Recent Submissions

  • Tammimäki, Anne; Aonurm-Helm, Anu; Männistö, Pekka T. (2018)
    1.Catechol-O-methyltransferase (COMT) is involved in the O-methylation of l-DOPA, dopamine, and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2.To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral l-DOPA levels, and metabolism after l-DOPA (10mg kg(-1)) plus carbidopa (30mg kg(-1)) administration by gastric tube in wild-type (WT) and MB-COMT-deficient mice. l-DOPA and 3-O-methyl-l-DOPA (3-OMD) levels were assayed in plasma, duodenum, and liver. 3.We showed that the selective lack of MB-COMT did not alter the total COMT activity, COMT enzyme kinetics, l-DOPA levels, or the total O-methylation of l-DOPA but delayed production of 3-OMD in plasma and peripheral tissues.
  • Casteras, Jean-Baptiste; Holopainen, Ilkka; Ripoll, Jaime B. (2017)
    We study the Dirichlet problem at infinity on a Cartan-Hadamard manifold M of dimension n 2 for a large class of operators containing, in particular, the p-Laplacian and the minimal graph operator. We extend several existence results obtained for the p-Laplacian to our class of operators. As an application of our main result, we prove the solvability of the asymptotic Dirichlet problem for the minimal graph equation for any continuous boundary data on a (possibly non rotationally symmetric) manifold whose sectional curvatures are allowed to decay to 0 quadratically.
  • Karisto, Petteri; Kisdi, Eva (2017)
    The pattern of connectivity between local populations or between microsites supporting individuals within a population is a poorly understood factor affecting the evolution of dispersal. We modify the well-known Hamilton May model of dispersal evolution to allow for variable connectivity between microsites. For simplicity, we assume that the microsites are either solitary, i.e., weakly connected through costly dispersal, or part of a well-connected cluster of sites with low-cost dispersal within the cluster. We use adaptive dynamics to investigate the evolution of dispersal, obtaining analytic results for monomorphic evolution and numerical results for the co-evolution of two dispersal strategies. A monomorphic population always evolves to a unique singular dispersal strategy, which may be an evolutionarily stable strategy or an evolutionary branching point. Evolutionary branching happens if the contrast between connectivities is sufficiently high and the solitary microsites are common. The dimorphic evolutionary singularity, when it exists, is always evolutionarily and convergence stable. The model exhibits both protected and unprotected dimorphisms of dispersal strategies, but the dimorphic singularity is always protected. Contrasting connectivities can thus maintain dispersal polymorphisms in temporally stable environments.
  • Dovemark, Marianne; Kosunen, Sonja; Kauko, Jaakko; Magnúsdottír, Berglind; Hansen, Petteri; Rasmussen, Palle (2018)
  • Lehtimaki, Jaakko I.; Fenix, Aidan M.; Kotila, Tommi M.; Balistreri, Giuseppe; Paavolainen, Lassi; Varjosalo, Markku; Burnette, Dylan T.; Lappalainen, Pekka (2017)
    Contractile actomyosin bundles, stress fibers, are crucial for adhesion, morphogenesis, and mechanosensing in nonmuscle cells. However, the mechanisms by which nonmuscle myosin II (NM-II) is recruited to those structures and assembled into functional bipolar filaments have remained elusive. We report that UNC-45a is a dynamic component of actin stress fibers and functions as a myosin chaperone in vivo. UNC-45a knockout cells display severe defects in stress fiber assembly and consequent abnormalities in cell morphogenesis, polarity, and migration. Experiments combining structured-illumination microscopy, gradient centrifugation, and proteasome inhibition approaches revealed that a large fraction of NM-II and myosin-1c molecules fail to fold in the absence of UNC-45a. The remaining properly folded NM-II molecules display defects in forming functional bipolar filaments. The C-terminal UNC-45/Cro1/She4p domain of UNC-45a is critical for NM-II folding, whereas the N-terminal tetratricopeptide repeat domain contributes to the assembly of functional stress fibers. Thus, UNC-45a promotes generation of contractile actomyosin bundles through synchronized NM-II folding and filament-assembly activities.
  • Mahiout, Selma; Linden, Jere; Esteban, Javier; Sanchez-Perez, Ismael; Sankari, Satu; Pettersson, Lars; Håkansson, Helen; Pohjanvirta, Raimo (2017)
    The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and tasquinimod, respectively, which are intended for the treatment of autoimmune diseases and cancer. Here, we toxicologically assessed the novel compounds in Sprague-Dawley rats, after a single dose (8.75-92.5 mg/kg) and 5-day repeated dosing at the highest doses achievable (IMA-08401: 100 mg/kg/day; and IMA-07101: 75 mg/kg/day). There were no overt clinical signs of toxicity, but body weight gain was marginally retarded, and the treatments induced minimal hepatic extramedullary haematopoiesis. Further, both the absolute and relative weights of the thymus were significantly decreased. Cyp1a1 gene expression was substantially increased in all tissues examined. The hepatic induction profile of other AHR battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The only marked alterations in serum clinical chemistry variables were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and kidney retinol and retinyl palmitate concentrations were affected largely in the same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1 effectively in H4IIE cells. Altogether, these novel compounds appear to act as potent activators of the AHR, but lack some major characteristic toxicities of dioxins. They therefore represent promising new selective AHR modulators. (C) 2017 Elsevier Inc. All rights reserved.
  • Hotta, Jaakko; Saari, Jukka; Koskinen, Miika; Hlushchuk, Yevhen; Forss, Nina; Hari, Riitta (2017)
    Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q <.05, false discovery rate-corrected) included the hand representation area in the sensorimotor cortex, inferior frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control. Perspective: This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS. (C) 2016 by the American Pain Society
  • Pinola, Pekka; Puukka, Katri; Piltonen, Terhi T.; Puurunen, Johanna; Vanky, Eszter; Sundström-Poromaa, Inger; Stener-Victorin, Elisabet; Hirschberg, Angelica Linden; Ravn, Pernille; Andersen, Marianne Skovsager; Glintborg, Dorte; Mellembakken, Jan Roar; Ruokonen, Aimo; Tapanainen, Juha; Morin-Papunen, Laure C. (2017)
    Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30-39, and > 39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on. (C) 2016 by American Society for Reproductive Medicine.
  • Rantala, Kati Elina; Ahonen, Pertti Pellervo; Alasuutari, Noora Kristiina; Kauppila, Jussi; Kautto, Petrus; Kuokkanen, Kanerva Eliisa; Römpötti, Essi; Saarenpää, Karoliina; Tala, Jyrki; Uusikylä, Petri (Valtioneuvoston kanslia, 2018)
    Valtioneuvoston selvitys- ja tutkimustoiminnan julkaisusarja
    Tutkimuksessa on pyritty tuottamaan kattava, realistinen ja moniulotteinen yleiskuva sääntelytaakasta Suomessa. Erityisenä tavoitteena on ollut tunnistaa yrityksiin, kansalaistoimintaan ja yksittäisten ihmisten viranomaisasiointiin kohdistuvan turhan taakan keskeisimmät lähteet. Turhaa sääntelytaakkaa syntyy mm. seuraavista tekijöistä: epäselvä ja nopeasti muuttuva sääntely, ristiriitaiset ja päällekkäiset vaatimukset, kohtuuttoman raskaat menettelytavat asioinnissa viranomaisten kanssa ja sääntelyn epäyhtenäinen toimeenpano. Edes summittaisen ja uskottavan, numeerisen kokonaisarvion antaminen sääntelytaakasta ilman laajoja varaumia on mahdotonta. Tulosten mukaan 1) sääntelytaakka on epämääräinen käsite, mutta ilmiönä moniulotteinen, 2) sääntelytaakan mittaaminen on vaikeaa, 3) sääntelyn hallinta ja ongelmat toimeenpanossa muodostavat keskeisen osan sääntelytaakkaa, 4) kohdetahojen kokemukset sääntelytaakasta ovat monimuotoisia. Raportissa esitetään 15 kehittämisehdotusta koskien sääntelytaakan kohdentumista, sääntelyn toimeenpanoa ja lainvalmisteluprosesseja
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J.K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Talvitie, J.; Tuuva, T. (2018)
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Tuuva, T.; Talvitie, J. (2018)
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J.K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2018)
  • The ALICE collaboration; Acharya, S.; Brucken, E.J.; Chang, B.; Kim, D.J.; Litichevskyi, V.; Mieskolainen, M.M.; Orava, R.; Rak, J.; Räsänen, S.S.; Saarinen, S.; Slupecki, M.; Snellman, T.W.; Trzaska, W.H.; Vargyas, M.; Viinikainen, J. (2018)
  • Pasanen, Päivi Hannele (2018)