High-throughput biochemical profiling reveals sequence determinants of dCas9 off-target binding and unbinding.

abstract：:The DNA-binding domain of c-Myb consists of three homologous tandem repeats of 52 amino acids. The structure of the third (C-terminal) repeat obtained by NMR analysis has a conformation related to the helix-turn-helix motif. To identify the role of each repeat in the sequence recognition of DNA, we analyzed specific i...

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

authors： Tanikawa J,Yasukawa T,Enari M,Ogata K,Nishimura Y,Ishii S,Sarai A

更新日期：1993-10-15 00:00:00

abstract：:Variation in the multiplication rate of blood stage malaria parasites is often positively correlated with the severity of the disease they cause. The rodent malaria parasite Plasmodium yoelii yoelii has strains with marked differences in multiplication rate and pathogenicity in the blood. We have used genetic analysis...

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

authors： Pattaradilokrat S,Culleton RL,Cheesman SJ,Carter R

更新日期：2009-04-28 00:00:00

abstract：:The intrinsic role of endogenous IL-17A in spontaneous intestinal tumorigenesis has not been addressed previously to our knowledge. Ablation of IL-17A significantly reduced tumor development in mice bearing a heterozygote mutation in the adenomatous polyposis coli (APC) gene (Apc(Min/+) mice). There was also a decreas...

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

authors： Chae WJ,Gibson TF,Zelterman D,Hao L,Henegariu O,Bothwell AL

更新日期：2010-03-23 00:00:00

abstract：:Nodules harboring nitrogen-fixing rhizobia are a well-known trait of legumes, but nodules also occur in other plant lineages, with rhizobia or the actinomycete Frankia as microsymbiont. It is generally assumed that nodulation evolved independently multiple times. However, molecular-genetic support for this hypothesis ...

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

authors： van Velzen R,Holmer R,Bu F,Rutten L,van Zeijl A,Liu W,Santuari L,Cao Q,Sharma T,Shen D,Roswanjaya Y,Wardhani TAK,Kalhor MS,Jansen J,van den Hoogen J,Güngör B,Hartog M,Hontelez J,Verver J,Yang WC,Schijlen E,Repin

更新日期：2018-05-15 00:00:00

abstract：:TCR-mediated recognition of beta-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer(+) cells isolated...

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

authors： Arrenberg P,Halder R,Dai Y,Maricic I,Kumar V

更新日期：2010-06-15 00:00:00

abstract：:An unbiased survey has been made of the stable, most abundant multi-protein complexes in Desulfovibrio vulgaris Hildenborough (DvH) that are larger than Mr approximately 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively ...

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

authors： Han BG,Dong M,Liu H,Camp L,Geller J,Singer M,Hazen TC,Choi M,Witkowska HE,Ball DA,Typke D,Downing KH,Shatsky M,Brenner SE,Chandonia JM,Biggin MD,Glaeser RM

更新日期：2009-09-29 00:00:00

abstract：:If X(1), X(2),... are independent random variables with zero expectation and finite variances, the cumulative sums S(n) are, on the average, of the order of magnitude S(n), where S(n) (2) = E(S(n) (2)). The occasional maxima of the ratios S(n)/S(n) are surprisingly large and the problem is to estimate the extent of th...

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

authors： Feller W

更新日期：1969-07-01 00:00:00

abstract：:Three major oxidation products of 2'-deoxycytidine (dC)--5-hydroxy-2'-deoxycytidine (oh5dC), 5-hydroxy-2'-deoxyuridine (oh5dU), and 5,6-dihydroxy-5,6-dihydro-2'-deoxyuridine (dUg)--were analyzed from enzymatically hydrolyzed DNA with reversed-phase high-performance liquid chromatography coupled to electrochemical dete...

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

authors： Wagner JR,Hu CC,Ames BN

更新日期：1992-04-15 00:00:00

abstract：:Unfolded RNase A is known to contain an equilibrium mixture of two forms, a slow-folding form (U(1)) and a fast-folding form (U(2)). If U(1) is produced after unfolding by the slow cis-trans isomerization of proline residues about X-Pro imide bonds, then the formation of U(1) should be catalyzed by strong acids. There...

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

authors： Schmid FX,Baldwin RL

更新日期：1978-10-01 00:00:00

abstract：:To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, t...

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

authors： Knight GM,Griffiths UK,Sumner T,Laurence YV,Gheorghe A,Vassall A,Glaziou P,White RG

更新日期：2014-10-28 00:00:00

abstract：:For brain functions such as working memory and motor planning, neuronal circuits are able to sustain persistent activity after transient inputs. Theoretical studies have suggested that persistent activity can exist in recurrently connected networks as active reverberation. However, the actual cellular processes underl...

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

authors： Lau PM,Bi GQ

更新日期：2005-07-19 00:00:00

abstract：:Specific [3H]retinoic acid (RA)-binding sites in nuclear and cytosolic extracts prepared from human myeloblastic leukemia HL-60 cells have been detected by sucrose density gradient sedimentation and size-exclusion high-performance liquid chromatography (HPLC) analyses. This RA-binding activity migrated as a single pea...

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

authors： Nervi C,Grippo JF,Sherman MI,George MD,Jetten AM

更新日期：1989-08-01 00:00:00

abstract：:Procedures are described for the isolation of conditional lethal mutants of mouse L-60T cells. The mutant lines were temperature sensitive by the following criteria: (a) colony-forming ability, (b) growth in suspension culture, and (c) rate of uptake of tritiated-thymidine. ...

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

authors： Thompson LH,Mankovitz R,Baker RM,Till JE,Siminovitch L,Whitmore GF

更新日期：1970-06-01 00:00:00

abstract：:Recent experimental data on the equilibrium binding of myosin subfragment 1 (S-1) to regulated actin filaments in the presence and in the absence of Ca(2+) are analyzed by using a linear Ising model. In the model, each tropomyosin-troponin unit (including seven sites on the actin filament) can be in one of two possibl...

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

authors： Hill TL,Eisenberg E,Greene L

更新日期：1980-06-01 00:00:00

abstract：:The toxic, mutagenic, and carcinogenic effects of alkylating agents have been attributed to their ability to damage DNA. Reaction at the O6 position of guanine results in miscoding during DNA replication, has been shown to be mutagenic in both bacteriophage and bacteria, and may be responsible for malignant transforma...

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

authors： Brennand J,Margison GP

更新日期：1986-09-01 00:00:00

abstract：:Treatment of the third component of human complement (C3) with methylamine results in a loss of hemolytic function and the appearance of a thiol group. Studies with [14C]methylamine have indicatd a stoichiometric and covalent reaction with the native protein. Hydrazine-inactivated C3 and C3b prepared with bovine tryps...

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

authors： Tack BF,Harrison RA,Janatova J,Thomas ML,Prahl JW

更新日期：1980-10-01 00:00:00

abstract：:Many studies have reported age-related changes in immune responses that could be due to alterations in lymphoid cell numbers or functions. Here we report the results of studies using immunofluorescent staining and in vitro assays of cellular function to compare the expression of cell surface antigens on lymphocytes fr...

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

authors： Sidman CL,Luther EA,Marshall JD,Nguyen KA,Roopenian DC,Worthen SM

更新日期：1987-11-01 00:00:00

abstract：:Oxygen free radicals are highly reactive species generated by many cellular oxidation-reduction processes. These radicals damage cellular constituents and have been causally implicated in the pathogenesis of many human diseases. We report here that oxygen free radicals generated by Fe2+ in aqueous solution are mutagen...

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

authors： Loeb LA,James EA,Waltersdorph AM,Klebanoff SJ

更新日期：1988-06-01 00:00:00

abstract：:The cDNA sequences encoding the adult alpha- and beta-globin polypeptides of a marsupial, the native cat Dasyurus viverrinus, have been cloned and their nucleotide sequences have been determined. Using these cDNA clones we have determined the chromosomal location of the native cat alpha- and beta-globin genes by in si...

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

authors： Wainwright B,Hope R

更新日期：1985-12-01 00:00:00

abstract：:Bacteriophage lambda integrates into the chromosome of its Escherichia coli host by means of a site-specific recombination between a locus on the phage chromosome (phage att site) and a locus on the bacterial chromosome (bacterial att site). The nucleotide sequence of four lambda att sites altered in site-specific rec...

