Yale-NUS College

Wnt signaling regulates metazoan development and homeostasis, in part by β-catenin-dependent activation and repression of a large number of genes. However, Wnt signaling also regulates genes independent of β-catenin, genes that are less well-characterized. In this study, using a pan-Wnt inhibitor, we performed a comprehensive transcriptome analysis in a Wnt-addicted orthotopic cancer model to delineate the β-catenin-dependent and independent arms of Wnt signaling. We find that while a large percentage of Wnt-regulated genes are regulated by β-catenin, 10% of these genes are regulated independent of β-catenin. Interestingly, a large proportion of these β-catenin-independent genes are Wnt-repressed. Among the β-catenin-dependent genes, more than half are repressed by β-catenin. We used this dataset to investigate the mechanisms by which Wnt/β-catenin signaling represses gene expression, revealing the role of a cis-regulatory motif, the negative regulatory element (NRE). The NRE motif is enriched in the promoters of β-catenin repressed genes and is required for their repression. This provides a comprehensive analysis of the β-catenin-independent arm of the Wnt signaling pathway in a cancer model and suggests that a cis-regulatory grammar may determine Wnt-dependent gene activation versus repression.

Offset analgesia (OA) is a substantial decrease in pain perception after a minor reduction in noxious stimulus intensity. The peripheral mechano- and heat-sensitive A-fibre nociceptors (AMH-I and AMH-II) and the C-fibre nociceptors (CMH) are hypothesised to contribute to OA. These nociceptors differ in initial response latency, peak response latency, and heat threshold, and the AMH-II fibres may be absent from the palm. Stimuli targeting those different nociceptive properties were used to decide which nociceptors critically contribute to OA. Healthy volunteers (N = 64) underwent 16 unique trials with continuous noxious heat (45-47°C). These trials included 3-second (short) or 12-second (long) periods of increased noxious heat (46-48°C), or an intense 0.2 seconds pulse of heat (51°C). Stimuli were delivered to the dorsum (back) and palm of the hands. Notable OA effects were observed for long-duration trials on both the dorsum and palm of the hand. Offset analgesia was inconsistently present and much smaller for the short-duration trials and for the pulse trials. Pain ratings generally increased more slowly during palm stimulation compared with dorsum stimulation. The demonstration of OA on the palm suggests that AMH-II nociceptors are either not critical for OA or that the AMH-II nociceptors are present in the palm. The small OA after the intense pulse and the substantial reduction in OA during the short trials suggests that AMH-I nociceptors are not necessary for OA and that the faster response of the AMH-II or CMH nociceptors is not sufficient to generate OA.

Discovering new superionic materials is essential for advancing solid-state batteries, which offer improved energy density and safety compared to traditional lithium-ion batteries with liquid electrolytes. Conventional computational methods for identifying such materials are resource-intensive and not easily scalable. Recently, universal interatomic potential models have been developed using equivariant graph neural networks. These models are trained on extensive datasets of first-principles force and energy calculations. One can achieve significant computational advantages by leveraging them as the foundation for traditional methods of assessing the ionic conductivity, such as molecular dynamics or nudged elastic band techniques. However, the generalization error from model inference on diverse atomic structures arising in such calculations can compromise the reliability of the results. In this work, we propose an approach for the quick and reliable screening of ionic conductors through the analysis of a universal interatomic potential. Our method incorporates a set of heuristic structure descriptors that effectively employ the rich knowledge of the underlying model while requiring minimal generalization capabilities. Using our descriptors, we rank lithium-containing materials in the Materials Project database according to their expected ionic conductivity. Eight out of the ten highest-ranked materials are confirmed to be superionic at room temperature in first-principles calculations. Notably, our method achieves a speed-up factor of approximately 50 compared to molecular dynamics driven by a machine-learning potential, and it is at least 3000 times faster compared to first-principles molecular dynamics.

In the mirror test of visual self-recognition, if an animal responds to its reflection as its own, rather than how it would respond to a novel individual, the animal may have the capacity to recognize itself in mirrors. Previous studies have offered little information about self-recognition of domestic cats. Here we explore two phenomena that may shed light on whether cats recognize their own reflections or reflective images by gleaning data from social media. We examine TikTok videos where pet owners show cats reflective images with augmented reality (AR) filters; and YouTube videos where cats interact with mirrors. Behavioral sequence analysis revealed little support that cats understand reflective images. Few TikTok cats responded to augmented reality images, and their responses may have been triggered by other cues, such as human touch. In YouTube videos, cats fell into five behavioral clusters, two which were aggressive, and two which were curious. Even curious cats showed little evidence that they have the prerequisite conditions to be tested for mirror self-recognition. We consider whether distinct clusters may indicate that cat personality influences how cats respond to their reflections. We discuss the utility of social media for addressing questions of animal cognition.

