Browsing by Subject "MATURATION"

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Now showing items 21-31 of 31
  • Varimo, Tero; Huttunen, Heta; Miettinen, Paivi Johanna; Kariola, Laura; Hietamaki, Johanna; Tarkkanen, Annika; Hero, Matti; Raivio, Taneli (2017)
    Introduction: We describe the etiology, MRI findings, and growth patterns in girls who had presented with signs of precocious puberty (PP), i.e., premature breast development or early menarche. Special attention was paid to the diagnostic findings in 6- to 8-year-olds. Materials and methods: We reviewed the medical records of 149 girls (aged 0.710.3 years) who had been evaluated for PP in the Helsinki University Hospital between 2001 and 2014. Results: In 6- to 8-year-old girls, PP was most frequently caused by idiopathic gonadotropin-releasing hormone (GnRH)-dependent PP (60%) and premature thelarche (PT; 39%). The former subgroup grew faster (8.7 +/- 2.0 cm/year, n = 58) than the girls with PT (7.0 +/- 1.1 cm/year, n = 32) (P <0.001), and the best discrimination for GnRH-dependent PP was achieved with a growth velocity cut-off value of 7.0 cm/year (sensitivity 92% and specificity 58%) [area under the curve 0.82, 95% confidence interval (CI) 0.730.91, P <0.001]. Among asymptomatic and previously healthy 6- to 8-year-old girls with GnRH-dependent PP, one (1.7%, 95% CI 0.39.7%) had a pathological brain MRI finding requiring surgical intervention (craniopharyngioma). In girls younger than 3 years, the most frequent cause of breast development was PT, and, in 3- to 6-year-olds, GnRH-dependent PP. Conclusion: In 6- to 8-year-old girls, analysis of growth velocity is helpful in differentiating between PT and GnRH-dependent PP. Although the frequency of clinically relevant intracranial findings in previously healthy, asymptomatic 6- to 8-year-old girls was low, they can present without any signs or symptoms, which favors routine MRI imaging also in this age group.
  • Partanen, Eino; Kujala, Teija; Tervaniemi, Mari; Huotilainen, Minna (2013)
    We investigated the neural correlates induced by prenatal exposure to melodies using brains' event-related potentials (ERPs). During the last trimester of pregnancy, the mothers in the learning group played the ‘Twinkle twinkle little star’ -melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive prenatal exposure to a melody induces neural representations that last for several months.
  • Korpela, Katri; Costea, Paul; Coelho, Luis Pedro; Kandels-Lewis, Stefanie; Willemsen, Gonneke; Boomsma, Dorret I.; Segata, Nicola; Bork, Peer (2018)
    Vertical transmission of bacteria from mother to infant at birth is postulated to initiate a life-long host-microbe symbiosis, playing an important role in early infant development. However, only the tracking of strictly defined unique microbial strains can clarify where the intestinal bacteria come from, how long the initial colonizers persist, and whether colonization by other strains from the environment can replace existing ones. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Only strains from the classes Actinobacteria and Bacteroidia, which are essential components of the infant microbiome, are transmitted from the mother and persist for at least 1 yr. In contrast, maternal strains of Clostridia, a dominant class in the mother's gut microbiome, are not observed in the infant. Caesarean-born infants show a striking lack of maternal transmission at birth. After the first year, strain influx from the family environment occurs and continues even in adulthood. Fathers appear to be more frequently donors of novel strains to other family members than receivers. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time.
  • Stepanenko, Olesya V.; Stepanenko, Olga V.; Kuznetsova, Irina M.; Verkhusha, Vladislav V.; Turoverov, Konstantin K. (2014)
  • Urrila, Anna S.; Artiges, Eric; Massicotte, Jessica; Miranda, Ruben; Vulser, Helene; Bezivin-Frere, Pauline; Lapidaire, Winok; Lemaitre, Herve; Penttilae, Jani; Conrod, Patricia J.; Garavan, Hugh; Martinot, Marie-Laure Paillere; Martinot, Jean-Luc; IMAGEN Consortium (2017)
    Here we report the first and most robust evidence about how sleep habits are associated with regional brain grey matter volumes and school grade average in early adolescence. Shorter time in bed during weekdays, and later weekend sleeping hours correlate with smaller brain grey matter volumes in frontal, anterior cingulate, and precuneus cortex regions. Poor school grade average associates with later weekend bedtime and smaller grey matter volumes in medial brain regions. The medial prefrontal anterior cingulate cortex appears most tightly related to the adolescents' variations in sleep habits, as its volume correlates inversely with both weekend bedtime and wake up time, and also with poor school performance. These findings suggest that sleep habits, notably during the weekends, have an alarming link with both the structure of the adolescent brain and school performance, and thus highlight the need for informed interventions.
