Biology subjects

Jiao, G.

Publications and source records attributed to Jiao, G..

11 recordsLinked to original sources

bioRxiv2026

A neurofunctional signature of romantic love predicts rewards on social media, effects of oxytocin and drug-cue reactivity

Romantic love is a selective motivational state supporting pair bonding, yet its neural representation and relation to other affiliative-rewarding experiences remain unclear. Across eight fMRI studies (n=420) spanning naturalistic affiliative-reward, pharmacological and addiction-relevant experiments, we developed and evaluated multivariate whole-brain decoders of romantic love and friendship. Both signatures engaged mesocorticolimbic reward systems and the precuneus, yet were dissociable at the whole-brain level and in their recruitment of social-cognitive systems. The love signature generalized to reward on social media, was specific to positive valence, and did not track sweet-taste or monetary reward, indicating a distinct social-affiliative reward representation. Oxytocin selectively increased love - but not friendship - signature reactivity to the romantic partner. In an independent drug-cue-reactivity dataset, the love signature specifically identified heavy cannabis users. These findings establish a dissociable neurofunctional signature of romantic love in conserved bonding circuits that extend to digital affiliation and are co-opted in addiction.

neuroscience↗

bioRxiv2026

PBRM1-VHL cooperation rewires lipid and iron metabolism to promote ferroptosis resistance in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is initiated by biallelic loss of the tumor suppressor VHL followed by additional genomic alterations, including loss of tumor suppressors PBRM1, BAP1 or SETD2. Although ccRCC is known to be intrinsically sensitive to ferroptosis, the contribution of PBRM1 to this vulnerability, and how it interfaces with VHL loss, has remained unexplored. Using isogenic ccRCC and non-transformed cell models, we show that re-expression of PBRM1 and/or VHL attenuates GPX4-inhibitor-induced ferroptosis, and that the two tumor suppressors act cooperatively: dual reconstitution confers the greatest protection, suppresses lipid peroxidation, and preserves redox homeostasis. Time-resolved RNA-seq reveals that PBRM1 and VHL establish additive, largely non-overlapping "ground-state" transcriptional programs. Integrated pharmacogenomic, CRISPR dependency, and lipidomic analyses converge on two protective axes: restricted labile iron and MUFA-biased membrane remodeling. These findings identify PBRM1 as a previously unrecognized modulator of ferroptosis and define a cooperative chromatin-metabolic axis that buffers ferroptotic cell death in ccRCC.

cell biology↗

bioRxiv2025

PBRM1-Dependent PBAF Targeting is Required for EMT and Metastasis in Breast Cancer

SWI/SNF chromatin remodelers utilize ATP to mobilize nucleosomes on DNA and are represented by three biochemically distinct subcomplexes, the more abundant cBAF and the less abundant PBAF and GBAF subcomplexes. Patient mutations and genetic studies have identified important roles for PBAF subunits in development and disease; however, relating PBAF-mediated phenotypes to biochemical function in chromatin regulation and gene expression has been challenging. Further complicating matters, cell-based systems often do not reflect the phenotypes and genotypes observed with PBAF mutations in vivo. Here we show that the PBRM1 subunit of PBAF is critical for the completion of TGFB1-mediated epithelial-mesenchymal transition of mammary cells in vitro as well as the metastasis of murine breast cancers in vivo. Using epigenomics to profile different stages of EMT, we find that PBRM1 is necessary for targeting PBAF to inducible promoters marked by H3K14ac alone. We further find that PBRM1 facilitates DNA accessibility at sites bound by TGF{beta}1-inducible transcription factors, such as Atf3, for the induction of genes involved in migration, cell survival, and inflammation. Our model allows us to separate constitutive vs inducible gene expression to help explain some of the context-dependent phenotypes observed with PBRM1 deletion. In addition, we provide evidence that while PBRM1 deletions can promote the initiation of certain cancers in early stages, PBAF may be a vulnerability in late-stage metastatic cancers.

molecular biology↗

bioRxiv2024

Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice.

Key pointsBicra/Gltscr1 homozygous knockout mice are perinatal lethal with aberrant liver resident macrophage gene expression and function. Dysfunctional macrophages result in accumulation of immature nucleated red blood cells in peripheral blood and liver of the knockout mice. GLTSCR1, a protein encoded by the Bicra gene, is a defining subunit of the SWI/SNF (also called mammalian BAF) chromatin remodeling subcomplex called GBAF/ncBAF. To determine the role of GLTSCR1 during mouse development, we generated a Bicra germline knockout mouse using CRISPR/Cas9. Mice with homozygous loss of Bicra were born at Mendelian ratios but were small, pale and died within 24 hours after birth. Histology indicated blood-related defects including defective erythroblastic islands and irregularly sized red blood cells. Gene expression profiling of fetal livers pinpointed a defect in liver resident macrophages involved in the last stage of erythrocyte maturation, resulting in accumulation of nucleated erythrocytes in Bicra-/- pups. Together, these results demonstrate that Bicra is critical for fetal liver macrophage function during development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/618940v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@150ac36org.highwire.dtl.DTLVardef@15a4758org.highwire.dtl.DTLVardef@2176aorg.highwire.dtl.DTLVardef@14f5d49_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVisual AbstractC_FLOATNO C_FIG

developmental biology↗

bioRxiv2024

A neurofunctional signature of affective arousal generalizes across valence domains and distinguishes subjective experience from autonomic reactivity

