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.
  • 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.
  • 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.
  • 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.
  • Kekkonen, Mari; Hebert, Paul D. N. (2014)
    The analysis of DNA barcode sequences with varying techniques for cluster recognition provides an efficient approach for recognizing putative species (operational taxonomic units, OTUs). This approach accelerates and improves taxonomic workflows by exposing cryptic species and decreasing the risk of synonymy. This study tested the congruence of OTUs resulting from the application of three analytical methods (ABGD, BIN, GMYC) to sequence data for Australian hypertrophine moths. OTUs supported by all three approaches were viewed as robust, but 20% of the OTUs were only recognized by one or two of the methods. These OTUs were examined for three criteria to clarify their status. Monophyly and diagnostic nucleotides were both uninformative, but information on ranges was useful as sympatric sister OTUs were viewed as distinct, while allopatric OTUs were merged. This approach revealed 124 OTUs of Hypertrophinae, a more than twofold increase from the currently recognized 51 species. Because this analytical protocol is both fast and repeatable, it provides a valuable tool for establishing a basic understanding of species boundaries that can be validated with subsequent studies.
  • Saha, Shreya; Hafren, Anders; Makinen, Kristiina (2019)
    One large open reading frame (ORF) encodes 10 potyviral proteins. We compared the accumulation of cylindrical inclusion (CI) protein from the middle, coat protein (CP) from the 3'end, and Renilla luciferase (RLUC) from two distinct locations in potato virus A (PVA) RNA. 5' RLUC was expressed from an rluc gene inserted between the P1 and helper component proteinase (HCPro) cistrons, and 3' RLUC was expressed from the gene inserted between the RNA polymerase and CP cistrons. Viral protein and RNA accumulation were quantitated (i) when expressed from PVA RNA in the presence of ectopically expressed genome-linked viral protein (VPg) and auxiliary proteins and (ii) at different time points during natural infection. The rate and timing of 3' RLUC and CP accumulation were found to be different from those of 5' RLUC and Cl. Ectopic expression of VPg boosted PVA RNA, 3' RLUC, and, together with HCPro, CP accumulation, whereas 5' RLUC and CI accumulation remained unaffected regardless of the increased viral RNA amount. In natural infection, the rate of the noteworthy minute early accumulation of 3' RLUC accelerated toward the end of infection. 5' RLUC accumulation, which was already pronounced at 2 days postinfection, increased moderately and stabilized to a constant level by day 5, whereas PVA RNA and CP levels continued to increase throughout the infection. We propose that these observations connect with the mechanisms by which potyvirus infection limits CP accumulation during early infection and specifically supports its accumulation late in infection, but follow-up studies are required to understand the mechanism of how this occurs. IMPORTANCE The results of this study suggest that the dynamics of potyviral protein accumulation are regulated differentially from the 3' end of viral RNA than from the rest of the genome, the significance of which would be to satisfy the needs of replication early and particle assembly late in infection.
  • Alonso Serra, Juan Antonio; Shi, Xueping; Peaucelle, Alexis; Rastas, Pasi; Bourdon, Matthieu; Immanen, Juha; Takahashi, Junko; Koivula, Hanna; Eswaran, Gugan; Muranen, Sampo Johannes; Help-Rinta-Rahko, Hanna; Smolander, Olli-Pekka; Su, Chang; Safronov, Omid; Gerber, Lorenz; Salojärvi, Jarkko; Hagqvist, Risto; Mähönen, Ari Pekka; Helariutta, Yrjö; Nieminen, Kaisa (2020)
    Tree architecture has evolved to support a top-heavy above-ground biomass, but this integral feature poses a weight-induced challenge to trunk stability. Maintaining an upright stem is expected to require vertical proprioception through feedback between sensing stem weight and responding with radial growth. Despite its apparent importance, the principle by which plant stems respond to vertical loading forces remains largely unknown. Here, by manipulating the stem weight of downy birch (Betula pubescens) trees, we show that cambial development is modulated systemically along the stem. We carried out a genetic study on the underlying regulation by combining an accelerated birch flowering program with a recessive mutation at the ELIMAKI locus (EKI), which causes a mechanically defective response to weight stimulus resulting in stem collapse after just 3 months. We observed delayed wood morphogenesis in eki compared with WT, along with a more mechanically elastic cambial zone and radial compression of xylem cell size, indicating that rapid tissue differentiation is critical for cambial growth under mechanical stress. Furthermore, the touch-induced mechanosensory pathway was transcriptionally misregulated in eki, indicating that the ELIMAKI locus is required to integrate the weight-growth feedback regulation. By studying this birch mutant, we were able to dissect vertical proprioception from the gravitropic response associated with reaction wood formation. Our study provides evidence for both local and systemic responses to mechanical stimuli during secondary plant development.
