Browsing by Subject "SECRETION"

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  • Bennet, Louise; Nilsson, Christopher; Mansour-Aly, Dina; Christensson, Anders; Groop, Leif; Ahlqvist, Emma (2021)
    Background Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro- and microvascular complications between diabetes patients of Middle Eastern and European origin. Methods This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro- and microvascular complications were assessed using cox-regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. Findings In Iraqi immigrants versus native Swedes, severe insulin-deficient diabetes was almost twice as common (27.9 vs. 16.2% p <0.001) but severe insulin-resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06-3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05-0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. Interpretation People with diabetes, born in the Middle East present with a more insulin-deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.
  • Hematy, Kian; De Bellis, Damien; Wang, Xin; Mähönen, Ari Pekka; Geldner, Niko (2022)
    The exocyst is the main plasma membrane vesicle-tethering complex in eukaryotes and is composed of eight different subunits. Yet, in plant genomes, many subunits display multiple copies, thought to reflect evolution of complex subtypes with divergent functions. In Arabidopsis thaliana root endodermal cells, the isoform EXO70A1 is required for positioning of CASP1 at the Casparian Strip Domain, but not for its non-targeted secretion to the plasma membrane. Here, we show that exo84b resembles exo70a1 mutants regarding CASP1 mistargeting and secretion of apoplastic proteins, but exo84b additionally affects secretion of other integral plasma membrane proteins. Moreover, conditional, cell-type-specific gene editing of the single-copy core component SEC6 allows visualization of secretion defects in plant cells with a complete lack of exocyst complex function. Our approach opens avenues for deciphering the complexity/diversity of exocyst functions in plant cells and enables analysis of central trafficking components with lethal phenotypes. Genetic analysis of exocyst isoforms reveals their distinct roles in cargo secretion.
  • Kohva, E.; Varimo, T.; Huopio, H.; Tenhola, S.; Voutilainen, R.; Toppari, J.; Miettinen, P. J.; Vaaralahti, K.; Viinamäki, J.; Backman, J. T.; Hero, M.; Raivio, T. (2020)
    STUDY QUESTION: Does treatment of constitutional delay of growth and puberty (CDGP) in boys with aromatase inhibitor letrozole (Lz) or conventional low-dose testosterone (T) have differing effects on developing seminiferous epithelium? SUMMARY ANSWER: Anti-Mullerian hormone (AMH) declined similarly in both treatment groups, and the two Sertoli cell-derived markers (AMH and inhibin B (iB)) exhibited differing responses to changes in gonadotrophin milieu. WHAT IS KNOWN ALREADY: Boys with CDGP may benefit from puberty-inducing medication. Peroral Lz activates gonadotrophin secretion, whereas intramuscular low-dose T may transiently suppress gonadotrophins and iB. STUDY DESIGN, SIZE, DURATION: Sera of 28 boys with CDGP who participated in a randomised, controlled, open-label trial at four paediatric centres in Finland between August 2013 and January 2017 were analysed. The patients were randomly assigned to receive either Lz (2.5 mg/day) (n = 15) or T (I mg/kg/month) (n = 13) for 6 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 28 patients were at least 14 years of age, showed first signs of puberty, wanted medical attention for CDGP and were evaluated at 0, 3, 6 and 12 months of visits. AMH levels were measured with an electrochemiluminescence immunoassay and L2 levels with liquid chromatography coupled with tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: AMH levels decreased in both treatment groups during the 12-month follow-up (P <0.0001). Between 0 and 3 months, the changes in gonadotrophin levels (increase in the Lz group, decrease in the T group) correlated strongly with the changes in levels of iB (FSH vs iB, r = 0.55, P=0.002; LH vs iB, r =0.72, P LIMITATIONS, REASONS FOR CAUTION: The original trial was not blinded for practical reasons and included a limited number of participants. WIDER IMPLICATIONS OF THE FINDINGS: In early puberty, treatment-induced gonadotrophin stimulus was unable to counteract the androgen-mediated decrease in AMH, while changes in iB levels were associated with changes in gonadotrophin levels. AMH decreased similarly in both groups during the treatment, reassuring safety of developing seminiferous epithelium in both treatment approaches. Since a fixed dose of Li induced variable serum Lz levels with a desired puberty-promoting effect in all boys, more research is needed to aim at a minimal efficient dose per weight.
