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  • Loponen, Tiina; Lallukka, Tea; Holstila, Ansku; Lahti, Jouni (BioMed Central, 2015)
    Abstract Background Physical activity level and overweight have shown associations with mental health problems but it is not known whether the risk of mental health problems due to overweight varies by physical activity. We examined joint association of physical activity and overweight with subsequent psychotropic medication among 40–60-year-old employees. Methods The questionnaire survey data were derived from Helsinki Health Study baseline postal questionnaires in 2000–02 among employees of the City of Helsinki aged 40–60 years (n = 8960, response rate 67 %). Baseline survey data were linked with prospective register data on prescribed psychotropic medication (ATC-codes N05 and N06, except N06D) among those with written consent (74 %) for such linkage. The analyses included 6169 responders (78 % women, corresponding to the target population). We divided participants into six groups according to their baseline self-reported body mass index and leisure-time physical activity using physically highly active normal-weight participants as a reference group. We used Cox regression analysis adjusted for age, gender, psychotropic medication prior to baseline, and socioeconomic position, marital status, working conditions, limiting long-standing illness, alcohol use, and smoking. Results At baseline, 49 % were overweight and 23 % were physically inactive. After adjusting for age and gender, inactive normal-weight (hazard ratio (HR) 1.3, 95 % CI 1.1–1.5), moderately active overweight (HR 1.3, 95 % CI 1.1–1.5) and inactive overweight (HR 1.4, 95 % CI 1.2–1.6) had higher risk for any psychotropic medication compared with group of highly active normal-weight. After adjusting for prior medication, only the inactive overweight group had higher risk (HR 1.4, 95 % CI 1.2–1.6). Other covariates made but a minor contribution to the examined associations. For antidepressants the associations were somewhat stronger than for sedatives. Conclusions Both normal-weight and physical activity help prevent psychotropic medication but physical activity dominates the association over normal-weight.
  • Tenorio-Laranga, Jofre; Montoliu, Carmina; Urios, Amparo; Hernandez-Rabaza, Vicente; Ahabrach, Hanan; García-Horsman, J. A; Felipo, Vicente (BioMed Central, 2015)
    Abstract Background Liver failure in experimental animals or in human cirrhosis elicits neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory events in neurodegenerative diseases: PREP protein levels are increased in brain glial cells upon neuroinflammatory insults, but the circulating PREP activity levels are decreased in multiple sclerosis patients in a process probably mediated by bioactive peptides. In this work, we studied the variation of PREP levels upon liver failure and correlated it with several inflammatory markers to conclude on the relation of PREP with systemic and/or neuroinflammation. Methods PREP enzymatic activity and protein levels measured with immunological techniques were determined in the brain and plasma of rats with portacaval shunt (PCS) and after treatment with ibuprofen. Those results were compared with the levels of PREP measured in plasma from cirrhotic patients with or without minimal hepatic encephalopathy (MHE). Levels of several pro-inflammatory cytokines and those of NO/cGMP homeostasis metabolites were measured in PCS rats and cirrhotic patients to conclude on the role of PREP in inflammation. Results In PCA rats, we found that PREP levels are significantly increased in the hippocampus, striatum and cerebellum, that in the cerebellum the PREP increase was significantly found in the extracellular space and that the levels were restored to those measured in control rats after administration of an anti-inflammatory agent, ibuprofen. In cirrhotic patients, circulatory PREP activity was found to correlate to systemic and neuroinflammatory markers and had a negative correlation with the severity of the disease, although no clear relation to MHE. Conclusions These results support the idea that PREP levels could be used as indicators of cirrhosis severity in humans, and using other markers, it might contribute to assessing the level of neuroinflammation in those patients. This work reports, for the first time, that PREP is secreted to the extracellular space in the cerebellum most probably due to glial activation and supports the role of the peptidase in the inflammatory response.