  • Quach, Bryan C.; Bray, Michael J.; Gaddis, Nathan C.; Liu, Mengzhen; Palviainen, Teemu; Minica, Camelia C.; Zellers, Stephanie; Sherva, Richard; Aliev, Fazil; Nothnagel, Michael; Young, Kendra A.; Marks, Jesse A.; Young, Hannah; Carnes, Megan U.; Guo, Yuelong; Waldrop, Alex; Sey, Nancy Y. A.; Landi, Maria T.; McNeil, Daniel W.; Drichel, Dmitriy; Farrer, Lindsay A.; Markunas, Christina A.; Vink, Jacqueline M.; Hottenga, Jouke-Jan; Iacono, William G.; Kranzler, Henry R.; Saccone, Nancy L.; Neale, Michael C.; Madden, Pamela; Rietschel, Marcella; Marazita, Mary L.; McGue, Matthew; Won, Hyejung; Winterer, Georg; Grucza, Richard; Dick, Danielle M.; Gelernter, Joel; Caporaso, Neil E.; Baker, Timothy B.; Boomsma, Dorret I.; Kaprio, Jaakko; Hokanson, John E.; Vrieze, Scott; Bierut, Laura J.; Johnson, Eric O.; Hancock, Dana B. (2020)
    Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerstrom Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N=33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r(g)=0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking. There is strong genetic evidence for cigarette smoking behaviors, yet little is known on nicotine dependence (ND). Here, the authors perform a genome-wide association study on ND in 58,000 smokers, identifying five genome-wide significant loci.
  • Smits, Dins; Brigis, Girts; Pavare, Jana; Urtane, Inga; Kovalovs, Sandis; Barengo, Noel Christopher (2020)
    Background The problem of nonadherence to therapy is a key reason of insufficient asthma control. Evaluating the beliefs about asthma medication, cognitive and emotional perceptions may help to identify patients with poor adherence to treatment in clinical practice which need additional attention in order to increase the likelihood of them taking their asthma medication according to the prescribed treatment protocol. The purpose of this study is to assess whether beliefs about asthma medication, cognitive and emotional factors are related to poor treatment adherence of asthma medication in a sample of asthma patients in Latvia. Methods Study subjects were asthma patients attending outpatient pulmonologist consultations in Latvia during September 2013 to December 2015. Beliefs about asthma medicine, cognitive and emotional factors related to asthma were determined in a cross-sectional, self-administered survey. The validated Beliefs about Medicines Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Treatment adherence was assessed using 5-item version of the Medication Adherence Reporting Scale (MARS). The total sample size was 352 patients. Logistic regression models were used to predict poor adherence to asthma treatment. The validity of each logistic regression model was assessed by the Hosmer/Lemeshow test. The main outcome measure was self-reported adherence to treatment. Results The more the patients agreed with the statement "My future health depends on my asthma medication" the lower the possibility of poor adherence to asthma treatment (OR 0.42; 95% CI 0.24-0.74). The more concerned the patients were in regard to long-term effects of their medication (OR 2; 95% CI 1.22-3.27), the higher the probability of poor treatment adherence. Conclusions Screening asthma patients using the BMQ may help to identify those to benefit from interventions targeting their concerns and medication beliefs in order to improve adherence to asthma medication.