Transcriptional silencing may not necessarily depend on the continuous residence of a sequence‐specific repressor at a control element and may act via a “hit and run” mechanism. Due to limitations in assays that detect transcription factor (TF) binding, such as chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq), this phenomenon may be challenging to detect and therefore its prevalence may be underappreciated. To explore this possibility, erythroid gene promoters that are regulated directly by GATA1 in an inducible system are analyzed. (...) It is found that many regulated genes are bound immediately after induction of GATA1 but the residency of GATA1 decreases over time, particularly at repressed genes. Furthermore, it is shown that the repressive mark H3K27me3 is seldom associated with bound repressors, whereas, in contrast, the active (H3K4me3) histone mark is overwhelmingly associated with TF binding. It is hypothesized that during cellular differentiation and development, certain genes are silenced by repressive TFs that subsequently vacate the region. Catching such repressor TFs in the act of silencing via assays such as ChIP‐seq is thus a temporally challenging prospect. The use of inducible systems, epitope tags, and alternative techniques may provide opportunities for detecting elusive “hit and run” transcriptional silencing. Also see the video abstract here https://youtu.be/vgrsoP_HF3g. (shrink)

Cofactor squelching is the term used to describe competition between transcription factors (TFs) for a limited amount of cofactors in a cell with the functional consequence that TFs in a given cell interfere with the activity of each other. Since cofactor squelching was proposed based primarily on reporter assays some 30 years ago, it has remained controversial, and the idea that it could be a physiologically relevant mechanism for transcriptional repression has not received much support. However, recent genome‐wide studies have (...) demonstrated that signal‐dependent TFs are very often absent from the enhancers that are acutely repressed by those signals, which is consistent with an indirect mechanism of repression such as squelching. Here we review these recent studies in the light of the classical studies of cofactor squelching, and we discuss how TF cooperativity in so‐called hotspots and super‐enhancers may sensitize these to cofactor squelching. (shrink)

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering (...) role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

The ontogeny of the vertebrate retina has been a topic of interest to developmental biologists and human geneticists for many decades. Understanding the unfolding of the genetic program that transforms a field of progenitors cells into a functionally complex and multi‐layered sensory organ is a formidable challenge. Although classical genetic studies succeeded in identifying the key regulators of retina specification, understanding the architecture of their gene network and predicting their behavior are still a distant hope. The emergence of next‐generation sequencing (...) platforms revolutionized the field unlocking the access to genome‐wide datasets. Emerging techniques such as RNA‐seq, ChIP‐seq, ATAC‐seq, or single cell RNA‐seq are used to characterize eye developmental programs. These studies provide valuable information on the transcriptional and cis‐regulatory profiles of precursors and differentiated cells, outlining the trajectories that connect each intermediate state. Here, recent systems biology efforts are reviewed to understand the genetic programs shaping the vertebrate retina. (shrink)

The analysis of genetic and epigenetic mechanisms of the genotype–phenotypic connection has, so far, only been possible in a handful of genetic model systems. Recent technological advances, including next‐generation sequencing methods such as RNA‐seq, ChIP‐seq and RAD‐seq, and genome‐editing approaches including CRISPR‐Cas, now permit to address these fundamental questions of biology also in organisms that have been studied in their natural habitats. We provide an overview of the benefits and drawbacks of these novel techniques and experimental approaches that can (...) now be applied to ecological and evolutionary vertebrate models such as sticklebacks and cichlid fish. We can anticipate that these new methods will increase the understanding of the genetic and epigenetic factors influencing adaptations and phenotypic variation in ecological settings. These new arrows in the methodological quiver of ecologist will drastically increase the understanding of the genetic basis of adaptive traits – leading to a further closing of the genotype–phenotype gap. -/- . (shrink)

A key challenge for understanding transcriptional regulation is being able to measure transcription factor (TF)‐DNA binding events with sufficient spatial and temporal resolution; that is, when and where TFs occupy their cognate sites. A recent study by Para et al. has highlighted the dynamics underlying the activation of gene expression by a master regulator TF. This study provides concrete evidence for a long‐standing hypothesis in biology, the “hit‐and‐run” mechanism, which was first proposed decades ago. That is, gene expression is dynamically (...) controlled by a TF that transiently binds and activates a target gene, which might stay in a transcriptionally active state after the initial binding event has ended. Importantly, the experimental procedure introduced, TARGET, provides a useful way for identifying multiple target genes transiently bound by their regulators, which can be used in conjunction with other well‐established methods to improve our understanding of transcriptional regulatory dynamics. (shrink)