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

authors： Hoess RH,Landy A

更新日期：1978-11-01 00:00:00

abstract：:In this paper we solve several boundary value problems for the Helmholtz equation on polygonal domains. We observe that when the problems are formulated as the boundary integral equations of potential theory, the solutions are representable by series of appropriately chosen Bessel functions. In addition to being analy...

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

authors： Serkh K,Rokhlin V

更新日期：2016-08-16 00:00:00

abstract：:Wild-type p53 protein is a growth modulator whose inactivation has been found to be a key event in malignant transformation. Reconstitution of wild-type p53 in the p53-nonproducer, Abelson murine leukemia virus-transformed pre-B-cell line L12 gave rise to stably growing clones. Wild-type p53-producer derived cell line...

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

authors： Shaulsky G,Goldfinger N,Peled A,Rotter V

更新日期：1991-10-15 00:00:00

abstract：:KRAS mutant tumors are largely recalcitrant to targeted therapies. Genetically engineered mouse models (GEMMs) of Kras mutant cancer recapitulate critical aspects of this disease and are widely used for preclinical validation of targets and therapies. Through comprehensive profiling of exomes and matched transcriptome...

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

authors： Chung WJ,Daemen A,Cheng JH,Long JE,Cooper JE,Wang BE,Tran C,Singh M,Gnad F,Modrusan Z,Foreman O,Junttila MR

更新日期：2017-12-19 00:00:00

abstract：:Collectivistic cultures have been characterized as having harmonious, cooperative ingroup relationships. However, we find evidence that people in collectivistic cultures are more vigilant toward ingroup members, mindful of their possible unethical intentions. Study 1 found that Chinese participants were more vigilant ...

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

authors： Liu SS,Morris MW,Talhelm T,Yang Q

更新日期：2019-07-16 00:00:00

abstract：:REPRESSOR OF SILENCING 1 (ROS1) is a DNA demethylation enzyme that was previously identified during a genetic screen for the silencing of both RD29A-LUC and 35S-NPTII transgenes on a T-DNA construct. Here we performed a genetic screen to identify additional mutants in which the 35S-NPTII transgene is silenced. We iden...

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

authors： Li X,Qian W,Zhao Y,Wang C,Shen J,Zhu JK,Gong Z

更新日期：2012-07-10 00:00:00

abstract：:The potential involvement of ceramide-related signaling processes in the induction of apoptosis by tumor necrosis factor alpha was assessed by multiple biochemical strategies in the human leukemic cell lines HL-60 and U937 and the murine fibrosarcoma cell lines L929/LM and WEHI 164/13. Exposure of these cells to tumor...

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

authors： Jarvis WD,Kolesnick RN,Fornari FA,Traylor RS,Gewirtz DA,Grant S

更新日期：1994-01-04 00:00:00

abstract：:The sphinganine analog mycotoxin, AAL-toxin, induces a death process in plant and animal cells that shows apoptotic morphology. In nature, the AAL-toxin is the primary determinant of the Alternaria stem canker disease of tomato, thus linking apoptosis to this disease caused by Alternaria alternata f. sp. lycopersici. ...

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

authors： Lincoln JE,Richael C,Overduin B,Smith K,Bostock R,Gilchrist DG

更新日期：2002-11-12 00:00:00

abstract：:A fraction of the unintegrated viral DNA that appears early after infection of mouse cells by Moloney leukemia virus is infectious. The infectivity could be deomonstrated by an XC plaque assay of the cells exposed to DNA co-precipitated with calcium phosphate. The number of plaques deriving from closed-circular, super...

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

authors： Smotkin D,Gianni AM,Rozenblatt S,Weinberg RA

更新日期：1975-12-01 00:00:00

abstract：:Cofilin-actin rods are inclusion-like structures that are induced by certain chemical or physical stresses in cultured cells, and the rods formed in neurons are thought to be associated with neurodegeneration. Here, we cloned an Aplysia cofilin homolog and overexpressed it in cultured neurons. Overexpressed cofilin fo...

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

authors： Jang DH,Han JH,Lee SH,Lee YS,Park H,Lee SH,Kim H,Kaang BK

更新日期：2005-11-01 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