We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long‐range transcriptional regulation. Several observations suggest that (...) TADs can indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied. (shrink)

Recent investigations have revealed 1) that the isochores of the human genome group into two super‐families characterized by two different long‐range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC‐poor, gene‐poor isochores are low‐heterogeneity sequences with oligo‐A spikes that mold the lamina‐associated domains (LADs), whereas GC‐rich, gene‐rich isochores are characterized by single or multiple GC peaks that mold the topologically associating (...) domains (TADs). The formation of these “primary TADs” may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the “gene spaces”/“spatial compartments”) resolves the longstanding problems of “non‐coding DNA,” “junk DNA,” and “selfish DNA” leading to a new vision of the genome as shaped by DNA sequences. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number (...) of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

The spatial organization of genomes is becoming increasingly understood. In mammals, where it is most investigated, this organization ties in with transcription, so an important research objective is to understand whether gene activity is a cause or a consequence of genome folding in space. In this regard, the phenomena of X‐chromosome inactivation and reactivation open a unique window of investigation because of the singularities of the inactive X chromosome. Here we focus on the cause–consequence nexus between genome conformation and (...) transcription and explain how recent results about the structural changes associated with inactivation and reactivation of the X chromosome shed light on this problem. (shrink)

Chromosomes are not randomly packed and positioned into the nucleus but folded in higher‐order chromatin structures with defined functions. However, the genome of a fertilized embryo undergoes a dramatic epigenetic reprogramming characterized by extensive chromatin relaxation and the lack of a defined three‐dimensional structure. This reprogramming is followed by a slow genome refolding that gradually strengthens the chromatin architecture during preimplantation development. Interestingly, genome refolding during early development coincides with a progressive loss of developmental potential suggesting a (...) link between chromatin organization and cell plasticity. In agreement, loss of chromatin architecture upon depletion of the insulator transcription factor CTCF in embryonic stem cells led to the upregulation of the transcriptional program found in totipotent cells of the embryo, those with the highest developmental potential. This essay will discuss the impact of genome folding in controlling the expression of transcriptional programs involved in early development and their plastic‐associated features. (shrink)

Local differences in chromatin organisation may profoundly affect the activity of eukaryotic genomes. Regulation at the level of DNA packaging requires the targeting of structural proteins and histone‐modifying enzymes to specific sites and their stable or dynamic interaction with the nucleosomal fiber. The “chromodomain”, a domain shared by many regulators of chromatin structure, has long been suspected to serve as a module mediating chromatin interactions in a variety of different protein contexts. However, recent functional analyses of a (...) number of different chromodomains revealed an unexpected diversity of interaction targets, including histones, DNA and even RNA. The chromodomains of today seem to have evolved from a common ancestral fold to fulfill various functions in different molecular contexts. Combining information gained from recent functional and structural studies of chromodomains with a bioinformatic classification of their structure could lead to the definition of sequence motifs with predictive quality for chromodomain function. BioEssays 26:133–140, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The various models of chromatin fiber folding that have been proposed over the years are considered and evaluated. It is concluded that the radial loop / scaffold model is strongly supported by the available evidence, although the term ‘scaffold’ may be an unfortunate one. The scaffold is not a solid rod running the length of the chromatid but rather appears to be an aggregation of discrete anchoring complexes for the loops of the fiber. Despite support for this model, (...) there is a need for more evidence to resolve the questions that remain. (shrink)

Topologically associating domain (TAD) boundaries are the flanking edges of TADs, also known as insulated neighborhoods, within the 3D structure of genomes. A prominent feature of TAD boundaries in mammalian genomes is the enrichment of clustered CTCF sites often with mixed orientations, which can either block or facilitate enhancer–promoter (E‐P) interactions within or across distinct TADs, respectively. We will discuss recent progress in the understanding of fundamental organizing principles of the clustered CTCF insulator codes at TAD boundaries. Specifically, both inward‐ (...) and outward‐oriented CTCF sites function as topological chromatin insulators by asymmetrically blocking improper TAD‐boundary‐crossing cohesin loop extrusion. In addition, boundary stacking and enhancer clustering facilitate long‐distance E‐P interactions across multiple TADs. Finally, we provide a unified mechanism for RNA‐mediated TAD boundary function via R‐loop formation for both insulation and facilitation. This mechanism of TAD boundary formation and insulation has interesting implications not only on how the 3D genome folds in the Euclidean nuclear space but also on how the specificity of E‐P interactions is developmentally regulated. (shrink)

