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M15 White Phosphorous grenade http //www.globalsecurity.org/military/systems/munitions/m15.htm M15 White Phosphorous grenade The M15 White Phosphorous grenade is a bursting type grenade used for signaling, screening, and incendiary purposes. M15の白リン手榴弾 M15の白リン手榴弾は信号、煙幕、焼夷の目的に使用される爆発タイプ手榴弾です。 (1) Body -- sheet metal. (2) Filler -- 15 ounces of white phosphorus. (3) Fuze -- M206A2. (4) Weight -- 31 ounces. (5) Capabilities -- the average soldier can throw the grenade 30 meters. The grenade has a bursting radius of 17 meters. All friendly personnel within this 17-meter area should be in a covered position to avoid being struck by burning particles. The WP filler burns for about 60 seconds at a temperature of 5,000 degrees Fahrenheit. This intense heat causes the smoke produced by the grenade to rise quite rapidly, especially in cool climates. This makes the M15 grenade less desirable for use as a screening agent. 能力--平均的な兵隊ならこの手榴弾を30メーター投げることができます。 この手榴弾の爆発半径は17メーターです。 友軍兵士は、この17メーターの領域の中のいるときは、燃えている破片が当たらないように、遮蔽された場所にいなくてはなりません。白リン充填物はおよそ60秒の間華氏5,000度で燃えます。この高温によって手榴弾が発生する煙を、寒冷地においてでさえ、瞬時に立ち上げます。そのためにM15手榴弾は煙幕弾としての使用上の不具合が少ないのです。 (6) Color/markings -- grey with one yellow band and yellow markings. (7) First aid -- treat burns caused by WP in the same way as ordinary burns. If particles of WP are embedded in the flesh, immerse the wound in water or pack with wet cloths to halt combustion. Then pick out or squeeze out the WP. The particles will reignite spontaneously if allowed to dry. Apply copper sulphate solution to halt combustion of the WP particles. This permits them to be removed without igniting. 応急処置--普通のやけどと同様に、WPによって引き起こされたやけどを扱ってください。 WPの粒子が肉に埋め込まれるなら、傷を水に浸すか、またはぬれた布で荷造りして、燃焼を止めてください。 そして、WPをつまみ取るか、または絞り出してください。 もし乾くままにさせると、粒子は自然に再発火するでしょう。 硫酸銅溶液を利用してWP粒子の燃焼を止めてください。 硫酸銅溶液は、WP粒子が再発火しないで取り除かれることを許容します。 References GRENADES AND PYROTECHNIC SIGNALS Field Manual FM 23-30 DEPARTMENT OF THE ARMY, 27 December 1988
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Hold me, Darling Come and listen to me (Hey! Girl!) Trust me, Baby Wanna be your boy (Again! Please!) Oh yes! I know just how you feel So mad... Oh please! Smile at me! I am sorry that I did too much lying Oh Girl, I regret I was a jerk, and I was a fool! (Come on! Girl! Smile! Easy, girl!) (Come on! Girl! Smile! Easy, girl!) ★ Come on, Baby Don t be upset with me (Hey! Girl!) Kiss me, Hug me, Just give me a chance (Again! Please!) Oh no, I am such a big mess Without you ★★ Oh! Please, hear me out May be a fool, but I love you so much Oh Girl, don t leave me You are my princess, You are my love Listen, Baby How about we go out Tonight? (Hey! Girk!) Trust me, Baby Wanna be your boy (Again! Please!) My Girl! I even got the red Fiat Just for you Oh please! Let me take you out I know you d look gorgeous in your new pink dress Oh Girl, you ll take my breath away I need that smile now back on your face! (Come on! Girl! Smile! Let me take you out) (Come on! Girl! Smile! I wanna make it up) ★ Repeat ★★ Repeat ★★ Repeat
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本シリーズの最終作。人気曲投票をもとに選ばれた従来の曲に加え、THE FINAL独自の新曲や待望の『beatmania III』曲、その他のBEMANIシリーズの移植曲を含め、全189曲の収録を実現。代わりにムービーは大幅に縮小され、それまでの「カウンターフレーム」と小型ムービー画面を組み合わせたものがデフォルトのスキンとなった。その他、新たに「STEALTH」オプション(従来の「HIDDEN+SUDDEN」に該当。同モードが兄弟機種の『beatmania IIDX』に倣って譜面中間で一瞬オブジェが表示される仕様に変更されたのに伴い、従来の「オブジェが一切見えないモード」として登場)と曲順のカテゴリチェンジが搭載。 また、プロデューサーを務めたKAGEの「末永くプレイして欲しい」という意向から、本作では隠し解禁コマンドが従来の「プレイヤーが打ち込む形式で、電源を切ったらリセット」ではなく、当時の『IIDX』と同様にテストモードでのコマンド入力方式（オペレーター向け内部設定）となり、電源を切っても解禁された状態が保存される仕様となった。前作の隠し解禁コマンドが特に煩雑であったことから、リリースから年月を経て古くからのファンが久しぶりに触れる時に、解禁コマンドを忘れてしまったことで困ることがないようにとの配慮があったものと思われる。 『beatmania』の歴史を限界まで詰め込んだ本作は、多くのファンからの熱い期待に大いに応える出来で、今もなお日本のあちこちで現役で稼動している。一部のユーザーからはコンシューマー版が発売される事を熱望されている。 （『wikipedia/beatmaniaの項』） ◆通常選択可能楽曲／THE FINALオリジナル 2.14.13 birdman calling for distiny CAT MAN fellows FIRE WIRE HIT N SLAP LA BRISE D ETE LOVE D RIVE NURUHACHI one seek perfect sunrise PURE DREAM RE-ROOTS SAVIOR SHOX special energy SYNTH 1997 taulanaewn ULTRA 赤カーテン 蝶の羽 ◆通常選択可能楽曲／beatmania III移植曲 12.4? All is vanity? ASK? Badboy flygirl? EAST MEETS WEST? feeling of love? Jam & Marmalade? Keep On Liftin ? Live together? mnemoniq? Overwhelming? qingdao? Rest my mind? Shake it down? Stay with me? Twin Bee (Generation X)? ◆通常選択可能楽曲／移植曲 Ain t It Good BAILA！ BAILA！ BODY BRILLIANT 2U CANDY☆ DANCE THE NIGHT AWAY Dr.LOVE GAMBOL GAMELAN DE COUPLE gentle stress Happy Man IMPLANTATION Jet World KISS KISS KISS MGS2 missionR Quickening VOIDDD 大見解 西新宿清掃曲 ◆通常選択可能曲／旧曲 2 GORGEOUS 4U 2 GORGEOUS 4U (EMULATE MIX)? 20,NOVEMBER (HARD MIX)? 20,NOVEMBER (NAGUREO KIDDING STYLE)? 20,NOVEMBER (RADIO EDIT)? 20,NOVEMBER (SINGLE MIX)? 22DUNK? 321 STARS? 7000 QUESTIONS ACID BOMB AFRONOVA PRIMEVAL AIR ALIENHEAD AREA CODE ASIAN 573 ATTACK THE MUSIC ATTACK THE MUSIC [49 MUSIC MIX] BABY BABY GIMME YOUR LOVE 2002 BEGINNING OF LIFE BEGINNING OF LIFE [THE GROUND PULSE MIX] BELIEVE AGAIN [HYPER MEGA MIX] BE LOVIN CALDERA CAPPUCCINO BOSSA CATCH IT! CHAIN CHAIN [CONNECTION MIX] CHAMPION CODE RED COME AND GET IT CRYMSON CRYMSON [SCARLET MIX] CYCLE DEEP CLEAR EYES DEEP IN YOU DENIM DENIM [ELECTRO MIX] DISABLED THE FLAW DISCO DANCING DISCO DOG DO YOU LOVE ME? DO YOU LOVE ME? [SOFT LANDING MIX] DRUNK MONKY E-MOTION E-MOTION [2ND MIX] E-MOTION [ROMANTIC STYLE] FEEL THE LIGHT FIND OUT FIRE DUB FREE KICKER GENOM SCREAMS GENOM SCREAMS [SPIRITUAL MIX] GREED EATER GUILTY HEALEN HELL SCAPER HELL SCAPER [SLASHING MIX] HIGHER HUNTING FOR YOU HYSTERIA 2001 JACK AND MARK GET BUSY! JAM JAM REGGAE KEEP ON MOVIN KOUYOU LIFE GOES ON LIGHT MOTION LINN1999 LIQUID RAIN LOGICAL DASH LOVE SO GROOVY LOVE SO GROOVY [12INCH VERSION] LOVE S THEME OF BEATMANIA LUV TO ME LUV TO ME [DISCO MIX] MANMACHINE PLAYS JAZZ METALGEAR SOLID [MAIN THEME] MOMENT MONOTONE MY DJ NOFIA OVERDOSER [AMBIENT MIX] OVERDOSER [DRIVING DUB MIX] OVERDOSER [ROMO MIX] PARANOIA MAX [DIRTY MIX] PARANOIA MAX [FUNKY BLEEP MIX] PEACE DREAM PEACE-OUT PINK DREAM PRINCE ON A STAR QUICK MASTER [REFORM VERSION] R3 REFERENCE RELEASE YOUR MIND RESOLVE ROCK THE BEATZ RUGGED ASH SALAMANDER BEAT CRUSH MIX SALAMANDER BEAT CRUSH MIX [CRASH MIX] S.D.Z S.F.M SKA A GO GO SKA A GO GO [PERFECT MIX] SODA (DRUM N BASS) SOMETHING SPECIAL SPARKER STEEL CAGE SUPER HIGHWAY SUPER HIGHWAY [SUPER SUBWAY MIX] SURGE LINE TEAR IT UP TETRAQ THE FALL THRASH TRAXX TOKAI TURNING THE MOTOR OVER U GOTTA GROOVE VIRTUAL DRUMMER WATER FLAME WATERING WHAT IS LOVE? WHAT S NEXT? WILD I/O ZANZIBAR 超楽C-E-Z ホワイトレクチャー 夜間行 [MA-REMIX] ◆隠し曲／THE FINALオリジナル COREDESAT ◆隠し曲／移植曲 12.4 CLOUDY MUSIC Miracle Moon RETROFUTURE The least 100sec.
