TY - JOUR. T1 - Design of allosteric hammerhead ribozymes activated by ligand-induced structure stabilization. AU - Soukup, Garrett. AU - Breaker, Ronald R.. PY - 1999/7/15. Y1 - 1999/7/15. N2 - Background: Ribozymes can function as allosteric enzymes that undergo a conformational change upon ligand binding to a site other than the active site. Although allosteric ribozymes are not known to exist in nature, nucleic acids appear to be well suited to display such advanced forms of kinetic control. Current research explores the mechanisms of allosteric ribozymes as well as the strategies and methods that can be used to create new controllable enzymes. Results: In this study, we exploit the modular nature of certain functional RNAs to engineer allosteric ribozymes that are activated by flavin mononucleotide (FMN) or theophylline. By joining an FMN- or theophylline-binding domain to a hammerhead ribozyme by different stem II elements, we have identified a minimal connective bridge comprised of a G·U ...
A hammerhead ribozyme was demonstrated to be a metalloenzyme. By controlling the metal-binding ability of the hammerhead ribozyme in the presence or absence of a specific sequence of interest, we engineered an allosterically controllable ribozyme, designated the maxizyme. Hybrid ribozymes were then constructed by coupling the site-specific cleavage activity of a hammerhead ribozyme with the unwinding activity of an endogenous RNA helicase. This leads to extremely efficient cleavage of target mRNA, not only in vitro, but also in vivo, and eliminates one of the major problems arising in the application of ribozymes for cleavage of mRNA in vivo: that many target sites on the RNA were previously inaccessible to cleavage owing to secondary and/or tertiary structure formation. Since hybrid ribozymes can efficiently attack target sites within mRNA, libraries were made of hybrid ribozymes with randomized binding arms, which were then introduced into cells. This procedure made it possible to readily ...
View Notes - Lecture8 from BIOC 100A at UCSC. 25 26 The hammerhead ribozyme (plant virus) Martick & Scott, Cell 2006 27 Group I intron ribozyme Golden et al, and cech Science (1998) 28 Acid-Base
Ribozyme-Catalyzed Transcription of an Active Ribozyme Aniela Wochner, James Attwater, Alan Coulson, and Philipp Holliger* Science 8 April 2011: Vol. 332 no. 6026 pp. 209-212 doi: 10.1126/science.1200752 For molecular biology lovers! Michael Yarus offer a very nice presentation of the paper: Climbing in 190 Dimensions doi: 10.1126/science.1205379A critical event in the origin of life is…
Despite great progress in the treatment of AIDS, the Human Immunodeficiency Virus type I (HIV-1) remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In this paper we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. Based on the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment can not be inferred solely from the results of the in vitro experiments. ...
Hammerhead ribozyme, molecular model. Ribozymes are RNA (ribonucleic acid) molecules that catalyse certain biochemical reactions. Until their discovery in the 1980s, it was thought only proteins had this ability. Most ribozymes catalyse their own cleavage, or that of other RNAs, but some also have roles within ribosomes, the location of protein synthesis. - Stock Image F009/6228
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Purpose: To investigate enzymatic performance of a proven hammerhead ribozyme (hhRz) against human rod opsin (hRHO) in a smaller supportive RNA scaffold in a mutation-independent gene silencing therapeutic strategy for autosomal dominant retinitis pigmentosa. VAI RNA of chicken embryonic lethal orphan (CELO) virus was chosen as a smaller (91 nt) scaffold for the hhRz (725 HH16) (prior human VAI scaffolds ,160 nt). Smaller chimeras allow 3D RNA algorithms for structural design and biophysical investigation of hhRz structure/function performance.. Methods: CELO-VAI scaffold, designed using RNAStructure, was PCR constructed with partially overlapping DNA primers, then directionally ligated into pNEB193-T7. hhRz cDNA or control sequence was cloned into an adapter placed at a unique CELO-VAI restriction site. Target hRHO fragment cDNA (510 nt RNA) containing the hhRz cleavage site was cloned into pBlueScript. Transcription with T7 RNA polymerase generated chimeric CELO-VAI-hhRzs and target RNA to ...
