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Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED
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A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization
DEVELOPMENTAL CELL 2016 NOV 7; 39(3):302-315
The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high density hESCs localize their receptors to transforming growth factor 13 at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge. This relocalization insulates cells at the center from apically applied ligands while maintaining response to basally presented ones. In addition, BMP4 directly induces the expression of its own inhibitor, NOGGIN, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors to predict human fate positioning in gastruloids and, potentially, the human embryo.
Cohen JE
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Statistics of Primes (and Probably Twin Primes) Satisfy Taylor's Law from Ecology
AMERICAN STATISTICIAN 2016 NOV; 70(4):399-404
Taylor's law, which originated in ecology, states that, in sets of measurements of population density, the sample variance is approximately proportional to a power of the sample mean. Taylor's law has been verified for many species ranging from bacterial to human. Here, we show that the variance V(x) and the mean M(x) of the primes not exceeding a real number x obey Taylor's law asymptotically for large x. Specifically, V(x) similar to (1/3)(M(x))(2) as x -> infinity. This apparently new fact about primes shows that Taylor's law may arise in the absence of biological processes, and that patterns discovered in biological data can suggest novel questions in numbertheory. If the Hardy-Littlewood twin primes conjecture is true, then the identical Taylor's law holds also for twin primes. Taylor's law holds in both instances because the primes (and the twin primes, given the conjecture) not exceeding x are asymptotically uniformly distributed on the integers in [2,x]. Hence, asymptotically M(x) similar to x/2, V(x) similar to x(2)/12. Higher-order moments of the primes (twin primes) not exceeding x satisfy a generalized Taylor's law. The 11,078,937 primes and 813,371 twin primes not exceeding 2 x 10(8) illustrate these results.
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G, Karapostoli G, Kenzie M, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Nash J, Nikitenko A, Pela J, Pesaresi M, Petridis K, Raymond DM, Richards A, Rose A, Seez C, Sharp P, Tapper A, Uchida K, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leggat D, Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Pastika N, Scarborough T, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Gastler D, Lawson P, Rankin D, Richardson C, Rohlf J, St John J, Sulak L, Zou D, Alimena J, Berry E, Bhattacharya S, Cutts D, Demiragli Z, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Laird E, Landsberg G, Mao Z, Narain M, Sagir S, Sinthuprasith T, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Gardner M, Ko W, Lander R, 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, Farrell C, Hauser J, Ignatenko M, Rakness G, Saltzberg D, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Rikova MI, Jandir P, Kennedy E, Lacroix F, Long OR, Luthra A, Malberti M, Negrete MO, Shrinivas A, Sumowidagdo S, Wei H, Wimpenny S, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Holzner A, Kelley R, Klein D, Kovalskyi D, Letts J, Macneill I, Olivito D, Padhi S, Palmer C, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Tu Y, Vartak A, Wasserbaech S, Welke C, Wurthwein F, Yagil A, Della Porta GZ, Barge D, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Gran J, Incandela J, Justus C, Mccoll N, Mullin SD, Richman J, Stuart D, To W, West C, Yoo J, Anderson D, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Pierini M, Spiropulu M, Vlimant JR, Xie S, Zhu RY, Azzolini V, Calamba A, Carlson B, Ferguson T, Iiyama Y, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Jensen F, Johnson A, Krohn M, Mulholland T, Nauenberg U, Smith JG, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Ryd A, Skinnari L, Sun W, Tan SM, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Wittich P, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Hu Z, Jindariani S, Johnson M, Joshi U, Jung AW, Klima B, Kreis B, Kwan S, Lammel S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, No JMMF, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Whitbeck A, Yang F, Yin H, Acosta D, Avery P, Bortignon P, Bourilkov D, Carnes A, Carver M, Curry D, Das S, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Muniz L, Rank D, Rinkevicius A, Shchutska L, Snowball M, Sperka D, Wang SJ, Yelton J, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Veeraraghavan V, Weinberg M, Bhopatkar V, Hohlmann M, Kalakhety H, Mareskas-Palcek 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, Silkworth C, Turner P, Varelas N, Wu Z, Zakaria M, Bilki