Diversity and function of anti-modified protein autoantibodies in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease particularly affecting synovial joints. Anti-citrullinated protein autoantibodies (ACPA) are detected in the serum of about 2/3 of RA patients and are being used to classify the disease. These autoantibodies may occur years before any signs of arthritis which implies that they are a cause rather than a consequence of disease. By using modified autoantigens to detect ACPAs in large patient cohorts and by purifying polyclonal autoantibodies from patients, the hunt for disease promoting autoantigens has been going on for decades. However, the relationship between ACPA specificity and any functional effects remains unclear. In order to understand the evolution, specificity, and function of autoreactive B cells in RA, the focus of this thesis is the generation of monoclonal antibodies (mAbs) from paired variable heavy- and light-chain immunoglobulin (Ig) sequences from identified single B cells from various RA tissue compartments. We have identified citrulline-reactive autoantibody producing plasma cells in the synovium of RA patients with established disease. By generating single plasma cell derived mAbs, we learned that such autoantibodies may be directly involved in the pathogenesis of RA by promoting bone degrading osteoclasts. The mAbs were all multireactive to citrulline-peptides and citrullinated proteins, but with unique distinct binding patterns. We recognized glycine in +1 position to the citrulline and a fraction of the citrulline-reactive mAbs cross-reacted with carbamyl-peptides. In addition, the identified plasma cells displayed features of high somatic mutations and fragment antigen binding (Fab) variable N-glycosylation sites introduced by affinity maturation. By analyzing a selection of RA patient B cell derived mAbs for reactivity against apoptotic cells and activated neutrophils, we learned that a subset of the citrulline reactive mAbs bound nuclear antigens. Interestingly, a fraction of these mAbs could target nuclear histones independently of the citrullinating enzyme PAD by binding to acetylated histones. We explored the extent of the ACPA mAb multireactivity and cross-reactivity by acknowledging the importance of neighboring amino acids in addition to glycine in +1 to the citrulline. By analyzing the bone marrow plasma cell repertoire of RA patients, we observed differences in Ig-frequencies and variable Fab N-linked glycosylation sites between ACPA+ and ACPA- patients. We also found RA patient bone marrow plasma cell clonotypes. In addition, we identified citrulline-reactive bone marrow plasma cells that could bind activated neutrophils which strengthen previous reports of citrullinated histones as ACPA targets. Lastly, we identified autoantibodies against the oxidation-induced post translational protein modification adducts malondialdehyde (MDA) and malondialdehyde-acetaldehyde (MAA) in the bone marrow and lung of RA patients and individuals that also harbor ACPAs. A majority of these autoantibodies, that can promote osteoclastogenesis, need cross-linked MAA-protein for recognition independent of protein backbone. Taken together, the generation of RA patient single B cell derived mAbs, have revealed remarkable features of the autoreactivity that increases the understanding of B cell involvement in the pathogenesis of RA

Selective Friendship? A Study of Immigrant Segregation within Finnish Classrooms

This thesis investigates the within-school segregation of Finnish students using survey data on friendships. The difference in academic performance between students with and without immigrant backgrounds is large, and in order to make it smaller, the study environment for students with immigrant backgrounds must be understood. Identifying the extent to which students with immigrant background experience a different social environment is one step in that direction. Individual segregation is the extent to which the social network of an individual is composed of individuals similar to each other regarding some specific trait. This study investigates the existence of individual segregation in Finnish schools using information on who the fifth grade students participating in the study are friends with. The individual segregation level is calculated based on the background of friends, dividing students into two groups: students with or without immigrant backgrounds. This gives an indication of the possible segregation at an individual level, created through friend choice. Additionally, the correlation between individual level segregation and age at arrival to Finland and academic skills respectively is studied. Clear evidence of individual level segregation among immigrants is found. Students with immigrant backgrounds are more likely to have friends with immigrant backgrounds and more likely to be lonely, as in have no friends. However, neither correlation between in- dividual segregation and age at arrival nor correlation between individual segregation and academic skills can be found. This could be explained by problems with the data, but can also indicate that peer effects in class are smaller than what was expected based on previous research. It seems that also segregation patterns differ from what has been found in similar American studies. More research need to be done, but this thesis shows that students with immigrant backgrounds experience a different social environment when it comes to friends than students with non-immigrant backgrounds do, as the share of friends with im- migrant backgrounds is significantly higher for students who themselves have immigrant backgrounds

Building Biospheres Reserves through Collaborative Governance : a study of organisational forms and collaborative processes in Sweden’s biosphere reserves