We explore RNA catalysis to learn about the catalytic potential of RNA and to decipher what is fundamental to all biological catalysts through comparison with protein enzyme catalysis. These studies also define the unique properties of RNA and proteins lead to catalytic and behavioral distinctions. The fundamental properties and behaviors of RNA molecules that we uncover teach us about how the potential function of RNA early in evolution and about the function of RNA molecules in modern-day biology. This knowledge may also be applied as RNA is co-opted for medical, technological and industrial applications.. Energy from binding interactions can be used to facilitate reactions of bond substrates, a fundamental precept of enzymology posited by Jencks for protein enzymes and demonstrated in our studies of RNA enzymes.. We currently focus on the group I ribozyme, the most well-studied catalytic RNA in both structure and function. We harness previous studies, including multiple crystal structures, a ...
We explore RNA catalysis to learn about the catalytic potential of RNA and to decipher what is fundamental to all biological catalysts through comparison with protein enzyme catalysis. These studies also define the unique properties of RNA and proteins lead to catalytic and behavioral distinctions. The fundamental properties and behaviors of RNA molecules that we uncover teach us about how the potential function of RNA early in evolution and about the function of RNA molecules in modern-day biology. This knowledge may also be applied as RNA is co-opted for medical, technological and industrial applications.. Energy from binding interactions can be used to facilitate reactions of bond substrates, a fundamental precept of enzymology posited by Jencks for protein enzymes and demonstrated in our studies of RNA enzymes.. We currently focus on the group I ribozyme, the most well-studied catalytic RNA in both structure and function. We harness previous studies, including multiple crystal structures, a ...
Since the discovery of catalytic RNA molecules (ribozymes), intense research has been devoted to understand their structure and activity. Among RNA molecules, the large ribozymes, namely group I and group II introns and RNase P, are of special importance. The first two ribozymes are known for their ability to perform self-splicing while RNase P is responsible for the 5′-end maturation of tRNA in bacteria, archea, and eukaryotes. All three groups of ribozymes show a significant requirement for metal ions in order to establish the active tertiary structure that enables catalysis. The primary role of both monovalent and divalent metal ions is to screen the negative charge associated with the phosphate sugar backbone, but the metal ions also play an active role in catalysis. Biochemical and biophysical investigations, supported by recent findings from X-ray crystal structures, allow clarifying and rationalizing both the structural and catalytic roles of metal ions in large ribozymes. In ...
RNA enzymes or ribozymes can act as endoribonucleases, catalyzing the cleavage of RNA molecules with a sequence specificity of cleavage greater than that of known ribonucleases and approaching that of the DNA restriction endonucleases, thus serving as RNA sequence specific endoribonucleases. An example is a shortened form of the self-splicing ribonsomal RNA intervening sequence of Tetrahymena (L-19 IVS RNA). Site-specific mutagenesis of the enzyme active site of the L-19 IVS RNA alters the substrate sequence specificity in a predictable manner, allowing a set of sequence-specific endoribonucleases to be synthesized. Varying conditions allow the ribozyme to act as a polymerase (nucleotidyltransferase), a dephosphorylase (acid phosphatase or phosphotransferase) or a sequence-specific endoribonuclease.
View Cell Theory from BIOLOGY MCB2010 at Broward College. • Genetic material -> catalyst (RNA catalyst not regulated. Protein catalyst can be regulated.) • Metabolism (get energy -> grow
3′,5′-Cyclic GMP spontaneously nonenzymatically polymerizes in a base-catalyzed reaction affording G oligonucleotides. When reacted with fully or partially sequence-complementary RNA (oligo C), the abiotically generated oligo G RNA displays a typical ribozyme activity consisting of terminal ligation accompanied by cleavage of an internal phosphate site of the donor oligonucleotide stem upon attack of the acceptor 3′ terminal OH. This reaction is dubbed Ligation following Intermolecular Cleavage (LIC). In a prebiotic perspective, the ability of oligo G polynucleotides to react with other sequences outlines a simple and possible evolutionary scenario based on the autocatalytic properties of RNA.