  • Heinonen, Jussi S.; Kurz, Mark D. (ELSEVIER BV, 2015)
    The massive outpourings of Karoo and Ferrar continental flood basalts (CFBs) ~180 Ma ago mark the initial Jurassic rifting stages of the Gondwana supercontinent. The origin and sources of these eruptions have been debated for decades, largely due to difficulties in defining their parental melt and mantle source characteristics. Recent findings of Fe- and Mg-rich dikes (depleted ferropicrite suite) from Vestfjella, western Dronning Maud Land, Antarctica, have shed light on the composition of the deep sub-Gondwanan mantle: these magmas have been connected to upper mantle sources presently sampled by the Southwest Indian Ocean mid-ocean ridge basalts (SWIR MORBs) or to high 3He/4He plume-entrained non-chondritic primitive mantle sources formed early in Earth’s history. In an attempt to determine their He isotopic composition and relative contributions from magmatic, cosmogenic, and radiogenic He sources, we performed in-vacuo stepwise crushing and melting analyses of olivine mineral separates, some of which were abraded to remove the outer layer. The best estimate for the mantle isotopic composition is given by a sample with the highest amount of He released (> 50%) during the first crushing step of an abraded coarse fraction. It has a 3He/4He of 7.03 ± 0.23 (2σ) times the atmospheric ratio (Ra), which is indistinguishable from those measured from SWIR MORBs (6.3‒7.3 Ra; source 3He/4He ~6.4–7.6 Ra at 180 Ma) and notably lower than in the most primitive lavas from the North Atlantic Igneous Province (up to 50 Ra), considered to represent the epitome magmas from non-chondritic primitive mantle sources. Previously published trace element and isotopic (Sr, Nd, and Pb) compositions do not suggest a direct genetic link to any modern hotspot of Indian or southern Atlantic Oceans. Although influence of a mantle plume cannot be ruled out, the high magma temperatures and SWIR MORB-like geochemistry of the suite are best explained by supercontinent insulation of a precursory Indian Ocean upper mantle source. Such a model is also supported by the majority of the recent studies on the structure, geochronology, and petrology of the Karoo CFBs.
  • Hanifeh, Mohsen; Heilmann, Romy M; Sankari, Satu; Rajamäki, Minna M; Mäkitalo, Laura; Syrjä, Pernilla; Kilpinen, Susanne; Suchodolski, Jan S; Steiner, Jörg M; Spillmann, Thomas (BioMed Central, 2015)
    Abstract Background Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively. Results Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p < 0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p < 0.05). Moreover, its concentration was higher in the jejunum than in the duodenum. Conclusions This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation.
  • Heinonen, Jussi S.; Jennings, Eleanor S.; Riley, Teal R. (ELSEVIER BV, 2015)
    Calculating reliable temperatures of Mg-rich magmas is problematic because melt composition and KD(Fe-Mg)ol-liq, the key parameters of many traditional thermometers, are difficult to constrain precisely. The recently developed Al-in-olivine thermometer [Coogan, L.A., Saunders, A.D., Wilson, R.N., 2014. Aluminum-in-olivine thermometry of primitive basalts: Evidence of an anomalously hot mantle source for large igneous provinces. Chemical Geology 368, 1–10] circumvents these problems by relying on the temperature-dependent exchange of Al between olivine and spinel crystallising in equilibrium with each other. This thermometer is used to re-evaluate the crystallisation temperatures of the most Mg-rich magma type identified from the Karoo large igneous province (LIP), known as the Vestfjella depleted ferropicrite suite. Previous temperature estimates for the suite were based on olivine-melt equilibria and indicated anomalously high crystallisation temperatures in excess of 1600 °C. We also present crystallisation temperatures for another Antarctic Karoo magma type, Group 3 dykes from Ahlmannryggen, which are derived from a pyroxene-rich mantle source. Our high-precision analysis of Al in olivine-spinel pairs indicate crystallisation temperatures from 1391±42 °C to 1481±35 °C for the Vestfjella depleted ferropicrite suite (Fo88–92) and from 1253±64 °C to 1303±40 °C for the Group 3 dykes (Fo79–82). Although the maximum temperature estimates for the former are over 100 °C lower than the previously presented estimates, they are still ~200 °C higher than those calculated for mid-ocean ridge basalts using the same method. Although exact mantle potential temperatures are difficult to estimate, the presented results support elevated sub-Gondwanan upper mantle temperatures (generated by a mantle plume or internal mantle heating) during the generation of the Karoo LIP.
