Biology subjects

Yang, Y.-P.

Publications and source records attributed to Yang, Y.-P..

5 recordsLinked to original sources

bioRxiv2026

Organoid modeling of tumor-associated macrophages reveals phagocytosis checkpoint blockade-induced conversion to an immunosuppressive SPP1+ phenotype

Tumor-associated macrophages (TAM) exert essential functions during the immune response to cancer. However, investigations of TAM within a native human tumor microenvironment (TME) have been impeded by a lack of appropriate model systems. Here, patient-derived organoids (PDO) from air-liquid interface (ALI)-grown tumor fragments, containing a human TME that encompassed stroma and immune subsets, robustly preserved TAM that were maintained by endogenous CSF-1 and appropriately responded to polarization signals. Antibody blockade of the CD47 regulatory checkpoint in organoids stimulated phagocytosis and remodeled TAM cytokine secretion profiles that were confirmed in anti-CD47 phase I trial patients. Amongst PDO histologies screened, anti-CD47 tumor killing was notable in clear cell renal cell carcinoma (ccRCC) which was associated with increased TAM infiltration. PDO contained diverse previously described TAM subsets; however, anti-CD47 reprogrammed organoid TAM toward an immunosuppressive SPP1+ phenotype, highlighting a negative feedback mechanism. Our findings uncover a resistance circuit engaged by macrophage checkpoint blockade and position ALI PDO as a robust translational platform for dissecting human macrophage biology and informing precision immunotherapy.

cancer biology↗

bioRxiv2023

The Role of Attention in Multi Attribute Decision Making

Real-life decisions typically involve multiple options, each with multiple attributes affecting value. In such complex cases, sequential shifts of attention to specific options and attributes are thought to guide the decision process. We designed a task that allowed us to monitor attention in monkeys engaged in such multi-attribute decisions. We recorded pre-supplementary motor area neurons encoding action value signals reflecting the decision process. Attention guides this process through two mechanisms. First, attention enhances the activity of neurons representing the currently sampled option, independent of the attended option value. Second, attention up-regulates the gain of information integration towards the evolving value estimate for the attended option. In contrast, we found no evidence for a third suggested mechanism, in which only the attended option is represented. Instead, attention influences the ongoing information accumulation and competition between the options by modulating the strength of the value information that drives this circuit.

neuroscience↗

bioRxiv2021

Competitive asymmetry confers polyploid advantage under environmental stress

O_LICompetitive asymmetry across heterogeneous environments is crucial for the success of polyploid plants, however, little is known about it. As the major force in plant evolution, polyploids are predicted to maintain the competitive dominance relative to diploids under increased stress conditions. C_LIO_LITo evaluate the hypothesis of competitive asymmetry, we competed tetraploid and diploid plants of perennial herbaceous Chrysanthemum indicum L. (Asteraceae) at different relative frequencies under low and high water stress. We quantified the interaction intensity between competing plants of the same (intraploidy) and different ploidy levels (interploidy), and measured functional traits related to gas exchange and plant water use to understand the underlying mechanisms. C_LIO_LIStronger competitive effects of the tetraploid on diploid provided evidence for the competitive asymmetry between polyploid and diploid plants in C. indicum. Such competitive asymmetry was not only maintained under drought (increased water stress), but also translated into higher fitness of the tetraploid consistently across water stress conditions. Functional traits associated with fast growth and efficient water use likely explained the competitive dominance of the tetraploid. C_LIO_LIThese results will advance our understanding of species interactions between polyploid and diploid plants, and provide insights into population dynamics and species distribution under environmental change. C_LI

ecology↗

bioRxiv2020

Overt visual attention and value computation in complex risky choice

Traditional models of decision making under uncertainty explain human behavior in simple situations with a minimal set of alternatives and attributes. Some of them, such as prospect theory, have been proven successful and robust in such simple situations. Yet, less is known about the preference formation during decision making in more complex cases. Furthermore, it is generally accepted that attention plays a role in the decision process but most theories make simplifying assumptions about where attention is deployed. In this study, we replace these assumptions by measuring where humans deploy overt attention, i.e. where they fixate. To assess the influence of task complexity, participants perform two tasks. The simpler of the two requires participants to choose between two alternatives with two attributes each (four items to consider). The more complex one requires a choice between four alternatives with four attributes each (16 items to consider). We then compare a large set of model classes, of different levels of complexity, by considering the dynamic interactions between uncertainty, attention and pairwise comparisons between attribute values. The task of all models is to predict what choices humans make, using the sequence of observed eye movements for each participant as input to the model. We find that two models outperform all others. The first is the two-layer leaky accumulator which predicts human choices on the simpler task better than any other model. We call the second model, which is introduced in this study, TNPRO. It is modified from a previous model from management science and designed to deal with highly complex decision problems. Our results show that this model performs well in the simpler of our two tasks (second best, after the accumulator model) and best for the complex task. Our results suggest that, when faced with complex choice problems, people prefer to accumulate preference based on attention-guided pairwise comparisons.

neuroscience↗

bioRxiv2020

Primate anterior insular cortex represents economic decision variables postulated by Prospect theory

In humans, risk attitude is highly context-dependent, varying with wealth levels or for different potential outcomes, such as gains or losses. These behavioral effects are well described by Prospect Theory, with the key assumption that humans represent the value of each available option asymmetrically as gain or loss relative to a reference point. However, it remains unknown how these computations are implemented at the neuronal level. Using a new token gambling task, we found that macaques, like humans, change their risk attitude across wealth levels and gain/loss contexts. Neurons in their anterior insular cortex (AIC) encode the reference point (i.e. the current wealth level of the monkey) and the asymmetric value function (i.e. option value signals are more sensitive to change in the loss than in the gain context) as postulated by Prospect Theory. In addition, changes in the activity of a subgroup of AIC neurons are correlated with the inter-trial fluctuations in choice and risk attitude. Taken together, we find that the role of primate AIC in risky decision-making is to monitor contextual information used to guide the animals willingness to accept risk.

neuroscience↗