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Srivastava DB, Leon K, Osmundson J, Garner AL, Weiss LA, Westblade LF, Glickman MS, Landick R, Darst SA, Stallings CL, Campbell EA
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Structure and function of CarD, an essential mycobacterial transcription factor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013 JUL 30; 110(31):12619-12624
CarD, an essential transcription regulator in Mycobacterium tuberculosis, directly interacts with the RNA polymerase (RNAP). We used a combination of in vivo and in vitro approaches to establish that CarD is a global regulator that stimulates the formation of RNAP-holoenzyme open promoter (RPo) complexes. We determined the X-ray crystal structure of Thermus thermophilus CarD, allowing us to generate a structural model of the CarD/RPo complex. On the basis of our structural and functional analyses, we propose that CarD functions by forming protein/protein and protein/DNA interactions that bridge the RNAP to the promoter DNA. CarD appears poised to interact with a DNA structure uniquely presented by the RPo: the splayed minor groove at the double-stranded/single-stranded DNA junction at the upstream edge of the transcription bubble. Thus, CarD uses an unusual mechanism for regulating transcription, sensing the DNA conformation where transcription bubble formation initiates.
Orlova M, Cobat A, Huong NT, Ba NN, Thuc NV, Spencer J, Nedelec Y, Barreiro L, Thai VH, Abel L, Alcais A, Schurr E
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Gene Set Signature of Reversal Reaction Type I in Leprosy Patients
PLOS GENETICS 2013 JUL; 9(7):? Article e1003624
Leprosy reversal reactions type 1 (T1R) are acute immune episodes that affect a subset of leprosy patients and remain a major cause of nerve damage. Little is known about the relative importance of innate versus environmental factors in the pathogenesis of T1R. In a retrospective design, we evaluated innate differences in response to Mycobacterium leprae between healthy individuals and former leprosy patients affected or free of T1R by analyzing the transcriptome response of whole blood to M. leprae sonicate. Validation of results was conducted in a subsequent prospective study. We observed the differential expression of 581 genes upon exposure of whole blood to M. leprae sonicate in the retrospective study. We defined a 44 T1R gene set signature of differentially regulated genes. The majority of the T1R set genes were represented by three functional groups: i) pro-inflammatory regulators; ii) arachidonic acid metabolism mediators; and iii) regulators of anti-inflammation. The validity of the T1R gene set signature was replicated in the prospective arm of the study. The T1R genetic signature encompasses genes encoding pro- and anti-inflammatory mediators of innate immunity. This suggests an innate defect in the regulation of the inflammatory response to M. leprae antigens. The identified T1R gene set represents a critical first step towards a genetic profile of leprosy patients who are at increased risk of T1R and concomitant nerve damage.
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Klein B, Lellouch J, Marinov A, Mccartin J, Rios AAO, Ryckbosch D, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Walsh S, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Popov A, Selvaggi M, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alves GA, Martins MC, Martins T, Pol ME, Souza MHG, Alda WL, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Malek M, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Jorge LS, Sznajder A, Manganote EJT, Pereira AV, Anjos TS, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PC, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Sultanov G, Vutova M, Dimitrov A, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang 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Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Benhabib L, Bianchini L, Bluj M, Busson P, Chariot C, Daci N, Dahms T, Dalchenko M, Dobrzynski L, Florent A, de Cassagnac RG, Haguenauer M, Mine P, Mironov C, Naranjo IN, Nguyen M, Ochando C, Paganini P, Sabes D, Salerno R, Sirois Y, Veelken C, Zabi A, Agram JL, Andrea J, Bloch D, Bodin D, Brom JM, Chabert EC, Collard C, Conte E, Drouhin F, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Juillot P, Le Bihan AC, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Brochet S, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Sgandurra L, Sordini V, Tschudi Y, Vander Donckt M, Verdier P, Viret S, Tsamalaidze Z, Autermann C, Beranek S, Calpas B, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Klein K, Merz J, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Sprenger