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  • Kasteenpohja, Teija; Marttunen, Mauri; Aalto-Setälä, Terhi; Perälä, Jonna; Saarni, Samuli I; Suvisaari, Jaana (BioMed Central, 2015)
    Abstract Background Under-treated depression may be especially harmful in early adulthood. The aims of this study are to describe treatments received for depressive disorders, to define factors associated with treatment adequacy and dropouts from treatment in a Finnish general population sample of young adults. Methods A nationally representative two-stage cluster sample of 1894 Finns aged 19 to 34 years was sent a questionnaire containing several mental health screens. All screen positives and a random sample of screen negatives were invited to participate in a mental health assessment including a SCID interview. Case records from mental health treatments for the same sample were obtained for the final diagnostic assessment. Based on all available information, receiving antidepressant pharmacotherapy for at least two months with at least four visits with any type of physician or at least eight sessions of psychotherapy within 12 months or at least four days of hospitalization were regarded as minimally adequate treatment. Treatment dropout was rated if the treatment strategy was assessed to be adequate according to the case records but the patient discontinued the visits. Results Of participants with depressive disorders (n = 142), 40.9% received minimally adequate treatment. In multiple logistic regression models, substance use disorder and female gender were associated with at least one visit with a physician, while having major depressive disorder was associated with visits with a physician at least 4 times a year. Women had higher odds of having received any psychotherapy and psychotherapy lasting for at least 8 sessions in a year. Low education and a history of suicide attempt were associated with increased odds of treatment dropout. None of the factors explained the final outcome of minimally adequate treatment. Conclusions Treatment adequacy in the present study was better than previously seen, but more efforts are needed to provide adequate treatment for young adults, especially those with low education and suicidality.
  • Ma, Li; Piirainen, Sami; Kulesskaya, Natalia; Rauvala, Heikki; Tian, Li (BioMed Central, 2015)
    Abstract Background Social deficit is one of the core symptoms of neuropsychiatric diseases, in which immune genes play an important role. Although a few immune genes have been shown to regulate social and emotional behaviors, how immune gene network(s) may jointly regulate sociability has not been investigated so far. Methods To decipher the potential immune-mediated mechanisms underlying social behavior, we first studied the brain microarray data of eight inbred mouse strains with known variations in social behavior and retrieved the differentially expressed immune genes. We then made a protein-protein interaction analysis of them to find the major networks and explored the potential association of these genes with the behavior and brain morphology in the mouse phenome database. To validate the expression and function of the candidate immune genes, we selected the C57BL/6 J and DBA/2 J strains among the eight inbred strains, compared their social behaviors in resident-intruder and 3-chambered social tests and the mRNA levels of these genes, and analyzed the correlations of these genes with the social behaviors. Results A group of immune genes were differentially expressed in the brains of these mouse strains. The representative C57BL/6 J and DBA/2 J strains displayed significant differences in social behaviors, DBA/2 J mice being less active in social dominance and social interaction than C57BL/6 J mice. The mRNA levels of H2-d1 in the prefrontal cortex, hippocampus, and hypothalamus and C1qb in the hippocampus of the DBA/2 J strain were significantly down-regulated as compared to those in the C57BL/6 J strain. In contrast, Polr3b in the hippocampus and Tnfsf13b in the prefrontal cortex of the DBA/2 J strain were up-regulated. Furthermore, C1qb, Cx3cl1, H2-d1, H2-k1, Polr3b, and Tnfsf13b were predicted to be associated with various behavioral and brain morphological features across the eight inbred strains. Importantly, the C1qb mRNA level was confirmed to be significantly correlated with the sociability in DBA/2 J but not in C57BL/6 J mice. Conclusions Our study provided evidence on the association of immune gene network(s) with the brain development and behavior in animals and revealed neurobiological functions of novel brain immune genes that may contribute to social deficiency in animal models of neuropsychiatric disorders.
  • Zhang, Yanlei; Ning, Feng; Sun, Jianping; Pang, Zengchang; Wang, Xiaoyong; Kapur, Anil; Sintonen, Harri; Qiao, Qing (BioMed Central, 2015)
    Abstract Background Screening for type 2 diabetes helps detect previously unknown diabetes and identify people with pre-diabetes, but the adverse impact of such screening on individuals labelled as pre-diabetes or classified as normal, is less known. In this study the health-related quality of life (HRQoL), depression and lifestyle changes in a rural Chinese population are assessed three years after a screening program. Methods A total of 647 (39.1%) individuals with pre-diabetes and 1009 (60.9%) individuals with normoglycaemia from a population-based diabetes screening program in 2009 were re-examined in 2012–2013. Changes at the end of 3 years in HRQoL, depression, BMI, weight, frequency of physical activity and vegetable intake were assessed. Results In men with normoglycaemia the mean (SD) 15D scores were 0.974 (0.04) at baseline and 0.973 (0.05) at follow-up; and 0.971 (0.05) and 0.966 (0.06) for men with pre-diabetes. In women the scores were 0.973 (0.05) and 0.963 (0.06) for normoglycaemia and 0.959 (0.06) and 0.954 (0.07) for pre-diabetes, respectively. Compared to baseline, the HRQoL was slightly lower at 3 years in all groups but the change was not considered to be clinically important, and was only statistically significant for women with normoglycaemia (p < 0.05). The depression score was slightly elevated in women, but not in men. No significant changes in BMI were noticed, but weight increased slightly in the normoglycemia group (p < 0.05). Screening had a significant positive impact on physical activity and vegetable intake. Conclusions This population-based diabetes screening program generated long-term positive changes toward a healthy lifestyle as measured by physical activity and vegetable intake for all the participants without adverse effects on the HRQoL and depression.
  • Fortino, Vittorio; Smolander, Olli-Pekka; Auvinen, Petri; Tagliaferri, Roberto; Greco, Dario (BioMed Central, 2014)
    Abstract Background Inferring operon maps is crucial to understanding the regulatory networks of prokaryotic genomes. Recently, RNA-seq based transcriptome studies revealed that in many bacterial species the operon structure vary with the change of environmental conditions. Therefore, new computational solutions that use both static and dynamic data are necessary to create condition specific operon predictions. Results In this work, we propose a novel classification method that integrates RNA-seq based transcriptome profiles with genomic sequence features to accurately identify the operons that are expressed under a measured condition. The classifiers are trained on a small set of confirmed operons and then used to classify the remaining gene pairs of the organism studied. Finally, by linking consecutive gene pairs classified as operons, our computational approach produces condition-dependent operon maps. We evaluated our approach on various RNA-seq expression profiles of the bacteria Haemophilus somni, Porphyromonas gingivalis, Escherichia coli and Salmonella enterica. Our results demonstrate that, using features depending on both transcriptome dynamics and genome sequence characteristics, we can identify operon pairs with high accuracy. Moreover, the combination of DNA sequence and expression data results in more accurate predictions than each one alone. Conclusion We present a computational strategy for the comprehensive analysis of condition-dependent operon maps in prokaryotes. Our method can be used to generate condition specific operon maps of many bacterial organisms for which high-resolution transcriptome data is available.