  • IDEFICS and I.Family consortia; Thumann, Barbara F.; Michels, Nathalie; Felső, Regina; Kaprio, Jaakko; Börnhorst, Claudia (2020)
    Background Short sleep duration has been suggested to lead to insulin resistance both directly by altering glucose metabolism and indirectly through obesity. This study aims to investigate associations between nocturnal sleep duration and insulin resistance considering abdominal obesity as a mediator. Methods We analysed data of 3 900 children aged 2–15 years participating in the second (2009/10) and third (2013/14) examination wave of the European IDEFICS/I.Family study (hereafter referred to as baseline and follow-up). Information on nocturnal sleep duration was collected by questionnaires and age-standardised (SLEEP z-score). The homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose obtained from blood samples; waist circumference (WAIST) was measured with an inelastic tape. HOMA and WAIST were used as indicators for insulin resistance and abdominal obesity, respectively, and transformed to age- and sex-specific z-scores. Cross-sectional and longitudinal associations between SLEEP z-score and HOMA z-score were investigated based on a path model considering WAIST z-score as a mediator adjusting for relevant confounders. Results Cross-sectionally, baseline SLEEP z-score was negatively associated with baseline WAIST z-score (unstandardised effect estimate -0.120, 95% confidence interval [-0.167; -0.073]). We observed no direct effect of baseline SLEEP z-score on baseline HOMA z-score but a negative indirect effect through baseline WAIST z-score (-0.042 [-0.058; -0.025]). Longitudinally, there was no direct effect of baseline SLEEP z-score on HOMA z-score at follow-up but a negative indirect effect through both baseline WAIST z-score and WAIST z-score at follow-up (-0.028 [-0.040; -0.016]). Conclusions Our results do not support the hypothesis of an association between short sleep duration and insulin resistance independent of abdominal obesity. However, longer sleep duration may exert short and long term beneficial effects on insulin resistance through its beneficial effects on abdominal obesity.
  • Fan, Yuxin; Wang, Leishen; Liu, Huikun; Zhang, Shuang; Tian, Huiguang; Shen, Yun; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Hu, Gang; Liu, Ming (2020)
    Introduction To evaluate the single association of postpartum beta-cell dysfunction and insulin resistance (IR), as well as different combinations of postpartum beta-cell dysfunction, IR, obesity, and a history of gestational diabetes mellitus (GDM) with postpartum type 2 diabetes risk. Research design and methods The study included 1263 women with prior GDM and 705 women without GDM. Homeostatic model assessment was used to estimate homeostatic model assessment of beta-cell secretory function (HOMA-%beta) and homeostatic model assessment of insulin resistance (HOMA-IR). Results Multivariable-adjusted ORs of diabetes across quartiles of HOMA-%beta and HOMA-IR were 1.00, 1.46, 2.15, and 6.25 (p(trend) Conclusions beta-cell dysfunction or IR was significantly associated with postpartum diabetes. IR and beta-cell dysfunction, together with obesity and a history of GDM, had the highest ORs of postpartum diabetes risk.
  • Ligthart, Kate; Belzer, Clara; de Vos, Willem M.; Tytgat, Hanne L.P. (2020)
    Cell-surface-located proteinaceous appendages, such as flagella and fimbriae or pili, are ubiquitous in bacterial communities. Here, we focus on conserved type IV pili (T4P) produced by bacteria in the intestinal tract, one of the most densely populated human ecosystems. Computational analysis revealed that approximately 30% of known intestinal bacteria are predicted to produce T4P. To rationalize how T4P allow intestinal bacteria to interact with their environment, other microbiota members, and host cells, we review their established role in gut commensals and pathogens with respect to adherence, motility, and biofilm formation, as well as protein secretion and DNA uptake. This work indicates that T4P are widely spread among the known members of the intestinal microbiota and that their contribution to human health might be underestimated.