服部良一,児嶋長次郎,リジン残基13Cメチル化NMR法による相互作用解析と構造変化の検出,生物物理 56, 288-289 (2016). DOI: 10.2142/biophys.56.288 田中好幸,DNA分子を利用した水銀除染法及び機能性核酸構造解析法の開発研究,The ANNALS of Intelligent Cosmos Academic Foundation 14, 9-12 (2010). Yoshiyuki Tanaka and Akira Ono, Structural Studies on MercuryII-mediated T-T Base-pair with NMR Spectroscopy (Chapter 16), In Nick Hadjiliadis and Einar Sletten Eds., "Metal Complexes - DNA Interactions", John Wiley & Sons, West Sussex, UK (2009). DOI: 10.1002/9781444312089 Ikumi kawahara, Kaichiro Haruta, Chojiro Kojima, and Yoshiyuki Tanaka, NMR studies of HAC1 mRNA, Nucleic Acids Symposium Series 53, 269-270 (2009). Hisaaki Tateoka, Ikumi Kawahara, Satomi Hasegawa, Kaichiro Haruta, Yoshinori Kondo, Chojiro Kojima, and Yoshiyuki Tanaka, Preparations of hammerhead ribozymes for investigations of their cleavable sequences, Nucleic Acids ...
2MTJ: Nuclear Magnetic Resonance Structure of the III-IV-V Three-Way Junction from the Varkud Satellite Ribozyme and Identification of Magnesium-Binding Sites Using Paramagnetic Relaxation Enhancement.
Researchers: Andrew Babiskin, Travis Bayer, Chase Beisel, Stephanie Culler, Katie Galloway, Kevin Hoff, Maung Nyan Win We are exploring the design strategies for constructing molecular switches that act in vivo as both biosensors and ligand-controlled regulators of gene expression in bacteria, yeast, and mammalian cell culture. Much of our effort is focused on the design of nucleic acid-based molecular sensors, although the design of some protein-based sensors is being explored as well. In the area of trans-acting molecular switches, we are exploring the design of sensors that act through diverse gene regulation mechanisms such as the RNA interference (RNAi) pathway, ribozyme-based cleavage, and the antisense pathway. In the area of cis-acting molecular switches, we are exploring the design of sensors that act through regulatory mechanisms such as alternative splicing, RNase III cleavage, ribozyme-based cleavage, and internal ribosome entry site (IRES) activity. In order to effectively monitor ...
The hammerhead ribozyme is a small RNA motif that catalyzes the cleavage and ligation of RNA. The well-studied minimal hammerhead… Expand ...
The second extended Meyer quote youve dug up is just awful. In addition to the whole protein-dominated ribosome, Meyer claims that 1) peptidyl transferase ribozymes are made of ribosomal RNA and 2) that these ribozymes are quite limited because they require another catalyst. (1) is wrong - the Zhang and Cech papers he cites _evolved_ ribozymes from random sequence, they are not free-standing ribosomal RNA. With (2) its hard to tell what Meyer was even thinking: my best guess is that the other catalyst hes referring to is magnesium, which is the only thing that could be considered another catalyst mentioned in the Zhang and Cech paper. If so, thats absurd - first, they dont even show that magnesium is playing a catalytic role, it may just be required for ribozyme folding (as it is for proper folding and function of the protein dominated ribosome); second, even if it is a cofactor involved directly in catalysis, that is incredibly common, not a weakness of the ribozyme. Many enzymes, ...