Arousal is fundamental for affective experience and, together with valence, defines the core affective space. Precise brain models of affective arousal are lacking, leading to continuing debates of whether the neural systems generalize across valence domains and are separable from those underlying autonomic arousal or wakefulness. Here, we combined naturalistic fMRI with predictive modeling to develop a brain affective arousal signature (BAAS, discovery-validation design, n=60, 36). We demonstrate its (1) sensitivity and generalizability across mental processes and valence, and (2) neural distinction from autonomic arousal, wakefulness, and stimulation modality (24 studies, n=868). Affective arousal was encoded in distributed cortical-subcortical (e.g., prefrontal, PAG) systems with local similarities in thalamo-amygdala-insula systems between affective and autonomous arousal. We demonstrate application of the BAAS to improve specificity of established valence-specific neuromarkers. Our study provides a biologically plausible model for affective arousal that aligns with the affective space and has a high application potential.

neuroscience↗

bioRxiv2023

A neural signature for the subjective experience of threat anticipation under uncertainty

Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining a novel uncertain shock anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we trained a brain model that accurately predicted the intensity of subjective experience of anxious arousal on the population and individual level. In a series of analyses utilizing available fMRI datasets, we further demonstrate that the signature specifically predicted anxious anticipation and was not sensitive in predicting pain, general anticipation or unspecific arousal. The signature was functionally and spatially distinguishable from representations of subjective fear or negative affect. We developed a sensitive, generalizable, and specific neuromarker for subjective anxious arousal experienced during uncertain threat anticipation that can facilitate model development and clinical translation.

neuroscience↗

bioRxiv2023

A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional nearinfrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural selfregulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.

neuroscience↗

bioRxiv2022

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use

Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward or social brain, and the associations with the level of problematic smartphone or social media use. We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a comparably large sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding were employed to further characterize the identified regions. Higher levels of FOMO associated with lower cortical thickness in the precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analysis decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

neuroscience↗

bioRxiv2022

Angiotensin blockade enhances motivational reward learning via enhancing ventral striatal prediction error and frontostriatal communication

Adaptive human learning utilizes reward prediction errors (RPEs) that scale the differences between expected and actual outcomes to optimize future choices. Depression has been linked with biased RPE signaling and an exaggerated impact of negative outcomes on learning which may promote amotivation and anhedonia. The present proof-of-concept study combined computational modelling and multivariate decoding with neuroimaging to determine the influence of the selective competitive angiotensin II type 1 receptor antagonist losartan on learning from positive or negative outcomes and the underlying neural mechanisms in healthy humans. In a double-blind, between-subjects, placebo-controlled pharmaco-fMRI experiment, 61 healthy male participants (losartan, n=30; placebo, n=31) underwent a probabilistic selection reinforcement learning task incorporating a learning and transfer phase. Losartan improved choice accuracy for the hardest stimulus pair via increasing expected value sensitivity towards the rewarding stimulus relative to the placebo group during learning. Computational modelling revealed that losartan reduced the learning rate for negative outcomes and increased exploitatory choice behaviors while preserving learning for positive outcomes. These behavioral patterns were paralleled on the neural level by increased RPE signaling in orbitofrontal-striatal regions and enhanced positive outcome representations in the ventral striatum (VS) following losartan. In the transfer phase, losartan accelerated response times and enhanced VS functional connectivity with left dorsolateral prefrontal cortex when approaching maximum rewards. These findings elucidate the potential of losartan to reduce the impact of negative outcomes during learning and subsequently facilitate motivational approach towards maximum rewards in the transfer of learning. This may indicate a promising therapeutic mechanism to normalize distorted reward learning and fronto-striatal functioning in depression.

neuroscience↗

bioRxiv2021

Common and distinct neurofunctional representations of core and social disgust in the brain: An ALE meta-analysis and MACM characterization

Disgust represents a multifaceted defensive-avoidance response. On the behavioral level, the response includes withdrawal and a disgust-specific facial expression. While both serve the avoidance of pathogens, the latter additionally transmits social-communicative information. Given that common and distinct brain representation of the primary defensive-avoidance response (core disgust) and encoding of the social-communicative signal (social disgust) remain debated, we employed neuroimaging meta-analyses to (1) determine brain systems generally engaged in disgust processing, and (2) segregate common and distinct brain systems for core and social disgust. Disgust processing, in general, engaged a bilateral network encompassing the insula, amygdala, occipital and prefrontal regions. Core disgust evoked stronger reactivity in left-lateralized threat detection and defensive response network including amygdala, occipital and frontal regions while social disgust engaged a right-lateralized superior temporal-frontal network engaged in social cognition. Anterior insula, inferior frontal and fusiform regions were commonly engaged during core and social disgust, suggesting a common neural basis. We demonstrate a common and separable neural basis of primary disgust responses and encoding of associated social-communicative signals.

neuroscience↗

bioRxiv2021

Modulation of the renin-angiotensin system inhibits memory advantage for negative emotional material via decreasing hippocampus activation and its coupling with the amygdala

Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of post-traumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy and preventing the dysregulations already during exposure to threatening events may attenuate the development of PTSD-symptomatology. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-fMRI design, the present proof-of-concept study examined the potential of a single dose of angiotensin II type 1 receptor (AT1R) antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n=29) or placebo treatment (n=30) and a surprise memory test after 24h washout. LT generally improved memory performance and abolished emotional memory enhancement for negative yet not positive material while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. On the network level LT reduced coupling between hippocampus and basolateral amygdala during successful memory formation of negative stimuli. Our findings suggest that LT may have the potential to attenuate memory formation for negative yet not positive information by decreasing hippocampus activity and its functional coupling strength with amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD-symptomatology.

neuroscience↗