeting the pathogenicity of C. sakazakii and developing quorum-sensing inhibitors.

molecular biology↗

Knockout of OsSWEET15 impaired rice embryo formation and seed-setting

we show that the knockout of a sugar transporter gene OsSWEET15 led to a significant drop in rice fertility because near half of the knockout mutant spikelets bore blighted or empty grains. The rest spikelets bore fertile grains with slightly reduced weight. Notably, the ovaries in the blighted grains of the ossweet15 mutants expanded after flowering but terminated development before the endosperm cellularization stage and aborted subsequently. GUS and GFP representing OsSWEET15 expression showed that the protein was strongly expressed in the embryo surrounding region (ESR) which was supposed to supply nutrients for the embryo development. These results joined with the proteins sucrose transport capacity and plasma membrane localization suggest that OsSWEET15 plays a prominent role during the caryopsis formation stage probably by releasing sucrose from the ESR to support the embryo development. By contrast, the empty grains were probably caused by the reduced pollen viability of the ossweet15 mutants. Investigation of the makeup of ossweet11 mutant grains revealed similar phenotypes that were observed in the ossweet15 mutants. These results indicate that both OsSWETT15 and OsSWEET11 play important and similar roles during rice pollen development, caryopsis formation, and seed-setting in addition to their function in seed-filling that was demonstrated previously.

plant biology↗

CRISPR-based targeted haplotype-resolved assemblies of a megabase region

Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved de novo assemblies of targeted genomic regions with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assemblies, our targeted approach achieved comparable completeness and accuracy with greatly reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.

genomics↗

GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance

The ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non- self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA- based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.

cell biology↗

Fluorescence visualization of deep-buried hollow organs

High-definition fluorescence imaging of deep-buried organs is still challenging. Here, we develop bright fluorophores emitting to 1700 nm by enhancing electron donating ability and reducing donor-acceptor distance. In parallel, the heavy water functions as the solvent of the delicately designed fluorophores, effectively reducing the fluorescent signal loss caused by the absorption by water. The near-infrared-II (NIR-II, 900-1880 nm) emission is eventually recovered and extended beyond 1400 nm. Compared with the spectral range beyond 1500 nm, the one beyond 1400 nm gives a more accurate fluorescence visualization of the hollow organs, owing to the absorption-induced scattering suppression. In addition, the intraluminal lesions containing much water are simultaneously negatively stained, leading to a stark contrast for precise diagnosis. Eventually, the intraluminally perfused fluorescent probes are excreted from mice and thus no obvious side effects emerge. This general method can provide new avenues for future biomedical imaging of deep and highly scattering tissues.

bioengineering↗

Structure prediction of the druggable fragments in SARS-CoV-2 untranslated regions

The outbreak of the COVID-19 pandemic has led to intensive studies of both the structure and replication mechanism of SARS-CoV-2. In spite of some secondary structure experiments being carried out, the 3D structure of the key function regions of the viral RNA has not yet been well understood. At the beginning of COVID-19 breakout, RNA-Puzzles community attempted to envisage the three-dimensional structure of 5'- and 3'-Un-Translated Regions (UTRs) of the SARS-CoV-2 genome. Here, we report the results of this prediction challenge, presenting the methodologies developed by six participating groups and discussing 100 RNA 3D models (60 models of 5'-UTR and 40 of 3'-UTR) predicted through applying both human experts and automated server approaches. We describe the original protocol for the reference-free comparative analysis of RNA 3D structures designed especially for this challenge. We elaborate on the deduced consensus structure and the reliability of the predicted structural motifs. All the computationally simulated models, as well as the development and the testing of computational tools dedicated to 3D structure analysis, are available for further study.

bioinformatics↗

High-performance Saccharomyces cerevisiae-based biosensor for heavy metal detection

Heavy metals, i.e., Cu(II), are harmful to the environment. There is an increasing demand to develop inexpensive detection methods for heavy metals. Here, we developed a yeast biosensor with reduced-noise and improved signal output for potential on-site copper ion detection. The copper-sensing circuit was achieved by employing a secondary genetic layer to control the galactose-inducible (GAL) system in Saccharomyces cerevisiae. The reciprocal control of the Gal4 activator and Gal80 repressor under copper-responsive promoters resulted in a low-noise and ultrasensitive yeast biosensor for the copper ion detection. Furthermore, we developed a betaxanthin-based colorimetric assay, as well as 2-phenylethanol and styrene-based olfactory outputs for the copper ion detection. Notably, our engineered yeast sensor confers a narrow range switch-like behavior, which can give a "yes/no" response when coupled with betaxanthin-based visual phenotype. Taken together, we envision that the design principle established here might be applicable for developing other sensing systems for various chemical detections. IMPORTANCEThe accumulation of heavy metals in the environment led to an imbalance with environmental and ecological impacts, and there is an increasing demand for inexpensive methods that permit on-site detection of heavy metals. In this study, a yeast biosensor with reduced-noise and improved signal output was developed. We used a betaxanthin-based colorimetric assay for monitoring the copper contamination in water samples, which confers a switch-like behavior with a "yes/no" response. In addition, we also explored the 2-phenylethanol and styrene-based outputs for copper detection, which might be useful for olfactory detection of heavy metals.

