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  • 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 ClinicalTrials.gov identifier NCT02130141
  • 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 4.2.1.1) 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Traoré, Oumar; Nyholm, Outi; Siitonen, Anja; Bonkoungou, Isidore J O; Traoré, Alfred S; Barro, Nicolas; Haukka, Kaisa (BioMed Central, 2015)
    Abstract Background This study investigated the prevalence, serotypes and antimicrobial sensitivity patterns of Salmonella enterica in environment in Ouagadougou, Burkina Faso. A total of 476 samples, consisting of 36 samples of tap water, 51 samples of well water, 87 samples of channel water, 44 samples of reservoir water, 238 samples of fish, and 20 samples of lettuce were examined using standard bacteriological procedures for Salmonella. Results Salmonella were isolated from 98 samples. Salmonella were rare in drinking water, since they were not found at all from the tap water, and only in 2 % of well water. Salmonella were more common in the water of reservoir of Tanghin (15 %), reservoir of Yamtenga (20 %), and in the water channels in the city (from 20 to 31 %). Salmonella were commonly isolated from the fish (24 %) caught from the reservoir of Tanghin and from the lettuce (50 %) irrigated with water from Tanghin. The Salmonella isolates were found to represent 50 different serotypes. The 11 most common serotypes were Salmonella Bredeney and S. Colindale (both 8.2 %), S. Muenster (6.1 %), S. Korlebu (5.1 %), S. Eastbourne and S. Poona (both 4.1 %), and S. Agona, S. Derby, S. Drac, S. Senftenberg, S. Waycross (each 3.1 %), accounting for 51.3 % of all the isolates. In general, the Salmonella strains were sensitive to the antimicrobials tested, but two strains were resistant to streptomycin and many more intermediate to streptomycin or sulphonamide. Conclusion This study highlights the common prevalence of Salmonella and the high diversity of Salmonella serotypes in aquatic environment in Ouagadougou, Burkina Faso. Therefore, various human activities linked to water and consumption of water-related products, such as fish and lettuce, can lead to human Salmonella infections.
  • Autio, Karoliina P M; Ruotsalainen, Janne J; Anttila, Marjukka O; Niittykoski, Minna; Waris, Matti; Hemminki, Akseli; Vähä-Koskela, Markus J V; Hinkkanen, Ari E (BioMed Central, 2015)
    Abstract Background Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of ~2 × 105 plaque forming units of parental A7(74) strain. Results VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.
  • Tripathi, Sushil; Flobak, Åsmund; Chawla, Konika; Baudot, Anaïs; Bruland, Torunn; Thommesen, Liv; Kuiper, Martin; Lægreid, Astrid (BioMed Central, 2015)
    Abstract Background The gastrointestinal peptide hormones cholecystokinin and gastrin exert their biological functions via cholecystokinin receptors CCK1R and CCK2R respectively. Gastrin, a central regulator of gastric acid secretion, is involved in growth and differentiation of gastric and colonic mucosa, and there is evidence that it is pro-carcinogenic. Cholecystokinin is implicated in digestion, appetite control and body weight regulation, and may play a role in several digestive disorders. Results We performed a detailed analysis of the literature reporting experimental evidence on signaling pathways triggered by CCK1R and CCK2R, in order to create a comprehensive map of gastrin and cholecystokinin-mediated intracellular signaling cascades. The resulting signaling map captures 413 reactions involving 530 molecular species, and incorporates the currently available knowledge into one integrated signaling network. The decomposition of the signaling map into sub-networks revealed 18 modules that represent higher-level structures of the signaling map. These modules allow a more compact mapping of intracellular signaling reactions to known cell behavioral outcomes such as proliferation, migration and apoptosis. The integration of large-scale protein-protein interaction data to this literature-based signaling map in combination with topological analyses allowed us to identify 70 proteins able to increase the compactness of the map. These proteins represent experimentally testable hypotheses for gaining new knowledge on gastrin- and cholecystokinin receptor signaling. The CCKR map is freely available both in a downloadable, machine-readable SBML-compatible format and as a web resource through PAYAO ( http://sblab.celldesigner.org:18080/Payao11/bin/ ). Conclusion We have demonstrated how a literature-based CCKR signaling map together with its protein interaction extensions can be analyzed to generate new hypotheses on molecular mechanisms involved in gastrin- and cholecystokinin-mediated regulation of cellular processes.
  • Valo, Satu; Kaur, Sippy; Ristimäki, Ari; Renkonen-Sinisalo, Laura; Järvinen, Heikki; Mecklin, Jukka-Pekka; Nyström, Minna; Peltomäki, Päivi (BioMed Central, 2015)
    Abstract Background Lynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first “hit” to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular “hits” required for tumor development. To this end, MMR protein expression and coordinated promoter methylation were examined in colorectal specimens prospectively collected from LS mutation carriers (n = 55) during colonoscopy surveillance (10/2011–5/2013), supplemented with retrospective specimens. Results Loss of MMR protein corresponding to the gene mutated in the germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50–68 % in low-grade dysplasia adenomas, and 100 % in high-grade dysplasia adenomas and carcinomas. Promoter methylation as a putative “second hit” occurred in 1/56 (2 %) of tumors with silenced MMR protein. A general hypermethylation tendency was evaluated by two gene sets, eight CpG island methylator phenotype (CIMP) genes, and seven candidate tumor suppressor genes linked to colorectal carcinoma (CRC). Hypermethylation followed the same trend as MMR protein loss and was present in some low-grade dysplasia adenomas that still expressed MMR protein suggesting the absence of a “second hit.” To assess prospectively collected normal mucosa for carcinogenic “fields,” the specimen donors were stratified according to age at biopsy (50 years or below vs. above 50 years) and further according to the absence vs. presence of a (previous or concurrent) diagnosis of CRC. In mutation carriers over 50 years old, two markers from the candidate gene panel (SFRP1 and SLC5A8) revealed a significantly elevated average degree of methylation in individuals with CRC diagnosis vs. those without. Conclusions Our findings emphasize the importance and early appearance of epigenetic alterations in LS-associated tumorigenesis. The results serve early detection and assessment of progression of CRC.
  • Grönthal, Thomas; Ollilainen, Matti; Eklund, Marjut; Piiparinen, Heli; Gindonis, Veera; Junnila, Jouni; Saijonmaa-Koulumies, Leena; Liimatainen, Riitta; Rantala, Merja (BioMed Central, 2015)
    Abstract Background Methicillin resistant Staphylococcus pseudintermedius (MRSP) and Staphylococcus aureus (MRSA) are common multi-drug resistant (MDR) bacteria in dogs. In 2012–2013 three dogs of the Guide Dog School of the Finnish Federation of the Visually Impaired were found to be MRSP positive. Guide dogs have regular contact with each other during their first year of life and prolonged contact when in training. Since dogs are placed in different parts of Finland after training, there is a risk for national spread of MDR bacteria. In this study the prevalence of MRSP and MRSA, as well as the risk factors for MRSP were determined in the Finnish guide dog population. MRSP isolates were investigated using molecular methods and compared to the earlier isolates. Results Out of 132 tested dogs 4 were MRSP positive thus giving the prevalence estimate of 3% (95% CI: 1–8%) for MRSP in the target population. MRSA was not detected (prevalence estimate 0%, 95% CI: 0–3%). Risk factors associated with MRSP were being a breeding bitch (OR = 8.4; 95% CI: 1.1–64.1, P = 0.012), the number of veterinary visits (OR = 1.23; 95% CI: 1.0–1.5, P = 0.025) and number of antimicrobial courses (OR = 1.63; 95% CI: 1.0–2.55; P = 0.035). Identified MRSP isolates belonged to five different sequence types (ST45, 71, 402, 403 and 404). All ST71 isolates carried SCCmec II-III, while the SCCmec type of the ST45 and ST402 (a single locus variant of ST45) isolates were non-typeable with the method used. Conclusions MRSP and MRSA had low prevalence in the studied dog population despite the close contact between dogs, and the MRSP population was heterogenic. Antimicrobial therapy and veterinary visits are risk factors for MRSP even among a small case group.
  • Virtanen, Jorma I; Vehkalahti, Kimmo I; Vehkalahti, Miira M (BioMed Central, 2015)
    Abstract Background Health behaviors play a major role in the prevention of the most common oral diseases. To investigate health behaviors related to the potential transmission of oral bacteria from mother to child using novel multiple correspondence analysis (MCA). Methods Mothers (n = 313) with children under three years attending two municipal child health clinics in Finland completed a self-administered questionnaire on health knowledge and behaviors such as sharing a spoon with their child, kissing on the lips, and the mothers’ tooth brushing, smoking, age, and level of education. We used MCA to reveal the relationships between the mothers’ behaviors and background factors, along with unconditional, binary, multivariable logistic regression models, odds ratios (OR) and their 95 % confidence intervals (95 %CI). Results Of the mothers, 38 % kissed their child on the lips and 14 % shared a spoon with their child; 11 % believed that oral bacteria cannot be transmitted from mother to child. Two-thirds (68 %) of them reported tooth brushing twice daily, and 80 % were non-smokers. MCA revealed two diverging dimensions of the mothers’ behaviors: a ‘horizontal’ one showing clear evidence of relationships between tooth brushing, smoking, age and education, whereas the ‘vertical’ one revealed the mothers’ habits of kissing the child on the lips and sharing a spoon related to each other. Spoon sharing was related to the kissing on lips (OR 10.3), a higher level of education (OR 3.1), and, inversely, older age (OR 0.1), whereas kissing on lips behavior was inversely related to a higher level of education (OR 0.5). Conclusion The study revealed two diverging dimensions of the mothers’ health behaviors. More emphasis in health education ought to be put to how to avoid bacterial transmission from caregiver to child during feeding.
  • Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid R; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Phillips, Kelly-Anne; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K (BioMed Central, 2015)
    Abstract Background Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. Methods Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. Results The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05–1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91–1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17–2.45). Conclusions ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.
  • Lienemann, Taru; Kyyhkynen, Aino; Halkilahti, Jani; Haukka, Kaisa; Siitonen, Anja (BioMed Central, 2015)
    Abstract Background Salmonella enterica spp. enterica serotype Typhimurium (STM) is the most common agent of domestically acquired salmonellosis in Finland. Subtyping methods which allow the characterization of STM are essential for effective laboratory-based STM surveillance and for recognition of outbreaks. This study describes the diversity of Finnish STM isolates using phage typing, antimicrobial susceptible testing, pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem repeat analysis (MLVA), and compares the discriminatory power and the concordance of these methods. Results A total of 375 sporadic STM isolates were analysed. The isolates were divided into 31 definite phage (DT) types, dominated by DT1 (47 % of the isolates), U277 (9 % of the isolates) and DT104 (8 % of the isolates). Of all the isolates, 62 % were susceptible to all the 12 antimicrobials tested and 11 % were multidrug resistant. Subtyping resulted in 83 different XbaI-PFGE profiles and 111 MLVA types. The three most common XbaI-PFGE profiles (STYM1, STYM7 and STYM8) and one MLVA profile with three single locus variants accounted for 56 % and 49 % of the STM isolates, respectively. The studied isolates showed a genetic similarity of more than 70 % by XbaI-PFGE. In MLVA, 71 % of the isolates lacked STTR6 and 77 % missed STTR10p loci. Nevertheless, the calculated Simpson’s diversity index for XbaI-PFGE was 0.829 (95 % CI 0.792−0.865) and for MLVA 0.867 (95 % CI 0.835−0.898). However, the discriminatory power of the 5-loci MLVA varied among the phage types. The highest concordance of the results was found between XbaI-PFGE and phage typing (adjusted Wallace coefficient was 0.833 and adjusted Rand coefficient was 0.627). Conclusions In general, the calculated discriminatory power was higher for genotyping methods (MLVA and XbaI-PFGE) than for phenotyping methods (phage typing). Overall, comparable diversity indices were calculated for PFGE and MLVA (both DI > 0.8). However, MLVA was phage type dependent providing better discrimination of the most common phage types. Furthermore, 5-loci MLVA was a less laborious method and easier to interpret than XbaI-PFGE. Thus, the laboratory-based surveillance of the Finnish human STM infections has been conducted with a combination of phage typing, antimicrobial susceptibility testing and 5-loci MLVA since January 2014.
  • Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid R; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Phillips, Kelly-Anne; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K (BioMed Central, 2015)
    Abstract Background Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. Methods Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. Results The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05–1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91–1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17–2.45). Conclusions ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.
  • Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H. A; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha (BioMed Central, 2015)
    Abstract Background Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs’ lifecycle has been omitted. Results We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. Conclusions The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.
  • Chong, Sun-Li; Derba-Maceluch, Marta; Koutaniemi, Sanna; Gómez, Leonardo D; McQueen-Mason, Simon J; Tenkanen, Maija; Mellerowicz, Ewa J (BioMed Central, 2015)
    Abstract Background Expressing microbial polysaccharide-modifying enzymes in plants is an attractive approach to custom tailor plant lignocellulose and to study the importance of wall structures to plant development. Expression of α-glucuronidases in plants to modify the structures of glucuronoxylans has not been yet attempted. Glycoside hydrolase (GH) family 115 α-glucuronidases cleave the internal α-D-(4-O-methyl)glucopyranosyluronic acid ((Me)GlcA) from xylans or xylooligosaccharides. In this work, a GH115 α-glucuronidase from Schizophyllum commune, ScAGU115, was expressed in Arabidopsis thaliana and targeted to apoplast. The transgene effects on native xylans’ structures, plant development, and lignocellulose saccharification were evaluated and compared to those of knocked out glucuronyltransferases AtGUX1 and AtGUX2. Results The ScAGU115 extracted from cell walls of Arabidopsis was active on the internally substituted aldopentaouronic acid (XUXX). The transgenic plants did not show any change in growth or in lignocellulose saccharification. The cell wall (Me)GlcA and other non-cellulosic sugars, as well as the lignin content, remained unchanged. In contrast, the gux1gux2 double mutant showed a 70% decrease in (Me)GlcA to xylose molar ratio, and, interestingly, a 60% increase in the xylose content. Whereas ScAGU115-expressing plants exhibited a decreased signal in native secondary walls from the monoclonal antibody UX1 that recognizes (Me)GlcA on non-acetylated xylan, the signal was not affected after wall deacetylation. In contrast, gux1gux2 mutant was lacking UX1 signals in both native and deacetylated cell walls. This indicates that acetyl substitution on the xylopyranosyl residue carrying (Me)GlcA or on the neighboring xylopyranosyl residues may restrict post-synthetic modification of xylans by ScAGU115 in planta. Conclusions Active GH115 α-glucuronidase has been produced for the first time in plants. The cell wall–targeted ScAGU115 was shown to affect those glucuronate substitutions of xylan, which are accessible to UX1 antibody and constitute a small fraction in Arabidopsis, whereas majority of (Me)GlcA substitutions were resistant, most likely due to the shielding by acetyl groups. Plants expressing ScAGU115 did not show any defects under laboratory conditions indicating that the UX1 epitope of xylan is not essential under these conditions. Moreover the removal of the UX1 xylan epitope does not affect lignocellulose saccharification.