Histone variant exchange is a novel epigenetic regulator of cognition. We speculate that H2A.Z, a variant of canonical histone H2A, exerts unique effects on transcription during distinct stages of memory formation, ultimately acting to maintain memory of previous transcriptional states and poise genes for re‐activation. Hippocampus‐dependent memory formation is initiated by transient expression of memory‐related genes, which support the storage of recently acquired memories. Soon after, memories undergo systems consolidation, which transfers memories from the hippocampus to the cortex for (...) long‐term storage, and requires ongoing re‐activation of memory‐related genes. We speculate that learning‐induced H2A.Z eviction from nucleosomes initially contributes to stimulus‐induced transcriptional induction needed for the initial process of memory consolidation. During systems consolidation, we speculate that delayed incorporation of H2A.Z into nucleosomes of memory‐related genes in the cortex is needed to poise genes for rapid re‐activation, thus supporting the long‐term process of memory stabilization.Also watch the Video Abstract. (shrink)

Histone variants are specialized histones which replace their canonical counterparts in specific nucleosomes. Together with histone post‐translational modifications and DNA methylation, they contribute to the epigenome. Histone variants are incorporated at specific locations by the concerted action of histone chaperones and ATP‐dependent chromatin remodelers. Recent studies have shown that the histone chaperone FACT plays key roles in preventing pervasive incorporation of two histone variants: H2A.Z and CenH3/CENP‐A. In addition, Spt6, another histone chaperone, was also shown to be important for (...) appropriate H2A.Z localization. FACT and Spt6 are both associated with elongating RNA polymerase II. Based on these two examples, we propose that the establishment and maintenance of histone variant genomic distributions depend on a transcription‐coupled epigenome editing (or surveillance) function of histone chaperones. (shrink)

In vertebrates, single cell analyses of replication timing patterns brought to light a very well controlled program suggesting a tight regulation on initiation sites. Mapping of replication origins with different methods has revealed discrete preferential sites, enriched in promoters and potential G‐quadruplex motifs, which can aggregate into initiation zones spanning several tens of kilobases (kb). Another characteristic of replication origins is a nucleosome‐free region (NFR). A modified yeast strain containing a humanized origin recognition complex (ORC) fires new origins at NFRs (...) revealing their regulatory role. In cooperation with NFRs, the histone variant H2A.Z facilitates ORC loading through di‐methylation of lysine 20 of histone H4. Recent studies using genome editing methods show that efficient initiation sites associated with transcriptional activity can synergize over several tens of kb by establishing physical contacts and lead to the formation of early domains of DNA replication demonstrating a co‐regulation between replication initiation and transcription. (shrink)

The remodel the structure of chromatin (RSC) nucleosome remodeling complex is a conserved chromatin regulator with roles in chromatin organization, especially over nucleosome depleted regions therefore functioning in gene expression. Recent reports in Saccharomyces cerevisiae have identified specificities in RSC activity toward certain types of nucleosomes. RSC has now been shown to preferentially evict nucleosomes containing the histone variant H2A.Z in vitro. Furthermore, biochemical activities of distinct RSC complexes has been found to differ when their nucleosome substrate is partially (...) unraveled. Mammalian BAF complexes, the homologs of yeast RSC and SWI/SNF complexes, are also linked to nucleosomes with H2A.Z, but this relationship may be complex and extent of conservation remains to be determined. The interplay of remodelers with specific nucleosome substrates and regulation of remodeler outcomes by nucleosome composition are tantalizing questions given the wave of structural data emerging for RSC and other SWI/SNF family remodelers. (shrink)

The haploid male germ cell differentiation program controls essential steps of male gametogenesis and relies partly on a significant number of sex chromosome‐linked genes. These genes need to escape chromosome‐wide transcriptional repression of sex chromosomes, which occurs during meiosis and is largely maintained in post‐meiotic cells. A newly discovered histone lysine modification, crotonylation (Kcr), marks X/Y‐linked genes that are active in post‐meiotic male germ cells. Histone Kcr, by conferring resistance to transcriptional repressors, could be a dominant element in maintaining these (...) genes active in the globally repressive environment of haploid cell sex chromosomes. Furthermore, the same mark was found associated with post‐meiotically activated genes on autosomes. Histone Kcr therefore appears to be an indicator of the male haploid cell gene expression program and a notable element of genome programming in the post‐meiotic phases of spermatogenesis. (shrink)

Alternative non‐B‐DNA conformations formed under physiological conditions by sequences called flipons include left‐handed Z‐DNA, three‐stranded triplexes, and four‐stranded i‐motifs and quadruplexes. These conformations accumulate and release energy to enable the local assembly of cellular machines in a context specific manner. In these transactions, nucleosomes store power, serving like rechargeable batteries, while flipons smooth energy flows from source to sink by acting as capacitors or resistors. Here, I review the known biological roles for flipons. I present recent and unequivocal findings showing (...) how innate immune responses are regulated by Z‐flipons that identify endogenous RNAs as self. Evidence is also presented supporting important roles for other flipon classes. In these examples, the dynamic exchange of energy between flipons and nucleosomes enables rapid switching of genetic programs without altering flipon sequence. The increased phenotypic diversity enabled by flipons drives their natural selection, with adaptations evolving faster than is possible by codon mutation alone. (shrink)

Our main result is that the following cardinal arithmetic assumption, which is a slight weakening of GCH, “2κ is a finite successor of κ for every cardinal κ”, implies that in any countably tight compactum X there is a discrete subspace D with . This yields a confirmation of Alan Dow’s Conjecture 2 from [A. Dow, Closures of discrete sets in compact spaces, Studia Math. Sci. Hung. 42 227–234].

This study analyses the problem of change. The problem of change can be defined from the point of view of Parmenides who thought there is no change at all. This study explains how change can be viewed as narrative. If we accept that change is narrative, such approach will enable us to look at the central problem in metaphysics, the problem of change, from a fresh perspective and apply Bakhtinian concepts of ‘carnival’, ‘grotesque’, ‘dialogic relationship’, and ‘unfinalizability’ to change. The (...) discussions on change usually have been revolving around the observed system. Bakhtinian perception shows another theoretical orientation by highlighting the role of the observer who decides what the change is. Regarding the question of change for a specific object, a few questions are significant: For whom is the change happening? What is changing? When is the change happening? Where is the change happening? (shrink)

Speeches and persuasion dominate Plato’s Crito. This paper, paying particular attention to the final passage in the dialogue, shows that the focus on speeches, persuasion and allusions to many other elements of rhetoric is an integral part of Plato’s severe criticism of democracy, one of the main points of the Crito. Speeches allow members of a democracy – represented in our dialogue by Crito – firstly to break the law for self-interested reasons while considering themselves still to be law-abiding citizens, (...) and secondly to feel that they are in a tolerant society preferring logos/persuasive speech above bia/compulsion. Socrates counters Crito’s speeches with speeches of his own, not only to defeat him at his own game, but also to make him aware how dangerous the game is. Real knowledge is preferable to speeches, but a democracy without speeches and rhetoric is doomed. (shrink)

This chapter contains section titled: Organizing the Notes for On Certainty Groundlessness and Language‐games Searching for Primary Links Between Language and Reality Seeing Logic and Practice Pictures, Propositions and Reality Forms of Life Practices and Parallels Is the Title on Certainty a Happy One? Is on Certainty a Polemic against Moore? Is Wittgenstein's Main Interest in Moore's Propositions the Nature of Nonsense? Does Wittgenstein Say that the Propositions he is Interested in Form a Class, and Does he Say the Same (...) of all of Them? Are Wittgenstein's Propositions Context‐free? What is the Connection between Wittgenstein's Propositions and Logic? Is Wittgenstein Appealing to Primitive, Pre‐linguistic Reactions as the Basis of our Language‐games? What is Meant by the Sureness in Our Language‐games? How are Our Conclusions Related to the Notions of a Form of Life or World‐picture? How do Wittgenstein's Conclusions Differ from Some Classical and Contemporary Views of Our Relation to the World? Rhees's Development of Wittgenstein's Concerns. (shrink)

With age might come a decline in crucial driving skills. The effect of a collision warning system on older drivers' head movements behavior at intersections was examined.Methods: Twenty-six old-adults, between 55 and 64 years of age, and 16 Older drivers between 65 and 83 years of age, participated in the study. A CWS and a front-back in-vehicle camera were installed in each of the participants' own vehicles for 6 months. The CWS was utilized to identify unsafe events during naturalistic driving (...) situations, and the IVC was used to capture head direction at intersections. The experimental design was conducted in three phases, 2 months each. Unsafe events were recorded by the CWS during all phases of the study. In the second phase, the CWS feedback was activated to examine its effect on drivers' head movement' behavior at intersections.Results: Older drivers drove significantly more hours in total during the intervention phase than the baseline phase and the carryover phase. The study revealed no significant differences between the head movements of older and old-adult drivers at intersections. For intersection on the left direction, a significant improvement in drivers' head movements' behavior was found at T-junctions, turns and four-way intersections from phase 1 to phase 3, however, two intersection types presented a decrease along the study phases. The head movements' behavior at roundabouts and merges was better at phase 1 compared to phase 3. There was no significant reduction of the mean number of CWS unsafe events across the study phases.Conclusions: The immediate feedback provided by the CWS was effective in terms of participants' head movements at certain intersections but was harmful in others. However, older drivers drove many more hours during the active feedback phase, implying that they trusted the system. Therefore, in the light of this complex picture, using the technological feedback with older drivers should be followed with an additional mediation or follow-up to ensure safety. (shrink)

In this paper some results of a study among psychiatric patients in a large mental hospital in the Netherlands are presented. We focus on the following issues: - the religious and spiritual beliefs and activities of the inpatients; - both the positive and the negative influence of their religion and their religious coping on their mental problems as well as on their existential well-being. The results are discussed briefly within the theoretical notions of religious coping, adressing the positive influence especially (...) of religious beliefs, relying on God and religious social support in psychological and existential times of crisis. (shrink)

Microbial genome sequencing has entered a new phase, where DNA sequence information is gathered from entire microbial communities (metagenomics or environmental genomics) rather than from individual microorganisms. By providing access to the genetic material of vast numbers of organisms, most of which are organisms that have never been isolated or cultivated, a new level of insight is being gained into the diversity and extent of the microbial processes that are presently occuring in environmental communities. By extending metagenomic‐based approaches to the (...) study of very complex and methodologically recalcitrant soil environments, a recent study has found that ammonia‐oxidizing archaea are more abundant in many soils than bacteria.1 These findings not only highlight the undoubtedly critical yet unknown roles that archaea play in global nutrient cycles but illustrate the importance of genomic studies for informing us about the functional capacity of life on Earth. BioEssays 29: 11–14, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

There is a well-known remark in Wittgenstein's Philosophical Investigations which even some philosophers sympathetic to his work have found very hard to accept. It reads:Philosophy may in no way interfere with the actual use of language;it can in the end only describe it.For it cannot give it any foundation either.It leaves everything as it is. Surely, it is said, that is carrying matters too far. Wittgenstein's hyperbole should be excused as a harmless stylistic flourish.