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http //www.globalsecurity.org/military/systems/munitions/m15.htm M15 White Phosphorous grenade cf. M34 WHITE PHOSPHORUS HAND GRENADE The M15 White Phosphorous grenade is a bursting type grenade used for signaling, screening, and incendiary purposes. (1) Body -- sheet metal. (2) Filler -- 15 ounces of white phosphorus. (3) Fuze -- M206A2. (4) Weight -- 31 ounces. (5) Capabilities -- the average soldier can throw the grenade 30 meters. The grenade has a bursting radius of 17 meters. All friendly personnel within this 17-meter area should be in a covered position to avoid being struck by burning particles. The WP filler burns for about 60 seconds at a temperature of 5,000 degrees Fahrenheit. This intense heat causes the smoke produced by the grenade to rise quite rapidly, especially in cool climates. This makes the M15 grenade less desirable for use as a screening agent. 能力--普通の軍人は30個のメーターを手榴弾に投げることができます。 手榴弾には、17メーターのはち切れる半径があります。 この17メーターの領域の中のすべての好意的な人員が燃焼粒子によって打たれるのを避ける覆われた立場にいるべきです。 WPフィラーは約60秒間、華氏5,000度の温度で燃えます。 この猛暑で、手榴弾によって作り出された煙は、特に涼しい気候で全く急速に上昇します。 これで、M15手榴弾はスクリーニング剤としての使用には、より望ましくなくなります。 (6) Color/markings -- grey with one yellow band and yellow markings. (7) First aid -- treat burns caused by WP in the same way as ordinary burns. If particles of WP are embedded in the flesh, immerse the wound in water or pack with wet cloths to halt combustion. Then pick out or squeeze out the WP. The particles will reignite spontaneously if allowed to dry. Apply copper sulphate solution to halt combustion of the WP particles. This permits them to be removed without igniting. 応急処置--普通のやけどと同様にWPによって引き起こされたやけどを扱ってください。 WPの粒子が肉に埋め込まれるなら、傷を水に浸すか、またはぬれた布で荷造りして、燃焼を止めてください。 そして、WPを選ぶか、または絞り出してください。 乾性であることが許容されていると、粒子は自然に再発火するでしょう。 銅の硫酸塩溶液を適用して、WP粒子の燃焼を止めてください。 これは、それらが発火せずに取り除かれることを許可します。 References GRENADES AND PYROTECHNIC SIGNALS Field Manual FM 23-30 DEPARTMENT OF THE ARMY, 27 December 1988 白リン弾デマ関連
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TEC-/- BTK-/- double mutant T cells exhibit severely impaired T cell activitity. RLK-/-ITK-/- double mutant celles exhibit severely imparired Th2 responses. Grb2(+/-) mice disrupt T cell signaling networks and development. Dendric cells and macrophages of MEK3 deficient mice have impaired IL12 production. Bam32(-/-) B cell develop normally but have impaired T-independent antibody responses in vivo. T-cell and B-cell of RAP1A deficient mice impair integrin-mediated cell adhesion. T-cell of WASP deficient mice impair the proliferaction and antigen receptor cap formation in response to anti-CD3zeta stimulation. T-cell of SHB defective mice impair the phosphorylation of LAT and consequently the activation of MAP kinase pathways. B-cell of 3BP2 (-/-) deficient mice have defective in proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to BCR ligation. B-cell of Vav2(-/-) deficient mice are defective in the ability to switch immunoglobulin class. T-cell of Vav1(-/-) deficient mice exhibit impaired antigen receptor signaling. Vav1(-/-)Vav2(-/-) mice exhibit greatly reduced the mature B-cells. Vav-1-/-Vav-2-/- B cells were unresponsive to BCR-driven proliferation in vitro and to thymus-indepen-dent antigen in vivo. Fyn-deficient mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. T cell from mice deficient in LCK is required for normal signal transduction through the TCR. T cells from mice deficient in SLAP-130/Fyb show markedly impaired proliferation. B cell of chicken deficient ITK reduce IP3 generation and phospholipase C gamma 2 tyrosine phosphorylation. T cell of mice deficient ITK reduce IP3 generation and phospholipase C gamma 1 tyrosine phosphorylation. T cell of mice deficient ITK have failure of Th2 development. Mice deficient in ITK have reduced proliferative responses to MHC stimulation and to anti-TCR cross-linking Mutations in Btk cause X-linked immunodeficiency. Gads(GRAP2) has a role in thymocyte proliferaction for maturation of T-cells. Gads(GRAP2) has a role for homeostatic proliferaction in B cells. Grap negatively regulates T-cell proliferation. Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transuduction. B cell signaling causes tyrosine phosphorylation of Gab1, and in turn SHP2 bind to Gab1 Gab1 phosophorylation potentiate the phosphorylation of Akt, PI3K-dependent response. RasGRP1 mediates Ras activation following TCR stimulatioin. RasGRP1 and RasGRP3 induces RAS activation in B-cell to response to T-cell stimulation. Grb2-hSos1-PLCgamma1-p36/p38-ZAP70 complexes localize in the vicinity of TCR-zeta Gads(Grap2) plays an important role in T-cell signaling via its association with SLP-76 and LAT. Lck is required for normal signal transduction through the TCR. ZAP-70 plays crucial roles in T-cell activation and development. Syk triggers cellular activation in T-cell. TEC-/- BTK-/- double mutant T cells exhibit severely impaired T cell activitity. 1 J Exp Med. 2000 Dec 4;192(11) 1611-24. Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk. Ellmeier W, Jung S, Sunshine MJ, Hatam F, Xu Y, Baltimore D, Mano H, Littman DR. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine. wilfried.ellmeier@univie.ac.at The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton s tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220(+)CD43(+) stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)M(lo)IgD(hi) B cells. Although Tec/Btk(null) mice were able to form germinal centers, the response to T cell-dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients. Publication Types Research Support, Non-U.S. Gov t PMID 11104803 [PubMed - indexed for MEDLINE] RLK-/-ITK-/- double mutant celles exhibit severely imparired Th2 responses. 1 Nat Immunol. 2001 Dec;2(12) 1183-8. Mutation of Tec family kinases alters T helper cell differentiation. Schaeffer EM, Yap GS, Lewis CM, Czar MJ, McVicar DW, Cheever AW, Sher A, Schwartzberg PL. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. The Tec kinases Rlk and Itk are critical for full T cell receptor (TCR)-induced activation of phospholipase C-gamma and mitogen-activated protein kinase. We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type 1 (TH1) and TH2 cytokines. Consistent with these biochemical defects, Itk-/- mice did not generate effective TH2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired Rlk-/-Itk-/- mice were able to mount a TH2 response and produced TH2 cytokines in response to this challenge. In addition, Rlk-/-Itk-/- cells showed impaired TCR-induced repression of the TH2-inducing transcription factor GATA-3, suggesting a potential mechanism for TH2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4+ TH cell differentiation. Publication Types Research Support, Non-U.S. Gov t Research Support, U.S. Gov t, P.H.S. PMID 11702066 [PubMed - indexed for MEDLINE] Grb2(+/-) mice disrupt T cell signaling networks and development. 1 Nat Immunol. 2001 Jan;2(1) 29-36. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T, Chan AC. Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. The developmental processes of positive and negative selection in the thymus shape the T cell antigen receptor (TCR) repertoire and require the integration of multiple signaling networks. These networks involve the efficient assembly of macromolecular complexes and are mediated by multimodular adaptor proteins that permit the functional integration of distinct signaling molecules. We show here that decreased expression of the adaptor protein Grb2 in Grb2+/- mice weakens TCR-induced c-Jun N-terminal kinase (JNK) and p38, but not extracellular signal-regulated kinase (ERK), activation. In turn, this selective effect decreases the ability of thymocytes to undergo negative, but not positive, selection. We also show that there are differences in the signaling thresholds of the three mitogen-activated protein kinase (MAPK) families. These differences may provide a mechanism by which quantitative differences in signal strength can alter the balance of downstream signaling pathways to induce the qualitatively distinct biological outcomes of proliferation, differentiation or apoptosis. PMID 11135575 [PubMed - indexed for MEDLINE] Dendric cells and macrophages of MEK3 deficient mice have impaired IL12 production. 