  • Albert, Katrina; Raymundo, Diana P.; Panhelainen, Anne; Eesmaa, Ave; Shvachiy, Liana; Araujo, Gabriela R.; Chmielarz, Piotr; Yan, Xu; Singh, Aastha; Cordeiro, Yraima; Palhano, Fernando L.; Foguel, Debora; Luk, Kelvin C.; Domanskyi, Andrii; Voutilainen, Merja H.; Huttunen, Henri J.; Outeiro, Tiago F.; Saarma, Mart; Almeida, Marcius S.; Airavaara, Mikko (2021)
    A molecular hallmark in Parkinson's disease (PD) pathogenesis are a-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth factor that is mostly resident in the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of the beneficial effects of CDNF can be protecting neurons from the toxic effects of alpha-synuclein. Here, we investigated the effects of CDNF on alpha-synuclein aggregation in vitro and in vivo. We found that CDNF directly interacts with alpha-synuclein with a KD = 23 +/- 6 nM and reduces its auto-association. Using nuclear magnetic resonance (NMR) spectroscopy, we identified interaction sites on the CDNF protein. Remarkably, CDNF reduces the neuronal internalization of alpha-synuclein fibrils and induces the formation of insoluble phosphorylated alpha-synuclein inclusions. Intra-striatal CDNF administration alleviates motor deficits in rodents challenged with a-synuclein fibrils, though it did not reduce the number of phosphorylated alpha-synuclein inclusions in the substantia nigra. CDNF's beneficial effects on rodent behavior appear not to be related to the number of inclusions formed in the current context, and further study of its effects on the aggregation mechanism in vivo are needed. Nonetheless, the interaction of CDNF with a-synuclein, modifying its aggregation, spreading, and associated behavioral alterations, provides novel insights into the potential of CDNF as a therapeutic strategy in PD and other synucleinopathies.
  • Koskinen, Maarit K.; Lempainen, Johanna; Löyttyniemi, Eliisa; Helminen, Olli; Hekkala, Anne; Härkönen, Taina; Kiviniemi, Minna; Simell, Olli; Knip, Mikael; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta (2018)
    Context: A declining first-phase insulin response (FPIR) is characteristic of the disease process leading to clinical type 1 diabetes. It is not known whether reduced FPIR depends on class II human leukocyte antigen (HLA) genotype, islet autoimmunity, or both. Objective: To dissect the role of class II HLA DR-DQ genotypes and biochemical islet autoantibodies in the compromised FPIR. Design, Setting, Participants: A total of 438 children with defined HLA DR-DQ genotype in the prospective Finnish Type 1 Diabetes Prediction and Prevention Study were analyzed for FPIR in a total of 1149 intravenous glucose tolerance tests and were categorized by their HLA DR-DQ genotype and the number of biochemical islet autoantibodies at the time of the first FPIR. Age-adjusted hierarchical linear mixed models were used to analyze repeated measurements of FPIR. Main Outcome Measure: The associations between class II HLA DR-DQ genotype, islet autoantibody status, and FPIR. Results: A strong association between the degree of risk conferred by HLA DR-DQ genotype and positivity for islet autoantibodies existed (P <0.0001). FPIR was inversely associated with the number of biochemical autoantibodies (P <0.0001) irrespective of HLA DR-DQ risk group. FPIR decreased over time in children with multiple autoantibodies and increased in children with no biochemical autoantibodies (P <0.0001 and P = 0.0013, respectively). Conclusions: The class II HLA DR-DQ genotype association with FPIR was secondary to the association between HLA and islet autoimmunity. Declining FPIR was associated with positivity for multiple islet autoantibodies irrespective of class II HLA DR-DQ genotype.
  • Majala, Susanna; Vesterinen, Tiina; Seppänen, Hanna; Mustonen, Harri; Sundström, Jari; Schalin-Jäntti, Camilla; Gullichsen, Risto; Schildt, Jukka; Kemppainen, Jukka; Arola, Johanna; Kauhanen, Saila (2022)
    Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
  • Kallio-Kujala, I. J.; Bennett, R. C.; Raekallio, M. R.; Yatkin, E.; Meierjohann, A.; Savontaus, E.; Scheinin, M.; Spillmann, T.; Vainio, O. M. (2018)
    The commonly used sedative alpha(2)-adrenoceptor agonist dexmedetomidine has adverse cardiovascular effects in dogs that can be prevented by concomitant administration of the peripherally acting alpha(2)-adrenoceptor antagonist MK-467. An ancillary effect of dexmedetomidine is to decrease insulin release from the pancreas, whereas MK-467 stimulates insulin release. This study assessed the effects of co-administered dexmedetomidine and MK-467 in a canine glibenclamide-induced hypoglycaemia model. In a randomised, cross-over experiment, eight beagle dogs received five intravenous treatments, comprising two administrations of saline, with dexmedetomidine or dexmedetomidine and MK-467, and three administrations of glibenclamide, with saline, dexmedetomidine or dexmedetomidine and MK-467. Plasma concentrations of glucose, lactate, insulin, glucagon and the test drugs were monitored. Administration of glibenclamide significantly increased insulin secretion and decreased blood glucose concentrations. Dexmedetomidine counteracted glibenclamide-evoked hypoglycaemia. This was opposed by the alpha(2)-adrenoceptor antagonist MK-467, but the glibenclamide-evoked hypoglycaemia was not potentiated by co-administration of dexmedetomidine and MK-467. None of the dogs developed uncontrolled hypoglycaemia. Thus, the combination of dexmedetomidine and MK-467 appeared to be safe in this canine hypoglycaemia model. Nevertheless, when MK-467 is used to alleviate the undesired cardiovascular effects of alpha(2)-adrenoceptor agonists in dogs, it should be used with caution in animals at risk for hypoglycaemia because of its insulin-releasing and hypoglycaemic effects. (C) 2018 The Author(s). Published by Elsevier Ltd.
  • Boren, Jan; Adiels, Martin; Bjornson, Elias; Matikainen, Niina; Söderlund, Sanni; Rämö, Joel; Ståhlman, Marcus; Ripatti, Pietari; Ripatti, Samuli; Palotie, Aarno; Mancina, Rosellina M.; Hakkarainen, Antti; Romeo, Stefano; Packard, Chris J.; Taskinen, Marja-Riitta (2020)
    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. The transmembrane 6 superfamily member 2 (TM6SF2) E167K genetic variant associates with NAFLD and with reduced plasma triglyceride levels in humans. However, the molecular mechanisms underlying these associations remain unclear. We hypothesized that TM65F2 E167K affects hepatic very low-density lipoprotein (VLDL) secretion and studied the kinetics of apolipoprotein 13100 (apoB100) and triglyceride metabolism in VLDL in homozygous subjects. In 10 homozygote TM6SF2 E167K carriers and 10 matched controls, we employed stable-isotope tracer and compartmental modeling techniques to determine apoB100 and triglyceride kinetics in the 2 major VIOL subtractions: large triglyceride-rich VLDL, and smaller, less triglyceride-rich VLDL2. VLDL1-apoB100 production was markedly reduced in homozygote TM6SF2 E167K carriers compared with controls. Likewise. VLDL,-triglyceride production was 35% lower in the TMSSF2 E167K carriers. In contrast, the direct production rates for VLDL2 apo13100 and triglyceride were not different between carriers and controls. In conclusion, the TM6SF2 E167K genetic variant was linked to a specific reduction in hepatic secretion of large triglyceride-rich VLDL1. The impaired secretion of VLDL1 explains the reduced plasma triglyceride concentration and provides a basis for understanding the lower risk of cardiovascular disease associated with the TM6SF2 E167K genetic variant.
  • Ristagno, Giuseppe; Masson, Serge; Tiainen, Marjaana; Bendel, Stepani; Bernasconi, Roberto; Varpula, Tero M; Milani, Valentina; Vaahersalo, Jukka; Magnoli, Michela; Spanuth, Eberhard; Barlera, Simona; Latini, Roberto; Hoppu, Sanna; Pettila, Ville; Skrifvars, Markus; FINNRESUSCI Study Grp (2016)
    Background: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. Methods: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score >= 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. Results: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p <0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p <0.0001; AUC = 0.70 +/- 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p <0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p <0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 +/- 0. 04 (p <0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). Conclusions: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.
