Coxsackievirus B1 infections are associated with the initiation of insulin-driven autoimmunity that progresses to type 1 diabetes

Aims/hypothesis Islet autoimmunity usually starts with the appearance of autoantibodies against either insulin (IAA) or GAD65 (GADA). This categorises children with preclinical type 1 diabetes into two immune phenotypes, which differ in their genetic background and may have different aetiology. The aim was to study whether Coxsackievirus group B (CVB) infections, which have been linked to the initiation of islet autoimmunity, are associated with either of these two phenotypes in children with HLA-conferred susceptibility to type 1 diabetes. Methods All samples were from children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study. Individuals are recruited to the DIPP study from the general population of new-born infants who carry defined HLA genotypes associated with susceptibility to type 1 diabetes. Our study cohort included 91 children who developed IAA and 78 children who developed GADA as their first appearing single autoantibody and remained persistently seropositive for islet autoantibodies, along with 181 and 151 individually matched autoantibody negative control children, respectively. Seroconversion to positivity for neutralising antibodies was detected as the surrogate marker of CVB infections in serial follow-up serum samples collected before and at the appearance of islet autoantibodies in each individual. Results CVB1 infections were associated with the appearance of IAA as the first autoantibody (OR 2.4 [95% CI 1.4, 4.2], corrected p = 0.018). CVB5 infection also tended to be associated with the appearance of IAA, however, this did not reach statistical significance (OR 2.3, [0.7, 7.5], p = 0.163); no other CVB types were associated with increased risk of IAA. Children who had signs of a CVB1 infection either alone or prior to infections by other CVBs were at the highest risk for developing IAA (OR 5.3 [95% CI 2.4, 11.7], p <0.001). None of the CVBs were associated with the appearance of GADA. Conclusions/interpretation CVB1 infections may contribute to the initiation of islet autoimmunity being particularly important in the insulin-driven autoimmune process.Peer reviewe

Programmed death-ligand 1 and tumor-infiltrating lymphocytes (TILs) – low TIL density may predict poorer long-term prognosis in T1 laryngeal cancer

We evaluated the prognostic role of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in T1 glottic laryngeal squamous cell carcinoma (LSCC). T1 glottic LSCC patients (n = 174) treated at five Finnish university hospitals between 2003 and 2013 were included. Tissue microarray (TMA) blocks were used for PD-L1 immunohistochemistry. TILs were scored from intratumoral and stromal regions in whole tissue sections. Of 174 patients, 92 (53%) had negative, 66 (38%) intermediate, and 16 (9%) high PD-L1 levels. Of 80 patients whose TILs were analyzed, 50 (63%) had low and 30 (38%) high stromal TIL density. Patients with a local recurrence or a new primary tumor of the larynx had lower TIL density than had other patients (p = 0.047). High PD-L1 expression with low stromal TIL density was associated with inferior 5-year disease-specific survival (85% vs. 100%, p = 0.02). In conclusion, in patients treated for T1 glottic LSCC, low stromal TIL density was associated with local recurrences and new primary tumors of the larynx. High PD-L1 expression with low stromal TIL density may be associated with worse survival in T1 glottic LSCC.Peer reviewe

Living plant collections policy of the Finnish Museum of Natural History

The collections policy of the Finnish Museum of Natural History Luomus is hierarchically structured. The general collections policy defines the overall principles and guidelines. The sub-collections policies, such as the Living collections policy, comply with and apply the general collections policy and specify its guidelines and instructions, taking the special nature of the sub-collections into account. The living plant collections policy guides the care of the collections in the botanic gardens and the seed bank, excluding DNA and tissue samples which are covered by a separate genomic resources policy. The purpose of the collections policy is to help guide the care of the garden collections and the processing of information relating to the collections, thereby providing the basis for developing the botanic gardens.Non peer reviewe

Recommended reading list of early publications on atomic layer deposition-Outcome of the "Virtual Project on the History of ALD"

Atomic layer deposition (ALD), a gas-phase thin film deposition technique based on repeated, self-terminating gas-solid reactions, has become the method of choice in semiconductor manufacturing and many other technological areas for depositing thin conformal inorganic material layers for various applications. ALD has been discovered and developed independently, at least twice, under different names: atomic layer epitaxy (ALE) and molecular layering. ALE, dating back to 1974 in Finland, has been commonly known as the origin of ALD, while work done since the 1960s in the Soviet Union under the name "molecular layering" (and sometimes other names) has remained much less known. The virtual project on the history of ALD (VPHA) is a volunteer-based effort with open participation, set up to make the early days of ALD more transparent. In VPHA, started in July 2013, the target is to list, read and comment on all early ALD academic and patent literature up to 1986. VPHA has resulted in two essays and several presentations at international conferences. This paper, based on a poster presentation at the 16th International Conference on Atomic Layer Deposition in Dublin, Ireland, 2016, presents a recommended reading list of early ALD publications, created collectively by the VPHA participants through voting. The list contains 22 publications from Finland, Japan, Soviet Union, United Kingdom, and United States. Up to now, a balanced overview regarding the early history of ALD has been missing; the current list is an attempt to remedy this deficiency. (C) 2016 Author(s).Peer reviewe

