Articles from TUHAT CRIS

 

Recent Submissions

  • Palonen, Pauliina; Kemppinen, Johanna; Karhu, Saila (International Society for Horticultural Science, ISHS, 2020)
    Acta Horticulturae
  • Palonen, Pauliina; Laine, Tuomo Kalevi (International Society for Horticultural Science, ISHS, 2020)
    Acta Horticulturae
  • Karhu, Saila; Bles, C.; Laine, Kalle; Palonen, Pauliina (International Society for Horticultural Science, ISHS, 2020)
    Acta Horticulturae
  • Smit, Margot E.; Llavata-Peris, Cristina; Roosjen, Mark; van Beijnum, Henriette; Novikova, Daria; Levitsky, Victor; Sevilem, Iris; Roszak, Pawel; Slane, Daniel; Juergens, Gerd; Mironova, Victoria; Brady, Siobhan M.; Weijers, Dolf (2020)
    Development of plant vascular tissues involves tissue identity specification, growth, pattern formation and cell-type differentiation. Although later developmental steps are understood in some detail, it is still largely unknown how the tissue is initially specified. We used the early Arabidopsis embryo as a simple model to study this process. Using a large collection of marker genes, we found that vascular identity was specified in the 16-cell embryo. After a transient precursor state, however, there was no persistent uniform tissue identity. Auxin is intimately connected to vascular tissue development. We found that, although an AUXIN RESPONSE FACTOR5/MONOPTEROS (ARF5/MP)-dependent auxin response was required, it was not sufficient for tissue specification. We therefore used a large-scale enhanced yeast one-hybrid assay to identify potential regulators of vascular identity. Network and functional analysis of candidate regulators suggest that vascular identity is under robust, complex control. We found that one candidate regulator, the G-class bZIP transcription factor GBF2, can modulate vascular gene expression by tuning MP output through direct interaction. Our work uncovers components of a gene regulatory network that controls the initial specification of vascular tissue identity.
  • Kallio, Pauliina; Jokinen, Elina; Högström, Jenny; Das, Suvendu; Heino, Sarika; Lähde, Marianne; Brodkin, Jefim; Korhonen, Emilia A.; Alitalo, Kari (2020)
    Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage. Tumor-bearing mice were treated with anti-Ang2 antibodies every 3 or 4 days starting 3 days before 3 x 2 Gy or 4 x 0.5 Gy whole-body or tumor-focused radiation. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal tumors. Single-cell RNA-sequencing revealed that Ang2 blocking rescued radiation-induced decreases inT cells and cells of the monocyte/macrophage lineage. In addition, anti-Ang2 enhanced radiation-induced apoptosis in cultured endothelial cells. In vivo, combination treatment decreased tumor vasculature and increased tumor necrosis in comparison with tumors treated with monotherapies. These results suggest that a combination of Ang2-blocking antibodies with radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice. Significance: These findings offer a preclinical rationale for further testing of the use of radiation in combination with Ang2-blocking antibodies to improve the overall outcome of cancer treatment.
  • Szanto, Timea; Lassila, Riitta; Lemponen, Marja; Lehtinen, Elina; Neerman-Arbez, Marguerite; Casini, Alessandro (2021)
    The outcome of congenital fibrinogen defects (CFD) is often unpredictable. Standard coagulation assays fail to predict the clinical phenotype. We aimed to assess the pheno- and genotypic associations of thrombin generation (TG) and ROTEM in CFD. We measured fibrinogen (Fg) activity and antigen, prothrombin fragments F1+2, and TG by ST Genesia(R) with both Bleed- and ThromboScreen in 22 patients. ROTEM was available for 11 patients. All patients were genotyped for fibrinogen mutations. Ten patients were diagnosed with hypofibrinogenemia, nine with dysfibrinogenemia, and three with hypodysfibrinogenemia. Among the 17 mutations, eight were affecting the Fg gamma chain, four the Fg B beta chain, and five the Fg A alpha chain. No statistical difference according to the clinical phenotypes was observed among FGG and FGA mutations. Median F1+2 and TG levels were normal among the different groups. Fg levels correlated negatively with F1+2 and peak height, and positively with lag time and time to peak. The pheno- and genotypes of the patients did not associate with TG. FIBTEM by ROTEM detected hypofibrinogenemia. Our study suggests an inverse link between low fibrinogen activity levels and enhanced TG, which could modify the structure-function relationship of fibrin to support hemostasis.