  • Huovinen, Ville; Bucci, Marco; Lipponen, Heta; Kiviranta, Riku; Sandboge, Samuel; Raiko, Juho; Koskinen, Suvi; Koskensalo, Kalle; Eriksson, Johan G.; Parkkola, Riitta; Iozzo, Patricia; Nuutila, Pirjo (2016)
    Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring's mother's obesity status. 37 frail elderly females (mean age 71.9 +/- 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI = 28.1 kg/m(2)) were studied before and after a four-month individualized resistance training intervention. Nine age-and sex-matched non-frail controls (maternal BMI
  • Markkanen, Helene M.; Pekkarinen, Tuula; Hamalainen, Esa; Valimaki, Matti J.; Alfthan, Henrik V.; Stenman, Ulf-Hakan (2017)
    Objective: Data on the effect of gender on the interpretation of the GHRH plus arginine stimulation test (GHRH + ARG test) is controversial. We validated the GHRH + ARG stimulation test in control subjects and patients with organic or idiopathic pituitary disease and a suspicion of adult growth hormone deficiency (AGHD) using the Immulite 2000 XPi GH assay. Design: We studied 126 apparently healthy adults (median age 38.8 years) and 34 patients with a suspicion of AGHD (median age 42.2 years). Identification of AGHD with the GHRH + ARG test was investigated with commonly accepted BMI-related consensus cut-off limits for peak GH concentrations. Serum samples collected during the GHRH + ARG test were analysed for GH in 2014-2015. Serum IGF-1 concentrations were studied as a reference. Results: In 14 of 65 (22%) control males the GH peak value was below the BMI-related cut-off limits for GH sufficiency indicating a false diagnosis of AGHD. All control females had a normal GHRH + ARG response. Median peak GH response was significantly (p <0.001) higher in female (39.3 mu g/L) than in male controls (21 mu g/L). According to consensus cut-offs all but one young female patient had a deficient response compatible with a diagnosis of AGHD. Conclusions: The GH response to stimulation by GHRH + ARG is gender-dependent, being lower in healthy males than in females. Gender should be considered when defining cut-off limits for peak GH concentrations in the GHRH + ARG test. The presently used BMI-related cut-off levels will lead to a significant misclassification of males as GH deficient.
  • Niemi, Outi; Laine, Pia; Koskinen, Patrik; Pasanen, Miia; Pennanen, Ville; Harjunpaa, Heidi; Nykyri, Johanna; Holm, Liisa; Paulin, Lars; Auvinen, Petri; Palva, E. Tapio; Pirhonen, Minna (2017)
    Bacteria of the genus Pectobacterium are economically important plant pathogens that cause soft rot disease on a wide variety of plant species. Here, we report the genome sequence of Pectobacterium carotovorum strain SCC1, a Finnish soft rot model strain isolated from a diseased potato tuber in the early 1980's. The genome of strain SCC1 consists of one circular chromosome of 4,974,798 bp and one circular plasmid of 5524 bp. In total 4451 genes were predicted, of which 4349 are protein coding and 102 are RNA genes.
