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Artykuły w czasopismach na temat "I-motif DNA"
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Wright, Elisé P., Mahmoud A. S. Abdelhamid, Michelle O. Ehiabor, Melanie C. Grigg, Kelly Irving, Nicole M. Smith i Zoë A. E. Waller. "Epigenetic modification of cytosines fine tunes the stability of i-motif DNA". Nucleic Acids Research 48, nr 1 (28.11.2019): 55–62. http://dx.doi.org/10.1093/nar/gkz1082.
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Abstract i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications.
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Saha, Puja, Deepanjan Panda, Diana Müller, Arunabha Maity, Harald Schwalbe i Jyotirmayee Dash. "In situ formation of transcriptional modulators using non-canonical DNA i-motifs". Chemical Science 11, nr 8 (2020): 2058–67. http://dx.doi.org/10.1039/d0sc00514b.
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Li, Tao, i Michael Famulok. "I-Motif-Programmed Functionalization of DNA Nanocircles". Journal of the American Chemical Society 135, nr 4 (22.01.2013): 1593–99. http://dx.doi.org/10.1021/ja3118224.
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Dong, Yuanchen, Zhongqiang Yang i Dongsheng Liu. "DNA Nanotechnology Based on i-Motif Structures". Accounts of Chemical Research 47, nr 6 (20.05.2014): 1853–60. http://dx.doi.org/10.1021/ar500073a.
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Phan, Anh Tuân, i Jean-Louis Leroy. "Intramolecular i-Motif Structures of Telomeric DNA". Journal of Biomolecular Structure and Dynamics 17, sup1 (styczeń 2000): 245–51. http://dx.doi.org/10.1080/07391102.2000.10506628.
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Butcher, David, i Jaroslava Miksovska. "DNA i-MOTIF Probed by Photoacoustic Calorimetry". Biophysical Journal 106, nr 2 (styczeń 2014): 64a. http://dx.doi.org/10.1016/j.bpj.2013.11.434.
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Gade, Chandrasekhar Reddy, i Nagendra K. Sharma. "Hybrid DNA i-motif: Aminoethylprolyl-PNA (pC 5 ) enhance the stability of DNA (dC 5 ) i-motif structure". Bioorganic & Medicinal Chemistry Letters 27, nr 24 (grudzień 2017): 5424–28. http://dx.doi.org/10.1016/j.bmcl.2017.11.004.
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Zeng, Huang, Shuangshuang Kang, Yu Zhang, Ke Liu, Qian Yu, Ding Li i Lin-Kun An. "Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands". International Journal of Molecular Sciences 22, nr 4 (8.02.2021): 1711. http://dx.doi.org/10.3390/ijms22041711.
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Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of VEGF promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a limited number of chemotypes as the selective ligands of VEGF promoter i-motif, which leaves much room for development. Herein, we report the discovery of the natural oleanolic acid scaffold as a novel chemotype for the development of selective ligands of VEGF i-motif. A series of oleanolic acid derivatives as VEGF promoter i-motif ligands were synthesized. Subsequent evaluations showed that 3c could selectively bind to and stabilize VEGF promoter i-motif without significant binding to G-quadruplex, duplex DNA, and other oncogene i-motifs. Cell-based assays indicated that 3c could effectively downregulate VEGF gene transcription and expression in MCF-7 cells, inhibit tumor cells proliferation and migration, and induce cancer cells apoptosis. This work provides evidence of VEGF promoter i-motif as an anticancer target and will facilitate future efforts for the discovery of oleanolic acid-based selective ligands of VEGF promoter i-motif.
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Dalyan, Ye B., L. G. Aslanyan i I. V. Vardanyan. "THE INFLUENCE OF UREA ON G-QUADRUPLEX AND i-MOTIF STRUCTURES IN COMPLEMENTARY DNA SEQUENCES". Proceedings of the YSU A: Physical and Mathematical Sciences 54, nr 2 (252) (17.08.2020): 115–22. http://dx.doi.org/10.46991/pysu:a/2020.54.2.115.