  • Castrén, Eeva; Sillat, Tarvo; Oja, Sofia; Noro, Ariel; Laitinen, Anita; Konttinen, Yrjö T; Lehenkari, Petri; Hukkanen, Mika; Korhonen, Matti (BioMed Central, 2015)
    Abstract Introduction Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks. Altered media could, however, influence stem cell differentiation and we address this experimentally. Methods We examined human MSC differentiation into the osteoblast lineage using in vitro two- and three-dimensional cultures with PLP or FCS as cell culture medium supplements. Differentiation was followed by quantitative polymerase chain reaction, and alkaline phosphatase activity, matrix formation and matrix calcium content were quantified. Results Three-dimensional culture, where human MSCs were grown on collagen sponges, markedly stimulated osteoblast differentiation; a fourfold increase in calcium deposition could be observed in both PLP and FCS groups. PLP-grown cells showed robust osteogenic differentiation both in two- and three-dimensional MSC cultures. The calcium content of the matrix in the two-dimensional PLP group at day 14 was 2.2-fold higher in comparison to the FCS group (p < 0.0001), and at day 21 it was still 1.3-fold higher (p < 0.001), suggesting earlier calcium accumulation to the matrix in the PLP group. This was supported by stronger Alizarin Red staining in the PLP group at day 14. In two-dimesional PLP cultures, cellular proliferation appeared to decrease during later stages of differentiation, while in the FCS group the number of cells increased throughout the experiment. In three-dimensional experiments, the PLP and FCS groups behaved more congruently, except for the alkaline phosphatase activity and mRNA levels which were markedly increased by PLP. Conclusions Human PLP was at least equal to FCS in supporting osteogenic differentiation of human MSCs in two- and three-dimensional conditions; however, proliferation was inferior. As PLP is free of animal components, and thus represents reduced risk for xenogeneic infection, its use for human MSC-induced bone repair in the clinic by the three-dimensional live implants presented here appears a promising therapy option.
  • Mustonen, Terhi; Kimmel, Jyrki; Hakala, Jussi; Häkkinen, Jukka (SAGE PUBLICATIONS, INC., 2015)
  • Tenkanen, Henrikki Toivo Olavi; Salonen, Maria; Lattu, Matti Petteri; Toivonen, Tuuli Kaarina (PERGAMON, 2015)
    Accessibility and transportation possibilities are key factors influencing societal conditions and land use patterns in rural areas. Thus, information on the spatial patterns of accessibility and transportation can be of paramount importance in understanding regional differences in development, human livelihood and land use patterns. Analysing spatio-temporal transportation patterns is particularly challenging in areas where everyday transportation is based on unscheduled public transportation and a naturally controlled seasonal transportation network, such as rivers. Here, our aim is to provide information on the seasonal dynamics of riverine transportation and its effects on accessibility patterns in Peruvian Amazonia. We analysed riverine transportation speeds using a low-cost GPS-based riverboat observation system. Spatio-temporal accessibility patterns were generalised from the GPS-observations that were classified according to seasons into the high water season, intermediate season and low water season. We show that navigation along the rivers has a clear seasonal and directional (upstream/downstream) variation, which varies with different types of rivers based on channel morphology. In addition, we conducted interviews with local people to study their perceptions of the seasonal changes in navigation and the accuracy of transportation schedules. As the travel distances in Peruvian Amazonia are generally long, seasonal and directional differences have clear impacts on the overall accessibility patterns in the area and on the livelihoods of riverine inhabitants. Furthermore, the lack of clearly scheduled transportation causes considerable uncertainty about transportation options for local communities. The baseline information of the seasonal and directional variation of riverine transportation and travel speeds provided by our work is usable in further accessibility and livelihood analyses for Peruvian Amazonia, but it may also be useful in other areas relying on riverine transportation.
  • Lehtomäki, Joona Aleksi; Tuominen, Sakari; Toivonen, Tuuli Kaarina; Leinonen, Antti (Public Library of Science, 2015)
    The boreal region is facing intensifying resource extraction pressure, but the lack of comprehensive biodiversity data makes operative forest conservation planning difficult. Many countries have implemented forest inventory schemes and are making extensive and up-to-date forest databases increasingly available. Some of the more detailed inventory databases, however, remain proprietary and unavailable for conservation planning. Here, we investigate how well different open and proprietary forest inventory data sets suit the purpose of conservation prioritization in Finland. We also explore how much priorities are affected by using the less accurate but open data. First, we construct a set of indices for forest conservation value based on quantitative information commonly found in forest inventories. These include the maturity of the trees, tree species composition, and site fertility. Secondly, using these data and accounting for connectivity between forest types, we investigate the patterns in conservation priority. For prioritization, we use Zonation, a method and software for spatial conservation prioritization. We then validate the prioritizations by comparing them to known areas of high conservation value. We show that the overall priority patterns are relatively consistent across different data sources and analysis options. However, the coarse data cannot be used to accurately identify the high-priority areas as it misses much of the fine-scale variation in forest structures. We conclude that, while inventory data collected for forestry purposes may be useful for forest conservation purposes, it needs to be detailed enough to be able to account for more fine-scaled features of high conservation value. These results underline the importance of making detailed inventory data publicly available. Finally, we discuss how the prioritization methodology we used could be integrated into operative forest management, especially in countries in the boreal zone.
