Kylä pohjoisessa:Suvannon kylän kulttuuriympäristöselvitys ja maisemasuunnitelma

Tiivistelmä. Diplomityö sijoittuu Pelkosenniemellä sijaitsevaan Suvannon kylään, joka on valtakunnallisesti merkittävä kulttuuriympäristö. Kauniissa ja viljavassa jokilaaksossa sijaitsevalla kylällä on pitkä historia. 1900-luvun alussa elinvoimaisimmillaan oleva kylä hyötyi omavaraisesta maataloudesta, mutta elinkeinorakenteen muutoksen vuoksi kylän väestö on pienentynyt jatkuvasti. Tämän myötä kaunis kylämiljöö on muuttunut suuresti. Rakennukset ovat huonossa kunnossa ja perinnemaisemalle tyypilliset luonnonniityt ovat alkaneet kasvaa umpeen. Tämä työ pyrkii löytämään vastauksia perinnemaiseman säilyttämiseksi ja palauttamiseksi. Diplomityössä perehdytään kylän historiaan, luontoon ja elinkeinoihin. Suvannon vieressä virtaavan Kitisen patoamisen vaikutukset kylään on nostettu omaksi teemaksi. Nykytilanteeseen on pureuduttu laajan maisema-analyysin kautta, joka selvittää muuttunutta maisemaa ja luo pohjan työssä esiteltävälle maisemasuunnitelmalle. Maisemasuunnitelmassa on esitetty keinoja muuttuneiden alueiden palauttamiseksi ja säilyneiden alueiden suojelemiseksi. Suvannossa tarvitaan mittavia maisemanhoidollisia toimenpiteitä, kuten metsien ja pensoittuneiden alueiden raivausta, laidunnusta ja niittoa. Tavoitteena on mahdollisimman monimuotoinen ja perinteitä kunnioittava, viihtyisä kyläympäristö. Suunnitelmassa on etsitty keinoja myös kylämaiseman elävöittämiselle ja mahdollisen matkailun lisääntymiselle. Diplomityö ottaa kantaa myös Suvannon osayleiskaavaan, jossa on ongelmallisia kohtia maisemanhoidon toteuttamiseksi. Työn lopussa esitellään yhden pihapiirin kunnostussuunnitelma, jota voidaan pitää esimerkkinä myös kylän muiden pihapiirien hoidolle. Diplomityö toimii toivon mukaan ponnahduslautana ja ohjenuorana Suvannossa tapahtuvalle pitkäjänteiselle perinnetyölle, jonka avulla valtakunnallisesti arvokas kulttuuriympäristö saataisiin säilytettyä

Puukerrostalo Oulun Linnanmaalle

Tiivistelmä. Kandidaatintyönä suunnittelin puukerrostalon Oulun Linnanmaalle. Työ koostuu kolmesta kurssista, asemakaavasuunnittelusta (YS), asuntosuunnittelusta (NARK) ja kerrostalokurssista (RO). Näistä painotan työssäni asuntosuunnittelun osuutta. Asemakaavasuunnittelussa pohdittiin Linnanmaantien, Alakyläntien ja Syynimaan välisen alueen maankäyttöä ja sen pohjalta toteutin yleissuunnitelman, sekä asemakaavaehdotuksen. Ehdotuksessani halusin kannustaa ihmisiä liikkumaan parantamalla samalla alueen monimuotoisuutta. Asukkaille halusin taata hyvät liikenneyhteydet, runsaat aktiviteetit ja mielenkiintoisen luonnon suoraan pihalta. Asuntosuunnittelu toteutettiin kilpailuna, jossa piti suunnitella puukerrostalo Puulinnanmaan nurkassa sijaitsevalle tontille. Ehdotuksessani paneuduin puurakentamisen tuomiin mahdollisuuksiin luoda uudenlaista ja jännittävää opiskelija-asumista. Tuloksena oli asuntomoduuleista koostuva hiutalemainen rakenne, jonka jokaisessa sakarassa on asunto. Tämä mahdollistaa omakotitalomaisen asumisen jopa yksiöissä, joista näkymät avautuvat kolmeen ilmansuuntaan. Porraskäytävien välissä on yhteistiloja ja suurempia asuntoja. Muotokieleltään rakennus eroaa muusta rakennuskannasta, mutta ottaa pienipiirteisyydellään kantaa Puulinnanmaan rakeisuuteen. Kerrostalokurssin rakennusopin vaiheessa muutin työni rakennettavaan muotoon ja hioin suunnitelman detaljitasolle asti. Rakennuksesta tuli tätä kautta uskottava ja yksityiskohdista rakentui lopulta toimiva ja kaunis kokonaisuus. Pihan toiminnot tarkentuivat ja sen orgaaninen muotokieli tuli pehmentämään rakennuksen särmikkyyttä. Kandidaatintyöni tarjoaa uudenlaista näkökulmaa asuntosuunnitteluun ja luo uskoa puun käytettävyyteen ja mahdollisuuksiin myös kerrostalorakentamisessa. Tervetuloa tutustumaan työhöni

