A Comprehensive View of the Epigenetic Landscape Part I: DNA Methylation, Passive and Active DNA Demethylation Pathways and Histone Variants

In multicellular organisms, all the cells are genetically identical but turn genes on or off at the right time to promote differentiation into specific cell types. The regulation of higher-order chromatin structure is essential for genome-wide reprogramming and for tissue-specific patterns of gene expression. The complexity of the genome is regulated by epigenetic mechanisms, which act at the level of DNA, histones, and nucleosomes. Epigenetic machinery is involved in many biological processes, including genomic imprinting, X-chromosome inactivation, heterochromatin formation, and transcriptional regulation, as well as DNA damage repair. In this review, we summarize the recent understanding of DNA methylation, cytosine derivatives, active and passive demethylation pathways as well as histone variants. DNA methylation is one of the well-characterized epigenetic signaling tools. Cytosine methylation of promoter regions usually represses transcription but methylation in the gene body may have a positive correlation with gene expression. The attachment of a methyl group to cytosine residue in the DNA sequence is catalyzed by enzymes of the DNA methyltransferase family. Recent studies have shown that the Ten-Eleven translocation family enzymes are involved in stepwise oxidation of 5-methylcytosine, creating new cytosine derivatives including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. Additionally, histone variants into nucleosomes create another strategy to regulate the structure and function of chromatin. The replacement of canonical histones with specialized histone variants regulates accessibility of DNA, and thus may affect multiple biological processes, such as replication, transcription, DNA repair, and play a role in various disorders such as cancer

A comprehensive view of the epigenetic landscape part I : DNA methylation, passive and active DNA demethylation pathways and histone variants

In multicellular organisms, all the cells are genetically identical but turn genes on or off at the right time to promote differentiation into specific cell types. The regulation of higher-order chromatin structure is essential for genome-wide reprogramming and for tissue-specific patterns of gene expression. The complexity of the genome is regulated by epigenetic mechanisms, which act at the level of DNA, histones, and nucleosomes. Epigenetic machinery is involved in many biological processes, including genomic imprinting, X-chromosome inactivation, heterochromatin formation, and transcriptional regulation, as well as DNA damage repair. In this review, we summarize the recent understanding of DNA methylation, cytosine derivatives, active and passive demethylation pathways as well as histone variants. DNA methylation is one of the well-characterized epigenetic signaling tools. Cytosine methylation of promoter regions usually represses transcription but methylation in the gene body may have a positive correlation with gene expression. The attachment of a methyl group to cytosine residue in the DNA sequence is catalyzed by enzymes of the DNA methyltransferase family. Recent studies have shown that the Ten-Eleven translocation family enzymes are involved in stepwise oxidation of 5-methylcytosine, creating new cytosine derivatives including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. Additionally, histone variants into nucleosomes create another strategy to regulate the structure and function of chromatin. The replacement of canonical histones with specialized histone variants regulates accessibility of DNA, and thus may affect multiple biological processes, such as replication, transcription, DNA repair, and play a role in various disorders such as cancer

Nucleon scalar and tensor charges using lattice QCD simulations at the physical value of the pion mass

We present results on the light, strange and charm nucleon scalar and tensor charges from lattice QCD, using simulations with $N_f=2$ flavors of twisted mass Clover-improved fermions with a physical value of the pion mass. Both connected and disconnected contributions are included, enabling us to extract the isoscalar, strange and charm charges for the first time directly at the physical point. Furthermore, the renormalization is computed non-perturbatively for both isovector and isoscalar quantities. We investigate excited state effects by analyzing several sink-source time separations and by employing a set of methods to probe ground state dominance. Our final results for the scalar charges are $g_S^u = 5.20(42)(15)(12)$, $g_S^d = 4.27(26)(15)(12)$, $g_S^s=0.33(7)(1)(4)$, $g_S^c=0.062(13)(3)(5)$ and for the tensor charges $g_T^u = 0.782(16)(2)(13)$, $g_T^d = -0.219(10)(2)(13)$, $g_T^s=-0.00319(69)(2)(22)$, $g_T^c=-0.00263(269)(2)(37)$ in the $\overline{\rm MS}$ scheme at 2~GeV. The first error is statistical, the second is the systematic error due to the renormalization and the third the systematic arising from possible contamination due to the excited states.Comment: 20 pages and 13 figure

Дифференциально−диагностические нейрофизиологические корреляты эмоционально−личностных и поведенческих расстройств у подростков с мозговой дисфункцией

Представлены результаты исследования функциональной активности головного мозга у подростков с мозговой дисфункцией и эмоциональными, личностными, поведенческими расстройствами. Выявлены нейрофизиологические корреляты изменений характера и поведения больных подростков.The findings of brain functional activity investigation in teenagers with cerebral dysfunction as well as emotional, personality, behavioral disorders are reported. Neurophysiological correlates of the character and behavior changes in teen−agers were revealed

Discrimination of bovine milk from non-dairy milk by lipids fingerprinting using routine matrix-assisted laser desorption ionization mass spectrometry

An important sustainable development goal for any country is to ensure food security by producing a sufficient and safe food supply. This is the case for bovine milk where addition of non-dairy milks such as vegetables (e.g., soya or coconut) has become a common source of adulteration and fraud. Conventionally, gas chromatography techniques are used to detect key lipids (e.g., triacylglycerols) has an effective read-out of assessing milks origins and to detect foreign milks in bovine milks. However, such approach requires several sample preparation steps and a dedicated laboratory environment, precluding a high throughput process. To cope with this need, here, we aimed to develop a novel and simple method without organic solvent extractions for the detection of bovine and non-dairy milks based on lipids fingerprint by routine MALDI-TOF mass spectrometry (MS). The optimized method relies on the simple dilution of milks in water followed by MALDI-TOF MS analyses in the positive linear ion mode and using a matrix consisting of a 9:1 mixture of 2,5-dihydroxybenzoic acid and 2-hydroxy-5-methoxybenzoic acid (super-DHB) solubilized at 10 mg/mL in 70% ethanol. This sensitive, inexpensive, and rapid method has potential for use in food authenticity applications

Isospin-0 ππ\pi\pi s-wave scattering length from twisted mass lattice QCD

We present results for the isospin-0 $\pi\pi$ s-wave scattering length calculated with Osterwalder-Seiler valence quarks on Wilson twisted mass gauge configurations. We use three $N_f = 2$ ensembles with unitary (valence) pion mass at its physical value (250$\sim$MeV), at 240$\sim$MeV (320$\sim$MeV) and at 330$\sim$MeV (400$\sim$MeV), respectively. By using the stochastic Laplacian Heaviside quark smearing method, all quark propagation diagrams contributing to the isospin-0 $\pi\pi$ correlation function are computed with sufficient precision. The chiral extrapolation is performed to obtain the scattering length at the physical pion mass. Our result $M_\pi a^\mathrm{I=0}_0 = 0.198(9)(6)$ agrees reasonably well with various experimental measurements and theoretical predictions. Since we only use one lattice spacing, certain systematics uncertainties, especially those arising from unitary breaking, are not controlled in our result.Comment: 21 pages, 5 figures, 6 table