  • Syrjänen, Leo; Valanne, Susanna; Kuuslahti, Marianne; Tuomela, Tea; Sriram, Ashwin; Sanz, Alberto; Jacobs, Howard T; Rämet, Mika; Parkkila, Seppo (BioMed Central, 2015)
    Abstract Background Carbonic anhydrases (CAs, EC are ubiquitous enzymes that catalyze the reversible hydration reaction of carbon dioxide. CAs are present as six structurally divergent enzyme families: α, β, γ, δ, ζ and η. β-CAs have a wide distribution across different species including invertebrates. Previously, we showed that Drosophila melanogaster β-CA is a highly active mitochondrial enzyme. In this study, we investigated the function of Drosophila β-CA by silencing the expression of the β-CA gene using UAS/GAL4-based RNA interference (RNAi) in Drosophila in vivo. Results Crossing β-CA RNAi lines over ubiquitous Actin driver flies did not produce any viable progeny, indicating that β-CA expression is required for fly development. RNAi silencing of β-CA ubiquitously in adult flies did not affect their survival rate or function of mitochondrial electron transport chain. Importantly, β-CA RNAi led to impaired reproduction. All β-CA knockdown females were sterile, and produced few or no eggs. Whole ovaries of knockdown females looked normal but upon cadherin staining, there was an apparent functional defect in migration of border cells, which are considered essential for normal fertilization. Conclusions These results indicate that although Drosophila β-CA is dispensable for survival of adult flies, it is essential for female fertility.
  • Koli, Raika; Köhler, Klaus; Tonteri, Elina; Peltonen, Juha; Tikkanen, Heikki; Fogelholm, Mikael (BioMed Central, 2015)
    Abstract Background Several studies have shown that cocoa and cocoa-containing foods have the potential to lower blood pressure and improve endothelial function. Most of the studies reporting the beneficial effects of dark chocolate on blood pressure have been short (≤ 4 weeks). The aim of the present 8-wks (weeks) study was to assess the effects of regular consumption of dark chocolate during a reduced snack consumption intervention on blood pressure and other cardiovascular risk factors in mildly hypertensive individuals. Design This was a randomized, controlled, cross-over trial involving 22 adults (8 women, 14 men), aged 33–64 y, BMI 27.7 ± 3.7 kg/m2 with mild hypertension. During the intervention period (8-wks) the participants reduced the intake of habitual snacks and replaced them with dark chocolate (49 g/day). In the control period, they only reduced the snacks without any added chocolate. Data (blood lipid profile, glucose, insulin, 24 h blood pressure) was collected in the beginning and end of both periods (intervention and control), and some variables also in the run-in and run-out periods (weight, body fat percentage, blood pressure, arterial stiffness index, diet and physical activity). Results Daily consumption of dark chocolate had no effects on 24 h blood pressure, resting blood pressure (mean ± SD, pre 142 ± 11.5/89 ± 8.4 mmHg vs. post 142 ± 14.2/88 ± 9.4 mmHg in systolic and diastolic blood pressure, respectively) or arterial stiffness (mean ± SD, pre 7.68 ± 0.88 vs. post 7.76 ± 0.89). Weight was reduced by 1.0 ± 2.2 kg during the control (reduced snack only) period, but was unchanged while eating chocolate (p < 0.027 between the treatments). Conclusion The data collected in this study indicates that inclusion of dark chocolate daily in the diet had no significant effects on blood pressure or other cardiovascular risk factors during a reduced snack period. Trial registration identifier NCT02130141
  • Lee, Jamie; Prokopec, Stephenie D; Watson, John D; Sun, Ren X; Pohjanvirta, Raimo; Boutros, Paul C (BioMed Central, 2015)
    Abstract Background 2,3,7,8–tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 μg/kg) in adult male and female C57BL/6Kuo mice. Results Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of “AHR-core” genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Conclusions Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
  • Kaunisto, Jaana; Kelloniemi, K.; Sutinen, E.; Hodgson, U.; Piilonen, A.; Kaarteenaho, R.; Mäkitaro, R.; Purokivi, M.; Lappi-Blanco, E.; Saarelainen, S.; Kankaanranta, H.; Mursu, A.; Kanervisto, M.; Salomaa, E-R.; Myllärniemi, M. (BioMed Central, 2015)
