Biology subjects

Ma, Y.

Publications and source records attributed to Ma, Y..

At least 451 records · Page 25Linked to original sources

bioRxiv2020

A Heat-labile Enterotoxin B Subunit Mutant (LTB26) of Escherichia coli Enhances Mucosal Immune adjuvanticity via Increased BCR Activity

Although several SARS-COV-2 vaccines have been approved, no one oral live vaccine is available. Here, an oral SARS-COV-2 RBD live vaccine containing LTB26 adjuvant has been developed. BALB/c mice are oral vaccinated with attenuated Salmonella typhimurium SL7207 containing pcDNA3.1-LTB26RBD or pcDNA3.1-RBD plasmids. The result shows that the high level of RBD specific antibody is produced in pcDNA3.1- LTB26RBD treatment. The mechanism indicates that LTB26 enhances RBD antibody production by significantly upregulating the activity of MHC II+ DCs and CD19+CD45+ B cells. LTB26 mutant is derived from heat-labile enterotoxin B subunit (LTB) wild type of Escherichia coli with enhanced immune adjuvanticity. Based on the pre-experiment result that SL7207 interferes the function of LTB26, the purified LTB26 was mixed with purified human rotavirus VP8 antigen to explore the mechanism of adjuvant. The results suggests that LTB26 enhances mucosal immune responses via increased of BCR and MHC II+ expression. Furthermore, LTB26 promotes both Th1 and Th2 cell mediated immunity. Therefore, LTB26 maybe a potent adjuvant for mucosal vaccine development in view of the safety of LTB26 than LT toxin.

immunology↗

bioRxiv2020

NOGEA: Network-Oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting new drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

systems biology↗

bioRxiv2020

Endosomal free fatty acid receptor 2 signaling is essential for propionate-induced anorectic gut hormone release

The ability of propionate, a short chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management and glycaemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2); a GPCR that activates Gi and Gq/11 pathways. However, how pleiotropic GPCR signaling mechanisms in the gut regulates appetite is poorly understood. Here, we identify propionate-mediated G protein signaling is spatially directed within the cell via the targeting of FFA2 to very early endosomes. Furthermore, propionate activates an endosomal Gi/p38 signaling pathway, which is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts. Our study reveals that intestinal metabolites can engage membrane trafficking pathways and endosomal signaling platforms to orchestrate complex GPCR pathways within the gut.

cell biology↗

bioRxiv2020

The effects of human umbilical cord mesenchymal stem cell transplantation on female fertility preservation in mice

Female fertility is the capacity to produce oocytes and achieve fertilization and pregnancy, and these outcomes are impaired by age, diseases, environment and social pressure. However, there is no effective therapy that preserves female reproductive ability. Mesenchymal stromal cells (MSCs) can exhibit multidirectional differentiation potential, and they have gained great attention as a tool for preserving female fertility. Therefore, this study uses human umbilical cords-MSCs (Huc-MSCs) to preserve and restore fertility in aging female mice and chemotherapy-damaged mice through the rescue of ovarian function and the reconstruction of the fallopian tubes and uterus. In our study, 2 mouse models were generated: aging mice (37 weeks old) and chemotherapy-damaged mice. Then, we injected Huc-MSCs into mice through the tail vein. After treatment, the effect of MSCs on the ovary, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological analysis and statistical analysis. The levels of E2 and FSH exhibited a significant recovery after HUC-MSC transplantation both in aging mice and mice treated with chemotherapy. Huc-MSC treatment also increased the numbers of primordial, developing and preovulatory follicles in the ovaries of mice. Meanwhile, MSCs have been shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as regenerating the cilia in fallopian tubes and reforming glands and chorionic villi in the uterus. Therefore, it is suggested that Huc-MSCs may represent an effective potential treatment for preserving female fertility through recovery from chemotherapy damage and rescuing female reproductive organs from the effects of aging.

cell biology↗

bioRxiv2020

A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy

Despite impressive responses in some patients, immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Nearly all preclinical immunotherapy studies utilize transplant tumor models, but cure rates of transplant tumor models treated with immunotherapy often overestimate patient responses. Here, we show that transplant tumors are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous tumors. We generated a single-cell atlas of tumor-infiltrating immune cells from transplant and primary tumors treated with radiation and immunotherapy, which reveals striking differences in their immune landscapes. Although radiotherapy remodels myeloid cell phenotypes in primary and transplant tumors, only transplant tumors are enriched for CD8+ T cells that mediate tumor clearance while mice with primary sarcomas demonstrate tumor-specific tolerance. These results identify distinct microenvironments in tumors that coevolve with the immune system, which promote tolerance that must be overcome for immune-mediated cancer cures.

