Live Tissue Imaging Sheds Light on Cell Level Events During Ectodermal Organ Development

Embryonic development of ectodermal organs involves a very dynamic range of cellular events and, therefore, requires advanced techniques to visualize them. Ectodermal organogenesis proceeds in well-defined sequential stages mediated by tissue interactions. Different ectodermal organs feature shared morphological characteristics, which are regulated by conserved and reiterative signaling pathways. A wealth of genetic information on the expression patterns and interactions of specific signaling pathways has accumulated over the years. However, the conventional developmental biology methods have mainly relied on two-dimensional tissue histological analyses at fixed time points limiting the possibilities to follow the processes in real time on a single cell resolution. This has complicated the interpretation of cause and effect relationships and mechanisms of the successive events. Whole-mount tissue live imaging approaches are now revealing how reshaping of the epithelial sheet for the initial placodal thickening, budding morphogenesis and beyond, involve coordinated four dimensional changes in cell shapes, well-orchestrated cell movements and specific cell proliferation and apoptosis patterns. It is becoming evident that the interpretation of the reiterative morphogenic signals takes place dynamically at the cellular level. Depending on the context, location, and timing they drive different cell fate choices and cellular interactions regulating a pattern of behaviors that ultimately defines organ shapes and sizes. Here we review how new tissue models, advances in 3D and live tissue imaging techniques have brought new understanding on the cell level behaviors that contribute to the highly dynamic stages of morphogenesis in teeth, hair and related ectodermal organs during development, and in dysplasia contexts.Peer reviewe

Finnish Early Childhood Education and Care Leaders’ Perceptions of Pedagogical Leadership and Assessment of the Implementation of the National Core Curriculum in Times of Change

Finnish early childhood education and care (ECEC) experienced system-wide changes in legislation, curriculum, and teachers’ and centre leaders’ qualification requirements between 2013 and 2018. Through these changes, the Finnish ECEC follows the global trends shifting the focus of ECEC from care towards education. The data are leaders’ (N = 41) written responses to three open-ended questions in a survey completed in 2018. The analytical framework draws on the models of educational change and human capital for pedagogical leadership. The framework directs focus on leaders’ understanding about and realisation of these new policies in their ECEC centres. Results indicate that leaders have the capacity to interpret and lead the curriculum process. However, to secure the coherence in and quality of ECEC, guidance that is more systematic and instruments (e.g. for development of pedagogy), that support the implementation of the curriculum and its assessment are needed.Finnish early childhood education and care (ECEC) experienced system-wide changes in legislation, curriculum, and teachers’ and centre leaders’ qualification requirements between 2013 and 2018. Through these changes, the Finnish ECEC follows the global trends shifting the focus of ECEC from care towards education. The data are leaders’ (N = 41) written responses to three open-ended questions in a survey completed in 2018. The analytical framework draws on the models of educational change and human capital of pedagogical leadership. The framework directs focus on leaders’ understanding about and realisation of these new policies in their ECEC centres. Results indicate that leaders have the capacity to interpret and lead the curriculum process. However, to secure the coherence in and quality of ECEC, guidance that is more systematic and instruments (e.g. for development of pedagogy) that support the implementation of the curriculum and its assessment are needed.Peer reviewe

Epidemiological, clinical and molecular characterization of Lynch-like syndrome : A population-based study

Colorectal carcinomas that are mismatch repair (MMR)-deficient in the absence of MLH1 promoter methylation or germline mutations represent Lynch-like syndrome (LLS). Double somatic events inactivating MMR genes are involved in the etiology of LLS tumors. Our purpose was to define the clinical and broader molecular hallmarks of LLS tumors and the population incidence of LLS, which remain poorly characterized. We investigated 762 consecutive colorectal carcinomas operated in Central Finland in 2000-2010. LLS cases were identified by a stepwise protocol based on MMR protein expression, MLH1 methylation and MMR gene mutation status. LLS tumors were profiled for CpG Island Methylator Phenotype (CIMP) and somatic mutations in 578 cancer-relevant genes. Among 107 MMR-deficient tumors, 81 (76%) were attributable to MLH1 promoter methylation and 9 (8%) to germline mutations (Lynch syndrome, LS), leaving 14 LLS cases (13%) (3 remained unclassified). LLS carcinomas were diagnosed at a mean age of 65 years (vs. 44 years in LS, p <0.001), had a proximal to distal ratio of 1:1, and all were BRAF V600E-negative. Two somatic events in MMR genes were identifiable in 11 tumors (79%). As novel findings, the tumors contained an average of 31 nonsynonymous somatic mutations/Mb and 13/14 were CIMP-positive. In conclusion, we establish the epidemiological, clinical and molecular characteristics of LLS in a population-based study design. Significantly more frequent CIMP-positivity and lower rates of somatic mutations make a distinction to LS. The absence of BRAF V600E mutation separates LLS colorectal carcinomas from MLH1-methylated colorectal carcinomas with CIMP-positive phenotype.Peer reviewe

Kasvatus- ja opetusalan johtajien näkemyksiä johtamisosaamisesta ja sen kehittämistarpeista

Tässä artikkelissa tarkastellaan Helsingin yliopistossa kasvatus- ja opetusalan johtamisen täydennyskoulutukseen osallistuneiden varhaiskasvatuksen ja perusopetuksen johtajien näkemyksiä johtamisosaamisen kehittämisestä ja oman johtajuutensa kehittämistarpeista. Tutkimuksessa on selvitetty johtajien suhtautumista itsensä johtamiseen: kokevatko johtajat omaavansa riittävästi osaamista nykyiseen työtehtäväänsä, sekä millaista osaamista johtajat kokevat tarvitsevansa lisää ja millaisia kehittämistarpeita heillä on. Tutkimusaineisto (N=87) kerättiin Likert-asteikollisia ja avoimia kysymyksiä sisältäneellä sähköisellä kyselylomakkeella osana täydennyskoulutuksen arviointia ja kehittämistä syksyllä 2018. Aineisto analysoitiin tilastollisin ei-parametrisin menetelmin sekä teorialähtöisellä sisällönanalyysillä. Osaamisen ja osaamistarpeiden luokittelussa käytettiin kompetenssihierarkiamallia. Tulokset osoittavat, että johtajat olivat erittäin halukkaita itsensä kehittämiseen, valmiita ottamaan uusia tehtäviä ja haasteita vastaan sekä tarvittaessa valmiita muuttamaan toimintamallejaan. Johtajien kuvaamat vahvuudet ja haasteet asettuivat johtamisen perusosaamisen tasolle, kun taas johtamisen suhdetoiminnan ja symbolisten tehtävien taso jäi osaamistarpeen kuvauksissa niukaksi. Avainsanat johtajuus, itsensä johtaminen, varhaiskasvatus, perusopetus, kasvatus- ja opetusalaPeer reviewe

Opettajan tuki oppijan metakognitiivisen tietoisuuden kehittymiselle

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Tytöt ja pojat koulussa – Miten selättää poikien heikko suoriutuminen

Viimeisimmät kansainväliset arvioinnit ovat osoittaneet tyttöjen ja poikien välisten erojen oppimistuloksissa kasvaneen ja etenkin poikien osaamisen heikentyneen. Tämän hankkeen tavoitteena oli selvittää, mitkä yksilö-, luokka- ja koulutason tekijät selittävät tyttöjen ja poikien eroja osaamisessa, oppimiseen liittyvissä asenteissa ja motivaatiossa. Lisäksi kartoitettiin sellaisia pedagogisia ratkaisuja ja interventioita, joilla on pystytty tasoittamaan tyttöjen ja poikien välisiä osaamiseroja. Hanke jakaantui kahteen eri osakokonaisuuteen. Ensimmäinen osa sisältää kirjallisuuskatsauksen ja osaamiserojen tarkastelun alakoulussa. Kirjallisuuskatsauksessa tarkasteltiin aiempia suomalaisia ja kansainvälisiä tutkimustuloksia siitä, mitkä yksilö-, luokka-, koulu- ja yhteiskuntatason tekijät selittävät tyttöjen ja poikien välisiä eroja osaamisessa. Alakoululaisten osaamiserojen tarkastelussa hyödynnettiin Alkuportaat-seurantatutkimuksen ja TIMSS 2015 -tutkimuksen aineistoja sekä hankkeessa kerättyjä opettaja- ja rehtorikyselyitä ja oppilas- ja opettajahaastatteluita. Hankkeen toisessa osassa tarkasteltiin osaamiseroja yläkoulussa. Siinä hyödynnettiin Helsingin ja Tampereen yliopistojen sekä Terveyden ja hyvinvoinnin laitoksen (THL) yhteistyönä keräämää MetLoFIN-aineistoa, valtakunnallista luokanmuodostusta koskevaa kyselyaineistoa sekä hankkeessa kerättyjä oppilas- ja rehtorihaastatteluita ja rehtorikysely

Defects in Innate Immunity Render Breast Cancer Initiating Cells Permissive to Oncolytic Adenovirus

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Oncolytic Adenovirus With Temozolomide Induces Autophagy and Antitumor Immune Responses in Cancer Patients

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Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance

Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs (n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p < 0.0005). The majority of incident cancers (21/28) were detected after previous colonoscopy without any pathological findings. On the molecular level, incident cancers presented with a significantly lower KRAS codon 12/13 (1/23, 4.3% vs. 11/21, 52%; p = 0.0005) and pathogenic TP53 mutation frequency (0/17, 0% vs. 7/21, 33.3%; p = 0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating APC mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. The proportion of MMR deficiency-related mutational events was significantly higher in incident compared to prevalent CRC (p = 0.018). In conclusion, our study identifies a set of features indicative of biological differences between incident and prevalent cancers in LS, which should further be monitored in prospective LS screening studies to guide towards optimized prevention protocols.Peer reviewe