Articles

Recent Submissions

  • Alijoki, Alisa; Suhonen, Eira Anneli; Nislin, Mari; Kontu, Elina; Sajaniemi, Nina (2013)
  • Kokko, Tiina; Pesonen, Henri; Kontu, Elina; Pirttimaa, Raija (2015)
  • Alanko, Anna Maija; Hellman, Carin Matilda Emelie (University of Helsinki Centre for Research on Addiction, Control and Governance (CEACG), 2017)
  • Elo, Teresa; Lindfors, Paivi H.; Lan, Qiang; Voutilainen, Maria; Trela, Ewelina; Ohlsson, Claes; Huh, Sung-Ho; Ornitz, David M.; Poutanen, Matti; Howard, Beatrice A.; Mikkola, Marja L. (2017)
    Mammary gland development begins with the appearance of epithelial placodes that invaginate, sprout, and branch to form small arborized trees by birth. The second phase of ductal growth and branching is driven by the highly invasive structures called terminal end buds (TEBs) that form at ductal tips at the onset of puberty. Ectodysplasin (Eda), a tumor necrosis factor-like ligand, is essential for the development of skin appendages including the breast. In mice, Eda regulates mammary placode formation and branching morphogenesis, but the underlying molecular mechanisms are poorly understood. Fibroblast growth factor (Fgf) receptors have a recognized role in mammary ductal development and stem cell maintenance, but the ligands involved are ill-defined. Here we report that Fgf20 is expressed in embryonic mammary glands and is regulated by the Eda pathway. Fgf20 deficiency does not impede mammary gland induction, but compromises mammary bud growth, as well as TEB formation, ductal outgrowth and branching during puberty. We further show that loss of Fgf20 delays formation of Eda-induced supernumerary mammary buds and normalizes the embryonic and postnatal hyperbranching phenotype of Eda overexpressing mice. These findings identify a hitherto unknown function for Fgf20 in mammary budding and branching morphogenesis.
  • Huang, Weini; Traulsen, Arne; Werner, Benjamin; Hiltunen, Teppo; Becks, Lutz (2017)
    Trade-offs play an important role in evolution. Without trade-offs, evolution would maximize fitness of all traits leading to a "master of all traits". The shape of trade-offs has been shown to determine evolutionary trajectories and is often assumed to be static and independent of the actual evolutionary process. Here we propose that coevolution leads to a dynamical trade-off. We test this hypothesis in a microbial predator-prey system and show that the bacterial growth-defense trade-off changes from concave to convex, i.e., defense is effective and cheap initially, but gets costly when predators coevolve. We further explore the impact of such dynamical trade-offs by a novel mathematical model incorporating de novo mutations for both species. Predator and prey populations diversify rapidly leading to higher prey diversity when the trade-off is concave (cheap). Coevolution results in more convex (costly) trade-offs and lower prey diversity compared to the scenario where only the prey evolves.
  • Matilainen, Olli; Sleiman, Maroun S. Bou; Quiros, Pedro M.; Garcia, Susana M. D. A.; Auwerx, Johan (2017)
    Age-associated changes in chromatin structure have a major impact on organismal longevity. Despite being a central part of the ageing process, the organismal responses to the changes in chromatin organization remain unclear. Here we show that moderate disturbance of histone balance during C. elegans development alters histone levels and triggers a stress response associated with increased expression of cytosolic small heat-shock proteins. This stress response is dependent on the transcription factor, HSF-1, and the chromatin remodeling factor, ISW-1. In addition, we show that mitochondrial stress during developmental stages also modulates histone levels, thereby activating a cytosolic stress response similar to that caused by changes in histone balance. These data indicate that histone and mitochondrial perturbations are both monitored through chromatin remodeling and involve the activation of a cytosolic response that affects organismal longevity. HSF-1 and ISW-1 hence emerge as a central mediator of this multi-compartment proteostatic response regulating longevity.
  • Kallioniemi, Arto; Zaleskiené, Irene; Lalor, John; Misiejuk, Dorota (2010)
  • Matilainen, Mia; Kallioniemi, Arto (2011)
    There has been much discussion about the most suitable model of religious education (RE hereafter) in public schools all around Europe. The Finnish model of RE has attracted great interest, because in Finland RE is given according to one’s own religion. The Finnish model of RE is very unique and it emphasises the right of religious minorities to participate in RE according to their own religion in state-owned schools. In this article we examine headmasters’ conceptions of the current Finnish RE solution from the perspective of human rights. The study is based on qualitative interviews. Headmasters presented both advantages and disadvantages of the current RE solution. These advantages are briefly: freedom of religion, an opportunity to get RE according to one´s own religion, knowing one´s own roots, an opportunity to understand people from different religious backgrounds and an opportunity to study other religions for those students who are not members of religious communities. The limits of the solution are that it puts students into their own religious groups and this limits possibilities for religious dialogue, which should be one of the key elements of modern RE. RE has a strong potential to promote human rights. It is important to discuss different models of arranging education from the viewpoint of human rights. The human rights viewpoint should be central when dealing with the aims, contents and organization structure of RE. Different interpretations of religious freedom and the right to religious education are important considerations especially for RE.
  • Poulter, Saila; Kallioniemi, Arto (2014)
  • Ubani, Martin; Kallioniemi, Arto; Poulter, Saila (2015)
  • Haller-Kikkatalo, Kadri; Alnek, Kristi; Metspalu, Andres; Mihailov, Evelin; Metskula, Kaja; Kisand, Kalle; Pisarev, Heti; Salumets, Andres; Uibo, Raivo (2017)
    The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto) immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.
  • Gurarie, Eliezer; Fleming, Christen H.; Fagan, William F.; Laidre, Kristin L.; Hernandez-Pliego, Jesus; Ovaskainen, Otso (2017)
    Background: Continuous time movement models resolve many of the problems with scaling, sampling, and interpretation that affect discrete movement models. They can, however, be challenging to estimate, have been presented in inconsistent ways, and are not widely used. Methods: We review the literature on integrated Ornstein-Uhlenbeck velocity models and propose four fundamental correlated velocity movement models (CVM's): random, advective, rotational, and rotational-advective. The models are defined in terms of biologically meaningful speeds and time scales of autocorrelation. We summarize several approaches to estimating the models, and apply these tools for the higher order task of behavioral partitioning via change point analysis. Results: An array of simulation illustrate the precision and accuracy of the estimation tools. An analysis of a swimming track of a bowhead whale (Balaena mysticetus) illustrates their robustness to irregular and sparse sampling and identifies switches between slower and faster, and directed vs. random movements. An analysis of a short flight of a lesser kestrel (Falco naumanni) identifies exact moments when switches occur between loopy, thermal soaring and directed flapping or gliding flights. Conclusions: We provide tools to estimate parameters and perform change point analyses in continuous time movement models as an R package (smoove). These resources, together with the synthesis, should facilitate the wider application and development of correlated velocity models among movement ecologists.
  • Steinzeig, Anna; Molotkov, Dmitry; Castren, Eero (2017)
    Growing interest in long-term visualization of cortical structure and function requires methods that allow observation of an intact cortex in longitudinal imaging studies. Here we describe a detailed protocol for the "transparent skull" (TS) preparation based on skull clearing with cyanoacrylate, which is applicable for long-term imaging through the intact skull in mice. We characterized the properties of the TS in imaging of intrinsic optical signals and compared them with the more conventional cranial window preparation. Our results show that TS is less invasive, maintains stabile transparency for at least two months, and compares favorably to data obtained from the conventional cranial window. We applied this method to experiments showing that a four-week treatment with the antidepressant fluoxetine combined with one week of monocular deprivation induced a shift in ocular dominance in the mouse visual cortex, confirming that fluoxetine treatment restores critical-period-like plasticity. Our results demonstrate that the TS preparation could become a useful method for long-term visualization of the living mouse brain.
  • Majander, Anna; Bowman, Richard; Poulton, Joanna; Antcliff, Richard J.; Reddy, M. Ashwin; Michaelides, Michel; Webster, Andrew R.; Chinnery, Patrick F.; Votruba, Marcela; Moore, Anthony T.; Yu-Wai-Man, Patrick (2017)
    Background The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. Methods Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m. 3460G>A, m. 11778G>A or m. 14484T>C. Results In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m. 3460G>A and m. 14484T>C mutations compared with the m. 11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) >= 0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA Conclusions Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.
  • Nivala, Outi; Faccio, Greta; Arvas, Mikko; Permi, Perttu; Buchert, Johanna; Kruus, Kristiina; Mattinen, Maija-Liisa (2017)
    Background: Despite of the presence of sulfhydryl oxidases (SOXs) in the secretomes of industrially relevant organisms and their many potential applications, only few of these enzymes have been biochemically characterized. In addition, basic functions of most of the SOX enzymes reported so far are not fully understood. In particular, the physiological role of secreted fungal SOXs is unclear. Results: The recently identified SOX from Aspergillus tubingensis (AtSOX) was produced, purified and characterized in the present work. AtSOX had a pH optimum of 6.5, and showed a good pH stability retaining more than 80% of the initial activity in a pH range 4-8.5 within 20 h. More than 70% of the initial activity was retained after incubation at 50 degrees C for 20 h. AtSOX contains a non-covalently bound flavin cofactor. The enzyme oxidised a sulfhydryl group of glutathione to form a disulfide bond, as verified by nuclear magnetic resonance spectroscopy. AtSOX preferred glutathione as a substrate over cysteine and dithiothreitol. The activity of the enzyme was totally inhibited by 10 mM zinc sulphate. Peptide-and protein-bound sulfhydryl groups in bikunin, gliotoxin, holomycin, insulin B chain, and ribonuclease A, were not oxidised by the enzyme. Based on the analysis of 33 fungal genomes, SOX enzyme encoding genes were found close to nonribosomal peptide synthetases (NRPS) but not with polyketide synthases (PKS). In the phylogenetic tree, constructed from 25 SOX and thioredoxin reductase sequences from IPR000103 InterPro family, AtSOX was evolutionary closely related to other Aspergillus SOXs. Oxidoreductases involved in the maturation of nonribosomal peptides of fungal and bacterial origin, namely GliT, HlmI and DepH, were also evolutionary closely related to AtSOX whereas fungal thioreductases were more distant. Conclusions: AtSOX (55 kDa) is a fungal secreted flavin-dependent enzyme with good stability to both pH and temperature. A Michaelis-Menten behaviour was observed with reduced glutathione as a substrate. Based on the location of SOX enzyme encoding genes close to NRPSs, SOXs could be involved in the secondary metabolism and act as an accessory enzyme in the production of nonribosomal peptides.