cancer biology↗

bioRxiv2020

Reconstruction and dynamics of human intestinal microbiome observed in situ

Gut microbiome are studied primarily using fecal samples in humans and we gained vital knowledge of compositional and functional capacities of gastro-intestinal microbial communities. Yet, fecal materials limit our ability to investigate microbial dynamics in different locations along GI-tract (in situ), nor in finer temporal scales as they are infrequent. With a technology developed originally for fecal material transplantation, colonic transendoscopic enteral tubing, we were able to sample ileocecal microbiome twice daily, and carried out metagenomic as well as metatranscriptomic analyses. Ileocecal and fecal microbiome are similar in metagenomic profiling, yet their active genes (in metatranscriptomes) are highly distinct. Both were perturbed after laxatives and then became more similar to microbiome prior to treatment, demonstrating resilience as an innate property of gut microbiome. Ileocecal microbiome transcriptomes sampled during day and night revealed diurnal rhythmes exist in certain bacterial species and functional pathways, in particular those related to short-chain fatty acid production. Lastly, metabolomic analysis in fecal and urine samples mirrored the perturbance and recovery in gut microbiome, indicating crucial contribution of gut microbiome to many of the key metabolites involved in host health. Our study provides interesting novel insights into human gut microbiome, and demonstrates the inner resilience, diurnal rhythmes and potential consequences to the host.

microbiology↗

bioRxiv2020

Clustering of CD3ζ is sufficient to initiate T cell receptor signaling

T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of CD3{zeta} chains in a light controlled manner. We showed that spatial clustering of the CD3{zeta} intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of CD3{zeta}, Zap70, PLC{gamma}, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate CD3{zeta} phosphorylation upon CD3{zeta} clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed CD3{zeta} clusters at the plasma membrane. Taken together, our data suggest that clustering of the TCR can initialize proximal TCR signaling and thus constitute a biophysical mechanism of TCR triggering.

immunology↗

bioRxiv2020

Common postzygotic mutational signature in multiple healthy adult tissues related to embryonic hypoxia

Postzygotic mutations are acquired in all of the normal tissues throughout an individuals lifetime and hold clues for identifying mutagenesis causing factors. The process and underlying mechanism of postzygotic mutations in normal tissues is still poorly understood. In this study, we investigated postzygotic mutation spectra in healthy individuals by optimized ultra-deep exome sequencing of time series samples from the same volunteer and samples from different individuals. In cells of blood, sperm, and muscle, we resolved three common types of mutational signature. Two of them are known to represent clock-like mutational processes, and their proportions in mutation profiles associated with polymorphisms of epigenetic regulation genes, suggesting the contribution of personal genetic backgrounds to underlying biological process. Notably, the third signature, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type were likely to occur early in embryo development even before the tissue differentiation, as indicated by their relatively high allele frequencies, sharing variants between multiple tissues, and lacking of age-related accumulation. Almost all tumors shown in public datasets did not have this signature detected except for 19.6% of clear cell renal cell carcinoma samples, which featured by activation of the hypoxia-induced signaling pathway. Moreover, in vitro activation of HIF signaling pathway successfully introduced the corresponding mutation profile of this signature in a culture-expanded human embryonic stem cell line. Therefore, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggest hypoxic conditions in the early stage of embryo development may be a crucial factor for the C>T transitions at GpCpN sites and individual genetic background also related to shaping human postzygotic mutation profiles.

genetics↗

bioRxiv2020

Transcriptome analysis reveals the effects of transgenic expression of the Gal4 protein on normal gene expression in silkworm tissues

The Gal4/upstream activating sequence(UAS) system, a well-known genetic tool, has been widely used to analyze gene function in many organisms, including the silkworm (Bombyx mori), a model lepidopteran insect. Several studies have suggested that Gal4 protein activation in tissues can negatively affect transgenic individuals; however, whether and to what extent the Gal4 protein affects normal endogenous gene expression have rarely been studied. Here, we analyzed the transcriptomes of transgenic silkworms expressing the Gal4 protein at high levels in both the wing disc (WD) and epidermis (EP) and investigated gene expression changes in both tissues. Overall, 24,593 genes were identified in the WD and EP libraries, and 2,025 and 2,488 were identified as significant differentially expressed genes(DEGs) in the WD and EP between the transgenic and control groups, respectively. These DEGs were further annotated by gene function classification and pathway assessment using public databases. In addition, 506 DEGs were shared (common) between both tissues. Of these, 97 genes were commonly upregulated, and 234 were commonly downregulated; many of them were annotated to be involved in metabolic processes such as "fat digestion and absorption", "glycine, serine and threonine metabolism" and "glutathione metabolism" and in signal transduction pathways such as the "Rap1 signaling pathway", "MAPK signaling pathway" and "Hippo signaling pathway". Overall, this work enhances understanding of the effects of transgenic Gal4 protein expression on normal gene expression in silkworm tissues and suggests that researchers should pay attention to unexpected effects when using the Gal4/UAS system to study gene function.