  • Gagnon, Joseph Calvin; Swank, Jacqueline M. (2021)
    A national study of clinical directors examined professional development (PD) focused on mental health provided to professionals in juvenile justice facilities for adjudicated youth. A total of 85 clinical directors responded to a mail survey (45% return rate). The survey questions related to (a) topics of staff training and the basis for choosing topics, (b) which professionals participated in each PD topic, (c) training format and frequency of PD, (d) recommended attributes of PD, (e) methods of evaluating PD, and (f) adequacy of PD and how can it be improved. For each topic, PD was typically provided once per year and face to face, rather than online. PD participation rates were commonly in the 30% and 40% ranges for professionals other than clinical directors and counselors, with teachers, correctional officers, administrators, and teaching assistants receiving PD the least. Rarely did PD include recommended attributes of PD, and it was commonly viewed as ineffective. Implications for research and practice related to PD and its relationship to youth reentry from juvenile justice facilities are discussed.
  • The CMS collaboration; Sirunyan, A. M.; Tumasyan, A.; Eerola, P.; Forthomme, Laurent; Kirschenmann, H.; Österberg, K.; Voutilainen, M.; Brücken, Erik; Garcia, F.; Havukainen, J.; Karimäki, V.; Kim, Minsuk; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Luukka, P.; Tuuva, T. (2021)
  • Finndiane Study Grp; Haukka, Jani; Sandholm, Niina; Valo, Erkka; Forsblom, Carol; Harjutsalo, Valma; Cole, Joanne B.; McGurnaghan, Stuart J.; Colhoun, Helen M.; Groop, Per-Henrik (2021)
    Genome-wide association studies (GWAS) and linkage studies have had limited success in identifying genome-wide significantly linked regions or risk loci for diabetic nephropathy (DN) in individuals with type 1 diabetes (T1D). As GWAS cohorts have grown, they have also included more documented and undocumented familial relationships. Here we computationally inferred and manually curated pedigrees in a study cohort of >6,000 individuals with T1D and their relatives without diabetes. We performed a linkage study for 177 pedigrees consisting of 452 individuals with T1D and their relatives using a genome-wide genotyping array with >300,000 single nucleotide polymorphisms and PSEUDOMARKER software. Analysis resulted in genome-wide significant linkage peaks on eight chromosomal regions from five chromosomes (logarithm of odds score >3.3). The highest peak was localized at the HLA region on chromosome 6p, but whether the peak originated from T1D or DN remained ambiguous. Of other significant peaks, the chromosome 4p22 region was localized on top of ARHGAP24, a gene associated with focal segmental glomerulosclerosis, suggesting this gene may play a role in DN as well. Furthermore, rare variants have been associated with DN and chronic kidney disease near the 4q25 peak, localized on top of CCSER1.
