University of Turku

Paturi P., Aye M.M., Soman A., Notthoff C., Kluth P., Strickland N., Huhtinen H.

Aye M.M., Rivasto E., Rijckaert H., Huhtinen H., Paturi P.

Jeevannavar A., Florenza J., Divne A., Tamminen M., Bertilsson S.

Abstract Single-cell transcriptomics is a key tool for unravelling metabolism and tissue diversity in model organisms. Its potential for elucidating the ecological roles of microeukaryotes, especially non-model ones, remains largely unexplored. This study employed the Smart-seq2 protocol on Ochromonas triangulata, a microeukaryote lacking a reference genome, showcasing how transcriptional states align with two distinct growth phases: a fast-growing phase and a slow-growing phase. Besides the two expected expression clusters, each corresponding to either growth phase, a third transcriptional state was identified across both growth phases. Metabolic mapping revealed a boost of photosynthetic activity in the fast growth over the slow growth stage, as well as down-regulation trend in pathways associated with ribosome functioning, CO2 fixation, and carbohydrate catabolism characteristic of the third transcriptional state. In addition, carry-over rRNA reads recapitulated the taxonomic identity of the target while revealing distinct bacterial communities, in co-culture with the eukaryote, each associated with distinct transcriptional states. This study underscores single-cell transcriptomics as a powerful tool for characterizing metabolic states in microeukaryotes without a reference genome, offering insights into unknown physiological states and individual-level interactions with different bacterial taxa. This approach holds broad applicability to describe the ecological roles of environmental microeukaryotes, culture-free and reference-free, surpassing alternative methods like metagenomics or metatranscriptomics.

Grimland M., Mori Y., Lesinskiene S., Li L., Ong S.H., Praharaj S.K., Wiguna T., Zamani Z., Heinonen E., Gilbert S., Brunstein Klomek A., Sourander A., the EACMHS Study Group

The widespread use of the Internet among teenagers has raised concerns about cyberbullying and its impact on adolescent well-being. This study examined the association between cyberbullying victimization and suicide attempts among adolescents in high-income and low/middle-income countries. Data from six countries (Singapore, China, Iran, Indonesia, India, and Lithuania) were collected as part of the Eurasian Child Mental Health Study. A total sample of 9892 adolescents aged 13–15 years old (51.9% girls) was analyzed. Generalized estimating equation models with school-wise clusters were conducted. The prevalence of suicide attempts was 4.8%, with higher rates among girls. Cyberbullying victimization only was reported by 5.4% of the participants, while traditional bullying victimization only was reported by 19.2%. The study found that being a victim of combined (both traditional and cyberbullying) had the highest odds of suicide attempt in both high-income and low/middle-income countries. Emotional symptoms were identified as a moderator, influencing the association between combined bullying victimization and suicide attempt. These findings highlight the urgent need for global efforts to prevent and intervene in cyberbullying and its detrimental effects on adolescent mental health. The study emphasizes the importance of examining regional risk factors and implementing targeted interventions to address this growing public health concern.

Wang J., Kartiosuo N., Raitakari O., Viikari J., Juonala M., Bazzano L., Sinaiko A.R., Steinberger J., Daniels S.R., Venn A., Magnussen C., Woo J.G., Ramakrishnan R., Urbina E.M., Kähönen M., et. al.

Abstract Aims The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomisations and drug trials. However, the association between childhood HDL-C and its changes and adult ASCVD remains undefined. This study aimed to determine this association. Methods Participants: Children in the International Childhood Cardiovascular Cohort (i3C) Consortium with childhood HDL-C and adult ASCVD follow-up. Age- and sex-standardized HDL-C z-scores were calculated for childhood (3-19 years), early childhood (3-11 years), and adolescence (12-19 years); Low HDL-C defined as <1.03mmol/L; Participants classified as consistently normal, low-to-normal, normal-to-low, and consistently low based on HDL-C status at early childhood and adolescence. ASCVD events: Identified using self-reports adjudicated by medical records or death registries. Analysis: Cox proportional hazards models quantified the associations between childhood HDL-C and adult ASCVD. Results The study included 38,589 participants (49.7% males, mean age in 2016: 46.4 years) with 779 ASCVD and 784 imputed ASCVD events. After adjusting for sex, cohort, age and HDL-C measurement year, higher HDL-C z-scores in childhood, early childhood and adolescence were associated with lower adult ASCVD risk (HRs: 0.81-0.82), with the lowest risk at HDL-C >1.50mmol/L. Normal-to-low (HR 1.38, 95%CI 1.04-1.82) and consistently low (HR 1.94, 95%CI 1.45-2.63) childhood HDL-C increased adult ASCVD risk compared to consistently normal HDL-C. Adjusting for BMI and triglycerides weakened these associations. Conclusions Childhood and adolescent HDL-C were prospectively and inversely associated with adult ASCVD, suggesting that low HDL-C could be a risk maker of adult ASCVD. Future replications, mechanistic studies and Mendelian randomisations on childhood HDL-C may clarify its causal effects on adult ASCVD.

