Center for Environmental Health

ObjectivesBrown adipose tissue (BAT) dissipates energy via non-shivering thermogenesis, but durable thermogenic benefit requires sustained cold remodeling that stabilizes a cold-adapted tissue state. While most studies have focused on adipocyte-intrinsic pathways that drive acute activation, how stromal niche cells—particularly the vasculature—sense and coordinate long-term adaptation remains poorly defined. Because GPCRs are key sensors of extracellular and neurohumoral cues, we mapped GPCR expression across mouse and human BAT at single-nucleus resolution and identified adhesion GPCRs as a prominent family enriched in vascular cells, with endothelial ADGRF5(GPR116) emerging as a leading candidate regulator.MethodsSingle-nucleus RNA sequencing of mouse and human BAT was used to map GPCR expression across cell types. Global, inducible endothelial-specific, and adipocyte-specific ADGRF5(GPR116) knockout mouse models were each challenged with acute and prolonged cold exposure. Endothelial and adipocyte states were analyzed using single-nucleus RNA sequencing transcriptional profiling, functional vascular assays, and cell–cell communication modeling.ResultsEndothelial deletion of ADGRF5(GPR116) impaired the ability of mice to sustain thermogenesis during prolonged cold exposure, whereas adipocyte-specific deletion did not affect thermogenic capacity in vivo. Loss of endothelial ADGRF5(GPR116) did not alter endothelial cell abundance, but induced endothelial transcriptional reprogramming characterized by disrupted quiescent remodeling programs, shifts in endothelial state with EndMT-like features, and context-dependent alterations in barrier-associated pathways, occurring in the absence of immune cell infiltration or overt fibrosis. Adipocyte reclustering revealed a failure to acquire a fully cold-adapted thermogenic state, with thermogenically inefficient programs and adrenergic hyporesponsiveness, despite preserved sympathetic input. CellChat and NicheNet analyses predicted altered endothelial-derived paracrine signaling capable of reshaping adipocyte identity.ConclusionsEndothelial ADGRF5(GPR116) is a critical regulator of vascular adaptation during sustained cold exposure and supports full acquisition of the thermogenic adipocyte state through endothelial identity and paracrine signaling.

In 2025, psycholinguistic research has the benefit of large, high-quality datasets of human behavior, and massively-scalable metrics for variables of interest like frequency and association. This means we have more data than ever before to shed light on classic language processing phenomena like associative priming. But in order to build and test rigorous theories against this data, we also need computational modeling tools that can simulate cognitive mechanisms and generate quantitative predictions at the same scale. In this paper, we assemble one such case, adapting the ACT-R cognitive modeling framework to make use of association metrics derived from language model embeddings, in service of a scalable model of associative priming in the Lexical Decision Task. ACT-R implements a model of memory retrieval that can use itemwise predictors like frequency and association to predict task response times (RTs), via interpretable and meaningfully-parameterized components like spreading activation. But currently, ACT-R's spreading activation calculations rely on manually-coded similarity scores, which are labor-intensive and prone to inaccuracies, particularly for large vocabularies. In this study, we replace these hand-coded associations with cosine similarity scores derived from Word2Vec and BERT embeddings, thereby improving both scalability and predictive accuracy while retaining ACT-R's interpretability. We compare various versions of our model against observed human RTs from the Semantic Priming Project dataset, observing impressive item-wise prediction accuracy, and achieving the strongest alignment with a model where spreading activation is penalized via a scalable approximation of the classic “fan effect.” These findings provide a proof of concept for integrating embedding-based representations into algorithmic-level models of language processing. More than an insight into models of priming, we see this as a first step toward scalable and specific models of more complex phenomena.

Same-level falls are the most frequent type of occupational accidents in Japan, and approximately 35% of these accidents occurred among healthcare and retail workers. The aim of this study was to analyze the status of same-level falls in the healthcare and retail industries, where many such incidents occur, with a focus on outdoor same-level falls and to elucidate their characteristics. This study targeted occupational accidents due to same-level falls that resulted in four or more days of absence from work among healthcare and retail workers, based on data from the 2021 Occupational Injury Database. From 29,605 occupational injury cases, we identified 2,536 same-level falls and ultimately extracted 2,424 cases for analysis. A physical therapist and industrial physician collaborated to conduct a detailed textual examination of the selected cases in terms of accident onset status. Variables related to the cause of the accident, causative substances, and accident locations were prepared. For the analysis, simple tabulation and cross-aggregation were performed. A chi-square test was used to investigate the correlations between accident location, accident cause, and causative substances. The mean age of the injured workers was 57.0 years (standard deviation, 12.7). The accident location was outdoors in 35.9% of cases. In winter (December to February), the proportion of outdoor accidents increased between 44.2% and 49.5%. The most common cause of outdoor accidents was slipping (35.4%), and the most common causative substance was snow/ice (20.6%). Snow/ice was involved in 44.1% of the same-level falls that occurred outdoors during winter, with some occurring in parking lots while transporting other people. The results revealed that, in addition to indoor same-level falls, outdoor same-level falls during winter were common among healthcare and retail workers. We found that slipping on snow or ice was the primary cause of these accidents. Therefore, it is important that, in addition to risk reduction measures targeting indoor same-level falls, preventive measures should be introduced for outdoor same-level falls among healthcare and retail workers.

We previously described an increased incidence of HIV among individuals infected with Wuchereria bancrofti (WB). However, no host, parasite, or viral factors were reported as directly associated with the increase in HIV incidence in this group. To investigate this, we compared T cell phenotypes between WB+ and WB− women. Flow cytometry analysis of activation and differentiation markers on CD4 T cells, as well as HIV entry receptor CCR5 was performed on cervical and peripheral blood samples from 54 women living without HIV (WLWoH). Additionally, HPV testing was performed on their specimens and for 13 WLWH. WB infection was associated with a significantly increased frequency of CD3+γδ2+ T cells in the cervical mucosa (median 4.0% vs. 1.4%, p = 0.012). Contrary to our expectations, we found lower frequencies of CCR5 on total, memory and activated memory CD4 T cells in the WB+ group. However, differences diminished after accounting for age and site of recruitment. WB and HIV infections were associated with an increased likelihood of high-risk human papillomavirus (HR HPV) positivity. (WB status: odds ratio (OR) 4.1, p = 0.066; HIV status: OR 5.5, p = 0.068). Our findings suggest immunological mechanisms by which WB increases the risk for other infections, e.g., HIV and HR HPV, albeit independent of the CCR5 receptor.

SummaryWe conducted genomic surveillance during the 2022-2023 northern hemisphere influenza season at a university in the southwestern US to assess how local diversity and evolution compared to national trends. We identified 100 positive samples (19%) from clinical swabs collected at a student health clinic and observed a dominance of subtype A(H3N2) which was consistent nationally for that season. However, we found stark differences when examining H3 clades, including an early dominance of 3C.2a1b.2a.2a.3a.1 variants contrasting from country level data in which 3C.2a1b.2a.2b variants were most abundant. We found known H3 amino acid substitutions in epitope sites and estimated vaccine effectiveness to be 0.13–0.48 which aligns with national estimates for that season. Importantly, 3C.2a1b.2a.2a.3a.1 became the dominant H3 clade nationally in 2023–2024 and 2024–2025, highlighting the potential for localized genomic surveillance in semi-closed, highly dense university settings and its potential for early insight of seasonal influenza diversity.

An integrated framework is introduced and applied to assess the health impact of airborne pollution with greater physiological relevance, moving beyond conventional exposure metrics. Measured particle number size distribution data was integrated with a regional respiratory tract deposition fractions to estimate total and alveolar deposited particle surface area concentrations. Land use regression modeling, combined with randomized commuting patterns, enabled the evaluation of city-specific alveolar surface area deposition doses, providing new insight into localized average exposure and its implications for public health. The results showed that although the mean street-level air pollution in Lithuania is higher than in other European cities, the urban background levels are on the same level. We found that the total respiratory deposited surface area concentration is up to 18-fold higher due to coarse particles, which also determines alveolar deposited particle surface area dose. Our findings advocate for using integrated pollution assessments and region-specific policies rather than broad diesel vehicle-targeted bans. The proposed methodology is expected to enhance traditional exposure assessments by switching to lung deposited surface area, which can be further refined by incorporating daytime activity patterns, socio-economic status, and personal health conditions.