1 EMBO J. 1999 Apr 1;18(7) 1845-57. Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. Lu HT, Yang DD, Wysk M, Gatti E, Mellman I, Davis RJ, Flavell RA. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. The p38 mitogen-activated protein kinase (MAPK) pathway, like the c-Jun N-terminal kinase (JNK) MAPK pathway, is activated in response to cellular stress and inflammation and is involved in many fundamental biological processes. To study the role of the p38 MAPK pathway in vivo, we have used homologous recombination in mice to inactivate the Mkk3 gene, one of the two specific MAPK kinases (MAPKKs) that activate p38 MAPK. Mkk3(-/-) mice were viable and fertile; however, they were defective in interleukin-12 (IL-12) production by macrophages and dendritic cells. Interferon-gamma production following immunization with protein antigens and in vitro differentiation of naive T cells is greatly reduced, suggesting an impaired type I cytokine immune response. The effect of the p38 MAPK pathway on IL-12 expression is at least partly transcriptional, since inhibition of this pathway blocks IL-12 p40 promoter activity in macrophage cell lines and IL-12 p40 mRNA is reduced in MKK3-deficient mice. We conclude that the p38 MAP kinase, activated through MKK3, is required for the production of inflammatory cytokines by both antigen-presenting cells and CD4(+) T cells. PMID 10202148 [PubMed - indexed for MEDLINE] Bam32(-/-) B cell develop normally but have impaired T-independent antibody responses in vivo. 1 Immunity. 2003 Oct;19(4) 621-32. Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival. Han A, Saijo K, Mecklenbrauker I, Tarakhovsky A, Nussenzweig MC. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA. Bam32 is an adaptor protein recruited to the plasma membrane upon B cell receptor (BCR) crosslinking in a phosphoinositol 3-kinase (PI3K)-dependent manner; however, its physiologic function is unclear. To determine its physiologic function, we produced Bam32-deficient mice. Bam32(-/-) B cells develop normally but have impaired T-independent antibody responses in vivo and diminished responses to BCR crosslinking in vitro. Biochemical analysis revealed that Bam32 acts in a novel pathway leading from the BCR to MAPK/ERK Kinases (MEK1/2), MAPK/ERK Kinase Kinase-1 (MEKK1), extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (p38). This pathway appears to be initiated by hematopoietic progenitor kinase-1 (HPK1), which interacts directly with Bam32, and differs from all previously characterized BCR signaling pathways in that it is required for normal BCR-mediated proliferation but not for B cell survival. PMID 14563325 [PubMed - indexed for MEDLINE] T-cell and B-cell of RAP1A deficient mice impair integrin-mediated cell adhesion. 1 Mol Cell Biol. 2006 Jan;26(2) 643-53. Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele JS, Zwartkruis FJ. Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany. Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rap1 in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1-/- cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins. PMID 16382154 [PubMed - indexed for MEDLINE] T-cell of WASP deficient mice impair the proliferaction and antigen receptor cap formation in response to anti-CD3zeta stimulation. 1 Immunity. 1998 Jul;9(1) 81-91. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, Liu CH, Hagemann TL, Kwan SP, Ferrini R, Davidson L, Bhan AK, Alt FW. Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115, USA. The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-independent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3epsilon stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-Ig stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans. PMID 9697838 [PubMed - indexed for MEDLINE] T-cell of SHB defective mice impair the phosphorylation of LAT and consequently the activation of MAP kinase pathways. 9 Sep 24;274(39) 28050-7. Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells. Lindholm CK, Gylfe E, Zhang W, Samelson LE, Welsh M. Department of Medical Cell Biology, Box 571, Biomedicum, Uppsala University, S-75123 Uppsala, Sweden. Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the TCR zeta-chain in Jurkat cells. We now report that Shb also associates with phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation. Nuclear factor for activation of T cells is a major target for Ras and calcium signaling pathways in T cells following TCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma1 and resulting in the activation of transcription of the interleukin-2 gene. PMID 10488157 [PubMed - indexed for MEDLINE] B-cell of 3BP2 (-/-) deficient mice have defective in proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to BCR ligation. 1 Mol Cell Biol. 2006 Jul;26(14) 5214-25. 3BP2 deficiency impairs the response of B cells, but not T cells, to antigen receptor ligation. de la Fuente MA, Kumar L, Lu B, Geha RS. Division of Immunology, Children s Hospital, 300 Longwood Ave., Boston, MA 02115, USA. The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-gamma (PLC-gamma); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development, proliferation, cytokine secretion, and signaling in response to T-cell receptor (TCR) ligation were all normal in 3BP2(-/-) mice. 3BP2(-/-) mice had increased accumulation of pre-B cells in the bone marrow and a block in the progression of transitional B cells in the spleen from the T1 to the T2 stage, but normal numbers of mature B cells. B-cell proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to B-cell receptor (BCR) ligation were all impaired. These results suggest that 3BP2 is important for BCR, but not for TCR signaling. PMID 16809760 [PubMed - indexed for MEDLINE] B-cell of Vav2(-/-) deficient mice are defective in the ability to switch immunoglobulin class. 1 Nat Immunol. 2001 Jun;2(6) 542-7. Comment in Nat Immunol. 2001 Jun;2(6) 482-4. Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Doody GM, Bell SE, Vigorito E, Clayton E, McAdam S, Tooze R, Fernandez C, Lee IJ, Turner M. Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation. PMID 11376342 [PubMed - indexed for MEDLINE] T-cell of Vav1(-/-) deficient mice exhibit impaired antigen receptor signaling. 1 Nature. 1995 Mar 30;374(6521) 474-7. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Fischer KD, Zmuldzinas A, Gardner S, Barbacid M, Bernstein A, Guidos C. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells. PMID 7700360 [PubMed - indexed for MEDLINE] Vav1(-/-)Vav2(-/-) mice exhibit greatly reduced the mature B-cells. Vav-1-/-Vav-2-/- B cells were unresponsive to BCR-driven proliferation in vitro and to thymus-indepen-dent antigen in vivo. 1 Nat Immunol. 2001 Jun;2(6) 548-55. Comment in Nat Immunol. 2001 Jun;2(6) 482-4. Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Tedford K, Nitschke L, Girkontaite I, Charlesworth A, Chan G, Sakk V, Barbacid M, Fischer KD. Abteilung Physiologische Chemie, Universitat Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. Vav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases. Mutation of Vav-1 disrupts T cell development and T cell antigen receptor-induced activation, but has comparatively little effect on B cells. We found that combined deletion of both Vav-1 and Vav-2 in mice resulted in a marked reduction in mature B lymphocyte numbers. Vav-1(-/-)Vav-2(-/-) B cells were unresponsive to B cell antigen receptor (BCR)-driven proliferation in vitro and to thymus-independent antigen in vivo. BCR-stimulated intracellular calcium mobilization was greatly impaired in Vav-1(-/-)Vav-2(-/-) B cells. These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function. PMID 11376343 [PubMed - indexed for MEDLINE] Fyn-deficient mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen. 1 Cell. 1992 Sep 4;70(5) 751-63. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Appleby MW, Gross JA, Cooke MP, Levin SD, Qian X, Perlmutter RM. Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195. Considerable evidence supports the hypothesis that the nonreceptor protein tyrosine kinase p59fyn participates in signal transduction from the T cell receptor (TCR). To examine this hypothesis in detail, we have produced mice that lack the thymic isoform of p59fyn but retain expression of the brain isoform of the protein. fynTnull mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen, while peripheral T cells, following what appears to be a normal maturation sequence, reacquire significant signaling capabilities. These data confirm that p59fynT plays a pivotal role in TCR signal transduction and demonstrate that additional developmentally regulated signaling components also contribute to TCR-induced lymphocyte activation. PMID 1516132 [PubMed - indexed for MEDLINE] Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. 1 Nature. 1992 May 14;357(6374) 161-4. Comment in Nature. 1993 Jan 21;361(6409) 213. Profound block in thymocyte development in mice lacking p56lck. Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann KU, Veillette A, et al. Ontario Cancer Institute, University of Toronto, Canada. The protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells. Lck associates specifically with the cytoplasmic domains of both CD4 and CD8 T-cell surface glycoproteins and interacts with the beta-chain of the interleukin-2 receptor, which implicates Lck activity in signal transduction during thymocyte ontogeny and activation of mature T cells. Here we generate an lck null mutation by homologous recombination in embryonic stem cells to evaluate the role of p56lck in T-cell development and activation. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. Mature, single-positive thymocytes are not detectable in these mice and there are only very few peripheral T cells. These results illustrate the crucial role of this T-cell-specific tyrosine kinase in the thymocyte development. PMID 1579166 [PubMed - indexed for MEDLINE] T cell from mice deficient in LCK is required for normal signal transduction through the TCR. 1 Cell. 1992 Aug 21;70(4) 585-93. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Straus DB, Weiss A. Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143. Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR. PMID 1505025 [PubMed - indexed for MEDLINE] T cells from mice deficient in SLAP-130/Fyb show markedly impaired proliferation. 1 Science. 2001 Sep 21;293(5538) 2263-5. Coupling of the TCR to integrin activation by Slap-130/Fyb. Peterson EJ, Woods ML, Dmowski SA, Derimanov G, Jordan MS, Wu JN, Myung PS, Liu QH, Pribila JT, Freedman BD, Shimizu Y, Koretzky GA. The Abramson Family Cancer Research Institute, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. SLAP-130/Fyb (SLP-76-associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb-deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals. PMID 11567141 [PubMed - indexed for MEDLINE] B cell of chicken deficient ITK reduce IP3 generation and phospholipase C gamma 2 tyrosine phosphorylation. 1 J Exp Med. 1996 Jul 1;184(1) 31-40. A role for Bruton s tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2. Takata M, Kurosaki T. Department of Oncology and Immunology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA. Defects in the gene encoding Bruton s tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions. PMID 8691147 [PubMed - indexed for MEDLINE] T cell of mice deficient ITK reduce IP3 generation and phospholipase C gamma 1 tyrosine phosphorylation. 1 J Exp Med. 1998 May 18;187(10) 1721-7. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. Liu KQ, Bunnell SC, Gurniak CB, Berg LJ. Program of Immunology, Division of Medical Sciences, Harvard University, Boston, Massachusetts 02115, USA. Itk, a Tec family tyrosine kinase, plays an important but as yet undefined role in T cell receptor (TCR) signaling. Here we show that T cells from Itk-deficient mice have a TCR-proximal signaling defect, resulting in defective interleukin 2 secretion. Upon TCR stimulation, Itk-/- T cells release normal amounts of calcium from intracellular stores, but fail to open plasma membrane calcium channels. Since thapsigargin-induced store depletion triggers normal calcium entry in Itk-/- T cells, an impaired biochemical link between store depletion and channel opening is unlikely to be responsible for this defect. Biochemical studies indicate that TCR-induced inositol 1,4,5 tris-phosphate (IP3) generation and phospholipase C gamma1 tyrosine phosphorylation are substantially reduced in Itk-/- T cells. In contrast, TCR-zeta and ZAP-70 are phosphorylated normally, suggesting that Itk functions downstream of, or in parallel to, ZAP-70 to facilitate TCR-induced IP3 production. These findings support a model in which quantitative differences in cytosolic IP3 trigger distinct responses, and in which only high concentrations of IP3 trigger the influx of extracellular calcium. PMID 9584150 [PubMed - indexed for MEDLINE] T cell of mice deficient ITK have failure of Th2 development. 1 Immunity. 1999 Oct;11(4) 399-409. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells. Fowell DJ, Shinkai K, Liao XC, Beebe AM, Coffman RL, Littman DR, Locksley RM. Department of Medicine, University of California San Francisco 94143, USA. Naive Itk-deficient CD4+ T cells were unable to establish stable IL-4 production, even when primed in Th2-inducing conditions. In contrast, IFNgamma production was little affected. Failure to express IL-4 occurred even among cells that had gone through multiple cell divisions and was associated with a delay in the kinetics and magnitude of NFATc nuclear localization. IL-4 production was restored genetically by retroviral reconstitution of Itk or biochemically by augmenting the calcium flux with ionomycin. In vivo, Itk-deficient mice were unable to establish functional Th2 cells. Development of protective Th1 cells was unimpeded. These data define a nonredundant role for Itk in modulating signals from the TCR/CD28 pathways that are specific for the establishment of stable IL-4 but not IFNgamma expression. PMID 10549622 [PubMed - indexed for MEDLINE] Mice deficient in ITK have reduced proliferative responses to MHC stimulation and to anti-TCR cross-linking 1 Immunity. 1995 Dec;3(6) 757-69. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Liao XC, Littman DR. Department of Microbiology and Immunology, University of California, San Francisco 94143-0414, USA. Itk is a T cell protein tyrosine kinase (PTK) that, along with Btk and Tec, belongs to a family of cytoplasmic PTKs with N-terminal pleckstrin homology domains. Btk plays a critical role in B lymphocyte development. To determine whether Itk has an analogous role in T lymphocytes, we used gene targeting to prepare mice lacking expression of Itk. Such animals had decreased numbers of mature thymocytes, an effect most clearly observed in mice expressing T cell receptor (TCR) transgenes. Mature T cells from Itk-deficient mice had reduced proliferative responses to allogeneic MHC stimulation and to anti-TCR cross-linking, but responded normally to stimulation with phorbol ester plus ionomycin or with IL-2. These results provide genetic evidence that Itk is involved in T cell development and also suggest that Itk has an important role in proximal events in TCR-mediated signaling pathways. PMID 8777721 [PubMed - indexed for MEDLINE] Mutations in Btk cause X-linked immunodeficiency. 1 Semin Immunol. 1998 Aug;10(4) 309-16. Btk function in B cell development and response. Satterthwaite AB, Li Z, Witte ON. Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095-1662, USA. Mutations in Bruton s tyrosine kinase (Btk) result in the B cell immunodeficiencies XLA in humans and Xid in mice. Both the maintenance of peripheral B cell numbers and their response to B cell antigen receptor (BCR) crosslinking depend on Btk. Btk integrates signals from multiple cell surface receptors, including BCR and G-protein coupled receptors. These Btk dependent signals control B cell proliferation and survival by mediating Ca2+ flux, activating JNK and p38 and inducing cell cycle regulatory genes. Publication Types Review PMID 9695187 [PubMed - indexed for MEDLINE] Gads(GRAP2) has a role in thymocyte proliferaction for maturation of T-cells. 1 Science. 2001 Mar 9;291(5510) 1987-91. Requirement for the SLP-76 adaptor GADS in T cell development. Yoder J, Pham C, Iizuka YM, Kanagawa O, Liu SK, McGlade J, Cheng AM. Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA. GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling. PMID 11239162 [PubMed - indexed for MEDLINE] Gads(GRAP2) has a role for homeostatic proliferaction in B cells. 1 Eur J Immunol. 2005 Apr;35(4) 1184-92. Expression and function of the adaptor protein Gads in murine B cells. Yankee TM, Draves KE, Clark EA. Department of Immunology, University of Washington, Seattle, USA. tyankee@kumc.edu Nearly all hematopoietic receptors are dependent on adaptor proteins for the activation of downstream signaling pathways. The Gads adaptor protein is expressed in many hematopoietic tissues, including bone marrow, lymph node, and spleen. Using intracellular staining, we detected Gads protein in a number cells, including B cells, T cells, NK cells, monocytes, and plasmacytoid DC, but not in macrophages, neutrophils, or monocyte-derived DC. In the B cell compartment, Gads was first expressed after immature B cells leave the bone marrow and was down-regulated after B cell antigen receptor (BCR) ligation. Female Gads(-/-) mice had increased numbers of splenic B cells, as compared to female Gads(+/+) mice, suggesting a role for Gads in B cell homeostasis. Although B cell production and turnover of splenic B cell subsets appeared normal in Gads(-/-) mice, homeostatic proliferation was significantly impaired in Gads(-/-) B cells. Whereas BCR ligation can induce apoptosis in wild-type transitional stage 1 (T1) B cells, Gads(-/-) T1 B cells were resistant to BCR-induced apoptosis. Gads(-/-) B cells also showed increased BCR-mediated calcium mobilization. We conclude that Gads may have a negative regulatory role in signaling through survival pathways, and is necessary for normal homeostatic proliferation in B cells. PMID 15761845 [PubMed - indexed for MEDLINE] Grap negatively regulates T-cell proliferation. 1 Mol Cell Biol. 2002 May;22(10) 3230-6. Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and interleukin-2 induction. Shen R, Ouyang YB, Qu CK, Alonso A, Sperzel L, Mustelin T, Kaplan MH, Feng GS. Program in Signal Transduction Research, The Burnham Institute, La Jolla, California 92037, USA. Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues. Grap(-/-) lymphocytes isolated from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2 production, and c-fos induction in response to mitogenic T-cell receptor (TCR) stimulation, compared to wild-type cells. Ectopic expression of Grap led to a suppression of Elk-1-directed transcription induced by the Ras/Erk pathway, without having effects on gene expression mediated by Jnk and p38 mitogen-activated protein kinases. Together, these data suggest that Grap, unlike Grb2, acts as a negative regulator of TCR-stimulated intracellular signaling by downregulating signal relay through the Ras/Erk pathway. PMID 11971956 [PubMed - indexed for MEDLINE] Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transuduction. 1 J Biol Chem. 2001 Nov 30;276(48) 45175-83. Epub 2001 Sep 25. Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules. Yamasaki S, Nishida K, Hibi M, Sakuma M, Shiina R, Takeuchi A, Ohnishi H, Hirano T, Saito T. Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. To maintain various T cell responses and immune equilibrium, activation signals triggered by T cell antigen receptor (TCR) must be regulated by inhibitory signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has been shown to be involved in the downstream signaling from cytokine receptors. We investigated the functional role of Gab2 in TCR-mediated signal transduction. Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2 mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding capacity also impaired the inhibitory activity, and the pleckstrin homology domain-deletion mutant revealed a crucial function of the pleckstrin homology domain for localization to the plasma membrane. These results suggest that Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transduction by mediating the recruitment of inhibitory molecules to the TCR signaling complex. PMID 11572860 [PubMed - indexed for MEDLINE] B cell signaling causes tyrosine phosphorylation of Gab1, and in turn SHP2 bind to Gab1 Gab1 phosophorylation potentiate the phosphorylation of Akt, PI3K-dependent response. 1 J Biol Chem. 2001 Apr 13;276(15) 12257-65. Epub 2001 Jan 22. The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. Ingham RJ, Santos L, Dang-Lawson M, Holgado-Madruga M, Dudek P, Maroun CR, Wong AJ, Matsuuchi L, Gold MR. Departments of Microbiology and Immunology and Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. B cell antigen receptor (BCR) signaling causes tyrosine phosphorylation of the Gab1 docking protein. This allows phosphatidylinositol 3-kinase (PI3K) and the SHP2 tyrosine phosphatase to bind to Gab1. In this report, we tested the hypothesis that Gab1 acts as an amplifier of PI3K- and SHP2-dependent signaling in B lymphocytes. By overexpressing Gab1 in the WEHI-231 B cell line, we found that Gab1 can potentiate BCR-induced phosphorylation of Akt, a PI3K-dependent response. Gab1 expression also increased BCR-induced tyrosine phosphorylation of SHP2 as well as the binding of Grb2 to SHP2. We show that the pleckstrin homology (PH) domain of Gab1 is required for BCR-induced phosphorylation of Gab1 and for Gab1 participation in BCR signaling. Moreover, using confocal microscopy, we show that BCR ligation can induce the translocation of Gab1 from the cytosol to the plasma membrane and that this requires the Gab1 PH domain as well as PI3K activity. These findings are consistent with a model in which the binding of the Gab1 PH domain to PI3K-derived lipids brings Gab1 to the plasma membrane, where it can be tyrosine-phosphorylated and then act as an amplifier of BCR signaling. PMID 11278704 [PubMed - indexed for MEDLINE] RasGRP1 mediates Ras activation following TCR stimulatioin. RasGRP1 and RasGRP3 induces RAS activation in B-cell to response to T-cell stimulation. 