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  • 451.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Cunningham, Gregory
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Ladermann, Alexandre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;La Tour Hosp, Div Orthopaed & Trauma Surg, Geneva, Switzerland..
    Ozturk, Mehmet
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Hoffmeyer, Pierre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Carouge Radiol Diagnost Ctr, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 498Article in journal (Refereed)
    Abstract [en]

    Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the postoperatory outcome. 13 patients with shoulder apprehension (30.03 +/- 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

  • 452. Zanchi, Davide
    et al.
    Cunningham, Gregory
    Lädermann, Alexandre
    Ozturk, Mehmet
    Hoffmeyer, Pierre
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Structural white matter and functional connectivity alterations in patients with shoulder apprehension2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42327Article in journal (Refereed)
    Abstract [en]

    Previous functional magnetic resonance imaging (fMRI) findings indicate that shoulder apprehension is more complex than a pure mechanical problem of the shoulder, showing a direct modification in functional brain networks associated with motor inhibition and emotional regulation. The current study extends these findings by investigating further structural alterations in patients with shoulder apprehension compared to controls. 14 aged patients with shoulder apprehension (27.3 ± 2.0 years) and 10 matched healthy controls (29.6 ± 1.3 years) underwent clinical and fMRI examination including fMRI and diffusion tensor imaging (DTI). Tract-based spatial statistics procedure was used to analyze white matter (WM) alterations. Functional images were analyzed investigating resting state network connectivity. DTI results were correlated with different shoulder clinical scores and functional connectivity networks. Fractional anisotropy (FA), representing white matter integrity, is increased in the left internal capsule and partially in the thalamus in patients compared to controls. Moreover, FA correlates negatively with simple shoulder test (SST) scores (p < .05) and positively with a functional connectivity network qualitatively replicating previous results (p < .01). This study extends previous findings, showing that in addition to functional changes, structural white matter changes are also present in patients with shoulder apprehension.

  • 453.
    Zanchi, Davide
    et al.
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Meyer-Gerspach, Anne Christin
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    Suenderhauf, Claudia
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Janach, Katharina
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    le Roux, Carel W.
    Univ Coll Dublin, Conway Inst, Diabet Complicat Res Ctr, Dublin, Ireland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Affidea CDRC Ctr Diagnost Radiolog Carouge, Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Drewe, Jurgen
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Beglinger, Christoph
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Wlnerhanssen, Bettina K.
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland.;St Clara Hosp, Dept Res, Basel, Switzerland..
    Borgwardt, Stefan
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Differential effects of L-tryptophan and L-leucine administration on brain resting state functional networks and plasma hormone levels2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35727Article in journal (Refereed)
    Abstract [en]

    Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation.

  • 454.
    Zanni, Giulia
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Michno, Wojciech
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Di Martino, Elena
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Tjärnlund-Wolf, Anna
    Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mason, Charlotte Elizabeth
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Hellspong, Gustaf
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Blomgren, Klas
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pediat Oncol, Stockholm, Sweden..
    Hanrieder, Jorg
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;Chalmers, Dept Chem & Chem Engn, Gothenburg, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, London WC1E 6BT, England..
    Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 40726Article in journal (Refereed)
    Abstract [en]

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry-(ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

  • 455.
    Zaton, Michal
    et al.
    Univ Silesia, Fac Earth Sci, Bedzinska 60, PL-41200 Sosnowiec, Poland.;KNOW Leading Natl Res Ctr, Ctr Polar Studies, Sosnowiec, Poland..
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Kear, Benjamin P.
    Uppsala University, Music and Museums, Museum of Evolution.
    Boreal earliest Triassic biotas elucidate globally depauperate hard substrate communities after the end-Permian mass extinction2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36345Article in journal (Refereed)
    Abstract [en]

    The end-Permian mass extinction constituted the most devastating biotic crisis of the Phanerozoic. Its aftermath was characterized by harsh marine conditions incorporating volcanically induced oceanic warming, widespread anoxia and acidification. Bio-productivity accordingly experienced marked fluctuations. In particular, low palaeolatitude hard substrate communities from shallow seas fringing Western Pangaea and the Tethyan Realm were extremely impoverished, being dominated by monogeneric colonies of filter-feeding microconchid tubeworms. Here we present the first equivalent field data for Boreal hard substrate assemblages from the earliest Triassic (Induan) of East Greenland. This region bordered a discrete bio-realm situated at mid-high palaeolatitude (> 30 degrees N). Nevertheless, hard substrate biotas were compositionally identical to those from elsewhere, with microconchids encrusting Claraia bivalves and algal buildups on the sea floor. Biostratigraphical correlation further shows that Boreal microconchids underwent progressive tube modification and unique taxic diversification concordant with changing habitats over time. We interpret this as a post-extinction recovery and adaptive radiation sequence that mirrored coeval subequatorial faunas, and thus confirms hard substrate ecosystem depletion as a hallmark of the earliest Triassic interval globally.

  • 456.
    Zhang, Jiang
    et al.
    Department of Physics, Shandong University, Jinan, China.
    Kyaw, Thi Ha
    Centre for Quantum Technologies, NUS, Singapore.
    Tong, Dianmin
    Department of Physics, Shandong University, Jinan, China.
    Sjöqvist, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. Uppsala universitet.
    Kwek, Leong Chuan
    Centre for Quantum Technologies, NUS, Singapore.
    Fast non-Abelian geometric gates via transitionless quantum driving2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 18414Article in journal (Refereed)
    Abstract [en]

    A practical quantum computer must be capable of performing high fidelity quantum gates on a set of quantum bits (qubits). In the presence of noise, the realization of such gates poses daunting challenges. Geometric phases, which possess intrinsic noise-tolerant features, hold the promise for performing robust quantum computation. In particular, quantum holonomies, i.e., non-Abelian geometric phases, naturally lead to universal quantum computation due to their non-commutativity. Although quantum gates based on adiabatic holonomies have already been proposed, the slow evolution eventually compromises qubit coher- ence and computational power. Here, we propose a general approach to speed up an implementation of adiabatic holonomic gates by using transitionless driving techniques and show how such a universal set of fast geometric quantum gates in a superconducting circuit architecture can be obtained in an all geometric approach. Compared with standard non-adiabatic holonomic quantum computation, the holonomies ob- tained in our approach tends asymptotically to those of the adiabatic approach in the long run-time limit and thus might open up a new horizon for realizing a practical quantum computer. 

  • 457.
    Zhang, Lu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ding, Zhoujie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Heyman, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C32017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5400Article in journal (Refereed)
    Abstract [en]

    IgG3, passively administered together with small proteins, induces enhanced primary humoral responses against these proteins. We previously found that, within 2 h of immunization, marginal zone (MZ) B cells capture IgG3-antigen complexes and transport them into splenic follicles and that this requires the presence of complement receptors 1 and 2. We have here investigated the localization of IgG3 anti-2, 4, 6-trinitrophenyl (TNP)/biotin-ovalbumin-TNP immune complexes in the follicles and the involvement of classical versus total complement activation in this process. The majority (50-90%) of antigen inside the follicles of mice immunized with IgG3-antigen complexes co-localized with the follicular dendritic cell (FDC) network. Capture of antigen by MZ B cells as well as antigen deposition on FDC was severely impaired in mice lacking C1q or C3, and lack of either C1q or C3 also impaired the ability of IgG3 to enhance antibody responses. Finally, IgG3 efficiently primed for a memory response against small proteins as well as against the large protein keyhole limpet hemocyanine.

  • 458.
    Zhang, Lu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ding, Zhoujie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Heyman, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    IgG3-Antigen Complexes Are Deposited on Follicular Dendritic Cells in the Presence of C1q and C3In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Article in journal (Other academic)
  • 459.
    Zhang, Rong
    et al.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Knapp, Michael
    Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany..
    Suzuki, Kentaro
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Kajioka, Daiki
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Schmidt, Johanna M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Inst Anat, Bonn, Germany..
    Winkler, Jonas
    Univ Bonn, Inst Anat, Bonn, Germany..
    Yilmaz, Oeznur
    Univ Bonn, Inst Anat, Bonn, Germany..
    Pleschka, Michael
    Univ Bonn, Inst Anat, Bonn, Germany..
    Cao, Jia
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Kockum, Christina Clementson
    Univ Lund Hosp, Dept Pediat Surg, Lund, Sweden..
    Barker, Gillian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Holmdahl, Gundela
    Queen Silvias Childrens Hosp, Dept Pediat Surg, Gothenburg, Sweden..
    Beaman, Glenda
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Keene, David
    Woolf, Adrian S.
    Univ Manchester, Manchester Acad Hlth Sci, Inst Human Dev, Manchester M13 9PL, Lancs, England.;Royal Manchester Childrens Hosp, Manchester, Lancs, England..
    Cervellione, Raimondo M.
    Cent Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Paediat Urol, Manchester, Lancs, England..
    Cheng, Wei
    Capital Inst Pediat, Dept Pediat Surg, Beijing, Peoples R China.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Paediat, Clayton, Vic, Australia.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Surg, Clayton, Vic, Australia.;Beijing United Family Hosp, Dept Surg, Beijing, Peoples R China..
    Wilkins, Simon
    Cabrini Monash Univ, Cabrini Hosp, Dept Surg, Melbourne, Vic, Australia.;Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia..
    Gearhart, John P.
    Johns Hopkins Sch Med, Div Pediat Urol, Baltimore, MD USA..
    Sirchia, Fabio
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Di Grazia, Massimo
    IRCCS Burlo Garofalo, Inst Maternal & Child Hlth, Trieste, Italy..
    Ebert, Anne-Karolin
    Univ Hosp Ulm, Dept Urol & Pediat Urol, Ulm, Germany..
    Roesch, Wolfgang
    St Hedwig Hosp Barmherzige Bruder, Dept Pediat Urol, Regensburg, Germany..
    Ellinger, Joerg
    Univ Hosp Bonn, Dept Urol, Bonn, Germany..
    Jenetzky, Ekkehart
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;Johannes Gutenberg Univ Mainz, Dept Child & Adolescent Psychiat & Psychotherapy, Mainz, Germany..
    Zwink, Nadine
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Feitz, Wout F.
    Radboud Univ Nijmegen, Med Ctr, Pediat Urol Ctr, Dept Urol, Nijmegen, Netherlands..
    Marcelis, Carlo
    Radboud Univ Nijmegen, Med Ctr, Dept Genet, Nijmegen, Netherlands..
    Schumacher, Johannes
    Univ Bonn, Inst Human Genet, Bonn, Germany..
    Martinon-Torres, Federico
    Hosp Clin Univ Santiago, Translat Pediat & Infect Dis, Santiago De Compostela, Spain.;Inst Invest Sanitaria Santiago Santiago, GENVIP Res Grp Www Genvip Org, Galicia, Spain..
    Hibberd, Martin Lloyd
    Genome Inst Singapore, Singapore, Singapore..
    Khor, Chiea Chuen
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Barth, Sandra
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Boyadjiev, Simeon A.
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Brusco, Alfredo
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Ludwig, Michael
    Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany..
    Newman, William
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Nordenskjold, Agneta
    Karolinska Univ Hosp, Astrid Lindgren Children Hosp, Pediat Surg, Stockholm, Sweden..
    Yamada, Gen
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Odermatt, Benjamin
    Univ Bonn, Inst Anat, Bonn, Germany..
    Reutter, Heiko
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Childrens Hosp, Dept Neonatol & Pediat Intens Care, Bonn, Germany.;Univ Bonn, Bonn, Germany..
    ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42170Article in journal (Refereed)
    Abstract [en]

    Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

  • 460.
    Zhang, Shuping
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. Shandong Univ, Sch Life Sci, Inst Ecol & Biodivers, Jinan 250100, Shandong, Peoples R China.
    Isermann, Maike
    Bremen Univ, Dept Ecol, Vegetat Ecol & Conservat Biol, FB 2, D-28359 Bremen, Germany..
    Gan, Wenhao
    Shandong Univ, Sch Life Sci, Inst Ecol & Biodivers, Jinan 250100, Shandong, Peoples R China..
    Breed, Martin
    Univ Adelaide, Sch Biol Sci, Adelaide, SA 5005, Australia..
    Invasive Rosa rugosa populations outperform native populations, but some populations have greater invasive potential than others2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5735Article in journal (Refereed)
    Abstract [en]

    Increased performance of invasive plant species in their introduced range vs. their native range has been previously documented. However, performance differences among invasive populations have rarely been explored, despite this information being central to understanding the evolution of invasiveness as well as being a useful basis to inform management of invasive species. To examine variation in performance among populations of Rosa rugosa in its introduced range, and whether introduced populations perform better than native populations, we quantified growth and reproductive traits in five invasive populations in northwest Europe and two native and declining populations in China. Overall, we found that the introduced R. rugosa populations we sampled performed significantly better than the sampled native populations for growth and reproductive traits (2 to 4 fold increase). However, there was significant variation for most traits among the five invasive populations, demonstrating that some introduced populations we sampled were more successful invaders than others. Our findings provide a useful foundation for management of invasive R. rugosa in Europe, and support the recent call for more intra-species research in invasive species biology.

  • 461. Zhang, Xinyu
    et al.
    Qin, Jiaqian
    Liu, Hanyu
    Zhang, Shiliang
    Ma, Mingzhen
    Luo, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Liu, Riping
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Pressure-induced zigzag phosphorus chain and superconductivity in boron monophosphide2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 8761Article in journal (Refereed)
    Abstract [en]

    We report on the prediction of the zinc-blende structure BP into a novel C2/m phase from 113 to 208 GPa which possesses zigzag phosphorus chain structure, followed by another P4(2)/mnm structure above 208 GPa above using the particle-swarm search method. Strong electron-phonon coupling lambda in compressed BP is found, in particular for C2/m phase with the zigzag phosphorus chain, which has the highest lambda (0.56-0.61) value among them, leading to its high superconducting critical temperature T-c (9.4 K-11.5 K), which is comparable with the 4.5 Kto 13 Kvalue of black phosphorus phase I (orthorhombic, Cmca). This is the first system in the boron phosphides which shows superconductivity from the present theoretical calculations. Our results show that pressure-induced zigzag phosphorus chain in BP exhibit higher superconducting temperature T-C, opening a new route to search and design new superconductor materials with zigzag phosphorus chains.

  • 462.
    Zhang, Youwei
    et al.
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China.;Chinese Acad Sci, Shanghai Inst Microsyst & Informat Technol, State Key Lab Funct Mat Informat, Changning Rd 865, Shanghai 200050, Peoples R China..
    Li, Hui
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Wang, Haomin
    Chinese Acad Sci, Shanghai Inst Microsyst & Informat Technol, State Key Lab Funct Mat Informat, Changning Rd 865, Shanghai 200050, Peoples R China..
    Xie, Hong
    Chinese Acad Sci, Shanghai Inst Microsyst & Informat Technol, State Key Lab Funct Mat Informat, Changning Rd 865, Shanghai 200050, Peoples R China..
    Liu, Ran
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Qiu, Zhi-Jun
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Thickness Considerations of Two-Dimensional Layered Semiconductors for Transistor Applications2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 29615Article in journal (Refereed)
    Abstract [en]

    Layered two-dimensional semiconductors have attracted tremendous attention owing to their demonstrated excellent transistor switching characteristics with a large ratio of on-state to off-state current, I-on/I-off. However, the depletion-mode nature of the transistors sets a limit on the thickness of the layered semiconductor films primarily determined by a given I-on/I-off as an acceptable specification. Identifying the optimum thickness range is of significance for material synthesis and device fabrication. Here, we systematically investigate the thickness-dependent switching behavior of transistors with a wide thickness range of multilayer-MoS2 films. A difference in I-on/I-off by several orders of magnitude is observed when the film thickness, t, approaches a critical depletion width. The decrease in I-on/I-off is exponential for t between 20 nm and 100 nm, by a factor of 10 for each additional 10 nm. For t larger than 100 nm, I-on/I-off approaches unity. Simulation using technical computer-aided tools established for silicon technology faithfully reproduces the experimentally determined scaling behavior of I-on/I-off with t. This excellent agreement confirms that multilayer-MoS2 films can be approximated as a homogeneous semiconductor with high surface conductivity that tends to deteriorate I-on/I-off. Our findings are helpful in guiding material synthesis and designing advanced field-effect transistors based on the layered semiconductors.

  • 463. Zhang, Youwei
    et al.
    Li, Hui
    Wang, Lu
    Wang, Haomin
    Xie, Xiaomin
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Liu, Ran
    Qiu, Zhi-Jun
    Photothermoelectric and photovoltaic effects both present in MoS22015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 7938-Article in journal (Refereed)
    Abstract [en]

    As a finite-energy-bandgap alternative to graphene, semiconducting molybdenum disulfide (MoS2) has recently attracted extensive interest for energy and sensor applications. In particular for broad-spectral photodetectors, multilayer MoS2 is more appealing than its monolayer counterpart. However, little is understood regarding the physics underlying the photoresponse of multilayer MoS2. Here, we employ scanning photocurrent microscopy to identify the nature of photocurrent generated in multilayer MoS2 transistors. The generation and transport of photocurrent in multilayer MoS2 are found to differ from those in other low-dimensional materials that only contribute with either photovoltaic effect (PVE) or photothermoelectric effect (PTE). In multilayer MoS2, the PVE at the MoS2-metal interface dominates in the accumulation regime whereas the hot-carrier-assisted PTE prevails in the depletion regime. Besides, the anomalously large Seebeck coefficient observed in multilayer MoS2, which has also been reported by others, is caused by hot photo-excited carriers that are not in thermal equilibrium with the MoS2 lattice.

  • 464. Zhang, Zhifei
    et al.
    Holmer, Lars E.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Skovsted, Christian B.
    Brock, Glenn A.
    Budd, Graham E.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Fu, Dongjing
    Zhang, Xingliang
    Shu, Degan
    Han, Jian
    Liu, Jianni
    Wang, Haizhou
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Butler, Aodhan
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Li, Guoxiang
    A sclerite-bearing stem group entoproct from the early Cambrian and its implications2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 1066-Article in journal (Refereed)
    Abstract [en]

    The Lophotrochozoa includes disparate tentacle-bearing sessile protostome animals, which apparently appeared in the Cambrian explosion, but lack an uncontested fossil record. Here we describe abundant well preserved material of Cotyledion tylodes Luo et Hu, 1999, from the Cambrian (Series 2) Chengjiang deposits, reinterpreted here as a stem-group entoproct. The entoproct affinity is supported by the sessile body plan and interior soft anatomy. The body consists of an upper calyx and a lower elongate stalk with a distal holdfast. The soft anatomy includes a U-shaped gut with a mouth and aboral anus ringed by retractable marginal tentacles. Cotyledion differs from extant entoprocts in being larger, and having the calyx and the stalk covered by numerous loosely-spaced external sclerites. The description of entoprocts from the Chengjiang biota traces the ancestry of yet another lophotrochozoan phylum back to the Cambrian radiation, and has important implications for the earliest evolution of lophotrochozoans.

  • 465.
    Zhang, Zhifei
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Holmer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Wang, Haizhou
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Butler, Aodhán D.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    An early Cambrian agglutinated tubular lophophorate with brachiopod characters2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 4682-Article in journal (Refereed)
    Abstract [en]

    The morphological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last common ancestor. Only fossils of stem groups can help discover the morphological transitions that occurred along the roots of these phyla. Here, we describe a tubular fossil Yuganotheca elegans gen.et sp. nov. from the Cambrian (Stage 3) Chengjiang Lagerstätte (Yunnan, China) that exhibits an unusual combination of phoronid, brachiopod and tommotiid (Cambrian problematica) characters, notably a pair of agglutinated valves, enclosing a horseshoe-shaped lophophore, supported by a lower bipartite tubular attachment structure with a long coelomic pedicle providing anchorage. The discovery has important implications for the early evolution of lophotrochozoans, suggesting rooting of brachiopods into the sessile lophotrochozoans and the origination of their bivalved bauplan preceding the biomineralization of shell valves in crown brachiopods.

  • 466.
    Zhou, Ang
    et al.
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia.
    Taylor, Amy E.
    Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England;Univ Bristol, UKCTAS, Bristol, Avon, England;Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
    Karhunen, Ville
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Zhan, Yiqiang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Rovio, Suvi P.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
    Lahti, Jari
    Helsinki Collegium Adv Studies, Helsinki, Finland;Univ Helsinki, Dept Psychol & Logoped, Fac Med, Helsinki, Finland.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lyall, Donald M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Auvinen, Juha
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere Univ Hosp, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Hutri-Kahonen, Nina
    Univ Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Tampere Univ Hosp, Dept Pediat, Tampere, Finland.
    Perala, Mia Maria
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki, Finland.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mahajan, Anubha
    Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford OX3 7BN, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Power, Chris
    UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England.
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Raitakari, Olli T.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Veijola, Juha
    Univ Oulu, Dept Psychiat, Res Unit Clin Neurosci, Oulu, Finland;Univ Hosp Oulu, Dept Psychiat, Oulu, Finland.
    Jarvelin, Marjo-Riitta
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Univ Oulu, Bioctr Oulu, Oulu, Finland.
    Munafo, Marcus R.
    Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England;Univ Bristol, UKCTAS, Bristol, Avon, England;Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Div Cardiovasc Med, Dept Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Llewellyn, David J.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hypponen, Elina
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia;UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7526Article in journal (Refereed)
    Abstract [en]

    Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid-to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (beta = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; beta = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P-heterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P >= 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

  • 467. Zhu, J.
    et al.
    Zhang, J. L.
    Kong, P. P.
    Zhang, S. J.
    Yu, X. H.
    Zhu, J. L.
    Liu, Q. Q.
    Li, X.
    Yu, R. C.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Yang, W. G.
    Shen, G. Y.
    Mao, H. K.
    Weng, H. M.
    Dai, X.
    Fang, Z.
    Zhao, Y. S.
    Jin, C. Q.
    Superconductivity in Topological Insulator Sb2Te3 Induced by Pressure2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2016-Article in journal (Refereed)
    Abstract [en]

    Topological superconductivity is one of most fascinating properties of topological quantum matters that was theoretically proposed and can support Majorana Fermions at the edge state. Superconductivity was previously realized in a Cu-intercalated Bi2Se3 topological compound or a Bi2Te3 topological compound at high pressure. Here we report the discovery of superconductivity in the topological compound Sb2Te3 when pressure was applied. The crystal structure analysis results reveal that superconductivity at a low-pressure range occurs at the ambient phase. The Hall coefficient measurements indicate the change of p-type carriers at a low-pressure range within the ambient phase, into n-type at higher pressures, showing intimate relation to superconducting transition temperature. The first principle calculations based on experimental measurements of the crystal lattice show that Sb2Te3 retains its Dirac surface states within the low-pressure ambient phase where superconductivity was observed, which indicates a strong relationship between superconductivity and topology nature.

  • 468.
    Zidar, Josefina
    et al.
    Linkoping Univ, Dept Phys Chem & Biol, IFM Biol, SE-58183 Linkoping, Sweden.
    Campderrich, Irene
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, SE-75007 Uppsala, Sweden;Neiker Tecnalia, Dept Anim Prod, Vitoria 01080, Spain.
    Jansson, Emelie
    Linkoping Univ, Dept Phys Chem & Biol, IFM Biol, SE-58183 Linkoping, Sweden.
    Wichman, Anette
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, SE-75007 Uppsala, Sweden.
    Winberg, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Keeling, Linda
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, SE-75007 Uppsala, Sweden.
    Løvlie, Hanne
    Linkoping Univ, Dept Phys Chem & Biol, IFM Biol, SE-58183 Linkoping, Sweden.
    Environmental complexity buffers against stress-induced negative judgement bias in female chickens2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5404Article in journal (Refereed)
    Abstract [en]

