BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice.

abstract：:Each person's genome sequence has thousands of missense variants. Practical interpretation of their functional significance must rely on computational inferences in the absence of exhaustive experimental measurements. Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequen...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Miosge LA,Field MA,Sontani Y,Cho V,Johnson S,Palkova A,Balakishnan B,Liang R,Zhang Y,Lyon S,Beutler B,Whittle B,Bertram EM,Enders A,Goodnow CC,Andrews TD

更新日期：2015-09-15 00:00:00

abstract：:We examine the IFN-alpha/beta-independent activation of cellular transcription that constitutes an early antiviral response of cells against influenza A and B viruses, which cause widespread epidemics in humans. We show that influenza B virus induces the synthesis in human cells of several mature mRNAs encoded by gene...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kim MJ,Latham AG,Krug RM

更新日期：2002-07-23 00:00:00

abstract：:The human isoform 2 of pantothenate kinase (PanK2) is localized to the mitochondria, and mutations in this protein are associated with a progressive neurodegenerative disorder. PanK2 inhibition by acetyl-CoA is so stringent (IC50 < 1 microM) that it is unclear how the enzyme functions in the presence of intracellular ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Leonardi R,Rock CO,Jackowski S,Zhang YM

更新日期：2007-01-30 00:00:00

abstract：:The role of DNA polymerase alpha (pol alpha) and DNA primase has been investigated in the simian virus 40 (SV40) DNA replication system in vitro. Removal of pol alpha and primase activities from crude extracts of HeLa cells or monkey cells by use of an anti-pol alpha immunoaffinity column resulted in the loss of repli...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Murakami Y,Wobbe CR,Weissbach L,Dean FB,Hurwitz J

更新日期：1986-05-01 00:00:00

abstract：:The cellular form of the Prion protein (PrPC) is necessary for prion replication in mice. To determine whether it is also sufficient, we expressed PrP under the control of various cell- or tissue-specific regulatory elements in PrP knockout mice. The interferon regulatory factor-1 promoter/Emu enhancer led to high PrP...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Raeber AJ,Sailer A,Hegyi I,Klein MA,Rülicke T,Fischer M,Brandner S,Aguzzi A,Weissmann C

更新日期：1999-03-30 00:00:00

abstract：:IL-2-PE40 is a chimeric protein composed of human interleukin 2 (IL-2) genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. IL-2-PE40, which is extremely cytotoxic to IL-2 receptor-positive cells, was examined for its ability to prevent graft rejection...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Lorberboum-Galski H,Barrett LV,Kirkman RL,Ogata M,Willingham MC,FitzGerald DJ,Pastan I

更新日期：1989-02-01 00:00:00

abstract：:DNA extracted from Dane particles has been characterized by gel electrophoresis and restriction enzyme cleavage with endonuclease R-HaeIII (from Hemophilus aegyptius). Dane particle DNA is proposed to be a double-stranded circular DNA approximately 3600 nucleotides in length containing a single-stranded gap of 600-210...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Summers J,O'Connell A,Millman I

更新日期：1975-11-01 00:00:00

abstract：:In recent years, advertisers and magazine editors have been widely criticized for taking digital photo retouching to an extreme. Impossibly thin, tall, and wrinkle- and blemish-free models are routinely splashed onto billboards, advertisements, and magazine covers. The ubiquity of these unrealistic and highly idealize...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kee E,Farid H

更新日期：2011-12-13 00:00:00

abstract：:Cardiotoxin VII4 from Naja mossambica mossambica crystallizes in space group P61 (a = b = 73.9 A; c = 59.0 A) with two molecules of toxin (molecular mass = 6715 Da) in the asymmetric unit. The structure was solved by using a combination of multiple isomorphous replacement and density modification methods. Model buildi...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rees B,Samama JP,Thierry JC,Gilibert M,Fischer J,Schweitz H,Lazdunski M,Moras D

更新日期：1987-05-01 00:00:00

abstract：:Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotei...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Xu K,Rajashankar KR,Chan YP,Himanen JP,Broder CC,Nikolov DB

更新日期：2008-07-22 00:00:00

abstract：:Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme cataly...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Lundström P,Mulder FA,Akke M

更新日期：2005-11-22 00:00:00

abstract：:An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, gene...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Sellers WR,Rodgers JW,Kaelin WG Jr

更新日期：1995-12-05 00:00:00

abstract：:The binding of invariant chain to major histocompatibility complex (MHC) proteins is an important step in processing of MHC class II proteins and in antigen presentation. The question of how invariant chain can bind to all MHC class II proteins is central to understanding these processes. We have employed molecular mo...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Lee C,McConnell HM

更新日期：1995-08-29 00:00:00

abstract：:Death of pancreatic β cells is a pathological hallmark of type 1 diabetes (T1D). However, the molecular mechanisms of β cell death and its regulation are poorly understood. Here we describe a unique regulatory pathway of β cell death that comprises microRNA-21, its target tumor suppressor PDCD4, and its upstream trans...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Ruan Q,Wang T,Kameswaran V,Wei Q,Johnson DS,Matschinsky F,Shi W,Chen YH

更新日期：2011-07-19 00:00:00

abstract：:Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T antigen) synergistically increased transcription from both the early and the late promoters of papovavirus JC in ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Renner K,Leger H,Wegner M

更新日期：1994-07-05 00:00:00

abstract：:Recent studies have suggested that Paleozoic hyperoxia enabled animal gigantism, and the subsequent hypoxia drove a reduction in animal size. This evolutionary hypothesis depends on the argument that gas exchange in many invertebrates and skin-breathing vertebrates becomes compromised at large sizes because of distanc...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kaiser A,Klok CJ,Socha JJ,Lee WK,Quinlan MC,Harrison JF

