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  • Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Kojima, Miki; Kubosaki, Atsutaka; Manabe, Ri-ichiroh; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A.; Babina, Magda; Baillie, J. Kenneth; Barnett, Timothy C.; Beckhouse, Anthony G.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J.; Clevers, Hans C.; Davis, Carrie A.; Detmar, Michael; Dohi, Taeko; Edge, Albert S. B.; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Ferrai, Carmelo; Fisher, Malcolm E.; Forrester, Lesley M.; Fujita, Rie; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gingeras, Thomas; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Hitchens, Kelly J.; Hume, David A.; Ikawa, Tomokatsu; Ishizu, Yuri; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klein, Sarah; Klinken, S. Peter; Knox, Alan J.; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Mackay-sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J.; Motohashi, Hozumi; Mummery, Christine L.; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W.; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M.; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G.; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O.; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R. R.; Hayashizaki, Yoshihide (Nature Publishing Group, 2017)
    In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
  • Yuan, Xiaojing; Liu, Huikun; Wang, Leishen; Zhang, Shuang; Zhang, Cuiping; Leng, Junhong; Dong, Ling; Lv, Li; Lv, Fengjun; Tian, Huiguang; Qi, Lu; Tuomilehto, Jaakko; Hu, Gang (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2016)
    Aims: We aimed to examine the association of gestational hypertension and chronic hypertension at the inter-conception examination with type 2 diabetes risk among women with a history of gestational diabetes. Methods: We conducted a population-based study among 1261 women who had a history of gestational diabetes at 1-5 years after delivery in Tianjin, China. Logistic regression or Cox regression was used to assess the associations of gestational hypertension and chronic hypertension at the inter-conception examination with pre-diabetes and type 2 diabetes risks. Results: Gestational diabetic women who had a history of gestational hypertension but did not use antihypertensive drugs during pregnancy had a 3.94-fold higher risk (95% CI: 1.94-8.02) of developing type 2 diabetes compared with those who were normotensive in index pregnancy. Compared with gestational diabetic women who had normal blood pressure at the inter-conception examination, hypertensive women at the inter-conception examination were 3.38 times (95% CI: 1.66-6.87) and 2.97 times (95% CI: 1.75-5.05) more likely to develop diabetes and prediabetes, respectively. The odds ratios of type 2 diabetes and prediabetes associated with each 5 mmHg increase in systolic blood pressure were 125 (95% CI: 1.03-1.51) and 120 (95% CI: 1.06-135). Each 5 mmHg increase in diastolic blood pressure contributed to a 1.49-fold higher risk (95% CI: 1.18-1.88) for type 2 diabetes and a 1.42-fold higher risk (95% CI: 1.22-1.65) for prediabetes. Conclusions: For women with prior gestational diabetes, gestational hypertension and chronic hypertension at the inter-conception examination were risk factors for type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
  • Vuorilehto, Maria S.; Melartin, Tarja K.; Riihimaki, Kirsi; Isometsa, Erkki T. (Elsevier Scientific Publ. Co, 2016)
    Background: Primary health care bears the main responsibility for treating depression in most countries. However, few studies have comprehensively investigated provision of pharmacological and psychosocial treatments, their continuity, or patient attitudes and adherence to treatment in primary care. Methods: In the Vantaa Primary Care Depression Study, 1111 consecutive primary care patients in the City of Vantaa, Finland, were screened for depression with Prime-MD, and 137 were diagnosed with DSM-IV depressive disorders via SCID-I/P and SCID-Il interviews. The 100 patients with current major depressive disorder (MDD) or partly remitted MDD at baseline were prospectively followed up to 18 months, and their treatment contacts and the treatments provided were longitudinally followed. Results: The median number of patients' visits to a general practitioner during the follow-up was five; of those due to depression two. Antidepressant treatment was offered to 82% of patients, but only 50% commenced treatment and adhered to it adequately. Psychosocial support was offered to 49%, but only 29% adhered to the highly variable interventions. Attributed reasons for poor adherence varied, including negative attitude, side effects, practical obstacles, or no perceived need. About one-quarter (23%) of patients were referred to specialized care at some time-point. Limitations: Moderate sample size. Data collected in 2002-2004. Conclusions: The majority of depressive patients in primary health care had been offered pharmacotherapy, psychotherapeutic support, or both. However, effectiveness of these efforts may have been limited by lack of systematic follow-up and poor adherence to both pharmacotherapy and psychosocial treatment. (C) 2016 Elsevier B.V. All rights reserved.
  • Halko, Marja-Liisa; Miettinen, Topi Olli Oskari (PUBLIC LIBRARY OF SCIENCE, 2017)
    In this paper, we study a two-party pie-sharing problem in the presence of asymmetries in the stakeholders' private endowments. Both the two stakeholders and third-party arbitrators may influence the outcome. We consider Nash-demand negotiations, where the two stakeholders place demands and share the pie accordingly if demands are compatible, and elicit dictatorial allocations from the stakeholders and the arbitrators. The Nash demands by stakeholders are strategic; the dictatorial allocations by stakeholders and arbitrators are non-strategic. We are interested in the influence of the past arbitrator experience on stakeholder allocations and demands and the past stakeholder experience on third-party arbitration allocations. We find that the ex-arbitrators' stakeholder allocations differ more from the impartial ideal than the stakeholder allocations by those without arbitration experience. In contrast with previous findings, the arbitration outcomes do not depend on the asymmetries in the previous stakeholder roles.
  • Laanto, Elina; Mantynen, Sari; De Colibus, Luigi; Marjakangas, Jenni; Gillum, Ashley; Stuart, David I.; Ravantti, Janne J.; Huiskonen, Juha T.; Sundberg, Lotta-Riina (National Academy of Sciences, 2017)
    Viruses have impacted the biosphere in numerous ways since the dawn of life. However, the evolution, genetic, structural, and taxonomic diversity of viruses remain poorly understood, in part because sparse sampling of the virosphere has concentrated mostly on exploring the abundance and diversity of dsDNA viruses. Furthermore, viral genomes are highly diverse, and using only the current sequence-based methods for classifying viruses and studying their phylogeny is complicated. Here we describe a virus, FLiP (Flavobacterium-infecting, lipid-containing phage), with a circular ssDNA genome and an internal lipid membrane enclosed in the icosahedral capsid. The 9,174-nt-long genome showed limited sequence similarity to other known viruses. The genetic data imply that this virus might use replication mechanisms similar to those found in other ssDNA replicons. However, the structure of the viral major capsid protein, elucidated at near-atomic resolution using cryo-electron microscopy, is strikingly similar to that observed in dsDNA viruses of the PRD1-adenovirus lineage, characterized by a major capsid protein bearing two beta-barrels. The strong similarity between FLiP and another member of the structural lineage, bacteriophage PM2, extends to the capsid organization (pseudo T = 21 dextro) despite the difference in the genetic material packaged and the lack of significant sequence similarity.
  • Subramanian, Vigneshwari; Prusis, Peteris; Xhaard, Henri; Wohlfahrt, Gerd (The Royal Society of Chemistry, 2016)
    Proteochemometrics, a method that simultaneously uses protein and ligand description, was used to model the target-ligand interaction space of 95 kinases and 1572 inhibitors. To build models, we applied 3-dimensional field-based description of the receptors, which allows the visualization of receptor and ligand features relevant for activity within the spatial framework of the binding sites. Receptor fields were derived from knowledge-based potentials and Schrodinger's WaterMaps, while ligands were described by different 1D, 2D and 3D descriptors. Besides good interpretability, which is important for inhibitor design, the obtained proteochemometric models also predicted external test sets with active and inactive ligands or additional protein targets for ligands with more than 80% accuracy and AUCs above 0.8.
  • Duarte, Luís; Khriachtchev, Leonid; Fausto, Rui; Reva, Igor (The Royal Society of Chemistry, 2016)
    2,2'-Dihydroxyazobenzene (DAB), 2,2'-azotoluene (AT) and azobenzene (AB) were isolated in argon and xenon matrices and their molecular structures and photochemical transformations were characterized by infrared spectroscopy and theoretical calculations. All these compounds can adopt the E and Z isomeric forms around the central CNNC moiety, which can be enriched by several conformational and tautomeric modifications for DAB and AT. A number of DAB and AT isomeric forms were identified for the first time. For DAB, the E azo-enol isomer with two intramolecular six-membered quasi-rings formed via OH . . . N hydrogen bonds was found after deposition. Irradiation with UV light generated a different E azo-enol form with two intramolecular H-bonded five- membered quasi-rings. Phototransformation was shown to be reversible and the forms could be interconverted by irradiation at different wavelengths. The isomerization between these two forms constitutes a direct experimental observation of an E -> E isomerization in azobenzene-type molecules. Further irradiation generated a form(s) bearing both OH and NH groups. For AT, two E isomers with the CH3 groups forming five- membered and five/ six-membered quasi-rings with the azo group were observed in the as-deposited matrices. Irradiation of AT with UV light generated a Z form that can be converted back to the E form at different irradiation wavelengths. E-AB was deposited in a xenon matrix and both E -> Z and Z -> E phototransformations were observed (contrary to what was previously reported in an argon matrix where only the Z -> E conversion occurred). AB photoisomerization becomes more pronounced at elevated temperatures, thus indicating that the matrix effects responsible for hindering the AB photoisomerization are essentially due to steric restrictions. The different photoisomerization channels observed for these compounds are discussed in terms of a small-amplitude pedal motion.