In June 2019, Sweden received its seventh biosphere reserve. Biosphere reserves are part of UNESCO’s global programme Man and the Biosphere (MAB), which commenced in 1971 with the aim of enhancing the relationship between humans and the environment. There are more than 700 biosphere reserves in the world that strive to be model areas for sustainable societal development. In total, Sweden’s biosphere reserves account for about seven per cent of the country’s total surface area. The report describes the development that has taken place in Sweden’s biosphere reserves regarding their organisational structures and their formation processes. The report is based on semi-structured interviews and conversations with about 60 key informants in combination with extensive analysis of documents. Based on the biosphere reserves’ mission to promote collaboration and dialogue for sustainable societal development, the report describes the challenges and success factors that have emerged since their establishment and discusses these in relation to issues concerning organisational change, representativeness, legitimacy and organisational effects. The report shows that the biosphere reserves are characterised by extensive collaboration among different stakeholders and organisations, but run the risk of mission drift due to their hybrid organisational character and their interactive working methods. The report also reveals several significant qualitative results of the biosphere reserves’ organisational processes. In several of the biosphere reserves, people have started to perceive and relate to their environments in new ways as a result of the work. The collaborative work processes have also contributed to resolving several natural resourcerelated conflicts. Finally, the report provides recommendations for supporting the work with biosphere reserves in Sweden

Shared Places, Separate Spaces : Constructing Cultural Spaces through two National Languages in Finland

Finland is a bilingual country with 2 national languages, Finnish and Swedish. The Swedish-speaking school institution aims to protect the minority language by maintaining a monolingual school space. In this article, the construction of linguistic and ethnic difference in educational discourse and practice related to the national languages in Finland is analyzed by using discourse analysis, feminist and post-structural theories. By analyzing ethnographic data and public debate, we argue that discursive and material practices related to spatiality have a significant role in constructing difference and otherness in the Finnish school context. Essentialist categories are produced but also contested from the positions within the cultural spaces at school and in society at large.Peer reviewe

Bluetonguen maahantulo ja leviäminen Suomessa : riskiprofiili

Bluetongue (BT) on vektorivälitteinen märehtijöiden virustauti, joka kuuluu Suomessa vastustettavien, helposti leviävien eläintautien ryhmään. Taudin oireet ovat epäspesifisiä, ja niihin kuuluvat muun muassa kuume, haavaumat suun limakalvoilla, nielemisvaikeudet, turvotukset pään alueella ja ontuminen. Bluetongue-tautia ei ole koskaan todettu Suomessa. Viime vuosina BT-tautipurkauksia on todettu aikaisempaa pohjoisempana. Suomen kannalta lähimpiä tautipurkauksia on todettu Ruotsissa ja Norjassa. Tässä riskiprofiilissa tarkastellaan BT:n maahan tuloon ja tartunnan edelleen leviämiseen liittyviä riskitekijöitä sekä tartunnan leviämisen seurauksia. Tarkastelussa on huomioitu Suomen ilmaston ja eläinpopulaation erityispiirteet. Lisäksi on selvitetty taudin mahdollisia seurauksia, sekä millä edellytyksillä tartunta voisi Suomessa jäädä endeemiseksi. Suomessa esiintyy ainakin neljä Culicoides-suvun lajia, jotka on ulkomailla yhdistetty BT-virukseen. Ilmatieteen laitoksen kymmenen viime vuoden tilastojen mukaan lämpötilat ovat olleet riittävän korkeita tarpeeksi pitkään mahdollistaakseen polttiaisen ja BT-viruksen lisääntymisen ja leviämisen koko maassa, mutta ilmastolliset olosuhteet ovat taudin kannalta suotuisimmat Ahvenanmaalla, Etelä- ja Länsi-Suomessa.Blåtunga (BT) är en vektorburen virussjukdom som drabbar idisslare, och räknas i Finland till de djursjukdomar som med lätthet sprider sig och som skall bekämpas genom myndighetsåtgärder. Sjukdomens symptom är ospecifika, men i dem ingår bland annat feber, erosioner i munslemhinnan, svårigheter att svälja, svullnader i huvudregionen och hälta. Blåtunga har aldrig påträffats i Finland. Under de senaste åren har sjukdomsutbrott av BT påträffats längre norrut än tidigare. De för Finland närmaste sjukdomsutbrotten har påträffats i Sverige och Norge. Riskfaktorer som påverkar sjukdomens möjlighet att komma till Finland, dess fortsatta möjlighet att spridas inom landet och dess följder har granskats i denna riskprofil. Klimatförhållanden och djurpopulationens särdrag har speciellt beaktats. Dessutom har sjukdomens konsekvenser och möjligheter att förbli endemisk i landet studerats. I Finland finns åtminstone fyra slag av Culicoides-svidknott som har kopplats ihop med BT-virus utomlands. Enligt Finlands meteorologiska instituts 10 senaste års statistik har temperaturen visat sig ha varit tillräckligt hög tillräckligt länge för att möjliggöra att vektorerna och BT-virus skulle kunna föröka sig och spridas i hela landet, men väderleksförhållandena är ur ett sjukdomsperspektiv mest fördelaktiga på Åland och i södra och västra Finland.Bluetongue (BT) is a vector-borne viral disease of ruminants, which is classified in Finland as an easily spreading disease which has to be controlled. The symptoms of the disease are non-specific, and are for example fever, erosions on the mucous membrane of the mouth, difficulties in swallowing, swellings in the head and lameness. Bluetongue has never been found in Finland. In the last few years, Bluetongue outbreaks have been detected further north than previously. The outbreaks closest to Finland have been in Sweden and Norway. In this risk profile we study the risk factors related to BT coming to Finland and spreading further and what the consequences would be if the disease should spread. In the study, the Finnish climate and the specific features of the animal population have been taken into account. In addition, the possible consequences of the disease and under what conditions the disease could remain endemic in Finland have been investigated. In Finland there are at least four species of the Culicoides family which have been connected with the BT virus abroad. According to the statistics of the Finnish Meteorological Institute for the last ten years, the temperatures have been high enough for long enough in order to make it possible for the Culicoides biting midges and the BT virus to increase and to spread throughout the whole country. The climatic conditions however, are more favourable to the disease on Åland and in Southern and Western Finland

Afrikkalaisen sikaruton mahdollisia maahantuloreittejä : riskiprofiili

Afrikkalainen sikarutto on lakisääteisesti vastustettava helposti leviävä sikojen ja villisikojen virustauti, jolla on myös vakavia sosioekonomisia vaikutuksia. Akuutissa tautimuodossa eläimillä esiintyy syömättömyyttä, korkeaa kuumetta, verenpurkaumia iholla, veristä ulostetta sekä mahdollisesti ripulia. Kuolleisuus on lähes 100 % ja tauti johtaa kuolemaan 7-10 vrk tartunnan jälkeen. Tauti ei tartu ihmisiin. Tautia esiintyy sekä kesy- että villisioissa suurimmassa osassa Saharan eteläpuolista Afrikkaa ja Sardiniassa. Vuodesta 2007 lähtien tautia on esiintynyt Kaukasuksen alueella ja vuonna 2011 lähellä Suomen rajaa: Leningradin alueella ja Kuolan niemimaalla. Tässä riskiprofiilissa kartoitetaan reitit ja tapahtumasarjat, jotka voivat johtaa siihen, että afrikkalainen sikarutto tulee Suomeen ensimmäisen kerran. Näistä oleellisimmat ovat: maahantulo infektioalueella matkustaneiden ihmisten mukana, infektoituneen lihan tai lihatuotteen mukana, elävien kesysikojen ja sperman mukana, kontaminoituneiden eläinkuljetusajoneuvojen mukana, kansainvälisen liikenteen ruokajätteen mukana ja Suomeen vaeltavan infektoituneen villisian mukana. Tilatason tautisuojaus sekä tehokas ja kohdennettu tiedottaminen taudin vaaroista ovat avainasemassa, kun halutaan suojata Suomen sikaelinkeinoa afrikkalaiselta sikarutolta.Afrikansk svinpest är en virussjukdom som bör bekämpas genom lag. Sjukdomen förekommer hos svin och vildsvin, den överförs lätt och har även betydande socioekonomiska följder. I det akuta stadiet förekommer hos djuren aptitlöshet, hög feber, hematomer på huden, blod i avföringen samt eventuellt diarré. Dödligheten är nästan 100 procent och sjukdomen leder till döden 7-10 dygn efter smittan. Sjukdomen smittar inte på människor. Sjukdomen förekommer både hos tama svin och vildsvin i största delen av Afrika söder om Sahara och på Sardinien. Från och med 2007 har sjukdomen förekommit i Kaukasusregionen och år 2011 nära gränsen till Finland: kring Leningrad och på Kolahalvön. I den här riskprofilen utreds rutter och händelseförlopp som kan leda till att den afrikanska svinpesten för första gången påträffas i Finland. De mest väsentliga är: människor som reser in i landet från resor i infektionsområdet, infekterat kött eller köttprodukter, levande tama svin och sperma, kontaminerade djurtransportfordon, matavfall från internationell trafik och infekterade vildsvin som strövar över gränsen till Finland. De viktigaste medlen för att skydda den finska svinindustrin från den afrikanska svinpesten är att skydda gårdar mot sjukdomen samt en effektiv och riktad information om sjukdomens faror.The African swine fever is a viral disease that spreads easily to domestic pigs and wild boar and has considerable socioeconomic consequences as well. Statutory measures are required to combat African swine fever. In the acute phase of the disease pigs can show symptoms including high fever, haemorrhages in the skin, anorexia, blood in stool and possibly diarrhea. Mortality rates can reach almost 100 per cent, and death appears within 7-10 days from infection. The disease is not spread to humans. The disease occurs as well as in domestic pigs as in wild boar in the largest part of sub-Saharan Africa and in Sardinia. Since 2007 the disease has occurred in the Caucasus region and in 2011 near the border of Finland: the Leningrad region and the Kola Peninsula. In the risk profile different routes and chains of events which could lead to the African swine fever entering Finland for the first time are identified and described. The most obvious ones are: people who have travelled in the infected area, infected meat or meat products, with domestic pigs and sperm, contaminated transport vehicles, catering waste from international transport and infected wild boars crossing the border to Finland. The key measures to protect the Finnish swine industry from the African swine fever are high biosecurity of farms and effective and aimed information on the risks of the disease