BackgroundMicrobial communities in mangrove sediments play vital ecological roles that underpin the functioning of the overall mangrove ecosystem. Fungal communities, in particular, are known to play crucial roles across sediment systems, yet their roles in mangrove sediments, especially in deeper layers, remain poorly understood without a comprehensive inter-domain characterization. To better understand fungal roles in sediment horizons, 10 sediment cores extending down to a depth of 1 m were taken in three mangrove sites to characterise the archaeal, bacterial, and fungal communities at 10 cm depth intervals.ResultsWe demonstrate that sediment depth has distinct effects on the three microbial communities. While fungal community compositions were similar across sediment depths, bacterial and archaeal community compositions were stratified into three distinct layers, surface (10–30 cm), subsurface (40–60 cm), and deep (70–100 cm). Co-occurrence networks were then constructed to investigate the roles of fungi in these sediment layers, where fungi were consistently identified as keystone taxa in maintaining the microbial network topology, with co-domain interactions constituting more than half of all interactions. Even in the deepest layer, fungal nodes still retained high betweenness centralities, acting as network hubs to potentially augment microbial interactions vital for the functioning of the overall ecosystem.ConclusionsOverall, our results emphasise the important role of fungi in mediating microbial interactions across sediment depths even in deep, anoxic sediment layers, and highlight the importance of cross-domain interactions as integral to a more holistic understanding of the mangrove microbiome.

Abstract Molecular switches are often thought of as nanoscopic equivalents to the electrical buttons and knobs ubiquitous in everyday life. However, mechanical force is rarely used to reversibly trigger rearrangements at the atomic scale, due to the difficulty in selectively breaking certain bonds, while keeping others intact. Here, we introduce two new mechanophores based on dithienylethene (DTE), which can be toggled between two states by ultraviolet light and sonication. Attaching various lengths of poly(ϵ‐caprolactone) either to the 2,2′ or the 5,5′ positions of the DTE core allowed us to study the kinetics of its mechanochemical cycloreversion. We employed computational methods to understand the root causes of the observed mechano‐regiochemical differences. Lastly, we show that our best performing DTE‐polymer conjugate can undergo numerous switching cycles by the alternating action of electromagnetic radiation and mechanical force.

ABSTRACT This paper examines the evolving trends in Chinese student mobility to Thailand, highlighting three distinct phases shaped by changes in the higher education: the dominance of Thai language programmes (1990–2010), the rise of business and international programmes (2010–2020), and the increasing preference for graduate studies (2020 onwards). By analysing the economic, cultural, and institutional factors facilitating these shifts, this paper positions Thailand as an emerging alternative study destination for Chinese students. It highlights the significance of this migration within the context of Thailand’s declining fertility rate and labour shortages, focusing on how Thai universities have adapted through active recruitment strategies targeting Chinese students. This paper also addresses the push and pull factors underpinning this migration and the pursuit of alternative educational pathways among Chinese youth. Additionally, it explores the strategic role of Sino-Thai collaborations under the BRI and their broader implications for educational mobility and economic ties.

Primates, the most colorful mammalian radiation, have previously served as an interesting model to test the functions and evolutionary drivers of variation in eye color. We assess the contribution of photo-regulatory and communicative functions to the external eye appearance of nine macaque species representing all the branches of their radiation. Macaques’ well described social structure and wide geographical distribution make them interesting to explore. We find that (1) the posterior option of the anterior eyeball is more pigmented closer to the equator, suggesting photoprotective functions. We also find that (2) the temporal side of the eyeball is more heavily pigmented than the nasal side. This suggests that eyeball pigmentation in macaques is distributed to reduce damage to the corneal limbus. The inclusion of a translocated population of M. fuscata in our analyses also suggests that external eye appearance may change quickly, perhaps owing to phenotypic plasticity. We find no evidence that communicative functions drive variation in external eye appearance in macaques. These results suggest that the amount of light in a species’ environment drives variation in eye coloration across macaque species. Furthermore, the geographical distribution of macaques hints at important factors that have yet to be accounted for, such as the reflectivity of the terrain a given species inhabits.