更新日期：2007-08-07 00:00:00

abstract：:The great mass extinctions of the fossil record were a major creative force that provided entirely new kinds of opportunities for the subsequent explosive evolution and diversification of surviving clades. Today, the synergistic effects of human impacts are laying the groundwork for a comparably great Anthropocene mas...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Jackson JB

更新日期：2008-08-12 00:00:00

abstract：:Chromosome rearrangements, such as large deletions, inversions, or translocations, mediate migration of large DNA segments within or between chromosomes, which can have major effects on cellular genetic control. A method for chromosome manipulation would be very useful for studying the consequences of large-scale DNA ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Van Deursen J,Fornerod M,Van Rees B,Grosveld G

更新日期：1995-08-01 00:00:00

abstract：:GSTs catalyze the conjugation of glutathione with a wide variety of hydrophobic compounds, generally resulting in nontoxic products that can be readily eliminated. In contrast to many other organisms, the malarial parasite Plasmodium falciparum possesses only one GST isoenzyme (PfGST). This GST is highly abundant in t...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Fritz-Wolf K,Becker A,Rahlfs S,Harwaldt P,Schirmer RH,Kabsch W,Becker K

更新日期：2003-11-25 00:00:00

abstract：:Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results rev...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Vihervaara A,Sergelius C,Vasara J,Blom MA,Elsing AN,Roos-Mattjus P,Sistonen L

更新日期：2013-09-03 00:00:00

abstract：:Recently, the highly invasive Asian tiger mosquito, Aedes albopictus, rapidly displaced resident populations of the yellow fever mosquito, Aedes aegypti in the southeastern United States and in Bermuda. Although multiple mechanisms of competitive displacement have been hypothesized, recent evidence of cross-inseminati...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bargielowski IE,Lounibos LP,Carrasquilla MC

更新日期：2013-02-19 00:00:00

abstract：:The flatworm Macrostomum lignano features a duo-gland adhesive system that allows it to repeatedly attach to and release from substrates in seawater within a minute. However, little is known about the molecules involved in this temporary adhesion. In this study, we show that the attachment of M. lignano relies on the ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Wunderer J,Lengerer B,Pjeta R,Bertemes P,Kremser L,Lindner H,Ederth T,Hess MW,Stock D,Salvenmoser W,Ladurner P

更新日期：2019-03-05 00:00:00

abstract：:The reversible association of alpha and beta gamma subunits of GTP-binding proteins is important for signal transmission from a variety of cell-surface receptors to intracellular effectors. Previous work showed that 1,6-bis(maleimido)hexane, which crosslinks cysteine residues, crosslinks alpha o and alpha i-1 to beta ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Thomas TC,Schmidt CJ,Neer EJ

更新日期：1993-11-01 00:00:00

abstract：:A remarkable property of tetrapod bone is its ability to detect and remodel areas where damage has accumulated through prolonged use. This process, believed vital to the long-term health of bone, is considered to be initiated and orchestrated by osteocytes, cells within the bone matrix. It is therefore surprising that...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Atkins A,Dean MN,Habegger ML,Motta PJ,Ofer L,Repp F,Shipov A,Weiner S,Currey JD,Shahar R

更新日期：2014-11-11 00:00:00

abstract：:Our previous work [Levinger, L. & Varshavsky, A. (1982) Cell 28, 375-385] has shown that D1, a 50-kilodalton chromosomal protein of Drosophila melanogaster, is specifically associated with isolated nucleosomes that contain a complex A + T-rich satellite DNA with buoyant density of 1.688 g/ml. We show here that D1 is a...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Levinger L,Varshavsky A

更新日期：1982-12-01 00:00:00

abstract：:Mixed-metal oxides play a very important role in many areas of chemistry, physics, materials science, and geochemistry. Recently, there has been a strong interest in understanding phenomena associated with the deposition of oxide nanoparticles on the surface of a second (host) oxide. Here, scanning tunneling microscop...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Park JB,Graciani J,Evans J,Stacchiola D,Ma S,Liu P,Nambu A,Sanz JF,Hrbek J,Rodriguez JA

更新日期：2009-03-31 00:00:00

abstract：:The mammary glands of prepubertal estrogen receptor (ER)beta-- mice are morphologically indistinguishable from those of WT littermates. It appears that, although ERbeta is expressed in the mouse mammary gland, it is not involved in ductal growth of the gland. In this study, we examined the possibility that ERbeta has ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Förster C,Mäkela S,Wärri A,Kietz S,Becker D,Hultenby K,Warner M,Gustafsson JA

更新日期：2002-11-26 00:00:00

abstract：:Down-regulation of mitogenic signaling in mammalian cells relies in part on endosomal trafficking of activated receptors into lysosomes, where the receptors are degraded. These events are mediated by ubiquitination of the endosomal cargo and its consequent sorting into multivesicular bodies that form at the surfaces o...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Lu Q,Hope LW,Brasch M,Reinhard C,Cohen SN

更新日期：2003-06-24 00:00:00

abstract：:Pseudohypoparathyroidism type Ia (PHP-Ia) results from the loss of one allele of G(salpha), causing resistance to parathyroid hormone and other hormones that transduce signals via G(s). Most G(salpha)mutations cause the complete loss of protein expression, but some cause loss of function only, and these have provided ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Makita N,Sato J,Rondard P,Fukamachi H,Yuasa Y,Aldred MA,Hashimoto M,Fujita T,Iiri T

更新日期：2007-10-30 00:00:00

abstract：:To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kobayashi M,Aida M,Nagaoka H,Begum NA,Kitawaki Y,Nakata M,Stanlie A,Doi T,Kato L,Okazaki IM,Shinkura R,Muramatsu M,Kinoshita K,Honjo T

更新日期：2009-12-29 00:00:00