  • Haen, Silke M.; Heinonen, Mari; Kauffold, Johannes; Heikinheimo, Markku; Hoving, Lia L.; Soede, Nicoline M.; Peltoniemi, Olli A. T. (2019)
    Contents The aim of this study was to investigate the relationship of progesterone (P) and luteinizing hormone (LH) during recognition and establishment of pregnancy in the gilt. Therefore, the effects of eliminating episodic LH pulses on P patterns were determined during early pregnancy. To this end, a slow-release GnRH implant deslorelin was used for GnRH down-regulation. A group of gilts (GnRHa, n = 8) was implanted with the GnRH-agonist on Day 11 of pregnancy, while a control group (C, n = 5) was treated with a non-impregnated placebo implant. Blood was collected via a vena cava caudalis catheter at 10-min intervals for 8 hr on Day 16 and 21 of pregnancy. As expected, the GnRH implant reduced LH secretion (p <0.01) and abolished LH pulses completely at Day 16 and Day 21 of pregnancy. On Day 16, there was no difference in P levels between the treatments. However, on Day 21, the GnRH-agonist treatment led to significantly increased P concentrations (p <0.01) compared with the control gilts. Progesterone was secreted in a pulsatile manner in both treatment groups and no relationship between LH pulsatility and P pulsatility was observed. In conclusion, abolishment of LH pulsatility did not affect the pulsatile pattern of P secretion but led to an unexpected overall increase in P on Day 21 of pregnancy; this effect was delayed and occurred 10 days after commencing treatment with the GnRH depot agonist. The elevation of P on Day 21 of pregnancy in the GnRHa group suggests either a reduced negative feedback effect or an increased autocrine response by the corpora lutea.
  • Tverring, Jonas; Vaara, Suvi T.; Fisher, Jane; Poukkanen, Meri; Pettila, Ville; Linder, Adam; FINNAKI Study Grp (2017)
    Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP)is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011-1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2-3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5-82.4%) and IDI 0.053 (95% CI 0.029-0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers.
  • Robciuc, Marius R.; Metso, Jari; Sima, Anca; Ehnholm, Christian; Jauhiainen, Matti (2010)
    Background: phospholipid transfer protein (PLTP) plays important roles in lipoprotein metabolism and atherosclerosis and is expressed by macrophages and macrophage foam cells (MFCs). The aim of the present study was to determine whether the major protein from HDL, apoA-I, affects PLTP derived from MFCs. Results: as cell model we used human THP-1 monocytes incubated with acetylated LDL, to generate MFC. The addition of apoA-I to the cell media increased apoE secretion from the cells, in a concentration dependent fashion, without affecting cellular apoE levels. In contrast, apoA-I had no effect on PLTP synthesis and secretion, but strongly induced the PLTP activity in the media. ApoA-I also increased phospholipid transfer activity of PLTP isolated from human plasma. This effect was dependent on apoA-I concentration but independent on apoA-I lipidation status. ApoE, ApoA-II and apoA-IV, but not immunoglobulins or bovine serum albumin, also increased PLTP activity. We also report that apoA-I protects PLTP from heat inactivation. Conclusion: apoA-I enhances the phospholipid transfer activity of PLTP secreted from macrophage foam cells without affecting the PLTP mass.
  • Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsen, Bjorn; Gullstrom, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter (2016)
    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time.
  • Hasan, S.; Saha, S.; Junnikkala, S.; Orro, T.; Peltoniemi, O.; Oliviero, C. (2019)
    Resin acid-enriched composition (RAC) mainly containing tall oil fatty acid with an active component of resin acid (RA) can improve the microbial population in the digestive system, change the microbial fermentation, and improve the feed conversion ratio. We investigated the effects of dietary supplementation of RAC on sow colostrum yield (CY), colostrum composition and gut microbiota. Tall oil fatty acid and RA are commonly termed RAC and CLA, pinolenic, abietic, dehydrobiotic acids are characteristic components of RAC. The experiment was conducted in three trials in three respective herds. Sows were fed with a control diet and the same diet supplemented with 5 g RAC/day per sow during the last week of gestation. The 16S ribosomal RNA gene sequencing technique was used to assess sows' faecal microbiota populations at farrowing. Colostrum nutritional composition, acute phase proteins (APPs) and immunoglobulin (Ig) content were also assessed. Individual piglets were weighed at birth and 24 h after the birth of first piglets in order to calculate CY and later at 3 to 4 weeks to calculate average daily gain. The RAC-fed sows had significantly higher IgG levels (P0.05), but those fed RAC had higher levels of colostrum serum amyloid A. Colostrum yield was significantly higher in RAC-fed sows in herds 2 and 3 with heavier piglets between 3 and 4 weeks of age (P0.05). Resin acid-enriched composition supplementation significantly increased some beneficial and fermentative bacteria (Romboutsia and Clostridium sensu stricto) than the control diet (P