  • The CMS collaboration; Sirunyan, A. M.; Tumasyan, A.; Eerola, P.; Forthomme, Laurent; Kirschenmann, H.; Österberg, K.; Voutilainen, M.; Brücken, Erik; Garcia, F.; Havukainen, J.; Karimäki, V.; Kim, Minsuk; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Luukka, P.; Tuuva, T. (2021)
  • Rose, Clemence; Rissanen, Matti P.; Iyer, Siddharth; Duplissy, Jonathan; Yan, Chao; Nowak, John B.; Colomb, Aurelie; Dupuy, Regis; He, Xu-Cheng; Lampilahti, Janne; Tham, Yee Jun; Wimmer, Daniela; Metzger, Jean-Marc; Tulet, Pierre; Brioude, Jerome; Planche, Celine; Kulmala, Markku; Sellegri, Karine (2021)
    Sulfuric acid (H2SO4) is commonly accepted as a key precursor for atmospheric new particle formation (NPF). However, direct measurements of [H2SO4] remain challenging, thereby preventing the determination of this important quantity, and, consequently, a complete understanding of its contribution to the NPF process. Several proxies have been developed to bridge the gaps, but their ability to predict [H2SO4] under very specific conditions, such as those encountered in volcanic plumes (including, in particular, high sulfur dioxide mixing ratios), has not been evaluated so far. In this context, the main objective of the present study was to develop new proxies for daytime [H2SO4] under volcanic plume conditions and compare their performance to that of the proxies available in the literature. Specifically, the data collected at Maido during the OCTAVE (Oxygenated organic Compounds in the Tropical Atmosphere: variability and atmosphere-biosphere Exchanges) 2018 campaign, in the volcanic eruption plume of the Piton de la Fournaise, were first used to derive seven proxies based on knowledge of the sulfur dioxide (SO2) mixing ratio, global radiation, condensation sink (CS) and relative humidity (RH). A specific combination of some or all of these variables was tested in each of the seven proxies. In three of them (F1-F3), all considered variables were given equal weight in the prediction of [H2SO4], whereas adjusted powers were allowed (and determined during the fitting procedure) for the different variables in the other four proxies (A1-A4). Overall, proxies A1-A4 were found to perform better than proxies F1-F3, with, in particular, improved predictive ability for [H2SO4] > 2 x 10(8) cm(-3). The CS was observed to play an important role in regulating [H2SO4], whereas the inclusion of RH did not improve the predictions. A last expression accounting for an additional sink term related to cluster formation, S1, was also tested and showed a very good predictive ability over the whole range of measured [H2SO4]. In a second step, the newly developed proxies were further evaluated using airborne measurements performed in the passive degassing plume of Etna during the STRAP (Synergie Transdisciplinaire pour Repondre aux Aleas lies aux Panaches volcaniques) 2016 campaign. Increased correlations between observed and predicted [H2SO4] were obtained when the dependence of predicted [H2SO4] on the CS was the lowest and when the dependence on [SO2] was concurrently the highest. The best predictions were finally retrieved by the simple formulation of F2 (in which [SO2] and radiation alone were assumed to explain the variations in [H2SO4] with equal contributions), with a pre-factor adapted to the STRAP data. All in all, our results illustrate the fairly good capacity of the proxies available in the literature to describe [H2SO4] under volcanic plume conditions, but they concurrently highlight the benefit of the newly developed proxies for the prediction of the highest concentrations ([H2SO4] > 2-3 x 10(8) cm(-3)). Moreover, the contrasting behaviours of the new proxies in the two investigated datasets indicate that in volcanic plumes, like in other environments, the relevance of a proxy can be affected by changes in environmental conditions and that location-specific coefficients do logically improve the predictions.
  • Härkönen, Heidi (2010)
  • Härkönen, Heidi Kristiina (2016)
  • Härkönen, Heidi (2020)
    [Opinion: Cuba’s Economic Crisis Created Plenty of Suffering].