    Abstract Background The FinnishIPF registry is a prospective, longitudinal national registry study on the epidemiology of idiopathic pulmonary fibrosis (IPF). It was designed to describe the characteristics, management and prognosis of prevalent and incident IPF patients. The study was initiated in 2012. Methods We present here results limited to five university hospitals. Patients with IPF were screened from hospital registries using ICD-10 diagnosis codes J84.1 and J84.9. All patients who gave informed consent were included and evaluated using novel diagnostic criteria. Point prevalence on the 31st of December in 2012 was calculated using the reported population in each university hospital city as the denominator. Results Patients with ICD-10 codes J84.1 and J84.9 yielded a heterogeneous group – on the basis of patient records assessed by pulmonologists only 20–30 % of the cases were IPF. After clinical, radiological and histological re-evaluation 111 of 123 (90 %) of patients fulfilled the clinical criteria of IPF. The estimated prevalence of IPF was 8.6 cases/100 000. 60.4 % were men. Forty four percent of the patients were never-smokers. At diagnosis, the patients’ mean age was 73.5 years and mean FVC was 80.4 % and DLCO 57.3 % of predicted. Conclusions Our results suggest that hospital registries are inaccurate for epidemiological studies unless patients are carefully re-evaluated. IPF is diagnosed in Finland at a stage when lung function is still quite well preserved. Smoking in patients with IPF was less common than in previous reports.
  • Mikonranta, Lauri; Mappes, Johanna; Laakso, Jouni; Ketola, Tarmo (BioMed Central, 2015)
    Abstract Background Pathogens evolve in a close antagonistic relationship with their hosts. The conventional theory proposes that evolution of virulence is highly dependent on the efficiency of direct host-to-host transmission. Many opportunistic pathogens, however, are not strictly dependent on the hosts due to their ability to reproduce in the free-living environment. Therefore it is likely that conflicting selection pressures for growth and survival outside versus within the host, rather than transmission potential, shape the evolution of virulence in opportunists. We tested the role of within-host selection in evolution of virulence by letting a pathogen Serratia marcescens db11 sequentially infect Drosophila melanogaster hosts and then compared the virulence to strains that evolved only in the outside-host environment. Results We found that the pathogen adapted to both Drosophila melanogaster host and novel outside-host environment, leading to rapid evolutionary changes in the bacterial life-history traits including motility, in vitro growth rate, biomass yield, and secretion of extracellular proteases. Most significantly, selection within the host led to decreased virulence without decreased bacterial load while the selection lines in the outside-host environment maintained the same level of virulence with ancestral bacteria. Conclusions This experimental evidence supports the idea that increased virulence is not an inevitable consequence of within-host adaptation even when the epidemiological restrictions are removed. Evolution of attenuated virulence could occur because of immune evasion within the host. Alternatively, rapid fluctuation between outside-host and within-host environments, which is typical for the life cycle of opportunistic bacterial pathogens, could lead to trade-offs that lower pathogen virulence.
  • Tabassum, Rubina; Sivadas, Ambily; Agrawal, Vartika; Tian, Haozheng; Arafat, Dalia; Gibson, Greg (BioMed Central, 2015)
    Abstract Background Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N = 1 phenotypes. Methods Whole blood samples from four African American women, four Caucasian women, and four Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNA-Seq, miRNA-Seq, and Illumina Methylation 450 K arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. Results Longitudinal omic profiles were in general highly consistent over time, with an average of 67 % variance in transcript abundance, 42 % in CpG methylation level (but 88 % for the most differentiated CpG per gene), and 50 % in miRNA abundance among individuals, which are all comparable to 74 % variance among individuals for 74 clinical traits. One third of the variance could be attributed to differential blood cell type abundance, which was also fairly stable over time, and a lesser amount to expression quantitative trait loci (eQTL) effects. Seven conserved axes of covariance that capture diverse aspects of immune function explained over half of the variance. These axes also explained a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that were significantly up-regulated or down-regulated in each person and were in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes had individually divergent methylation levels, but these did not overlap with the transcripts, and fewer than 20 % of genes had significantly correlated methylation and gene expression. Conclusions People express an “omic personality” consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions.
