Background Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored. Methods EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo. Results In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3β, and transcription factors, including HIF1α, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo. Conclusions Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.

The abundance of insect and fungal pests under a changing climate may threaten historic interiors, libraries and museums, with warmer, potentially more humid winters. This work examines local and indoor climate, insects and fungi in a historic library near Vienna. It reveals a mostly dry and cool environment for the storage of books, but few visitors to induce changes. Temperature and relative humidity have been monitored for 12 months (2021-07/2022-07), with 14 monitors positioned insect traps (blunder traps and some pheromone traps). Fungi in air, on surfaces and in settled dust were also sampled. Winter temperatures in library cupboards and behind shelves were slightly warmer (~1 °C) and more humid than in the library environment. Over the last decade there have been infestations of the biscuit beetles (Stegobium paniceum) but since treatment with sulfuryl difluoride, Anthrenus sp. have dominated. Silverfish are also present, but only in one corner. Fungal outbreaks have also been found, but over five years fungi in air samples have shifted from Penicillium commune and P. chrysogenum to Aspergillus sp. The stable environment at Klosterneuburg is suitable for books, yet insects and mould present suggests vigilance remains necessary, as some microenvironments (e.g., cupboards) can be at risk and there may be materials with high water content, hygroscopic or of nutritional value.

Climate change not only affects the biodiversity of natural habitats, but also the flora and fauna within cities. An increase in average temperature and changing precipitation, but additionally extreme weather events with heat waves and flooding, are forecast. The climate in our cities and, thus, also inside buildings is influenced by the changing outdoor climate and urban heat islands. A further challenge to ecosystems is the introduction of new species (neobiota). If these species are pests, they can cause damage to stored products and materials. Much cultural heritage is within buildings, so changes in the indoor climate also affect pests (insect and fungi) within the museums, storage depositories, libraries, and historic properties. This paper reviews the literature and presents an overview of these complex interactions between the outdoor climate, indoor climate, and pests in museums. Recent studies have examined the direct impact of climate on buildings and collections. The warming of indoor climates and an increased frequency or intensity of extreme weather events are two important drivers affecting indoor pests such as insects and fungi, which can severely damage collections. Increases in activity and new species are found, e.g., the tropical grey silverfish Ctenolepisma longicaudatum has been present in many museums in recent years benefitting from increased indoor temperatures.