Zur Interaktion von Anthracyclinen und Anthracyclinonen mit DNS / Interaction of Anthracyclines and Anthracyclinones with DNA

1970 ◽  
Vol 25 (4) ◽  
pp. 362-367 ◽  
Author(s):  
H. Berg ◽  
K. Eckardt
Keyword(s):  
Binding Constants ◽  
Cooperative Interaction ◽  
Sugar Residue ◽  
Binding Mechanism ◽  
Buffer Solution ◽  
Binding Ability ◽  
Weak Binding ◽  
Order Of Magnitude ◽  
Dna Complex

It was shown by the polarographic data of the complexes between antracycline antibiotics and DNA that in contrast to their biological inactive aglycones and other antracyclinones, a cooperative interaction of the intercalating chromophore as well as the sugar residue of the anthracycline molecules, is generally responsible for the complex formation with DNA.The high complex binding constants of the antracyclines daunomycin, nogalamycin, galirubin A and galirubin B measured in dimethylsulfoxid-buffer solution are in the same order of magnitude as those of actinomycins. On the other hand, only a weak binding ability of the aglycones daunomycinon, ε-pyrromycinon and aklavinon, as well as of other investigated anthracyclinones and model hydroxyanthraquinones, could be observed.No significant influence of the number and positions of the chromophore hydroxyls could be noticed.The results suggest that the first outerphase addition of the sugar residues to the backbone of the helix gives the necessary space of time for the slower intercalation process of the planar chromophore.In the case of denatured DNA, the antibiotic-DNA-complex has a lowered stability.The important role of the sugar residue for the binding mechanism strongly suggests that modifications of the nature and position of the basic sugar residue should be most valuable for the synthesis of new effective anthracyclines.

scholarly journals The Regulator of Nitrate Assimilation in Ascomycetes Is a Dimer Which Binds a Nonrepeated, Asymmetrical Sequence

1998 ◽  
Vol 18 (3) ◽  
pp. 1339-1348 ◽  
Author(s):  
Joseph Strauss ◽  
M. Isabel Muro-Pastor ◽  
Claudio Scazzocchio
Keyword(s):  
Nitrate Assimilation ◽  
Binding Studies ◽  
Binding Ability ◽  
Zinc Cluster ◽  
First Case ◽  
Vitro Binding ◽  
Nitrate Induction ◽  
Dna Complex

ABSTRACT The regulation of nitrate assimilation seems to follow the same pattern in all ascomycetes where this process has been studied. We show here by in vitro binding studies and a number of protection and interference techniques that the transcription factor mediating nitrate induction in Aspergillus nidulans, a protein containing a binuclear zinc cluster DNA binding domain, recognizes an asymmetrical sequence of the form CTCCGHGG. We further show that the protein binds to its consensus site as a dimer. We establish the role of the putative dimerization element by its ability to replace the analogous element of the cI protein of phage λ. Mutagenesis of crucial leucines of the dimerization element affect both the binding ability of the dimer and the conformation of the resulting protein-DNA complex. This is the first case to be described where a dimer recognizes such an asymmetrical nonrepeated sequence, presumably by each monomeric subunit making different contacts with different DNA half-sites.

scholarly journals Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

2021 ◽  
Author(s):  
Chuan Chen ◽  
Wenqiang Liu ◽  
Jiayin Guo ◽  
Yuanyuan Liu ◽  
Xuelian Liu ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Rrna Synthesis ◽  
Binding Ability ◽  
Transcriptome Regulation ◽  
Early Embryos ◽  
Intrinsic Mechanism ◽  
Regulatory Rnas

AbstractN6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the m6A-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of m6A in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.

scholarly journals Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130018 ◽  
Author(s):  
Andrea I. Ramos ◽  
Scott Barolo
Keyword(s):  
Transcription Factor ◽  
Binding Affinity ◽  
Binding Sites ◽  
Target Genes ◽  
Gene Activation ◽  
Transcriptional Response ◽  
Morphogen Gradients ◽  
Weak Binding ◽  
Initial Hypothesis

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

scholarly journals Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 834
Author(s):  
Frederike A. Hartl ◽  
Jatuporn Ngoenkam ◽  
Esmeralda Beck-Garcia ◽  
Liz Cerqueira ◽  
Piyamaporn Wipa ◽  
...  
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cooperative Interaction ◽  
Tcr Signaling ◽  
Binding Motifs ◽  
Adaptive Immune

The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαβ heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling.

scholarly journals Quantitative Support for Borowski’s Theory of Gravitation

2013 ◽  
Vol 17 ◽  
pp. 67-71 ◽  
Author(s):  
Michael A. Persinger
Keyword(s):  
Dark Matter ◽  
Gravitational Constant ◽  
Planetary Motion ◽  
Free Oscillations ◽  
Energy Equivalence ◽  
Order Of Magnitude ◽  
Theory Of Gravitation

The Borowski Theory of Gravitation (BTG) indicates that movements of mass such as planets through space are determined by differential pressures from dark matter. One of the consequences of the final epoch is that there would be no matter but only distance. Quantitative solutions indicate that the tensor to set universal average dark matter pressure equal to G, the gravitational constant, would require that the terminal length would be ~2.2∙1069 m or effectively identical to current estimates of energy equivalence of the universal mass. For the earth’s orbit the force from the dark pressure is the same order of magnitude as the force associated with the product of the planet’s mass and background free oscillations whose origins are still ambiguous. The convergences of solutions suggest that the BTG may reveal alternative interpretations and mechanisms for the role of gravitation in planetary motion.

Brachyspira Species Avidity to Colonic Mucins from Pigs with and without Brachyspira hyodysenteriae Infection is Species-Specific and Varies between Strains

2021 ◽  
Author(s):  
Macarena P. Quintana-Hayashi ◽  
Mattias Erhardsson ◽  
Maxime Mahu ◽  
Vignesh Venkatakrishnan ◽  
Freddy Haesebrouck ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Hierarchical Cluster ◽  
Swine Industry ◽  
Binding Ability ◽  
Orthogonal Projections ◽  
Brachyspira Hyodysenteriae ◽  
Projections To Latent Structures ◽  
Latent Structures ◽  
Species Specific

Brachyspira hyodysenteriae is commonly associated with swine dysentery (SD), a disease that has an economic impact in the swine industry. B. hyodysenteriae infection results in changes to the colonic mucus niche with a massive mucus induction, which substantially increases the amount of B. hyodysenteriae binding sites in the mucus. We have previously determined that a B. hyodysenteriae strain binds to colon mucins in a manner that differs between pigs and mucin types. Here, we investigated if adhesion to mucins is a trait observed across a broad set of B. hyodysenteriae strains and isolates and furthermore at a genus level ( B. innocens, B. pilosicoli, B. murdochii, B. hampsonii and B. intermedia strains). Our results show that binding to mucins appears to be specific to B. hyodysenteriae , and within this species, the binding ability to mucins varies between strains/isolates, increases to mucins from pigs with SD, and is associated to sialic acid epitopes on mucins. Infection with B. hyodysenteriae strain 8dII results in mucin glycosylation changes in the colon including a shift in sialic acid containing structures. Thus, we demonstrate through hierarchical cluster analysis and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) models of the relative abundances of sialic acid-containing glycans, that sialic acid containing structures in the mucin O -glycome are good predictors of B. hyodysenteriae strain 8dII infection in pigs. The results emphasize the role of sialic acids in governing B. hyodysenteriae interactions with its host, which may open perspectives for therapeutic strategies.

Order of magnitude enhancement of inherently selective atomic layer deposition of zirconia on silicon without deposition on copper: The role of precursor

Vacuum ◽  
2021 ◽  
pp. 110686
Author(s):  
Soumya Saha ◽  
Gregory Jursich ◽  
Abhijit H. Phakatkar ◽  
Tolou Shokuhfar ◽  
Christos G. Takoudis
Keyword(s):  
Atomic Layer Deposition ◽  
Atomic Layer ◽  
Layer Deposition ◽  
Order Of Magnitude

scholarly journals Characterizing the Water Storage Capacity and Hydrological Role of Mountain Peatlands in the Arid Andes of North-Central Chile

Water ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1071 ◽  
Author(s):  
Remi Valois ◽  
Nicole Schaffer ◽  
Ronny Figueroa ◽  
Antonio Maldonado ◽  
Eduardo Yáñez ◽  
...  
Keyword(s):  
High Altitude ◽  
Storage Capacity ◽  
Water Storage ◽  
Catchment Scale ◽  
North Central ◽  
Central Chile ◽  
Water Storage Capacity ◽  
Order Of Magnitude ◽  
Local Water

High-altitude peatlands in the Andes, i.e., bofedales, play an essential role in alpine ecosystems, regulating the local water balance and supporting biodiversity. This is particularly true in semiarid Chile, where bofedales develop near the altitudinal and hydrological limits of plant life. The subterranean geometry and stratigraphy of one peatland was characterized in north-central Chile using Electrical Resistivity Tomography (ERT), Ground Penetrating Radar (GPR) and core extraction. Two sounding locations, two transversal and one longitudinal profile allowed a 3D interpretation of the bofedal’s internal structure. A conceptual model of the current bofedal system is proposed. Geophysical results combined with porosity measurements were used to estimate the bofedal water storage capacity. Using hydrological data at the watershed scale, implications regarding the hydrological role of bofedales in the semiarid Andes were then briefly assessed. At the catchment scale, bofedal water storage capacity, evapotranspiration losses and annual streamflow are on the same order of magnitude. High-altitude peatlands are therefore storing a significant amount of water and their impact on basin hydrology should be investigated further.

scholarly journals Role of Groundwater-Borne Geogenic Phosphorus for the Internal P Release in Shallow Lakes

Water ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1783 ◽  
Author(s):  
Catharina S. Nisbeth ◽  
Søren Jessen ◽  
Ole Bennike ◽  
Jacob Kidmose ◽  
Kasper Reitzel
Keyword(s):  
Lake Sediment ◽  
Trophic State ◽  
Driving Factor ◽  
Original Source ◽  
Depth Profiles ◽  
P Release ◽  
Order Of Magnitude ◽  
The One ◽  
Total P

This study explores the under-investigated issue of groundwater-borne geogenic phosphorus (P) as the potential driving factor behind accumulation of P in lake sediment. The annual internally released P load from the sediment of the shallow, hypereutrophic and groundwater-fed lake, Nørresø, Denmark, was quantified based on total P (TP) depth profiles. By comparing this load with previously determined external P loadings entering the lake throughout the year 2016–2017, it was evident that internal P release was the immediate controller of the trophic state of the lake. Nevertheless, by extrapolating back through the Holocene, assuming a groundwater P load corresponding to the one found at present time, the total groundwater P input to the lake was found to be in the same order of magnitude as the total deposit P in the lake sediment. This suggests that groundwater-transported P was the original source of the now internally cycled P. For many lakes, internal P cycling is the immediate controller of their trophic state. Yet, this does not take away the importance of the external and possibly geogenic origin of the P accumulating in lake sediments, and subsequently being released to the water column.

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