27 research outputs found

    ”Tartten aikuisten apua tehtĂ€viin, mutta niitĂ€ on kyllĂ€ mukava tehdĂ€.”:esikoululaisten nĂ€kemyksiĂ€ vahvuuksistaan mielenkiinnonkohteistaan ja tuen tarpeistaan: keskustelu symbolein -pelin avulla

    Get PDF
    TiivistelmÀ. Esiopetuksessa lapselle laaditaan yhteistyössÀ lapsen, huoltajien ja opettajien kanssa pedagoginen suunnitelma, joka ohjaa lapsen koko esiopetusvuoden toimintaa. TÀmÀn yksilöllisen ja tavoitteellisen suunnittelun lÀhtökohtana ovat lapsen vahvuudet, mielenkiinnonkohteet ja tuen tarpeet. Pedagogisissa asiakirjoissa lapsen oma nÀkökulma tulee vaihtelevasti esille nÀkyvÀksi. TÀmÀn tutkimuksen tarkoituksena on selvittÀÀ, miten lapsi kertoo omista vahvuuksistaan, mielenkiinnonkohteistaan ja tuen tarpeistaan Keskustelu symbolein -pelin avulla ja kuinka Keskustelu symbolein -peli tukee lapsen ilmaisua. Tutkimuksessa kuvataan myös, miten lapsen vahvuudet, mielenkiinnonkohteet ja tuen tarpeet on tuotu esille lapsen pedagogisissa asiakirjoissa. Laadullisen tutkimuksen aineisto koostui viiden lapsen Keskustelu symbolein -pelin taulujen valokuvista ja lapsen pedagogisista asiakirjoista. Tutkimuksen aineisto analysoitiin neljÀssÀ vaiheessa. Analysoinnissa yhdistettiin sisÀllönanalyysin ja Barthesin semioottisen kuvatulkintamallin menetelmiÀ. TÀmÀn tutkimuksen tuloksissa saatiin selville, ettÀ Keskustelu symbolein -pelissÀ lapsen aktiivinen rooli ja omat nÀkemykset tulivat vahvasti esille. LisÀksi saatiin selville, ettÀ Keskustelu symbolein -peli auttoi lapsia tunnistamaan ja tarkemmin pohtimaan omia vahvuuksiaan, mielenkiinnonkohteitaan ja tuen tarpeitaan. Tutkimus osoitti myös, ettÀ Keskustelu symbolein -peli tuki lapsen ilmaisua ja oli tÀten toimiva menetelmÀ kehityskeskusteluissa kÀytettÀvÀksi. TÀmÀn tutkimuksen johtopÀÀtöksenÀ voidaan todeta, ettÀ Keskustelu symbolein-peli tuo lasten omat nÀkökulmat taidoistaan esille laajemmin ja monitahoisemmin verrattuna siihen, mitÀ lasten pedagogisiin asiakirjoihin oli kirjattu. Keskustelu symbolein-peliÀ pelatessaan lapsella on aktiivisempi rooli ja valta siitÀ mitÀ kertoo. Lapsi sijoittaessaan kuvia eri pohjille pystyy kertomaan omia nÀkemyksiÀÀn, vaikka hÀnen kielelliset taitonsa eivÀt siihen riittÀisi. LisÀksi lapsi pÀÀsee osallistumaan ja vaikuttamaan oman pedagogisen asiakirjan tekemiseen, kun hÀnen Keskustelu symbolein -pelissÀ ilmaisemat nÀkemyksensÀ kirjataan siihen

    Peripheral inflammation preceeding ischemia impairs neuronal survival through mechanisms involving miR‐127 in aged animals

    Get PDF
    Envelliment; Inflamació; MicroARNEnvejecimiento; Inflamación; MicroARNAging; Inflammation; MicroRNAIschemic stroke, the third leading cause of death in the Western world, affects mainly the elderly and is strongly associated with comorbid conditions such as atherosclerosis or diabetes, which are pathologically characterized by increased inflammation and are known to influence the outcome of stroke. Stroke incidence peaks during influenza seasons, and patients suffering from infections such as pneumonia prior to stroke exhibit a worse stroke outcome. Earlier studies have shown that comorbidities aggravate the outcome of stroke, yet the mediators of this phenomenon remain obscure. Here, we show that acute peripheral inflammation aggravates stroke‐induced neuronal damage and motor deficits specifically in aged mice. This is associated with increased levels of plasma proinflammatory cytokines, rather than with an increase of inflammatory mediators in the affected brain parenchyma. Nascent transcriptomics data with mature microRNA sequencing were used to identify the neuron‐specific miRNome, in order to decipher dysregulated miRNAs in the brains of aged animals with stroke and co‐existing inflammation. We pinpoint a previously uninvestigated miRNA in the brain, miR‐127, that is highly neuronal, to be associated with increased cell death in the aged, LPS‐injected ischemic mice. Target prediction tools indicate that miR‐127 interacts with several basally expressed neuronal genes, and of these we verify miR‐127 binding to Psmd3. Finally, we report reduced expression of miR‐127 in human stroke brains. Our results underline the impact of peripheral inflammation on the outcome of stroke in aged subjects and pinpoint molecular targets for restoring endogenous neuronal capacity to combat ischemic stroke.This study was supported by Emil Aaltonen Foundation, Academy of Finland and Finnish Cultural Foundation

    Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation

    Get PDF
    Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.Peer reviewe

    Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation

    Get PDF
    Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.Peer reviewe

    Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia

    Get PDF
    MicroRNAs are well characterized in their role in silencing gene expression by targeting 3ÂŽ-UTR of mRNAs in cytoplasm. However, recent studies have shown that miRNAs have a role in the regulation of genes in the nucleus, where they are abundantly located. We show here that in mouse endothelial cell line (C166), nuclear microRNA miR-466c participates in the regulation of vascular endothelial growth factor a (Vegfa) gene expression in hypoxia. Upregulation of Vegfa expression in response to hypoxia was significantly compromised after removal of miR-466c with CRISPR-Cas9 genomic deletion. We identified a promoter-associated long non-coding RNA on mouse Vegfa promoter and show that miR-466c directly binds to this transcript to modulate Vegfa expression. Collectively, these observations suggest that miR-466c regulates Vegfa gene transcription in the nucleus by targeting the promoter, and expands on our understanding of the role of miRNAs well beyond their canonical role

    PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia

    Get PDF
    Summary Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations. The APOE4 genotype impairs phagocytosis, migration, and metabolic activity of iMGLs but exacerbates their cytokine secretion. This indicates that APOE4 iMGLs are fundamentally unable to mount normal microglial functionality in AD.Peer reviewe

    Circular economy inspired imaginaries for sustainable innovations

    Get PDF
    In this chapter, Narayan and Tidström draw on the concept of imaginaries to show how Circular Economy (CE) can facilitate values that enable sustainable innovation. Innovation is key for sustainability, however, understanding and implementing sustainable innovation is challenging, and identifying the kind of actions that could direct sustainable innovations is important. The findings of this study indicate that CE-inspired imaginaries enable collaboration and by relating such imaginaries to common and shared social and cultural values, intermediaries could motivate actors into taking actions that contribute to sustainable innovation.fi=vertaisarvioitu|en=peerReviewed

    Measurement report : Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the Hyytiala boreal forest

    Get PDF
    The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiala, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (mu L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.Peer reviewe

    Measurement report : Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the Hyytiala boreal forest

    Get PDF
    The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiala, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (mu L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.Peer reviewe

    Validity of digital imaging of fiber-optic transillumination in caries detection on proximal tooth surfaces

    Get PDF
    Abstract Objective: The aim of our study was to evaluate the validity of the digital imaging fiber-optic transillumination (DIFOTI) method in comparison with clinical visual examination (CV) and bitewing (BW) radiography on detecting caries lesions on proximal surfaces of teeth. Materials and Methods: Proximal tooth surfaces of premolars and molars () of 91 voluntary university students aged from 18 to 30 years were examined with CV, BW radiography, and the DIFOTI method. Results: DIFOTI detected more initial and manifested caries lesions compared with CV and BW. Of the analyzed tooth surfaces, 69.8% were classified as sound by DIFOTI, 80.3% by BW, and 91.6% by CV. Initial caries lesions were found in 21.2% of the surfaces by DIFOTI, in 14.1% by BW, and in 6.2% by CV, whereas the proportions for manifested dental caries lesions were 9.0%, 5.6%, and 2.2%, respectively. The interexaminer agreement regarding the DIFOTI findings between an experienced clinician and a fifth-year dental student was high: for initial and for manifested caries lesions. Conclusions: The noninvasive DIFOTI method seems to offer a potential tool for everyday clinical practice. In clinical use, DIFOTI finds well even initial caries lesions on proximal surfaces, thus providing an instrument for detecting lesions potential for arresting as well as for monitoring the outcome after preventive measures
    corecore