  • Viitasaari, Elina; Raekallio, Marja; Valros, Anna; Peltoniemi, Olli; Hänninen, Laura; Heinonen, Mari (BioMed Central, 2015)
    Abstract No research has been reported on the effect of intramuscular ketoprofen administration on the feeding behavior of tail-bitten pigs. In order to investigate this, a longitudinal, double blind, placebo-controlled field trial was conducted with a total of 77 pigs from a finishing herd. Pigs received either ketoprofen (KET) or a placebo (PLAC) intramuscularly for three days and procaine penicillin for five days after the tail was first observed to be damaged. Pigs were followed from day −2 to day 3 with respect to a noted tail wound. Only new incidence of tail biting was included. Nine to 11 pigs per pen were reared with a single automatic feeder. A transponder attached to the ear of each pig recorded times of entrance and exit to the feeder and feed consumed. To calculate average daily weight gain (ADG), pigs were weighed at days 0, 6 and 13. Time spent at the feeder by visit and on a daily basis, and mean daily intervals between feeder visits per pig were computed in minutes. Daily feeding rate (FR) was calculated from the feeder data (consumed feed (g) / time at the feeder (s)). Placebo pigs consumed more feed and spent more time at the feeder on day 1 than KET pigs (P < 0.05). For all pigs, FR increased from day 1 to day 3 (P < 0.05). Feeder visit intervals were longer and frequency lower on day 0 compared with other days (P < 0.05). Average feed consumption and time spent at the feeder per day decreased on day 0 and returned to the initial level on day 1 (P < 0.05 for both). No effect on ADG was recorded. Intramuscular administration of ketoprofen induced little change in feeding behavior and had no effect on weight gain. Placebo-treated pigs may have used feed as an analgesic and calming substance to some degree, leading to temporarily increased feed consumption.
  • Sousa, Sofia; Brion, Régis; Lintunen, Minnamaija; Kronqvist, Pauliina; Sandholm, Jouko; Mönkkönen, Jukka; Kellokumpu-Lehtinen, Pirkko-Liisa; Lauttia, Susanna; Tynninen, Olli; Joensuu, Heikki; Heymann, Dominique; Määttä, Jorma A (BioMed Central, 2015)
    Abstract Introduction The immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumor type. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2-macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. The role of TAMs is not fully understood in breast cancer progression. Methods Macrophage infiltration (CD68) and activation status (HLA-DRIIα, CD163) were evaluated in a large cohort of human primary breast tumors (562 tissue microarray samples), by immunohistochemistry and scored by automated image analysis algorithms. Survival between groups was compared using the Kaplan-Meier life-table method and a Cox multivariate proportional hazards model. Macrophage education by breast cancer cells was assessed by ex vivo differentiation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of breast cancer cell conditioned media (MDA-MB231, MCF-7 or T47D cell lines) and M1 or M2 inducing cytokines (respectively IFN-γ, IL-4 and IL-10). Obtained macrophages were analyzed by flow cytometry (CD14, CD16, CD64, CD86, CD200R and CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) and zymography (matrix metalloproteinase 9, MMP-9). Results Clinically, we found that high numbers of CD163+ M2-macrophages were strongly associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological ductal type (p<0.001) in the studied cohort of human primary breast tumors. We demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype. Furthermore, the more aggressive mesenchymal-like cell line MDA-MB231, which secretes high levels of M-CSF, skews macrophages toward the more immunosuppressive M2c subtype. Conclusions This study demonstrates that human breast cancer cells influence macrophage differentiation and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.
  • Jokelainen, Pikka; Velström, Kaisa; Lassen, Brian (BioMed Central, 2015)
    Abstract Background Although the prevalence of human Toxoplasma gondii infections is high in Estonia, no information is available on the prevalence of infections in the local animal populations. Wild boars are a good indicator species for estimating the prevalence and spread of T. gondii and were thus investigated in this nationwide cross-sectional study. Volunteer hunters sampled cardiac or skeletal muscle of 471 wild boars legally hunted for human consumption in Estonia during the hunting season of 2012–2013. Serosanguineous meat juice samples were obtained from thawed tissue samples, diluted 1:40, and screened for specific anti-T. gondii IgG antibodies with a commercial direct agglutination test. Results Almost one-quarter (113; 24%) of the wild boars examined were seropositive for T. gondii. The seroprevalence did not differ significantly between age groups or sexes. The seroprevalence was lowest in Viljandimaa, which is located in the southern part of Estonia. In other counties, the infection was evenly prevalent. Conclusions In Estonia, wild boars are commonly exposed to T. gondii, which is endemic and widespread. The consumption of raw or undercooked meat of Estonian wild boars may pose an infection risk to humans and other hosts.