1 Immunol Lett. 2006 May 15;105(1) 77-82. Epub 2006 Feb 20. The role of RasGRPs in regulation of lymphocyte proliferation. Coughlin JJ, Stang SL, Dower NA, Stone JC. Department of Biochemistry, University of Alberta, Edmonton, Alta., Canada T6G 2H7. RasGRP1 links TCR signaling to Ras in T cells, while both RasGRP1 and RasGRP3 link BCR signaling to Ras in B cells. T cells deficient in RasGRP1 have defective proliferative responses as do B cells deficient in both RasGRP1 and RasGRP3, confirming the importance of Ras activation in lymphocyte proliferation. While aged Rasgrp1-/- mice develop late-onset autoimmunity characterized by splenomegaly and the presence of anti-nuclear antibodies (ANA), the additional loss of RasGRP3 expression inhibits this phenotype. We show here that the autoimmunity in Rasgrp1-/- mice is T cell dependent. Compared to wildtype, Rasgrp1-/- T cells induce greater in vitro B cell proliferation that is due, at least in part, to increased production of interleukin-4 (IL-4). Rasgrp1 Rasgrp3 double mutant B cells are less responsive to this T cell stimulation. The reduced double mutant B cell proliferative response was paralleled by decreased induction of cyclin D2 upon stimulation with IL-4 and anti-IgM. Taken together these results suggest that double mutant mice fail to generate autoimmunity due to their decreased B cell cyclin D2 accumulation, and thus proliferation, in response to the elevated levels of IL-4 produced by mutant T cells. PMID 16530850 [PubMed - indexed for MEDLINE] Grb2-hSos1-PLCgamma1-p36/p38-ZAP70 complexes localize in the vicinity of TCR-zeta 1 J Biol Chem. 1995 Aug 4;270(31) 18428-36. Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR. Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB. Department of Medicine, UCLA School of Medicine 90024, USA. Signaling by the T-cell antigen receptor (TCR) involves both phospholipase C (PLC)-gamma 1 and p21ras activation. While failing to induce Shc/Grb2 association, ligation of the TCR/CD3 receptor in Jurkat T-cells induced hSos1-Grb2 complexes. In addition to hSos1, Grb2 participates in the formation of a tyrosine phosphoprotein complex that includes 145-, 95-, 70-, 54-, and 36-38-kDa proteins. p145 was identified as PLC-gamma 1 and p70 as the protein tyrosine kinase, ZAP-70. Although of the same molecular weight, p95 was not recognized by an anti-serum to p95 Vav. The SH2 domains of Grb2 and PLC-gamma 1 were required for the formation of this protein complex. In anti-CD3-treated cells, Grb2 redistributed from the cytosol to a particulate cell compartment along with p36/p38, ZAP-70, and PLC-gamma 1. Part of the Grb2 complex associated with the particulate compartment could be extracted with Nonidet P-40, while the rest was Nonidet P-40 insoluble. In both the detergent-soluble and -insoluble fractions, Grb2 coimmunoprecipitated with the zeta-chain of the TCR. Taken together, these results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70 complexes, which localize in the vicinity of TCR-zeta. PMID 7629168 [PubMed - indexed for MEDLINE] Gads(Grap2) plays an important role in T-cell signaling via its association with SLP-76 and LAT. 1 Curr Biol. 1999 Jan 28;9(2) 67-75. The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Liu SK, Fang N, Koretzky GA, McGlade CJ. Department of Medical Biophysics, University of Toronto, The Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Research Institute, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. BACKGROUND The adaptor protein Gads is a Grb2-related protein originally identified on the basis of its interaction with the tyrosine-phosphorylated form of the docking protein Shc. Gads protein expression is restricted to hematopoietic tissues and cell lines. Gads contains a Src homology 2 (SH2) domain, which has previously been shown to have a similar binding specificity to that of Grb2. Gads also possesses two SH3 domains, but these have a distinct binding specificity to those of Grb2, as Gads does not bind to known Grb2 SH3 domain targets. Here, we investigated whether Gads is involved in T-cell signaling. RESULTS We found that Gads is highly expressed in T cells and that the SLP-76 adaptor protein is a major Gads-associated protein in vivo. The constitutive interaction between Gads and SLP-76 was mediated by the carboxy-terminal SH3 domain of Gads and a 20 amino-acid proline-rich region in SLP-76. Gads also coimmunoprecipitated the tyrosine-phosphorylated form of the linker for activated T cells (LAT) adaptor protein following cross-linking of the T-cell receptor; this interaction was mediated by the Gads SH2 domain. Overexpression of Gads and SLP-76 resulted in a synergistic augmentation of T-cell signaling, as measured by activation of nuclear factor of activated T cells (NFAT), and this cooperation required a functional Gads SH2 domain. CONCLUSIONS These results demonstrate that Gads plays an important role in T-cell signaling via its association with SLP-76 and LAT. Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways. PMID 10021361 [PubMed - indexed for MEDLINE] Lck is required for normal signal transduction through the TCR. 1 Cell. 1992 Aug 21;70(4) 585-93. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Straus DB, Weiss A. Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143. Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR. PMID 1505025 [PubMed - indexed for MEDLINE] ZAP-70 plays crucial roles in T-cell activation and development. Syk triggers cellular activation in T-cell. 1 Mol Cell Biol. 1998 Mar;18(3) 1388-99. Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Williams BL, Schreiber KL, Zhang W, Wange RL, Samelson LE, Leibson PJ, Abraham RT. Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA. T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development. However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered by the lack of a suitable T-cell model for biochemical and genetic analyses. In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driven transcription. These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells. However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation. Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells. PMID 9488454 [PubMed - indexed for MEDLINE]
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2008年のレースで思ったことなどを・・・。 WSB R1 カタール ドーハ ロサイルサーキット（2/23） とうとう始まったワールドスーパーバイク。結果は下記ですが・・・。 ちょっと、ドゥカティばっかじゃん。 これでいいのかなぁ、今年のレギュレーション。 レース１結果 Pos ライダー メーカ 国 タイム 1 Troy Bayliss Ducati AUS 36 11.468 2 Max Biaggi Ducati ITA 0 0.396 3 Troy Corser Yamaha AUS 0 1.878 4 Ruben Xaus Ducati ESP 0 4.487 5 Max Neukirchner Suzuki GER 0 7.505 6 Carlos Checa Honda ESP 0 9.639 7 Fonsi Nieto Suzuki ESP 0 9.725 8 Yukio Kagayama Suzuki JPN 0 19.537 9 Michel Fabrizio Ducati ITA 0 23.156 10 Jakub Smrz Ducati CZE 0 24.429 11 Roberto Rolfo Honda ITA 0 27.595 12 Kenan Sofuoglu Honda TUR 0 27.979 13 Gregorio Lavilla Honda ESP 0 28.237 14 Noriyuki Haga Yamaha JPN 0 30.205 15 Regis Laconi Kawasaki FRA 0 31.882 20 Sebastien Gimbert Yamaha FRA 0 41.743 21 Shinichi Nakatomi Yamaha JPN 0 43.183 23 David Checa Yamaha ESP 0 43.892 レース２結果 Pos ライダー メーカ 国 タイム 1 Fonsi Nieto Suzuki ESP 36 12.963 2 Ruben Xaus Ducati ESP 0 0.301 3 Max Biaggi Ducati ITA 0 1.321 4 Troy Bayliss Ducati AUS 0 6.452 5 Michel Fabrizio Ducati ITA 0 7.627 6 Lorenzo Lanzi Ducati ITA 0 9.117 7 Troy Corser Yamaha AUS 0 10.806 8 Max Neukirchner Suzuki GER 0 11.661 9 Jakub Smrz Ducati CZE 0 13.269 10 Kenan Sofuoglu Honda TUR 0 14.563 11 Carlos Checa Honda ESP 0 15.953 12 Makoto Tamada Kawasaki JPN 0 16.748 13 Noriyuki Haga Yamaha JPN 0 18.356 14 Gregorio Lavilla Honda ESP 0 26.311 15 Roberto Rolfo Honda ITA 0 26.560 18 Sebastien Gimbert Yamaha FRA 0 28.650
https://w.atwiki.jp/elvis/pages/1328.html