D, Weber H, Wittmer B, Zhukov V, Ata M, Caudron J, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Kreuzer P, Merschmeyer M, Meyer A, Olschewski M, Padeken K, Papacz P, Pieta H, Reithler H, Schmitz SA, Sonnenschein L, Steggemann J, Teyssier D, Thuer S, Weber M, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Lingemann J, Nowack A, Nugent IM, Perchalla L, Pooth O, Stahl A, Martin MA, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Costanza F, Pardos CD, Dorland T, Eckerlin G, Eckstein D, Flucke G, Geiser A, Glushkov I, Gunnellini P, Habib S, Hauk J, Hellwig G, Jung H, Kasemann M, Katsas P, Kleinwort C, Kluge H, Kramer M, Krucker D, Kuznetsova E, Lange W, Leonard J, Lipka K, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Naumann-Emme S, Novgorodova O, Nowak F, Olzem J, Perrey H, Petrukhin A, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Riedl C, Ron E, Salfeld-Nebgen J, Schmidt R, Schoerner-Sadenius T, Sen N, Stein M, Walsh R, Wissing C, Blobel V, Enderle H, Erfle J, Gebbert U, Gorner M, Gosselink M, Haller J, Heine K, Hoing RS, Kaussen G, Kirschenmann H, Klanner R, Lange J, Peiffer T, Pietsch N, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Schroder M, Schum T, Seidel M, Sibille J, Sola V, Stadie H, Steinbruck G, Thomsen J, Troendle D, Vanelderen L, Barth C, Baus C, Berger J, Boser C, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Guthoff M, Hackstein C, Hartmann F, Hauth T, Heinrich M, Held H, Hoffmann KH, Husemann U, Katkov I, Komaragiri JR, Kornmayer A, Pardo PL, Martschei D, Mueller S, Mueller T, Niegel M, Nurnberg A, Oberst O, Ott J, Quast G, Rabbertz K, Ratnikov F, Ratnikova N, Rocker S, Schilling FP, Schott G, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Zeise M, Anagnostou G, Daskalakis G, Geralis T, 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GB, Parida B, Sudhakar K, Wickramage N, Banerjee S, Dugad S, Arfaei H, Bakhshiansohi H, Etesami SM, Fahim A, Hesari H, Jafari A, Khakzad M, Najafabadi MM, Mehdiabadi SP, Safarzadeh B, Zeinali M, Grunewald M, Abbrescia M, Barbone L, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Fiippis N, De Palma M, Fiore L, Iaselli G, Maggi G, Maggi M, Marangelli B, My S, Nuzzo S, Pacifico N, Pompili A, Pugliese G, Selvaggi G, Silvestris L, Singh G, Venditti R, Verwilligen P, Zito G, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi P, Castro A, Cavallo FR, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Meneghelli M, Montanari A, Navarria FL, Odorici F, Perrotta A, Primavera F, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Chiorboli M, Costa S, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Fabbricatore P, Musenich R, Tosi S, Benaglia A, De Guio F, Di Matteo L, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Massironi A, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, De Cosa A, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bellan P, Biasotto M, Bisello D, Branca A, Carlin R, Checchia P, Dorigo T, Galanti M, Gasparini F, Gasparini U, Giubilato P, Gozzelino A, Gulmini M, Kanishchev K, Lacaprara S, Lazzizzera I, Margoni M, Meneguzzo AT, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Vanini S, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Vitulo P, Biasini M, Bilei GM, Fano L, Lariccia P, Mantovani G, Menichelli M, Nappi A, Romeo F, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri P, Bagliesi G, Boccali T, Broccolo G, Castaldi R, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Kraan A, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PC, Vernieri C, Barone L, Cavallari F, Del Re D, Diemoz M, Fanelli C, Grassi M, Longo E, Margaroli F, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Soffi L, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Cartiglia N, Casasso S, Costa M, Dattola D, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Potenza A, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Tamponi U, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, La Licata C, Marone M, Montanino D, Penzo A, Schizzi A, Zanetti A, Kim TY, Nam SK, Chang S, Kim DH, Kim GN, Kim JE, Kong DJ, Oh YD, Park H, Son DC, Kim JY, Kim ZJ, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim TJ, Lee KS, Park SK, Roh Y, Choi M, Kim JH, Park C, Park IC, Park S, Ryu G, Choi Y, Choi YK, Goh J, Kim MS, Kwon E, Lee B, Lee J, Lee S, Seo H, Yu I, Grigelionis I, Juodagalvis A, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Lopez-Fernandez R, Martinez-Ortega J, Sanchez-Hernandez A, Villasenor-Cendejas LM, Moreno SC, Valencia FV, Ibarguen HAS, Linares EC, Pineda AM, Reyes-Santos MA, Krofcheck D, Bell AJ, Butler PH, Doesburg R, Reucroft S, Silverwood H, Ahmad M, Asghar MI, Butt J, Hoorani HR, Khalid S, Khan WA, Khurshid T, Qazi S, Shah MA, Shoaib M, Bialkowska H, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Wrochna G, Zalewski P, Brona G, Bunkowski K, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Wolszczak W, Almeida N, Bargassa P, David A, Faccioli P, Parracho PCF, Gallinaro M, Antunes JR, Seixas J, Varela J, Vischia P, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Laney A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Skatchkov N, Smirnov V, Zarubin A, Evstyukhin S, Golovtsov V, Ivanov Y, Kim V, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Erofeeva M, Gavrilov V, Lychkovskaya N, Popov V, Safronov G, Semenov S, Spiridonov A, Stolin V, Vlasov E, Zhokin A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Markina A, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Azhgirey I, Bayshev I, Bitioukov S, Kachanov V, Kalinin A, Konstantinov D, Krychkine V, Petrov V, Ryutin R, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Ekmedzic M, Krpic D, Milosevic J, Aguilar-Benitez M, Maestre JA, Battilana C, Calvo E, Cerrada M, Llatas MC, Colino N, De La Cruz B, Peris AD, Vazquez DD, Bedoya CF, Ramos JPF, Ferrando A, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, Merino G, De Martino EN, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Santaolalla J, Soares MS, Willmott C, Albajar C, de Troconiz JF, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Iglesias LL, Gomez JP, Cifuentes JAB, Cabrillo IJ, Calderon A, Chuang SH, Campderros JD, Fernandez M, Gomez G, Sanchez JG, Graziano A, Jorda C, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Sanchez FJM, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Auzinger G, Bachtis M, Lon PB, Ball AH, Barney D, Bendavid J, Benitez JF, Bernet C, Bianchi G, Bloch P, Bocci A, Bonato A, Bondu O, Botta C, Breuker H, Camporesi T, Cerminara G, Christiansen T, Perez JAC, Colafranceschi S, d'Enterria D, Dabrowski A, De Roeck A, 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Belknap DA, Borrello L, Carlsmith D, Cepeda M, Dasu S, Friis E, Grogg KS, Grothe M, Hall-Wilton R, Herndon M, Herve A, Kaadze K, Klabbers P, Klukas J, Lanaro A, Lazaridis C, Loveless R, Mohapatra A, Mozer MU, Ojalvo I, Pierro GA, Ross I, Savin A, Smith WH, Swanson J
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Measurement of the Lambda(0)(b) lifetime in pp collisions at root s=7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2013 JUL; ?(7):? Article 163
A measurement of the Lambda(0)(b) lifetime using the decay Lambda(0)(b) -> J/psi Lambda in protonproton collisions at root s = 7TeV is presented. The data set, corresponding to an integrated luminosity of about 5 fb(-1), was recorded with the CMS experiment at the Large Hadron Collider using triggers that selected dimuon events in the J/psi mass region. The Lambda(0)(b) lifetime is measured to be 1.503 +/- 0.052 (stat.) +/- 0.031 (syst.) ps
Nakano H, Burgents JE, Nakano K, Whitehead GS, Cheong C, Bortner CD, Cook DN
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Migratory properties of pulmonary dendritic cells are determined by their developmental lineage
MUCOSAL IMMUNOLOGY 2013 JUL; 6(4):678-691
The chemokine receptor, CCR7, directs the migration of dendritic cells (DCs) from peripheral tissue to draining lymph nodes (LNs). However, it is unknown whether all pulmonary DCs possess migratory potential. Using novel Ccr7(gfp) reporter mice, wefound that Ccr7 is expressed in CD103(+) and a CD14(med/Io) subset of CD11b(hi) classical (c) DCs but not in monocyte-derived (mo) DCs, including Ly-6C(hi) CD11b(hi) inflammatory DCs and CD14(hi) CD11b(hi) DCs. Consequently, cDCs migrated to lung-draining LNs but moDCs did not. Mice lacking the chemokine receptor, CCR2, also lacked inflammatory DCs in the lung after lipopolysaccharide inhalation but retained normal levels of migratory DCs. Conversely, the lungs of fms-like tyrosine kinase 3 ligand (Flt3L)-deficient mice lacked cDCs but retained moDCs, which were functionally mature but did not express Ccr7 and were uniformly non-migratory. Thus, the migratory properties of pulmonary DCs are determined by their developmental lineage.
Coelho-dos-Reis JGA, Passos L, Duarte MC, Araujo MG, Campi-Azevedo AC, Teixeira-Carvalho A, Peruhype-Magalhaes V, Trindade BC, Dias RD, Martins ML, Carneiro-Proietti ABD, Guedes AC, Goncalves DU, Martins OA
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Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders
PLOS NEGLECTED TROPICAL DISEASES 2013 JUL; 7(7):? Article e2328
In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+)HLA-DR+, CD8(+) T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-alpha/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.