  • Benoit, Isabelle; Culleton, Helena; Zhou, Miaomiao; DiFalco, Marcos; Aguilar-Osorio, Guillermo; Battaglia, Evy; Bouzid, Ourdia; Brouwer, Carlo P J M; El-Bushari, Hala B O; Coutinho, Pedro M; Gruben, Birgit S; Hildén, Kristiina S; Houbraken, Jos; Barboza, Luis A J; Levasseur, Anthony; Majoor, Eline; Mäkelä, Miia R; Narang, Hari-Mander; Trejo-Aguilar, Blanca; van den Brink, Joost; vanKuyk, Patricia A; Wiebenga, Ad; McKie, Vincent; McCleary, Barry; Tsang, Adrian; Henrissat, Bernard; de Vries, Ronald P (BioMed Central, 2015)
    Abstract Background Plant biomass is the major substrate for the production of biofuels and biochemicals, as well as food, textiles and other products. It is also the major carbon source for many fungi and enzymes of these fungi are essential for the depolymerization of plant polysaccharides in industrial processes. This is a highly complex process that involves a large number of extracellular enzymes as well as non-hydrolytic proteins, whose production in fungi is controlled by a set of transcriptional regulators. Aspergillus species form one of the best studied fungal genera in this field, and several species are used for the production of commercial enzyme cocktails. Results It is often assumed that related fungi use similar enzymatic approaches to degrade plant polysaccharides. In this study we have compared the genomic content and the enzymes produced by eight Aspergilli for the degradation of plant biomass. All tested Aspergilli have a similar genomic potential to degrade plant biomass, with the exception of A. clavatus that has a strongly reduced pectinolytic ability. Despite this similar genomic potential their approaches to degrade plant biomass differ markedly in the overall activities as well as the specific enzymes they employ. While many of the genes have orthologs in (nearly) all tested species, only very few of the corresponding enzymes are produced by all species during growth on wheat bran or sugar beet pulp. In addition, significant differences were observed between the enzyme sets produced on these feedstocks, largely correlating with their polysaccharide composition. Conclusions These data demonstrate that Aspergillus species and possibly also other related fungi employ significantly different approaches to degrade plant biomass. This makes sense from an ecological perspective where mixed populations of fungi together degrade plant biomass. The results of this study indicate that combining the approaches from different species could result in improved enzyme mixtures for industrial applications, in particular saccharification of plant biomass for biofuel production. Such an approach may result in a much better improvement of saccharification efficiency than adding specific enzymes to the mixture of a single fungus, which is currently the most common approach used in biotechnology.
  • Holopainen, Jani; Toppinen, Anne; Perttula, Sini (MDPI, 2015)
    The aim of this explorative study is to find out how the EU Timber Regulation (EUTR) has affected the forest and chain of custody (CoC) certification strategies and practices among the Finnish wood industry companies. We are especially interested to find out whether more integrated strategies and collaborative networks have emerged for enhanced communications throughout the industry value chains. This qualitative interview study included both EUTR ex ante and ex post analysis, based on three rounds of managerial and expert interviews during 2011-2015. The results indicate that the EUTR appears to have enforced the supplier-client relations in the Finnish wood industry value chain. The sector still lacks integrated communication strategies with better understanding of customer and stakeholder values, which could contribute to more cohesive communication and marketing efforts reflecting the values of the whole industry. The certification practices are fairly spontaneously implemented following the traditional industry culture, which is not supportive of innovations and gaining competitive advantages in the broader material markets. Furthermore, the existence of two parallel forest certificates (Forest Stewardship Council (FSC) and Programme for the Endorsement of Forest Certification (PEFC)) seems to hamper the effective communication and building of an image of sustainable wood products among customers and end consumers, groups that are also exposed to more general environmental communication, e.g., in the building material markets.