  • Arnulfo, Gabriele; Narizzano, Massimo; Cardinale, Francesco; Fato, Marco M; Palva, Jaakko M (BioMed Central, 2015)
    Abstract Background Invasive monitoring of brain activity by means of intracerebral electrodes is widely practiced to improve pre-surgical seizure onset zone localization in patients with medically refractory seizures. Stereo-Electroencephalography (SEEG) is mainly used to localize the epileptogenic zone and a precise knowledge of the location of the electrodes is expected to facilitate the recordings interpretation and the planning of resective surgery. However, the localization of intracerebral electrodes on post-implant acquisitions is usually time-consuming (i.e., manual segmentation), it requires advanced 3D visualization tools, and it needs the supervision of trained medical doctors in order to minimize the errors. In this paper we propose an automated segmentation algorithm specifically designed to segment SEEG contacts from a thresholded post-implant Cone-Beam CT volume (0.4 mm, 0.4 mm, 0.8 mm). The algorithm relies on the planned position of target and entry points for each electrode as a first estimation of electrode axis. We implemented the proposed algorithm into DEETO, an open source C++ prototype based on ITK library. Results We tested our implementation on a cohort of 28 subjects in total. The experimental analysis, carried out over a subset of 12 subjects (35 multilead electrodes; 200 contacts) manually segmented by experts, show that the algorithm: (i) is faster than manual segmentation (i.e., less than 1s/subject versus a few hours) (ii) is reliable, with an error of 0.5 mm ± 0.06 mm, and (iii) it accurately maps SEEG implants to their anatomical regions improving the interpretability of electrophysiological traces for both clinical and research studies. Moreover, using the 28-subject cohort we show here that the algorithm is also robust (error < 0.005 mm) against deep-brain displacements (< 12 mm) of the implanted electrode shaft from those planned before surgery. Conclusions Our method represents, to the best of our knowledge, the first automatic algorithm for the segmentation of SEEG electrodes. The method can be used to accurately identify the neuroanatomical loci of SEEG electrode contacts by a non-expert in a fast and reliable manner.
  • Kuchenbaecker, Karoline B; Neuhausen, Susan L; Robson, Mark; Barrowdale, Daniel; McGuffog, Lesley; Mulligan, Anna M; Andrulis, Irene L; Spurdle, Amanda B; Schmidt, Marjanka K; Schmutzler, Rita K; Engel, Christoph; Wappenschmidt, Barbara; Nevanlinna, Heli; Thomassen, Mads; Southey, Melissa; Radice, Paolo; Ramus, Susan J; Domchek, Susan M; Nathanson, Katherine L; Lee, Andrew; Healey, Sue; Nussbaum, Robert L; Rebbeck, Timothy R; Arun, Banu K; James, Paul; Karlan, Beth Y; Lester, Jenny; Cass, Ilana; Registry, Breast C F; Terry, Mary B; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Steele, Linda; v O Hansen, Thomas; Ejlertsen, Bent; Gerdes, Anne-Marie; Nielsen, Finn C; Dennis, Joe; Cunningham, Julie; Hart, Steven; Slager, Susan; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Weitzel, Jeffrey N; Tafur, Isaac; Hander, Mary; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Roversi, Gaia; Scuvera, Giulietta; Bonanni, Bernardo; Mariani, Paolo; Volorio, Sara; Dolcetti, Riccardo; Varesco, Liliana; Papi, Laura; Tibiletti, Maria G; Giannini, Giuseppe; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D G; Frost, Debra; Eccles, Diana; Douglas, Fiona; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Ong, Kai-ren; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M J; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Ellis, Steve; Godwin, Andrew K; Rhiem, Kerstin; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg; Niederacher, Dieter; Sutter, Christian; Steinemann, Doris; Bogdanova-Markov, Nadja; Kast, Karin; Varon-Mateeva, Raymonda; Wang-Gohrke, Shan; Gehrig, Andrea; Markiefka, Birgid; Buecher, Bruno; Lefol, Cédrick; Stoppa-Lyonnet, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Barjhoux, Laure; Faivre, Laurence; Longy, Michel; Sevenet, Nicolas; Sinilnikova, Olga M; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Isaacs, Claudine; Van Maerken, Tom; Claes, Kathleen; Piedmonte, Marion; Andrews, Lesley; Hays, John; Rodriguez, Gustavo C; Caldes, Trinidad; de la Hoya, Miguel; Khan, Sofia; Hogervorst, Frans B; Aalfs, Cora M; de Lange, JL; Meijers-Heijboer, Hanne E; van der Hout, Annemarie H; Wijnen, Juul T; van Roozendaal, KEP; Mensenkamp, Arjen R; van den Ouweland, Ans M; van Deurzen, Carolien H; van der Luijt, Rob B; Olah, Edith; Diez, Orland; Lazaro, Conxi; Blanco, Ignacio; Teulé, Alex; Menendez, Mireia; Jakubowska, Anna; Lubinski, Jan; Cybulski, Cezary; Gronwald, Jacek; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Arason, Adalgeir; Maugard, Christine; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Olswold, Curtis; Lindor, Noralane; Pankratz, Vernon S; Hallberg, Emily; Wang, Xianshu; Szabo, Csilla I; Vijai, Joseph; Jacobs, Lauren; Corines, Marina; Lincoln, Anne; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne G; Pfeiler, Georg; Tea, Muy-Kheng; Phelan, Catherine M; Mai, Phuong L; Greene, Mark H; Rennert, Gad; Imyanitov, Evgeny N; Glendon, Gord; Toland, Amanda E; Bojesen, Anders; Pedersen, Inge S; Jensen, Uffe B; Caligo, Maria A; Friedman, Eitan; Berger, Raanan; Laitman, Yael; Rantala, Johanna; Arver, Brita; Loman, Niklas; Borg, Ake; Ehrencrona, Hans; Olopade, Olufunmilayo I; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Antoniou, Antonis C (BioMed Central, 2014)
    Abstract Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10−6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Conclusions Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction.
