Eastern Finland Laboratory Center

Abstract Activating mutations in KRAS occur at high frequency in colorectal, lung, and pancreatic cancers, which together account for a substantial proportion of global cancer mortality. Mutant KRAS is constitutively biased toward the GTP-bound state, driving persistent proliferative signaling, but simultaneously imposes oncogenic stresses that threaten cellular homeostasis. To sustain transformation, KRAS-mutant cells engage adaptive stress-response mechanisms, many of which converge on translational control mediated by the eIF2-eIF2B axis. While eIF2B is classically known as a guanine nucleotide exchange factor (GEF) for eIF2 during translation initiation, its potential role in directly regulating oncogenic signaling pathways has remained unexplored. Here, we identify a non-canonical function of eIF2B as a direct activator of mutant KRAS signaling. We demonstrate that eIF2B forms a tripartite complex with SOS and mutant KRAS at the plasma membrane (PM), thereby enhancing KRAS activation and tumorigenic signaling. Biochemical assays and structural modeling support an interaction between the catalytic ε subunit of eIF2B and the allosteric Ras-binding site of SOS, stabilizing SOS in an active conformation. This interaction potentiates SOS-mediated GDP/GTP exchange on mutant KRAS and promotes KRAS nanoclustering at the PM. Importantly, eIF2B exhibits marked specificity for mutant KRAS4B, but not KRAS4A, HRAS, or NRAS. This selectivity arises from KRAS4B’s unique polybasic membrane-anchoring domain and from eIF2B-dependent remodeling of plasma membrane lipid composition. eIF2B enhances glycosphingolipid (GSL) biosynthesis, particularly GM3 and SM4, through translational upregulation of B4GALT5, generating a membrane environment that preferentially supports mutant KRAS4B anchoring and signaling. Disruption of GSL synthesis impairs formation of the eIF2B:SOS:KRAS complex and selectively reduces mutant KRAS activation. Notably, eIF2B’s stimulation of mutant KRAS signaling occurs independently of eIF2α phosphorylation, separating its translational stress-response function from its oncogenic signaling role. Functionally, eIF2B promotes tumor growth specifically in KRAS-mutant cancer models, including human xenografts and an autochthonous KRAS G12C-driven lung adenocarcinoma model. Clinically, high expression of eIF2Bε correlates with poorer outcomes in patients with KRAS-mutant tumors. Our findings identify eIF2B as a previously unrecognized regulator of mutant KRAS-driven tumorigenesis that links translational control, membrane lipid remodeling, and oncogenic signaling. By coordinating SOS activation, KRAS membrane nanoclustering, and selective translation, eIF2B emerges as a central modulator of KRAS oncogenic output and a potential therapeutic and prognostic target. In vivo targeting of eIF2B supports its use as a combinatorial strategy with KRAS inhibition to broaden the therapeutic window in KRAS-mutant cancers. This abstract was edited and refined with the assistance of generative artificial intelligence to improve clarity and conciseness. Citation Format: Hyungdong Kim, Shiqi Diao, Kwang-Jin Cho, Hyun-Ro Lee, Junchen Liu, Pascal Egea, Tatu Pantsar, Milla Kurki, Nour Ghaddar, Shuo Wang, Jia Yi Zou, Mehdi Amiri, Ritchel Gannaban, John F. Hancock, Kylie M. Rice, Atsuo Sasaki, John Asara, Brajendra Tripathi, Douglas Lowy, Rosalie Lawrence, Maria Hatzoglou, Carlos R. Azpilcueta-Nicolas, Jean-Philip Lumb, John Columbus, Thomas J. Turbyville, Christopher B. Marshall, Mitsuhiko Ikura, Jay T. Groves, Nahum Sonenberg, Peter Walter, Antonis E. Koromilas. eIF2B Selectively Anchors and Activates Mutant KRAS4B [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics; 2026 Mar 5-8; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_1):Abstract nr B001.

Abstract. Global climate models (GCMs) face uncertainties in estimating Earth's radiative budget due to aerosol-cloud interactions (ACI). Accurate particle number size distributions (PNSDs) are crucial for improving ACI representation, requiring precise modelling of aerosol sources and sinks. Using a Lagrangian trajectory framework, we examine how clouds and precipitation influence aerosols during transport, and thereby influence aerosol–cloud relationships in the boreal forest. Two GCMs, the United Kingdom Earth System Model (UKESM1) and ECHAM6.3-HAM2.3-MOZ1.0 with the SALSA2.0 aerosol module (ECHAM-SALSA), are complemented with model-derived trajectories and evaluated against in-situ observations, which are accompanied by reanalysis trajectories. Overall aerosol–precipitation trends are similar between GCMs and observations. However, seasonal differences emerge: in summer, UKESM1 exhibits more efficient aerosol removal via precipitation than ECHAM-SALSA and observations, whereas in winter, the opposite is observed. These differences coincide with key variables controlling aerosol activation, such as sub-grid scale updraught velocities and PNSDs. For example, in winter, removal of total aerosol mass in ECHAM-SALSA was stronger than in UKESM1, coinciding with higher activated fractions and larger sub-grid scale updraught velocities in ECHAM-SALSA. For both GCMs, cloud processing along trajectories increased SO4 mass, mainly in the accumulation mode, consistent with observations and model parametrizations. Discrepancies arise more from differences in PNSDs and updraught velocities than from wet removal parametrizations, an example being the underrepresentation of small particles in UKESM1. While our findings are representative of boreal region with predominantly stratiform precipitation, further work is needed to evaluate their applicability to other regions.

Interactions with air pollutants can modify pollen properties, thereby altering their allergenicity and even the severity of pollen-induced symptoms. This study aimed to examine whether birch pollen collected from locations with varying degrees of urbanization and traffic exposure differs in allergen content and immunotoxic properties. To our knowledge, this is the first study to integrate in situ birch pollen sampling across contrasting urban environments with morphological, chemical, and immunotoxic profiling in two complementary human cell models. Birch pollen samples were collected from four locations in Kuopio, Finland, including a low-traffic residential area, an urban park, and two sites adjacent to major roads and a highway. Elemental composition was analyzed using scanning electron microscopy. Pollen viability and allergen content were assessed by trypan blue staining and ELISA. Immunotoxic properties of pollen, including viability, metabolic activity, oxidative stress, and cytokine production, were assessed using two cellular models: a co-culture of human alveolar epithelium and macrophages, and peripheral blood mononuclear cells (PBMCs). Pollen from high-traffic locations contained more metallic elements. Allergen (Bet v 1) concentrations were 2.6-fold higher in pollen from the highway site compared to the pollen collected from the residential area. Pollen viability followed a similar pattern, lowest near the highway and highest in the residential area. Pollen from the city center induced the highest cytokine (i.e., TNF-α, GM-CSF, and MIP-1β) release in airway cell model. While cell viability and metabolic activity remained largely unaffected, oxidative stress responses varied, with the highest levels observed in pollen from highway-adjacent trees. These findings suggest that pollen collected near high-traffic areas may have increased potential to trigger allergic inflammation and respiratory distress. The elemental composition of pollen and the immune responses it induced varied across sampling sites, indicating the complexity by which environmental factors can influence pollen properties and potential health effects.

Relative humidity and water activity (aH) reductions have been known to suppress the hydration of anhydrous cement clinker phases. However, the relationship between ye’elimite (C4A3$) hydration kinetics and water activity remain unclear. This study employs experimental and thermodynamic modeling approaches to investigate the influence of water activity on ye’elimite hydration in the “C4A3$ + water”, and “C4A3$ + gypsum + water” systems. Experimental findings indicate that as water activity decreases, C4A3$ hydration diminishes until the reaction is brought to a halt at a threshold aH. The critical aH and corresponding solubility constant of C4A3$ (KC4A3S¯) estimated from thermodynamic analysis are 0.46 and 10–24.554, respectively. Critical aH and KC4A3S¯ are fundamental data for the numerical modeling of hydration in C4A3$-based cementitious systems. Additionally, thermodynamic modeling was employed to reveal the effects of isopropanol ingress on the precipitation-dissolution of hydrated phase assemblage and the speciation in the aqueous pore solution.

ABSTRACT This present article reports on the experiences of parents of children with cancer who participated in an emotionally focused Hold Me Tight (HMT) group intervention. A purposive sample of 24 parents was recruited from 3‐day HMT courses. Focus group conversations were conducted at the end of each course and analysed using Interpretative Phenomenological Analysis (IPA). The 3‐day HMT group intervention resulted in experiences that strengthened parents' personal well‐being and couple resilience. Individual, couple, and family‐related meanings emerged in these conversations. The subthemes of the individual‐related meanings included identifying the need for self‐exploration, enabling a new form of self‐observation, increasing self‐understanding, and improving personal well‐being and resilience. The subthemes of the couple‐related meanings were identifying and processing couple relationship dynamics, increasing understanding of relationship interactions, facilitating prevention and coping with challenging situations, and strengthening the mutual emotional connection. The subtheme of the family‐related meanings was increasing understanding of family interactions. These results suggest the need for further research on HMT group interventions for this target population.

