Toivonen R.K.,University of Turku |
Emani R.,University of Turku |
Munukka E.,University of Turku |
Rintala A.,University of Turku |
And 8 more authors.
Diabetologia | Year: 2014
Aims/hypothesis: Gut microbiota (GM) and diet both appear to be important in the pathogenesis of type 1 diabetes. Fermentable fibres (FFs), of which there is an ample supply in natural, diabetes-promoting diets, are used by GM as a source of energy. Our aim was to determine whether FFs modify GM and diabetes incidence in the NOD mouse. Methods: Female NOD mice were weaned to a semisynthetic diet and the effects of FF supplementation on diabetes incidence and insulitis were evaluated. Real-time quantitative PCR was employed to determine the effects imposed to gene transcripts in the colon and lymph nodes. Changes to GM were analysed by next-generation sequencing. Results: NOD mice fed semisynthetic diets free from FFs were largely protected from diabetes while semisynthetic diets supplemented with the FFs pectin and xylan (PX) resulted in higher diabetes incidence. Semisynthetic diet free from FFs altered GM composition significantly; addition of PX changed the composition of the GM towards that found in natural-diet-fed mice and increased production of FF-derived short-chain fatty acid metabolites in the colon. The highly diabetogenic natural diet was associated with expression of proinflammatory and stress-related genes in the colon, while the semisynthetic diet free from FFs promoted Il4, Il22, Tgfβ and Foxp3 transcripts in the colon and/or pancreatic lymph node. PX in the same diet counteracted these effects and promoted stress-related IL-18 activation in gut epithelial cells. 16S RNA sequencing revealed each diet to give rise to its particular GM composition, with different Firmicutes to Bacteroidetes ratios, and enrichment of mucin-degrading Ruminococcaceae following diabetes-protective FF-free diet. Conclusions/interpretation: FFs condition microbiota, affect colon homeostasis and are important components of natural, diabetes-promoting diets in NOD mice. © 2014, Springer-Verlag Berlin Heidelberg.
Elo L.L.,University of Turku |
Elo L.L.,Turku Center for Biotechnology |
Schwikowski B.,Institute Pasteur Paris
Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery | Year: 2012
The popularity of proteomics in biomedical research has grown with the development of advanced measurement technologies. This has enabled highthroughput protein expression profiling, modification-specific proteomics, and global protein-protein interaction maps. Although proteomics has great potential in providing deeper understanding of the role of individual proteins and protein networks in disease and in unveiling the underlying disease mechanisms, challenges arise in transforming the large-scale experimental data into biomedical knowledge for clinical practice and drug development. In particular, sophisticated computational tools are required to interpret the high-dimensional proteomic datasets that typically reflect not only biological information, but also technical biases and limitations. This review gives an overview of the role of data mining in biomedical applications of proteomics, with a focus on data from mass spectrometry-based expression profiling studies. © 2011 Wiley Periodicals, Inc.
Hartiala P.,University of Turku |
Hytonen J.,University of Turku |
Yrjanainen H.,University of Turku |
Honkinen M.,University of Turku |
And 4 more authors.
Journal of Immunology | Year: 2010
Lyme borreliosis is a tick-borne bacterial infection that in many cases is limited to the skin. However, in some patients the bacterium evades the immune response and disseminates into various organs. Dendritic cells (DCs) are among the first cells to meet invading pathogens in the skin. We have previously shown that CD38, an ectoenzyme involved in the migration of DCs and generally upregulated by microbial stimuli, is not upregulated in Borrelia garinii-stimulated DCs. In this paper, we characterize the cellular events that lead to the absence of CD38 on the DC surface after B. garinii stimulation and investigate the consequences of absent CD38 expression for the migration of DCs in vitro and in vivo. The data show that 1) effective signaling via p38 MAPK (and STAT1 and NF-κB) is needed for CD38 expression and 2) TLR2 stimulation, as opposed to TLR4 stimulation, does not induce IFN-β autocrine loop-dependent expression of CD38 and secretion of IL-12. Further, we show that 3) B. garinii-stimulated DCs do not migrate effectively toward CCL19 and CCL21 and 4) after B. garinii infection of mice, the number of DCs migrating from the infection site to draining lymph nodes is only half that induced by Escherichia coli infection. Our results provide evidence for the first time that different TLR use results in different CD38 expression, which correlates with the migratory potential of DCs. Copyright © 2010 by The American Association of Immunologists, Inc.
Lahti L.,University of Helsinki |
Lahti L.,Wageningen University |
Torrente A.,European Bioinformatics Institute |
Torrente A.,Charles III University of Madrid |
And 4 more authors.
Nucleic Acids Research | Year: 2013
Rapid accumulation of large and standardized microarray data collections is opening up novel opportunities for holistic characterization of genome function. The limited scalability of current preprocessing techniques has, however, formed a bottleneck for full utilization of these data resources. Although short oligonucleotide arrays constitute a major source of genome-wide profiling data, scalable probe-level techniques have been available only for few platforms based on pre-calculated probe effects from restricted reference training sets. To overcome these key limitations, we introduce a fully scalable online-learning algorithm for probe-level analysis and pre-processing of large microarray atlases involving tens of thousands of arrays. In contrast to the alternatives, our algorithm scales up linearly with respect to sample size and is applicable to all short oligonucleotide platforms. The model can use the most comprehensive data collections available to date to pinpoint individual probes affected by noise and biases, providing tools to guide array design and quality control. This is the only available algorithm that can learn probe-level parameters based on sequential hyperparameter updates at small consecutive batches of data, thus circumventing the extensive memory requirements of the standard approaches and opening up novel opportunities to take full advantage of contemporary microarray collections. © 2013 The Author(s) 2013.