Altered Mucosal-Associated Invariant T Cells Phenotype in Children with Newly Diagnosed Type 1 Diabetes but not in Autoantibody-Positive At-Risk Children

Introduction: Mucosal-associated invariant T (MAIT) cells are unconventional T cells, enriched in the gut. They express an invariant T-cell receptor and recognize riboflavin metabolites from bacteria presented by MHC-Ib-related protein 1 (MR1) molecules. Alterations in gut microbiota have been reported in patients with type 1 diabetes (T1D), even before the onset of the disease. These changes can potentially alter the frequency or phenotype of circulating MAIT cells. Methods: We characterized peripheral blood MAIT cells in a cohort of 51 children with newly diagnosed T1D, 27 at-risk children positive for multiple autoantibodies (AAb+) and 113 age-matched healthy children. Using multi-colour flow cytometry, we analysed the frequency, surface phenotype and cytokine production of MAIT cells. In addition, we characterized the frequency and surface phenotype of blood MAIT cells in 26 patients with long-standing T1D and 25 age-matched healthy controls. Results: No significant differences in MAIT cell frequency were observed between the study groups. Further phenotyping revealed that the expression of CD8, CD27, CCR5 and β7 integrin on MAIT cells was lower in children with newly diagnosed T1D compared to AAb+ and healthy children. The frequency of MAIT cells producing IFN-γ was also lower in children with newly diagnosed T1D, but the frequencies of IL-17A- and IL-4-secreting MAIT cells were similar in the study groups. Finally, the capacity of MAIT cells to be activated in vitro by E.coli bacteria through MR1 was comparable between the study groups. However, none of these changes was observed in adult patients with long-standing T1D. In contrast, a decreased frequency of MAIT cells and increased CD25 expression was observed in adult T1D patients with a short duration after diagnosis. Conclusion: There are subtle changes in the circulating MAIT compartment in patients with T1D at the onset of the disease as well as after clinical diagnosis, but not in AAb+ at-risk subjects including progression to clinical disease. Consequently, the alterations in blood MAIT cells are likely associated with the clinical manifestation of the disease rather than being features of earlier T1D autoimmunity

Mucosal-associated invariant T cell alterations during the development of human type 1 diabetes

Aims/hypothesis Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise derivatives of bacterial riboflavin metabolites presented by MHC-Ib-related protein 1 (MR1) molecules and are important effector cells for mucosal immunity. Their development can be influenced by the intestinal microbiome. Since the development of type 1 diabetes has been associated with changes in the gut microbiome, this can be hypothesised to lead to alterations in circulating MAIT cells. Accordingly, peripheral blood MAIT cell alterations have been reported previously in patients with type 1 diabetes. However, a comprehensive analysis of the frequency and phenotype of circulating MAIT cells at different stages of type 1 diabetes progression is currently lacking. Methods We analysed the frequency, phenotype and functionality of peripheral blood MAIT cells, as well as gamma delta T cells, invariant natural killer T (iNKT) cells and natural killer (NK) cells with flow cytometry in a cross-sectional paediatric cohort (aged 2-15) consisting of 51 children with newly diagnosed type 1 diabetes, 27 autoantibody-positive (AAb(+)) at-risk children, and 113 healthy control children of similar age and HLA class II background. The frequency of MAIT cells was also assessed in a separate cross-sectional adult cohort (aged 19-39) of 33 adults with established type 1 diabetes and 37 healthy individuals of similar age. Results Children with newly diagnosed type 1 diabetes displayed a proportional increase of CD8(-)CD27(-)MAIT cells compared with healthy control children (median 4.6% vs 3.1% of MAIT cells, respectively, p = 0.004), which was associated with reduced expression of C-C chemokine receptor (CCR)5 (median 90.0% vs 94.3% of MAIT cells, p = 0.02) and beta 7 integrin (median 73.5% vs 81.7% of MAIT cells, p = 0.004), as well as decreased production of IFN-gamma (median 57.1% vs 69.3% of MAIT cells, p = 0.04) by the MAIT cells. The frequency of MAIT cells was also decreased in AAb(+)children who later progressed to type 1 diabetes compared with healthy control children (median 0.44% vs 0.96% of CD3(+)T cells, p = 0.04), as well as in adult patients with a short duration of type 1 diabetes (less than 6 years after diagnosis) compared with control individuals (median 0.87% vs 2.19% of CD3(+)T cells, p = 0.007). No alterations in gamma delta T cell, iNKT cell or NK cell frequencies were observed in children with type 1 diabetes or in AAb(+) children, with the exception of an increased frequency of IL-17A(+)gamma delta T cells in children with newly diagnosed diabetes compared with healthy control children (median 1.58% vs 1.09% of gamma delta T cells, p = 0.002). Conclusions/interpretation Changes in the frequency and phenotype of circulating MAIT cells were detectable before, at the onset and after diagnosis of type 1 diabetes in cross-sectional cohorts. Our results suggest a possible temporal association between peripheral blood MAIT cell alterations and the clinical onset of type 1 diabetes.Peer reviewe

