Biology subjects

Thompson, J. C.

Publications and source records attributed to Thompson, J. C..

13 recordsLinked to original sources

bioRxiv2026

rpSTS Stimulation Disrupts Shared Neural Responses to Social Content during Naturalistic Viewing

Shared understanding of common experiences can foster feelings of social closeness and friendship, and help us understand those experiences. Recent work has suggested that patterns of neural activity shared across individuals, especially throughout the default mode network, may underlie shared representations. Here we used repetitive transcranial magnetic stimulation (rTMS) and functional magnetic resonance imaging during movie watching to show that shared neural patterns to common experiences rely on the encoding of social information from the environment by the right posterior superior temporal sulcus (rpSTS). An encoding model of movie features showed that rTMS selectively degraded social feature encoding in rpSTS, leaving low-level visual encoding in early visual cortex intact. Using natural language processing (NLP)-based analysis, we found that rpSTS stimulation was associated with reduced memory and intersubject pattern similarity across DMN and limbic networks during scenes central to the movie narrative. Projecting scene embeddings onto NLP-based concept axes revealed reductions in memory and neural pattern similarity for scenes conveying helplessness and empathy following rTMS. These findings provide causal evidence that the rpSTS is a key region that encodes shared social information into common neural representations, and suggest that disrupting its input leads DMN representations to become idiosyncratic.

neuroscience↗

bioRxiv2026

The Red Blood Cell Surface Defines a Distinct Tumor DNA Compartment for Liquid Biopsy

Red blood cells (RBCs) modulate host inflammatory responses by scavenging mitochondrial and pathogen DNA. However, how RBC surface properties govern the capture of tumor-derived DNA remains poorly understood. We show that RBCs tether and retain tumor-derived DNA on their surface, forming a distinct circulating pool of RBC-bound tumor DNA (rtDNA). Desialylation increased DNA capture in a Toll-like receptor 9 (TLR9)-dependent manner, identifying RBC surface sialylation and TLR9 as a regulator of DNA binding. In mice bearing lung cancer xenografts, rtDNA was detected in all animals and its abundance correlated with tumor burden, whereas tumor DNA was undetectable in matched plasma samples. In patients with lung cancer, the majority of detected mutant tumor DNA was associated with RBCs rather than plasma, and RBC-derived mutations were concordant with molecular alterations identified in matched tumor tissue. Collectively, these findings establish the RBC surface as a tunable site of tumor-DNA capture and retention and challenge the plasma-centric paradigm of liquid biopsy by identifying a distinct cellular reservoir of tumor-derived genetic material.

cancer biology↗

bioRxiv2025

The Reward Positivity Does Not Encode Current Reward Value

Successful behavioral adaptation requires an ongoing assessment of rewarding outcomes based on ones current state. A frontocentral ERP associated with reward feedback, the reward positivity (RewP), has been linked to reflect information about reward value and motivational states. It is, however, unclear if changes in the RewP are influenced by changes in reward value as a function of motivational state. To examine this, hungry participants (n=31) completed two rounds of a modified Doors Task incorporating Pavlovian conditioning during EEG recordings and obtained feedback associated with sweet and savory food reinforcers equally matched in pleasantness and desirability. Participants underwent reinforcer devaluation, a paradigm designed to isolate inference-based behavior based on decreasing reward value, in between rounds by eating one of the foods to satiety. Prior to devaluation, participants were hungry and rated both food reinforcers equally pleasant. After devaluation, participants were sated and rated the devalued food, but not the non-devalued food, significantly less pleasant, suggesting a sensory-specific change in reward value. Logistic regression of win-stay/lose-switch behavior during the Doors Task shows participants made sensory-specific adjustments in food preferences during post-devaluation. Non-parametric permutation tests based on the tmax statistic performed revealed no significant differences in RewP amplitudes, suggesting the RewP is insensitive to reinforcer devaluation. This could not be explained by differences in perceived pleasantness or desirability. These findings suggest that affective and motivational factors such as tracking inferences based on decreases in reward value did not modulate the RewP.

neuroscience↗

bioRxiv2024

Effects of Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine on intracellular calcium, mitochondrial function, and viability in human nasal epithelial cells

Pseudomonas aeruginosa is an opportunistic pathogen that produces phenazine metabolites pyocyanin and 1-hydroxyphenazine that have been suggested to have detrimental effects on mitochondrial function and reactive oxygen species (ROS) production. Prior studies have suggested activation of Ca2+ signaling by pyocyanin in an airway cell line, while others have shown apoptotic effects on cancer cells. Ca2+ is tightly linked to both normal mitochondrial function as well as mitochondrial ROS and apoptosis during mitochondrial Ca2+ overload. We found that pyocyanin but not 1-hydroxyphenazine induced both cytosolic and mitochondrial Ca2+ increases in RPMI 2650 and primary human nasal epithelial cells (HNEC). Similar results were seen in HNEC air-liquid interface (ALI) cells, but these cells did not display a cytosolic Ca2+ response after treatment with pyocyanin. In RPMI 2650, activation of PKC, ER Ca2+ release, and PLC inhibition, indicated potential GPCR activation from pyocyanin. Similarly, ROS production increased after treatment with pyocyanin, but not 1-hydroxyphenazine in all 3 cell types, but with stark differences in CF and non-CF ALIs. In HNEC ALI, pyocyanin reduced ciliary beat frequency (CBF) after 4 hours, while 1-hydroxpyhenazine did not. Despite this, both pyocyanin and 1-hydroxyphenazine decreased in cell viability in RPMI 2650 nasal carcinoma cells but not in HNEC at 24 hours. However, in both RPMI 2650 and HNEC, mitochondrial membrane potential acutely decreased after treatment with either pyocyanin or 1-hydroxyphenazine. Finally, 24-hour pyocyanin treatment decreased expression of ER stress genes in some cancer cells, but not in non-cancerous HNEC. Our data suggest that Ca2+ signaling is not required for acute effects of 1-hydroxyphenazine or pyocyanin on mitochondrial function. The greater sensitivity of RPMI 2650 cells to pyocyanin-induced and 1-hydroxyphenzine-induced cytotoxicity compared with primary cells suggests that these compounds might have some applicability in treating nasal squamous carcinomas or other types of head and neck squamous carcinomas. Although the exact mechanisms of pyocyanin induced apoptosis remains uncertain, the downregulation of the ER stress response may play a role.

physiology↗

bioRxiv2024

Pseudomonas aeruginosa metabolite 3-oxo-C12HSL induces apoptosis through T2R14 and the mitochondrial calcium uniporter

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. HNSCCs have high mortality rates and current treatments can be associated with severe morbidities. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. We previously discovered that bitter taste receptor 14 (T2R14), a GPCR, kills HNSCC cells when activated by bitter agonists. We are now investigating endogenous bitter ligands that exist in HNSCC tumor microenvironment (TME). The TME includes cells, signaling molecules, and microbes that can greatly influence treatment responses and overall prognosis in HNSCC. Pseudomonas aeruginosa is a gram-negative bacterium that colonizes/infects HNSCC patients. 3-oxo-C12SHL is a quorum-sensing N-acyl homoserine lactone (AHL) secreted by P. aeruginosa which is also a bitter compound. 3-oxo-C12HSL induces apoptosis but this has never been linked to T2R activation. We hypothesized that 3-oxo-C12HSL induces apoptosis in HNSCC via T2R14. We show that 3-oxo-C12HSL activates intracellular Ca2+ responses in HNSCC cells. This is inhibited with T2R14 antagonization. 3-oxo-C12HSL may activate additional Ca2+ channels as the Ca2+ dynamics are independent from store-operated calcium entry (SOCE). 3-oxo-C12HSL inhibits cell viability, depolarizes mitochondria, and produces ROS. This induces apoptosis in HNSCC cells. In a comparative screen of quorum-sensing AHLs, 3-oxo-C12HSL was the only AHL that elicited both a Ca2+ response and reduced cell viability. These results suggest that P. aeruginosa may play a significant role in modulating an anti-tumor TME through 3-oxo-C12HSL. Moreover, 3-oxo-C12HSL could be a novel, higher-affinity bitter therapeutic for HNSCC. Further research is warranted to elucidate the mechanisms of other endogenous T2R agonists present in the TME.

physiology↗

bioRxiv2024

Bitter Taste Receptor Agonists Induce Apoptosis in Papillary Thyroid Cancer

BackgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with a 20% recurrence rate. Bitter taste receptors (T2Rs) and their genes (TAS2Rs) may regulate survival in solid tumors. This study examined T2R expression and function in PTC cells. MethodsThree PTC cell lines (MDA-T32, MDA-T68, MDA-T85) were analyzed for expression using RT-qPCR and immunofluorescence. Live cell imaging measured calcium responses to six bitter agonists. Viability and apoptosis effects were assessed using crystal violet and caspase 3/7 activation assays. Genome analysis of survival was conducted. ResultsTAS2R14 was consistently highly expressed in all cell lines. Five bitter agonists produced significant calcium responses across all cell lines. All bitter agonists significantly decreased viability and induced apoptosis. Higher TAS2R14 expression correlated with better progression-free survival in patients (p<0.05). ConclusionsT2R activation by bitter agonists induces apoptosis and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.

cancer biology↗

bioRxiv2023

Dynamic Multiplexed Control and Modeling of Optogenetic Systems Using the High-Throughput Optogenetic Platform, Lustro

The ability to control cellular processes using optogenetics is inducer-limited, with most optogenetic systems responding to blue light. To address this limitation we leverage an integrated framework combining Lustro, a powerful high-throughput optogenetics platform, and machine learning tools to enable multiplexed control over blue light-sensitive optogenetic systems. Specifically, we identify light induction conditions for sequential activation as well as preferential activation and switching between pairs of light-sensitive spit transcription factors in the budding yeast, Saccharomyces cerevisiae. We use the high-throughput data generated from Lustro to build a Bayesian optimization framework that incorporates data-driven learning, uncertainty quantification, and experimental design to enable the prediction of system behavior and the identification of optimal conditions for multiplexed control. This work lays the foundation for designing more advanced synthetic biological circuits incorporating optogenetics, where multiple circuit components can be controlled using designer light induction programs, with broad implications for biotechnology and bioengineering. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/572411v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1d560ecorg.highwire.dtl.DTLVardef@1ce5614org.highwire.dtl.DTLVardef@1756e3corg.highwire.dtl.DTLVardef@986683_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2021

Social stratification without genetic differentiation at the site of Kulubnarti in Christian Period Nubia

Nubia has been a corridor for the movement of goods, culture, and people between sub-Saharan Africa, Egypt, and West Eurasia since prehistory, but little is known about the genetic landscape of the region prior to the influence of the Islamic migrations that began in the late 1st millennium CE. We report genome-wide data for 66 individuals from the site of Kulubnarti ([~]650-1000 CE), increasing the number of ancient individuals with genome-level data from the Nile Valley from three to 69. Our results shed light on the genetic ancestry of a Christian Period group and help to address a long-standing question about the relationships among people buried in two neighboring cemeteries who show skeletal evidence of differences in morbidity and mortality that are broadly suggestive of differences in social status. We find that the Kulubnarti Nubians were admixed with [~]43% Nilotic-related ancestry on average (individual proportions varied between [~]36-54%) and the remaining ancestry reflecting a West Eurasian-related gene pool likely introduced into Nubia through Egypt, but ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The admixed ancestry at Kulubnarti reflects interactions between genetically-distinct people in northeast Africa spanning almost a millennium, with West Eurasian ancestry disproportionately associated with females, highlighting the impact of female mobility in this region. We find no significant differences in ancestry among individuals from the two plausibly socially-stratified cemeteries at Kulubnarti, supporting hypotheses that the groups may have been socially divided but were not genetically distinct. We identify seven pairs of inter-cemetery relatives as close as second-degree, suggesting that any social divisions at Kulubnarti did not prevent mixing between groups. Present-day Nubians are not directly descended from the Christian Period people from Kulubnarti without additional admixture, attesting to the dynamic history of interaction that continues to shape the cultural and genetic landscape of Nubia.

genomics↗

bioRxiv2020

Shared heritability of face and brain shape distinct from cognitive traits

Evidence from both model organisms and clinical genetics suggests close coordination between the developing brain and face1-8, but it remains unknown whether this developmental link extends to genetic variation that drives normal-range diversity of face and brain shape. Here, we performed a multivariate genome-wide association study of cortical surface morphology in 19,644 European-ancestry individuals and identified 472 genomic loci influencing brain shape at multiple levels. We discovered a substantial overlap of these brain shape association signals with those linked to facial shape variation, with 76 common to both. These shared loci include transcription factors with cell-intrinsic roles in craniofacial development, as well as members of signaling pathways involved in brain-face crosstalk. Brain shape heritability is equivalently enriched near regulatory regions active in either brain organoids or in facial progenitor cells. However, brain shape association signals shared with face shape are distinct from those shared with behavioral-cognitive traits or neuropsychiatric disorder risk. Together, we uncover common genetic variants and candidate molecular players underlying brain-face interactions. We propose that early in embryogenesis, the face and the brain mutually shape each other through a combination of structural effects and paracrine signaling, but this interplay may have little impact on later brain development associated with cognitive function.

genetics↗

bioRxiv2019

Temporal Dynamics of the Neural Representation of Social Relationships

Humans can rapidly encode information from faces to support social judgments and facilitate interactions with others. We can also recall complex knowledge about those individuals, such as their social relationships with others, but the timecourse of this process has not been examined in detail. This study addressed the temporal dynamics of emerging visual and social relationship information using electroencephalography (EEG) and representational similarity analysis (RSA). Participants became familiar with a 10-person social network, and were then shown faces of that networks members while EEG was recorded. To examine the temporal dynamics of the cognitive processes related to face perception, we compared the similarity structure of neural pattern responses to models of visual processing, face shape similarity, person identity, and social connectedness. We found that all types of information are associated with neural patterns after a face is seen. Visual and identity models became significant early after image onset, but only the identity model stayed associated with neural patterns until 400 ms. Models representing social connections were also present beginning around 200 ms, even in the absence of an explicit task to think about the friendships among the network members. A partial correlation showed that visual and social information contribute uniquely to person perception, although differences were found between models of social connection. This study highlights the speed and salience of social information relating to group dynamics that are present in the brain during person perception. Significance StatementWe live our lives in social groups where complex relationships form among and around us. It is likely that some of the information about social relationships that we observe is integral during person perception, to better help us interact in differing situations with a variety of people. However, when exactly this information becomes relevant has been unclear. In this study, we present evidence that information reflecting observed relationships among a social network is spontaneously represented in whole-brain patterns shortly following visual perception, and is uniquely present around 400 ms. These results are consistent with neuroimaging studies showing spontaneous spatial representation of social network characteristics, and contribute novel insights into the timing of these neural processes.

neuroscience↗

bioRxiv2017

Alpha power reflects suppression of Pavlovian bias during social reinforcement learning

Socially appropriate behavior involves learning actions that are valued by others and those that have a social cost. Facial expressions are one way that others can signal the social value of our actions. The rewarding or aversive properties of signals such as smiles or frowns also evoke automatic approach or avoidance behaviors in receivers, and a Pavlovian system learns cues that predict rewarding or aversive outcomes. In this study, we examined the computational and neural mechanisms underlying interactions between Pavlovian and Instrumental systems during social reinforcement learning. We found that Pavlovian biases to approach cues predicting social reward and avoid cues predicting social punishment interfered with Instrumental learning from social feedback. While the computations underlying Pavlovian and Instrumental interactions remained the same as when learning from monetary feedback, Pavlovian biases from social outcomes to approach or withdraw were not significantly correlated with biases from money. Trial-by-trial measures of alpha (8-14Hz) EEG power was associated with suppression of Pavlovian bias to social outcomes, while suppression of bias from money was associated with theta (4-7Hz) EEG power. Our findings demonstrate how emotional reactions to feedback from others are balanced with the instrumental value of that feedback to guide social behavior.\n\nSignificance statementA smile from another can be a signal to continue what we are doing, while an angry scowl is a sure sign to stop. Feedback from others such as this plays an important role in shapeing social behavior. The rewarding nature of a smile (or the aversive nature of a scowl) can also lead to automatic tendencies to approach (or avoid), and we can learn situations that predict positive or negative social outcomes. In this study, we examined the brain mechanisms that come into play when the instrumental demands of a situation are in conflict with our automatic biases to approach or withdraw, such as when we have to approach someone who is scowling at us or withdraw from someone who is smiling.

neuroscience↗

bioRxiv2017

The neural representational space of social memory

Social functioning involves learning about the social networks in which we live and interact; knowing not just our friends, but also who is friends with our friends. Here we utilized a novel incidental learning paradigm and representational similarity analysis (RSA), a functional MRI multivariate pattern analysis technique, to examine the relationship between learning social networks and the brain's response to the faces within the networks. We found that accuracy of learning face pair relationships through observation is correlated with neural similarity patterns to those pairs in the left temporoparietal junction (TPJ), the left fusiform gyrus, and the subcallosal ventromedial prefrontal cortex (vmPFC), all areas previously implicated in social cognition. This model was also significant in portions of the cerebellum and thalamus. These results show that the similarity of neural patterns represent how accurately we understand the closeness of any two faces within a network, regardless of their true relationship. Our findings indicate that these areas of the brain not only process knowledge and understanding of others, but also support learning relations between individuals in groups.\n\nSignificance StatementKnowledge of the relationships between people is an important skill that helps us interact in a highly social world. While much is known about how the human brain represents the identity, goals, and intentions of others, less is known about how we represent knowledge about social relationships between others. In this study, we used functional neuroimaging to demonstrate that patterns in human brain activity represent memory for recently learned social connections.

neuroscience↗

bioRxiv2017

Alterations in cortical thickness and structural connectivity are associated with symptom severity in bulimia nervosa

Bulimia nervosa (BN) is a serious psychiatric illness defined by preoccupation with weight and shape, episodic binge-eating and compensatory behaviors. Although diagnosed BN has been associated with diffuse grey matter volume reductions, characterization of brain structure alterations in women with a range of BN symptoms has yet to be made. This study examined whether changes in cortical thickness (CT) scaled with BN symptom severity in a sample of 33 adult women (n = 10 BN; n = 5 EDNOS-BN). Our second objective was to assess global structural connectivity (SC) of CT and to determine if individual differences in global SC relate to BN symptom severity. We used the validated Eating Disorder Examination Questionnaire (EDE-Q; Fairburn & Beglin, 1994) as a continuous measure of BN symptom severity. Increased EDE-Q score was negatively related to global CT and local CT in the left middle frontal gyrus, right superior frontal gyrus and bilateral orbitofrontal cortex (OFC) and temporoparietal regions. Moreover, analysis of global SC indicated that BN-related cortical thinning preferentially occurred in regions with high global connectivity. Finally, we showed that individuals contribution to global SC at the group level were significantly related to EDE-Q score, where increased EDE-Q score correlated with reduced connectivity of the left OFC and middle temporal cortex and increased connectivity of the right superior parietal lobule. Our findings offer novel insight into CT alterations in BN and further suggest that the combination of CT and structural connectivity measures may be sensitive to individual differences in BN symptom severity.

neuroscience↗