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In the present study, the methods of circular dichroism and UV/Vis spectrophotometry were used to study the influence of urea on the structural transitions i-motif $\leftrightarrows$ unfolded single strand in cytosine-rich ${\text{d[3}^{\prime}\text{-(CCCAAT)}_{3}\text{CCC-5)}^{\prime}]}$ region of telomeric DNA (Tel22C) and G-quadruplex $\leftrightarrows$ unfolded single strand in complementary guanine-rich strand ${\text{d[5}^{\prime}\text{-A(GGGTTA)}_{3}\text{GGG-3}^{\prime}]}$ (Tel22G) at pH 5.5 and 400 mM Na+. Under these conditions, Tel22C and Tel22G were found to form stable i-motif and G-quadruplex structures. It has been shown that urea (0-8 M) destabilizes the i-motif and G-quadruplex structures, but unlike thermal denaturation, it does not destroy the structures completely. The melting processes of G-quadruplex and i-motif are separated in the temperature scale (at any concentration of urea, the melting of the G-quadruplex starts at temperatures where the melting of the i-motifs has already been completed).
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Martins, Alexandra, Christian H. Gross i Stewart Shuman. "Mutational Analysis of Vaccinia Virus Nucleoside Triphosphate Phosphohydrolase I, a DNA-Dependent ATPase of the DExH Box Family". Journal of Virology 73, nr 2 (1.02.1999): 1302–8. http://dx.doi.org/10.1128/jvi.73.2.1302-1308.1999.
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ABSTRACT Vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH-I) is a DNA-dependent ATPase that serves as a transcription termination factor during viral mRNA synthesis. NPH-I is a member of the DExH box family of nucleic acid-dependent nucleoside triphosphatases (NTPases), which is defined by the presence of several conserved sequence motifs. We have assessed the contributions of individual amino acids (underlined) in motifs I (GxGKT), II (DExHN), III (SAT), and VI (QxxGRxxR) to ATP hydrolysis by performing alanine scanning mutagenesis. Significant decrements in ATPase activity resulted from mutations at nine positions: Lys-61 and Thr-62 (motif I); Asp-141, Glu-142, His-144, and Asn-145 (motif II); and Gln-472, Arg-476, and Arg-479 (motif VI). Structure-function relationships at each of these positions were clarified by introducing conservative substitutions and by steady-state kinetic analysis of the mutant enzymes. Comparison of our findings for NPH-I with those of mutational studies of other DExH and DEAD box proteins underscores similarities as well as numerous disparities in structure-activity relationships. We conclude that the functions of the conserved amino acids of the NTPase motifs are context dependent.
Rozprawy doktorskie na temat "I-motif DNA"
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Jolad, Vandana V. "Structure and dynamics of a DNA i-motif". Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414277.
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Cui, Yunxi. "Regulation Analysis of DNA G-quadruplex and i-Motif bySingle-Molecule Laser Tweezers". Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581.
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Day, Henry. "Investigating the effect of small molecule ligands and cations on i-motif DNA". Thesis, University of East Anglia, 2015. https://ueaeprints.uea.ac.uk/53444/.
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The i-motif is an alternative DNA secondary structure motif formed in sequences rich in cytosine, consisting of four strands, stabilised by hemi-protonated cytosine-cytosine+ base pairs. The motif forms in sequences complimentary to the G-quadruplex however, far less is known about the i-motif and most research to date has focused on its application in nanotechnology. Despite this, recent progress in the field has indicated that the i-motif may be a possible therapeutic target in certain cases. In order to study this structure in more detail a chemical tool box of ligands and conditions is needed, which can be used to probe its potential biological function. Herein the effect of small molecule ligands and cations has been investigated. A previously identified i-motif binding compound BisA has been characterised in detail with a range of biophysical experiments, showing that it does bind to the i-motif but causes the DNA to condense. A high throughput screen has been carried out finding a number of potential new i-motif binding ligands and, through a range of experiments, two lead compounds mitoxantrone and tilorone have been identified with micromolar affinities from which novel i-motif binding analogues and structure activity relationships can be developed. Finally, the effect of cations on the i-motif has been studied, including a wider selection from across the periodic table than has previously been investigated. This has shown that at neutral pH, silver (I) ions have the ability to induce i-motif formation and that this is reversible in the presence of cysteine. While at acidic pH, copper (II) ions have the ability to induce hairpin formation reversibly in the presence of EDTA. This could enable the formation of multiple structures from the same oligonucleotide sequence in response to different conditions. The combination of these results should provide useful tools to further study the i-motif structure.
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Butcher, David S. "Thermodynamics and Kinetics of Ligand Photodissociation in Heme Proteins and Formation of DNA i-Motif". FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3259.
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Heme proteins carry out a diverse array of functions in vivo while maintaining a well-conserved 3-over-3 α-helical structure. Human hemoglobin (Hb) is well-known for its oxygen transport function. Type 1 non-symbiotic hemoglobins (nsHb1) in plants and bacterial flavohemoglobins (fHb) from a variety of bacterial species have been predicted to carry out a nitric oxide dioxygenase function. In nsHb1 and fHb this function has been linked to protection from nitrosative stress. Herein, I combine photoacoustic calorimetry (PAC), transient absorption spectroscopy (TA), and classical molecular dynamics (cMD) simulations to characterize molecular mechanism of diatomic ligand interactions with a hexa-coordinate globin from plant (rice hemoglobin), bacterial flavohemoglobins and human hemoglobin.
In rice type 1 non-symbiotic hemoglobin (rHb1), the dynamics and energetics of structural changes associated with ligand photodissociation is strongly impacted by solvent and temperature, namely CO escape from the protein matrix is slower at pH = 6.0 compare to neutral pH (ns) due to the CD loop reorganization which forms a pathway for ligand escape. In human hemoglobin, exogenous allosteric effectors modulate energetics of conformational changes associated with the CO and O2 escape although the effectors impact on rate constants for ligand association is small. The conformational dynamics associated with ligand photorelease from fHbs from Cupriavidus necator (FHP) and Staphylococcus aureus (HMPSa) are strongly modulated by the presence of azole drugs indicating that drug association modulates structural properties of the heme binding pocket.
In addition, we carried out a study of the formation of the DNA intercalated motif (i-motif). The formation of the structure is strongly favored at acidic pH; therefore, PAC was combined with a 2-nitrobenzaldehyde pH-jump to probe formation of the i-motif on fast timescales. i-Motif folding is two-step process with the initial protonation of cytosine residues being endothermic with ΔHfast=8.5 ± 7.0 kcal mol-1 and ΔVfast=10.4 ± 1.6 mL mol-1 and subsequent nucleation/i-motif folding (τ = 140 ns) with ΔHslow=-51.5 ± 4.8 kcal mol-1 and ΔVslow=-6.6 ± 0.9 mL mol-1. The above results indicate that PAC can be employed to study diverse biochemical reactions such as DNA folding, drug binding and ligand photorelease from proteins.
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Benabou, Zdaou Sanae. "Application of analytical and chemometric methodologies to study complex bioanalytical processes involving DNA i-motif structures". Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663796.
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The i-motif is a DNA structure formed by cytosine-rich sequences that consists of parallel- stranded duplexes held together by intercalated base pairs. The in vitro formation of this structure in DNA sequences corresponding to the promoter regions of several oncogenes, such as c-kit, c-myc or bcl-2, has been demonstrated. Recently, the first direct evidence for its in vivo presence in human cells and control regulatory functions has been proven. This structure is not only interesting from a biophysical and biomedical point of view, but also for their potential application in Analytical Chemistry or Nanotechnology.
The present Doctoral Thesis deals with the application of analytical and chemometric methodologies to study complex bioanalytical processes involving DNA i-motif structures. The sequences studied correspond to those found at cytosine-rich regions found near the promoter regions of the nmyc and SMARCA4 genes. On the one hand, the stability of the i- motif structures formed by these sequences according to variations of pH, temperature, ionic strength, or presence of ligands in steady-state conditions has been studied. On the other hand, the potential of ultrafast spectroscopies for the study of fast kinetic processes triggered by light has been evaluated. Through the Thesis, curve resolution methods, either based on soft-, hard- or hybrid-modelling have been used extensively to model the biochemical processes of interest.
The steady-state studies have demonstrated that the stability against pH or temperature variations of the three different kinds of cytosine-rich sequences mentioned above is strongly dependent on the number of the C·C+ base pairs, but also on the contribution of other factors, such as the base composition and length of the loops and the presence of additional stabilising structures (hairpins) in the DNA sequence. The studies performed at ultrafast time scales have revealed that the photochemical process induced by UV-lamp irradiation and monitored by rapid-scan FTIR involves the formation of dimeric photoproducts in folded and unfolded sequences. The study of processes monitored by time-resolved fluorescence in the scale of picoseconds has shown that i-motif relaxation is detected by the presence of fast lifetimes in the pH range between 4 and 6, associated with intrinsic conformational changes at the fluorescent site. In this last study, one or two
different i-motif structures have been detected in the nmyc and in the shortest DNA sequences studied, respectively.
Finally, the application of multivariate resolution methods, based either on hard- or soft- modelling, has allowed the recovery of valuable chemical information from evolutionary processes of DNA. Besides, the adaptation and application of hybrid hard- and soft- modelling has been shown to be a useful approach to detect intermediate temperature- dependent conformational transitions and to avoid the effect of baseline drifts in the estimation of the melting temperature, as well to retrieve rate constants from the kinetic information present in rapid-scan FTIR difference spectra.La estructura de l’ADN coneguda com “i-motif” es forma en seqüències riques en bases citosina (C). L’esquelet de l’i-motif està format per parells de bases C·C+ intercalats i estabilitzats per ponts d’hidrogen. S'ha demostrat la formació in vitro d'aquesta estructura en seqüències d'ADN corresponents a les regions promotores de diversos oncògens, com el c-kit, el c-myc o el bcl-2. Recentment, s'ha demostrat la primera evidència de la seva presència in vivo. La present Tesi Doctoral tracta de l'aplicació de metodologies analítiques i quimiomètriques per estudiar processos bioanalítics complexos que en els que intervenen aquestes estructures. Les seqüències estudiades corresponen a les regions promotores dels gens nmyc i SMARCA4. D'una banda, s'ha estudiat l'estabilitat de les estructures formades per aquestes seqüències segons variacions de pH, temperatura, força iònica o presència de lligands en condicions d'estat estacionari. D'altra banda, s'ha avaluat el potencial d'espectroscòpia ultraràpida per a l'estudi de processos cinètics ràpids provocats per la llum. Al llarg de la Tesi, els mètodes de resolució multivariant, ja sigui basats en models flexibles, rígids o híbrids, s'han utilitzat àmpliament per modelitzar els processos d'interès. Els estudis d'estat estacionari han demostrat que l'estabilitat davant el pH o les variacions de temperatura de les tres diferents seqüències riques en citosina esmentades anteriorment depèn molt del nombre de parells de bases de C·C+, però també de la contribució d'altres factors, com ara la composició de la base i la longitud dels bucles. A partir d'estudis ultraràpids, el procés fotoquímic induït per la irradiació de llum UV i l'IR d'escaneig ràpid s'ha relacionat amb la formació de fotoproductes dimèrics en seqüències plegades i desplegades. L'estudi dels processos seguits mitjançant fluorescència resolta en el temps ha demostrat l’existència de més d’una espècie associada amb l’estructura i-motif en el cas de les seqüencies curtes. Finalment, l'aplicació de mètodes de resolució multivariant, basats tant en models rígids o flexibles, han permès extreure informació química valuosa dels processos evolutius de l'ADN. A més, s'ha demostrat que l'adaptació i l'aplicació del modelatge híbrid ha permet calcular les constants cinètiques i detectar transicions dependents de la temperatura.
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Kendrick, Samantha Lynn. "Characterization and Molecular Targeting of the Bcl-2 i-Motif for Modulation of Gene Expression and Induction of Chemosensitivity in Lymphoma". Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/193638.
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The nature of DNA has captivated scientists for more than fifty years. The discovery of the double-helix model of DNA by Watson and Crick in 1953 not only established the primary structure of DNA, but also provided the mechanism behind DNA function. Since then, the demonstration of DNA secondary structure formation has allowed for the proposal that the dynamics of DNA itself can function to modulate transcription. We demonstrate for the first time the i-motif DNA secondary structure formed from an element within the Bcl-2 promoter region has potential to serve as a cellular molecular target for modulation of gene expression. Unlike typical oncogenes, Bcl-2 acts by promoting cellular survival rather than increasing cellular proliferation. The over-expression of Bcl-2, most notably in lymphomas, has been associated with the development of chemoresistance.Transcriptional regulation of Bcl-2 is highly complex and a guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to Bcl-2 promoter activity. We have demonstrated that the C-rich strand is capable of forming an intramolecular i-motif DNA secondary structure with a transition pH of 6.6 and a predominant 8:5:7 loop using mutational studies coupled with circular dichroic spectra and thermal stability analyses. In addition, a novel assay involving the sequential incorporation of a fluorescent thymine analog at each thymine position provided evidence of a capping structure within the top loop region of the i-motif. Two different classes of steroids either stabilize or destabilize the i-motif structure and this differential interaction results in the activation or repression of Bcl-2 expression. The i-motif stabilizing steroid significantly up-regulated Bcl-2 gene and protein expression in BJAB Burkitt's lymphoma cells while the destabilizing steroid down-regulated Bcl-2 expression in B95.8 Burkitt's and Granta-519 mantle cell lymphoma cells, as well as in a SCID mouse lymphoma model. More importantly, the down-regulation of Bcl-2 led to chemosensitization of etoposide-resistant lymphoma cells demonstrating that Bcl-2 i-motif interactive small molecules can act as chemosensitizing agents. Conversely, compounds that up-regulate Bcl-2 by stabilization of the i-motif have potential for use as neuroprotective agents.
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Jonchhe, Sagun. "SINGLE-MOLECULE MECHANOCHEMICAL STUDY OF DNA STRUCTURES INSIDE NANOCONFINEMENT". Kent State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1626344589505522.
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Uribe, Diana Judith. "Defining the Role of Secondary DNA Structures and Transcription Factors on the Transcriptional Control of the HIF-1alpha and VEGF Promoters". Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/145466.
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Angiogenesis is known to be induced and maintained in tumors by the constant expression of the hypoxia inducible factor 1 alpha (HIF-1α) and human vascular endothelial growth factor (VEGF). In fact, tumor recurrence, aggressive metastatic legions and patient mortality rates are known to be positively correlated with overexpression of these two proteins. The HIF-1α and VEGF promoters contain a polypurine/polypyrimidine (pPu/pPy) tract, which are known to play critical roles in their transcriptional regulation, and are structurally dynamic where they can undergo a conformational transition between B-DNA, single stranded DNA and atypical secondary DNA structures such as G-quadruplexes and i-motifs. We hypothesize that the i-motif and G-quadruplex structures can form within the pPu/pPy tracts of the HIF-1α and VEGF proximal promoters, which play important roles in the transcriptional regulation of these genes by acting as scaffolds for alternative transcription factor binding sites. The purpose of this dissertation was to elucidate the transcriptional regulation of the HIF-1α and VEGF genes through the atypical DNA structures that form within the pPu/pPy tracts of their proximal promoters. We investigated the interaction of the C-rich and guanine-rich (G-rich) strands of both of these tracts with transcription factors heterogeneous nuclear ribonucleoprotein (hnRNP) K and nucleolin, respectively, both in vitro and in vivo and their potential role in the transcriptional control of HIF-1α and VEGF. In this dissertation, we demonstrate that both nucleolin and hnRNP K bind selectively to the G- and C-rich sequences, respectively, in the pPu/pPy tract of the HIF-1α and VEGF promoters. Specifically, the small interfering RNA-mediated silencing of either nucleolin or hnRNP K resulted in the down-regulation of basal VEGF gene, and the opposite effect was seen when the transcription factors were overexpressed, suggesting that they act as activators of VEGF transcription. Taken together, the identification of transcription factors that can recognize and bind to atypical DNA structures within pPu/pPy tracts will provide new insight into mechanisms of transcriptional regulation of the HIF-1α and VEGF gene.
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Selvam, Sangeetha. "Molecular Population Dynamics of DNA Tetraplexes using Magneto-Optical Tweezers". Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1516742116760289.
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Brown, Robert Vincent. "The Regulatory Significance and Molecular Targeting of Novel Non-B-DNA Secondary Structures Formed from the PDGFR-Beta Core Promoter Nuclease Hypersensitivity Element". Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/337361.
Pełny tekst źródłaKsiążki na temat "I-motif DNA"
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Notizbücher, MSED. Mein Lauftagebuch : Trainingstagebuch für Läufer und Jogger ♦ Lauflogbuch für über 200 Einträge ♦ 6x9 Format I Motiv: In my dna. Independently Published, 2019.
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Notizbucher, Msed. Mein Lauftagebuch : Trainingstagebuch Für läufer und Jogger ♦ Lauflogbuch Für über 200 Einträge ♦ 6x9 Format I Motiv: Running in My Dna. Independently Published, 2019.
Znajdź pełny tekst źródłaCzęści książek na temat "I-motif DNA"
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Endo, Masayuki, Xiwen Xing i Hiroshi Sugiyama. "Direct Observation of the Formation and Dissociation of Double-Stranded DNA Containing G-Quadruplex/i-Motif Sequences in the DNA Origami Frame Using High-Speed AFM". W Methods in Molecular Biology, 299–308. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9666-7_17.
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Naegeli, Hanspeter. "Molecular Recognition Strategies I: One Enzyme-One Substrate Motifs". W Mechanisms of DNA Damage Recognition in Mammalian Cells, 71–92. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4684-6468-9_4.
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Bhavsar-Jog, Yogini P., Samantha M. Reilly i Randy M. Wadkins. "DNA G-Quadruplexes and I-Motifs in Therapeutics and Diagnostics". W Chemical Biology of Nucleic Acids, 441–58. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-54452-1_24.
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Kowollik, Eva. "The Motif of the Hidden Child in Goran Paskaljević’s Film Kad svane dan and Filip David’s Novel Kuća sećanja i zaborava". W Jewish Literatures and Cultures in Southeastern Europe, 251–64. Wien: Böhlau Verlag, 2021. http://dx.doi.org/10.7767/9783205212904.251.
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Parameswari, Ettiyagounder, Tamilselvan Ilakiya, Veeraswamy Davamani, Periasami Kalaiselvi i Selvaraj Paul Sebastian. "Metallothioneins: Diverse Protein Family to Bind Metallic Ions". W Heavy Metals - Their Environmental Impacts and Mitigation. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97658.
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Metallothionein’s (MTs) are the lower molecular weight (6-7 kDa) proteins that are found to be present in almost all organism types ranging from prokaryotes to eukaryotes species. MT are the metal detecting proteins that can mitigate the effect caused by the excess metal ions. They are also found to be involved in cellular process such as cell growth regulation, ROS (Reactive Oxygen Species) and DNA repair. The protein was termed as Metallothionein due to the unusual higher metal (metallo) and the sulfur (thiol) content. They are further grouped into 3 classes viz., class I, II and III. The Class I and II MTs are polypeptides that were obtained from direct gene products, the class III MTs are from the cysteine-rich non-translational molecules that are termed as phytochelatins. The metal ions are been sequestered through the MTs with Cys rich motifs. All the cysteines are present in the reduced form and are been co-ordinated through the mercaptide bonds. The cysteines present in the MTs are preserved across the species, it is supposed that, cysteines are essential for the function and the MTs are required for the life. Metallothionins structure, conservation in evolution, their ubiquitous nature of occurrence, the genes redundancy and the programmed MTs synthesis in development, regeneration and reproduction of living organisms are some of the weighty arguments in suspecting MTs to also serve others and perhaps the high particular metal-related cellular roles. In this chapter, there is a detailed discussion about Metallothionein its structure, occurrence and function.
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Benavente, Fran, i Glòria Salvadó-Corretger. "Sculpting the Body, Sculpting History". W ReFocus: The Films of Joao Pedro Rodrigues and Joao Rui Guerra da Mata, 15–27. Edinburgh University Press, 2022. http://dx.doi.org/10.3366/edinburgh/9781474460804.003.0002.
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Chapter two focus on the body, which is one of the central themes and motifs in the works of João Pedro Rodrigues. One of his objectives as a filmmaker is to explore the body, thinking about its complex figuration. Indeed, the body in his films can have many forms and shapes (transformed and sculptural or chiselled), it is a plural body, inhabited by the ghost of history, the animal body and the spiritual body. As such, this chapter uses the body, or its traces in its absence, as the common thread to think about cinema. In order to do that this study explores the “lesser” films by Rodrigues like China China (2007); Red Dawn (2011); The Last Time I saw Macao (2011) or Mahjong (2013) looking at issues like spectral bodies and memory or experiences lived in real life.
Streszczenia konferencji na temat "I-motif DNA"
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Petrović, Slobodan. "RETORIKA KAO VEŠTINA LIČNOG PREZENTOVANJA". W 4th International Scientific Conference – EMAN 2020 – Economics and Management: How to Cope With Disrupted Times. Association of Economists and Managers of the Balkans, Belgrade, Serbia, 2020. http://dx.doi.org/10.31410/eman.2020.483.
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Retorika kao veština koja odlikuje intelektualce od nastanka sveta jedino je i oružje i oruđe koje čovek putem izgovorene reči može da koristi kako bi sebe ili odbranio ili prezentovao. Ova drevna veština predstavljala je, a i danas predstavlja vrlinu odabranih, ukras umnih, filozofsku dubinu, misaonu širinu i esenciju izgovorene reči. Pretvoriti misli u jednostavne i širokom auditorijumu umno razumljive reči, svakako je sposobnost veštih govornika, koji kao cilj i motiv imaju isključivo lično prezentovanje i profesionalno profilisanje, kroz niz manipulativnih, retorički spretno izgovorenih, misaono i praktično opravdanih teza koje se teško ili lako opovrgavaju, što determiniše govornika kao dobrog ili lošeg. Suština je da je retorika način ličnog prezentovanja sopstvene ličnosti, kroz koju individua ispoljava sopstveni ili stav lica koje ju je angažovalo, a da pri tom uspe svojim govorom da zaintrigira i uslovno rečeno povede auditorijum. Kroz istoriju civilizacije ova drevna, možda i najstarija veština imala je svoje promotere, to su bili najveći umovi sveta, svetske religijske istorije, filozofske tradicije, kulturološke tekovine, političke borbe, pohlepe velikana i odbrane lagodnosti monarhističkih predstavnika. Sve do današnjih dana ova tehnika izgovorene reči predstavlja izazov koji se vežba, sa kojim se čovek ne mora roditi, ukoliko je dovoljno uporan da savlada sve tajne dobrog javnog nastupa, sposobnost percepcije sebe, cilja, alata i rezultata koji se ostvaruje efektom izgovorene reči.
Raporty organizacyjne na temat "I-motif DNA"
1
Baszler, Timothy, Igor Savitsky, Christopher Davies, Lauren Staska i Varda Shkap. Identification of bovine Neospora caninum cytotoxic T-lymphocyte epitopes for development of peptide-based vaccine. United States Department of Agriculture, marzec 2006. http://dx.doi.org/10.32747/2006.7695592.bard.
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The goal of the one-year feasibility study was to identify specific cytotoxic T-lymphocyte (CTL) epitopes to Neosporacaninum in the natural bovine host in order to make progress toward developing an effective peptide-based vaccine against bovine neosporosis. We tested the hypothesis that: N. caninum SRS2 peptides contain immunogenicCTLepitope clusters cross-presented by multiple bovine MHC-I and MHC-IIhaplotypes. The specific objectives were: (1) Map bovine CTLepitopes of N. caninum NcSRS-2 and identify consensus MHC-I and class-II binding motifs; and (2) Determine if subunit immunization with peptides containing N. caninum-specificCTLepitopes cross-reactive to multiple bovine MHChaplotypes induces a CTL response in cattle with disparate MHChaplotypes. Neosporosis is a major cause of infectious abortion and congenital disease in cattle, persisting in cattle herds via vertical transmission.5 N. caninum abortions are reported in Israel; a serological survey of 52 Israeli dairy herds with reported abortions indicated a 31% infection rate in cows and 16% infection rate in aborted fetuses.9,14 Broad economic loss due to bovine neosporosis is estimated at $35,000,000 per year in California, USA, and $100,000,000 (Australian) per year in Australia and New Zealand.13 Per herd losses in a Canadian herd of 50 cattle are estimated more conservatively at $2,305 (Canadian) annually.4 Up to date practical measures to reduce losses from neosporosis in cattle have not been achieved. There is no chemotherapy available and, although progress has been made toward understanding immunity to Neospora infections, no efficacious vaccine is available to limit outbreaks or prevent abortions. Vaccine development to prevent N. caninum abortion and congenital infection remains a high research priority. To this end, our research group has over the past decade: 1) Identified the importance of T-lymphocyte-mediated immunity, particularly IFN-γ responses, as necessary for immune protection to congenital neosporosis in mice,1,2,10,11 and 2) Identified MHC class II restricted CD4+ CTL in Neosporainfected Holstein cattle,16 and 3) Identified NcSRS2 as a highly conserved surface protein associated with immunity to Neospora infections in mice and cattle.7,8,15 In this BARD-funded 12 month feasibility study, we continued our study of Neospora immunity in cattle and successfully completed T-lymphocyte epitope mapping of NcSRS2 surface protein with peptides and bovine immune cells,15 fulfilling objective 1. We also documented the importance of immune responses NcSRS2 by showing that immunization with native NcSRS2 reduces congenital Neospora transmission in mice,7 and that antibodies to NcSRS2 specifically inhibition invasion of placental trophoblasts.8 Most importantly we showed that T-lymphocyte responses similar to parasite infection, namely induction of activated IFN-γ secreting Tlymphocytes, could be induced by subunit immunization with NcSRS2 peptides containing the Neospora-specificCTLepitopes (Baszler et al, In preparation) fulfilling objective 2. Both DNA and peptide-based subunit approaches were tested. Only lipopeptide-based NcSRS2 subunits, modified with N-terminal linked palmitic acid to enhance Toll-like receptors 2 and 1 (TLR2-TLR1), stimulated robust antigen-specific T-lymphocyte proliferation, IFN-γ secretion, and serum antibody production across different MHC-IIhaplotypes. The discovery of MHC-II cross-reactive T-cellinducing parasite peptides capable of inducing a potentially protective immune response following subunit immunization in cattle is of significant practical importance to vaccine development to bovine neosporosis. In addition, our findings are more widely applicable in future investigations of protective T-cell, subunit-based immunity against other infectious diseases in outbred cattle populations.
2
Palmer, Guy, Varda Shkap, Wendy Brown i Thea Molad. Control of bovine anaplasmosis: cytokine enhancement of vaccine efficacy. United States Department of Agriculture, marzec 2007. http://dx.doi.org/10.32747/2007.7695879.bard.
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Anaplasmosis an arthropod-born disease of cattle caused by the rickettsia Anaplasma marginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently development of a safe, effective vaccine is a high priority. In this collaborative project we focused on two approaches to vaccine development. The first focused o n improving antigen delivery to livestock and specifically examined how DNA vaccines could be improved to enhance priming and expansion of the immune response. This research resulted in development and testing of two novel vaccine delivery systems--one that targeted antigen spread among dendritic cells (the key cell in priming immune responses and a follow-on construct that also specifically targeted antigen to the endosomal-lysosomal compartment the processing organelle within the dendritic cell that directs vaccine antigen to the MHC class ll-CD4* T cell priming pathway). The optimized construct targeting vaccine antigen to the dendritic cell MHC class II pathway was tested for ability to prime A. marginale specific immune responses in outbred cattle. The results demonstrated both statistically significant effects of priming with a single immunization, continued expansion of the primary immune response including development of high affinity lgG antibodies and rapid recall of the memory response following antigen challenge. This portion of the study represented a significant advance in vaccine delivery for livestock. Importantly the impact of these studies is not limited to A. marginale a s the targeting motifs are optimized for cattle and can be adapted to other cattle vaccinations by inserting a relevant pathogen-specific antigen. The second approach (which represented an addition to the project for which approval was requested as part of the first annual report) was a comparative approach between A . marginale and the Israel A . centrale vaccines train. This addition was requested as studies on Major Surface Protein( MSP)- 2 have shown that this antigen is highly antigenically variable and presented solely as a "static vaccine" antigen does not give cross-strain immunity. In contrast A. . centrale is an effective vaccine which Kimron Veterinary institute has used in the field in Israel for over 50 years. Taking advantage of this expertise, a broad comparison of wild type A. marginale and vaccine strain was initiated. These studies revealed three primary findings: i) use of the vaccine is associated with superinfection, but absence of clinical disease upon superinfection with A. marginale; ii) the A. centrale vaccine strain is not only less virulent but transmission in competent in Dermacentor spp. ticks; and iii) some but not all MSPs are conserved in basic orthologous structure but there are significant polymorphisms among the strains. These studies clearly indicated that there are statistically significant differences in biology (virulence and transmission) and provide a clear path for mapping of biology with the genomes. Based on these findings, we initiated complete genome sequencing of the Israel vaccine strain (although not currently funded by BARD) and plant to proceed with a comparative genomics approach using already sequenced wild-type A. marginale. These findings and ongoing collaborative research tie together filed vaccine experience with new genomic data, providing a new approach to vaccine development against a complex pathogen.
3
Altstein, Miriam, i Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, sierpień 2013. http://dx.doi.org/10.32747/2013.7593398.bard.
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The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.