genomics↗

bioRxiv2020

Cross-feeding between Thauera aminoaromatica and Rhodococcus pyridinivorans drove quinoline biodegradation in a denitrifying bioreactor

The complex bacterial community is predominated by several taxa, such as Thauera and Rhodococcus, in a quinoline-degrading denitrifying bioreactor. Yet it remains unclear about how the interactions between the different bacteria mediate the quinoline metabolism in denitrifying condition. In this study, we designed a sequence-specific amplification to guide the isolation of the most predominant bacteria and obtained four strains of Thauera aminoaromatica, the representative of one key member in the bioreactor. Test on these isolates demonstrated that all of them were unable to strive on quinoline but could efficiently degrade 2-hydroxyquinoline, the hypothesized primary intermediate of quinoline catabolism, under nitrate-reducing condition. However, another isolate, Rhodococcus pyridinivorans YF3, corresponding to the second abundant taxon in the same bioreactor, was found to degrade quinoline via 2-hydroxyquinoline. The end products and removal rate of quinoline by isolate YF3 were largely varied with the quantity of available oxygen. Specifically, quinoline could only be converted into 2-hydroxyquinoline without further transformation under the condition with insufficient oxygen, e.g. less than 0.5% initial oxygen in the vials. However, if were aerobically pre-cultured in the medium with quinoline the resting cells of YF3 could anaerobically convert quinoline into 2-hydroxyquinoline. A two-strain consortium constructed with isolates from Thauera (R2) and Rhodococcus (YF3) demonstrated an efficient denitrifying degradation of quinoline. Thus, we experimentally proved that the metabolism interaction based on the 2-hydroxyquinoline cross-feeding between two predominant bacteria constituted the mainstream of quinoline degradation. This work sheds light on the understanding of mechanism of quinoline removal in the denitrifying bioreactor. ImportanceWe experimentally verified the most predominant Thauera sp. was indeed active degrader for the intermediate metabolites and the second abundant taxon Rhodococcus exerted, however, key function for opening the food box for a complex quinoline-degrading community. An ecological guild composed of two isolates was assembled, revealing the different roles of keystone organisms in the microbial community. This study, to our best knowledge, is the first report on the cross feeding between the initial attacker with unprofitable catalysis of reluctant heterocyclic compounds and the second bacterium which then completely degrade the compound transformed by the first bacterium. These results could be a significant step forward towards elucidation of microbial mechanism for quinoline denitrifying degradation.

microbiology↗

bioRxiv2020

Analysis of metagenome-assembled genomes from the mouse gut microbiota reveals distinctive strain-level characteristics

The laboratorial mouse harbors a unique gut microbiota with potential value for human microbiota-associated studies. Mouse gut microbiota has been explored at the genus and species levels, but features rarely been showed at the strain level. The identification of 833,051 and 658,438 nonredundant genes of faeces and gut content samples from the laboratorial C57/BL mice showed over half of these genes were newly found compared to the previous mouse gut microbial gene catalogue. Metagenome-assembled genomes (MAGs) was used to reconstruct 46 nonredundant MAGs belonging to uncultured specieses. These MAGs included members across all phyla in mouse gut (i.e. Firmicutes, Bacteroidetes, Proteobacteria, Deferribacteres, Verrucomicrobia, and Tenericutes) and allowed a strain-level delineating of the mouse gut microbiota. Comparison of MAGs with human gut colonies revealed distinctive genomic and functional characteristics of mouses Bacteroidetes and Firmicutes strains. Genomic characteristics of rare phyla in mouse gut microbiota were demonstrated by MAG approach, including strains of Mucispirillum schaedleri, Parasutterella excrementihominis, Helicobacter typhlonius, and Akkermansia muciniphila. ImportanceThe identification of nonredundant genes suggested the existence of unknown microbes in the mouse gut samples. The metagenome-assembled genomes (MAGs) instantiated the specificity of mouse gut species and revealed an intestinal microbial correlation between mouse and human. The cultivation of faeces and gut contents sample validated the existence of MAGs and estimate their accuracy. Full-length 16S ribosomal RNA gene sequencing enabled taxonomic characterization. This study highlighted a unique ecosystem in the gut of laboratorial mice that obviously differed with the human gut flora at the strain level. The outcomes may be beneficial to researches based on laboratorial mouse models.

microbiology↗

bioRxiv2020

KALRN Mutations Promote Anti-tumor Immunity and Immunotherapy Response in Cancer

BackgroundKALRN (kalirin RhoGEF kinase) is mutated in a wide range of cancers. Nevertheless, the association between KALRN mutations and the pathogenesis of cancer remains unexplored. The identification of biomarkers for cancer immunotherapy response is important considering that immunotherapies show beneficial effects only in a subset of cancer patients. MethodsWe explored the correlation between KALRN mutations and anti-tumor immunity in 10 cancer cohorts from The Cancer Genome Atlas (TCGA) program by the bioinformatics approach. Moreover, we verified the findings from bioinformatics analysis by in vitro experiments. Furthermore, we explored the correlation between KALRN mutations and immunotherapy response in four cancer cohorts receiving immune checkpoint blockade therapy. ResultsWe found that anti-tumor immune signatures were stronger in KALRN-mutated than in KALRN-wildtype cancers. Moreover, KALRN mutations correlated with increased tumor mutation burden and the microsatellite instability or DNA damage repair deficiency genomic properties which may explain the elevated anti-tumor immunity in KALRN-mutated cancers. Furthermore, we found that PD-L1 expression was significantly upregulated in KALRN-mutated versus KALRN-wildtype cancers. The enhanced anti-tumor immune signatures and PD-L1 expression in KALRN-mutated cancers may favor the response to immune checkpoint blockade therapy in this cancer subtype, as evidenced in four cancer cohorts receiving anti-PD-1/PD-L1/CTLA-4 immunotherapy. We further revealed that the significant association between KALRN mutations and increased anti-tumor immunity was attributed to that KALRN mutations compromised the function of KALRN target Rho GTPases on regulating DNA damage repair pathways. ConclusionsThe KALRN mutation is a useful biomarker for predicting the response to immunotherapy in cancer patients.

immunology↗

bioRxiv2020

A variant in SMOC2, inhibiting BMP signaling by competitively binding to BMPR1B, causes multiple epiphyseal dysplasia

Previously study showed that SMOC, a matricellular protein, inhibits BMP signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In our study, exome sequencing revealed a missense mutation (c.1076T>G, p.Leu359Arg) in EC domain of SMOC2 in a Chinese family with multiple epiphyseal disease (MED). The pathogenicity of this SMOC2 variant was verified by Smoc2L359R/L359R knock-in mice. Of note, decreasing phosphorylation of SMAD1/5/9 was detected in growth plates and primary chondrocytes from Smoc2L359R/L359R mice. Furthermore, binding affinity of mutant SMOC2 with collagen IX and HSPG in the extracellular matrix of cartilage were reduced while binding affinity with BMPRIB was intact. In addition, in contrast to previously results, that SMOC2 cannot antagonize BMP activity in the presence of a constitutively activated BMP receptor. These results support that SMOC2 with p.Leu359Arg variant act as an antagonist of canonical BMP pathway by competitively binding with BMP receptors.

genomics↗

bioRxiv2020

Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov

A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development.

bioinformatics↗

bioRxiv2020

Isolation and long-term expansion of a single adult human renal epithelial cell with efficient kidney regeneration capacity

A wide spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures which leads to loss of renal function. A reliable technological platform to culture and transplant adult human-derived cells with nephrogenic potential offers great hope to facilitate human kidney regeneration. Here, we show that in an appropriate feeder cell-based culture system, it is feasible to isolate and long-term expand the progenitor-like SOX9+ renal epithelial cells (SOX9+ RECs) from adult mammalians. Single cell-derived SOX9+ REC lines can be established from human needle biopsy or urine samples with molecular homogeneity and genomic stability maintained during culture. Such cells grown in 3D culture system could self-organize into renal organoids composed of proximal tubular, Loop of Henle (LOH) and distal tubular cells as illustrated by single cell transcriptomic analysis. Once being transplanted into the physically injured mouse kidney, the expanded single human SOX9+ RECs incorporated into the damaged area and demonstrated capacity of regenerating functional tubules in vivo. Altogether, the ability to extensively propagate human SOX9+ REC in culture whilst concomitantly maintaining their intrinsic lineage differentiation commitment suggests their future application in regenerative medicine.