Zhang MZM, Wu PYJ, Kelly FD, Nurse P, Hang HC
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Quantitative Control of Protein S-Palmitoylation Regulates Meiotic Entry in Fission Yeast
PLOS BIOLOGY 2013 JUL; 11(7):? Article e1001597
Protein S-palmitoylation, a lipid modification mediated by members of the palmitoyltransferase family, serves as an important membrane-targeting mechanism in eukaryotes. Although changes in palmitoyltransferase expression are associated with various physiological and disease states, how these changes affect global protein palmitoylation and cellular function remains unknown. Using a bioorthogonal chemical reporter and labeling strategy to identify and analyze multiple cognate substrates of a single Erf2 palmitoyltransferase, we demonstrate that control of Erf2 activity levels underlies the differential modification of key substrates such as the Rho3 GTPase in vegetative and meiotic cells. We show further that modulation of Erf2 activity levels drives changes in the palmitoylome as cells enter meiosis and affects meiotic entry. Disruption of Erf2 function delays meiotic entry, while increasing Erf2 palmitoyltransferase activity triggers aberrant meiosis in sensitized cells. Erf2-induced meiosis requires the function of the Rho3 GTPase, which is regulated by its palmitoylation state. We propose that control of palmitoyltransferase activity levels provides a fundamental mechanism for modulating palmitoylomes and cellular functions.
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CB1 receptor signaling regulates social anxiety and memory
GENES BRAIN AND BEHAVIOR 2013 JUL; 12(5):479-489
The endocannabinoid (eCB) system regulates emotion, stress, memory and cognition through the cannabinoid type 1 (CB1) receptor. To test the role of CB1 signaling in social anxiety and memory, we utilized a genetic knockout (KO) and a pharmacological approach. Specifically, we assessed the effects of a constitutive KO of CB1 receptors (CB1KOs) and systemic administration of a CB1 antagonist (AM251; 5mg/kg) on social anxiety in a social investigation paradigm and social memory in a social discrimination test. Results showed that when compared with wild-type (WT) and vehicle-treated animals, CB1KOs and WT animals that received an acute dose of AM251 displayed anxiety-like behaviors toward a novel male conspecific. When compared with WT animals, KOs showed both active and passive defensive coping behaviors, i.e. elevated avoidance, freezing and risk-assessment behaviors, all consistent with an anxiety-like profile. Animals that received acute doses of AM251 also showed an anxiety-like profile when compared with vehicle-treated animals, yet did not show an active coping strategy, i.e. changes in risk-assessment behaviors. In the social discrimination test, CB1KOs and animals that received the CB1 antagonist showed enhanced levels of social memory relative to their respective controls. These results clearly implicate CB1 receptors in the regulation of social anxiety, memory and arousal. The elevated arousal/anxiety resulting from either total CB1 deletion or an acute CB1 blockade may promote enhanced social discrimination/memory. These findings may emphasize the role of the eCB system in anxiety and memory to affect social behavior.
Armbruster M, Messa M, Ferguson SM, De Camilli P, Ryan TA
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Dynamin phosphorylation controls optimization of endocytosis for brief action potential bursts
ELIFE 2013 JUL 30; 2(?):? Article e00845
Modulation of synaptic vesicle retrieval is considered to be potentially important in steady-state synaptic performance. Here we show that at physiological temperature endocytosis kinetics at hippocampal and cortical nerve terminals show a bi-phasic dependence on electrical activity. Endocytosis accelerates for the first 15-25 APs during bursts of action potential firing, after which it slows with increasing burst length creating an optimum stimulus for this kinetic parameter. We show that activity-dependent acceleration is only prominent at physiological temperature and that the mechanism of this modulation is based on the dephosphorylation of dynamin 1. Nerve terminals in which dynamin 1 and 3 have been replaced with dynamin 1 harboring dephospho- or phospho-mimetic mutations in the proline-rich domain eliminate the acceleration phase by either setting endocytosis at an accelerated state or a decelerated state, respectively.
Josefowicz SZ
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Regulators of chromatin state and transcription in CD4 T-cell polarization
IMMUNOLOGY 2013 JUL; 139(3):299-308
Mature naive CD4 T-cells possess the potential for an array of highly specialized functions, from inflammatory to potently suppressive. This potential is encoded in regulatory DNA elements and is fulfilled through modification of chromatin and selective activation by the collaborative function of diverse transcription factors in response to environmental cues. The mechanisms and strategies employed by transcription factors for the programming of CD4 T-cell subsets will be discussed. In particular, the focus will be on co-operative activity of environmental response factors in the initial activation of regulatory DNA elements and chromatin alteration, and the subsequent role of master regulator' transcription factors in defining the fidelity and environmental responsiveness of different CD4 T-cell subsets.