Genome‐wide identification of transcription factor binding sites with the ChIP‐seq method is an extremely important scientific endeavor − one that should ideally be performed for every transcription factor in as many cell types as possible. A major hurdle on the way to this goal is the necessity for a specific, ChIP‐grade antibody for each transcription factor of interest, which is often not available. Here, we describe CETCh‐seq, a recently published method utilizing genome engineering with the CRISPR/Cas9 system to (...) circumvent the need for a specific antibody. Using the CETCh‐seq method, targeted genomic editing results in an epitope‐tagged transcription factor, which is recognized by a well‐characterized, standard antibody, efficacious for ChIP‐seq. We have used CETCh‐seq in human cancer cell lines as well as mouse embryonic stem cells. We find that roughly 60% of transcription factors tagged using CETCh‐seq produce a high quality ChIP‐seq map, a significant improvement over traditional antibody‐based methods. (shrink)

Long noncoding RNAs have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, (...) we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. © 2013 Elsevier Inc. (shrink)

Old Havana: Spirit of the Living City artistically captures the architecture, people, and daily life of La Habana Vieja through the lenses of two visionary photographers and colleagues, one American and the other Cuban. Chip Cooper and Néstor Martí began collaborating in 2008, documenting the picturesque features of the oldest and most historically rich quarter in Cuba's capital city at the behest of Eusebio Leal Spengler, the historian of the city of Havana and the director of the Habana Vieja (...) restoration project. Cooper's and Martí's images highlight the spirit of change and renewal underlying the restoration of this international treasure and its revival as a vibrant business and residential area. Inspired by the work of twentieth century American photographer Walker Evans, Cooper and Martí, through perspectives both unique and deeply entwined, capture the humanity of the city, in a language at once universal and transcendent. (shrink)

We live in a reactionary culture where divisive issues arise, people on either side throw stones, and everyone ends up more entrenched in their opinions than in reaching common ground--or even exhibiting common courtesy! If there ever was a time for Christians to understand and communicate God's truth about controversial and polarizing issues, it is now. Believers must develop convictions based on research, reason, and biblical truth--and be able (and willing) to communicate these convictions with a love and respect that (...) reflects God's own heart. In Culture Shock, bestselling author, pastor, and radio personality Chip Ingram shows readers how they can bring light rather than heat to the most controversial and divisive issues of our day. Covering topics such as right and wrong, sex, homosexuality, abortion, politics, and the environment, Culture Shock is every engaged believer's must-have guidebook to replacing reactionary hate with revolutionary love. (shrink)

Examines the growing popularity of alternative medicine, and discusses the mind-body connection in healing.

Desmond’s ambitious effort to re-conceive the problem of dialectic and otherness is both timely and provocative. Moving beyond the “generous hermeneutic” of Hegel exemplified in Art and the Absolute, Desmond develops more fully a discussion about the alleged “closure” of dialectical philosophies generally and Hegel’s philosophy specifically. Whereas Art and the Absolute tended to defend Hegel’s insights and achievements — at least in aesthetic theory — against a wide variety of critical approaches, the work under review attempts to engage seriously (...) the persistent charge of “closure” made against Hegelian speculative philosophy. Repeated by critics as various as Habermas, Heidegger, Lonergan, and Derrida, the charge is too widespread and too frequently levelled to ignore. At issue seems to be the very possibility of an “absolute” knowing. How is it possible to know absolutely without trimming up the edges of the knowable, dotting all i’s and crossing all t’s, and leaving nothing for future philosophers but the relationships of disciple, exegete, or rebel angel? It is of course arguable that the self-developing categorial criticism in terms of which Hegel develops his doctrine of absolute knowing renders such objections irrelevant, but Desmond does not opt for this strategy. Rather, in the development of his own original metaphysics of origin, Desmond attempts to “sublate” the Hegelian philosophy. (shrink)

While human lives are endlessly variable, our most memorable positive moments are dominated by four elements: elevation, insight, pride, and connection. If we embrace these elements, we can conjure more moments that matter. What if a teacher could design a lesson that he knew his students would remember twenty years later? What if a manager knew how to create an experience that would delight customers? What if you had a better sense of how to create memories that matter for your (...) children? This book delves into some fascinating mysteries of experience: Why we tend to remember the best or worst moment of an experience, as well as the last moment, and forget the rest. Why 'we feel most comfortable when things are certain, but we feel most alive when they're not.' And why our most cherished memories are clustered into a brief period during our youth. Readers discover how brief experiences can change lives, such as the experiment in which two strangers meet in a room, and 45 minutes later, they leave as best friends. (What happens in that time?) Or the tale of the world's youngest female billionaire, who credits her resilience to something her father asked the family at the dinner table. (What was that simple question?) Many of the defining moments in our lives are the result of accident or luck -- but why would we leave our most meaningful, memorable moments to chance when we can create them? The Power of Moments shows us how to be the author of richer experiences."--Dust jacket flap. (shrink)

We investigate 1 factor that influences the success of ideas or cultural representations by proposing that they have a habitat, that is, a set of environmental cues that encourages people to recall and transmit them. We test 2 hypotheses: (a) fluctuation: the success of an idea will vary over time with fluctuations in its habitat, and (b) competition: ideas with more prevalent habitats will be more successful. Four studies use subject ratings and data from newspapers to provide correlational support for (...) our 2 hypotheses, with a negative factoid, positive rumor, catchphrases, and variants of a proverb. Three additional experimental studies manipulate the topic of actual conversations and find empirical support for our theory, with catchphrases, proverbs, and slang. The discussion examines how habitat prevalence applies to a more extensive class of ideas and suggests how habitats may influence the process by which ideas evolve. (shrink)

It is no secret that Hegel, along with Vico, whom he never read, and Rousseau, whom he read with enthusiasm, regarded poetic meaning as historically prior to prosaic meaning - the figurative preceded the literal, the tropological antedated the logical per se. Indeed, Hegel went so far, in his Aesthetic, as to qualify poetry as “Man’s original grasp of truth”. Since, as we know, for Hegel the true is the whole, it would seem that this original grasp of the truth (...) would have to be accounted for in any speculative account of truth. (shrink)

Using research into learning from sequences of examples, we generate predictions about what cultural products become widely distributed in the social marketplace of ideas. We investigate what we term the Repetition‐Break plot structure: the use of repetition among obviously similar items to establish a pattern, and then a final contrasting item that breaks with the pattern to generate surprise. Two corpus studies show that this structure arises in about a third of folktales and story jokes. An experiment shows that jokes (...) with this structure are more interesting than those without the initial repetition. Thus, we document evidence for how a cognitive factor influences the cultural products that are selected in the marketplace of ideas. (shrink)

In the decade since the late George Armstrong Kelly announced in the pages of this journal that Richard Winfield’s project has something significant to contribute to the debate over the contemporary relevance of Hegel’s systematic philosophy, Winfield has produced a number of works in support of that claim. These works have established Winfield as an important neo-Hegelian thinker.

French interpretations of Hegel have been immensely influential in the past fifty years. One has only to think of the names Alexandre Kojève and Jean Hyppolite to begin to recognize the enormous debt which all students of Hegel owe to French scholarship in this period. Beyond the problems posed by the specific interpretations of Hegel advanced by Kojève and Hyppolite, however, there is also the task of beginning to assess the great influence upon subsequent French thought brought about by their (...) students, among whom are grouped a veritable pantheon of modern French thinkers. Maurice Merleau-Ponty, Alexandre Koyré, Raymond Aron, Maurice Blanchot, Jacques Lacan, and Georges Bataille, among others, all attended Kojèves’s lectures, while Michel Foucault and Jacques Derrida attended seminars with Hyppolite. (shrink)

Hegel has often been held by his critics to have failed in his efforts to achieve his professed goal to make of philosophy a science. Some of the major objections have been that he overlooked problems of finite, embodied existence, that he ignored the constitutive power of language, and that he did not make allowance for a creative unconscious. Wilfried Ver Eecke has written an oddly-titled work which traces the role of negation in the realms of child development, psychoanalysis, linguistics, (...) and Hegelian thought. In the course of his complex, nuanced study, he provides ample material for defending Hegel from these charges, even where he himself seems ambivalent about their validity. (shrink)

Gotthard Deutsch (1859–1921) taught at Hebrew Union College in Cincinnati from 1891 until his death, where he produced a card index of 70,000 ‘facts’ of Jewish history. This article explores the biography of this artefact of research and poses the following question: Does Deutsch’s index constitute a great unwritten work of history, as some have claimed, or are the cards ultimately useless ‘chips from his workshop’? It may seem a curious relic of positivistic history, but closer examination allows us to (...) interrogate the materiality of scholarly labor. The catalogue constitutes a total archive and highlights memory’s multiple registers, as both a prosthesis for personal recall and a symbol of a ‘human encyclopedia’. The article argues that this mostly forgotten scholar’s work had surprising repercussions: Deutsch’s student Jacob Rader Marcus (1896–1995) brought his teacher’s emphasis on facticity to the field of American Jewish history that he pioneered, catapulting a 19th-century positivism to the threshold of the 21st century. Deutsch’s index was at an inflection point of knowledge production, created as historians were shifting away from ‘facts’ but just before new technologies (also based on cards) enabled ‘big data’ on a larger scale. The article thus excavates a vision of monumentality but proposes we look past these objects as monuments to ‘heroic’ scholarship. Indeed, Deutsch’s index is massive but middling, especially when placed alongside those of Niklas Luhmann, Paul Otlet, or Gershom Scholem. It thus presents a necessary corrective to anointing such indexes as predecessors to the Internet and big data because we must keep their problematic positivism in perspective. (shrink)

In this position paper, we would like to promote the alternative approach positioned between the two extreme positions consisting in refusing any innovation or in adopting technology without questioning it. This approach proposes a reflexive and responsible innovation based on a compromise between industrial and economic potentialities and a common respect of our human rights and values. We argue that the “silence of the chips right” is timely, relevant and sustainable to face ethical challenges raised by IoT such as protecting (...) privacy, trust, social justice, autonomy or human agency. We believe this technical solution may support establishing an ethics of IoT embedded in the technology itself. Our position is not ‘technocratic’: we do not agree with discourses arguing technology can fix problems. Through the responsible research and innovation approach we promote the idea that only human agency and user empowerment constitute a valid answer to the ethical, legal and social issues raised by IoT. (shrink)

A brief review and classification of technology in general begins the paper, followed by an application of the classification to two specific marathon case studies: the 2018 Boston marathon and the 2017 Nike Breaking2 Project marathon. Then concepts from an array of sport philosophers are discussed to suggest an explanation for why each of the case studies strikes us as problematic. The conclusion provides a reasonable explanation for our misgivings, as well as an indication of how we might evaluate sporting (...) endeavors in the face of increasing technological innovation. (shrink)

Views on aging, such as self-perceptions of aging or age stereotypes are generated in early childhood and continue to develop throughout the entire lifespan. The ideas a person has about their own aging and aging in general influence their behavior toward older persons as well as their own actual aging, which is why VoA are already important in adolescence and young adulthood. The current study investigates VoA of young adults in different domains and how different family aspects are related to (...) VoA. From February to March 2021, N = 305 young adults [aged 18–30 years, Mage = 22.20 ] participated in an online survey, in which, in addition to sociodemographic variables and family aspects, self-perceptions of aging, age stereotypes, and the young adults’ ratings of their parents’ VoA were assessed. The results of stepwise regression analyses predicting the young adults’ VoA, revealed significant associations between the quality of contact with grandparents and the self-perceptions of aging of young adults. However, the frequency of contact was neither related to young adults’ self-perceptions of aging nor age stereotypes. Grandparents’ health status emerged as a significant moderator between the relationship of contact quality and the young adults’ self-perceptions of aging as continued growth and physical decline. Family climate was also found to be significantly related to young adults’ self-perceptions of aging. Similarities regarding VoA within the family were demonstrated, based on proxy report from the respondents. The results underline the importance of family aspects for the development of VoA in young adulthood, and the significance of interventions targeting these factors to combat ageism. (shrink)

Definition of the problem: The development of molecular genetics has provided tools not only for the diagnosis of genetic diseases and disease dispositions in affected individuals, but also for the detection of healthy carriers of recessive hereditary traits. The resulting, ethically controversial option of genetic population screening used to be restricted to a small number of rather rare diseases by methodological limitations which are now about to be overcome.

탈냉전 탈이념의 시대상을 피력하고, 21세기 세계사 주도권 참여를 위한한국인의 역사적 소명, 문명론적 근거를 제시한 저술.

The increasing flow of immigrants in many European countries and the growing presence of children from immigrant families in schools makes it relevant to study the development of prejudice in children. Parents play an important role in shaping children’s values and their attitudes toward members of other ethnic groups; an intergenerational transmission of prejudice has been found in a number of studies targeting adolescents. The present study aims to investigate the intergenerational transmission of ethnic prejudice in 3- to 9- year-old (...) children and its relations to parenting styles. Parents’ blatant and subtle ethnic prejudice and parenting style are measured together with children’s explicit and implicit ethnic prejudice in pupils and parents of preschool and primary schools in the region of Rome, Italy ( N = 318). Results show that parents’ subtle prejudice predicts children’s implicit prejudice regardless of the parenting style. Findings indicate that children might acquire prejudice by means of the parents’ implicit cognition and automatic behavior and educational actions. Implications for future studies and insights for possible applied interventions are discussed. (shrink)

The paper considers main features of two groups of logics for biological devices, called Physarum Chips, based on the plasmodium. Let us recall that the plasmodium is a single cell with many diploid nuclei. It propagates networks by growing pseudopodia to connect scattered nutrients. As a result, we deal with a kind of computing. The first group of logics for Physarum Chips formalizes the plasmodium behaviour under conditions of nutrient-poor substrate. This group can be defined as standard storage modification machines. (...) The second group of logics for Physarum Chips covers the plasmodium computing under conditions of nutrient-rich substrate. In this case the plasmodium behaves in a massively parallel manner and propagates in all possible directions. The logics of the second group are unconventional and deal with non-well-founded data such as infinite streams. (shrink)