Browsing by Subject "TRANSFORMATION"

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  • Bieron, Jacek; Filippin, Livio; Gaigalas, Gediminas; Godefroid, Michel; Jönsson, Per; Pyykkö, Pekka (2018)
    The relativistic multiconfiguration Dirac-Hartree-Fock and the nonrelativistic multiconfiguration Hartree-Fock methods have been employed to calculate the magnetic dipole and electric quadrupole hyperfine structure constants of zinc. The calculated electric field gradients for the 4s4p P-3(1)degrees and 4s4p P-3(2)degrees states, together with experimental values of the electric quadrupole hyperfine structure constants, made it possible to extract a nuclear electric quadrupole moment Q((67) Zn) = 0.122(10) b. The error bar was evaluated in a quasistatistical approach-the calculations were carried out with 11 different methods, and then the error bar was estimated from the differences between the results obtained with those methods.
  • Simola, Umberto; Cisewski-Kehe, Jessi; Gutmann, Michael U.; Corander, Jukka (2021)
    Approximate Bayesian Computation (ABC) methods are increasingly used for inference in situations in which the likelihood function is either computationally costly or intractable to evaluate. Extensions of the basic ABC rejection algorithm have improved the computational efficiency of the procedure and broadened its applicability. The ABC - Population Monte Carlo (ABC-PMC) approach has become a popular choice for approximate sampling from the posterior. ABC-PMC is a sequential sampler with an iteratively decreasing value of the tolerance, which specifies how close the simulated data need to be to the real data for acceptance. We propose a method for adaptively selecting a sequence of tolerances that improves the computational efficiency of the algorithm over other common techniques. In addition we define a stopping rule as a by-product of the adaptation procedure, which assists in automating termination of sampling. The proposed automatic ABC-PMC algorithm can be easily implemented and we present several examples demonstrating its benefits in terms of computational efficiency.
  • Randall, Ricardo S.; Miyashima, Shunsuke; Blomster, Tiina; Zhang, Jing; Elo, Annakaisa; Karlberg, Anna; Immanen, Juha; Nieminen, Kaisa; Lee, Ji-Young; Kakimoto, Tatsuo; Blajecka, Karolina; Melnyk, Charles W.; Alcasabas, Annette; Forzani, Celine; Matsumoto-Kitano, Miho; Mähönen, Ari Pekka; Bhalerao, Rishikesh; Dewitte, Walter; Helariutta, Yrjö; Murray, James A. H. (2015)
    Higher plant vasculature is characterized by two distinct developmental phases. Initially, a well-defined radial primary pattern is established. In eudicots, this is followed by secondary growth, which involves development of the cambium and is required for efficient water and nutrient transport and wood formation. Regulation of secondary growth involves several phytohormones, and cytokinins have been implicated as key players, particularly in the activation of cell proliferation, but the molecular mechanisms mediating this hormonal control remain unknown. Here we show that the genes encoding the transcription factor AINTEGUMENTA (ANT) and the D-type cyclin CYCD3;1 are expressed in the vascular cambium of Arabidopsis roots, respond to cytokinins and are both required for proper root secondary thickening. Cytokinin regulation of ANT and CYCD3 also occurs during secondary thickening of poplar stems, suggesting this represents a conserved regulatory mechanism.
  • Guo, Hui; Liu, Dongmei; Gao, Bin; Zhang, Xiaohui; You, Minli; Ren, Hui; Zhang, Hongbo; Almeida Santos, Helder; Xu, Feng (2016)
    Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.
  • Holmgren, Sara; D'amato, Dalia; Giurca, Alexandru (2020)
    This review article examines how social science literature co-produces various imaginaries of forest-based bioeconomy transformations and pathways for reaching desired ends. Based on an analysis of 59 research articles, we find that despite a growing number of social sciences studies on the forest-based bioeconomy, much of the research tends to replicate a bioeconomy imaginary articulated in EU and national bioeconomy policies and strategies. Accordingly, the research primarily reproduces a weak approach to sustainability, which prioritize economic growth and competitiveness. Expectations are largely directed at national and regional corporate interests and forest industrial renewal, while the state has a supportive rather than restricting role. We discuss the findings against the role of social sciences, and conclude that social science scholars may adopt various strategies if interested in opening up forest-based policy debates and offer alternative imaginaries of sustainable bioeconomy transformations.
  • Ma, Hao; Zhou, Bo; Li, Yiqun; Argyropoulos, Dimitris S. (2012)
  • Mkrtchyan, Satenik; Jakubczyk, Michal; Lanka, Suneel; Pittelkow, Michael; Iaroshenko, Viktor O. (2021)
    We describe a mechanism-guided discovery of a synthetic methodology that enables the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides utilizing a copper-catalyzed direct arylation. Readily available and structurally simple aryl precursors such as aryl boronic acids, aryl trialkoxysilanes and dimethyl-aryl-sulfonium salts were used as the source for the aryl substituents. The scope of the reactions was tested, and the reactions were insensitive to the electronic nature of the aryl groups, as both electron-rich and electron-deficient aryls were successfully introduced. A wide range of 2-bromo-2,2-difluoroacetamides as either aliphatic or aromatic secondary or tertiary amides were also reactive under the developed conditions. The described synthetic protocols displayed excellent efficiency and were successfully utilized for the expeditious preparation of diverse aromatic amides in good-to-excellent yields. The reactions were scaled up to gram quantities.
  • Butler, Don H.; Koivisto, Satu Mirjami; Brumfeld, Vlad; Shahack-Gross, Ruth (2019)
    Salmonid resources currently foster socioeconomic prosperity in several nations, yet their importance to many ancient circumpolar societies is poorly understood due to insufficient fish bone preservation at archaeological sites. As a result, there are serious gaps in our knowledge concerning the antiquity of northern salmonid fisheries and their impacts on shaping biodiversity, hunter-gatherer adaptations, and human-ecological networks. The interdisciplinary study presented here demonstrates that calcium-magnesium phosphate minerals formed in burned salmonid bones can preserve at ancient northern sites, thus informing on the early utilization of these resources despite the absence of morphologically classifiable bones. The minerals whitlockite and beta magnesium tricalcium phosphate were identified in rare morphologically classifiable Atlantic salmonid bones from three Mid-Holocene sites in Finland. Large amounts of beta magnesium tricalcium phosphate were also experimentally formed by burning modern Atlantic salmonid and brown trout bones. Our results demonstrate the value of these minerals as proxies for ancient northern salmonid fishing. Specifically, the whitlockite mineral was discovered in hearth sediments from the 5,600 year old Yli-Ii Kierikinkangas site on the Iijoki River in northern Finland. Our fine sieving and mineralogical analyses of these sediments, along with zooarchaeological identification of recovered bone fragments, have confirmed for the first time that the people living at this village did incorporate salmonids into their economies, thus providing new evidence for early estuary/riverine fisheries in northern Finland.
  • Iesce, Maria Rosaria; Lavorgna, Margherita; Russo, Chiara; Piscitelli, Concetta; Passananti, Monica; Temussi, Fabio; DellaGreca, Marina; Cermola, Flavio; Isidori, Marina (2019)
    Loratadine and desloratadine are second-generation antihistaminic drugs. Because of human administration, they are continuously released via excreta into wastewater treatment plants and occur in surface waters as residues and transformation products (TPs). Loratadine and desloratadine residues have been found at very low concentrations (ng/L) in the aquatic environment but their toxic effects are still not well known. Both drugs are light-sensitive even under environmentally simulated conditions and some of the photoproducts have been isolated and characterized. The aim of the present study was to investigate the acute and chronic ecotoxicity of loratadine, desloratadine and their light-induced transformation products in organisms of the aquatic trophic chain. Bioassays were performed in the alga Pseudokirchneriella subcapitata, the rotifer Brachionus calyciflorus and in two crustaceans, Thamnocephalus platyurus and Ceriodaphnia dubia. Loratadine exerted its acute and chronic toxicity especially on Ceriodaphnia dubia (LC50: 600 mu g/L, EC50: 28.14 mu g/L) while desloratadine showed similar acute toxicity among the organisms tested and it was the most chronically effective compound in Ceriodaphnia dubia and Pseudokirchneriella subcapitata. Generally, transformation products were less active in both acute and chronic assays.