  • Sopyllo, Konrad; Erickson, Andrew M.; Mirtti, Tuomas (2021)
    Simple Summary Prostate cancer treatment decisions are based on clinical stage and histological diagnosis, including Gleason grading assessed by a pathologist, in biopsies. Prior to staging and grading, serum or blood prostate-specific antigen (PSA) levels are measured and often trigger diagnostic examinations. However, PSA is best suited as a marker of cancer relapse after initial treatment. In this review, we first narratively describe the evolution of histological grading, the current status of Gleason pattern-based diagnostics and glance into future methodology of risk assessment by histological examination. In the second part, we systematically review the biomarkers that have been shown, independent from clinical characteristics, to correlate with clinically relevant end-points, i.e., occurrence of metastases, disease-specific mortality and overall survival after initial treatment of localized prostate cancer. Gleason grading remains the strongest prognostic parameter in localized prostate adenocarcinoma. We have here outlined the evolution and contemporary practices in pathological evaluation of prostate tissue samples for Gleason score and Grade group. The state of more observer-independent grading methods with the aid of artificial intelligence is also reviewed. Additionally, we conducted a systematic review of biomarkers that hold promise in adding independent prognostic or predictive value on top of clinical parameters, Grade group and PSA. We especially focused on hard end points during the follow-up, i.e., occurrence of metastasis, disease-specific mortality and overall mortality. In peripheral blood, biopsy-detected prostate cancer or in surgical specimens, we can conclude that there are more than sixty biomarkers that have been shown to have independent prognostic significance when adjusted to conventional risk assessment or grouping. Our search brought up some known putative markers and panels, as expected. Also, the synthesis in the systematic review indicated markers that ought to be further studied as part of prospective trials and in well characterized patient cohorts in order to increase the resolution of the current clinico-pathological prognostic factors.
  • Ruuskanen, Matti; Åberg, Fredrik; Männistö, Ville T.; Havulinna, Aki S.; Méric, Guillaume; Liu, Yang; Loomba, Rohit; Vazquez-Baeza, Yoshiki; Tripathi, Anupriya; Valsta, Liisa M.; Inouye, Michael; Jousilahti, Pekka; Salomaa, Veikko; Jain, Mohit; Knight, Rob; Lahti, Leo; Niiranen, Teemu J. (2021)
    Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (<60) in internal cross-region validation, consisting of 30% of the data not used in model training, with an average AUC of 0.75 and AUPRC of 0.56 (baseline at 0.30). In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Our models were also predictive of the high FLI group in a different Finnish cohort, consisting of 258 participants, with an average AUC of 0.77 and AUPRC of 0.51 (baseline at 0.21). Pathway analysis of representative genomes of the positively FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of, e.g., ethanol fermentation pathways. These results support several findings from smaller case–control studies, such as the role of endogenous ethanol producers in the development of the fatty liver.
  • Massarella, Kate; Nygren, Anja; Fletcher, Robert; Büscher, Bram; Kiwango, Wilhelm A; Komi, Sanna; Krauss, Judith E; Bukhi Mabele, Matthew; McInturff, Alex; Thomas Sandroni, Laila; Alagona, Peter S; Brockington, Dan; Coates, Robert; Duffy, Rosaleen; Ferraz, Katia; Koot, Stasja; Marchini, Silvio; Reis Persequillo, Alexandre (2021)
  • Toivonen, Ritva; Lilja, Anna; Vihemäki, Heini; Toppinen, Anne (2021)
  • Flores, Huber; Hossein Motlagh, Naser; Zuniga Corrales, Agustin; Liyanage, Mohan; Passananti, Monica; Tarkoma, Sasu; Youssef, Moustafa; Nurmi, Petteri (2021)
    Marine pollution is a growing worldwide concern, affecting the health of marine ecosystems, human health, and weather patterns. To reduce underwater pollution, it is critical to have access to accurate information about the extent of marine pollutants as otherwise appropriate countermeasures and cleaning measures cannot be chosen. Currently such information is difficult to acquire as existing monitoring solutions are highly laborious or costly, limited to specific pollutants, and have limited spatial and temporal resolution. In this article, we present a research vision of large-scale autonomous marine pollution monitoring that uses coordinated groups of autonomous underwater vehicles (AUV)s to monitor the extent and characteristics of marine pollutants. We highlight key requirements and reference technologies to establish a research roadmap for realizing this vision. We also address the feasibility of our vision, carrying out controlled experiments that address classification of pollutants and collaborative underwater processing, two key research challenges for our vision.

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