Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology ...would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. We produce a catalog of super-enhancers in a broad range of human cell types and find that super-enhancers associate with genes that control and define the biology of these cells. Interestingly, disease-associated variation is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes important in tumor pathogenesis. Thus, super-enhancers play key roles in human cell identity in health and in disease.
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•Catalog of super-enhancers in 86 human cell and tissue types•Disease-associated sequence variation is enriched in super-enhancers•Cancer cells generate super-enhancers at key tumor pathogenesis genes•Super-enhancers provide biomarkers for disease diagnosis and therapy
Super-enhancers in 86 human cell types have been cataloged. Disease-associated sequence variation is enriched in super-enhancers, and cancer cells generate super-enhancers at key tumor pathogenesis genes.
Gene expression analysis is a widely used and powerful method for investigating the transcriptional behavior of biological systems, for classifying cell states in disease, and for many other ...purposes. Recent studies indicate that common assumptions currently embedded in experimental and analytical practices can lead to misinterpretation of global gene expression data. We discuss these assumptions and describe solutions that should minimize erroneous interpretation of gene expression data from multiple analysis platforms.
Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on ...chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells.
There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between ...gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not employ this structural protein. Here, we show that the ubiquitously expressed transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements and forms dimers that facilitate the interaction of these DNA elements. Deletion of YY1 binding sites or depletion of YY1 protein disrupts enhancer-promoter looping and gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control.
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•YY1 generally occupies active enhancers and promoters across cell types•YY1 can form dimers and promote DNA interactions•Perturbation of YY1 binding disrupts enhancer-promoter looping and gene expression•YY1’s structural role accounts for diverse functions reported previously
YY1 is a structural regulator of enhancer-promoter interactions and facilitates gene expression.
Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA ...binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs.
According to a survey of the literature, nanofluids are superior to traditional fluids at transferring heat. A detailed analysis of the models mentioned above is crucial since there are large gaps in ...the illumination of current solutions for improving heat transfer in nanomaterials. The ongoing investigation's purpose is to ascertain the tiny size gold particles drift in free with the heat and mass transfer, buoyancy forces, thermophoresis, and Brownian motion of a micropolar nanofluid being transported through a porous medium in an asymmetric channel with a uniform magnetic field using a long-wavelength and low Reynolds number approximation. The resulting dimensionless nonlinear governing equations have been numerically solved using a MATLAB software and the Runge-Kutta-Fehlberg integration scheme. Two comparisons with previously investigated problems are also made to confirm our findings, and an excellent concurrence is discovered. As a result, trustworthy results are being given. Numerical solutions are used to describe the effects of different thermal-fluidic parameters on velocity profiles, temperature, concentration, micropolar rotation, pressure gradient, shear stress, heat flux, and nanoparticle volume flux, etc. Tables, graphs, and bar charts are used to present and discuss numerical results that have been produced. A comparison of the resulting numerical solution to earlier literature also reveals a satisfactory level of agreement. Insight into real-world applications such nanofluidic, energy conservation, friction reduction, and power generation are provided by this work. Furthermore, the Brownian and thermophoresis parameters behave significantly differently in a concentration field. On the other hand, the study puts forward an important note that for peristaltic flow of a micropolar fluid with nanoparticles can be controlled by suitably adjusting the micropolar parameter, thermophoresis parameter, nanoparticle Grashof number, and Brownian motion parameter.
New expected biologically active complexes for some of the first (Mn (II), Ni (II), Cu (II) and Zn (II)) and second (Rh (III) and Cd (II)) transitional metals rows with ...N‐(2‐Aminoethyl)‐1,3‐propanediamine as a ligand (AEPD)have been synthesized. All synthesized complexes were formed with 1:1 (metal: AEPD) stoichiometry except Ni (II) 1:2 (Ni: AEPD). The compounds were characterized by different analysis tools such as; elemental analysis, Fourier transform infrared (FTIR), 1H‐NMR, mass spectra, thermal analysis, electronic spectra, magnetic measurement and molar conductance techniques. AEPD ligand interacted with all metal ions as tridentate ligand by using the nitrogen atoms. On the other hand, density functional theory (DFT) calculations have been performed to confirm the optimized geometrical structures for both AEPD and its complexes. Furthermore, coordination compounds were screened for their potential antibacterial activities against six pathogenic bacteria as well as one kind of fungi in comparison to standard antibiotics by agar well diffusion method. The results show that most of the complexes exhibit antibacterial and antifungal activities against these organisms. Rh (III)‐AEPD complex exhibited the strongest antibacterial effect followed by the Cd (II) complex but as antifungal agents Cd (II) was the first and the second was Rh (III). Also, the anticancer activity was screened for these metal complexes against growth of human liver cancer HEPG2 tumor cell line and this inhibition activity of Cd (II) chelate was noticed to be more active with lowest IC50 than that of all other synthesized complexes. Unfortunately, Mn (II) and Rh (III) chelates lacked anticancer activity. The docking active sites interactions were evaluated using the selected protein for anticancer activity. Finally, antioxidant activity was studied. Mn (AEPD) showed maximum activity followed by complex of Rh (III).
Investigation of antimicrobial antioxidant and antitumor activities for a series of new expected biologically active complexes for some of the first and second transitional metals row. (Mn (II), Ni (II), Cu (II), Zn (II), Rh (III) & Cd (II)) with N‐(2‐Aminoethyl)‐1,3‐Propanediamine as a ligand (AEPD).
Abstract
In magnetic resonance imaging (MRI), this MRI is used for the diagnosis of the brain. The dynamic of these particles occurs under the action of the peristaltic waves generated on the ...flexible walls of the brain. Studying such fluid flow of a Fractional Second-Grade under this action is therefore useful in treating tissues of cancer. This paper deals with a theoretical investigation of the interaction of heat and mass transfer in the peristaltic flow of a magnetic field fractional second-grade fluid through a tube, under the assumption of low Reynolds number and long-wavelength. The analytical solution to a problem is obtained by using Caputo's definition. The effect of different physical parameters, the material constant, magnetic field, and fractional parameter on the temperature, concentration, axial velocity, pressure gradient, pressure rise, friction forces, and coefficient of heat and mass transfer are discussed with particular emphasis. The computed results are presented in graphical form. It is because the nature of heat and mass transfer coefficient is oscillatory which is following the physical expectation due to the oscillatory nature of the tube wall. It is perceived that with an increase in Hartmann number, the velocity decreases. A suitable comparison has been made with the prior results in the literature as a limiting case of the considered problem.
The significance of the study is to determine of transferred heat and mass impact on the magneto-hydrodynamic peristalsis of Jeffery nanofluid through porous media with inclined symmetric channels ...whose walls are induced by peristaltic motion within porous media. The aim of this investagtion is to study the influence of various types of parameters such as Brownian motion, thermophoresis, buoyancy forces, and magnetic fields are studies on concentration, temperature, and axial velocity. The numerical solution has been achieved according to the long-wavelength and low Reynolds number approximation utilizing the MATLAB bvp4c function. The resultant dimensions of nonlinear governing equations were approached numerically through the Runge-Kutta- Fehlberg integration scheme, a MATLAB program. The influence of different factors such as the ratio of relaxation to retardation times, nanoparticle Grashof number, and magnetic field was discussed on concentration, temperature, and velocity profiles. tables and graphs were used to demonstrate the numerically computed numerical results. Plotting graphs were utilized for evaluating the pertinent parameters impacts on the aforementioned quantities based on computational results. According to the findings, the effect of the parameters are significant.
The role of starch aerogel (St‐AG) and carboxymethyl cellulose (CMC) as biolgical active compounds, when they subjected for complexation with metal ions, is assessed in this work. The complexation is ...carried out with palladium(II) and copper(II) ions, in solid state. Different tools of analysis are carried out to characterize and elucidate the structures of these complexes, namely: elemental analysis, IR, thermal analysis, magnetic measurement and molar conductance techniques. All synthesized complexes are formed with 1:2 (metal:ligand) stoichiometry except the case of aerogel starch 1:1 (Pd:starch). All isolated complexes show a satisfactory cytotoxic effect results against colon cancer cell lines HCT11. Additionally, these complexes are screened for their antibacterial activities against two types of Gram positive and negative bacteria. Molecular docking investigation confirmed the cytotoxicity and antibacterial results. Proton–ligands association constants and their complex formation constants with some bivalent metal ions, using potentiometric method show that the complexes formed in solution have a stoichiometry of 1:1 metal:ligand. The effects of metal ion, ionic radius, electronegativity and nature of ligand on the formation constants are discussed. The formation constants of the complexes with 3D transition metals followed the order Mn2+ < Co2+ < Ni2+ < Cu2+ > Zn2+.
This work deals with evaluating the role of complexation of starch aerogel (St‐AG) and carboxymethyl cellulose (CMC) with palladium(II) and copper(II) ions to convert these nutrient‐based carbohydrates to biological active compounds. The antibacterial and antitumor activity testes together with molecular docking and stability of formation metal complexes are studied for confirming the stability and bioactivity of these complexes.
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