Enzyme. Enzymes ( /ˈɛnzaɪmz/) are large biological molecules responsible for the thousands of chemical interconversions that sustain life. They are highly selective catalysts, greatly accelerating both the rate and specificity of metabolic reactions, from the digestion of food to the synthesis of DNA. Most enzymes are proteins, although some catalytic RNA molecules have been identified. Enzymes adopt a specific three-dimensional structure, and may employ organic (e.g. biotin) and inorganic (e.g. magnesium ion) cofactors to assist in catalysis.. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates sufficient for life. Since enzymes are selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that ...
In this paper we outline therapeutic uses of ribonucleic enzymes (ribozymes) and small interfering RNA (siRNA). The discovery of ribozymes is described and the structure of hammerhead ribozymes and their mechanism of catalysis is explained. Application of ribozymes as antiviral agents for the treatment of cancer as well as viral infections is described. The article also describes the history and discovery of siRNA and explains the mechanism of its use as an antiviral agent. Ongoing clinical trials for si RNA-mediated therapeutical approaches are listed. ...
The broad goals of this proposal are to provide a molecular-level understanding of how RNA enzymes (ribozymes) catalyze chemical reactions. We are studying a se...
J.Mol.Biol. 2000; 297:309-319 PDF supplementary information. Expanding the structural and functional diversity of RNA: analog uridine triphosphates as candidates for in vitro selection of nucleic acids. Vaish NK, Fraley AW, Szostak JW, McLaughlin LW. Nucleic Acids Res. 2000 Sep 1;28(17):3316-22. PDF. Ribozyme-catalyzed tRNA aminoacylation. Lee N, Bessho Y, Wei K, Szostak JW, Suga H. Nat Struct Biol. 2000 Jan;7(1):28-33. PDF Optimized synthesis of RNA-protein fusions for in vitro protein selection. Liu R, Barrick JE, Szostak JW, Roberts RW. Methods Enzymol. 2000;318:268-93. 1999. In vitro Selection of functional nucleic acids. Wilson DW, Szostak JW. Ann. Rev. Biochem., 1999; 68:611-648. PDF 1998. In vitro selection and directed evolution. Szostak JW. 1998 Harvey Lecture Series. 1997-98;93:95-118. Review. Isolation and characterization of fluorophore-binding RNA aptamers. Holeman LA, Robinson SL, Szostak JW and Wilson C. Folding & Design, 1998; 3:423-431. Isolation of a fluorophore-specific DNA ...
The problem of the start of biological evolution in the ancient RNA world is considered. It is postulated that the appearance of catalytic RNAs - ribozymes - via spontaneous cis- and trans-rearrangeme
The VS ribozyme is one of the nucleolytic ribozymes, that catalyse the breakage of the phosphodiester bond at a particular site by a transesterification reaction in which the 2?-oxygen carries out a nucleophilic attack on the 3?-phosphorus. The reaction o
Ribozymes are ideal model systems for the vast number of non-protein coding RNAs found in all domains of life, since they have an easily detectable biological f...
IMPACT™ is a novel protein purification system using the inducible self-cleavage activity of a protein splicing element to separate the target protein and tag.
W rzs występują zaburzenia nabytej odpowiedzi immunologicznej przejawiające się autoreaktywnością limfocytów, gromadzeniem komórek pamięci, nadczynnością limfocytów B, preferencyjnym różnicowaniem limfocytów Th17 i upośledzeniem czynnościowym limfocytów Treg. W warunkach prawidłowych odpowiedź nabyta rozwija się w szpiku i obwodowych narządach limfatycznych (węzły chłonne, śledziona). Natomiast w przypadku rzs również w ekotopowej tkance limfatycznej. W rzs odpowiedź nabyta jest inicjowana przez czynniki genetyczne i środowiskowe. Głównym genetycznym czynnikiem ryzyka rozwoju rzs są geny kodujące cząsteczki HLA-DR ze „wspólnym epitopem" (DRSE+). Spośród wielu środowiskowych czynników ryzyka rozwoju rzs najlepiej udokumentowany jest wpływ palenia tytoniu, zwłaszcza u pacjentów, którzy w haplotypie mają cząsteczki HLA-DR zawierające „wspólny epitop" i wytwarzają przeciwciała swoiste dla cytrulinowanych peptydów. Najnowsze doniesienia ...