  • O'Toole, John M.; Pavlidis, Elena; Korotchikova, Irina; Boylan, Geraldine B.; Stevenson, Nathan J. (2019)
    For the premature newborn, little is known about changes in brain activity during transition to extra-uterine life. We aim to quantify these changes in relation to the longer-term maturation of the developing brain. We analysed EEG for up to 72 hours after birth from 28 infants born
  • Miklas, Jason W.; Clark, Elisa; Levy, Shiri; Detraux, Damien; Leonard, Andrea; Beussman, Kevin; Showalter, Megan R.; Smith, Alec T.; Hofsteen, Peter; Yang, Xiulan; Macadangdang, Jesse; Manninen, Tuula; Raftery, Daniel; Madan, Anup; Suomalainen, Anu; Kim, Deok-Ho; Murry, Charles E.; Fiehn, Oliver; Sniadecki, Nathan J.; Wang, Yuliang; Ruohola-Baker, Hannele (2019)
    Mitochondrial trifunctional protein deficiency, due to mutations in hydratase subunit A (HADHA), results in sudden infant death syndrome with no cure. To reveal the disease etiology, we generated stem cell-derived cardiomyocytes from HADHA-deficient hiPSCs and accelerated their maturation via an engineered microRNA maturation cocktail that upregulated the epigenetic regulator, HOPX. Here we report, matured HADHA mutant cardiomyocytes treated with an endogenous mixture of fatty acids manifest the disease phenotype: defective calcium dynamics and repolarization kinetics which results in a pro-arrhythmic state. Single cell RNA-seq reveals a cardiomyocyte developmental intermediate, based on metabolic gene expression. This intermediate gives rise to mature-like cardiomyocytes in control cells but, mutant cells transition to a pathological state with reduced fatty acid beta-oxidation, reduced mitochondrial proton gradient, disrupted cristae structure and defective cardiolipin remodeling. This study reveals that HADHA (tri-functional protein alpha), a monolysocardiolipin acyltransferase-like enzyme, is required for fatty acid beta-oxidation and cardiolipin remodeling, essential for functional mitochondria in human cardiomyocytes.
  • Bleidorn, Wiebke; Hill, Patrick L.; Back, Mitja D.; Denissen, Jaap J. A.; Hennecke, Marie; Hopwood, Christopher J.; Jokela, Markus; Kandler, Christian; Lucas, Richard E.; Luhmann, Maike; Orth, Ulrich; Wagner, Jenny; Wrzus, Cornelia; Zimmermann, Johannes; Roberts, Brent (2019)
    Personality traits are powerful predictors of outcomes in the domains of education, work, relationships, health, and well-being. The recognized importance of personality traits has raised questions about their policy relevance, that is, their potential to inform policy actions designed to improve human welfare. Traditionally, the use of personality traits in applied settings has been predicated on their ability to predict valued outcomes, typically under the assumption that traits are functionally unchanging. This assumption, however, is both untrue and a limiting factor on using personality traits more widely in applied settings. In this article, we present the case that traits can serve both as relatively stable predictors of success and actionable targets for policy changes and interventions. Though trait change will likely prove a more difficult target than typical targets in applied interventions, it also may be a more fruitful one given the variety of life domains affected by personality traits. Public Significance Statement This article presents the case that personality traits can serve both as predictors of success and actionable targets for policy changes and interventions. The field of personality psychology has now amassed evidence necessary to address the policy relevance of personality traits. To that end, we pose and answer critical questions regarding personality traits and their applicability for policy initiatives in applied settings.
  • Mobley, Kenyon B.; Granroth-Wilding, Hanna; Ellmen, Mikko; Orell, Panu; Erkinaro, Jaakko; Primmer, Craig R. (2020)
    Abstract In species with complex life cycles, life history theory predicts that fitness is affected by conditions encountered in previous life history stages. Here, we use a four-year pedigree to investigate if time spent in two distinct life history stages has sex-specific reproductive fitness consequences in anadromous Atlantic salmon (Salmo salar). We determined the amount of years spent in fresh water as juveniles (freshwater age, FW, measured in years), and years spent in the marine environment as adults (sea age, SW, measured in sea winters) on 264 sexually mature adults collected on a river spawning ground. We then estimated reproductive fitness as the number of offspring (reproductive success) and the number of mates (mating success) using genetic parentage analysis (>5000 offspring). Sea age is significantly and positively correlated with reproductive and mating success of both sexes whereby older and larger individuals gained the highest reproductive fitness benefits (females: 62.2% increase in offspring/SW and 34.8% increase in mate number/SW; males: 201.9% offspring/SW and 60.3% mates/SW). Younger freshwater age was significantly related to older sea age and thus increased reproductive fitness, but only among females (females: -33.9% offspring/FW and -32.4% mates/FW). This result implies that females can obtain higher reproductive fitness by transitioning to the marine environment earlier. In contrast, male mating and reproductive success was unaffected by freshwater age and more males returned at a younger age than females despite the reproductive fitness advantage of later sea age maturation. Our results show that the timing of transitions between juvenile and adult phases has a sex-specific consequence on female reproductive fitness, demonstrating a life-history trade-off between maturation and reproduction in wild Atlantic salmon.
  • Heiniö, Camilla; Havunen, Riikka; Santos, Joao; de Lint, Klaas; Cervera-Carrascon, Victor; Kanerva, Anna; Hemminki, Akseli (2020)
    In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment.
  • Heino, Terhi J.; Alm, Jessica J.; Halkosaari, Heikki J.; Välimäki, Ville-Valtteri (2016)
    Background and purpose-Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods-A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro -computed tomography (mu CT), and histology. Results-Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation-Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms.