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Kost RG, Leinberger-Jabari A, Evering TH, Holt PR, Neville-Williams M, Vasquez KS, Coller BS, Tobin JN
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Helping Basic Scientists Engage With Community Partners to Enrich and Accelerate Translational Research
ACADEMIC MEDICINE 2017 MAR; 92(3):374-379
Problem Engaging basic scientists in community-based translational research is challenging but has great potential for improving health. Approach In 2009, The Rockefeller University Center for Clinical and Translational Science partnered with Clinical Directors Network, a practice-based research network (PBRN), to create a community-engaged research navigation (CEnR-Nav) program to foster research pairing basic science and community-driven scientific aims. The program is led by an academic navigator and a PBRN navigator. Through meetings and joint activities, the program facilitates basic science-community partnerships and the development and conduct of joint research protocols. Outcomes From 2009-2014, 39 investigators pursued 44 preliminary projects through the CEnR-Nav program; 25 of those became 23 approved protocols and 2 substudies. They involved clinical scholar trainees, early-career physician-scientists, faculty, students, postdoctoral fellows, and others. Nineteen (of 25; 76%) identified community partners, of which 9 (47%) named them as coinvestigators. Nine (of 25; 36%) included T3-T4 translational aims. Seven (of 25; 28%) secured external funding, 11 (of 25; 44%) disseminated results through presentations or publications, and 5 (71%) of 7 projects publishing results included a community partner as a coauthor. Of projects with long-term navigator participation, 9 (of 19; 47%) incorporated T3-T4 aims and 7 (of 19; 37%) secured external funding. Next Steps The CEnR-Nav program provides a model for successfully engaging basic scientists with communities to advance and accelerate translational science. This model's durability and generalizability have not been determined, but it achieves valuable short-term goals and facilitates scientifically meaningful community-academic partnerships.
Lechien JR, Hsieh JW, Saussez S
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Unusual case of chronic maxillary rhinosinusitis
ENT-EAR NOSE & THROAT JOURNAL 2017 MAR; 96(3):100-104
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Konig A, Kratschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rad N, Rahbaran B, Rohringer H, Schieck J, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, De Wolf EA, Janssen X, Lauwers J, Van de Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, Daci N, De Bruyn I, Deroover K, Heracleous N, Lowette S, Moortgat S, Moreels L, Olbrechts A, Python Q, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Brun H, Caillol C, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Karapostoli G, Lenzi T, Leonard A, Luetic J, Maer-Schalk T, Marinov A, Randle-Conde A, Seva T, Vander Velde C, Vanlaer P, Yonamine R, Zenoni F, Zhang F, Cimmino A, Cornelis T, Dobur D, Fagot A, Garcia G, Gul M, Poyraz D, Salva S, Schofbeck R, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Beluffi C, Bondu O, Brochet S, Bruno G, Caudron A, Ceard L, De Visscher S, Delaere C, Delcourt M, Forthomme L, Francois B, Giammanco A, Jafari A, Jez P, Komm M, Lemaitre V, Magitteri A, Mertens A, Musich M, Nuttens C, Piotrzkowski K, Quertenmont L, Selvaggi M, Marono MV, Wertz S, Beliy N, Alda WL, Alves FL, Alves GA, Brito L, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Da Silveira GG, Damiao DD, Martins CD, De Souza SF, Guativa LMH, Malbouisson H, Figueiredo DM, Herrera CM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Ahuja S, Bernardes CA, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Moon CS, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Rodozov M, Stoykova S, Sultanov G, Vu-Tova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Fang W, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Cheng T, Jiang CH, Leggat D, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Zhang H, Zhao J, Asawatangtrakuldee C, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Hernandez CFG, Alvarez JDR, Sanabria JC, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Micanovic S, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Assran Y, Elkafrawy T, Kamel AE, Mahrous A, Calpas B, Kadastik M, Murumaa M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Peltola T, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, 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F, Iorio AOM, Lanza G, Lista L, Meola S, Merola M, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benato L, Biasotto M, Boletti A, De Oliveira ACA, Dall'Osso M, Manzano PD, Dorigo T, Dosselli U, Fantinel S, Fanzago F, Gasparini F, Gasparini U, Gulmini M, Lacaprara S, Margoni M, Meneguzzo AT, Pazzini J, Pozzobon N, Ronchese P, Torassa E, Ventura S, Zanetti M, Zotto P, Zucchetta A, Zumerle G, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Bilei GM, Ciangottini D, Fano L, Lariccia P, Leonardi R, Mantovani G, Menichelli M, Saha A, Santocchia A, Androsov K, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Castaldi R, Ciocci MA, Dell'Orso R, Donato S, Fedi G, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Cipriani M, D'imperio G, Del Re D, Diemoz M, Gelli S, Jorda C, Longo E, Margaroli F, 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Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Charaf O, Cooper SI, Henderson C, Rumerio P, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Berry E, Cutts D, Garabedian A, Hakala J, Heintz U, Jesus O, Laird E, Landsberg G, Mao Z, Narain M, Piperov S, Sagir S, Spencer E, Syarif R, Breedon R, Breto G, Burns D, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Gardner M, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Florent A, Hauser J, Ignatenko M, Saltzberg D, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Jandir P, Kennedy E, Lacroix F, Long OR, Malberti M, Negrete MO, Paneva MI, Shrinivas A, Wei H, Wimpenny S, Yates BR, Branson JG, Cerati GB, Cittolin S, Derdzinski M, Gerosa R, Holzner A, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Welke C, Wood J, Wurthwein F, Yagil A, Della Porta GZ, Bhandari R, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Gran J, Heller R, Incandela J, Mccoll N, Mullin SD, Ovcharova A, Richman J, Stuart D, Suarez I, West C, Yoo J, Anderson D, Apresyan A, Bendavid J, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Spiropulu M, Vlimant JR, Xie S, Zhu RY, Andrews MB, Azzolini V, Carlson B, Ferguson T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Jensen F, Johnson A, Krohn M, Mulholland T, Stenson K, Wagner SR, Alexander J, Chaves J, Chu J, Dittmer S, Mirman N, Kaufman GN, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Winn D, Abdullin S, Albrow M, Apollinari G, Banerjee S, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Cremonesi M, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hare D, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Magini N, Marraffino JM, Maruyama S, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Das S, Field RD, Furic IK, Konigsberg J, Korytov A, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Rank D, Shchutska L, Sperka D, Thomas L, Wang J, Wang S, Yelton J, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bein S, Diamond B, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Santra A, Weinberg M, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Kurt P, O'Brien C, Gonzalez IDS, Turner P, Varelas N, Wu Z, Zakaria M, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Anderson I, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Osherson M, Roskes J, Sarica U, Swartz M, Xiao M, Xin Y, You C, Al-Bataineh A, Baringer P, Bean A, Bowen J, Bruner C, Castle J, Kenny RP, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Sanders S, Stringer R, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Ferraioli C, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Kunkle J, Lu Y, Mignerey AC, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bi R, Bierwagen K, Brandt S, Busza W, Cali IA, Demiragli Z, Di Matteo L, Ceballos GG, Goncharov M, Hsu D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Krajczar K, Lai YS, Lee YJ, Levin A, Luckey PD, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Sumorok K, Tatar K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Benvenuti AC, Chatterjee RM, Evans A, Finkel A, Gude A, Hansen P, Kalafut S, Kao SC, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bartek R, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Knowlton D, Kravchenko I, Rodrigues AM, Meier F, Monroy J, Siado JE, Snow GR, Stieger B, Alyari M, Dolen J, George J, Godshalk A, Harrington C, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Baumgartel D, Chasco M, Hortiangtham A, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, Trocino D, Wang RJ, Wood D, Bhattacharya S, Hahn KA, Kubik A, Low JF, Mucia N, Odell N, Pollack B, Schmitt MH, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Smith G, Taroni S, Valls N, Wayne M, Wolf M, Woodard A, Alimena J, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Hughes R, Ji W, Liu B, Luo W, Puigh D, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Luo J, Marlow D, Medvedeva T, Mooney M, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Zuranski A, Malik S, Barker A, Barnes VE, Benedetti D, Folgueras S, Gutay L, Jha MK, Jones M, Jung AW, Jung K, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Sun J, Svyatkovskiy A, Wang F, Xie W, Xu L, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Redjimi R, Roberts J, Rorie J, Tu Z, Zabel J, Betchart B, Bodek A, De Barbaro P, Demina R, Duh YT, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Mesropian C, Chou JP, Contreras-Campana E, Gershtein Y, Espinosa TAG, Halkiadakis E, Heindl M, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Kyriacou S, Lath A, Nash K, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Heideman J, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Juska E, Kamon T, Krutelyov V, Mueller R, Pakhotin Y, Patel R, Perloff A, Pernie L, Rathjens D, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Wang Z, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Goodell J, Hirosky R, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, Wang Y, Wolfe E, Xia F, Clarke C, Harr R, Karchin PE, Lamichhane P, Sturdy J, Belknap DA, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Ojalvo I, Perry T, Pierro GA, Polese G, Ruggles T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Woods N
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Measurement and QCD analysis of double-differential inclusive jet cross sections in pp collisions at root s=8 TeV and cross section ratios to 2.76 and 7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2017 MAR 29; ?(3):? Article 156
A measurement of the double-differential inclusive jet cross section as a function of the jet transverse momentum p(T) and the absolute jet rapidity |y| is presented. Data from LHC proton-proton collisions at root s = 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1), have been collected with the CMS detector. Jets are reconstructed using the anti-k(T) clustering algorithm with a size parameter of 0.7 in a phase space region covering jet p(T) from 74 GeV up to 2.5 TeV and jet absolute rapidity up to |y| = 3.0. The low-p(T) jet range between 21 and 74 GeV is also studied up to |y| = 4.7, using a dedicated data sample corresponding to an integrated luminosity of 5.6 pb(-1). The measured jet cross section is corrected for detector effects and compared with the predictions from perturbative QCD at next-to-leading order (NLO) using various sets of parton distribution functions (PDF). Cross section ratios to the corresponding measurements performed at 2.76 and 7 TeV are presented. From the measured double-differential jet cross section, the value of the strong coupling constant evaluated at the Z mass is alpha(S)(M-Z) = 0.1164(-0.0043)(+0.0060) , where the errors include the PDF, scale, nonperturbative effects and experimental uncertainties, using the CT10 NLO PDFs. Improved constraints on PDFs based on the inclusive jet cross section measurement are presented.
Simunovic M, Brivanlou AH
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Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis
DEVELOPMENT 2017 MAR 15; 144(6):976-985
Cells have an intrinsic ability to self-assemble and self-organize into complex and functional tissues and organs. By taking advantage of this ability, embryoids, organoids and gastruloids have recently been generated in vitro, providing a unique opportunity to explore complex embryological events in a detailed and highly quantitative manner. Here, we examine how such approaches are being used to answer fundamental questions in embryology, such as how cells self-organize and assemble, how the embryo breaks symmetry, and what controls timing and size in development. We also highlight how further improvements to these exciting technologies, based on the development of quantitative platforms to precisely follow and measure subcellular and molecular events, are paving the way for a more complete understanding of the complex events that help build the human embryo.
Tangye SG, Pillay B, Randall KL, Avery DT, Phan TG, Gray P, Ziegler JB, Smart JM, Peake J, Arkwright PD, Hambleton S, Orange J, Goodnow CC, Uzel G, Casanova JL, Reyes SOL, Freeman AF, Su HC, Ma CS
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Dedicator of cytokinesis 8-deficient CD4(+) T cells are biased to a T(H)2 effector fate at the expense of T(H)1 and T(H)17 cells
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2017 MAR; 139(3):933-949
Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of- function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4(+) T cells to disease pathogenesis in these patients has not been thoroughly investigated. Objective: We sought to investigate the phenotype and function of DOCK8-deficient CD4(+) T cells to determine (1) intrinsic and extrinsic CD4 1 T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency. Methods: We performed in-depth analysis of the CD4(+) T-cell compartment of DOCK8-deficient patients. We enumerated subsets of CD4(+) T helper cells and assessed cytokine production and transcription factor expression. Finally, we determined the levels of IgE specific for staple foods and house dust mite allergens in DOCK8-deficient patients and healthy control subjects. Results: DOCK8-deficient memory CD4 1 T cells were biased toward a T(H)2 type, and this was at the expense of T(H)1 and T(H)17 cells. In vitro polarization of DOCK8-deficient naive CD4(+) T cells revealed the TH2 bias and TH17 defect to be T-cell intrinsic. Examination of allergen-specific IgE revealed plasma IgE from DOCK8-deficient patients is directed against staple food antigens but not house dust mites. Conclusion: Investigations into the DOCK8-deficient CD4(+) T cells provided an explanation for some of the clinical features of this disorder: the T(H)2 bias is likely to contribute to atopic disease, whereas defects in T(H)1 and T(H)17 cells compromise antiviral and antifungal immunity, respectively, explaining the infectious susceptibility of DOCK8-deficient patients.
Yin JL, Wong WS, Jang IC, Chua NH
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Co-expression of peppermint geranyl diphosphate synthase small subunit enhances monoterpene production in transgenic tobacco plants
NEW PHYTOLOGIST 2017 FEB; 213(3):1133-1144
Monoterpenes are important for plant survival and useful to humans. In addition to their function in plant defense, monoterpenes are also used as flavors, fragrances and medicines. Several metabolic engineering strategies have been explored to produce monoterpene in tobacco but only trace amounts of monoterpenes have been detected. We investigated the effects of Solanum lycopersicum 1-deoxy-d-xylulose-5-phosphate synthase (SlDXS), Arabidopsis thaliana geranyl diphosphate synthase 1 (AtGPS) and Menthaxpiperita geranyl diphosphate synthase small subunit (MpGPS.SSU) on production of monoterpene and geranylgeranyl diphosphate (GGPP) diversities, and plant morphology by transient expression in Nicotiana benthamiana and overexpression in transgenic Nicotiana tabacum. We showed that MpGPS.SSU could enhance the production of various monoterpenes such as (-)-limonene, (-)-linalool, (-)--pinene/-pinene or myrcene, in transgenic tobacco by elevating geranyl diphosphate synthase (GPS) activity. In addition, overexpression of MpGPS.SSU in tobacco caused early flowering phenotype and increased shoot branching by elevating contents of GA(3) and cytokinins due to upregulated transcript levels of several plastidic 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway genes, geranylgeranyl diphosphate synthases 3 (GGPPS3) and GGPPS4. Our method would allow the identification of new monoterpene synthase genes using transient expression in N.benthamiana and the improvement of monoterpene production in transgenic tobacco plants.
Fava VM, Manry J, Cobat A, Orlova M, Thuc NV, Moraes MO, Sales-Marques C, Stefani MMA, Latini ACP, Belone AF, Thai VH, Abel L, Alcais A, Schurr E
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A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy
PLOS GENETICS 2017 FEB; 13(2):? Article e1006637
Leprosy Type-1 Reactions (T1Rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. Here, we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R. We discovered, replicated and validated T1R-specific associations with SNPs located in chromosome region 10p21.2. Combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with T1R (p = 4.5x10(-8); OR = 1.54, 95% CI = 1.32-1.80). The T1R-risk locus was restricted to a lncRNA-encoding genomic interval with rs1875147 being an eQTL for the lncRNA. Since a genetic overlap between leprosy and inflammatory bowel disease (IBD) has been detected, we evaluated if the shared genetic control could be traced to the T1R endophenotype. Employing the results of a recent IBD GWAS meta-analysis we found that 10.6% of IBD SNPs available in our dataset shared a common risk-allele with T1R (p = 2.4x10(-4)). This finding points to a substantial overlap in the genetic control of clinically diverse inflammatory disorders.
Four studies in this issue report new mechanisms underlying the function of the chromatin remodeling SWI/SNF complex in controlling gene expression and suppressing tumor development, providing valuable insights into the treatment of cancers harboring mutations in genes encoding SWI/SNF complex subunits.
Manning LR, Popowicz AM, Padovan JC, Chait BT, Manning JM
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Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding
ANALYTICAL BIOCHEMISTRY 2017 FEB 15; 519(?):38-41
This report establishes a correlation between two known properties of the human embryonic hemoglobins their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect. (C) 2016 Elsevier Inc. All rights reserved.
Pereira AC, Gray JD, Kogan JF, Davidson RL, Rubin TG, Okamoto M, Morrison JH, McEwen BS
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Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole
MOLECULAR PSYCHIATRY 2017 FEB; 22(2):296-305
Alzheimer's disease (AD) and age-related cognitive decline represent a growing health burden and involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, this study characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes. A comparison of the effects of riluzole in rats against human AD data sets revealed that many of the gene changes in AD are reversed by riluzole. Expression changes identified by RNA-Seq were validated by qRT-PCR open arrays. Riluzole is known to increase the glutamate transporter EAAT2's ability to scavenge excess glutamate, regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an increase in EAAT2 expression in hippocampus, identifying a possible mechanism underlying the improved memory function after riluzole treatment.