cell biology↗

bioRxiv2020

mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC), as the most important type of renal carcinoma, has a high incidence and easy metastasis. Folliculin (FLCN) was identified as a tumor suppressor gene. Its deletions and mutations are associated with a potential risk of kidney cancer. At present, the specific molecular mechanism of FLCN-induced proliferation, invasion and migration in clear cell renal cell carcinoma remains elusive. In this study, we demonstrated that FLCN controled cell proliferation, invasion and migration through PI3K/mTORC2 pathway. FLCN combined with HIF2 in various normal and cancerous renal cells, and mTORC2 mediate FLCN effectively alleviated the deterioration of renal cancer cells by degrading HIF2. Silencing of FLCN showed promotion of HIF2 protein expression, which in turn led to an increase in downstream target genes Cyclin D1 and MMP9. Moreover, when interfering with siFLCN, HIF2 degradation rate was delayed, and the time of entry into the nucleus was advanced. Taken together, our study illustrated that mTORC2 promoted the specific molecular mechanism of HIF2 by down-regulated FLCN, and might be a new therapeutic target against renal cancer progression.

cell biology↗

bioRxiv2020

Multilevel integrative transcriptome analyses in humans and humanized mice define in vivo human lncRNA metabolic regulators

A growing number of long non-coding RNAs (lncRNAs) have emerged as vital metabolic regulators in research animals suggesting that lncRNAs could also play an important role in human metabolism. However, most human lncRNAs are non-conserved, vastly limiting our ability to identify human lncRNA metabolic regulators (hLMRs). As the sequence-function relation of lncRNAs has yet to be established, the identification of lncRNA metabolic regulators in animals often relies on their regulations by experimental metabolic conditions. But it is very challenging to apply this strategy to human lncRNAs because well-controlled human data are much limited in scope and often confounded by genetic heterogeneity. In this study, we establish an efficient pipeline to identify putative hLMRs that are metabolically sensitive, disease-relevant, and population applicable. We first progressively processed human transcriptome data to select human liver lncRNAs that exhibit highly dynamic expression in the general population, show differential expression in a metabolic disease population, and response to dietary intervention in a small disease cohort. We then experimentally demonstrated the responsiveness of selected hepatic lncRNAs to defined metabolic milieus in a liver-specific humanized mouse model. Furthermore, by extracting a concise list of protein-coding genes that are persistently correlated with lncRNAs in general and metabolic disease populations, we predicted the specific function for each hLMR. Using gain- and loss-of-function approaches in humanized mice as well as ectopic expression in conventional mice, we were able to validate the regulatory role of one non-conserved hLMR in cholesterol metabolism. Mechanistically, this hLMR binds to an RNA-binding protein, PTBP1, to modulate the transcription of cholesterol synthesis genes. In summary, our study provides a pipeline to overcome the variabilities intrinsic to human data to enable the efficient identification and functional definition of hLMRs. The combination of this bioinformatic framework and humanized murine model will enable broader systematic investigation of the physiological role of disease-relevant human lncRNAs in metabolic homeostasis.

physiology↗

bioRxiv2019

Pay to know me in your eyes: A computational account and oxytocin modulation of social evaluation

People are eager to know and recast the self in the eyes of others, even at a personal cost. However, it remains unknown what drives people to pursue costly evaluations of the self. Here, we propose that the evaluation of the self is valuable and that such subjective value placed on evaluation drives the costly-to-know behavior. By measuring the amount of money that individuals would forgo for the opportunity to know evaluations from other people (social evaluation) or a computer program (non-social evaluation), we quantified the subjective value individuals assigned to the evaluation on the self. The results from 5 studies (n = 375) lent cognitive and computational support for this hypothesis. Furthermore, the subjective value was modulated by the source and valence of the evaluation. Participants equally valued positive and negative non-social evaluations, characterized by a shared unknown aversion computation. However, individuals computed independent unknown aversion towards positive and negative social evaluations and placed a higher value on the opportunity to know another persons evaluation on positive than negative aspects. Such a valence-dependent valuation of the social evaluation was facilitated by oxytocin, a neuropeptide linked to linked to social feedback learning and valuation processes, which decreased the value ascribed to negative social evaluation. Taken together, the current study reveals the psychological and computational processes underlying self-image formation and updating and suggests a role of oxytocin in modulating the value of social evaluation.

neuroscience↗