A Consistent Systems Mechanics Model of the 3D Architecture and Dynamics of Genomes

Already for thousands of years mankind is aware of inheritance and its manipulation by mating and breeding. The discovery of the cell nucleus by A. van Leeuwenhook in the 17th century marks a start to elucidate the epically discussed evolutionary transfer of information in detail. Now after more than 170 years of research on the 3D architecture and dynamics of genomes and the co-evolved interaction networks of regulatory elements creating genome function - i.e. the storage, replication, and expression of genetic information—a consistent systems statistical mechanics genomics framework emerges for the first time. Obviously the structure and function of genomes co-evolved as an inseparable system allowing the physical storage, expression, and replication of genetic information. The DNA double helix and the nucleosome had been determined structurally at the very highest level already, including genome sequences and epigenetic histone modifications. That chromosomes form territories with functional relevant positioning within the cell nucleus and that chromosomal subdomains exist has been also determined to a fair degree of detail. Only recently, however, we were finally able to fill the much debated gap in-between by establishing that nucleosomes compact into a quasi-fibre folded into stable loops which form stable multi-loop aggregates/rosettes connected by linkers and hence creating chromosome arms and entire chromosomes. Interestingly, this has lead immediately to a consistent and cross-proven systems statistical mechanics genomic framework which is balancing stability/flexibility ensuring genome integrity, enabling expression/regulation of genetic information, as well as genome replication - all this in evolutionary perspectives as the natural outcome of Darwinian natural selection and Lamarkian self-referenced manipulation. Thus, genotype and phenotype are multilisticly entangled and beyond are embedded in genome ecology i(!)n- and environments. This not only opens the door to a true universal sequencing of genetic information, but also is the key for a general understanding of genomes, their function and evolution, as well as for applied diagnostics and treatment of disease, for future genome manipulation and engineering efforts, as far as the creation of artificial or extra-terrestrial live contexts

Studying the Neurobiology of Social Interaction with Transcranial Direct Current Stimulation—The Example of Punishing Unfairness

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects' propensity to punish unfair behavior is reduced significantl

Enhancers and silencers: an integrated and simple model for their function

Regulatory DNA elements such as enhancers, silencers and insulators are embedded in metazoan genomes, and they control gene expression during development. Although they fulfil different roles, they share specific properties. Herein we discuss some examples and a parsimonious model for their function is proposed. All are transcription units that tether their target promoters close to, or distant from, transcriptional hot spots (or 'factories')

Observation of 1D Behavior in Si Nanowires: Toward High-Performance TFETs

This article provides experimental evidence of one-dimensional behavior of silicon (Si) nanowires (NWs) at low-temperature through both transfer (Id−VG) and capaci- tance−voltage characteristics. For the first time, operation of Si NWs in the quantum capacitance limit (QCL) is experimentally demonstrated and quantitatively analyzed. This is of relevance since working in the QCL may allow, e.g., tunneling field-effect transistors (TFETs) to achieve higher on-state currents (Ion) and larger on-/off-state current ratios (Ion/Ioff), thus addressing one of the most severe limitations of TFETs. Comparison of the experimental data with simulations finds excellent agreement using a simple capacitor model

Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells

Background: Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is unclear how domain plasticity modulates genomic accessibility for soluble factors. Results: Here, we combine and compare a high-resolution topology analysis of interacting chromatin loci with fluorescence correlation spectroscopy measurements of domain dynamics in single living cells. We identify topologically and dynamically independent chromatin domains of ~1 Mb in size that are best described by a loop-cluster polymer model. Hydrodynamic relaxation times and gyration radii of domains are larger for open (161 ± 15 ms, 297 ± 9 nm) than for dense chromatin (88 ± 7 ms, 243 ± 6 nm) and increase globally upon chromatin hyperacetylation or ATP depletion. Conclusions: Based on the domain structure and dynamics measurements, we propose a loop-cluster model for chromatin domains. It suggests that the regulation of chromatin accessibility for soluble factors displays a significantly stronger dependence on factor concentration than search processes within a static network

Dynamic behavior of GFP–CLIP-170 reveals fast protein turnover on microtubule plus ends

Microtubule (MT) plus end–tracking proteins (+TIPs) specifically recognize the ends of growing MTs. +TIPs are involved in diverse cellular processes such as cell division, cell migration, and cell polarity. Although +TIP tracking is important for these processes, the mechanisms underlying plus end specificity of mammalian +TIPs are not completely understood. Cytoplasmic linker protein 170 (CLIP-170), the prototype +TIP, was proposed to bind to MT ends with high affinity, possibly by copolymerization with tubulin, and to dissociate seconds later. However, using fluorescence-based approaches, we show that two +TIPs, CLIP-170 and end-binding protein 3 (EB3), turn over rapidly on MT ends. Diffusion of CLIP-170 and EB3 appears to be rate limiting for their binding to MT plus ends. We also report that the ends of growing MTs contain a surplus of sites to which CLIP-170 binds with relatively low affinity. We propose that the observed loss of fluorescent +TIPs at plus ends does not reflect the behavior of single molecules but is a result of overall structural changes of the MT end

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Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin

The effect of trichostatin A (TSA)-induced histone acetylation on the interphase chromatin structure was visualized in vivo with a HeLa cell line stably expressing histone H2A, which was fused to enhanced yellow fluorescent protein. The globally increased histone acetylation caused a reversible decondensation of dense chromatin regions and led to a more homogeneous distribution. These structural changes were quantified by image correlation spectroscopy and by spatially resolved scaling analysis. The image analysis revealed that a chromatin reorganization on a length scale from 200 nm to >1 μm was induced consistent with the opening of condensed chromatin domains containing several Mb of DNA. The observed conformation changes could be assigned to the folding of chromatin during G1 phase by characterizing the effect of TSA on cell cycle progression and developing a protocol that allowed the identification of G1 phase cells on microscope coverslips. An analysis by flow cytometry showed that the addition of TSA led to a significant arrest of cells in S phase and induced apoptosis. The concentration dependence of both processes was studied

МУЗЕЇ ДНІПРОПЕТРОВСЬКОЇ ОБЛАСТІ НА СУЧАСНОМУ ЕТАПІ

Розглянуто діяльність музеїв, участь їх у краєзнавчому русі, кількісні та якісні показники розвитку музейної галузі Дніпропетровської області на сучасному етапіAuthors have examined museum activities, their role in the movement of local lore, quantitative and qualitative indices of museum development in the Dniepropetrovsk region at present stage