bioengineering↗

Pose-gait analysis for cetaceans with biologging tags

Biologging tags are a key enabling tool for investigating cetacean behavior and locomotion in their natural habitat. Identifying and then parameterizing gait from movement sensor data is critical for these investigations. But how best to characterize gait from tag data remains an open question. Further, the location and orientation of the tag on an animal in the field are variable and can change multiple times during deployment. As a result, the relative orientation of the tag with respect to (wrt) the animal must be determined before a wide variety of further analyses. Currently, custom scripts that involve specific manual heuristics methods tend to be used in the literature. These methods require a level of knowledge and experience that can affect the reliability and repeatability of the analysis. The authors of this work argue that an animals gait is composed of a sequence of body poses observed by the tag, demonstrating a specific spatial pattern in the data that can be utilized for different purposes. This work presents an automated data processing pipeline (and software) that takes advantage of the common characteristics of pose and gait of the animal to 1) Identify time instances associated with occurrences of relative motion between the tag and animal; 2) Identify the relative orientation of tag wrt the animals body for a given data segment; and 3) Extract gait parameters that are invariant to pose and tag orientation. The authors included biologging tag data from bottlenose dolphins, humpback whales, and beluga whales in this work to validate and demonstrate the approach. Results show that the average relative orientation error of the tag wrt the dolphins body after processing was within 11 degrees in roll, pitch, and yaw directions. The average precision and recall for identifying relative tag motion were 0.87 and 0.89, respectively. Examples of the resulting pose and gait analysis demonstrate the potential of this approach to enhance studies that use tag data to investigate movement and behavior. MATLAB source code and data presented in the paper were made available to the public (https://github.com/ding-z/cetacean-pose-gait-analysis.git), with suggestions related to tag data processing practices provided in this paper. The proposed analysis approach will facilitate the use of biologging tags to study cetacean locomotion and behavior.

animal behavior and cognition↗

Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its pathological conformational conversion

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by the selective death of motor neurons. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial ALS and sporadic ALS. SOD1 fibrils formed in vitro are able to incorporate into cells, transmit intercellularly, and share toxic properties with ALS inclusions. Here we produced amyloid fibrils in vitro from recombinant, full-length apo human SOD1 under semi-reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofibril with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3 to 55) and C-terminal segment (residues 86 to 153) with a structural break. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight {beta}-strands (to form a {beta}-barrel) and one -helix in the subunit of apo SOD1 convert into thirteen {beta}-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.

biochemistry↗

Genome-wide H3K9 Acetylation Level Increases with Age-Dependent Senescence of Flag Leaf in Rice (Oryza sativa)

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and epigenetic modification, but the precise mechanism is as of yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac and gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation-modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis-related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and also elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice. Significance statementGenome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and positively correlation the density and breadth of H3K9ac with transcript elongation and expression. Identified numerous H3K9 acetylation-modified gene expression targets reveal a complex regulatory network and metabolism-mediated senescence network that are associated with H3K9ac during leaf aging in rice.

plant biology↗

Diverse pathogens activate the host RIDD pathway to subvert BLOS1-directed immune defense

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1-dependent decay (RIDD) of mRNAs encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1 were resistant to infection. Non-functional Blos1 struggled to assemble the BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Blos1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal-destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus MHV also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work therefore establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

microbiology↗

Overlapping Representation of Basic Tastes in the Human Gustatory Cortex

The topological representation is a fundamental property of human primary sensory cortices. The human gustatory cortex (GC) responds to the five basic tastes: bitter, salty, sweet, umami, and sour. However, the topological representation of the human gustatory cortex remains controversial. Through functional magnetic resonance imaging(fMRI) measurements of human responses to the five basic tastes, the current study aimed to delineate the taste representations within the GC. During the scanning, the volunteers tasted solutions of the five basic tastes, then washed their mouths with the tasteless solution. The solutions were then sucked from the volunteers mouths, eliminating the action of swallowing. The results showed that the bilateral mid-insula activated most during the taste task, and the active areas were mainly in the precentral and central insular sulcus. However, the regions responding to the five basic tastes are substantially overlapped, and the analysis of contrasts between each taste response and the averaged response to the remaining tastes does not report any significant results. Furthermore, in the gustatory insular cortex, the multivariate pattern analysis (MVPA) was unable to distinguish the activation patterns of the basic tastes, suggesting the possibility of weakly clustered distribution of the taste-preference neural activities in the human insular cortex. In conclusion, the presented results suggest overlapping representations of the basic tastes in the human gustatory insular cortex.

neuroscience↗