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Program animal welfare: A scoping review of animal interaction programs and their welfare impact on zoo-housed animals
No full textAnimal Interaction Programs (AIPs) have become standard practice within zoos worldwide, however, there is a severe lack of empirical data on how these programs impact animal welfare. AIPs are operationally defined as a planned interaction between a visitor and an animal for educational and entertainment purposes and can be described as a type of Animal-Visitor Interaction (AVI), and can be classified as either direct or indirect and scripted or unscripted. Although these programs are prominent within zoos, there is currently not a comprehensive synthesis of current welfare literature that examines the welfare impact, taxonomic distribution, type, and prevalence of AIPs. The purpose of this scoping review was to synthesise welfare-related AIP literature to determine what is known about the welfare implications, identify key gaps and focus areas for future research, and to compare the prevalence, type, and species involved in AIPs within literature to see if it is reflected within zoos. Using the PRISMA-ScR framework, the review was conducted across three databases. A total of 49 articles were included within the review. Direct scripted AIPs were the most prominently investigated (43 %). Walkthrough programs were the most investigated type of AIP (23 %). There was a bias towards mammalian species (82 %), with less of a focus on avians (10 %), reptiles (4 %) or other taxa (4 %). This was not reflective of the types of AIPs and species represented in current programs offered in zoos, highlighting a crucial need to diversifying the species investigated within literature as well as investigating programs that are more commonly offered within zoos. Behavioural measures of welfare were the most utilised (70 %), with activity budgets being the most prominent. Generally, neutral or no changes in welfare were described (46 %), followed by positive (28 %), and negative (26 %) welfare impacts, however, welfare outcomes were generally mixed. There is a clear disparity between the types of programs and species represented in AIPs within literature compared to those offered in zoos as well as no clear welfare outcomes or factors that may be influencing these changes. This highlights a lack of understanding on the welfare impacts that these programs have and the factors that may be influencing them. It is critical to address this in future research to better understand the welfare impacts that AIPs have on animal welfare so that these programs can be evaluated and adjusted based on evidence rather than current practice.Bridget Cooper-Rogers, Paige Klingner, Alex Whittaker, Rebecca Forder, Eduardo J. Fernande
Semisynthetic indole alkaloids restrain the invasiveness of glioblastoma cell lines and inhibit human Aquaporin-1 water channels
No full textThe clinical challenge for treating glioblastoma (GBM) brain cancers is that even with best therapy, median survival time is still only ∼15 months after diagnosis. The unmet need is how to control lethal spreading of these highly invasive cells. We tackled this challenge by running blinded high-throughput screens of the rigorously curated Davis Open Access Compound Library. Positive hits captured a structurally-related array of five novel indole alkaloid compounds (RAD116, RAD117, RAD118, RAD119, RAD120) derived from a natural indole alkaloid scaffold (RAD114). The agents at 1 µM reduced invasiveness of pediatric and adult GBM lines U87-MG, U251-MG, KNS-42, and DBTRG-05 in transwell assays. RAD116 and RAD117 were most effective, reducing invasiveness in all lines up to 76 %. In adult lines, RAD118 and RAD119 reduced invasiveness by 27–47 %, and RAD120 blocked invasion by 14–32 %. RAD114 was least effective, causing 12–30 % reduction in two lines. The candidate mechanism of action involves block of Aquaporin-1 (AQP1) water channels, which are located in leading edges of GBM cells and linked to high cell motility. RAD117 blocked human AQP1 water flux in Xenopus laevis assays at sub-micromolar doses, making it the most potent inhibitor of AQP1 water channels identified to date. High potency and low toxicity of the novel indole alkaloids introduced here support feasibility for further preclinical testing, and may hold promise for future clinical translation as an adjunct therapy to hold GBM cells in place while other first line treatments are in progress.Kim K Wagner, Michael Fotiou, Shijin J. Suo, Sunita A Ramesh, Rohan A Davis, Andrea J Yoo
Quantifying the fatal and non-fatal burden of disease associated with child growth failure, 2000–2023: a systematic analysis from the Global Burden of Disease Study 2023
No full textBackground: Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF. Methods: In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than –1, underweight was defined as weight-for-age Z scores (WAZ) less than –1, and wasting was defined as weight-for-height Z scores (WHZ) less than –1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than –1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific. Findings: We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0–106) DALYs lost and 880 000 (517 000–1 170 000) deaths. This represented 17·9% (10·6–23·8) of 444 million (434–457) total under-5 DALYs and 18·8% (11·1–25·0) of all 4·67 million (4·59–4·75) under-5 deaths. Compared to stunting (33·0 million [24·1–42·2] DALYs, 373 000 [272 000–477 000] deaths) and wasting (39·2 million [23·8–53·0] DALYs, 428 000 [256 000–583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9–75·1) DALYs and 573 000 (236 000–824 000) deaths in children younger than 5 years in 2023
Boom, bust, and Fission: A Deep Dive into Uranium price explosiveness
No full textWe adopt a data-driven approach to examine uranium price explosiveness. We detect explosive episodes across varying durations and apply a LASSO-Logit framework to uncover key variables associated with price explosiveness. Our findings reveal that uranium price explosiveness is persistent, with positive explosiveness dominating and lasting an average of ten months. Variables such as dividend growth, monetary conditions, and expansion in the uranium sector significantly increase the likelihood of explosiveness. Additionally, uncertainty and geopolitical risks shape market dynamics. A local projections approach highlights that monetary tightening and uranium price momentum can sustain upward price pressures, while economic activity and sovereign debt risks exert downward forces. As uranium becomes increasingly vital to the transition toward a net-zero economy, our findings help bring greater transparency to a traditionally opaque commodity market.John Hua Fan, Adrian Fernandez-Perez, Ivan Indriawan, Neda Todorov
Dragonfly target-detecting neurons adapt to stimulus saliency
No full textThe dragonfly visual system contains neurons that respond to the movement of small targets, even when embedded in visual clutter. Some of these target-detecting neurons facilitate their spiking activity to targets moving along continuous trajectories and selectively attend to one target when presented in a pair. When a target is rapidly repeated, the spiking activity of these ‘small target motion detector’ (STMD) neurons decreases. This ‘adaptation’ is spatially localised with a time course dependent on the frequency of stimulation. Here, we presented rapidly repeating targets of varying contrast and direction, as well as perturbing facilitatory and selective pathways by evoking localised adaptation. Using extracellular electrophysiology, we show that higher target contrast elicits stronger adaptation; however, the time course of diminishing responses was similar across contrasts. This relationship between target saliency and adaptation is also observed with targets moving in the preferred direction causing stronger adaptation. Targets that jitter, as is likely the case during rapid head foveation of prey, induce less adaptation as the jitter radius increases. We observed that the strengthening effect of facilitation competes against suppressive adaptation. Moreover, we observed that STMDs are unlikely to selectively attend to targets that traverse an adapted location. These results provide insight into how dragonfly target-detecting neurons adapt their responsiveness to visual targets in their environment that would be encountered during flight when pursuing prey or conspecifics.Matthew B. Schwarz, Bernard J.E. Evans, David C. O, Carroll, Joseph M. Fabian, Steven D. Wiederma
An efficacious pedagogical space: the power of differentiating through explicit teaching
No full textIn current educational discourse, explicit teaching and differentiation are often positioned as disparate pedagogical approaches. This article challenges the notion that these approaches are inherently incompatible, arguing instead for a harmonious entwinement that enriches the learning experience and creates an efficacious pedagogical space for all students. Explicit teaching, supported by research as an effective strategy for building foundational knowledge, provides a clear and structured approach that helps students grasp new and complex concepts. Differentiation, meanwhile, promotes inclusivity by responding to students’ varying levels of readiness and learning needs, fostering equity without compromising rigour. We address misconceptions surrounding explicit teaching and differentiation, and highlight a number of principles shared by the two approaches. Through practice-based examples, the article illustrates how educators can differentiate when teaching explicitly—at every stage of an explicit teaching lesson. This approach leverages the strengths of explicit teaching and differentiation, creating a pedagogical space where all students can thrive. Ultimately, this provides an approach for teachers that can address the diverse range of learning needs of students, enhancing engagement and improving academic success.Tom Porta, Joanna Anderson, Gemma Scarparol
Leveraging polygenic risk scores to infer causal directions in genotype-by-environment interactions between complex traits
No full textAvailable online 07 February 2026Most existing genotype-by-environment interaction (G×E) methods assume a known causal direction as an assumption that often does not hold and can lead to biased estimates and spurious findings. To address this, we introduce the Genetic Causality Inference Model (GCIM), a novel approach designed to infer causal directions in G×E studies. GCIM integrates polygenic risk scores (PRS) for both the exposure and the outcome to strengthen causal inference and reduce spurious interaction signals. We evaluated GCIM using simulated data across varying genetic and residual correlation settings and compared its performance to existing PRS-by-environment (PRS×E) models under both null and alternative G×E scenarios. GCIM was also applied to real-world UK Biobank data in both causal directions. GCIM consistently outperformed existing methods by accurately identifying the absence of G×E variance and avoiding false positives, even in the presence of strong phenotypic heteroscedasticity due to residual heterogeneity. Other methods often generated spurious associations, especially under reverse causality. Applying GCIM to UK Biobank data, we investigated 11 circulating biomarkers (including liver enzymes, lipids, and inflammatory markers) and three anthropometric traits (BMI, body fat, and waist-tohip ratio [WHR]). GCIM identified that bilirubin modulates genetic effects on BMI and WHR, while body fat modulates genetic effects on C-reactive protein, with associations remaining significant after multiple testing corrections. Overall, GCIM provides a more reliable framework for GxE analysis, particularly under challenging conditions such as residual heterogeneity and uncertain causal direction. However, further development is needed to improve its statistical power.Zinabu Fentaw, Buu Truong, Dovini Jayasinghe, Chris Della Vedova, Gibran Hemani, Beben Benyamin, Elina Hyppönen, Hong Le
Targeted deletion of Cyp24a1 in the intestine reduces mucosal injury and preserves epithelial proliferation after 5-fluorouracil treatment
No full textData source: supplementary material, https://doi.org/10.1016/j.jsbmb.2025.106857Vitamin D has been proposed to attenuate chemotherapy-induced gastrointestinal mucositis (GM). In the intestine, local catabolism of active vitamin D [1,25-dihydroxyvitamin D₃] is mediated by the enzyme Cyp24a1. This study assessed whether deletion of Cyp24a1 specifically in intestinal epithelial cells can protect against 5-fluorouracil (5-FU)-induced intestinal injury and microbiome disruption in mice. Using the Cre-loxP system, Cyp24a1 was selectively ablated in the intestinal epithelium (IEC-KO mice). Male IEC-KO and Cyp24a1^fl/fl^ littermate control mice received a single intraperitoneal injection of 5-FU (450 mg/kg) or saline and were euthanised 48 h later. In control mice, 5-FU markedly reduced duodenal villous height and crypt area (p < 0.01), whereas IEC-KO mice retained intestinal architecture. Proliferation, measured by Ki-67 immunostaining, was preserved in both the small and large intestine of IEC-KO mice following 5-FU treatment (p < 0.05). Notably, colonic Tlr4 mRNA was significantly upregulated in IEC-KO mice (p < 0.001), with no corresponding increase in inflammatory cytokines. 16S rRNA sequencing revealed no change in overall microbial diversity; however, there were notable differences in the relative abundance of key taxa, such as Bifidobacteriaceae and Alistipes. These findings suggest that intestinal Cyp24a1 contributes to susceptibility to chemotherapy-induced intestinal injury and microbial dysbiosis, and that its deletion enhances epithelial regeneration, potentially via innate immune pathways
Automating Perdurant Meta-Property Assignment Using GPT-4
No full textConstructing ontologically coherent subsumption hierarchies for perdurant entities (e.g., events, processes) is a complex and labor-intensive task. While prior work has focused on endurants, automated support for perdurants remains limited. This paper examines whether large language models (LLMs), specifically GPT-4, can assign four ontologically grounded meta-properties to perdurant types. We design a prompting framework incorporating property definitions, domain context, and perspective, and evaluate it against a gold-standard dataset derived from the MAVEN taxonomy. Results show high agreement with human annotations under well-specified prompts, indicating GPT-4’s potential to reduce manual effort in perdurant classification. Our contribution formalizes the conditions enabling reliable LLM-based meta-property assignment for scalable ontology construction
Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management
No full textNeurodegenerative disorders, including Alzheimer's disease (AD), impose a significant burden on society due to their progressive nature and the associated healthcare costs. Autophagy, a vital cellular degradation process, has emerged as a promising therapeutic target in these disorders. This review aims to provide a comprehensive overview of autophagy's role in neurodegenerative diseases, focusing on AD. The pathogenesis of AD involves the accumulation of misfolded proteins, such as beta-amyloid (Aβ) and tau, leading to neuronal dysfunction and cognitive impairment. Autophagy can be crucial in clearing these protein aggregates and maintaining cellular homeostasis. Nevertheless, autophagic dysregulation and mitochondrial dysfunction contribute to further progression of neurodegeneration. Furthermore, recent studies have demonstrated the therapeutic potential of several plant-based phytoconstituents and repurposed molecules that modulate autophagy. These compounds target both mTOR-dependent and independent pathways, highlighting their potential to alleviate disease pathology. This review aims to pave the way for future research and development in this field