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  • de Vries, Ronald P; Riley, Robert; Wiebenga, Ad; Aguilar-Osorio, Guillermo; Amillis, Sotiris; Uchima, Cristiane A; Anderluh, Gregor; Asadollahi, Mojtaba; Askin, Marion; Barry, Kerrie; Battaglia, Evy; Bayram, Özgür; Benocci, Tiziano; Braus-Stromeyer, Susanna A; Caldana, Camila; Cánovas, David; Cerqueira, Gustavo C; Chen, Fusheng; Chen, Wanping; Choi, Cindy; Clum, Alicia; dos Santos, Renato A C; Damásio, André R d L; Diallinas, George; Emri, Tamás; Fekete, Erzsébet; Flipphi, Michel; Freyberg, Susanne; Gallo, Antonia; Gournas, Christos; Habgood, Rob; Hainaut, Matthieu; Harispe, María L; Henrissat, Bernard; Hildén, Kristiina S; Hope, Ryan; Hossain, Abeer; Karabika, Eugenia; Karaffa, Levente; Karányi, Zsolt; Kraševec, Nada; Kuo, Alan; Kusch, Harald; LaButti, Kurt; Lagendijk, Ellen L; Lapidus, Alla; Levasseur, Anthony; Lindquist, Erika; Lipzen, Anna; Logrieco, Antonio F; MacCabe, Andrew; Mäkelä, Miia R; Malavazi, Iran; Melin, Petter; Meyer, Vera; Mielnichuk, Natalia; Miskei, Márton; Molnár, Ákos P; Mulé, Giuseppina; Ngan, Chew Y; Orejas, Margarita; Orosz, Erzsébet; Ouedraogo, Jean P; Overkamp, Karin M; Park, Hee-Soo; Perrone, Giancarlo; Piumi, Francois; Punt, Peter J; Ram, Arthur F J; Ramón, Ana; Rauscher, Stefan; Record, Eric; Riaño-Pachón, Diego M; Robert, Vincent; Röhrig, Julian; Ruller, Roberto; Salamov, Asaf; Salih, Nadhira S; Samson, Rob A; Sándor, Erzsébet; Sanguinetti, Manuel; Schütze, Tabea; Sepčić, Kristina; Shelest, Ekaterina; Sherlock, Gavin; Sophianopoulou, Vicky; Squina, Fabio M; Sun, Hui; Susca, Antonia; Todd, Richard B; Tsang, Adrian; Unkles, Shiela E; van de Wiele, Nathalie; van Rossen-Uffink, Diana; Oliveira, Juliana V d C; Vesth, Tammi C; Visser, Jaap; Yu, Jae-Hyuk; Zhou, Miaomiao; Andersen, Mikael R; Archer, David B; Baker, Scott E; Benoit, Isabelle; Brakhage, Axel A; Braus, Gerhard H; Fischer, Reinhard; Frisvad, Jens C; Goldman, Gustavo H; Houbraken, Jos; Oakley, Berl; Pócsi, István; Scazzocchio, Claudio; Seiboth, Bernhard; vanKuyk, Patricia A; Wortman, Jennifer; Dyer, Paul S; Grigoriev, Igor V (BioMed Central, 2017)
    Abstract Background The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. Results We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. Conclusions Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
  • Verardo, Lucas L; Sevón-Aimonen, Marja-Liisa; Serenius, Timo; Hietakangas, Ville; Uimari, Pekka (BioMed Central, 2017)
    Abstract Background One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin. A bioinformatics analysis was performed to identify the most promising genes in the significant regions related to meat quality. Results Genome-wide association study (GWAS) revealed three significant chromosomal regions: one on chromosome 3 (39.9 Mb–40.1 Mb) and two on chromosome 15 (58.5 Mb–60.5 Mb and 132 Mb–135 Mb including PRKAG3). A conditional analysis with a significant SNP in the PRKAG3 region, MARC0083357, as a covariate in the model retained the significant SNPs on chromosome 3. Even though linkage disequilibrium was relatively high over a long distance between MARC0083357 and other significant SNPs on chromosome 15, some SNPs retained their significance in the conditional analysis, even in the vicinity of PRKAG3. The significant regions harbored several genes, including two genes involved in cyclic AMP (cAMP) signaling: ADCY9 and CREBBP. Based on functional and transcription factor-gene networks, the most promising candidate genes for meat pH are ADCY9, CREBBP, TRAP1, NRG1, PRKAG3, VIL1, TNS1, and IGFBP5, and the key transcription factors related to these genes are HNF4A, PPARG, and Nkx2-5. Conclusions Based on SNP association, pathway, and transcription factor analysis, we were able to identify several genes with potential to control muscle cell homeostasis and meat quality. The associated SNPs can be used in selection for better pork. We also showed that post-GWAS analysis reveals important information about the genes’ potential role on meat quality. The gained information can be used in later functional studies.
  • Ludwig, Anastasia; Rivera, Claudio; Uvarov, Pavel (BioMed Central, 2017)
    Abstract Background Cation-chloride cotransporters (CCCs) are indispensable for maintaining chloride homeostasis in multiple cell types, but K–Cl cotransporter KCC2 is the only CCC member with an exclusively neuronal expression in mammals. KCC2 is critical for rendering fast hyperpolarizing responses of ionotropic γ-aminobutyric acid and glycine receptors in adult neurons, for neuronal migration in the developing central nervous system, and for the formation and maintenance of small dendritic protrusions—dendritic spines. Deficit in KCC2 expression and/or activity is associated with epilepsy and neuropathic pain, and effective strategies are required to search for novel drugs augmenting KCC2 function. Results We revised current methods to develop a noninvasive optical approach for assessing KCC2 transport activity using a previously characterized genetically encoded chloride sensor. Our protocol directly assesses dynamics of KCC2-mediated chloride efflux and allows measuring genuine KCC2 activity with good spatial and temporal resolution. As a proof of concept, we used this approach to compare transport activities of the two known KCC2 splice isoforms, KCC2a and KCC2b, in mouse neuronal Neuro-2a cells. Conclusions Our noninvasive optical protocol proved to be efficient for assessment of furosemide-sensitive chloride fluxes. Transport activities of the N-terminal splice isoforms KCC2a and KCC2b obtained by the novel approach matched to those reported previously using standard methods for measuring chloride fluxes.
  • Koskinen, Lotta L E; Seppälä, Eija H; Weissl, Jutta; Jokinen, Tarja S; Viitmaa, Ranno; Hänninen, Reetta L; Quignon, Pascale; Fischer, Andrea; André, Catherine; Lohi, Hannes (BioMed Central, 2017)
    Abstract Background Idiopathic or genetic adult-onset epilepsy is a common neurological disorder in domestic dogs. Genetic association has been reported only with ADAM23 on CFA 37 in few breeds. To identify novel epilepsy genes, we performed genome-wide association (GWA) analyses in four new breeds, and investigated the association of the previously reported ADAM23 haplotype with the epilepsy phenotype in eight breeds. Results GWA analysis did not reveal new epilepsy loci. ADAM23 association (p < 0.05) was identified in five breeds. Combined analysis of all eight breeds showed significant association (p = 4.6e−6, OR 1.9). Conclusions Our results further support the role of ADAM23 in multiple breeds as a common risk gene for epilepsy with low penetrance. The lack of findings in the GWA analyses points towards inefficient capture of genetic variation by the current SNP arrays, causal variant(s) with low penetrance and possible phenocopies. Future work will include studies on ADAM23 function and expression in canine neurons, as well as whole-genome sequencing in order to identify additional IE genes.
  • Lázaro-Ibáñez, Elisa; Lunavat, Taral R; Jang, Su C; Escobedo-Lucea, Carmen; Oliver-De La Cruz, Jorge; Siljander, Pia; Lötvall, Jan; Yliperttula, Marjo (BioMed Central, 2017)
    Abstract Background Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed. Methods We isolated MVs and EXOs from PC-3 and LNCaP prostate cancer cells by differential centrifugation and compared them to EVs derived from the benign PNT2 prostate cells. The relative mRNA levels of 84 prostate cancer-related genes were investigated and validated using quantitative reverse transcription PCR arrays. Results Based on the mRNA abundance, MVs rather than EXOs were enriched in the analyzed transcripts, providing a snapshot of the tumor transcriptome. LNCaP MVs specifically contained significantly increased mRNA levels of NK3 Homeobox 1 (NKX3-1), transmembrane protease serine 2 (TMPRSS2), and tumor protein 53 (TP53) genes, whereas PC-3 MVs carried increased mRNA levels of several genes including, caveolin-2 (CAV2), glutathione S-transferase pi 1 (GSTP1), pescadillo ribosomal biogenesis factor 1 (PES1), calmodulin regulated spectrin associated protein 1 (CAMSAP1), zinc-finger protein 185 (ZNF185), and others compared to PNT2 MVs. Additionally, ETS variant 1 (ETV1) and fatty acid synthase (FASN) mRNAs identified in LNCaP- and PC-3- derived MVs highly correlated with prostate cancer progression. Conclusions Our study provides new understandings of the variability of the mRNA cargo of MVs and EXOs from different cell lines despite same cancer origin, which is essential to better understand the the proportion of the cell transcriptome that can be detected within EVs and to evaluate their role in disease diagnosis.
  • Hemilä, Harri; Suonsyrjä, Timo (BioMed Central, 2017)
    Abstract Background Atrial fibrillation (AF), a common arrhythmia contributing substantially to cardiac morbidity, is associated with oxidative stress and, being an antioxidant, vitamin C might influence it. Methods We searched the Cochrane CENTRAL Register, MEDLINE, and Scopus databases for randomised trials on vitamin C that measured AF as an outcome in high risk patients. The two authors independently assessed the trials for inclusion, assessed the risk of bias, and extracted data. We pooled selected trials using the Mantel-Haenszel method for the risk ratio (RR) and the inverse variance weighting for the effects on continuous outcomes. Results We identified 15 trials about preventing AF in high-risk patients, with 2050 subjects. Fourteen trials examined post-operative AF (POAF) in cardiac surgery patients and one examined the recurrence of AF in cardioversion patients. Five trials were carried out in the USA, five in Iran, three in Greece, one in Slovenia and one in Russia. There was significant heterogeneity in the effect of vitamin C in preventing AF. In 5 trials carried out in the USA, vitamin C did not prevent POAF with RR = 1.04 (95% CI: 0.86–1.27). In nine POAF trials conducted outside of the USA, vitamin C decreased its incidence with RR = 0.56 (95% CI: 0.47–0.67). In the single cardioversion trial carried out in Greece, vitamin C decreased the risk of AF recurrence by RR = 0.13 (95% CI: 0.02–0.92). In the non-US cardiac surgery trials, vitamin C decreased the length of hospital stay by 12.6% (95% CI 8.4–16.8%) and intensive care unit (ICU) stay by 8.0% (95% CI 3.0–13.0%). The US trials found no effect on hospital stay and ICU stay. No adverse effects from vitamin C were reported in the 15 trials. Conclusions Our meta-analysis indicates that vitamin C may prevent post-operative atrial fibrillation in some countries outside of the USA, and it may also shorten the duration of hospital stay and ICU stay of cardiac surgery patients. Vitamin C is an essential nutrient that is safe and inexpensive. Further research is needed to determine the optimal dosage protocol and to identify the patient groups that benefit the most.
