Browsing by Subject "INSIGHTS"

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  • Celaya, Christian A.; Orozco-Ic, Mesias; Dimitrova, Maria; Wirz, Lukas N.; Sundholm, Dage (2020)
    We propose a novel class of gold-containing molecules, which have been designed using conjugated carbon structures as templates. The sp-hybridized carbons of C-2 moieties are replaced with a gold atom and one of the adjacent carbons is replaced by nitrogen. Applying the procedure to hexadehydro[12]annulene yields the well-known cyclic trinuclear gold(i) carbeniate complex. Planar, tubular and cage-shaped complexes can be obtained by taking similar sp-hybridized carbon structures as the starting point.
  • Matlashov, Mikhail E.; Shcherbakova, Daria M.; Alvelid, Jonatan; Baloban, Mikhail; Pennacchietti, Francesca; Shemetov, Anton A.; Testa, Ilaria; Verkhusha, Vladislav V. (2020)
    Bright monomeric near-infrared (NIR) fluorescent proteins (FPs) are in high demand as protein tags for multicolor microscopy and in vivo imaging. Here we apply rational design to engineer a complete set of monomeric NIR FPs, which are the brightest genetically encoded NIR probes. We demonstrate that the enhanced miRFP series of NIR FPs, which combine high effective brightness in mammalian cells and monomeric state, perform well in both nanometer-scale imaging with diffraction unlimited stimulated emission depletion (STED) microscopy and centimeter-scale imaging in mice. In STED we achieve -40nm resolution in live cells. In living mice we detect -10(5) fluorescent cells in deep tissues. Using spectrally distinct monomeric NIR FP variants, we perform two-color live-cell STED microscopy and two-color imaging in vivo. Having emission peaks from 670nm to 720nm, the next generation of miRFPs should become versatile NIR probes for multiplexed imaging across spatial scales in different modalities.
  • Lindfors, S; Polianskyte-Prause, Z; Bouslama, R; Lehtonen, E; Mannerla, M; Nisen, H; Tienari, J; Salmenkari, H; Forsgard, R; Mirtti, T; Lehto, M; Groop, PH; Lehtonen, S (2021)
    Aims/hypothesis Chronic low-grade inflammation with local upregulation of proinflammatory molecules plays a role in the progression of obesity-related renal injury. Reduced serum concentration of anti-inflammatory adiponectin may promote chronic inflammation. Here, we investigated the potential anti-inflammatory and renoprotective effects and mechanisms of action of AdipoRon, an adiponectin receptor agonist. Methods Wild-type DBA/2J mice were fed with high-fat diet (HFD) supplemented or not with AdipoRon to model obesity-induced metabolic endotoxaemia and chronic low-grade inflammation and we assessed changes in the glomerular morphology and expression of proinflammatory markers. We also treated human glomeruli ex vivo and human podocytes in vitro with AdipoRon and bacterial lipopolysaccharide (LPS), an endotoxin upregulated in obesity and diabetes, and analysed the secretion of inflammatory cytokines, activation of inflammatory signal transduction pathways, apoptosis and migration. Results In HFD-fed mice, AdipoRon attenuated renal inflammation, as demonstrated by reduced expression of glomerular activated NF-kappa B p65 subunit (NF-kappa B-p65) (70%, p < 0.001), TNF alpha (48%, p < 0.01), IL-1 beta (51%, p < 0.001) and TGF beta (46%, p < 0.001), renal IL-6 and IL-4 (21% and 20%, p < 0.05), and lowered glomerular F4/80-positive macrophage infiltration (31%, p < 0.001). In addition, AdipoRon ameliorated HFD-induced glomerular hypertrophy (12%, p < 0.001), fibronectin accumulation (50%, p < 0.01) and podocyte loss (12%, p < 0.001), and reduced podocyte foot process effacement (15%, p < 0.001) and thickening of the glomerular basement membrane (18%, p < 0.001). In cultured podocytes, AdipoRon attenuated the LPS-induced activation of the central inflammatory signalling pathways NF-kappa B-p65, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38-MAPK) (30%, 36% and 22%, respectively, p < 0.001), reduced the secretion of TNF alpha (32%, p < 0.01), and protected against podocyte apoptosis and migration. In human glomeruli ex vivo, AdipoRon reduced the LPS-induced secretion of inflammatory cytokines IL-1 beta, IL-18, IL-6 and IL-10. Conclusions/interpretation AdipoRon attenuated the renal expression of proinflammatory cytokines in HFD-fed mice and LPS-stimulated human glomeruli, which apparently contributed to the amelioration of glomerular inflammation and injury. Mechanistically, based on assays on cultured podocytes, AdipoRon reduced LPS-induced activation of the NF-kappa B-p65, JNK and p38-MAPK pathways, thereby impelling the decrease in apoptosis, migration and secretion of TNF alpha. We conclude that the activation of the adiponectin receptor by AdipoRon is a potent strategy to attenuate endotoxaemia-associated renal inflammation.
  • Foulds, Chris; Royston, Sarah; Berker, Thomas; Nakopoulou, Efi; Bharucha, Zareen Pervez; Robison, Rosie; Abram, Simone; Ancic, Branko; Arapostathis, Stathis; Badescu, Gabriel; Bull, Richard; Cohen, Jed; Dunlop, Tessa; Dunphy, Niall; Dupont, Claire; Fischer, Corinna; Gram-Hanssen, Kirsten; Grandclement, Catherine; Heiskanen, Eva; Labanca, Nicola; Jeliazkova, Maria; Jorgens, Helge; Keller, Margit; Kern, Florian; Lombardi, Patrizia; Mourik, Ruth; Ornetzeder, Michael; Pearson, Peter J. G.; Rohracher, Harald; Sahakian, Marlyne; Sari, Ramazan; Standal, Karina; Zivcic, Lidija (2022)
    Decades of techno-economic energy policymaking and research have meant evidence from the Social Sciences and Humanities (SSH)-including critical reflections on what changing a society's relation to energy (efficiency) even means-have been underutilised. In particular, (i) the SSH have too often been sidelined and/or narrowly pigeonholed by policymakers, funders, and other decision-makers when driving research agendas, and (ii) the setting of SSH-focused research agendas has not historically embedded inclusive and deliberative processes. The aim of this paper is to address these gaps through the production of a research agenda outlining future SSH research priorities for energy efficiency. A Horizon Scanning exercise was run, which sought to identify 100 priority SSH questions for energy efficiency research. This exercise included 152 researchers with prior SSH expertise on energy efficiency, who together spanned 62 (sub-)disciplines of SSH, 23 countries, and a full range of career stages. The resultant questions were inductively clustered into seven themes as follows: (1) Citizenship, engagement and knowledge exchange in relation to energy efficiency; (2) Energy efficiency in relation to equity, justice, poverty and vulnerability; (3) Energy efficiency in relation to everyday life and practices of energy consumption and production; (4) Framing, defining and measuring energy efficiency; (5) Governance, policy and political issues around energy efficiency; (6) Roles of economic systems, supply chains and financial mechanisms in improving energy efficiency; and (7) The interactions, unintended consequences and rebound effects of energy efficiency interventions. Given the consistent centrality of energy efficiency in policy programmes, this paper highlights that well-developed SSH approaches are ready to be mobilised to contribute to the development, and/or to understand the implications, of energy efficiency measures and governance solutions. Implicitly, it also emphasises the heterogeneity of SSH policy evidence that can be produced. The agenda will be of use for both (1) those new to the energy-SSH field (including policyworkers), for learnings on the capabilities and capacities of energy-SSH, and (2) established energy-SSH researchers, for insights on the collectively held futures of energy-SSH research.