  • Määttä, Suvi; Lehto, Reetta; Nislin, Mari; Ray, Carola; Erkkola, Maijaliisa; Sajaniemi, Nina; Roos, Eva (BioMed Central, 2015)
    Abstract Background Effective interventions that target socioeconomic status (SES) differences to avoid the potential widening of inequalities in health are needed. Children at preschool age is a valuable intervention target since sedentary behaviors, physical activity (PA), dietary behaviors, and sleep habits, jointly called the energy balance-related behaviors (EBRBs), are established in early childhood and tend to persist later in life. The interventions are most effective, when they focus on evidence-based factors. One potential factor associated with EBRBs and SES is children’s stress regulation, which receives special attention in this study. Based on the socioecological approach, the combinations of multiple levels (e.g. individual, environmental, societal) of analysis and diverse methodologies (e.g. surveys, observations, biological measurements) are used to assess the healthfulness of environments (e.g. social, physical, learning, policy) in preschool and family settings. The intervention aimed to diminish SES differences in EBRBs is then conducted in the preschool setting. Methods/design The DAGIS study is divided into two phases. The first phase comprises focus group interviews and a cross-sectional survey. Parents and preschool personnel in low SES neighborhoods participated in interviews about children’s sedentary behaviors, dietary behaviors, and PA in 2014. In the cross-sectional survey beginning in autumn 2015, preschools will be recruited from a random sample of preschools in 3–5 municipalities in Southern Finland. A total of 800 children will wear an accelerometer for seven days. Children’s hair and saliva samples will be taken. Parents and preschool personnel will complete questionnaires on EBRBs, social and physical environments and SES factors. The quality of preschool environment is also observed. In the second phase, an intervention targeting to narrowing SES differences in EBRBs is conducted. The effects of the intervention will be evaluated in randomised controlled trial. The implementation of the intervention will also be evaluated. Conclusion If effective, this unique preschool-based study will be able to narrow the SES differences in preschool children’s EBRBs. This study is anticipated to identify the most important modifiable factors in preschool and family environmental settings associated with children’s EBRBs, especially in children from low SES backgrounds. Trial registration ISRCTN57165350 (January, 8th, 2015).
  • Aho, Velma T E; Pereira, Pedro A B; Haahtela, Tari; Pawankar, Ruby; Auvinen, Petri; Koskinen, Kaisa (BioMed Central, 2015)
    Abstract For a long time, the human lower airways were considered a sterile environment where the presence of microorganisms, typically revealed by culturing, was interpreted as an abnormal health state. More recently, high-throughput sequencing-based studies have led to a shift in this perception towards the notion that even in healthy conditions the lower airways show either transient presence or even permanent colonization by microorganisms. However, challenges related to low biomass and contamination in samples still remain, and the composition, structure and dynamics of such putative microbial communities are unclear. Here, we review the evidence for the presence of microbial communities in the human lower airways, in healthy subjects and within the context of medical conditions of interest. We also provide an overview of the methodology pertinent to high-throughput sequencing studies, specifically those based on amplicon sequencing, including a discussion of good practices and common pitfalls.
  • Örmälä-Odegrip, Anni-Maria; Ojala, Ville; Hiltunen, Teppo; Zhang, Ji; Bamford, Jaana K; Laakso, Jouni (BioMed Central, 2015)
    Abstract Background Consumer-resource interactions constitute one of the most common types of interspecific antagonistic interaction. In natural communities, complex species interactions are likely to affect the outcomes of reciprocal co-evolution between consumers and their resource species. Individuals face multiple enemies simultaneously, and consequently they need to adapt to several different types of enemy pressures. In this study, we assessed how protist predation affects the susceptibility of bacterial populations to infection by viral parasites, and whether there is an associated cost of defence on the competitive ability of the bacteria. As a study system we used Serratia marcescens and its lytic bacteriophage, along with two bacteriovorous protists with distinct feeding modes: Tetrahymena thermophila (particle feeder) and Acanthamoeba castellanii (surface feeder). The results were further confirmed with another study system with Pseudomonas and Tetrahymena thermophila. Results We found that selection by protist predators lowered the susceptibility to infections by lytic phages in Serratia and Pseudomonas. In Serratia, concurrent selection by phages and protists led to lowered susceptibility to phage infections and this effect was independent from whether the bacteria shared a co-evolutionary history with the phage population or not. Bacteria that had evolved with phages were overall more susceptible to phage infection (compared to bacteria with history with multiple enemies) but they were less vulnerable to the phages they had co-evolved with than ancestral phages. Selection by bacterial enemies was costly in general and was seen as a lowered fitness in absence of phages, measured as a biomass yield. Conclusions Our results show the significance of multiple species interactions on pairwise consumer-resource interaction, and suggest potential overlap in defending against predatory and parasitic enemies in microbial consumer-resource communities. Ultimately, our results could have larger scale effects on eco-evolutionary community dynamics.
  • Caburet, Sandrine; Anttonen, Mikko; Todeschini, Anne-Laure; Unkila-Kallio, Leila; Mestivier, Denis; Butzow, Ralf; Veitia, Reiner A (BioMed Central, 2015)
    Abstract Background Ovarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression. Methods We have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes. Results Our results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related. Conclusions Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation.
  • Guo, Baocheng; DeFaveri, Jacquelin; Sotelo, Graciela; Nair, Abhilash; Merilä, Juha (BioMed Central, 2015)
    Abstract Background The degree of genetic differentiation among populations experiencing high levels of gene flow is expected to be low for neutral genomic sites, but substantial divergence can occur in sites subject to directional selection. Studies of highly mobile marine fish populations provide an opportunity to investigate this kind of heterogeneous genomic differentiation, but most studies to this effect have focused on a relatively low number of genetic markers and/or few populations. Hence, the patterns and extent of genomic divergence in high-gene-flow marine fish populations remain poorly understood. Results We here investigated genome-wide patterns of genetic variability and differentiation in ten marine populations of three-spined stickleback (Gasterosteus aculeatus) distributed across a steep salinity and temperature gradient in the Baltic Sea, by utilizing >30,000 single nucleotide polymorphisms obtained with a pooled RAD-seq approach. We found that genetic diversity and differentiation varied widely across the genome, and identified numerous fairly narrow genomic regions exhibiting signatures of both divergent and balancing selection. Evidence was uncovered for substantial genetic differentiation associated with both salinity and temperature gradients, and many candidate genes associated with local adaptation in the Baltic Sea were identified. Conclusions The patterns of genetic diversity and differentiation, as well as candidate genes associated with adaptation, in Baltic Sea sticklebacks were similar to those observed in earlier comparisons between marine and freshwater populations, suggesting that similar processes may be driving adaptation to brackish and freshwater environments. Taken together, our results provide strong evidence for heterogenic genomic divergence driven by local adaptation in the face of gene flow along an environmental gradient in the post-glacially formed Baltic Sea.
  • Österman, Janina; Mousavi, Seyed A; Koskinen, Patrik; Paulin, Lars; Lindström, Kristina (BioMed Central, 2015)
    Abstract Background The symbiotic phenotype of Neorhizobium galegae, with strains specifically fixing nitrogen with either Galega orientalis or G. officinalis, has made it a target in research on determinants of host specificity in nitrogen fixation. The genomic differences between representative strains of the two symbiovars are, however, relatively small. This introduced a need for a dataset representing a larger bacterial population in order to make better conclusions on characteristics typical for a subset of the species. In this study, we produced draft genomes of eight strains of N. galegae having different symbiotic phenotypes, both with regard to host specificity and nitrogen fixation efficiency. These genomes were analysed together with the previously published complete genomes of N. galegae strains HAMBI 540T and HAMBI 1141. Results The results showed that the presence of an additional rpoN sigma factor gene in the symbiosis gene region is a characteristic specific to symbiovar orientalis, required for nitrogen fixation. Also the nifQ gene was shown to be crucial for functional symbiosis in both symbiovars. Genome-wide analyses identified additional genes characteristic of strains of the same symbiovar and of strains having similar plant growth promoting properties on Galega orientalis. Many of these genes are involved in transcriptional regulation or in metabolic functions. Conclusions The results of this study confirm that the only symbiosis-related gene that is present in one symbiovar of N. galegae but not in the other is an rpoN gene. The specific function of this gene remains to be determined, however. New genes that were identified as specific for strains of one symbiovar may be involved in determining host specificity, while others are defined as potential determinant genes for differences in efficiency of nitrogen fixation.
  • 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.
  • Monden, Christiaan W; Metsä-Simola, Niina; Saarioja, Saska; Martikainen, Pekka (BioMed Central, 2015)
    Abstract Background There is an average negative mental health effect for individuals who experience divorce. Little is known whether the pattern of such divorce effects varies within couples. We study whether the husband and wife experience similar harmful effects of divorce, whether they experience opposite effects, or whether divorce effects are purely individual. Methods We use Finnish registry data to compare changes over a period of 5 years in antidepressant use of husbands and wives from 4,558 divorcing couples to 108,637 continuously married pairs aged 40–64, all of whom were healthy at baseline. Results In the period three years before and after divorce antidepressant use increases substantially. However, the likelihood of uptake of antidepressant medication during this process of divorce by one partner appears to be independent of medication uptake in the other partner. In contrast, among continuously married couples there is a clear pattern of convergence: If one partner starts to use antidepressants this increases the likelihood of uptake of antidepressant medication in the other partner. Conclusions Our findings suggest that divorce effects on antidepressant use are individual and show no pattern of either convergence or divergence at the level of the couple. The increased incidence of antidepressant use associated with divorce occurs in individuals independent of what happens to their ex-partner.
  • Kulhánová, Ivana; Menvielle, Gwenn; Bopp, Matthias; Borrell, Carme; Deboosere, Patrick; Eikemo, Terje A; Hoffmann, Rasmus; Leinsalu, Mall; Martikainen, Pekka; Regidor, Enrique; Rodríguez-Sanz, Maica; Rychtaříková, Jitka; Wojtyniak, Bogdan; Mackenbach, Johan P (BioMed Central, 2014)
    Abstract Background Cause-of-death data linked to information on socioeconomic position form one of the most important sources of information about health inequalities in many countries. The proportion of deaths from ill-defined conditions is one of the indicators of the quality of cause-of-death data. We investigated educational differences in the use of ill-defined causes of death in official mortality statistics. Methods Using age-standardized mortality rates from 16 European countries, we calculated the proportion of all deaths in each educational group that were classified as due to “Symptoms, signs and ill-defined conditions”. We tested if this proportion differed across educational groups using Chi-square tests. Results The proportion of ill-defined causes of death was lower than 6.5% among men and 4.5% among women in all European countries, without any clear geographical pattern. This proportion statistically significantly differed by educational groups in several countries with in most cases a higher proportion among less than secondary educated people compared with tertiary educated people. Conclusions We found evidence for educational differences in the distribution of ill-defined causes of death. However, the differences between educational groups were small suggesting that socioeconomic inequalities in cause-specific mortality in Europe are not likely to be biased.