  • Hankonen, Nelli; Heino, Matti T J; Kujala, Emilia; Hynynen, Sini-Tuuli; Absetz, Pilvikki; Araújo-Soares, Vera; Borodulin, Katja; Haukkala, Ari (BioMed Central, 2017)
    Abstract Background Designing evidence-based interventions to address socioeconomic disparities in health and health behaviours requires a better understanding of the specific explanatory mechanisms. We aimed to investigate a comprehensive range of potential theoretical mediators of physical activity (PA) and screen time in different socioeconomic status (SES) groups: a high SES group of high school students, and a low SES group of vocational school students. The COM-B system, including the Theoretical Domains Framework (TDF), was used as a heuristic framework to synthesise different theoretical determinants in this exploratory study. Methods Finnish vocational and high school students (N = 659) aged 16–19, responded to a survey assessing psychological, social and environmental determinants of activity (PA and screen time). These determinants are mappable into the COM-B domains: capability, opportunity and motivation. The outcome measures were validated self-report measures for PA and screen time. The statistical analyses included a bootstrapping-based mediation procedure. Results Regarding PA, there were SES differences in all of the COM-B domains. For example, vocational school students reported using less self-monitoring of PA, weaker injunctive norms to engage in regular PA, and fewer intentions than high school students. Mediation analyses identified potential mediators of the SES-PA relationship in all of three domains: The most important candidates included self-monitoring (CI95 for b: 0.19–0.47), identity (0.04–0.25) and material resources available (0.01–0.16). However, SES was not related to most determinants of screentime, where there were mainly gender differences. Most determinants were similarly related with both behaviours in both SES groups, indicating no major moderation effect of SES on these relationships. Conclusions This study revealed that already in the first years of educational differentiation, levels of key PA determinants differ, contributing to socioeconomic differences in PA. The analyses identified the strongest mediators of the SES-PA association, but additional investigation utilising longitudinal and experimental designs are needed. This study demonstrates the usefulness of combining constructs from various theoretical approaches to better understand the role of distinct mechanisms that underpin socioeconomic health behaviour disparities.
  • Aserse, Aregu A; Woyke, Tanja; Kyrpides, Nikos C; Whitman, William B; Lindström, Kristina (BioMed Central, 2017)
    Abstract Rhizobium aethiopicum sp. nov. is a newly proposed species within the genus Rhizobium. This species includes six rhizobial strains; which were isolated from root nodules of the legume plant Phaseolus vulgaris growing in soils of Ethiopia. The species fixes nitrogen effectively in symbiosis with the host plant P. vulgaris, and is composed of aerobic, Gram-negative staining, rod-shaped bacteria. The genome of type strain HBR26T of R. aethiopicum sp. nov. was one of the rhizobial genomes sequenced as a part of the DOE JGI 2014 Genomic Encyclopedia project designed for soil and plant-associated and newly described type strains. The genome sequence is arranged in 62 scaffolds and consists of 6,557,588 bp length, with a 61% G + C content and 6221 protein-coding and 86 RNAs genes. The genome of HBR26T contains repABC genes (plasmid replication genes) homologous to the genes found in five different Rhizobium etli CFN42T plasmids, suggesting that HBR26T may have five additional replicons other than the chromosome. In the genome of HBR26T, the nodulation genes nodB, nodC, nodS, nodI, nodJ and nodD are located in the same module, and organized in a similar way as nod genes found in the genome of other known common bean-nodulating rhizobial species. nodA gene is found in a different scaffold, but it is also very similar to nodA genes of other bean-nodulating rhizobial strains. Though HBR26T is distinct on the phylogenetic tree and based on ANI analysis (the highest value 90.2% ANI with CFN42T) from other bean-nodulating species, these nod genes and most nitrogen-fixing genes found in the genome of HBR26T share high identity with the corresponding genes of known bean-nodulating rhizobial species (96–100% identity). This suggests that symbiotic genes might be shared between bean-nodulating rhizobia through horizontal gene transfer. R. aethiopicum sp. nov. was grouped into the genus Rhizobium but was distinct from all recognized species of that genus by phylogenetic analyses of combined sequences of the housekeeping genes recA and glnII. The closest reference type strains for HBR26T were R. etli CFN42T (94% similarity of the combined recA and glnII sequences) and Rhizobium bangladeshense BLR175T (93%). Genomic ANI calculation based on protein-coding genes also revealed that the closest reference strains were R. bangladeshense BLR175T and R. etli CFN42T with ANI values 91.8 and 90.2%, respectively. Nevertheless, the ANI values between HBR26T and BLR175T or CFN42T are far lower than the cutoff value of ANI (> = 96%) between strains in the same species, confirming that HBR26T belongs to a novel species. Thus, on the basis of phylogenetic, comparative genomic analyses and ANI results, we formally propose the creation of R. aethiopicum sp. nov. with strain HBR26T (=HAMBI 3550T=LMG 29711T) as the type strain. The genome assembly and annotation data is deposited in the DOE JGI portal and also available at European Nucleotide Archive under accession numbers FMAJ01000001-FMAJ01000062.