Single-cell characterization of dog allergen–specific T cells reveals TH2 heterogeneity in allergic individuals

BackgroundAllergen-specific type 2 CD4+ TH2 cells are critically involved in the pathogenesis of IgE-mediated allergic diseases. However, the heterogeneity of the TH2 response has only recently been appreciated.ObjectiveWe sought to characterize at the single-cell level the ex vivo phenotype, transcriptomic profile, and T-cell receptor (TCR) repertoire of circulating CD4+ T cells specific to the major dog allergens Can f 1, Can f 4, and Can f 5 in subjects with and without dog allergy.MethodsDog allergen–specific memory CD4+ T cells were detected ex vivo by flow cytometry using a CD154-based enrichment assay and single-cell sorted for targeted gene expression analysis and TCR sequencing.ResultsDog allergen–specific T-cell responses in allergic subjects were dominantly of TH2 type. TH2 cells could be phenotypically further divided into 3 subsets, which consisted of TH2-like (CCR6−CXCR3−CRTH2−), TH2 (CCR6−CXCR3−CRTH2+CD161−), and TH2A (CCR6−CXCR3−CRTH2+CD161+CD27−) cells. All these subsets were nonexistent within the allergen-specific T-cell repertoire of healthy subjects. Single-cell transcriptomic profiling confirmed the TH2-biased signature in allergen-specific T cells from allergic subjects and revealed a TH1/TH17 signature in nonallergic subjects. TCR repertoire analyses showed that dog allergen–specific T cells were diverse and allergic subjects demonstrated less clonality compared to nonallergic donors. Finally, TCR and transcriptomic analyses revealed a close relationship between TH2-like, TH2, and TH2A cells, with the last ones representing the most terminally differentiated and highly polarized subtype.ConclusionsOur study demonstrates heterogeneity within allergen-specific TH2 cells at the single-cell level. The results may be utilized for improving immune monitoring after allergen immunotherapy and for designing targeted immunomodulatory approaches.</p

FOXP3+ Regulatory T Cell Compartment Is Altered in Children With Newly Diagnosed Type 1 Diabetes but Not in Autoantibody-Positive at-Risk Children

The dysfunction of FOXP3-positive regulatory T cells (Tregs) plays a key role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, previous studies analyzing the peripheral blood Treg compartment in patients with T1D have yielded partially conflicting results. Moreover, the phenotypic complexity of peripheral blood Tregs during the development of human T1D has not been comprehensively analyzed. Here, we used multi-color flow cytometry to analyze the frequency of distinct Treg subsets in blood samples from a large cohort comprising of 74 children with newly diagnosed T1D, 76 autoantibody-positive children at-risk for T1D and 180 age- and HLA-matched control children. The frequency of CD4+CD25+CD127lowFOXP3+ Tregs was higher in children with T1D compared to control children, and this change was attributable to a higher proportion of naïve Tregs in these subjects. Further longitudinal analyses demonstrated that the increase in Treg frequency correlated with disease onset. The frequencies of the minor subsets of CD25+FOXP3low memory Tregs as well as CD25lowCD127lowFOXP3+ Tregs were also increased in children with T1D. Moreover, the ratio of CCR6-CXCR3+ and CCR6+CXCR3- memory Tregs was altered and the frequency of proliferating Ki67-positive and IFN-γ producing memory Tregs was decreased in children with T1D. The frequency of CXCR5+FOXP3+ circulating follicular T regulatory cells was not altered in children with T1D. Importantly, none of the alterations observed in children with T1D were observed in autoantibody-positive at-risk children. In conclusion, our study reveals multiple alterations in the peripheral blood Treg compartment at the diagnosis of T1D that appear not to be features of early islet autoimmunity

Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease

Objective. The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD). Material and methods. 291 newborn children positive for HLA-DQB1*02 and -DQA1*05 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay. Results. The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively. Conclusions. Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD.Peer reviewe

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases : Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological di-versity in the everyday living environment is a core reason for dysregulation of immune tolerance and - even-tually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). Conclusions: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.Peer reviewe

Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes

Aims/Hypothesis Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)-conferred T1D risk. Methods A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood. All the children carried HLA-DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D-associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen-2 [IA-2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan-Meier survival analysis and Log-rank test. Results Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D-associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015). Conclusion Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at-risk children and may thus protect these children from progressing to T1D during childhood.Peer reviewe

Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study

The metagenomic data presented in this article are related to the published research of "A Placebo-controlled doubleblinded test of the biodiversity hypothesis of immunemediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children"This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In inter-vention daycares, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil. In placebo daycares, children were exposed to visually similar as in intervention daycares, but microbially poor sand col-ored with peat. Sand, skin and gut metagenomics were an-alyzed at baseline and after 14 and 28 days of interven-tion by high throughput sequencing of bacterial 16S rRNA gene on the Illumina MiSeq platform. This dataset shows how skin bacterial community composition, including classes Gammaproteobacteria and Bacilli, changed, and how the rel-ative abundance of over 30 bacterial genera shifted on the skin of children in the intervention treatment, while no shifts occurred in the placebo group.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe