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Munteanu, C.

Publications and source records attributed to Munteanu, C..

3 recordsLinked to original sources

A novel IL-1β reporter assay identifies tolcapone as a caspase-1 suppressor targeting pyroptosis in endotoxemia

Unconventional protein secretion mediated by gasdermin D (GSDMD) pores is essential for the release of pro-inflammatory cytokines such as interleukin-1{beta} (IL-1{beta}), a major driver of many inflammatory pathologies. Despite extensive investigation over the years, discovery of IL-1{beta} secretion modulators has been hindered by the lack of robust, scalable experimental platforms. To date, IL-1{beta} related studies largely rely on primary cells and animal models, suitable for mechanistic studies but not readily scalable for high-throughput applications. Here, we engineered a CRISPR-based reporter cell line that allows quantitative monitoring of endogenous IL-1{beta} secretion while preserving the physiologically relevant inflammasome signaling. This platform faithfully recapitulated the response of primary macrophages to pathogen-associated molecular pattern (PAMPs) stimulation and supported the screening of an FDA-approved drug library comprising 1,398 compounds. Form this screen, we identified tolcapone as a potent inhibitor of IL-1{beta} secretion, reducing cytokine release by more than 80% across the screening pipeline. Mechanistically, tolcapone suppressed caspase-1 activation, thereby limiting GSDMD cleavage, pore formation, and the downstream maturation and secretion of IL-1{beta} and IL-18 in vitro. In vivo, tolcapone administration attenuated the acute inflammatory response in a lipopolysaccharide-induced endotoxemia model. Together, these findings establish our reporter platform as a robust tool for discovery of endogenous IL-1{beta} secretion modulators and identify tolcapone as a promising inhibitor of inflammasome-driven immune pathology.

immunology↗

Political legacies shape bear use of anthropogenic spaces

Romania hosts Europes largest brown bear population west of Russia, but rising human-bear encounters and related casualties raise concerns about their drivers and future population management. Using >10,000 encounter reports (2019-2024) in a hierarchical occupancy model accounting for detection processes, we show that bear presence in human-dominated spaces is linked to food conditioning, habituation, and shaped by historical management. Bears occur more often in high wildland-urban interface areas, especially those closer to communist-era elite-hunting grounds with feeding sites. These patterns reflect a long-term legacy of 1960s population management policies interacting with environmental and behavioral processes to shape recent bear behavior. We call for management addressing ecological and social sustainability by phasing out supplemental feeding, reducing habituation through a restored landscape of fear, improving public knowledge of bear ecology, and recognizing historical legacies to promote coexistence. HighlightsO_LIWe used hierarchical species occupancy models to analyze brown bears use of human-dominated spaces in Romania. C_LIO_LIBear detectability depends strongly on activity patterns of both bears and humans C_LIO_LIBear occurrence in anthropogenic spaces is strongly associated with high wildland-urban interface areas and abundant anthropogenic food waste. C_LIO_LIBear occurrence in WUI areas is modulated by historical population management legacies. C_LI

ecology↗

Historical remote sensing highlights long-term persistence of Emperor Penguin (Aptenodytes forsteri) colonies

Historical remote sensing imagery, including digital Landsat and analog Keyhole have potential to inform Antarctic conservation by providing insights into habitat and population dynamics. A case in point is that their long temporal range, extending as far back as the 1960s, offers an unparalleled look into the distribution of Emperor Penguin (Aptenodytes forsteri) colonies and their habitat. Here we demonstrate that Keyhole and Landsat sensors are capable of detecting presence and long-term change in penguin guano on sea-ice despite challenging environmental conditions. For 18 of the 66 known emperor penguin colonies, we confirmed their presence in images that predate earliest published records. We further used dense time series from 1960s to 2024 of the Cape Washington colony to exemplify change in guano area over time - but found little variation in guano area. We show that the guano area undergoes two distinct stages during a breeding season (a stable and clustered early stage, and a diffused and widespread late stage). We correlated guano area with penguin colony size and found that guano area correlates with colony size (Spearmans {rho} = 0.59, p-value = 0.017). Taken together, our results suggest long term resilience of penguin colonies in face of global change, and highlight that the use of historical remote sensing imagery across the Antarctic can inform conservation efforts and benefit the ongoing historical studies of penguin colony dynamics. We highlight the benefit of remote sensing for documenting otherwise inaccessible colonies and for quantifying and understanding historical colony dynamics.

ecology↗