Asumisjärjestelyjen vaikutus maatilan sukupolvenvaihdoksen onnistumiseen

Työn tavoitteena oli selvittää asumisjärjestelyjen vaikutus maatilan sukupolvenvaihdoksen onnistumiseen. Työn tilaajana oli Keski-Uudenmaan koulutuskuntayhtymän (Keuda) Saaren kartanon toimipiste. Tutkimus tehtiin nettikyselynä vuosina 2012-2018 Keudan EU-kurssilaisille, jotka joko olivat jo tehneet sukupolvenvaihdoksen maatilalla tai suunnittelivat sitä. He suorittivat kurssin täyttääkseen EU-tukikelpoisuusehdot Nuoren viljelijän aloitustukea varten. Tutkimuksessa myös haastateltiin luopujia teemahaastatteluna. Tutkimuksen tuloksena nousivat esiin ihmissuhteiden hyvänä säilymisen merkitys asumisjärjestelyiden onnistumisen edellytyksenä sekä maatilan töiden sujuminen riippumatta asumismuodosta sekä myös oliko asumismuodon valinta edellytys koko sukupolvenvaihdoksen toteutumiselle. Taloudelliset seikat olivat myös tärkeitä. Tutkimus osoittaa myös sen, että tärkeätä on tilan jatkuvuus, jopa asumisjärjestelyjen kustannuksella, sillä suurimmalle osalle tutkimukseen osallistuneista ei asumismuoto ollut kynnyskysymys sukupolvenvaihdoksen toteutumiselle.The aim of the thesis is to find out how the housing arrangements affect successful change of generation. A Webropol survey was used to gather the data. The students had made a change of generation or planned it. Also there was an interview on farms for older people, who had made a change of generation or were planning it. As results of the survey and interview was found how important relationships and the division of work load on the farms are. The survey shows the order of importance. The main importance is continuity in farms, even if you can not live as you want. The comissioner of the thesis was Keuda (Keuda Group, Vocational Education and Training, Natural Resources and the Environment)

Assembly and secretion of recombinant human collagens and gelatins in the yeast <em>Pichia pastoris</em>, and generation and analysis of knock-out mice for collagen prolyl 4-hydroxylase type I

Abstract Collagen molecules consist of three polypeptide chains that are coiled around each other to form a triple-helical structure. The formation of stable collagen triple helices requires the hydroxylation of proline residues catalyzed by collagen prolyl 4-hydroxylases (C-P4H). Vertebrate C-P4H is an ER-resident enzyme that consists of two catalytically active α subunits and two β subunits. Production of recombinant human collagen and gelatin could have numerous medical and industrial applications, but most recombinant systems lack the C-P4H activity. The yeast Pichia pastoris has been successfully engineered to produce stable human collagens and gelatins by co-expression of the collagen polypeptide chains with the two C-P4H subunits. This study examined the effect of deletion of the C-propeptide, or its replacement by a trimerizing foldon domain, on the assembly of type I and III collagen triple helices in P. pastoris. It was observed that the absence of the C-propeptide leads to inefficient collagen chain assembly whereas the replacement of C-propeptide with a foldon domain increased the assembly up to 3-fold. Moreover, the co-expression of α1(I) and α2(I) chains fused with foldon yielded heterotrimeric type I collagen molecules with a typical chain ratio of 2:1. As the foldon domain contains no information for collagen chain recognition, the present data indicate that the chain assembly is defined not only by the C-propeptides but also by other determinants present in the α chains. Another aspect studied here was the expression and secretion of gelatin fragments of varying size and conformation in P. pastoris. It was discovered that gelatin fragment size affects its secretion as the 90 kDa fragment was less efficiently secreted than the 45 kDa fragment. Secretion was also dependent on the fragment conformation as induction of the triple helix formation by either C-propeptide or foldon led to the accumulation of the fragments inside the yeast cells despite the presence of an efficient secretory signal. C-P4H was long assumed to exist as one type only but the cloning of several C-P4H α subunits raised questions concerning the specific roles of the C-P4H isoenzymes. The generation of mice lacking the type I C-P4H, which is regarded as the major C-P4H isoenzyme, indicated that this isoenzyme is essential for the embryonic development of the mouse. The embryos lacking type I C-P4H died at an early stage of their development due to the disruption of basement membranes. It was found that the basement membranes of the homozygous null embryos lacked type IV collagen whereas the fibrillar collagens were synthesized, although with altered morphology. The data reported here also demonstrate that the other C-P4H isoenzymes cannot compensate for the lack of type I isoenzyme