Angel Marcia Lippman? Address Book Deborah Schenck Dress Up Day at the Zoo Lissa Rovetch?Rob Hefferen? Wildlife Mitsuaki IwagoIsao Tezuka? Topiary Woman with Envelope (Charming Stationery Collection) Laura Stoddart? The Dog Addressed/Address Book Ruth Silverman? Woman with Sunflower with Envelope (Charming Stationery Collection) Laura Stoddart? Man with Tulip with Envelope (Charming Stationery Collection) Laura Stoddart? Desire 20 Assorted Notecards Envelopes Apla Holiday Cards with Cards and Envelope Holiday Cards (One Image and 20 Envelopes) Elisa Kleven? Bon Bon 2004 Calendar Noel Tolentino?Cosmic Debris Holiday Feast/Includes 20 Notecards (One Image and 20 Envelopes) Paulina Eccless? Birthday Party Invitation with Envelope (Charming Stationery Collection) Laura Stoddart? Boomer Doll Hecho En Mexico Address Book An Egg Is Quiet Dianna Hutts Aston?Sylvia Long Angel Holiday Cards (Gabriela/Includes 20 Notecards) Marcia Lippman? Thanksgiving Table Bed Bath Letter Folios with Other (Charming Stationery Collection) Laura Stoddart? Zeus The Flying Dog Garbanzo Smith?Amanda Sheperd? Letter Folios with Pens/Pencils (Charming Stationery Collection) Laura Stoddart? Holiday Cat/Includes 20 Notecards (One Image and 20 Envelopes) Ward Schumaker? Ten Copy Counter Seven Modern King? Cal 96 Breaking Bounds/Wall Lois Greenfield Cheap Eats in Italy Sandra A. Gustafson? Sweet Nothings Jill O Connor? Holiday Feasts Lou Seibert Pappas? Hockey! John S. Snyder? "Are We There Yet?" Barbara Govednik?Ellen Toomey? Costumes for Your Cat Lynn Chang So Crazy Japanese Toys JIMBO MATISON A Little Irish Cookbook (Little Books) John Murphy?Karen Bailey? Paranoids' Pocket Guide Cameron Tuttle Detail from Five Wise Storytellers Trying to Keep Warm/Includes 20 Notecards (One Image and 20 Envelopes) Sylvia Long Going Down 6-Pak Games for Your Brain Display (8-Copy Display) Tina L. Seelig? On the Surface of Things Images of the Extraordinary in Science Felice Frankel?G. M. Whitesides? Wor Case Scen D/B X16 Sur/X16 Tra Anne Taintor Line Notepad Bad Girl's Calling Cards 12-C Dspl (Be a Bad Girl) Chronicle Books Daisy Villeneuve Notepads 24-C Dspl (Dating Divas) Daisy de Villeneuve Khaki Baseball Cap Chronicle Gear Chronicle Books Yellow Submarine Ntpd 24cpy Display (We All Live...) Chronicle Books Bad Girls Notepads 24copy Dsply (Be a Bad Girl) Chronicle Books Greatcities Souvenir SF 13c Dsply (Hit the Road) Chronicle Books Greatcities Souvenir NY 13c Dsply (Hit the Road) Chronicle Books Everything I Ate 6-Copy Display Chronicle Books Angel (Espiritu/Includes 20 Notecards) Marcia Lippman? St. Francis Yacht Club Founded 1927 Kimball Livingston? Ltd Superfriend Wonder W Fold Mail Chronicle Books Ltd Popeye Gumby Fold Mail Chronicle Books Metreon Notecard (Single) Chronicle Books Metreon Postcard (Single) Chronicle Books DC Notepad 24-C Dspl (It's a Bird It's a Plane It's a Novel) DC ComicsDC Comics DC Comics? Iou Sex 12-Copy Display (Erotic Delights) Chronicle Books Christmas Mini-Classics 12c Display Cooper EdensMichael Hague? How to Be Pope 6copy Display Chronicle Books Beyond the Great Mountains 6-Pk Ed Young? Pixar Bookmark 36-Copy Display Chronicle Books 52 Series 12-Pk (Linens N Things) Worst Case 2005 Display Hula Honey Notepad 24-Copy Dis Nancy Drew Notepad 24-Copy Dis You Can Do It! Buy 6, Get 1 Fr Lohec Near Grandcolas? Treats, Recipes Crafts Holida Art Safari Sculpture Joyce Raimondo? Underachievers Man 6-C Count D Subversive Cross Beauty Parlor Wisdom 5-C Count Crouching Father 6-Copy Displa Ten Eternal Questions 5-C Coun Little Bk I Love You 6-C Count Scrappy Album 12-Copy Display In-Line Deck Display Fixture Little Puppet Book Assortment Klaartje Van Der Put? Look at Me Assortment Saddle Up 2004 Calendar Ocho Loco Press? Blue Plane (Match-the-Shape) Jane Sherman?Holly Mann? Voyages Photo Album Beth Nelson Return of the Jedi (Mighty Chronicles) John Whitman? Cal 96 Buddha Marcia Lippman? Frances Mayes's Tuscan Pleasures 2003 Calendar Frances Mayes? Shadow Games (Chronicle of the Black Company) Glen Cook? Seashell Journal Deborah Schenck Book Plates Refills Design S Two The Joseph Cornell Box Mensa for kids 75 brain bafflers Jewish Weddings for Grownups Everything You Need to Know to Plan a Unique and Memorable Wedding Carroll Stoner? Go Girl Address Book Gayle Steinbeigle? Standards A Chronicle of Books for Our Time Stanley E. Hyman? Bernice Chesler's Bed Breakfast in the Mid-Atlantic States Delaware, Maryland, New Jersey, New York, North Carolina, Pennsylvania, Virginia, Washington, D.C., West Virginia (Bed and Breakfast in the Mid-Atlantic States) Bernice Chesler? New York Panoramic 2003 Calendar Ann Rhoney? "I Hate The Word 'Relationship'," He Said Notepad (Dating Divas) Daisy De VilleneuvePocko Editions? Voyages A Writing Portfolio Beth Nelson Baby's Book (Giftworks) Two Women Boxing? Journal Dots Gayle Steibeigle?Gayle Steinbeigle? Grimm's Grimmest Wilhelm GrimmJacob GrimmTracy Arah Dockray?Maria Tatar? Farm Tractors 24 Postal Cards With Pictures of Tractors on `Em Art of the Midwest? Happy Birthday (Matchcard Greetings) Happy Birthday Happy Birthday (Matchcard Greetings) Matchcard Greetings Happy Birthday (Matchcard Greetings) The Lost Chronicle of Edward De Vere Andrew Field? Just for You (Matchcard Greetings) San Francisco Panoramic 2003 Calendar Chronicle Books Citizens a Chronicle of the French Revolution Simon Schama? Butterfly Wishes A Journal for Your Hopes and Dreams Bill Zimmerman?Stephano Vitale? Bionicle Chronicle 4 Mask of Light Chronicle of the Narvaez Expedition (Penguin Classics) Alvar Nunez Cabeza De Vaca? Xoxo (Matchcard Greetings) Market Analyst Heather Ramsay? U and Me (Matchcard Greetings) Cal 99 Hecho En Mexic0 Calendar Melanie Doherty? Diabetic Cookbook Hc Goodbody Nischan?Michel Nischan?Mary Goodbody? Diario De Mi Embarazo A. Christine, Ph.D. Harris Hatch Show Print 2003 Calendar With Poster Country Music Foundation? Sandman 2003 Calendar Inc. DC Comics? Superman 2003 Calendar Wonder Woman 2003 Calendar Inc. DC Comics? On Skates Happy Holidays (Matchcard Greetings) Daring! The Redstone Diary 2003 (Calendars) Julian Rothenstein?Mel Gooding? Season's Greetings (Matchcard Greetings) Car Talk And Clack Click?Bob And Ray Click and Clack? The Batman Masterpiece Edition The Caped Crusader's Golden Age (Batman) Les Daniels Matchcard Greetings Merry Christmas (Matchcard Greetings) Merry Christmas (Matchcard Greetings) Happy New Year (Matchcard Greetings) Happy Hannukah (Matchcard Greetings) Dog Bless America 2003 Calendar Jeff Sellis? Cootie Catcher Your Own Personal Fortune Teller Liven Up Any Party Amaze Your Friends and Family! (Cootie Catchers, Your Own Personal Fortune Teller) Steven Elliott?Christina LA Sala? Vice (Cootie Catchers, Your Own Personal Fortune Teller) Steven Elliott?Christina LA Sala? Holiday Hero Brad Finkle? The Perfect Day 40 Years of Surfer Magazine Sam George? Roses Journal Deborah Schenck Passion (Cootie Catchers, Your Own Personal Fortune Teller) Steven Elliott?Christina LA Sala? Flowers for the Table (Deluxe Notecards) Shaun Sullivan Senses (Cootie Catchers, Your Own Personal Fortune Teller) Steven Elliott?Christina LA Sala? Nick JR. Nursery Rhyme Time A Touc Chronicle Books Cal 98 Cats in the Sun Hans Silvester Cal 96 Cool Cat Cats in the Sun Ruled Hans Silvester Art of the Daguerreotype (Postal Cards) The J Paul Getty Trust? The Getty Center A Panoramic Postcard Book (Panoramic) The J Paul Trust? Hecho En Mexico Melanie Doherty? Cal 96 Ghosts Engagement Navy, Brown Hair G.I. Joe - Masterpiece Edition Navy, African-American G.I. Joe - Masterpiece Edition Air Force, Brown Hair G.I. Joe - Masterpiece Edition Air Force, African-American G.I. Joe - Masterpiece Edition G.I. Joe -Masterpiece Edition Marine Brown Hair San Francisco 2004 Calendar Thea Schrack? New York 2004 Panoramic Calendar Ann Rhoney? Superman 2004 Calendar Inc. DC Comics? Marine, African-American G.I. Joe - Masterpiece Edition Pansies 20 Assorted Notecards Envelopes Deborah Schenck Letters Two Women Boxing? Cal 96 Ghosts Aviation in the Second World War Philip Makanna? Cal 98 Angels Marcia Lippman? Parker Chronicle, 832-900 (Old English Library) Albert Hugh Smith? Cal 98 in Bloom Steven Rothfeld? Cal 98 Blossoms Deborah Schenck Cal 98 Hecho En Mexico Cal 98 Something Wonderful Artists Outside the Mainstream Nellie Mae Rowe?John Savitsky? Flora Antica Journal Deborah Schenck Cal 98 What Dogs Do Sharon Beals? Hope Is the Thing With Feathers A Personal Chronicle of Vanished Birds Christopher Cokinos? Deluxe Notecards Fletch Chronicle Gregory McDonald? The Fletch Chronicle, One Fletch Won, Fletch Too, Fletch and the Widow Bradley Gregory McDonald?
https://w.atwiki.jp/katasan-maple/pages/39.html
HP 意味 もし0になったら モンスターなどの攻撃を受け、HPが0になると、チャット以外に一切行動ができなくなる。ここで「確認」ボタンを押すと、一番近くの町に復活できる。 職業が「初心者」であれば特にペナルティは無いが、転職した後では経験値が下がる。下がる大きさはLUKに影響を受け、LUKが大きいほどペナルティは小さくなる。 また、ポイントアイテムの「翡翠のお守り」を買っておくと、上記の状態になってしまっても経験値が下がらなくなる。(*1) ステータスとして APをHPやMPに振り分けることができる。 AP再分配の書を使う時はHPまたはMPにAPを振っている場合のみHPに対して使える。そのとき、HPやMPのAPを返した時と再配布した時の増加減少量は職業によって値が決まっている。 HPやMPには下限値と上限値が存在し、職業やレベルによって異なる。(*2) 用途 スキルによってはHPやMPが無いと使えないものもある。(*3) 出典 「プレイのしかた」 「育成のしかた」 名前 コメント内容
https://w.atwiki.jp/twitterfatetrpg/pages/21.html
プレイヤー別の個人ページへのリンクです PL名 Twitter wiki内ページリンク 自由欄 邪神ちゃん。 @jyashin_chan こちら アルビノは良い文明。界隈に聖杯戦争を持ち込んだ犯人。大体此奴の所為。 第六天魔熊・くまさぶろう @Kumasaburo_Oda こちら だいたい七草がわるい。Twitter聖杯戦争の人類悪担当。 10pyo @tenpyo11 こちら 読み方はてんぴょう。泥課金はいいぞ。Twitterでよく闇堕ちする。 ゴミクズ @prominence4696 こちら 銀髪、黒髪はイイゾ。火力バカ担当。 毒蛇 @poison_snake77 こちら 運用方法がシンプルな鯖しか作れない人。シンプルに限界を目指す 乱痴気 @_RanTiKi こちら いいぞbot。とてもうるさい。誤字脱字誤変換担当。 そら。 @SKY_retu こちら カプ厨かも。色々な理由で見学席には「レワニード」名義で出没します。 時猫 @tokinekon こちら 我輩は猫である。クトゥルフコンバート猫 半額べんとう @price_2d100yen こちら FGO未プレイ。美味しいバニラを目指す。 柏葉しの @Dmu_34 こちら 少女となんかアレなお兄さん、あと騎士 カポチャぷぁん @gooooriiiii こちら 力こそぱわー。 ユニ @June0924_ac こちら 自称ヒロイン量産機。JKと眼鏡、たまに幼女 黒蝦蟇忍者 @njB8fKQQMYnRQmY こちら 変な鯖＝浪漫 あとノアール姉妹 一昨々日 @1204_sousaku こちら ナポレオンに並々ならぬ敵意を抱いている。 がぶ @gabutrpg こちら 比較的（PLが）善属性。基本脳筋。 笹っとね @tonikakusaikou こちら 別名スカラベサクレ ナイトウィザード布教bot 見学 @kengaku_san こちら wiki1000ページ目に相応しいあまりにも強すぎるいぬ🐶 伊右衛門 @___iemon___ こちら 唐突に生えたお茶です。伊右衛門です。呼び間違えちゃだめですよ。 ばーん @van＿trpg こちら 大魔王バーンと同じ名前のばーんです。よろしくお願いします。
https://w.atwiki.jp/0794/pages/95.html
｢Delbimaira there Confine Cu in oubliette with Gale Let s make it have a hard time later｣ Genesis said. ???Oubliette? Provide."That ･･･ Is it safe?" Cu by which Lobo from whom the body weakened had been hanging on considerably heard it. "Every thing to have hung on here is it was possible to go out" Gale said. Lobo who introduced oneself as "‥ My name is a hex ･･･ It is a total commander of the angel army Gelnia corps" hex said. ｢｢Hex. ?｣｣ Cu and Gale raised the voice. Get..why..hex..now..Genesis..introduce oneself..say. "When it was Genesis ･･･ Was the guy does take the shape of me and acting? ･･･ The angel army in this ･･･ already" The hex said. "To our regret, angel army Gelnia and the Gald corps were annihilated" Cu said. "Guys were carrying out the certain Dego invasion operation" hex said. "････ Surely ･･･ Genesis" Cu said. "Please did you do?" hex said. "My parents because of the guy" Cu shouted it. "You are integral. "Cu released the transformation so momentarily of listening from the hex. Penguin. The hex heard it. ｢It understands It is ..killing.. penguin. ..unpleasantness.. however now, and a true enemy is a satan army the angel army of parents when it is penguin s of me Cu small. ｣ Cu said. ｢Do you revenge it on the satan army?Let s go to same. ｣ Immediately after Gale s having said that Cuiiiiin Gale..transform..surprise..say..originally..appearance..Gale..say. "If so, I will also lend power. "An iris wing has come out from the back ..the hex s saying.. at the same time. However, the wing differed and shone greatly and terribly with the hex of the pretender who had seen the first first. ???Dorpis mountain? Zgogogogogogogogo ｢What commotion is it??｣ Genesis said. "It is an oubliette. " Delbimaira said. ???Oubliette? The fragment of Potopot and ice has dropped from the ceiling. Cu fired the Raje bazooka and the prison was destroyed. "It is possible to go out by this. " After a few minutes "" Coming Delbimaira applies the gun to the turn face quickly ..falling.. by Cu behind Delbimaira after immediately after having said and to the scout ..reducing.. .... quietly. "Put it together on the angel army so that it is not found by Genesis. " "Furnace that calmed down because it was able to do such a thing" Delbimaira said. ｢Keep quiet. I will otherwise shoot it. ｣ Cu ordered it. What Delbimaira meant was heard with bad grace. ???Dorpis mountain? "It was going to be able to meet the angel army if going to the other side" Delbimaira said. " ..".. Cu said. Immediately after that and It heard a shot. And, the head became asunder, and Delbimaira that guided it was exhausted. "The guy who was the enemy ..danger.. doesn t have his body ..there was a guy whom and Jo disregarded.." Genesis said. "Apparently, the companion might be not able to be called" Cu said. "Fight" hex said. "Go" Gale said. And, Gale, the hex, and Cu were thrown in to Genesis. ??????Chapter 1 Completion