The pollen data of Mätäjärvi, Turku, SW Finland

The exceptionally abundant herb pollen flora in the sediments of Mätäjärvi made it possible to investigate the ecological and cultural development in the center of the town of Turku, SW Finland during the period of AD 1200-1700. Based on a pollen sum of 1000 NAP and approx. 33 herb pollen taxa/sample (from among a total set of 72 herb pollen and spore taxa), the changes in the NAP groups of 1) aquatics and hygrophytes, 2) meadow vegetation and 3) primary indicators of human activity (weeds and ruderals) were studied and the indicators of urban settlement determined

Humppila Järvensuo – a preinvestigation for an archaeological and palaeobotanical project in SW Finland

An as yet unexcavated neolithic dwelling place of a type so far unknown in Finland is presented. The objects found and the nature of the site are reminiscent of bog 'dwellings' in the Eastern Baltic area. 14C dates on the artefacts cover the period 4200-4800 B.P. An increase in the heliophilous pollen flora together with the macrofossil records helps in determining the vertical position of the cultural layer in the gyttja. A rich macrofossil assemblage of useful plants (including Trapa natans) is recorded

Type 1 tyrosinemia in Finland: a nationwide study

Background Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. Results Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. Conclusions Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.Peer reviewe

Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris

It was recently reported that co-expression of the proal(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T., Kivirikko, K.I., 1997. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: formation of a stable enzyme tetramer requires coexpression with collagen and assembly of a stable collagen requires coexpression with prolyl 4-hydroxylase. EMBO J, 16, 6702-6712). These properly folded molecules accumulated inside the yeast cell, however, only similar to 10% were found in the culture medium. We report here that replacement of the authentic signal sequence of the human pro alpha 1(III) with the Saccharomyces cerevisiae alpha mating factor prepro sequence led only to a minor increase in the amount secreted. Immunoelectron microscopy studies indicated that the procollagen molecules accumulate in specific membranous vesicular compartments that are closely associated with the nuclear membrane. Prolyl 4-hydroxylase, an endoplasmic reticulum (ER) lumenal enzyme, was found to be located in the same compartments. Non-helical pro alpha 1(III) chains produced by expression without recombinant prolyl 4-hydroxylase likewise accumulated within these compartments, The data indicate that properly folded recombinant procollagen molecules accumulate within the ER and do not proceed further in the secretory pathway. This may be related to the large size of the procollagen molecule. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved

Type 1 tyrosinemia in Finland: a nationwide study

Background Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. Results Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. Conclusions Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.Peer reviewe

Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris

It was recently reported that co-expression of the proal(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T., Kivirikko, K.I., 1997. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: formation of a stable enzyme tetramer requires coexpression with collagen and assembly of a stable collagen requires coexpression with prolyl 4-hydroxylase. EMBO J, 16, 6702-6712). These properly folded molecules accumulated inside the yeast cell, however, only similar to 10% were found in the culture medium. We report here that replacement of the authentic signal sequence of the human pro alpha 1(III) with the Saccharomyces cerevisiae alpha mating factor prepro sequence led only to a minor increase in the amount secreted. Immunoelectron microscopy studies indicated that the procollagen molecules accumulate in specific membranous vesicular compartments that are closely associated with the nuclear membrane. Prolyl 4-hydroxylase, an endoplasmic reticulum (ER) lumenal enzyme, was found to be located in the same compartments. Non-helical pro alpha 1(III) chains produced by expression without recombinant prolyl 4-hydroxylase likewise accumulated within these compartments, The data indicate that properly folded recombinant procollagen molecules accumulate within the ER and do not proceed further in the secretory pathway. This may be related to the large size of the procollagen molecule. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.</p

Stabilization and reversal of child obesity in Andalusia using objective anthropometric measures by socioeconomic status

Background: Childhood obesity continues to be a significant public health issue worldwide. Recent national studies in Spain show a stable picture. However, prevalence and trends differ by socio-economic status, age, and region. We present the trend in childhood excess weight prevalence, aged 8–15 years, in Andalusia from 2011-2012 to 2015–2016 by socio-economic status. Results: Overall prevalence of excess weight decreased from 42.0% in 2011–2012 to 35.4% in 2015–2016. Overweight decreased from 28.2 to 24.2% and obesity from 13.8 to 11.2%. In 2011–2012 the prevalence of excess weight in boys was 46.0%and 37.9% in girls; in 2015–2016 the difference became significant with 41% of boys with excess weight compared with 30% in girls. Conclusions: Childhood excess weight prevalence in Andalusia has decreased slightly between 2011-2012 and 2015–2016. Notably, a decrease in obesity prevalence in girls aged 8–15 years was recorded. In 2011–2012 a social gradient for excess weight prevalence across three SES indicators was observed: in 2015–2016 this gradient disappeared. Nonetheless, prevalence remains too high

Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1. </p

Rare Copy Number Variants Observed in Hereditary Breast Cancer Cases Disrupt Genes in Estrogen Signaling and TP53 Tumor Suppression Network

Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 BRCA1, BRCA2, and PALB2 mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (P = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and TP53 centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer

RAD51B in Familial Breast Cancer.

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk