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https://www.readbyqxmd.com/read/29317534/linking-secondary-metabolites-to-gene-clusters-through-genome-sequencing-of-six-diverse-aspergillus-species
#1
Inge Kjærbølling, Tammi C Vesth, Jens C Frisvad, Jane L Nybo, Sebastian Theobald, Alan Kuo, Paul Bowyer, Yudai Matsuda, Stephen Mondo, Ellen K Lyhne, Martin E Kogle, Alicia Clum, Anna Lipzen, Asaf Salamov, Chew Yee Ngan, Chris Daum, Jennifer Chiniquy, Kerrie Barry, Kurt LaButti, Sajeet Haridas, Blake A Simmons, Jon K Magnuson, Uffe H Mortensen, Thomas O Larsen, Igor V Grigoriev, Scott E Baker, Mikael R Andersen
The fungal genus of Aspergillus is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus, and A. steynii) have been whole-genome PacBio sequenced to provide genetic references in three Aspergillus sections. A. taichungensis and A. candidus also were sequenced for SM elucidation...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29315638/comparative-genomics-and-transcriptomics-depict-ericoid-mycorrhizal-fungi-as-versatile-saprotrophs-and-plant-mutualists
#2
Elena Martino, Emmanuelle Morin, Gwen-Aëlle Grelet, Alan Kuo, Annegret Kohler, Stefania Daghino, Kerrie W Barry, Nicolas Cichocki, Alicia Clum, Rhyan B Dockter, Matthieu Hainaut, Rita C Kuo, Kurt LaButti, Björn D Lindahl, Erika A Lindquist, Anna Lipzen, Hassine-Radhouane Khouja, Jon Magnuson, Claude Murat, Robin A Ohm, Steven W Singer, Joseph W Spatafora, Mei Wang, Claire Veneault-Fourrey, Bernard Henrissat, Igor V Grigoriev, Francis M Martin, Silvia Perotto
Some soil fungi in the Leotiomycetes form ericoid mycorrhizal (ERM) symbioses with Ericaceae. In the harsh habitats in which they occur, ERM plant survival relies on nutrient mobilization from soil organic matter (SOM) by their fungal partners. The characterization of the fungal genetic machinery underpinning both the symbiotic lifestyle and SOM degradation is needed to understand ERM symbiosis functioning and evolution, and its impact on soil carbon (C) turnover. We sequenced the genomes of the ERM fungi Meliniomyces bicolor, M...
January 7, 2018: New Phytologist
https://www.readbyqxmd.com/read/29305842/vitamin-d-c3-epimer-in-a-mid-swedish-region-analytical-measurement-and-epidemiology
#3
Christos Karefylakis, Paul Pettersson-Pablo, Stefan Särnblad, Eva Rask, Manar Bitar, Anders Magnuson, Clas-Göran Eriksson
No abstract text is available yet for this article.
January 3, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29305699/forward-genetics-screen-coupled-with-whole-genome-resequencing-identifies-novel-gene-targets-for-improving-heterologous-enzyme-production-in-aspergillus-niger
#4
Morgann C Reilly, Joonhoon Kim, Jed Lynn, Blake A Simmons, John M Gladden, Jon K Magnuson, Scott E Baker
Plant biomass, once reduced to its composite sugars, can be converted to fuel substitutes. One means of overcoming the recalcitrance of lignocellulose is pretreatment followed by enzymatic hydrolysis. However, currently available commercial enzyme cocktails are inhibited in the presence of residual pretreatment chemicals. Recent studies have identified a number of cellulolytic enzymes from bacteria that are tolerant to pretreatment chemicals such as ionic liquids. The challenge now is generation of these enzymes in copious amounts, an arena where fungal organisms such as Aspergillus niger have proven efficient...
January 6, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29304337/alpha-to-beta-cell-reprogramming-stepping-toward-a-new-treatment-for-diabetes
#5
Anna B Osipovich, Mark A Magnuson
Beta cell replacement strategies hold promise for permanently treating type 1 diabetes. In Cell Stem Cell, Xiao et al. (2018) restore pancreatic beta cell mass and normalize blood glucose in diabetic mice by reprogramming pancreatic alpha to beta cells using Pdx1- and Mafa-expressing adeno-associated virus infused into the pancreatic duct.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29281693/expression-of-naturally-ionic-liquid-tolerant-thermophilic-cellulases-in-aspergillus-niger
#6
Saori Amaike Campen, Jed Lynn, Stephanie J Sibert, Sneha Srikrishnan, Pallavi Phatale, Taya Feldman, Joel M Guenther, Jennifer Hiras, Yvette Thuy An Tran, Steven W Singer, Paul D Adams, Kenneth L Sale, Blake A Simmons, Scott E Baker, Jon K Magnuson, John M Gladden
Efficient deconstruction of plant biomass is a major barrier to the development of viable lignocellulosic biofuels. Pretreatment with ionic liquids reduces lignocellulose recalcitrance to enzymatic hydrolysis, increasing yields of sugars for conversion into biofuels. However, commercial cellulases are not compatible with many ionic liquids, necessitating extensive water washing of pretreated biomass prior to hydrolysis. To circumvent this issue, previous research has demonstrated that several thermophilic bacterial cellulases can efficiently deconstruct lignocellulose in the presence of the ionic liquid, 1-ethyl-3-methylimadizolium acetate...
2017: PloS One
https://www.readbyqxmd.com/read/29273066/co-regulation-of-transcription-by-brg1-and-brm-two-mutually-exclusive-swi-snf-atpase-subunits
#7
Jesse R Raab, John S Runge, Camarie C Spear, Terry Magnuson
BACKGROUND: SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity...
December 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29213073/reversible-silencing-of-lumbar-spinal-interneurons-unmasks-a-task-specific-network-for-securing-hindlimb-alternation
#8
Amanda M Pocratsky, Darlene A Burke, Johnny R Morehouse, Jason E Beare, Amberly S Riegler, Pantelis Tsoulfas, Gregory J R States, Scott R Whittemore, David S K Magnuson
Neural circuitry in the lumbar spinal cord governs two principal features of locomotion, rhythm and pattern, which reflect intra- and interlimb movement. These features are functionally organized into a hierarchy that precisely controls stepping in a stereotypic, speed-dependent fashion. Here, we show that a specific component of the locomotor pattern can be independently manipulated. Silencing spinal L2 interneurons that project to L5 selectively disrupts hindlimb alternation allowing a continuum of walking to hopping to emerge from the otherwise intact network...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29211671/pharmacomechanical-catheter-directed-thrombolysis-for-deep-vein-thrombosis
#9
RANDOMIZED CONTROLLED TRIAL
Suresh Vedantham, Samuel Z Goldhaber, Jim A Julian, Susan R Kahn, Michael R Jaff, David J Cohen, Elizabeth Magnuson, Mahmood K Razavi, Anthony J Comerota, Heather L Gornik, Timothy P Murphy, Lawrence Lewis, James R Duncan, Patricia Nieters, Mary C Derfler, Marc Filion, Chu-Shu Gu, Stephen Kee, Joseph Schneider, Nael Saad, Morey Blinder, Stephan Moll, David Sacks, Judith Lin, John Rundback, Mark Garcia, Rahul Razdan, Eric VanderWoude, Vasco Marques, Clive Kearon
BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting)...
December 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29169673/design-and-synthesis-of-a-biaryl-series-as-inhibitors-for-the-bromodomains-of-cbp-p300
#10
Kwong Wah Lai, F Anthony Romero, Vickie Tsui, Maureen H Beresini, Gladys de Leon Boenig, Sarah M Bronner, Kevin Chen, Zhongguo Chen, Edna F Choo, Terry D Crawford, Patrick Cyr, Susan Kaufman, Yingjie Li, Jiangpeng Liao, Wenfeng Liu, Justin Ly, Jeremy Murray, Weichao Shen, John Wai, Fei Wang, Caicai Zhu, Xiaoyu Zhu, Steven Magnuson
A novel, potent, and orally bioavailable inhibitor of the bromodomain of CBP, compound 35 (GNE-207), has been identified through SAR investigations focused on optimizing al bicyclic heteroarene to replace the aniline present in the published GNE-272 series. Compound 35 has excellent CBP potency (CBP IC50 = 1 nM, MYC EC50 = 18 nM), a selectively index of >2500-fold against BRD4(1), and exhibits a good pharmacokinetic profile.