  • Garcia-Larsen, Vanessa; Arthur, Rhonda; Potts, James F; Howarth, Peter H; Ahlström, Matti; Haahtela, Tari; Loureiro, Carlos; Bom, Ana T; Brożek, Grzegorz; Makowska, Joanna; Kowalski, Marek L; Thilsing, Trine; Keil, Thomas; Matricardi, Paolo M; Torén, Kjell; van Zele, Thibaut; Bachert, Claus; Rymarczyk, Barbara; Janson, Christer; Forsberg, Bertil; Niżankowska-Mogilnicka, Ewa; Burney, Peter G J (BioMed Central, 2017)
    Abstract Background Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA2LEN) screening survey, in which 55,000 adults aged 15–75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA2LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient −2.34; 95% confidence interval [CI] −4.09, −0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted β-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
  • Bofah, Emmanuel A; Hannula, Markku S (Springer US, 2017)
    Abstract In large scale international assessment studies, questionnaires are typical used to query students’ home possessions. Composite scores are computed from responses to the home resource questionnaires and are used as a measure of family socioeconomic background in achievement comparison or for statistical control. This paper deals with profiling the socio-economic status (SES) of Ghanaian students’ in the context of the TIMSS 2011 study. Latent class analysis was used to profile students into respective SES classes based on the students’ responses to 11 questions concerning their home resources. The results showed three clearly distinct socio-economic profiles: high-, middle- and low-SES. Moreover, a discriminate analysis was conducted to explore the degree to which the groups are accurately classified. The discriminant analysis was able to correctly classify 92.20% of the individual students into their appropriate SES group. A gender comparison of these classes suggested stable measurement invariance for the latent class indicators. This article contributes to addressing the composition of SES by providing statistical criteria to evaluate SES using empirical data.
  • Kaasalainen, Martti; Aseyev, Vladimir; von Haartman, Eva; Karaman, Didem Ş; Mäkilä, Ermei; Tenhu, Heikki; Rosenholm, Jessica; Salonen, Jarno (Springer US, 2017)
    Abstract Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles’ properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles.
  • Mänty, Minna; Lallukka, Tea; Lahti, Jouni; Pietiläinen, Olli; Laaksonen, Mikko; Lahelma, Eero; Rahkonen, Ossi (BioMed Central, 2017)
    Abstract Background Sickness absence has been shown to be a risk marker for severe future health outcomes, such as disability retirement and premature death. However, it is poorly understood how all-cause and diagnosis-specific sickness absence is reflected in subsequent physical and mental health functioning over time. The aim of this study was to examine the association of all-cause and diagnosis-specific sickness absence with subsequent changes in physical and mental health functioning among ageing municipal employees. Methods Prospective survey and register data from the Finnish Helsinki Health Study and the Social Insurance Institution of Finland were used. Register based records for medically certified all-cause and diagnostic-specific sickness absence spells (>14 consecutive calendar days) in 2004–2007 were examined in relation to subsequent physical and mental health functioning measured by Short-Form 36 questionnaire in 2007 and 2012. In total, 3079 respondents who were continuously employed over the sickness absence follow-up were included in the analyses. Repeated-measures analysis was used to examine the associations. Results During the 3-year follow-up, 30% of the participants had at least one spell of medically certified sickness absence. All-cause sickness absence was associated with lower subsequent physical and mental health functioning in a stepwise manner: the more absence days, the poorer the subsequent physical and mental health functioning. These differences remained but narrowed slightly during the follow-up. Furthermore, the adverse association for physical health functioning was strongest among those with sickness absence due to diseases of musculoskeletal or respiratory systems, and on mental functioning among those with sickness absence due to mental disorders. Conclusions Sickness absence showed a persistent adverse stepwise association with subsequent physical and mental health functioning. Evidence on health-related outcomes after long-term sickness absence may provide useful information for targeted interventions to promote health and workability.
  • Davidsson, Pär; Broberg, Martin; Kariola, Tarja; Sipari, Nina; Pirhonen, Minna; Palva, E. T (BioMed Central, 2017)
    Abstract Background Oligogalacturonides (OGs) are important components of damage-associated molecular pattern (DAMP) signaling and influence growth regulation in plants. Recent studies have focused on the impact of long OGs (degree of polymerization (DP) from 10–15), demonstrating the induction of plant defense signaling resulting in enhanced defenses to necrotrophic pathogens. To clarify the role of trimers (trimeric OGs, DP3) in DAMP signaling and their impact on plant growth regulation, we performed a transcriptomic analysis through the RNA sequencing of Arabidopsis thaliana exposed to trimers. Results The transcriptomic data from trimer-treated Arabidopsis seedlings indicate a clear activation of genes involved in defense signaling, phytohormone signaling and a down-regulation of genes involved in processes related to growth regulation and development. This is further accompanied with improved defenses against necrotrophic pathogens triggered by the trimer treatment, indicating that short OGs have a clear impact on plant responses, similar to those described for long OGs. Conclusions Our results demonstrate that trimers are indeed active elicitors of plant defenses. This is clearly indicated by the up-regulation of genes associated with plant defense signaling, accompanied with improved defenses against necrotrophic pathogens. Moreover, trimers simultaneously trigger a clear down-regulation of genes and gene sets associated with growth and development, leading to stunted seedling growth in Arabidopsis.
  • Puolakkainen, Tero; Ma, Hongqian; Kainulainen, Heikki; Pasternack, Arja; Rantalainen, Timo; Ritvos, Olli; Heikinheimo, Kristiina; Hulmi, Juha J; Kiviranta, Riku (BioMed Central, 2017)
    Abstract Background Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Methods Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Results Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P < 0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treated mice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P < 0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice. Conclusions Our results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.
  • Kaunomäki, Jenni; Jokela, Markus; Kontio, Raija; Laiho, Tero; Sailas, Eila; Lindberg, Nina (BioMed Central, 2017)
    Abstract Background Patient aggression and violence against staff members and other patients are common concerns in psychiatric units. Many structured clinical risk assessment tools have recently been developed. Despite their superiority to unaided clinical judgments, staff has shown ambivalent views towards them. A constant worry of staff is that the results of risk assessments would not be used. The aims of the present study were to investigate what were the interventions applied by the staff of a psychiatric admission ward after a high risk patient had been identified, how frequently these interventions were used and how effective they were. Methods The data were collected in a naturalistic setting during a 6-month period in a Finnish psychiatric admission ward with a total of 331 patients with a mean age of 42.9 years (SD 17.39) suffering mostly from mood, schizophrenia-related and substance use disorders. The total number of treatment days was 2399. The staff assessed the patients daily with the Dynamic Appraisal of Situational Aggression (DASA), which is a structured violence risk assessment considering the upcoming 24 h. The interventions in order to reduce the risk of violence following a high DASA total score (≥4) were collected from the patients’ medical files. Inductive content analysis was used. Results There were a total of 64 patients with 217 observations of high DASA total score. In 91.2% of cases, at least one intervention aiming to reduce the violence risk was used. Pro re nata (PRN)-medication, seclusion and focused discussions with a nurse were the most frequently used interventions. Non-coercive and non-pharmacological interventions like daily activities associated significantly with the decrease of perceived risk of violence. Conclusion In most cases, a high score in violence risk assessment led to interventions aiming to reduce the risk. Unfortunately, the most frequently used methods were psychopharmacological or coercive. It is hoped that the findings will encourage the staff to use their imagination when choosing violence risk reducing intervention techniques.