<strong class="journal-contentHeaderColor">Abstract.</strong> General circulation models (GCMs) face uncertainties in estimating Earth's radiative budget due to aerosol-cloud interactions (ACI). Accurate aerosol number size distributions are crucial for improving ACI representation in GCMs, requiring precise modelling of aerosol source and sink processes throughout their lifetime. This study employs a Lagrangian trajectory framework to analyse how clouds and precipitation influence aerosol lifecycles during transport in the boreal forest. A comparison of two GCMs, the United Kingdom Earth System Model (UKESM1) and ECHAM6.3-HAM2.3-MOZ1.0 with the SALSA2.0 aerosol module (ECHAM-SALSA), is conducted. An evaluation against in-situ observations and reanalysis-based trajectories is performed. Results show that overall aerosol-precipitation trends are similar between GCMs and observations. However, seasonal differences emerge: in summer, UKESM1 exhibits more efficient aerosol removal via precipitation than ECHAM-SALSA and observations, whereas in winter, the opposite is observed. These were found to coincide with differences in key variables controlling aerosol activation, such as sub-grid scale updraughts and number size distributions. For example, in winter the removal of the total aerosol mass in ECHAM-SALSA was stronger compared to UKESM1, coinciding with higher activated fractions during airmass transport, which, on the other hand, were likely due to the larger sub-grid scale updraughts in ECHAM-SALSA. For both GCMs, investigation of aqueous-phase chemical processing along the trajectories showed clear increase of SO₄ mass for cloud-processed air masses when compared to clear sky conditions, in-line with the observations. As expected, based on the model parametrizations, these increases in SO₄ were mostly distributed to the accumulation mode aerosols.

Abstract. Fuel-operated auxiliary heaters (AH) are potentially significant additional sources of particle and gas phase pollution from vehicles, but information on their emissions is scarce. Especially understanding of AH exhaust−originated secondary aerosol formation is lacking. In this study, we measured the gas and particle emissions, including secondary emissions, of diesel- and gasoline-operated AHs used in passenger cars. Investigation revealed the importance of peak emissions during start and shutdown events of the heaters and differences between emissions of gasoline and diesel fuelled AHs. Namely, gasoline-operated AHs produced particles also under steady-state operating conditions, while their diesel counterparts did not. Furthermore, ambient air temperature was observed to impact the emission profiles, with, for example, higher NOx and particle mass emissions but lower particle number emissions observed in outdoor (−19 to −7 ℃) measurements compared to laboratory measurements (+25 ℃). However, further quantification is necessary to fully quantify the temperature-related effects to AH emissions. Our findings highlight the importance of characterizing also the atmospherically aged aerosols, specifically secondary organic aerosol formation, which was here simulated both by an environmental chamber and by an oxidation flow reactor. The particle mass in photochemically aged aerosols surpassed the fresh exhaust particulate mass emissions by 1 to 3 orders of magnitude, with the increase depending mainly on fuel, combustion conditions, and aging methods. Further research into formation pathways of secondary aerosols from precursors is still needed as well as quantification of vehicle fleet level AH emissions to enable estimation of atmospheric and air quality effects of AH usage.

Tertiary lymphoid structures (TLSs) associate with prognosis of many malignancies. However, the clinical significance of TLSs is not well-elucidated in nasopharyngeal carcinoma (NPC) patients. In this whole population-based multicenter study, a total of 115 patients treated for NPC were included. The patients were treated at the five Finnish university hospitals. TLSs were assessed in routine hematoxylin and eosin (HE)-stained sections. Presence of TLSs associates significantly with improved survival in NPC. Absence of TLSs had a significant association with a poor disease-specific survival of NPC with a hazard ratio (HR) of 1.96 (95 % CI 1.09-3.53, P = 0.025) in the multivariable analysis. Similarly, absence of TLSs associated with worse overall survival with a HR of 1.68 (95 % CI 1.02-2.75, P = 0.040). TLSs seem to be associated with prognosis of NPC patients. Having TLSs in NPC tumors correlates with good survival. The assessment of TLSs could aid in understanding the clinical behavior and in planning the treatment of NPC.