  • Zhivonitko, Vladimir V.; Sorochkina, Kristina; Chernichenko, Konstantin; Kotai, Bianka; Foldes, Tamas; Papai, Imre; Telkki, Ville-Veikko; Repo, Timo; Koptyug, Igor (The Royal Society of Chemistry, 2016)
    The parahydrogen-induced polarization (PHIP) phenomenon, observed when parahydrogen is used in H-2 addition processes, provides a means for substantial NMR signal enhancements and mechanistic studies of chemical reactions. Commonly, noble metal complexes are used for parahydrogen activation, whereas metal-free activation is rare. Herein, we report a series of unimolecular metal-free frustrated Lewis pairs based on an ansa-aminoborane (AAB) moiety in the context of PHIP. These molecules, which have a "molecular tweezers'' structure, differ in their substituents at the boryl site (-H, -Ph, -o-iPr-Ph, and -Mes). PHIP effects were observed for all the AABs after exposing their solutions to parahydrogen in a wide temperature range, and experimental measurements of their kinetic and thermodynamic parameters were performed. A theoretical analysis of their nuclear spin polarization effects is presented, and the roles of chemical exchange, chemical equilibrium and spin dynamics are discussed in terms of the key dimensionless parameters. The analysis allowed us to formulate the prerequisites for achieving strong polarization effects with AAB molecules, which can be applied for further design of efficient metal-free tweezers-like molecules for PHIP. Mechanistic (chemical and physical) aspects of the observed effects are discussed in detail. In addition, we performed quantum chemical calculations, which confirmed that the J-coupling between the parahydrogen-originated protons in AAB-H-2 molecules is mediated through dihydrogen bonding.
  • Benkyi, Isaac; Fliegl, Heike; Valiev, Rashid R.; Sundholm, Dage (The Royal Society of Chemistry, 2016)
    Magnetically induced current densities have been calculated and analyzed for a number of synthesized carbachlorins and carbaporphyrins using density functional theory and the gauge including magnetically induced current (GIMIC) method. Aromatic properties have been determined by using accurate numerical integration of the current flow yielding reliable current strengths and pathways that are related to the degree of aromaticity and the aromatic character of the studied molecules. All investigated compounds are found to be aromatic. However, the obtained aromatic pathways differ from those previously deduced from spectroscopic data and magnetic shielding calculations. For all studied compounds, the ring current divides into an outer and an inner branch at each pyrrolic subring, showing that all pi-electrons of the pyrrolic rings take part in the delocalization pathway. The calculations do not support the common notion that the main share of the current takes the inner route at the pyrrolic rings without an inner hydrogen and follows an 18 pi aromatic pathway. The aromatic pathways of the investigated carbaporphyrins and carbachlorins are very similar, since the current strength via the C-beta=C-beta' bond of the cyclopentadienyl ring of the carbaporphyrins is almost as weak as the current density passing the corresponding saturated C beta-C-beta' bond of the carbachlorins.
  • Wrigstedt, P.; Keskiväli, J.; Repo, T. (The Royal Society of Chemistry, 2016)
    We describe herein an efficient microwave-assisted aqueous biphasic dehydration of carbohydrates to 5-hydroxymethylfurfural (HMF). The effects of several alkali metal salts in aqueous phase, organic solvents as an extractive phase and Lewis acids are evaluated on the reaction. Specifically, starting from fructose, the use of bromide salts in aqueous phase and the common organic solvent MeCN or lignocellulose-derived gamma-valerolactone (GVL) as organic extractors are highly beneficial, leading to excellent HMF yields of up to 91% with HCl as a Bronsted acid catalyst. In conjunction with an isomerization catalyst, the method was applicable to glucose as well as various disaccharides and cellulose, affording HMF in notably good yields, particularly with GVL as an extractor and reusable Amberlyst-38(wet) as an acid catalyst. The exceptionally high HMF yields obtained in aqueous solutions is attributed to the combined effect of the biphasic reaction system and the application of microwaves, which ensures short reaction times and minimized by-product formation thereof.
  • Rauhalahti, M.; Munoz-Castro, A.; Sundholm, D. (The Royal Society of Chemistry, 2016)
    spherical and cavernous carbocage molecule exhibiting faces with larger ring sizes than regular fullerenes is a suitable species for investigating how molecular magnetic properties depend on the structure of the molecular framework. The studied all-carbon gaudiene (C-72) is a highly symmetrical molecule with three-and four-fold faces formed by twelve membered rings. Here, we attempt to unravel the magnetic response properties of C-72 by performing magnetic shielding and current density calculations with the external magnetic field applied in different directions. The obtained results indicate that the induced current density flows mainly along the chemical bonds that are largely perpendicular to the magnetic field direction. However, the overall current strength for different directions of the magnetic field is nearly isotropic differing by only 10% indicating that C-72 can to some extent be considered to be a spherical aromatic molecule, whose current density and magnetic shielding are ideally completely isotropic. The induced magnetic field is found to exhibit long-range shielding cones in the field direction with a small deshielding region located perpendicularly to the field outside the molecule. The magnetic shielding is isotropic inside the molecular framework of C-72, whereas an orientation-dependent magnetic response appears mainly at the exterior of the molecular cage.
  • Xu, Wen-hua; Pyykkö, Pekka (The Royal Society of Chemistry, 2016)
    It is explicitly verified that the atomic 7p(1) ground-state configuration of Lr originates from relativistic effects. Without relativity one has 6d(1). All three ionization potentials IP1-3 of Lr resemble those of Lu. Simple model studies on mono-and trihydrides, monocarbonyls or trichlorides suggest no major chemical differences between Lr and the lanthanides.
  • Lehmkuehler, Felix; Forov, Yury; Buening, Thomas; Sahle, Christoph J.; Steinke, Ingo; Julius, Karin; Buslaps, Thomas; Tolan, Metin; Hakala, Mikko; Sternemann, Christian (The Royal Society of Chemistry, 2016)
    We studied the structure and energetics of supercooled water by means of X-ray Raman and Compton scattering. Under supercooled conditions down to 255 K, the oxygen K-edge measured by X-ray Raman scattering suggests an increase of tetrahedral order similar to the conventional temperature effect observed in non-supercooled water. Compton profile differences indicate contributions beyond the theoretically predicted temperature effect and provide a deeper insight into local structural changes. These contributions suggest a decrease of the electron mean kinetic energy by 3.3 +/- 0.7 kJ (mol K)(-1) that cannot be modeled within established water models. Our surprising results emphasize the need for water models that capture in detail the intramolecular structural changes and quantum effects to explain this complex liquid.
  • Wirtanen, T.; Muuronen, M.; Hurmalainen, J.; Tuononen, H. M.; Nieger, M.; Helaja, J. (The Royal Society of Chemistry, 2016)
    With an excess of a strong acid, 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ) is shown to promote metal-free intermolecular oxidative dehydrogenative (ODH) 3,3'-coupling of 2-aryl-benzo[b]furans and 2-aryl-benzo[b]thiophenes up to 92% yield as demonstrated with 9 substrates. Based on the analysis of oxidation potentials and molecular orbitals combined with EPR, NMR and UV-Vis observations, the studied reaction is initiated by a DDQ-substrate charge transfer complex and presumably proceeds via oxidation of the substrate into an electrophilic radical cation that further reacts with another molecule of a neutral substrate. The coupling reactivity can easily be predicted from the oxidation potential of the substrate and the morphology of its frontier molecular orbitals. The intermolecular ODH coupling reaction allowed a concise total synthesis of the natural product shandougenine B.
  • Sahle, Christoph J.; Schroer, Martin A.; Juurinen, Iina; Niskanen, Johannes (The Royal Society of Chemistry, 2016)
    We present a study on the influence of the naturally occurring organic osmolytes tri-methylamine N-oxide (TMAO) and urea on the bulk structure of water using X-ray Raman scattering spectroscopy. Addition of TMAO is known to stabilize proteins in otherwise destabilizing aqueous urea solutions. The experimental X-ray Raman scattering spectra change systematically with increasing solute concentration revealing different effects on the structure of water due to the presence of the two osmolytes. Although these effects are distinct for both molecular species, they have mutually compensating influences on the spectra of the ternary water-TMAO-urea mixtures. This compensation effect seen in the spectra vanishes only at the highest studied ternary concentration of 4 M: 4 M (TMAO : urea). Our experiment shows that the hydrogen-bonding structure of water remains rather intact in the presence of the aforementioned osmolytes if both of them are present.