  • Fontana, Flavia; Albertini, Silvia; Correia, Alexandra; Kemell, Marianna Leena; Lindgren, Rici; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni Tapio; Ferrari, Franca; Almeida Santos, Helder (2018)
    Biohybrid nanosystems are at the center of personalized medicine, affording prolonged circulation time and targeting to the disease site, and serving as antigenic sources of vaccines. The optimization and functionality parameters of these nanosystems vary depending on the properties of the core particles. In this work, the effects of the core particles’ surface charge and hydrophobicity are evaluated on the nanosystem coating with vesicles derived from plasma membrane. The measured parameters are the dimensions, surface charge, shape, and stability of the biohybrid nanosystems, both in buffer and in biologically relevant media (plasma and simulated synovial fluid). Moreover, the cytocompatibility properties of the developed nanosystems are evaluated in different cell lines mimicking the target cell populations and other districts of the body involved in the distribution and elimination of the nanoparticles. Finally, the immunological profile of the particles is investigated, highlighting the absence of immune activation promoted by the nanoplatforms.
  • Hietanen, Joel; Sihvonen, Antti (2021)
    There is a rich tradition of inquiry in consumer research into how collective consumption manifests in various forms and contexts. While this literature has shown how group cohesion prescribes ethical and moral positions, our study explores how ethicality can arise from consumers and their relations in a more emergent fashion. To do so, we present a Levinasian perspective on consumer ethics through a focus on Restaurant Day, a global food carnival that is organized by consumers themselves. Our ethnographic findings highlight a non-individualistic way of approaching ethical subjectivity that translates into acts of catering to the needs of other people and the subversion of extant legislation by foregrounding personal responsibility. These findings show that while consumer gatherings provide participants a license to temporarily subvert existing roles, they also allow the possibility of ethical autonomy when the mundane rules of city life are renegotiated. These sensibilities also create ‘ethical surplus’, which is an affective excess of togetherness. In the Levinasian register, Restaurant Day thus acts as an inarticulable ‘remainder’—a trace of the possibility of being able to live otherwise alongside one another in city contexts.
  • Morandin, Claire; Brendel, Volker P.; Sundstrom, Liselotte; Helantera, Heikki; Mikheyev, Alexander S. (2019)
    Social insects provide systems for studying epigenetic regulation of phenotypes, particularly with respect to differentiation of reproductive and worker castes, which typically arise from a common genetic background. The role of gene expression in caste specialization has been extensively studied, but the role of DNA methylation remains controversial. Here, we perform well replicated, integrated analyses of DNA methylation and gene expression in brains of an ant (Formica exsecta) with distinct female castes using traditional approaches (tests of differential methylation) combined with a novel approach (analysis of co-expression and co-methylation networks). We found differences in expression and methylation profiles between workers and queens at different life stages, as well as some overlap between DNA methylation and expression at the functional level. Large portions of the transcriptome and methylome are organized into "modules" of genes, some significantly associated with phenotypic traits of castes and developmental stages. Several gene co-expression modules are preserved in co-methylation networks, consistent with possible regulation of caste-specific gene expression by DNA methylation. Surprisingly, brain co-expression modules were highly preserved when compared with a previous study that examined whole-body co-expression patterns in 16 ant species, suggesting that these modules are evolutionarily conserved and for specific functions in various tissues. Altogether, these results suggest that DNA methylation participates in regulation of caste specialization and age-related physiological changes in social insects.
  • Roet, Sander; Daub, Christopher; Riccardi, Enrico (2021)
    We propose to analyze molecular dynamics (MD) output via a supervised machine learning (ML) algorithm, the decision tree. The approach aims to identify the predominant geometric features which correlate with trajectories that transition between two arbitrarily defined states. The data-driven algorithm aims to identify these features without the bias of human “chemical intuition”. We demonstrate the method by analyzing the proton exchange reactions in formic acid solvated in small water clusters. The simulations were performed with ab initio MD combined with a method to efficiently sample the rare event, path sampling. Our ML analysis identified relevant geometric variables involved in the proton transfer reaction and how they may change as the number of solvating water molecules changes.
  • Beus, Maja; Savijoki, Kirsi; Patel, Jayendra; Yli-Kauhaluoma, Jari; Fallarero, Adyary; Zorc, Branka (2020)
    Quorum sensing inhibitors (QSIs) that specifically interfere with bacterial cell-to-cell communication are considered as an alternative approach to conventional antibacterial therapy. In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-negative Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-negative, mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides. The initial screening of eighteen fumardiamides with primaquine, mefloquine and chloroquine scaffolds identified chloroquine derivatives as the most promising QSIs. Tail-group optimization of chloroquine fumardiamides led to the most active compounds 27, 29 and 30 bearing aminoethyl or piperidine moieties. At 400 mu M concentration, these compounds inhibited the QS of C. violaceum strains in a manner similar to quercetin (the model QSI), while at the 40 mu M concentration their inhibitory effect was twice less than that of quercetin. As none of the compounds displayed a bactericidal effect and that the QS inhibition was specific to the CV026 strain, our findings indicate that the structurally optimized chloroquine derivatives could function as quorum quenching (QQ) agents with a potential to block the signaling without entering the cell. In conclusion, our finding provides an important step toward the further design of agents targeting cell-to-cell communication.
  • Gorvin, C.M.; Hannan, F.M.; Cranston, T.; Valta, Helena; Mäkitie, Outi; Schalin-Jäntti, Camilla; Thakker, R.V. (2018)
    G-protein subunit -11 (G(11)) couples the calcium-sensing receptor (CaSR) to phospholipase C (PLC)-mediated intracellular calcium (Ca-i(2+)) and mitogen-activated protein kinase (MAPK) signaling, which in the parathyroid glands and kidneys regulates parathyroid hormone release and urinary calcium excretion, respectively. Heterozygous germline loss-of-function G(11) mutations cause familial hypocalciuric hypercalcemia type 2 (FHH2), for which effective therapies are currently not available. Here, we report a novel heterozygous G(11) germline mutation, Phe220Ser, which was associated with hypercalcemia in a family with FHH2. Homology modeling showed the wild-type (WT) Phe220 nonpolar residue to form part of a cluster of hydrophobic residues within a highly conserved cleft region of G(11), which binds to and activates PLC; and predicted that substitution of Phe220 with the mutant Ser220 polar hydrophilic residue would disrupt PLC-mediated signaling. In vitro studies involving transient transfection of WT and mutant G(11) proteins into HEK293 cells, which express the CaSR, showed the mutant Ser220 G(11) protein to impair CaSR-mediated Ca-i(2+) and extracellular signal-regulated kinase 1/2 (ERK) MAPK signaling, consistent with diminished activation of PLC. Furthermore, engineered mutagenesis studies demonstrated that loss of hydrophobicity within the G(11) cleft region also impaired signaling by PLC. The loss-of-function associated with the Ser220 G(11) mutant was rectified by treatment of cells with cinacalcet, which is a CaSR-positive allosteric modulator. Furthermore, in vivo administration of cinacalcet to the proband harboring the Phe220Ser G(11) mutation, normalized serum ionized calcium concentrations. Thus, our studies, which report a novel G(11) germline mutation (Phe220Ser) in a family with FHH2, reveal the importance of the G(11) hydrophobic cleft region for CaSR-mediated activation of PLC, and show that allosteric CaSR modulation can rectify the loss-of-function Phe220Ser mutation and ameliorate the hypercalcemia associated with FHH2. (c) 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
  • Vainio, Annukka; Varho, Vilja; Tapio, Petri; Pulkka, Anna; Paloniemi, Riikka (2019)
    Achieving a sustainable energy transition is crucial for mitigating climate change. Citizens' acceptance of the transition is important for it to succeed. We explored citizens' images of the future energy forms and energy system in Finland, and the drivers of a sustainable energy transition. The data gathered with an online questionnaire targeting an adult population 17–75 years of age (N = 1012) were analysed with exploratory factor analysis and multiple linear regression. Four dimensions of future energy forms were identified: next-generation renewables, fossil energy, bioenergy, and established renewable vs. nuclear energy. Four dimensions of the future energy system were also identified: renewing the energy market, domestic power, small-scale producers, and consumer awareness. Five transition drivers were likewise identified: mainstreaming renewable energy, international actors, individual actions, changing values and economy, and emancipatory change. Mainstreaming renewable energy emerged as the key driver of transition, followed by individual actions. Generally, the sustainable energy transition was strongly supported by citizens' images, but different socio-economic groups preferred somewhat different images. Thus, the diversity of consumers' and citizens’ roles in the transition needs to be acknowledged and encouraged in legitimate national energy policies.
  • Multamäki, Elina; Nanekar, Rahul; Morozov, Dmitry; Lievonen, Topias; Golonka, David; Wahlgren, Weixiao Yuan; Stucki-Buchli, Brigitte; Rossi, Jari; Hytönen, Vesa P.; Westenhoff, Sebastian; Ihalainen, Janne A.; Möglich, Andreas; Takala, Heikki (2021)
    Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (Agp1). Whereas Agp1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While Agp1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes suggest the use of light-controllable histidine kinases and phosphatases for optogenetics. The bacteriophytochrome DrBphP from Deinococcus radiodurans shows high sequence homology to the histidine kinase Agp1 from Agrobacterium fabrum but lacks kinase activity. Here, the authors structurally and biochemically analyse DrBphP and Agp1, showing that DrBphP is a light-activatable phosphatase.
  • Abdullah; Henriquez, Claudia L.; Mehmood, Furrukh; Carlsen, Monica M.; Islam, Madiha; Waheed, Mohammad Tahir; Poczai, Peter; Croat, Thomas B.; Ahmed, Ibrar (2020)
    The subfamily Pothoideae belongs to the ecologically important plant family Araceae. Here, we report the chloroplast genomes of two species of the subfamily Pothoideae:Anthurium huixtlense(size: 163,116 bp) andPothos scandens(size: 164,719 bp). The chloroplast genome ofP. scandensshowed unique contraction and expansion of inverted repeats (IRs), thereby increasing the size of the large single-copy region (LSC: 102,956 bp) and decreasing the size of the small single-copy region (SSC: 6779 bp). This led to duplication of many single-copy genes due to transfer to IR regions from the small single-copy (SSC) region, whereas some duplicate genes became single copy due to transfer to large single-copy regions. The rate of evolution of protein-coding genes was affected by the contraction and expansion of IRs; we found higher mutation rates for genes that exist in single-copy regions as compared to those in IRs. We found a 2.3-fold increase of oligonucleotide repeats inP. scandenswhen compared withA. huixtlense, whereas amino acid frequency and codon usage revealed similarities. The ratio of transition to transversion mutations was 2.26 inP. scandensand 2.12 inA. huixtlense. Transversion mutations mostly translated in non-synonymous substitutions. The phylogenetic inference of the limited species showed the monophyly of the Araceae subfamilies. Our study provides insight into the molecular evolution of chloroplast genomes in the subfamily Pothoideae and family Araceae.
  • Lounela, Anu (2020)
    Climate change mitigation pilot projects (REDD+ - Reducing Emissions from Deforestation and forest Degradation) affect and interact with the local population in Central Kalimantan and many other parts of Indonesia. Rather than being politically and economically neutral activities, climate change mitigation projects tend to objectify the value of carbon, land and labour, contributing to a process of commodification of nature and social relations. In this specific case study, a set of values - equality and autonomy - central to the Ngaju people, the indigenous population in Central Kalimantan, become contested in the course of the climate change mitigation project. These central values are produced in everyday activities that include mobility and the productive base - subsistence and market-based production - among the Ngaju people. On the other hand, the climate change mitigation project-related environmental practices and actions produce values that point to individual (material) benefit and stratification of the society. The aim of the paper is to draw attention to and create understanding of value production and related tensions in the efforts to 'fix' environmental degradation problems through the climate change mitigation pilot project in Central Kalimantan.
  • Pettersson, Maria; Viljakainen, Heli; Loid, Petra; Mustila, Taina; Pekkinen, Minna; Armenio, Miriam; Andersson-Assarsson, Johanna C.; Makitie, Outi; Lindstrand, Anna (2017)
    Context: Only a few genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and nonsyndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center. Participants: CNV analysis was performed on 90 subjects with early-onset obesity and 67 normalweight controls. Subcutaneous adipose tissue from body mass index-discordant siblings was used for the gene expression analyses. Main Outcome Measures: We used custom high-density array comparative genomic hybridization with exon resolution in 1989 genes, including all known obesity loci. The expression of candidate genes was assessed using microarray analysis of messenger RNA from subcutaneous adipose tissue. Results: We identified rare CNVs in 17 subjects (19%) with obesity and 2 controls (3%). In three cases (3%), the identified variant involved a known syndromic lesion (22q11.21 duplication, 1q21.1 deletion, and 16p11.2 deletion, respectively), although the others were not known. Seven CNVs in 10 families were inherited and segregated with obesity. Expression analysis of 37 candidate genes showed discordant expression for 10 genes (PCM1, EFEMP1, MAMLD1, ACP6, BAZ2B, SORBS1, KLF15, MACROD2, ATR, and MBD5). Conclusions: Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.
  • Grunewald, M.; Kumar, S.; Sharife, H.; Volinsky, E.; Gileles-Hillel, A.; Licht, T.; Permyakova, A.; Hinden, L.; Azar, S.; Friedmann, Y.; Kupetz, P.; Tzuberi, R.; Anisimov, A.; Alitalo, K.; Horwitz, M.; Leebhoff, S.; Khoma, O. Z.; Hlushchuk, R.; Djonov, Valentin G; Abramovitch, R.; Tam, J.; Keshet, E. (2021)
    Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.
  • Savilammi, Tiina; Papakostas, Spiros; Leder, Erica H.; Vollestad, L. Asbjorn; Debes, Paul V.; Primmer, Craig R. (2021)
    Temperature is a key environmental parameter affecting both the phenotypes and distributions of organisms, particularly ectotherms. Rapid organismal responses to thermal environmental changes have been described for several ectotherms; however, the underlying molecular mechanisms often remain unclear. Here, we studied whole genome cytosine methylation patterns of European grayling (Thymallus thymallus) embryos from five populations with contemporary adaptations of early life history traits at either 'colder' or 'warmer' spawning grounds. We reared fish embryos in a common garden experiment using two temperatures that resembled the 'colder' and 'warmer' conditions of the natal natural environments. Genome-wide methylation patterns were similar in populations originating from colder thermal origin subpopulations, whereas single nucleotide polymorphisms uncovered from the same data identified strong population structure among isolated populations, but limited structure among interconnected populations. This was surprising because the previously studied gene expression response among populations was mostly plastic, and mainly influenced by the developmental temperature. These findings support the hypothesis of the magnified role of epigenetic mechanisms in modulating plasticity. The abundance of consistently changing methylation loci between two warmer-to-colder thermal origin population pairs suggests that local adaptation has shaped the observed methylation patterns. The dynamic nature of the methylomes was further highlighted by genome-wide and site-specific plastic responses. Our findings support both the presence of a plastic response in a subset of CpG loci, and the evolutionary role of methylation divergence between populations adapting to contrasting thermal environments.
  • Deptula, Paulina; Laine, Pia K.; Roberts, Richard J.; Smolander, Olli-Pekka; Vihinen, Helena; Piironen, Vieno; Paulin, Lars; Jokitalo, Eija; Savijoki, Kirsi; Auvinen, Petri; Varmanen, Pekka (2017)
    Background: Propionibacterium freudenreichii is an industrially important bacterium granted the Generally Recognized as Safe (the GRAS) status, due to its long safe use in food bioprocesses. Despite the recognized role in the food industry and in the production of vitamin B12, as well as its documented health-promoting potential, P. freudenreichii remained poorly characterised at the genomic level. At present, only three complete genome sequences are available for the species. Results: We used the PacBio RS II sequencing platform to generate complete genomes of 20 P. freudenreichii strains and compared them in detail. Comparative analyses revealed both sequence conservation and genome organisational diversity among the strains. Assembly from long reads resulted in the discovery of additional circular elements: two putative conjugative plasmids and three active, lysogenic bacteriophages. It also permitted characterisation of the CRISPR-Cas systems. The use of the PacBio sequencing platform allowed identification of DNA modifications, which in turn allowed characterisation of the restriction-modification systems together with their recognition motifs. The observed genomic differences suggested strain variation in surface piliation and specific mucus binding, which were validated by experimental studies. The phenotypic characterisation displayed large diversity between the strains in ability to utilise a range of carbohydrates, to grow at unfavourable conditions and to form a biofilm. Conclusion: The complete genome sequencing allowed detailed characterisation of the industrially important species, P. freudenreichii by facilitating the discovery of previously unknown features. The results presented here lay a solid foundation for future genetic and functional genomic investigations of this actinobacterial species.
  • Tuomikoski, Pauliina; Salomaa, Veikko; Havulinna, Aki; Airaksinen, Juhani; Ketonen, Matti; Koukkunen, Heli; Ukkola, Olavi; Kesaniemi, Y. Antero; Lyytinen, Heli; Ylikorkala, Olavi; Mikkola, Tomi S. (2016)
    Objectives: The role of postmenopausal hormone therapy (HT) in the incidence of acute coronary syndrome (ACS) has been studied extensively, but less is known of the impact of HT on the mortality risk due to an ACS. Study design and main outcome measures: We extracted from a population-based ACS register, FINAMI, 7258 postmenopausal women with the first ACS. These data were combined with HT use data from the National Drug Reimbursement Register; 625 patients (9%) had used various HT regimens. The death risks due to ACS before admission to hospital, 2-28, or 29-365 days after the incident ACS were compared between HT users and non-users with logistic regression analyses. Results: In all follow-up time points, the ACS death risks in HT ever-users were smaller compared to non-users. Of women with FIT ever use, 42% died within one year as compared with 52% of non-users (OR 0.62, p <0.001). Most deaths (84%) occurred within 28 days after the ACS, and in this group 36% of women with ever use of FIT (OR 0.73, p = 0.002) and 30% of women with >= 5 year FIT use (OR 0.54, p <0.001) died as compared to 43% of the non-users. Age 60 years at the HT initiation was accompanied with similar reductions in ACS mortality risk. Conclusions: Postmenopausal HT use is accompanied with reduced mortality risk after primary ACS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie; Hur, Yoon-Mi; Cozen, Wendy; Hwang, Amie E.; Mack, Thomas M.; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Tomizawa, Rie; Pietilainen, Kirsi H.; Rissanen, Aila; Siribaddana, Sisira H.; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Piirtola, Maarit; Aaltonen, Sari; Oncel, Sevgi Y.; Aliev, Fazil; Rebato, Esther; Hjelmborg, Jacob B.; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O.; Silberg, Judy L.; Eaves, Lindon J.; Cutler, Tessa L.; Ordonana, Juan R.; Sanchez-Romera, Juan F.; Colodro-Conde, Lucia; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E.; Kremen, William S.; Lyons, Michael J.; Busjahn, Andreas; Nelson, Tracy L.; Whitfield, Keith E.; Kandler, Christian; Jang, Kerry L.; Gatz, Margaret; Butler, David A.; Stazi, Maria A.; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E.; Buchwald, Dedra; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Jeong, Hoe-Uk; Swan, Gary E.; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L.; Aslan, Anna K. Dahl; McAdams, Tom A.; Eley, Thalia C.; Gregory, Alice M.; Tynelius, Per; Baker, Laura A.; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Spector, Timothy D.; Mangino, Massimo; Lachance, Genevieve; Burt, S. Alexandra; Klump, Kelly L.; Harris, Jennifer R.; Brandt, Ingunn; Nilsen, Thomas S.; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Corley, Robin P.; Huibregtse, Brooke M.; Bartels, Meike; van Beijsterveldt, Catharina E. M.; Willemsen, Gonneke; Goldberg, Jack H.; Rasmussen, Finn; Tarnoki, Adam D.; Tarnoki, David L.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Hopper, John L.; Sung, Joohon; Maes, Hermine H.; Turkheimer, Eric; Boomsma, Dorret I.; Sorensen, Thorkild I. A.; Kaprio, Jaakko (2017)
    Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m(2))], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins >= 20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 2029 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.