Liu M., Soon E.Y., Lange K., Juonala M., Kerr J.A., Liu R., Dwyer T., Wake M., Burgner D., Li L.

Background The adverse cardiovascular effects of smoking are well established. We aimed to investigate the less well‐understood effects of pregnancy smoke exposure on offspring cardiovascular health in early adolescence. Methods and Results Data were drawn from the nationally representative Longitudinal Study of Australian Children's Child Health CheckPoint. Mothers reported mean daily cigarettes smoked in each trimester (≤10 versus >10/day), and smoking cessation during pregnancy. Blood pressure, pulse wave velocity, carotid intima‐media thickness, and retinal microvascular parameters were measured in early adolescence (mean 11.5 years). Hypertension was defined as systolic blood pressure ≥120 or diastolic blood pressure ≥80 mm Hg. 187 (11.8%) of 1582 women (mean age 30.7±0.2 years), smoked during pregnancy, of whom 143 (76.5%) smoked throughout pregnancy, and 58 (31.0%) smoked >10 cigarettes/day. Compared with those born to nonsmoking mothers, the odds of hypertension in early adolescence were 1.44 (95% CI, 1.01–2.06) if mothers ever smoked, 1.99 (1.22–3.24) if mothers smoked >10 cigarettes/day, and 1.64 (1.11–2.42) if mothers smoked throughout pregnancy There was limited evidence of associations between smoking throughout pregnancy and other cardiovascular measures. Offspring of mothers who stopped smoking during pregnancy and nonsmokers had similar cardiovascular measures, apart from hypertension. Conclusions Offspring of mothers who smoked in pregnancy have increased risks of hypertension in adolescence, with increased risk with greater exposure intensity and duration. Mothers who stopped smoking during pregnancy had offspring with similar cardiovascular health to those born to nonsmokers. Our findings underscore the importance of specific strategies to stop maternal smoking before conception and during pregnancy.

Poosakkannu A., Xu Y., Suominen K.M., Meierhofer M.B., Sørensen I.H., Madsen J.J., Plaquin B., Guillemain M., Joyeux E., Keišs O., Lilley T.M., Lehikoinen A., Pulliainen A.T.

ABSTRACT Identifying the wildlife reservoirs of bacterial pathogens, spatially and temporally, is important for assessing the threats to human and the rest of the biosphere. Our objective was to study Europe-wide characteristics of the fecal microbiota of four highly mobile migratory vertebrates, that is, one bat ( Pipistrellus nathusii ) and three bird species ( Turdus merula , Anas platyrhynchos , Columba palumbus ). The 351 sample PacBio data set of almost the entire 16S rRNA gene with 438,997 amplicon sequence variants (ASVs) assigned 3,277 bacterial species. A significant proportion of the ASVs were assigned to bacterial genera having species pathogenic to human or animals. These pathogen ASVs accounted for 45% of all the ASVs and statistically were more frequent at higher latitudes and in younger age groups. In 36 samples, more than >90% of all the PacBio reads were assigned to these pathogenic genera. We designate to individuals of these samples a new term, that is, a pathogen bloomer. The pathogen bloomers, which did not display apparent macroscopic disease symptoms, were detected in Nathusius bat ( n = 8; Finland and Latvia), blackbird ( n = 6; Finland, Latvia and Denmark), and wood pigeon ( n = 22; Finland and France), but not in mallard. Key species-level taxonomic assignments in the pathogen bloomers were the two well-known enteropathogens ( Campylobacter jejuni or Escherichia coli ) and one emerging enteropathogen ( Escherichia marmotae ). Our data imply that the studied common migratory vertebrates may contribute to the transmission of bacterial pathogens across the European continent. IMPORTANCE The understanding of gut microbiota composition and dynamics in wild vertebrate populations, especially in highly mobile vertebrates, birds and bats, remains limited. Our study sheds light on the critical knowledge gap in how common pathogenic bacterial taxa of fecal microbiota are in migratory bats and birds in Europe. We found out that bacterial genera having species pathogenic to human or animals constituted a substantial portion of the fecal microbiota in all the studied host taxa. Most importantly, we identified asymptomatic individuals that were dysbiotic with bacterial pathogen overgrowth. These previously unknown pathogen bloomers appear as potent Europe-wide transmitters of bacterial pathogens, which cause, for example, diarrhea and bacteremia in human. Our findings may contribute to better understanding of seasonal disease hotspots and pathogen spillover risks related to migratory vertebrates.

de Morais E.F., Mäkitie A., Coletta R.D., Almangush A.

ABSTRACTBackgroundThis article aims to provide a broad overview of the oral squamous cell carcinoma (OSCC) tumor stroma, describing and discussing recent advances in the understanding of different stromal elements and their roles in tumor progression. We also describe potential new therapeutic approaches targeting the stroma.MethodsA literature review on the role of stromal biomarkers in OSCC was conducted. A narrative overview of current literature was undertaken to synthesize the contexts with elaboration and summary.ResultsThe crosstalk between cancer cells and the tumor stroma, a major driver of tumor progression and metastasis, has increasingly been unveiled. This review highlights the tumor‐to‐stroma ratio (TSR) as a valuable prognostic marker in OSCC, with high stromal content (TSR > 50%) linked to poorer survival. On the other hand, tumor‐infiltrating lymphocytes are associated with improved prognosis and longer survival. Furthermore, emerging markers, such as cancer‐associated fibroblasts and desmoplastic reactions, play significant roles in promoting tumor invasiveness and resistance to therapy. The review identifies gaps in current evidence and proposes directions for future research to further clarify the prognostic utility of stromal components.ConclusionsStromal markers provide valuable prognostic insights into OSCC and could enhance clinical decision‐making, emphasizing the complexity of OSCC progression.

Korsunova A., Kurilova M., Viholainen N., Lundberg P., Nenko O., Galaktionova A.

The circular economy vision assumes that consumers will be increasingly turning into users of circular services, enabled by various digital platforms. Yet while apps can help to connect and educate consumers on circularity, the app market can be overwhelming. Moreover, many digital tools are designed for consumers as independent rational individuals, interested in self-gain and self-education. Our study combines social learning theory, literature on circular consumption and digitalisation to highlight the need for digital solutions that could reinforce existing social relations and serve as enabling tools for neighbourhood-based approaches of reusing, sharing, renting and recycling together with close circles of friends, relatives or neighbours. Empirically, we draw on everyday experiences of front-runner citizens who have been implementing circularity, zero waste and sustainable consumption principles to examine whether and how digital platforms have facilitated their circularity in everyday life. Our study is based on a set of 40 semi-structured interviews, analysing the circular experiences of eco-activists and eco-influencers from Finland and the city of St Petersburg (Russia) and their use of digital platforms for circularity. Our results show that despite the flourishing app market, the circular citizens from our data often relied on ad-hoc solutions developed through social media platforms and messenger apps to facilitate their circular consumption in local communities with shared values regarding circularity. While these solutions might lack the sophistication and technical flexibility for convenient search and filtering, they still remain attractive due to their capacity to embed circular consumption locally and among preferred social circles.

Meng Y., Raitakari O.T., Magnussen C.G.

Shepherd A.

Quilted petticoats were a common garment in the wardrobes of many women in eighteenth-century Finland. Both fashionable and practical, these items were passed on from one generation to the next and often altered and refashioned by their later owners. This article examines three such petticoats in the collections of the Porvoo Museum in Finland and places the garments within the sociocultural and historical contexts of their time. Through the study of these petticoats and the use of inventory deed records, this article discusses the value of textiles in eighteenth-century Finland and how such garments can be used as historical sources.