In this article we criticize the way in which the concept of information is used in the biological sciences. First, we start by giving a revised and larger definition of genetic information, by underlining the fact that the linear sequence map of the human genome is an incomplete description of our genetic information. This is because information on genome function and gene regulation is also encoded in the way DNA molecule is folded up with proteins to form chromatin structures. (...) Secondly, we point forward the need of constructing a theory in which the informational language (code, program, computation) so characteristic of molecular biology be completed by (and somehow translated into) the language of dynamical systems (phase space, bifurcations, trajectories) and the language of topology (deformations, plasticity, forms). Our traditional modes of system representation, involving fixed sets of sequential states together with imposed mechanical laws, strictly pertain to an extremely limited class of systems that can be called simple (static) systems or mechanisms. Biological systems are not in this class, and they must be called complex or dynamic. Complex systems can only be in some sense approximated, locally and temporally, by simple ones. Such a fundamental change of viewpoint leads to a number of theoretical and experimental consequences. (shrink)

This paper is about non-fictional objects in fictions and their role as narrators. Two central claims are advanced. In part 1 it is argued that non-fictional objects such as you and me can be part of fictions. This commonsensical idea is elaborated and defended against objections. Building on it, it is argued in part 2 that non-fictional objects can be characters and narrators in fictional narratives. As a consequence, three fundamental and popular claims concerning narrators are rejected. In particular, it (...) is shown that some fictional narratives have non-fictional internal narrators, some have no internal fictional narrator, and, most controversially, that the author of a fictional narrative can be identical to its internal narrator. (shrink)

Researchers working on children's moral understanding maintain that the child's capacity to distinguish morality from convention shows that children regard moral violations as objectively wrong. Education in the moral domain. Cambridge: Cambridge University Press). However, one traditional way to cast the issue of objectivism is to focus not on conventionality, but on whether moral properties depend on our responses, as with properties like icky and fun. This paper argues that the moral/conventional task is inadequate for assessing whether children regard moral (...) properties as response-dependent. Unfortunately, children's understanding of response-dependent properties has been neglected in recent research. Two experiments are reported showing that children are more likely to treat properties like fun and icky as response-dependent than moral properties like good and bad. Hence, this helps support the claim that children are moral objectivists. (shrink)

In this paper I examine the relationship between interpreting a fiction and specifying its content. The former plays a major role in literary studies; the latter is of central concern in the philosophical debate on truth in fiction. After elucidating these activities, I argue that they do not coincide but have interesting interdependencies. In particular, I argue that correct interpretations are metaphysically grounded in fictional content. I discuss this claim in detail and show why it is not in tension with (...) the evidential claim that correct interpretations give us epistemic access to fictional content, which I also endorse. (shrink)

We offer an original argument for the existence of universal fictions—that is, fictions within which every possible proposition is true. Specifically, we detail a trio of such fictions, along with an easy-to-follow recipe for generating more. After exploring several consequences and dismissing some objections, we conclude that fiction, unlike reality, is unlimited when it comes to truth.

Recently, Xhignesse has argued that the principle of poetic licence, which roughly states that any class of propositions is true in some possible fiction, ought to be rejected. Here, we defend PPL from Xhignesse’s objection by demonstrating that, properly understood, his purported counter-example case is either irrelevant or unproblematic. The upshot is that Xhignesse has given us no reason to reject PPL.

The aim of this study was to initiate the exploration of debiasing methods applicable in real-life settings for achieving lasting improvement in decision making competence regarding multiple decision biases. Here, we tested the potentials of the analogical encoding method for decision debiasing. The advantage of this method is that it can foster the transfer from learning abstract principles to improving behavioral performance. For the purpose of the study, we devised an analogical debiasing technique for 10 biases (covariation detection, insensitivity to (...) sample size, base rate neglect, regression to the mean, outcome bias, sunk cost fallacy, framing effect, anchoring bias, overconfidence bias, planning fallacy) and assessed the susceptibility of the participants ( N = 154) to these biases before and 4 weeks after the training. We also compared the effect of the analogical training to the effect of ‘awareness training’ and a ‘no-training’ control group. Results suggested improved performance of the analogical training group only on tasks where the violations of statistical principles are measured. The interpretation of these findings require further investigation, yet it is possible that analogical training may be the most effective in the case of learning abstract concepts, such as statistical principles, which are otherwise difficult to master. The study encourages a systematic research of debiasing trainings and the development of intervention assessment methods to measure the endurance of behavior change in decision debiasing. (shrink)

Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans. Chromatin (...) domains are extended genomic regions defined by the continuous enrichment of a given histone modification. Here, we review recent work highlighting the presence of chromatin domains in multiple species, their structural aspects in the context of chromatin architecture, and their potential role on the regulation of genome activity. (shrink)

The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC‐binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in Drosophila (...) appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered. (shrink)

In this essay, I propose that DNA‐binding anti‐cancer drugs work more via chromatin disruption than DNA damage. Success of long‐awaited drugs targeting cancer‐specific drivers is limited by the heterogeneity of tumors. Therefore, chemotherapy acting via universal targets (e.g., DNA) is still the mainstream treatment for cancer. Nevertheless, the problem with targeting DNA is insufficient efficacy due to high toxicity. I propose that this problem stems from the presumption that DNA damage is critical for the anti‐cancer activity of these drugs. (...) DNA in cells exists as chromatin, and many DNA‐targeting drugs alter chromatin structure by destabilizing nucleosomes and inducing histone eviction from chromatin. This effect has been largely ignored because DNA damage is seen as the major reason for anti‐cancer activity. I discuss how DNA‐binding molecules destabilize chromatin, why this effect is more toxic to tumoral than normal cells, and why cells die as a result of chromatin destabilization. (shrink)

Disruptions in chromatin regulator genes are frequently the cause of neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are widely expressed in the brain, yet symptoms suggest that specific circuits can be preferentially altered when they are mutated. Using Drosophila allows targeted manipulation of chromatin regulators in defined neuronal classes, lineages, or circuits, revealing their roles in neuronal precursor self‐renewal, dendrite and axon targeting, neuron diversification, and the tuning of developmental signaling pathways. Phenotypes arising from chromatin regulator disruption (...) are context dependent – defined by interaction networks between the regulators, transcription factors, and chromatin remodeling complex partners. Future challenges are to determine the complexity of partner interactions, and to ascertain the degree to which cognitive deficits are due to loss of chromatin regulator activity in building a circuit or in maintaining homeostasis and activity within it. (shrink)

The process of chromatin diminution in Parascaris and Ascaris is a developmentally controlled genome rearrangement, which results in quantitative and qualitative differences in DNA content between germ line and somatic cells. Chromatin diminution involves chromosomal breakage, new telomere formation and DNA degradation. The programmed elimination of chromatin in presomatic cells might serve as an alternative way of gene regulation. We put forward a new hypothesis of how an ancient partial genome duplication and chromatin diminution may have (...) served to maintain the genetic balance in somatic cells and simultaneously endowed the germ line cells with a selective advantage. (shrink)

Eukaryotic genomes are packaged into a nucleoprotein complex known as chromatin. The term was introduced in 1879 by German cytologist Walther Flemming. While observing the processes of mitosis in a light microscope, Flemming coined the term to describe the easily stainable threads in the nucleus. He predicted that it would not have a long life: “The word chromatin may serve until its chemical nature is known, and meanwhile stands for that substance in the cell nucleus which is readily (...) stained”. However, Flemming’s prediction did not come true. Although the chemical nature of chromatin—a complex of nucleic acid and proteins—was already elucidated at the end of the 19th century, the.. (shrink)

Eukaryotic genome DNA is wrapped around core histones and forms a nucleosome structure. Together with associated proteins and RNAs, these nucleosomes are organized three‐dimensionally in the cell as chromatin. Emerging evidence demonstrates that chromatin consists of rather irregular and variable nucleosome arrangements without the regular fiber structure and that its dynamic behavior plays a critical role in regulating various genome functions. Single‐nucleosome imaging is a promising method to investigate chromatin behavior in living cells. It reveals local (...) class='Hi'>chromatin motion, which reflects chromatin organization not observed in chemically fixed cells. The motion data is like a gold mine. Data analyses from many aspects bring us more and more information that contributes to better understanding of genome functions. In this review article, we describe imaging of single‐nucleosomes and their tracked behavior through oblique illumination microscopy. We also discuss applications of this technique, especially in elucidating nucleolar organization in living cells. (shrink)

The eukaryotic genome is packaged into a periodic nucleoprotein structure termed chromatin. The repeating unit of chromatin, the nucleosome, consists of DNA that is wound nearly two times around an octamer of histone proteins. To facilitate DNA‐directed processes in chromatin, it is often necessary to rearrange or to mobilize the nucleosomes. This remodeling of the nucleosomes is achieved by the action of chromatin‐remodeling complexes, which are a family of ATP‐dependent molecular machines. Chromatin‐remodeling factors share a (...) related ATPase subunit and participate in transcriptional regulation, DNA repair, homologous recombination and chromatin assembly. In this review, we provide an overview of chromatin‐remodeling enzymes and discuss two possible mechanisms by which these factors might act to reorganize nucleosome structure. BioEssays 25:1192–1200, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

It is only recently, with the increasing interest in origami and folding in natural sciences and the humanities, that the fold as a new conception in a whole range of disciplines has begun to be conceived in a broader way. Folding as a material and structural process offers a new methodology to think about the close relationship of matter, form and code. It henceforth crosses out old dichotomies, such as the organic and the inorganic or nature and technology, (...) and blurs the boundaries between experimental, conceptual and historical approaches. This anthology aims to unfold this new interdisciplinary field and its disciplinary impact, ranging from materials science, biology, architecture, and mathematics to literature and philosophy. (shrink)

Activation of gene transcription in vivo is accompanied by an alteration of chromatin structure. The specific binding of transcriptional activators disrupts nucleosomal arrays, suggesting that the primary steps leading to transcriptional initiation involve interactions between activators and chromatin. The affinity of transcription factors for nucleosomal DNA is determined by the location of recognition sequences within nucleosomes, and by the cooperative interactions of multiple proteins targeting binding sites contained within the same nucleosomes. In addition, two distinct types of enzymatic (...) complexes facilitate binding of transcription factors to nucleosomal DNA. These include type A histone acetyltransferases (e.g. GCN5/ADA transcriptional adaptor complex) and ATP‐driven molecular machines that disrupt histone‐DNA interactions (e.g. SWI/SNF and NURF complexes). These observations raise the important question of what happens to the histones during chromatin remodeling. We discuss evidence supporting the retention of histones at transcription factorbound sequences as well as two alternative pathways of histone loss from gene control elements upon transcription factor binding: histone octamer sliding and histone dissociation. (shrink)

It is increasingly clear that chromatin is not just a device for packing DNA within the nucleus but also a dynamic material that changes as cellular environments alter. The precise control of chromatin modification in response to developmental and environmental cues determines the correct spatial and temporal expression of genes. Here, we review exciting discoveries that reveal chromatin participation in many facets of plant development. These include: chromatin modification from embryonic and meristematic development to flowering and (...) seed formation, the involvement of DNA methylation and chromatin in controlling invasive DNA and in maintenance of epigenetic states, and the function of chromatin modifying and remodeling complexes such as SWI/SNF and histone acetylases and deacetylases in gene control. Given the role chromatin structure plays in every facet of plant development, chromatin research will undoubtedly be integral in both basic and applied plant biology. BioEssays 24:234–243, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10055. (shrink)

The assembly of nucleosomes and higher‐order chromatin structures has been extensively studied in vitro. Provided that non‐specific charge interactions are controlled, all the information for correct assembly is found to be inherent in the macromolecular components. Cellular extracts which can assemble chromatin in vitro with nucleosomes correctly spaced on the DNA have been studied in detail and also used to investigate the role of chromatin structure in transcription. However, the mechanisms of chromatin assembly in vivo are (...) still controversial. (shrink)

We present a molecular model of eukaryotic gene transcription. For the β‐globin locus, we hypothesise that a transcription machine composed of multiple RNA polymerase II (PolII) assembles using the locus control region as a foundation. Transcription and locus remodelling can be achieved by pulling DNA through this multi‐PolII ‘reading head’. Once a transcription complex is formed, it may engage an active gene in several rounds of transcription. Observed intergenic sense and antisense transcripts may be the result of PolII pulling the (...) DNA through the reading head whilst searching for the promoter of a gene. Support for this hypothesis is provided using various data from the literature. In the model, DNA is packed in a 30‐nm chromatin fibre, thus gene regulatory regions separated by kilobases are close in space. This, and the need to store transcription‐induced supercoiling, may explain why functionally interacting regions are often separated by many kilobases. (shrink)

One facet of the control of gene expression is long‐range promoter regulation by distant enhancers. It is an important component of the regulation of genes that control metazoan development and has been appreciated for some time but the molecular mechanisms underlying this regulation have remained poorly understood. A recent study by Cleard and colleagues1 reports the first in vivo evidence of chromatin looping and boundary element promoter interaction. Specifically, they studied the function of a boundary element within the cis‐regulatory (...) region of the Abdominal‐B (Abd‐B) gene of Drosophila melanogaster. BioEssays 29: 7–10, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Graphical AbstractThe loosening of chromatin structures gives rise to unrestricted access to DNA and thus transcription factors (TFs) can bind to their otherwise masked target sequences. Regions bound by the same set of TFs tend to be located in close proximity and this might increase the probability of activating illegitimate genomic rearrangements.

The process by which the genetically identical cell lineages of a multicellular organism acquire the propensity to express distinct arrays of gene products is among the most significant and fascinating questions in modern biology. Not surprisingly, this complex process requires control at several levels, each level providing a condition that is necessary but not sufficient for transcription to occur. Evidence suggests that one level of control concerns a region of DNA much larger than the transcription unit itself – the (...) class='Hi'>chromatin domain. This domain must be in a specific chromatin conformation in order to permit transcription; other control mechanisms may be required to bring about overt transcription. A hypothesis concerning the nature of chromatin domains and the relationship between early replication and transcription potential is presented. (shrink)

Between the affirmative and the negative, the compositional and the oppositional, we need to rethink the difference between difference and contradiction. In this regard, the concept of ‘diplomacy’, as developed by Isabelle Stengers, is of particular significance. Whereas many adherents of an affirmative ontology of difference reduce contradiction to a caveat – ‘of course, antagonism is inevitable, but …’ – diplomacy makes contradiction its fundamental concern. This article explicates the significance of such a conception, via close readings of Stengers’ work (...) in relation to that of Gilles Deleuze, and Gottfried Wilhelm Leibniz. However, it also develops diplomacy in new directions, particularly relating the diplomatic ‘fold’ to the sovereign ‘cut’. The fold of coexistence, then, is achieved through diplomacy as a ‘labour of difference’, against ‘facile pluralism’, which takes worldly cohabitation as given. A diplomatic political ontology is neither bellicose nor pacific; rather, it dramatizes the possibility of peace from within a coercive historical reality. (shrink)

Specificities associated with chromosomal linearity are not restricted to telomeres. Here, recent results obtained on fission and budding yeast are summarized and an attempt is made to define subtelomeres using chromatin features extending beyond the heterochromatin emanating from telomeres. Subtelomeres, the chromosome domains adjacent to telomeres, differ from the rest of the genome by their gene content, rapid evolution, and chromatin features that together contribute to organism adaptation. However, current definitions of subtelomeres are generally based on synteny and (...) are largely gene‐centered. Taking into consideration both the peculiar gene content and dynamics as well as the chromatin properties of those domains, it is discussed how chromatin features can contribute to subtelomeric properties and functions, and play a pivotal role in the emergence of subtelomeres. (shrink)

Eukaryotic genomes are packaged into nucleosomal chromatin, and genomic activity requires the precise localization of transcription factors, histone modifications and nucleosomes. Classic work described the progressive reassembly and maturation of bulk chromatin behind replication forks. More recent proteomics has detailed the molecular machines that accompany the replicative polymerase to promote rapid histone deposition onto the newly replicated DNA. However, localized chromatin features are transiently obliterated by DNA replication every S phase of the cell cycle. Genomic strategies now (...) observe the rebuilding of locus‐specific chromatin features, and reveal surprising delays in transcription factor binding behind replication forks. This implies that transient chromatin disorganization during replication is a central juncture for targeted transcription factor binding within genomes. We propose that transient occlusion of regulatory elements by disorganized nucleosomes during chromatin maturation enforces specificity of factor binding. (shrink)

Given their commitment to practices, science studies have bestowed considerable attention upon objects. We have the boundary object, the standardized package, the network object, the immutable mobile, the fluid object, even a fire object has entered the scene. However, these objects do not provide us with a way of understanding their historicity. They are timeless, motionless pictures rather than things that change over time, and while enacting ‘historical moments’ they do not make visible the histories they contain within them. What (...) kind of object could embody history and make that history visible? Inspired by Michel Serres, I suggest the folded object is a way to attend to the temporality and spatiality of objects. In this article I explore this new object by unravelling the history of a DNA reference sequence. I show how, ever since it was produced in the early 1980s, attempts have been made to filter race out of the sequence. That effort has failed due to what one could call ‘political noise’. Making and remaking the sequence have left traces that cannot be erased. (shrink)

Just as the faithful replication of DNA is an essential process for the cell, chromatin structures of active and inactive genes have to be copied accurately. Under certain circumstances, however, the activity pattern has to be changed in specific ways. Although analysis of specific aspects of these complex processes, by means of model systems, has led to their further elucidation, the mechanisms of chromatin replication in vivo are still controversial and far from being understood completely. Progress has been (...) achieved in understanding: 1. The initiation of chromatin replication, indicating that a nucleosome‐free origin is necessary for the initiation of replication; 2. The segregation of the parental nucleosomes, where convincing data support the model of random distribution of the parental nucleosomes to the daughter strands; and 3. The assembly of histones on the newly synthesized strands, where growing evidence is emerging for a two‐step mechanism of nucleosome assembly, starting with the deposition of H3/H4 tetramers onto the DNA, followed by H2A/H2B dimers. (shrink)

It has long been assumed that the architectural proteins of chromatin (the histones, for example) are unrelated to their functional proteins (transcription factors, polymerases, etc). New studies(1,2)drastically change this perspective. It appears that a portion of the general transcription initiation complex TFIID is made up of proteins that not only carry marked sequence and structural resemblances to the core histones of the nucleosome, but also form an octameric complex similar to the histone octamer. This can now be seen as (...) part of a general pattern of continuity among structural and functional chromatin proteins. (shrink)

Historians have often described embryology and concepts of development in the period around 1800 in terms of “temporalization” or “dynamization”. This paper, in contrast, argues that a central epistemological category in the period was “rhythm”, which played a major role in the establishment of the emerging discipline of biology. I show that Caspar Friedrich Wolff’s epigenetic theory of development was based on a rhythmical notion, namely the hypothesis that organic development occurs as a series of ordered rhythmical repetitions and variations. (...) Presenting Christian Heinrich Pander’s and Karl Ernst von Baer’s theory of germ layers, I argue that Pander and Baer regarded folding as an organizing principle of ontogenesis, and that the principle’s explanatory power stems from their understanding of folding as a rhythmical figuration. In a brief discussion of the notion of rhythm in contemporary music theory, I identify an underlying physiological epistemology in the new musical concept of rhythm around 1800. The paper closes with a more general discussion of the relationship between the rhythmic episteme, conceptions of life, and aesthetic theory at the end of the eighteenth century. (shrink)

This paper discusses an exercise that Alida Liberman facilitated among participants at a Teaching and Learning workshop sponsored by the American Association of Philosophy Teachers (AAPT) aimed at helping instructors become more learner-centered in their pedagogy. The exercise was designed to place participants in the role of inadequately supported learners by asking them to fold an origami crane with varying levels of instruction and feedback. The failure of many participants to successfully fold cranes functioned as a striking analogy for student (...) failures to learn without explicit how-to instruction, goal-directed practice, and frequent, targeted feedback. In reflecting on the activity, participants developed strategies to become more learner-centered and to better support student success. This paper explains the origami exercise and the lessons it illustrates, and discusses how the lessons learned from the exercise can translate into specific tangible strategies for the classroom. (shrink)

The centriole is a widely conserved organelle required for the assembly of centrosomes, cilia, and flagella. Its striking feature – the nine‐fold symmetrical structure, was discovered over 70 years ago by transmission electron microscopy, and since elaborated mostly by cryo‐electron microscopy and super‐resolution microscopy. Here, we review the discoveries that led to the current understanding of how the nine‐fold symmetrical structure is built. We focus on the recent findings of the centriole structure in high resolution, its assembly pathways, and its (...) nine‐fold distributed components. We propose a model that the assembly of the nine‐fold symmetrical centriole depends on the concerted efforts of its core proteins. Also see the video abstract here:https://youtu.be/m4h_3II_WJo. (shrink)

For her entire childhood, Joanna's father, Bob, had a ritual: wake up at dawn, walk the dog, and sit down at the kitchen table with a blank pad of paper and plenty of colored markers to craft notes for his two children. Over the years, word games and puzzles for five-year-olds morphed into thoughtful guidance and reflections for his teenagers approaching adulthood. Now, with more than 3,500 of her father's colorful notes in hand, Joanna has decided that the lessons tucked (...) inside are worth sharing. Folded Wisdom highlights the collection of Bob's notes, telling a story filled with universal values that encourages meaningful self-reflection about how we all face successes and failures; express happiness and sadness; and communicate frustration, praise, and love to one another. Heartfelt and full of possibility for the future, a father's folded notes and drawings are timeless reminders of love. (shrink)

In this paper we introduce n -fold implicative basis logic and the related algebras called n -fold implicative BL-algebras. Also we define n -fold implicative filters and we prove some relations between these filters and construct quotient algebras via these filters.