Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

Do the Quality and Quantity of Honey Bee-Collected Pollen Vary Across an Agricultural Land-Use Gradient?

Pollen is the source of protein for most bee species, yet the quality and quantity of pollen is variable across landscapes and growing seasons. Understanding the role of landscapes in providing nutritious forage to bees is important for pollinator health, particularly in areas undergoing significant land-use change such as in the Northern Great Plains (NGP) region of the United States where grasslands are being converted to row crops. We investigated how the quality and quantity of pollen collected by honey bees (Apis mellifera L. [Hymenoptera: Apidae]) changed with land use and across the growing season by sampling bee-collected pollen from apiaries in North Dakota, South Dakota, and Minnesota, USA, throughout the flowering season in 2015-2016. We quantified protein content and quantity of pollen to investigate how they varied temporally and across a land-use gradient of grasslands to row crops. Neither pollen weight nor crude protein content varied linearly across the land-use gradient; however, there were significant interactions between land use and sampling date across the season, particularly in grasslands. Generally, pollen protein peaked mid-July while pollen weight had two maxima in late-June and late-August. Results suggest that while land use itself may not correlate with the quality or quantity of pollen resources collected by honey bees among our study apiaries, the nutritional landscape of the NGP is seasonally dynamic, especially in certain land covers, and may impose seasonal resource limitations for both managed and native bee species. Furthermore, results indicate periods of qualitative and quantitative pollen dearth may not coincide.

High-severity wildfire limits available floral pollen quality and bumble bee nutrition compared to mixed-severity burns.

High-severity wildfires, which can homogenize floral communities, are becoming more common relative to historic mixed-severity fire regimes in the Northern Rockies of the U.S. High-severity wildfire could negatively affect bumble bees, which are typically diet generalists, if floral species of inadequate pollen quality dominate the landscape post-burn. High-severity wildfires often require more time to return to pre-burn vegetation composition, and thus, effects of high-severity burns may persist past initial impacts. We investigated how wildfire severity (mixed- vs. high-severity) and time-since-burn affected available floral pollen quality, corbicular pollen quality, and bumble bee nutrition using percent nitrogen as a proxy for pollen quality and bumble bee nutrition. We found that community-weighted mean floral pollen nitrogen, corbicular pollen nitrogen, and bumble bee nitrogen were greater on average by 0.82%N, 0.60%N, and 1.16%N, respectively, in mixed-severity burns. This pattern of enhanced floral pollen nitrogen in mixed-severity burns was likely driven by the floral community, as community-weighted mean floral pollen percent nitrogen explained 87.4% of deviance in floral community composition. Only bee percent nitrogen varied with time-since-burn, increasing by 0.33%N per year. If these patterns persist across systems, our findings suggest that although wildfire is an essential ecosystem process, there are negative early successional impacts of high-severity wildfires on bumble bees and potentially on other pollen-dependent organisms via reductions in available pollen quality and nutrition. This work examines a previously unexplored pathway for how disturbances can influence native bee success via altering the nutritional landscape of pollen.

Nesting success of wood-cavity-nesting bees declines with increasing time since wildfire.

Bees require distinct foraging and nesting resources to occur in close proximity. However, spatial and temporal patterns in the availability and quantity of these resources can be affected by disturbances like wildfire. The potential for spatial or temporal separation of foraging and nesting resources is of particular concern for solitary wood-cavity-nesting bees as they are central-place, short-distance foragers once they have established their nest. Often the importance of nesting resources for bees have been tested by sampling foraging bees as a proxy, and nesting bees have rarely been studied in a community context, particularly postdisturbance. We tested how wood-cavity-nesting bee species richness, nesting success, and nesting and floral resources varied across gradients of wildfire severity and time-since-burn. We sampled nesting bees via nesting boxes within four wildfires in southwest Montana, USA, using a space-for-time substitution chronosequence approach spanning 3-25 years postburn and including an unburned control. We found that bee nesting success and species richness declined with increasing time postburn, with a complete lack of successful bee nesting in unburned areas. Nesting and floral resources were highly variable across both burn severity and time-since-burn, yet generally did not have strong effects on nesting success. Our results together suggest that burned areas may provide important habitat for wood-cavity-nesting bees in this system. Given ongoing fire regime shifts as well as other threats facing wild bee communities, this work helps provide essential information necessary for the management and conservation of wood-cavity-nesting bees.