Myllynen S.,Åbo Akademi University |
Wasberg M.,University of Turku |
Wasberg M.,Turku Center for Biotechnology
Journal of Electroanalytical Chemistry | Year: 2011
Electrochemical, metal-centred partial oxidation of the electrodeposited d8 Ru-Ru bonded chain [Ru0(bpy)(CO)2] n results in high electrical conductivity on the order of 10 -1 S cm-1. The partial oxidation of Ru0 is reversible in presence of charge-compensating PF6- and ClO4- anions, and quartz crystal microbalance data show that the doping/undoping process is accompanied with transfer of unsolvated electrolyte anions. For BF4- and Cl- the process is more complex and in the chloride-case the doping results in break-up of the polymer film. The conductivity of the film is linearly dependent on the electrochemically controlled doping level. Spectroscopic evidence for charge delocalisation is obtained in the near-IR region, with the absorbance proportional to the doping level. The conduction process is thermally activated and ohmic behaviour is found for films both in electrolyte and gas phase. The microscopic structure of dry polymeric films is studied by SEM and anisotropic growth of cone-shaped columns is found. Linear increase in film thickness with deposition charge is obtained above 20 μm with a volume yield corresponding to a density 90% of the X-ray diffraction derived value reported in literature. © 2011 Elsevier B.V. All rights reserved.
Parker D.J.,Center for Biological Diversity |
Parker D.J.,University of Jyväskylä |
Vesala L.,University of Tampere |
Ritchie M.G.,Center for Biological Diversity |
And 3 more authors.
Heredity | Year: 2015
For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis. © 2015 Macmillan Publishers Limited All rights reserved.
Vesala L.,University of Jyväskylä |
Salminen T.S.,University of Jyväskylä |
Laiho A.,Turku Center for Biotechnology |
Hoikkala A.,University of Jyväskylä |
Kankare M.,University of Jyväskylä
Insect Molecular Biology | Year: 2012
The importance of high and low temperature tolerance in adaptation to changing environmental conditions has evoked new interest in modulations in gene expression and metabolism linked with stress tolerance. We investigated the effects of rapid cold hardening and cold acclimatization on the chill coma recovery times of two Drosophila virilis group species, Drosophila montana and D. virilis, with different distributions and utilized a candidate gene approach to trace changes in their gene expression during and after the cold treatments. The study showed that cold acclimatization clearly decreases chill coma recovery times in both species, whereas rapid cold hardening did not have a significant effect. Microarray analysis revealed several genes showing expression changes during different stages of cold response. Amongst the 219 genes studied, two genes showed rather consistent expression changes: hsr-omega, which was up-regulated in both study species during cold acclimatization, and Eip71CD, which was down-regulated in nearly all of the cold treatments. In addition, 29 genes showed expression changes that were more treatment- and/or species specific. Overall, different stages of cold response elicited changes mainly in genes involved in heat shock response, circadian rhythm and metabolism. © 2011 The Royal Entomological Society.
Paul N.R.,University of Manchester |
Paul N.R.,CRUK Beatson Institute |
Jacquemet G.,University of Manchester |
Jacquemet G.,Turku Center for Biotechnology |
Caswell P.T.,University of Manchester
Current Biology | Year: 2015
Integrins are a family of heterodimeric receptors that bind to components of the extracellular matrix and influence cellular processes as varied as proliferation and migration. These effects are achieved by tight spatiotemporal control over intracellular signalling pathways, including those that mediate cytoskeletal reorganisation. The ability of integrins to bind to ligands is governed by integrin conformation, or activity, and this is widely acknowledged to be an important route to the regulation of integrin function. Over the last 15 years, however, the pathways that regulate endocytosis and recycling of integrins have emerged as major players in controlling integrin action, and studying integrin trafficking has revealed fresh insight into the function of this fascinating class of extracellular matrix receptors, in particular in the context of cell migration and invasion. Here, we review our current understanding of the contribution of integrin trafficking to cell motility. © 2015 Elsevier Ltd. All rights reserved.
Gupta B.,KIIT University |
Hawkins R.D.,University of Washington |
Hawkins R.D.,Turku Center for Biotechnology
Immunology and Cell Biology | Year: 2015
Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity. © 2015 Australasian Society for Immunology Inc.
McDonnell L.A.,Leiden University |
Corthals G.L.,Turku Center for Biotechnology |
Willems S.M.,Leiden University |
van Remoortere A.,Leiden University |
And 2 more authors.
Journal of Proteomics | Year: 2010
MALDI mass spectrometry is able to acquire protein profiles directly from tissue that can describe the levels of hundreds of distinct proteins. MALDI imaging MS can simultaneously reveal how each of these proteins varies in heterogeneous tissues. Numerous studies have now demonstrated how MALDI imaging MS can generate different protein profiles from the different cell types in a tumor, which can act as biomarker profiles or enable specific candidate protein biomarkers to be identified.MALDI imaging MS can be directly applied to patient samples where its utility is to accomplish untargeted multiplex analysis of the tissue's protein content, enabling the different regions of the tissue to be differentiated on the basis of previously unknown protein profiles/biomarkers. The technique continues to rapidly develop and is now approaching the cusp whereby its potential to provide new diagnostic/prognostic tools for cancer patients can be routinely investigated.Here the latest methodological developments are summarized and its application to a range of tumors is reported in detail. The prospects of MALDI imaging MS are then described from the perspectives of modern pathological practice and MS-based proteomics, to ensure the outlook addresses real clinical needs and reflects the real capabilities of MS-based proteomics of complex tissue samples. © 2010 Elsevier B.V.