November 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29155580/a-unique-approach-to-design-potent-and-selective-cyclic-adenosine-monophosphate-response-element-binding-protein-binding-protein-cbp-inhibitors
#11
Sarah M Bronner, Jeremy M Murray, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Patrick Cyr, Maureen H Beresini, Gladys de Leon Boenig, Zhongguo Chen, Edna F Choo, Kevin R Clark, Terry D Crawford, Hariharan Jayaram, Susan Kaufman, Ruina Li, Yingjie Li, Jiangpeng Liao, Xiaorong Liang, Wenfeng Liu, Justin Q Ly, Jonathan Maher, John S Wai, Fei Wang, Aijun Zheng, Xiaoyu Zhu, Steven R Magnuson
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we reported the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region, and then building into the LPF shelf. Herein we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29146137/the-impact-of-additives-on-the-phosphorus-potassium-and-sodium-content-of-commonly-consumed-meat-poultry-and-fish-products-among-patients-with-chronic-kidney-disease
#12
Arti Sharma Parpia, Mary L'Abbé, Marc Goldstein, Joanne Arcand, Bernadene Magnuson, Pauline Darling
OBJECTIVE: Patients with chronic kidney disease (CKD) are advised to limit their dietary intake of phosphorus and potassium as hyperphosphatemia and hyperkalemia are both associated with an increased risk of mortality. There is uncertainty concerning the actual content of these minerals in the Canadian food supply, as phosphorus and potassium are increasingly being used as food additives. This study aimed to determine the impact of food additives on the chemically analyzed content of phosphorus, potassium, sodium, and protein in commonly consumed meat, poultry, and fish products (MPFs)...
November 14, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29097293/quality-of-life-after-everolimus-eluting-stents-or-bypass-surgery-for-treatment-of-left-main-disease
#13
Suzanne J Baron, Khaja Chinnakondepalli, Elizabeth A Magnuson, David E Kandzari, John D Puskas, Ori Ben-Yehuda, Gerrit-Anne van Es, David P Taggart, Marie-Claude Morice, Nicholas J Lembo, W Morris Brown, Adrian Banning, Charles A Simonton, A Pieter Kappetein, Joseph F Sabik, Patrick W Serruys, Gregg W Stone, David J Cohen
BACKGROUND: The EXCEL trial compared outcomes in patients with unprotected left main coronary artery disease (LMCAD) treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) using everolimus-eluting stents. While rates of death, stroke, and myocardial infarction were similar at 36 months, event timing and repeat revascularization rates differed by treatment group. OBJECTIVES: To understand the effects of revascularization strategy from the patient's perspective, we performed a prospective quality of life (QoL) sub-study alongside the EXCEL trial...
October 20, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29094994/keep-listening-grammatical-context-reduces-but-does-not-eliminate-activation-of-unexpected-words
#14
Julia F Strand, Violet A Brown, Hunter E Brown, Jeffrey J Berg
To understand spoken language, listeners combine acoustic-phonetic input with expectations derived from context (Dahan & Magnuson, 2006). Eye-tracking studies on semantic context have demonstrated that the activation levels of competing lexical candidates depend on the relative strengths of the bottom-up input and top-down expectations (cf. Dahan & Tanenhaus, 2004). In the grammatical realm, however, graded effects of context on lexical competition have been predicted (Magnuson, Tanenhaus, & Aslin, 2008), but not demonstrated...
November 2, 2017: Journal of Experimental Psychology. Learning, Memory, and Cognition
https://www.readbyqxmd.com/read/29075325/rhodosporidium-toruloides-a-new-platform-organism-for-conversion-of-lignocellulose-into-terpene-biofuels-and-bioproducts
#15
Junko Yaegashi, James Kirby, Masakazu Ito, Jian Sun, Tanmoy Dutta, Mona Mirsiaghi, Eric R Sundstrom, Alberto Rodriguez, Edward Baidoo, Deepti Tanjore, Todd Pray, Kenneth Sale, Seema Singh, Jay D Keasling, Blake A Simmons, Steven W Singer, Jon K Magnuson, Adam P Arkin, Jeffrey M Skerker, John M Gladden
BACKGROUND: Economical conversion of lignocellulosic biomass into biofuels and bioproducts is central to the establishment of a robust bioeconomy. This requires a conversion host that is able to both efficiently assimilate the major lignocellulose-derived carbon sources and divert their metabolites toward specific bioproducts. RESULTS: In this study, the carotenogenic yeast Rhodosporidium toruloides was examined for its ability to convert lignocellulose into two non-native sesquiterpenes with biofuel (bisabolene) and pharmaceutical (amorphadiene) applications...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29074648/draft-nuclear-genome-sequence-of-the-halophilic-and-beta-carotene-accumulating-green-alga-dunaliella-salina-strain-ccap19-18
#16
Juergen E W Polle, Kerrie Barry, John Cushman, Jeremy Schmutz, Duc Tran, Leyla T Hathwaik, Won C Yim, Jerry Jenkins, Zaid McKie-Krisberg, Simon Prochnik, Erika Lindquist, Rhyan B Dockter, Catherine Adam, Henrik Molina, Jakob Bunkenborg, EonSeon Jin, Mark Buchheim, Jon Magnuson
The halotolerant alga Dunaliella salina is a model for stress tolerance and is used commercially for production of beta-carotene (=pro-vitamin A). The presented draft genome of the genuine strain CCAP19/18 will allow investigations into metabolic processes involved in regulation of stress responses, including carotenogenesis and adaptations to life in high-salinity environments.
October 26, 2017: Genome Announcements
https://www.readbyqxmd.com/read/29073101/utx-guided-neural-crest-function-underlies-craniofacial-features-of-kabuki-syndrome
#17
Karl B Shpargel, Joshua Starmer, Chaochen Wang, Kai Ge, Terry Magnuson
Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority of clinical features are modeled in mice carrying neural crest (NC) deletion of UTX, including craniofacial dysmorphism, cardiac defects, and postnatal growth retardation...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069383/effects-on-nasal-airflow-and-resistance-using-two-different-rme-appliances-a-randomized-controlled-trial
#18
Farhan Bazargani, Anders Magnuson, Björn Ludwig
Objectives: To evaluate and compare the effects of tooth-borne (TB) and tooth-bone-borne (TBB) rapid maxillary expansion (RME) on nasal airflow and resistance. Material and methods: Fifty-four consecutive patients who met the eligibility criteria were recruited from September 2010 to December 2015. Of these 54 subjects, 40 agreed to participate in the part of the study involving evaluation of nasal flow and resistance. The 40 subjects were allocated to either the TB group, mean age 9...
October 21, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28922338/does-the-%C3%AE-receptor-antagonist-esmolol-have-analgesic-effects-a-randomised-placebo-controlled-cross-over-study-on-healthy-volunteers-undergoing-the-cold-pressor-test
#19
Fredrik Ander, Anders Magnuson, Alex de Leon, Rebecca Ahlstrand
BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo...
September 15, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28914366/geriatric-assessment-with-management-intervention-in-older-adults-with-cancer-a-randomized-pilot-study
#20
Allison Magnuson, Tatyana Lemelman, Chintan Pandya, Molly Goodman, Marcus Noel, Mohammed Tejani, David Doughtery, William Dale, Arti Hurria, Michelle Janelsins, Feng Vankee Lin, Charles Heckler, Supriya Mohile
BACKGROUND: Older adults receiving cancer therapy have heightened risk for treatment-related toxicity. Geriatric assessment (GA) can identify impairments, which may contribute to vulnerability and adverse outcomes. GA management interventions can address these impairments and have the potential to improve outcomes when implemented. METHODS: We conducted a randomized pilot study comparing GA with management interventions versus usual care in patients with stage III/IV solid tumor malignancies (N = 71)...
September 15, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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