Browsing by Subject "WEB SERVER"

Sort by: Order: Results:

Now showing items 1-5 of 5
  • Popin, Rafael Vicentini; Delbaje, Endrews; de Abreu, Vinicius Augusto Carvalho; Rigonato, Janaina; Dorr, Felipe Augusto; Pinto, Ernani; Sivonen, Kaarina; Fiore, Marli Fatima (2020)
    The bloom-forming cyanobacterium Nodularia spumigena CENA596 encodes the biosynthetic gene clusters (BGCs) of the known natural products nodularins, spumigins, anabaenopeptins/namalides, aeruginosins, mycosporin-like amino acids, and scytonemin, along with the terpenoid geosmin. Targeted metabolomics confirmed the production of these metabolic compounds, except for the alkaloid scytonemin. Genome mining of N. spumigena CENA596 and its three closely related Nodularia strains-two planktonic strains from the Baltic Sea and one benthic strain from Japanese marine sediment-revealed that the number of BGCs in planktonic strains was higher than in benthic one. Geosmin-a volatile compound with unpleasant taste and odor-was unique to the Brazilian strain CENA596. Automatic annotation of the genomes using subsystems technology revealed a related number of coding sequences and functional roles. Orthologs from the Nodularia genomes are involved in the primary and secondary metabolisms. Phylogenomic analysis of N. spumigena CENA596 based on 120 conserved protein sequences positioned this strain close to the Baltic Nodularia. Phylogeny of the 16S rRNA genes separated the Brazilian CENA596 strain from those of the Baltic Sea, despite their high sequence identities (99% identity, 100% coverage). The comparative analysis among planktic Nodularia strains showed that their genomes were considerably similar despite their geographically distant origin.
  • Kaasinen, Eevi; Kuismin, Outi; Rajamäki, Kristiina; Ristolainen, Heikki; Aavikko, Mervi; Kondelin, Johanna; Saarinen, Silva; Berta, Davide G.; Katainen, Riku; Hirvonen, Elina A. M.; Karhu, Auli; Taira, Aurora; Tanskanen, Tomas; Alkodsi, Amjad; Taipale, Minna; Morgunova, Ekaterina; Franssila, Kaarle; Lehtonen, Rainer; Mäkinen, Markus; Aittomäki, Kristiina; Palotie, Aarno; Kurki, Mitja; Pietiläinen, Olli; Hilpert, Morgane; Saarentaus, Elmo; Niinimäki, Jaakko; Junttila, Juhani; Kaikkonen, Kari; Vahteristo, Pia; Skoda, Radek C.; Seppänen, Mikko R. J.; Eklund, Kari K.; Taipale, Jussi; Kilpivaara, Outi; Aaltonen, Lauri A. (2019)
    Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
  • Ravikumar, Balaguru; Aittokallio, Tero (2018)
    Introduction: Polypharmacology has emerged as an essential paradigm for modern drug discovery process. Multiple lines of evidence suggest that agents capable of modulating multiple targets in a selective manner may offer also improved balance between therapeutic efficacy and safety compared to single-targeted agents. Areas covered: Herein, the authors review the recent progress made in experimental and computational strategies for addressing the critical challenges with rational discovery of selective multi-targeted agents within the context of polypharmacological modelling. Specific focus is placed on multi-targeted mono-therapies, although examples of combinatorial polytherapies are also covered as an important part of the polypharmacology paradigm. The authors focus mainly on anti-cancer treatment applications, where polypharmacology is playing a key role in determining the efficacy-toxicity trade-off of multi-targeting strategies. Expert opinion: Even though it is widely appreciated that complex polypharmacological interactions can contribute both to therapeutic and adverse side-effects, systematic approaches for improving this balance by means of integrated experimental-computational strategies are still lacking. Future developments will be needed for comprehensive collection and harmonization of systems-wide target selectivity data, enabling better utilization and control for multi-targeted activities in the drug development process. Additional areas of future developments include model-based strategies for drug combination screening and improved pre-clinical validation options with animal models.
  • Zwir, Igor; Arnedo, Javier; Del-Val, Coral; Pulkki-Råback, Laura; Konte, Bettina; Yang, Sarah S.; Romero-Zaliz, Rocio; Hintsanen, Mirka; Cloninger, Kevin M.; Garcia, Danilo; Svrakic, Dragan M.; Rozsa, Sandor; Martinez, Maribel; Lyytikäinen, Leo-Pekka; Giegling, Ina; Kähönen, Mika; Hernandez-Cuervo, Helena; Seppälä, Ilkka; Raitoharju, Emma; de Erausquin, Gabriel A.; Raitakari, Olli; Rujescu, Dan; Postolache, Teodor T.; Sung, Joohon; Keltikangas-Jarvinen, Liisa; Lehtimäki, Terho; Cloninger, C. Robert (2020)
    Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five clusters of people with distinct profiles of character traits regardless of genotype. Third, we found 42 SNP sets that identified 727 gene loci and were significantly associated with one or more of the character profiles. Each character profile was related to different SNP sets with distinct molecular processes and neuronal functions. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of 95% of the 42 SNP sets in healthy Korean and German samples, as well as their associations with character. The identified SNPs explained nearly all the heritability expected for character in each sample (50 to 58%). We conclude that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes despite variable cultures and environments. These gene sets modulate specific molecular processes in brain for intentional goal-setting, self-reflection, empathy, and episodic learning and memory.
  • Zwir, Igor; Arnedo, Javier; Del-Val, Coral; Pulkki-Raback, Laura; Konte, Bettina; Yang, Sarah S.; Romero-Zaliz, Rocio; Hintsanen, Mirka; Cloninger, Kevin M.; Garcia, Danilo; Svrakic, Dragan M.; Rozsa, Sandor; Martinez, Maribel; Lyytikäinen, Leo-Pekka; Giegling, Ina; Kähönen, Mika; Hernandez-Cuervo, Helena; Seppälä, Ilkka; Raitoharju, Emma; de Erausquin, Gabriel A.; Raitakari, Olli; Rujescu, Dan; Postolache, Teodor T.; Sung, Joohon; Keltikangas-Jarvinen, Liisa; Lehtimäki, Terho; Cloninger, C. Robert (2020)
    Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.