  • Zhu, Duolong; Fu, Yuxin; Liu, Fulu; Xu, Haijin; Saris, Per Erik Joakim; Qiao, Mingqiang (2017)
    Background: The implementation of novel chassis organisms to be used as microbial cell factories in industrial applications is an intensive research field. Lactococcus lactis, which is one of the most extensively studied model organisms, exhibits superior ability to be used as engineered host for fermentation of desirable products. However, few studies have reported about genome reduction of L. lactis as a clean background for functional genomic studies and a model chassis for desirable product fermentation. Results: Four large nonessential DNA regions accounting for 2.83% in L. lactis NZ9000 (L. lactis 9 k) genome (2,530,294 bp) were deleted using the Cre-loxP deletion system as the first steps toward a minimized genome in this study. The mutants were compared with the parental strain in several physiological traits and evaluated as microbial cell factories for heterologous protein production (intracellular and secretory expression) with the red fluorescent protein (RFP) and the bacteriocin leucocin C (LecC) as reporters. The four mutants grew faster, yielded enhanced biomass, achieved increased adenosine triphosphate content, and diminished maintenance demands compared with the wild strain in the two media tested. In particular, L. lactis 9 k-4 with the largest deletion was identified as the optimum candidate host for recombinant protein production. With nisin induction, not only the transcriptional efficiency but also the production levels of the expressed reporters were approximately three-to fourfold improved compared with the wild strain. The expression of lecC gene controlled with strong constitutive promoters P5 and P8 in L. lactis 9 k-4 was also improved significantly. Conclusions: The genome-streamlined L. lactis 9 k-4 outcompeted the parental strain in several physiological traits assessed. Moreover, L. lactis 9 k-4 exhibited good properties as platform organism for protein production. In future works, the genome of L. lactis will be maximally reduced by using our specific design to provide an even more clean background for functional genomics studies than L. lactis 9 k-4 constructed in this study. Furthermore, an improved background will be potentially available for use in biotechology.
  • Arnold, Brian; Sohail, Mashaal; Wadsworth, Crista; Corander, Jukka; Hanage, William P.; Sunyaev, Shamil; Grad, Yonatan H. (2020)
    Identifying genetic variation in bacteria that has been shaped by ecological differences remains an important challenge. For recombining bacteria, the sign and strength of linkage provide a unique lens into ongoing selection. We show that derived alleles
  • Heinonen, Hanna-Riikka; Mehine, Miika; Mäkinen, Netta; Pasanen, Annukka; Pitkänen, Esa; Karhu, Auli; Sarvilinna, Nanna S.; Sjöberg, Jari; Heikinheimo, Oskari; Bützow, Ralf; Aaltonen, Lauri A.; Kaasinen, Eevi (2017)
    Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.
  • Nieminen, Jenni; Salomaa, Anna; Juhola, Sirkku (2021)
    There is an increasing need for urban sustainability transitions, though empirical cases that focus on the governance of these processes over time are not plentiful. This study addresses that gap by examining the governance of an urban transition in an eco-neighbourhood in Helsinki, using the framework of a multi-level perspective on socio-technical transitions and modes of governance. This study shows how the modes of governance have changed from the start of the planning in 1994-2018 and how the different dimensions of the urban planning regime have enabled or constrained a sustainability transition, based on a document analysis and semi-structured expert interviews. As for the modes of governance, hierarchical and network were most widely used. The plot assignment stipulations that contained sustainability requirements, as well as the collaborative area working group method, have been scaled up city-wide since. This study concludes that more process-focussed policy instruments are needed.
  • Tvingsholm, Siri Amanda; Hansen, Malene Bredahl; Clemmensen, Knut Kristoffer Bundgaard; Brix, Ditte Marie; Rafn, Bo; Frankel, Lisa B.; Louhimo, Riku; Moreira, Jose; Hautaniemi, Sampsa; Gromova, Irina; Jäättelä, Marja; Kallunki, Tuula (2018)
    Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. Analysis of primary breast cancer tissues reveals a gradual upregulation of MZF1 from normal breast epithelium to invasive ductal carcinoma and a negative correlation between several let-7 family members and MZF1 mRNA, suggesting that the inverse regulatory relationship between let-7 and MZF1 may play a role in the development of invasive breast cancer. Furthermore, we show that MZF1 regulates lysosome trafficking in ErbB2-positive breast cancer cells. In line with this, MZF1 depletion or let-7 expression inhibits invasion-promoting anterograde trafficking of lysosomes and invasion of ErbB2-expressing MCF7 spheres. The results presented here link MZF1 and let-7 to lysosomal processes in ErbB2-positive breast cancer cells that in non-cancerous cells have primarily been connected to the transcription factor EB. Identifying MZF1 and let-7 as regulators of lysosome distribution in invasive breast cancer cells, uncouples cancer-associated, invasion-promoting lysosomal alterations from normal lysosomal functions and thus opens up new possibilities for the therapeutic targeting of cancer lysosomes.
  • Rämö, Olli; Kumar, Darshan; Gucciardo, Erika; Joensuu, Merja; Saarekas, Maiju; Vihinen, Helena; Belevich, Ilya; Smolander, Olli-Pekka; Qian, Kui; Auvinen, Petri; Jokitalo, Eija (2016)
    Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets.
  • Liu, Fulu; Zhang, Yating; Qiao, Wanjin; Zhu, Duolong; Xu, Haijin; Saris, Per Erik Joakim; Qiao, Mingqiang (2019)
    Background After 2.83% genome reduction in Lactococcus lactis NZ9000, a good candidate host for proteins production was obtained in our previous work. However, the gene deletion process was time consuming and laborious. Here, we proposed a convenient gene deletion method suitable for large-scale genome reduction in L. lactis NZ9000. Results Plasmid pNZ5417 containing a visually selectable marker P-nisZ-lacZ was constructed, which allowed more efficient and convenient screening of gene deletion mutants. Using this plasmid, two large nonessential DNA regions, L-4A and L-5A, accounting for 1.25% of the chromosome were deleted stepwise in L. lactis 9k-3. When compared with the parent strain, the mutant L. lactis 9k-5A showed better growth characteristics, transformability, carbon metabolic capacity, and amino acids biosynthesis. Conclusions Thus, this study provides a convenient and efficient system for large-scale genome deletion in L. lactis through application of visually selectable marker, which could be helpful for rapid genome streamlining and generation of restructured L. lactis strains that can be used as cell factories.
  • Chattopadhyay, Subhayan; Zheng, Guoqiao; Sud, Amit; Yu, Hongyao; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Houlston, Richard; Hemminki, Kari (2018)
    Background Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer-to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors. Methods Using the Swedish Family-Cancer Database, we identified 35 928 individuals with primary myeloid cancer, including myeloproliferative neoplasms, acute myeloid leukaemia, chronic myeloid leukaemia, and myelodysplastic syndrome diagnosed between 1958 and 2015. The Swedish Family-Cancer Database includes every individual registered as a resident in Sweden starting in 1932, with full parental history. The primary endpoint was the assessment of relative risks (RRs) for second primary cancer, which we performed using means of incidence rate ratios, regressed over a generalised Poisson model. Findings Between 1958 and 2015, overall relative risk of second primary cancers was significantly increased after acute myeloid leukaemia (RR 1.29, 95% CI 1.17-1.41), chronic myeloid leukaemia (1.52, 1.35-1.69), myelodysplastic syndrome (1.42, 1.26-1.59), and all myeloproliferative neoplasms (1.37, 1.30-1.43) relative to the incidence of these cancers as first primary cancer. With myeloid neoplasia as a second primary cancer, risks were significantly increased for acute myeloid leukaemia (1.57, 1.48-1.65), chronic myeloid leukaemia (1.26, 1.13-1.40), and myelodysplastic syndrome (1.54, 1.42-1.67) relative to the incidence of these myeloid neoplasms as first primary cancers. Relative risk of upper aerodigestive tract cancer, squamous cell skin cancer, and non-Hodgkin lymphoma as second primary cancers were increased after all four types of myeloid neoplasia relative to their incidence as first primary cancers. High risks of myelodysplastic syndrome and acute myeloid leukaemia as second primary cancers were found after haematological cancers (RRs between 5.08 and 10.04). Interpretation The relative risks of second primary cancer are important for the long-term management of patients with myeloid cancers. The bi-directional associations of myeloid cancers with many other cancers suggest a number of candidate mechanisms that might contribute to the development and aetiology of a second primary cancer. These mechanisms might include immune dysfunction or the effects of treatment, and these should be assessed in future investigations. Copyright (c) 2018 Elsevier Ltd. All rights reserved.
  • Awad, Shady Adnan; Dufva, Olli; Ianevski, Aleksandr; Ghimire, Bishwa; Koski, Jan; Maliniemi, Pilvi; Thomson, Daniel; Schreiber, Andreas; Heckman, Caroline A.; Koskenvesa, Perttu; Korhonen, Matti; Porkka, Kimmo; Branford, Susan; Aittokallio, Tero; Kankainen, Matti; Mustjoki, Satu (2021)
    Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations,RUNX1mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate thatPHF6andBCORL1mutations,IKZF1deletions, and AID/RAG-mediated rearrangements are enriched inRUNX1(mut)BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primaryRUNX1(mut)CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity ofRUNX1(mut)blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells fromRUNX1(mut)patients to be highly responsive for mTOR-, BCL2-, and VEGFR inhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygousRUNX1(-/-)and heterozygousRUNX1(-/mut)BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role ofRUNX1mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treatingRUNX1(mut)BP-CML patients.
  • D'amato, Dalia; Droste, Nils; Winkler, Klara; Toppinen, Anne (2019)
    The continuous emergence of new ideas and terms simultaneously enables and impedes the advancement of sustainability, because of an increasingly complex conceptual landscape. This study aims at highlighting combinations of sustainability concepts (circular, green and bioeconomy) and of development models (growth, steady-state, degrowth) which selected researchers have considered priorities for pursuing sustainability transformations. Thirteen leading scholars working on sustainability issues were asked to rank 36 statements describing activities related to either circular, green, bio, growth, steady-state or degrowth economy. Using Q methodology, an exploratory approach to the identification of shared or diverging opinions, three archetypical perspectives were identified across the respondents: 1. circular solutions towards economic-environmental decoupling in a degrowth perspective; 2. a mix of circular and green economy solutions; 3. a green economy perspective, with an emphasis on natural capital and ecosystem services, and critical towards growth. Economic growth was perceived negatively across all perspectives, in contrast to the current lack of political and societal support for degrowth ideas. Neither did bioeconomy-oriented activities have support among the participating researchers, even though half of the respondents were working with bioeconomy issues, which are currently high on the political agenda. The lack of support for pro-growth and bioeconomy solutions are unexpected results given the current political discourses. While the results are not to be generalised beyond the sample, they provide valuable orientation for emerging and under-investigated research and policy directions. If bioeconomy policies are to be implemented on a broader scale, it seems worthwhile evaluating the acceptability of the bioeconomy agenda among various societal actors. Furthermore, our results point to the (still under-explored) potential of formulating synergic circular, green and bioeconomy policies, possibly without a focus on economic growth.