Researchers at University of Texas have identify the process through which the double stranded RNA is remodeled inside cells in both their normal and disease states.
Hammann and Westhof conclude that a combination of improved sequence searching algorithms and more functional screening assays is required to help identify novel classes of ribozymes. One approach they did not mention is sequence comparisons between different species. I may be biased by my work in the field of gene promoter evolution, but I would expect that comparing the sequences of known ribozymes in different species would yield some interesting insights into the general patterns of ribozyme conservation throughout evolution. Novel ribozymes could then conceivably be identified by screening genomes for regions of unknown function that display similar patterns of sequence conservation. ...
For the development of specific and effective basic genetic materials to inhibit replication of hepatitis C virus (HCV), HCV genome-targeting trans-splicing aptazyme, which activity is allosterically regulated by a specific ligand, was developed. The aptazyme was designed to be comprised of sequence of RNA aptamer to the ligand, communication module sequence which can transfer structural transition for inducing ribozyme activity upon binding the ligand to the aptamer, and trans-splicing ribozyme targeting +199 nt of HCV IRES. Especially, when the aptamer and the communication module was inserted at both P6 and P8 catalytic domain of the specific ribozyme, allosteric activity of the aptazyme was the most induced. The aptazyme was shown to induce activity of trans-splicing reaction specifically and efficiently only in the presence of the specific ligand, but neither in the absence of any ligand nor in the presence of control ligand. This aptazyme can be used as a specific and effective genetic ...
Large complex RNAs, like the Tetrahymena ribozyme, tend to have complex kinetic folding pathways with multiple intermediates. Are these intermediates required for folding, or are they the result of kinetic traps? One way to discriminate between these possibilities is to vary folding conditions such as temperature or ion concentration or to make mutations that may destabilize the folding intermediates and to see how these changes affect folding rates. In the present study, the effects of [Mg2+] and temperature on the rates of P3-P7 formation (kP3-P7) and folding to the catalytically active structure (koverall) were compared for the wild-type Tetrahymena ribozyme and the A183U mutant ribozyme. Reducing the [Mg2+] leads to an increase in the value of koverall and reveals the presence of an additional kinetic trap on the folding pathway of both ribozymes. Interestingly, this trap is stabilized by high [Mg2+]. Recent studies with the self-splicing Tetrahymena group I intron pre-RNA, from which the ...
BACKGROUND: Reverse genetics systems enable the manipulation of viral genomes and therefore serve as robust reverse genetic tools to study RNA viruses. A DNA-launched rescue system initiates the transcription of viral genomic cDNA from eukaryotic promoter in transfected cells, generating homogenous RNA transcripts in vitro and thus enhancing virus rescue efficiency. As one of the hazardous pathogens to ducklings, the current knowledge of the pathogenesis of duck astrovirus type 1 (DAstV-1) is limited. The construction of a DNA-launched rescue system can help to accelerate the study of the virus pathogenesis. However, there is no report of such a system for DAstV-1. METHODS: In this study, a DNA-launched infectious clone of DAstV-1 was constructed from a cDNA plasmid, which contains a viral cDNA sequence flanked by hammerhead ribozyme (HamRz) and a hepatitis delta virus ribozyme (HdvRz) sequence at both terminals of the viral genome. A silent nucleotide mutation creating a Bgl II site in the ORF2 ...
Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical ...
All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.
Ribozymes are currently a centerpiece in the ongoing debate on the origin of life. The ability of some RNA polymerizing ribozymes to synthesize functional products without the need for a DNA template[16] (they use an RNA template instead) makes RNA an attractive candidate for hypothetical primitive biochemistry. There is a growing body of chemical, molecular biological, and geological evidence which supports this hypothesis[17][18][19][20][21][22][23]. Additionally, the recent development of a self-replicating ribozyme derived from a viral ribozyme[24][25], demonstrates that self-replicating RNAs can exist. However, the evidence remains largely circumstantial as nothing conclusive has been found thus far and, even among biochemists, the hypothesis does have its detractors[26]. This hypothesis that life originated from RNA and ribonucleoprotein based biochemistry is called the RNA world hypothesis. It is considered by many biochemists to be the most plausible current hypothesis for the origin of ...
Enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules. Enzymes are principally classified and named according to the reaction they catalyse. The chemical reaction catalysed is the specific property that distinguishes one enzyme from another, and it is logical to use it as the basis for the classification and naming of enzymes. The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) classifies enzymes into families, using a four number code, on the basis of the reactions they catalyse. In this section you will find a series of brief reviews about various enzyme subfamilies, based on their functional activity in enzymology or characteristics as many drugs targets. ...
Two trajectories are possible in converting a GC base pair to an AU base pair. One of them passes through a GU base pair intermediate, the other through an AC mismatch intermediate (see figure 4; electronic supplementary material, figure S3). In our data, a ribozyme with the GU intermediate is always more active than that with the AC intermediate (from +1.4 to +22.7%; average = +10.3%). This confirms predictions of the relative effects of these two intermediates based on the geometry of base pairs [32], experimental measurements [33] and bioinformatic analysis of tRNA evolution [34]. Our data support a continuous ridge or neutral network model (see Landscapes caused by a base pair switch in Supporting Information, electronic supplementary material) of compensatory evolution in RNA secondary structure, because in our experiments, the GU intermediate shows a significant decrease in fitness only in a single instance, and in this instance the base pair switch is not compensatory but ...
Synthetic catalytic RNAs, i.e. ribozyme, including a hairpin portion, binding sites for binding to a human papilloma virus after viral base 419 and 434, respectively, and cleavage sites for cleaving the virus at the binding sites have been constructed.
488D: Capture and visualization of a catalytic RNA enzyme-product complex using crystal lattice trapping and X-ray holographic reconstruction.
Cells must have preceded by simpler chemical systems (protocells) that had the capacity of a spontaneous self-assembly process and the ability to confine chemical reaction networks together with a form of information. The presence of lipid molecules in the early Earth conditions is sufficient to ensure the occurrence of spontaneous self-assembly processes, not defined by genetic information, but related to their chemical amphiphilic nature. Ribozymes are plausible molecules for early life, being the first small polynucleotides made up of random oligomers or formed by non-enzymatic template copying. Compartmentalization represents a strategy for the evolution of ribozymes; the attachment of ribozymes to surfaces, such as formed by lipid micellar aggregates may be particular relevant if the surface itself catalyzes RNA polymerization.It is conceivable that the transition from pre-biotic molecular aggregates to cellular life required the coevolution of the RNA world, capable of synthesizing ...
Tumour cells can develop a lot of resistance mechanisms against cytostatic drugs. Examinations of three human tumour cell lines and their cisplatinresistant variants showed an association of elevated MRP2 expression and the occurrance of cisplatinresistance. Moreover, the cisplatinresistant cell lines were crossresistant against carboplatin. To examine further factors in context of cisplatinresistance the mutation status of p53 and the cellular glutathione content of the cell lines were determined. The MRP2-open reading frame of the cisplatinresistant ovarian carcinoma cell line A2780RCIS was used for transfection into the cisplatinsensitive cell line A2780. The transfectants showed an overexpression of MRP2 and a resistance against cisplatin and carboplatin. This could be confirmed with analysis of the cell cycle and apoptosis induction after treatment with cisplatin. Using computer aided folding analysis of MRP2 mRNA parts two possible ribozyme cleavage sites were selected. The constructed ...
The gaming focused manufacturer Razer announced the Hammerhead and Hammerhead Pro in-ear headphones, with the latter adding an omni-directional microphone with an in-line remote for phone-call control and convenient voice communication. Both in-ear headsets are machined out of aircraft-grade aluminum, include 9mm
4854 To gain insight into the molecular mechanisms by which human cells replicate DNA containing fork-blocking lesions, stable transfection of human fibroblasts with antisense or hammerhead ribozymes was used to eliminate expression of key replication proteins, e.g., the subunits of human Pol zeta (hRev3, hRev7) or hRev1, a protein necessary for hPol zeta-facilitated bypass. For studies of the role of these proteins, we identified transfectant cell strains expressing high levels of antisense, or lower than normal levels of mRNA, and assayed them for the cytotoxic and mutagenic effects of exposure to UV radiation or benzo(a)pyrene diol epoxide (BPDE). For studies of the role of hRev7, antibodies were available for identifying cell strains that no longer expressed this protein, or expressed it at decreased levels. Transfectants expressing high levels of antisense against hRev3 or hRev1, were found not to be significantly more sensitive to the cytotoxic effect of UV or BPDE (as measured by loss of ...
HA3459/3 Functional analysis of Hammerhead Ribozymes from plants. A personal Fellowship to Dr. Sandeep Ojha had been granted by the Fritz Thyssen Foundation. Further previous grants include a personal fellowship in the EU-Biotechnology program and the EU-Strep FOSRAK.. ...
As promised, my penultimate note will be on the epistemological indistinguishability of the Copenhagen interpretation and the many worlds hypothesis. If youve stuck with me this far, but didnt understand that last sentence... well, you know what? Im willing to say that thats entirely my fault - Im trying to write this for the layman, after all. What I mean is that, if either the Copenhagen interpretation or the many worlds hypothesis was true, we could not tell the difference between them. The reason for this is that, under the many worlds hypothesis, we can only describe the future in terms of a probabilistic idea space (this is in fact what the many worlds hypothesis says reality is like). However, in hindsight, we will see only a series of quantum events that played out probabilistically. But under the Copenhagen interpretation, we can only describe the future in terms of probabilities, and if we were to fully describe all possible futures, this would be exactly the same as the many ...
Hammerhead sharks by the hundreds swirl around Peter Klimley. This sounds like a nightmare with teeth, but for the adventurer and scientist, its just another swim with his favorite animal.. Klimley, a marine biologist at the University of California, Davis, has spent many hours in the water with these sharks-some more than four meters long. Although hammerheads have a "man-eater" reputation, theyve never harmed him. "I once wanted to get a hammerhead on the research boat, so I lassoed it by the tail," says Klimley. "I was afraid it would turn around and bite me, but it just swam faster.". As a teenager, Klimley raised tropical fish. He became interested in sharks as a college student. "There was something romantic about sharks," he says. "It was my dream to study sharks in the water. I believe that if you want to understand an animal, you have to enter its environment.". Scalloped hammerheads are one of the largest of the nine species of hammerheads. As a young scientist, Klimley heard about ...
Consider the following addendum to the article "Engineering and characterization of a superfolder green fluorescent protein" from nature biotechnology. Retraction: Identification of genes that function in the TNF-α-mediated apoptotic pathway using randomized hybrid ribozyme libraries. Hiroaki Kawasaki, Reiko Onuki, Eigo Suyama & Kazunari Taira Nat. Biotechnol. 20, 376-380 (2002) Although the gene discovery technology described in this paper has been demonstrated to have practical utility by several independent researchers, the first author of the paper failed to maintain a proper data notebook to support the results presented. As this constitutes nonadherence to the ethical standards in scientific research, and in accordance with the recommendations from the National Institute of Advanced Industrial Science & Technology (AIST), R. Onuki, E. Suyami and K. Taira respectfully retract this paper. H. Kawasaki declines to associate himself with this retraction and maintains that all the data ...
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