Becoming tolerable : Subject constitution of Roma mediators in Finnish schools

Although Finnish politics relating to the Roma tend to be perceived internationally as fairly successful, several obstacles exist for the Roma in education and the labour market. Training of Roma mediators has been actively promoted in Finland to improve the school performance and equality of Roma pupils. This article, based on ethnographic research, focuses on exploring how the current discursive terrain around the topics of tolerance and prejudice functions in the everyday work of mediators. It is argued that the present discourses in school expose the mediators to unequal power relations of tolerance. The terms for being tolerated are set by the potential tolerating actors, the school community. The mediators aim to supply knowledge about the Roma and try to address prejudices as representatives of the Roma. The study identified three different strategies that the mediators used when encountering prejudice: making sure one does not seem too different, parody and feigning naivety. The analysis suggests that the present discursive terrain creates obstacles to addressing inequalities, discrimination and racism in educational contexts. The responsibility for tackling discrimination is placed on the shoulders of individual Roma - not the whole school community.Peer reviewe

The Finnish mathematics teachers' lexicon : A focus on organisation and relationships

Peer reviewe

Taking steps towards institutionalizing multicultural education – The national curriculum of Finland

Internationally multicultural education research has pointed to the need to move from superficial to social justice-oriented multicultural education. However, realising this goal in policy and practice is a challenge. This study takes Finland as a case and examines the discursive developments of multicultural education in its national curriculum 1994–2014. Despite being a country which is known for emphasising equity and equality in education, superficial forms of multicultural education have prevailed. However, the results of this study show that the curricular discourse is clearly moving towards social justice education where multicultural perspectives are an integrated part of the curriculum. The 2014 curriculum, which came into effect 2016, emerges as a policy which aims to foster ethical and respectful students with a sense of fairness and an open attitude towards all kinds of diversity. The challenge for Finland is to ensure implementation and advance transformativeness in future curriculum reforms.Peer reviewe

Där förändringens vindar blåser

År 2007 anmälde två företag intresse att etablera vindkraftverk i ett skogsområde i Hälsingland. Frågan uppmärksammades av Gävleborgs fäbodförening (GFF) som ifrågasatte exploateringen. Den här uppsatsen undersöker hur GFF, genom att belysa fäbodbrukets, landskapets och vindkraftens historia, mobiliserar sig i konflikten. Inspirerad av narrativ analys har jag undersökt texter publicerade av GFF, med slutsatsen att historiebruk används för att belysa landskapets värde, att levandegöra platsen och att problematisera den förändring som vindkraft kommer att innebära. Fallet kan ses som ett exempel på hur marginaliserade verksamheter gör motstånd mot exploatering.In 2007 two companies expressed an interest in building wind turbines in a forest area in Hälsingland. A summer farm association in Gävleborg (GFF) opposed the proposed wind farm. This essay explores how the association uses narratives of the history of summer farms, landscapes and wind power to mobilize in the conflict. Inspired by narrative analysis I have studied texts published by GFF during the conflict and drawn the conclusion that history is used to elucidate the landscape’s values, to bring to life the importance of place and to problematize the changes that wind power inevitably will cause. The case can be seen as an example of a marginalised group’s resistance towards exploitation of land