Santonen M., Lahti A., Rad Z.J., Miettinen M., Ebrahimzadeh M., Lehtiö J., Snellman E., Laukkanen P., Punkkinen M., Kokko K., Parkkinen K., Eklund M.

Wiels W.A., Oomens J.E., Engelborghs S., Baeken C., von Arnim C.A., Boada M., Didic M., Dubois B., Fladby T., van der Flier W.M., Frisoni G.B., Fröhlich L., Gill K.D., Grimmer T., Hildebrandt H., et. al.

ImportanceDepressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.ObjectiveTo examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia.Design, Setting, and ParticipantsCross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.Main Outcomes and MeasuresAmyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.ResultsIn individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.Conclusions and RelevanceDepressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Dadson P., Honka M., Suomi T., Haridas P.A., Rokka A., Palani S., Goltseva E., Wang N., Roivainen A., Salminen P., James P., Olkkonen V.M., Elo L.L., Nuutila P.

In this study, we investigated the impact of bariatric surgery on the adipose proteome to better understand the metabolic and cellular mechanisms underlying weight loss following the procedure. A total of 46 patients with severe obesity were included, with samples collected both before and after bariatric surgery. Additionally, 15 healthy, non-obese individuals who did not undergo surgery served as controls and were studied once. We utilized quantitative liquid chromatography tandem mass spectrometry analysis to conduct a large-scale proteomic study on abdominal subcutaneous biopsies obtained from the study participants. Our proteomic profiling revealed that among the 2254 compared proteins, 46 were upregulated, and 34 were downregulated 6 months post-surgery compared to baseline (FDR < 0.01). We observed a downregulation of proteins associated with mitochondrial integrity, amino acid catabolism, and lipid metabolism in the patients with severe obesity compared to the controls. Bariatric surgery was associated with an upregulation in pathways related to mitochondrial function, protein synthesis, folding and trafficking, actin cytoskeleton regulation, and DNA binding and repair. These findings emphasize the significant changes in metabolic and cellular pathways following bariatric surgery, highlighting the potential mechanisms underlying the observed health improvements post-bariatric surgery. The data provided alongside this paper will serve as a valuable resource for the development of targeted therapeutic strategies for obesity and related metabolic complications.

Kearns M.L., Lahdenperä M., Galante L., Rautava S., Lagström H., Reynolds C.M.

Background/Objectives: Maternal Body Mass Index (BMI), diet quality, and their associated effects on offspring birth measures are well-established. Emerging evidence, largely from animal studies, has indicated paternal factors can influence offspring birth outcomes. However, this effect is poorly understood in humans. Our aim was to examine the association between paternal BMI and diet quality score and offspring birth measures. Methods: Participants from the STEPS (Steps to the healthy development) Study in Southwest Finland were recruited during the first trimester of pregnancy or after delivery. A total of 1586 fathers and their children were included for BMI analysis, and 208 fathers and their children were included for dietary analyses. Paternal BMI was calculated using self-reported weight and height at recruitment, and dietary behaviour was assessed using the Index of Diet Quality (IDQ) at 30 weeks’ gestation. Offspring birth weight and length z-scores were calculated using the recently published references specific to the Finnish population. Generalized linear model analyses were carried out to determine associations between paternal factors and offspring z-scores. Results: The mean paternal BMI was 26 (SD ± 3.5). Over half of the fathers were classed as having an unhealthy diet, classified as poor in adhering to nutrition recommendations including higher intakes of saturated fatty acids, and inadequate intakes of protein, saccharose, fibre, vitamins, and minerals. Paternal BMI was not significantly associated with offspring birth weight (β = 0.00 p = 0.884) or birth length (β = 0.00, p = 0.774) z-scores when adjusted for maternal and other paternal and parental factors. Paternal diet quality score was not associated with offspring birth weight (β = −0.01, p = 0.515) or birth length (β = 0.07 p = 0.291) z-scores. Conclusions: This study shows paternal BMI or diet quality at 30 weeks’ gestation does not significantly impact offspring birth measures. Given the known impact of nutrition on epigenetics, examining the potential influence of paternal factors at conception on offspring growth is of major importance and should be included in future studies.