B, Clarida W, Dilsiz K, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Sen S, Snyder C, Tan P, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Fehling D, Feng L, Gritsan AV, Maksimovic P, Martin C, Nash K, Osherson M, Swartz M, Xiao M, Xin Y, Baringer P, Bean A, Benelli G, Bruner C, Gray J, Kenny RP, Majumder D, Malek M, Murray M, Noonan D, Sanders S, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Saini LK, Skhirtladze N, Svintradze I, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Lu Y, Mignerey AC, Pedro K, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bierwagen K, Brandt S, Busza W, Cali IA, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Mcginn C, Niu X, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Sumorok K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Dahmes B, Finkel A, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Nourbakhsh S, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Meier F, Monroy J, Ratnikov F, Siado JE, Snow GR, Alyari M, Dolen J, George J, Godshalk A, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Rappoccio S, 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, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Trovato M, Velasco M, Won S, Brinkerhoff A, Dev N, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Meng F, Mueller C, Musienko Y, Pearson T, Planer M, Ruchti R, Smith G, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Kotov K, Ling TY, Liu B, Luo W, Puigh D, Rodenburg M, Winer BL, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Piroue P, Quan X, Saka H, Stickland D, Tully C, Werner JS, Zuranski A, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Miller DH, Neumeister N, Primavera F, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Sun J, Svyatkovskiy A, Wang F, Xie W, Xu L, Zablocki J, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, 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, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Petrillo G, Verzetti M, Vishnevskiy D, Demortier L, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Sheldon P, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Search for third-generation scalar leptoquarks in the t tau channel in proton-proton collisions at root s = 8 TeV (vol 7, 042, 2015)
JOURNAL OF HIGH ENERGY PHYSICS 2016 NOV 9; ?(11):? Article 056
Akiba K, Akbiyik M, Albrow M, Arneodo M, Avati V, Baechler J, Baillie OV, Bartalini P, Bartels J, Baur S, Baus C, Beaumont W, Behrens U, Berge D, Berretti M, Bossini E, Boussarie R, Brodsky S, Broz M, Bruschi M, Bussey P, Byczynski W, Noris JCC, Villar EC, Campbell A, Caporale F, Carvalho W, Chachamis G, Chapon E, Cheshkov C, Chwastowski J, Ciesielski R, Chinellato D, Cisek A, Coco V, Collins P, Contreras JG, Cox B, Damiao DD, Davis P, Deile M, D'Enterria D, Druzhkin D, Ducloue B, Dumps R, Dzhelyadin R, Dziurdzia P, Eliachevitch M, Fassnacht P, Ferro F, Fichet S, Figueiredo D, Field B, Finogeev D, Fiore R, Forshaw J, Medina AG, Gallinaro M, Granik A, von Gersdorff G, Giani S, Golec-Biernat K, Goncalves VP, Gottlicher P, Goulianos K, Grosslord JY, Harland-Lang LA, Van Haevermaet H, Hentschinski M, Engel R, Corral GH, Hollar J, Huertas L, Johnson D, Katkov I, Kepka O, Khakzad M, Kheyn L, Khachatryan V, Khoze VA, Klein S, van Klundert M, Krauss F, Kurepin A, Kurepin N, Kutak K, Kuznetsova E, Latino G, Lebiedowicz P, Lenzi B, Lewandowska E, Liu S, Luszczak A, Luszczak M, Madrigal JD, Mangano M, Marcone Z, Marquet C, Martin AD, Martin T, Hernandez MIM, Martins C, Mayer C, Mc Nulty R, Van Mechelen P, Macula R, da Costa EM, Mertzimekis T, Mesropian C, Mieskolainen M, Minafra N, Monzon IL, Mundim L, Murdaca B, Murray M, Niewiadowski H, Nystrand J, de Oliveira EG, Orava R, Ostapchenko S, Osterberg K, Panagiotou A, Papa A, Pasechnik R, Peitzmann T, Moreno LAP, Pierog T, Pinfold J, Poghosyan M, Pol ME, Prado W, Popov V, Rangel M, Reshetin A, Revol JP, Rijssenbeek M, Rodriguez M, Roland B, Royon C, Ruspa M, Ryskin M, Vera AS, Safronov G, Sako T, Schindler H, Salek D, Safarik K, Saimpert M, Santoro A, Schicker R, Seger J, Sen S, Shabanov A, Schafer W, Da Silveira GG, Skands P, Soluk R, van Spilbeeck A, Staszewski R, Stevenson S, Stirling WJ, Strikman M, Szczurek A, Szymanowski L, Takaki JDT, Tasevsky M, Taesoo K, Thomas C, Torres SR, Tricomi A, Trzebinski M, Tsybychev D, Turini N, Ulrich R, Usenko E, Varela J, Lo Vetere M, Tello AV, Pereira AV, Volyanskyy D, Wallon S, Wilkinson G, Wohrmann H, Zapp KC, Zoccarato Y
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LHC forward physics
JOURNAL OF PHYSICS G-NUCLEAR AND PARTICLE PHYSICS 2016 NOV; 43(11):? Article 110201
Lv ZJ, Krasnoslobodtsev AV, Zhang YL, Ysselstein D, Rochet JC, Blanchard SC, Lyubchenko YL
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Effect of Acidic pH on the Stability of alpha-Synuclein Dimers
BIOPOLYMERS 2016 OCT; 105(10):715-724