    Cognitive processes are often biased by emotions. In humans, affective disorders are accompanied by pessimistic judgement, while optimistic judgement is linked to emotional stability. Similar to humans, animals tend to interpret ambiguous stimuli negatively after experiencing stressful events, although the long-lasting impact on judgement bias has rarely been investigated. We measure judgement bias in female chicks (Gallus gallus domesticus) after exposure to cold stress, and before and after exposure to additional unpredictable stressors. Additionally, we explore if brain monoamines can explain differences in judgement bias. Chicks exposed to cold stress did not differ in judgement bias compared to controls, but showed sensitivity to additional stressors by having higher motivation for social reinstatement. Environmental complexity reduced stress-induced negative judgement bias, by maintaining an optimistic bias in individuals housed in complex conditions even after stress exposure. Moreover, judgement bias was related to dopamine turnover rate in mesencephalon, with higher activity in individuals that had a more optimistic response. These results demonstrate that environmental complexity can buffer against negative effects of additive stress and that dopamine relates to judgement bias in chicks. These results reveal that both internal and external factors can mediate emotionally biased judgement in animals, thus showing similarities to findings in humans.

  • 469.
    Zorzan, Eleonora
    et al.
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Elgendy, Ramy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Giantin, Mery
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Dacasto, Mauro
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Sissi, Claudia
    Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy.
    Whole-Transcriptome Profiling of Canine and Human in Vitro Models Exposed to a G-Quadruplex Binding Small Molecule2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17107Article in journal (Refereed)
    Abstract [en]

    G-quadruplexes (G4) are secondary nucleic acid structures that have been associated with genomic instability and cancer progression. When present in the promoter of some oncogenes, G4 structures can affect gene regulation and, hence, represent a possible therapeutic target. In this study, RNA-Seq was used to explore the effect of a G4-binding anthraquinone derivative, named AQ1, on the whole-transcriptome profiles of two common cell models for the study of KIT pathways; the human mast cell leukemia (HMC1.2) and the canine mast cell tumor (C2). The highest non-cytotoxic dose of AQ1 (2 mu M) resulted in 5441 and 1201 differentially expressed genes in the HMC1.2 and C2 cells, respectively. In both cell lines, major pathways such as cell cycle progression, KIT- and MYC-related pathways were negatively enriched in the AQ1-treated group, while other pathways such as p53, apoptosis and hypoxia-related were positively enriched. These findings suggest that AQ1 treatment induces a similar functional response in the human and canine cell models, and provide news insights into using dogs as a reliable translational model for studying G4-binding compounds.

  • 470.
    Åkerström, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Willenberg, Holger Sven
    Cupisti, Kenko
    Ip, Julian
    Moser, Ana
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Robinson, Bruce
    Iwen, Alexander K
    Dralle, Henning
    Walz, Martin K.
    Lehnert, Hendrik
    Sidhu, Stan
    Gomez-Sanchez, Celso
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Activating mutations in CTNNB1 in aldosterone producing adenomas2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19546Article in journal (Refereed)
    Abstract [en]

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalenceof 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitutea large proportion of PA cases and represent a surgically correctable form of the disease. The WNTsignaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling ismutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutationsin a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of thetumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Allof the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3.The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggestingactivation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and directmeasurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. Thisreport provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occurin APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway maybe important in APA formation.

  • 471.
    Šupraha, Luka
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Gerecht, Andrea Cornelia
    Probert, Ian
    Henderiks, Jorijntje
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Eco-physiological adaptation shapes the response of calcifying algae to nutrient limitation2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16499Article in journal (Refereed)
    Abstract [en]

    The steady increase in global ocean temperature will most likely lead to nutrient limitation in the photic zone. This will impact the physiology of marine algae, including the globally important calcifying coccolithophores. Understanding their adaptive patterns is essential for modelling carbon production in a low-nutrient ocean. We investigated the physiology of Helicosphaera carteri, a representative of the abundant but under-investigated flagellated functional group of coccolithophores. Two strains isolated from contrasting nutrient regimes (South Atlantic and Mediterranean Sea) were grown in phosphorus-replete and phosphorus-limited batch cultures. While growing exponentially in a phosphorus-replete medium, the Mediterranean strain exhibited on average 24% lower growth rate, 36% larger coccosphere volume and 21% lower particulate inorganic carbon (PIC) production than the Atlantic strain. Under phosphorus limitation, the same strain was capable of reaching a 2.6 times higher cell density than the Atlantic strain due to lower phosphorus requirements. These results suggest that local physiological adaptation can define the performance of this species under nutrient limitation.

78910 451 - 471 of 471
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