Environmental factors, such as acidic pH, facilitate the assembly of a-synuclein (a-Syn) in aggregates, but the impact of pH on the very first step of a-Syn aggregation remains elusive. Recently, we developed a single-molecule approach that enabled us to measure directly the stability of a-Syn dimers. Unlabeled a-Syn monomers were immobilized on a substrate, and fluorophore-labeled monomers were added to the solution to allow them to form dimers with immobilized a-Syn monomers. The dimer lifetimes were measured directly from the fluorescence bursts on the time trajectories. Herein, we applied the single-molecule tethered approach for probing of intermolecular interaction to characterize the effect of acidic pH on the lifetimes of a-Syn dimers. The experiments were performed at pH 5 and 7 for wild-type a-Syn and for two mutants containing familial type mutations E46K and A53T. We demonstrate that a decrease of pH resulted in more than threefold increase in the a-Syn dimers lifetimes with some variability between the a-Syn species. We hypothesize that the stabilization effect is explained by neutralization of residues 96-140 of a-Syn and this electrostatic effect facilitates the association of the two monomers. Given that dimerization is the first step of a-Syn aggregation, we posit that the electrostatic effect thereby contributes to accelerating a-Syn aggregation at acidic pH. (C) 2016 Wiley Periodicals, Inc.
Kimm SY, Tarin TV, Monette S, Srimathveeravalli G, Gerber D, Durack JC, Solomon SB, Scardino PT, Scherz A, Coleman J
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Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy
RADIOLOGY 2016 OCT; 281(1):109-118
Purpose: To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non-tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods: By using an institutional animal care and use committee-approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material-enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylineosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results: Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P,< .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 mm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion: WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. (C) RSNA, 2016
Gristick HB, von Boehmer L, West AP, Schamber M, Gazumyan A, Golijanin J, Seaman MS, Fatkenheuer G, Klein F, Nussenzweig MC, Bjorkman PJ
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Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2016 OCT; 23(10):906-915
HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-angstrom- and 3.9-angstrom-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46 derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.
Simunovic M, Evergren E, Golushko I, Prevost C, Renard HF, Johannes L, McMahon HT, Lorman V, Voth GA, Bassereau P
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How curvature-generating proteins build scaffolds on membrane nanotubes
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016 OCT 4; 113(40):11226-11231
Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube's length. Ourwork implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30-40% of a tube's surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes.
Wang SP, Wang LH
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Disease implication of hyper-Hippo signalling
OPEN BIOLOGY 2016 OCT; 6(10):? Article 160119
The Hippo signalling pathway regulates cellular proliferation, apoptosis and differentiation, thus exerting profound effects on cellular homeostasis. Inhibition of Hippo signalling has been frequently implicated in human cancers, indicating a well-known tumour suppressor function of the Hippo pathway. However, it is less certain whether and how hyperactivation of the Hippo pathway affects biological outcome in living cells. This review describes current knowledge of the regulatory mechanisms of the Hippo pathway, mainly focusing on hyperactivation of the Hippo signalling nexus. The disease implications of hyperactivated Hippo signalling have also been discussed, including arrhythmogenic cardiomyopathy, Sveinsson's chorioretinal atrophy, Alzheimer's disease, amyotrophic lateral sclerosis and diabetes. By highlighting the significance of disease-relevant Hippo signalling activation, this review can offer exciting prospects to address the onset and potential reversal of Hippo-related disorders.
Mitsui H, Kiecker F, Shemer A, Cannizzaro MV, Wang CQF, Gulati N, Ohmatsu H, Shah KR, Gilleaudeau P, Sullivan-Whalen M, Cueto I, McNutt NS, Suarez-Farinas M, Krueger JG
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Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria
JOURNAL OF INVESTIGATIVE DERMATOLOGY 2016 OCT; 136(10):2030-2040
Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change >2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFN gamma) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations.