The mechanisms used to establish embryonic polarity are still largely unknown. A recent paper(1) describes the expression pattern of the gene glp‐1, which is required for induction events during development of the nematode Caenorhabditis elegans. Although glp‐1 RNA is found throughout the early embryo, Glp‐1 protein is only expressed in anterior cells. This negative translational regulation in posterior cells is shown to be mediated through sequences in the glp‐1 3′ untranslated region (3′UTR). Thus in nematodes, as in Drosophila, translational (...) class='Hi'>repression is one mechanism used to establish the embryonic anterior‐posterior axis. (shrink)

The strong word and stance issue only from a strict will, a will that dares the error of reading all of reality as a text, and all prior texts as openings for its own totalizing and unique interpretations. Strong poets present themselves as looking for truth in the world, searching in reality and in tradition, but such a stance, as Nietzsche said, remains under the mastery of desire, of instinctual drives. So, in effect, the strong poet wants pleasure and not (...) truth; he wants what Nietzsche named as "the belief in truth and the pleasurable effects of this belief." No strong poet can admit that Nietzsche was accurate in this insight, and no critic need fear that any strong poet will accept and so be hurt by demystification. The concern of this book, as of my earlier studies in poetic misprision, is only with strong poets, which in this series of chapters is exemplified by the major sequence of High Romantic British and American poets: Blake, Wordsworth, Shelley, Keats, Tennyson, Browning, Yeats, Emerson, Whitman, and Stevens, but also throughout by two of the strongest poets in the European Romantic tradition: Nietzsche and Freud. By "poet" I therefore do not mean only verse-writer, as the instance of Emerson also should make clear. Harold Bloom is DeVane Professor of the Humanities at Yale University. This article is the first chapter of his new book, Poetry and Repression, to be published by the Yale University Press. The book completes a tetralogy, of which the earlier volumes are The Anxiety of Influence, A Map of Misreading, and Kabbalah and Criticism. See also: "Formalism, Savagery, and Care; or, The Function of Criticism Once Again" by Jerome J. McGann in Vol. 2, No. 3; "The Poet as Elaborator: Analytical Psychology as a Critical Paradigm" by David D. Cooper in Vol. 6, No. 1. (shrink)

The use of Drosophila chromosomal rearrangements and transposon constructs involving the white gene reveals the existence of repressive chromatin domains that can spread over considerable genomic distances. One such type of domain is found in heterochromatin and is responsible for classical position‐effect variegation. Another type of repressive domain is established, beginning at specific sequences, by complexes of Polycomb Group proteins. Such complexes, which normally regulate the expression of many genes, including the homeotic loci, are responsible for silencing, white gene variegation, (...) pairing‐dependent effects and insertional targeting. (shrink)

Innovative loss‐of‐function techniques developed in recent years have made it much easier to target specific genomic loci at transcriptional levels. CRISPR interference (CRISPRi) has been proven to be the most effective and specific tool to knock down any gene of interest in mammalian cells. The catalytically deactivated Cas9 (dCas9) can be fused with transcription repressors to downregulate gene expression specified by sgRNA complementary to target genomic sequence. Although CRISPRi has huge potential for gene knockdown, there is still a lack (...) of systematic guidelines for efficient and widespread use. Here we describe the working mechanism and development of CRISPRi, designing principles of sgRNA, delivery methods and applications in mammalian cells in detail. Finally, we propose possible solutions and future directions with regard to current challenges. (shrink)

Stefan Ramaekers and Joris Vlieghe’s ‘Infants, childhood and language in Agamben and Cavell: education as transformation’ is an insightful discussion of an important facet of educational experience. In the article, they consider a Fred Astaire dance sequence from the 1953 Vincente Minnelli film, The Band Wagon, in combination with a remarkable article about this same sequence by Stanley Cavell. On the strength of this, they develop an interesting line of thought regarding the experience of language, exploring connections between (...) the ideas of Cavell and Agamben. Rich and thought-provoking though their discussion is, I find that it deflects attention from the most important aspects of the film sequence and the literature that has developed in response – specifically regarding questions of race and praise. The present discussion attempts to address these matters. (shrink)

An extensive theoretical and research literature on organizational change and its implementation has been accumulating over the past fifty years. It is customary in this literature to find resistance to change mentioned as an inevitable consequence of organizational change initiatives. Yet there has been little discussion of the nature and forms of resistance that is institutionalized in organizational structure and processes. Furthermore, organization development perspectives on organizational change address management-initiated change, but not change proposed by advocates for the powerless and (...) disadvantaged. Focussing on institutionalized resistance from the standpoint of the advocate of fundamental change, this discussion proposes a typology consisting of a sequence of forms of active resistance to change, from denial through inaction to repression. The typology is illustrated by referring to responses of organizational decision makers to the efforts of employment equity change agents to address issues of systemic discrimination in the work place. The purpose of the typology is to assist change advocates, such as equality seekers, to name, analyze and think strategically about the institutionalized resistance they encounter, and about effective responses to the resistance. (shrink)

American Academy of Pediatrics (AAP) and American College of Medical Genetics (ACMG) recently provided two recommendations about predictive genetic testing of children. The Clinical Sequencing Exploratory Research Consortium's Pediatrics Working Group compared these recommendations, focusing on operational and ethical issues specific to decision making for children. Content analysis of the statements addresses two issues: (1) how these recommendations characterize and analyze locus of decision making, as well as the risks and benefits of testing, and (2) whether the guidelines conflict or (...) come to different but compatible conclusions because they consider different testing scenarios. These statements differ in ethically significant ways. AAP/ACMG analyzes risks and benefits using best interests of the child and recommends that, absent ameliorative interventions available during childhood, clinicians should generally decline to order testing. Parents authorize focused tests. ACMG analyzes risks and benefits using the interests of the child and other family members and recommends that sequencing results be examined for additional variants that can lead to ameliorative interventions, regardless of age, which laboratories should report to clinicians who should contextualize the results. Parents must accept additional analysis. The ethical arguments in these statements appear to be in tension with each other. (shrink)

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)

Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate with the expression of cancer genes. Therefore, the molecular mechanism underlying an individual's susceptibility to cancer has remained largely unknown. However, recent evaluations of the correlations between DNA methylation and gene expression levels across healthy and cancerous genomes have revealed enrichment of disease‐related DNA methylation variations within disease‐associated risk loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk loci often contain DNA methylation sites that closely define the (...) expression of prominent cancer genes, despite the lack of significant correlations between gene expression levels and the surrounding disease‐associated polymorphic sequences. We suggest that DNA methylation variations may obscure the effect of co‐residing risk sequence alleles. Analysis of enhancer methylation data may help to reveal the regulatory circuits underlying predisposition to cancers and other common diseases.Editor's suggested further reading in BioEssays DNA methylation reprogramming in cancer: Does it act by re‐configuring the binding landscape of Polycomb repressive complexes? Abstract. (shrink)

The de‐repression of transposable elements (TEs) in mammalian genomes is thought to contribute to genome instability, inflammation, and ageing, yet is viewed as a cell‐autonomous event. In contrast to mammalian cells, prokaryotes constantly exchange genetic material through TEs, crossing both cell and species barriers, contributing to rapid microbial evolution and diversity in complex communities such as the mammalian gut. Here, it is proposed that TEs released from prokaryotes in the microbiome or from pathogenic infections regularly cross the kingdom barrier (...) to the somatic cells of their eukaryotic hosts. It is proposed this horizontal transfer of TEs from microbe to host is a stochastic, ongoing catalyst of genome destabilization, resulting in structural and epigenetic variations, and activation of well‐evolved host defense mechanisms contributing to inflammation, senescence, and biological ageing. It is proposed that innate immunity pathways defend against the horizontal acquisition of microbial TEs, and that activation of this pathway during horizontal transposon transfer promotes chronic inflammation during ageing. Finally, it is suggested that horizontal acquisition of prokaryotic TEs into mammalian genomes has been masked and subsequently under‐reported due to flaws in current sequencing pipelines, and new strategies to uncover these events are proposed. (shrink)

In his latest book Christopher Bollas uses detailed studies of real clinical practice to illuminate a theory of psychoanalysis which privileges the human impulse to question. From earliest childhood to the end of our lives, we are driven by this impulse in its varying forms, and _The Infinite Question_ illustrates how Freud's free associative method provides both patient and analyst with answers and, in turn, with an ongoing interplay of further questions. At the book's core are transcripts of real analytical (...) sessions, accompanied by parallel commentaries which highlight key aspects of the free associative method in practice. These transcripts are contextualised by further discussion of the cases themselves, as well as a wider theoretical framework which places its emphasis on Freud's theory of the logic of sequence: by learning to listen to this free associative logic, Bollas argues, we can discover a richer and more complex unconscious voice than if we rely solely on Freud's theory of repressed ideas. Bollas demonstrates, in an eloquent and persuasive manner, how the Freudian position of evenly suspended attentiveness enables the analyst's unconscious to catch the drift of the patient's own unconscious. He also shows that to stimulate further questioning is often of more benefit to the analytical process than to jump to an interpretation. Yet whatever fascinating course a session may take, neither the patient nor the analyst can halt the progress of the self-propelling interrogative drive. _The Infinite Question_ will be invaluable to both the new student and the experienced psychoanalyst, read either on its own or as a practice-based extension of the theoretical ideas elaborated in its companion volume, _The Evocative Object World_. (shrink)

Early development in many animals is programmed by maternally inherited messenger RNAs. Many of these mRNAs are translationally dormant in immature oocytes, but are recruited onto polysomes during meiotic maturation, fertilization, or early embryogenesis. In contrast, other mRNAs that are translated in oocytes are released from polysomes during these later stages of development. Recent studies have begun to define the cis and trans elements that regulate both translational repression and translational induction of maternal mRNA. The inhibition of translation of (...) some mRNAs during early development is controlled by discrete sequences residing in the 3′ and 5′ untranslated regions, respectively. The translation of other RNAs is due to polyadenylation which, at least in oocytes of the frog Xenopus laevis, is regulated by a U‐rich cytoplasmic polyadenylation element (CPE). Although similar, the CPE sequences of various mRNAs are sufficiently different to be bound by different proteins. Two of these proteins and their interactions are described here. (shrink)

E4BP4, a mammalian basic leucine zipper (bZIP) transcription factor, was first identified through its ability to bind and repress viral promoter sequences. Subsequently, E4BP4 and homologues in other species have been implicated in a diverse range of processes including commitment to cell survival versus apoptosis, the anti‐inflammatory response and, most recently, in the mammalian circadian oscillatory mechanism. In some of these cases at least, E4BP4 appears to act antagonistically with members of the related PAR family of transcription factors with which (...) it shares DNA‐binding specificity. This diversity of function is mirrored by the regulatory pathways impinging on E4BP4, which include regulation by ras via the lymphokine IL‐3 in murine B‐cells, by thyroid hormone during Xenopus tail resorption, by glucocorticoids in murine fibroblasts and by calcium in rat smooth muscle cells. This article will cover the unfolding role/s of and regulation of E4BP4, E4BP4‐like proteins and PAR factors in species as diverse as mouse and C. elegans. BioEssays 24:1023–1029, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross‐talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about 15 proteins (...) to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB‐phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation‐induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon.The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. (shrink)

The role of RNA as a messenger in the expression of the genome has been long appreciated, but its functions in regulating chromatin and chromosome structure are no less interesting. Recent results have shown that small RNAs guide chromatin‐modifying complexes to chromosomal regions in a sequence‐specific manner to elicit transcriptional repression. However, sequence‐specific targeting by means of base pairing seems to be only one mechanism by which RNA is employed for epigenetic regulation. The focus of this review (...) is on large RNAs that act in the dosage‐compensation pathways of flies and mammals. These RNAs associate with chromatin over the length of whole chromosomes and are crucial for spreading epigenetic changes in chromatin structure. They do not appear to act in a sequence‐specific manner but might provide scaffolds for co‐operative binding of chromatin‐associated complexes that enable spreading of chromatin modifications. BioEssays 25:434–442, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Priming of lineage‐specific genes in pluripotent embryonic stem cells facilitates rapid and coordinated activation of transcriptional programmes during differentiation. There is growing evidence that pluripotency factors play key roles in priming tissue‐specific genes and in the earliest stages of lineage commitment. As differentiation progresses, pluripotency factors are replaced at some primed genes by related lineage‐specific factors that bind to the same sequences and maintain epigenetic priming until the gene is activated. Polycomb and trithorax group proteins bind many genes in pluripotent (...) cells generating bivalent domains that contain both active and repressive histone modifications. The properties of polycomb proteins suggest that they act as gatekeepers, helping to maintain silencing in pluripotent stem cells while establishing a chromatin environment that is permissive for priming by sequence‐specific factors. The overall effect of factor‐mediated priming is to initiate the input of information required for cell differentiation before the first lineage choices have been made. (shrink)

I'm pleased to have been offered the chance of replying to Joseph Frank's criticisms . He is a courteous opponent, though capable of a certain asperity. . . . Frank complains that his critics appear incapable of attending to what he really said in his original essay. It is the blight critics are born for; and it is undoubtedly sometimes caused by the venal haste of reviewers, and sometimes by native dullness, and sometimes by malice. But there are other reasons (...) why an author may sometimes feel himself to be misrepresented. One is that a genuinely patient and intelligent reader may be more interested in what the piece under consideration does not quite say than in what is expressly stated. Another is the consequence of fame. Frank's original article is over thirty years old; it crystallised what had been for the most part vague notions, ideas that were in the air, and gave them a memorable name. "Spatial form" entered the jargon of the graduate school and began an almost independent existence. The term might well be used by people who had never read the essay at all; or they might casually attribute to him loose inferences made by others from the general proposition—inferences he had already disallowed and now once more contests. It must be difficult, particularly for an exasperated author, to distinguish between these causes of apparent misrepresentation. But sometimes it can be done; and then it will appear that the effect of the first is far more interesting than that of the second cause. For the suggestion then must be that the author has repressed a desire to take a position which, in his manifest argument, he differentiates from his own. This, as it happens, is what he advances as an explanation of certain ambiguities in my Sense of an Ending; the least one can say is that it is perfectly possible. Frank Kermode is the author of The Sense of an Ending: Studies in the Theory of Fiction, Continuities, and Shakespeare, Spenser, Donne: Renaissance Essays; his works also include The Classic and The Genesis of Secrecy. His contributions to Critical Inquiry are "Novels: Recognition and Deception" , "A Reply to Denis Donoghue" , and "Secrets and Narrative Sequence". (shrink)

The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression (...) or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Rationality, Irrationality, and Depathologizing OCDBrent Kious, MD, PhD (bio)Pablo Hubacher argues that some persons with obsessive-compulsive disorder (OCD) do not, in virtue of OCD itself, exhibit what he calls “epistemic irrationality,” which is a matter of violating rational norms related to belief and inquiry (Hubacher, 2023). The argument is complex and meticulous, but ultimately not persuasive. I outline the argument, show how it is unsound, and articulate its most (...) troubling consequences. I end by inquiring about the goal of projects like this, which, I believe, is to examine the rationality of mental illnesses in order to show that they are or are not illnesses.Hubacher starts by noting that (some) persons with OCD appear “doxastically irrational”: when they exhibit obsessions, they err in how they form beliefs. Specifically, they seem to “jump to conclusions,” inferring that a feared outcome is probable or certain from scant evidence. However, psychological research shows that persons with OCD are not more likely to jump to conclusions than others. Hubacher also observes that jumping to conclusions involves the inference, “possibly P, therefore definitely P.” This inference is irrational but not specific to people with OCD, because many of us do it, and an account of the irrationality of OCD should identify OCD-specific deviations. Hubacher concludes that persons with OCD are not doxastically irrational. He next considers whether they exhibit “zetetic” irrationality, which involves violating epistemic norms of inquiry. This might identify the irrationality of OCD, since compulsions like repeatedly checking the stove are basically ways of getting evidence. But Hubacher introduces the phenomenon of sexually focused OCD, or S-OCD. Persons with S-OCD worry about whether they have sexual desires they regard as inappropriate—for instance, incestuous desires or homosexual desires. Hubacher does not think people with S-OCD are zetetically irrational, however. Their endless doubts are actually reasonable, since it is possible—even common—for people to have repressed sexual desires when those desires are stigmatized. If a person with S-OCD worries about having incestuous desires, the bare fact that he does not feel those desires in the usual way should not be reassuring to him: those desires could simply be repressed. Hubacher adds that [End Page 151] people with OCD have high intolerance of uncertainty, which he takes to mean that they approach inquiries with high standards for confirmation; they are not satisfied with evidence others would see as compelling. He concludes that people with S-OCD are neither zetetically nor doxastically irrational, and so not epistemically irrational.This is a surprising conclusion, but it results from an unsound argument. An initial problem is his assumption that the only way persons with OCD can be doxastically irrational is by jumping to conclusions. This ignores other possible ways of being doxastically irrational. For instance, it would be irrational to retain beliefs that have been disconfirmed by evidence (Hubacher might call this zetetic irrationality, but surely, my beliefs can be disconfirmed without active inquiry). Irrationally retaining disconfirmed beliefs might even capture what happens in OCD: the person with OCD thinks something awful is likely to be true, even though she gets copious disconfirming evidence.A second problem is in Hubacher’s interpretation of the psychological evidence about whether persons with OCD jump to conclusions. He cites two studies involving a very specific psychological test, the bead task, wherein a subject is asked to determine whether a random sequence of colored beads have been drawn from a jar with a preponderance of one color or another. A “jumping to conclusions bias” is taken to be an inclination to guess the jar after no more than two beads are revealed (Huq & Garety et al., 1988). Although a few studies have shown that persons with OCD do not have this jumping to conclusions bias, we cannot conclude that they do not often jump to conclusions in real life. One might imagine, for instance, that people with OCD are still quite likely to jump to conclusions with respect to their obsessions (i.e., things that are highly anxiety-provoking, where the anxiety affects the conclusions drawn). And most people with OCD are not obsessed about the colors of beads.A third... (shrink)

As well as having the remarkable ability to differentiate into all of the cell types in the embryo, embryonic stem (ES) cells also have the capacity to divide and self‐renew. Maintenance of pluripotency through repeated cell divisions indicates that the developmental plasticity of ES cells has a specific epigenetic basis. We propose that tightly localised regions of histone modification are formed in ES cells by binding of sequence‐specific transcription factors at genes that are destined for expression at later stages (...) of differentiation. These ‘early transcription competence marks’ would help to maintain pluripotency by preventing the spread of repressive chromatin modifications. We further propose that the presence of discrete histone modification marks in pluripotent cells facilitates the binding of lineage‐specific and general transcription factors to the marked regions as ES cells commit to different fates. By helping to organise the precisely timed responses of genes to the signals that determine lineage choice, the gene‐specific localised epigenetic marks would play a key role in the establishment of complex gene expression programmes in differentiating cells. BioEssays 27:1286–1293, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Expression and transposition of the Suppressor‐mutator (Spm) transposon of maize are controlled by interacting epigenetic and autoregulatory mechanisms. Methylation of critical element sequences prevents both transcription and transposition, heritably inactivating the element. The promoter, comprising the terminal 0.2 kb of the element, and a 0.35‐kb, highly GC‐rich, downstream sequence are the methylation target sequences. The element encodes two proteins necessary for transposition, TnpA and TnpD. There are multiple TnpA binding sites, both in the 5′ terminal promoter region and at (...) the element's 3′ end. In addition to its role in transposition, TnpA is both a positive and a negative regulator of transcription. TnpA represses the element's promoter when it is not methylated. When the element is inactive and its promoter methylated, TnpA activates the methylated promoter and facilitates both its transient and heritable demethylation. (shrink)

Genomes of higher eukaryotes contain abundant non‐coding repeated sequences whose overall biological impact is unclear. They comprise two categories. The first consists of retrotransposon‐derived elements. These are three major families of retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene‐rich regions and are found in promoters of genes while LINEs are concentrated in gene‐poor regions and are depleted from promoters. The second class consists of non‐coding tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with mammalian centromeres, heterochromatin (...) and telomeres. Terminal TTAGGG arrays are involved in telomere capping and satellite DNAs are located in heterochromatin, which is implicated in transcription silencing by gene repositioning (relocalization). It is unknown whether interstitial TTAGGG sequences, which are present in many vertebrates, have a function. Here, evidence will be presented that retroelements and TTAGGG arrays are involved in regulation of gene expression. Retroelements can provide binding sites for transcription factors and protect promoter CpG islands from repressive chromatin modifications, and may be also involved in nuclear compartmentalization of transcriptionally active and inactive domains. Interstitial telomere‐like sequences can form dynamically maintained three‐dimensional nuclear networks of transcriptionally inactive domains, which may be involved in transcription silencing like classic heterochromatin. BioEssays 30:338–348, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:SubStance 32.3 (2003) 109-132 [Access article in PDF] Passages Beyond the Resistance:René Char's Seuls demeurent and its Harmonics in Semprun and Foucault Van Kelly —Les actions du poète ne sont que la conséquence des énigmes de la poésie. —Le poète ne jouit que de la liberté des autres. René Char Spanish-born writer Jorge Semprun, in his memoir of deportation to Buchenwald, L'écriture ou la vie (1994), tells how in (...) spring 1945 he first came to read what is arguably René Char's first influential book of poetry, Seuls demeurent, and to recite on the liberated camp's assembly ground one of the keynote poems of the collection, "La liberté," as an emblem of his survival. Although Char had published several collections prior to World War II, Seuls demeurent was a major sign that something had changed in his poetry and politics, that he was about to entrer dans la carrière, to borrow the phrase that historian Olivier Wieviorka uses to describe the political and cultural ascension of French resisters in the postwar era. 1 A Gaullist officer, Marc, present at the liberation of Buchenwald in mid-April 1945, gave a copy of Seuls demeurent to Semprun, who had been deported for resistance activities in France. Semprun immediately felt that this book transcended what better-known writers had published from the late 1930s through early 1944, when he lost contact with a French literary scene he knew well (L'écriture, 79-87).Indeed, Seuls demeurent resonated so strongly in the post-Liberation years that it furnished a major reference point in Foucault's preface to his Folie et déraison (1961), where the philosopher links his own critique of social repression with Char's "Partage formel," the poetic sequence of aphorisms that concludes Seuls demeurent. Without mentioning his source (either poet or title of the poem), Foucault quotes from aphorism XXII, where Char praises the uncanny murmur he calls "étrangeté légitime," 2 and where we might hear the whispers of the Resister's legitimate revolt against repression as well as a legitimate strangeness or new self-assertive idiom within poetry. [End Page 109]It is interesting that Semprun and Foucault route their early encounters with Char's writing through the more explicitly poetical Seuls demeurent, and not through Feuillets d'Hypnos, a series of maxims, action portraits, and homages published in 1946 inGallimard's « Espoir » series, directed by Albert Camus, Char's friend. In Feuillets d'Hypnos, Char described, aphoristically more than anecdotally, his experience in the southern French Resistance. Seuls demeurent (and eventually other poems in a similar vein from his 1948 compendium Fureur et mystère, into which Seuls demeurent was merged alongside Feuillets d'Hypnos) purveyed Char's most lasting political and ideological impact on the generations represented by Semprun and Foucault.To understand how Seuls demeurent and the liberational poetics it initiated might spur two such nonconformist yet widely divergent left intellectual projects—Semprun's politique fiction, which resulted in novels like La deuxième mort de Ramón Mercader (1969), and Foucault's archeologies of social control—we must try to read Char's work back into the immediacy of its era, with the help of historians like H.R. Kedward, Henri Michel and others, despite the fact that Seuls demeurent is striated with discernible secondary work—the displacements and condensations that the Occupation and Liberation induced in its survivors and itinerants. Semprun and Foucault, in their quotations from Char's poetry, attest to the sense of personal empowerment that his voice effected. Perhaps something in his poetics, especially its mode of interaction with history, anticipated such readers.I will explore these ideas by showing, first, how in Seuls demeurent Char's poetic re-enactment of his passage through WWII foregrounds historical events and violence, but privileges poetry as a means of giving overriding sense to the war, and more specifically to the French internal Resistance, to the extent that it was morally distinct (if not always organizationally severed) from De Gaulle's external... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Archive, The Native American, and Jefferson’s ConvulsionsJonathan Elmer (bio)1 Saxa loquunturTrauma theory proposes that there are inscriptions that befuddle any clean divide between present and past, records that have been neither selected nor destroyed by evolutionary veto but remain in some kind of limbo, “in abeyance,” as Jacques Lacan phrases it, “awaiting attention.” In a typical maneuver, Lacan emphasizes a double meaning in the French—the “reality” awaiting attention (...) is “en souffrance” [Lacan 56]. Lacan’s wordplay injects a note of pathos into what might otherwise seem a merely cognitive or epistemological question about how, or whether, we can adequately access the historical archive, whether of individuals or of cultures. At its most basic, the psychoanalytic concept of trauma insists on this ambiguous coupling between affect and event, feeling and knowing: trauma names a happening about which one never fully knows how to feel, or feels how to know. In trauma theory—as in its various avatars in current debates about canons, about historical memory and forgetting, about cultural identity as imperiled or reclaimed or repressed—this ambiguity about the relation between affect and event becomes codified as an entanglement between the ethical and the cognitive. In “Archive Fever,” Jacques Derrida notes that the term “archive” itself harbors this ambiguity: the archive is at once the beginning and the authority, it puts into play two “orders of order,” the “sequential” and the “jussive,” “the commencement and the commandment” [9]. The divine fiat of creation is an image of the perfect coincidence of these two orders of order, while historical consciousness, in the West at least, might be understood as the progressive elaboration of the dissociation of commencement and commandment. Such a dissociation is never, perhaps, complete, which is why the question of knowing the commencement, the order of sequence of past events, always seems shadowed by an encounter with commandment, authority, ethical obligation.Derrida emphasizes a drive toward unification in the archive, what he calls the act of “consignation,” or “gathering together signs”: “Consignation aims to coordinate a single corpus, in a system or a synchrony in which all the elements articulate the unity of an ideal configuration. In an archive, there should not be any absolute dissociation, any heterogeneity or secret which could separate... or partition, in an absolute manner” [10]. Because his primary topic in this essay is Freud, Derrida goes on to demonstrate how this practice and ideal of consignation deconstruct themselves in the psychoanalytic archive. On the one hand, Freud’s innovations “made possible,” or so Derrida contends, the notion of an archive that “cannot be reduced to memory: neither to memory as conscious reserve, nor to memory as rememoration, as act of recalling” [58]. On the other hand, and despite his development of this concept of an immemorial archive, however, Freud “was incessantly [End Page 5] tempted to redirect the original interest he had for the psychic archive toward archeology.” Derrida quotes an astonishing passage from the 1896 paper “The Aetiology of Hysteria,” in which Freud indulges in the fantasy that never leaves psychoanalysis, and that evinces the profound implication of this theory with other archival projects, here the imperialist dramas of ethnography. The fantasy is one in which “stones talk”:Imagine that an explorer arrives in a little-known region where his interest is aroused by an expanse of ruins, with remains of walls, fragments of columns, and tablets with half-effaced and unreadable inscriptions. He may content himself with inspecting what lies exposed to view, with questioning the inhabitants—perhaps semi-barbaric people—who live in the vicinity, about what tradition tells them of the history and meaning of these archaeological remains, and with noting down what they tell him—and he may then proceed on his journey. But he may act differently. He may have brought picks, shovels and spades with him, and he may set the inhabitants to work with these implements. Together with them he may start upon the ruins, clear away the rubbish, and, beginning from the visible remains, uncover what is buried. If his work is crowned with success, the discoveries are self-explanatory: the ruined walls are part of the ramparts of... (shrink)

Nucleosomes “talk” to each other about their modification state to form extended domains of modified histones independently of the underlying DNA sequence. At the same time, DNA elements promote modification of nucleosomes in their vicinity. How do these site-specific and histone-based activities act together to regulate spreading of histone modifications along the genome? How do they enable epigenetic memory to preserve cell identity? Many models for the dynamics of repressive histone modifications emphasize the role of strong positive feedback loops, (...) which reinforce histone modifications by recruiting histone modifiers to preexisting modifications. Recent experiments question that repressive histone modifications are self-sustained independently of their genomic context, thereby indicating that histone-based feedback is relatively weak. In the present review, current models for the dynamics of histone modifications are compared and it is suggested that limitation of histone-based feedback is key to intrinsic confinement of spreading and coexistence of short- and long-term memory at different genomic loci. See also the video abstract here: https://youtu.be/3bxr_xDEZfQ. Communication between nucleosomes and site-specific recruitment of histone modifiers act together to enable spreading and epigenetic memory of histone modifications. This review essay compares current models that describe these phenomena and outline a mechanism for how epigenetic short- and long-term memory can coexist in the same cell. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:How The Mule Got Its Tale: Moretti’s Darwinian BricolageGeoffrey Winthrop-Young* (bio)Franco Moretti. Atlas Of The European Novel. London: Verso, 1998. [AN]Franco Moretti. Modern Epic: The World System From Goethe To García Márquez. Trans. Quentin Hoare. London: Verso, 1996. [ME]1. Darwinian Preliminaries1805: Cousin de Grainville, Le dernier homme. A world in which humans have displaced the oceans dies from ecological exhaustion. 1836: Louis Geoffroy, Napoléon et la conquête du monde. (...) A history in which Napoleon wins at Waterloo and becomes emperor of the world. 1854: Charlemagne-Ischir Defontenay, Star ou Psi de Cassiopée. A distant planetary system filled with its own mythologies, histories and migration patterns.... A litany of lost names and titles: dead, discarded, ignored, out of print, reduced to pulp and brief entries in reference books, known only to experts specializing in early French science fiction. Cut off from each other with little sense of coherence or continuity, two generations of writers had been probing the many possibilities of a new literary form, some of them in highly imaginative ways, but nobody could have foretold the fate of what Félix Bodin had named littérature futuriste. Suddenly, the literary equivalent of a mass extinction wiped out a broad spectrum of conjectural imaginations. Did they deserve their fate? Wrong question. Who is to blame for their disappearance? Cui bono? The prime suspect, no doubt, is Jules Verne. “It was as if SF had for sixty years sought in vain for an institutional ‘landing point,’” surmises Marc Angenot, before pointing out that Verne’s success coincided with, indeed was based on, the repression of a wide array of promising alternatives [64]. Displaying that jovial bluntness which in his days passed for commendable virility, he extracted certain formal features from his environment, eliminated the rest, and engineered his selections into a highly marketable literary model. A lot began with Verne, but a lot ended with him, too.At the outset a rapidly emerging set of random and undirected variations opens up a multiplicity of future possibilities; then a choice is made, a selection that locks in one particular variant while locking out the competition. Subsequently, a winner—who need not be the best or most promising candidate, but who by virtue of his selection manages to impose definite constraints on future developments—spawns a tradition that coasts along until another crisis is heralded by yet another round of proliferation and selection. Readers familiar with Franco Moretti’s work will recognize this Darwinian scenario, which provides the theoretical backbone for his analyses. In the programmatic essay “On Literary Evolution” in the revised edition of Signs Taken for Wonders, it allows him to whittle down the development of the European novel from its experimental phase in the eighteenth century to the victory of the Bildungsroman in the nineteenth century and its subsequent disintegration to what must be the shortest account of the history of the novel ever written: “Novels/novel/novels” [264]. In The Way of the World it helps explain how it was possible for the Bildungsroman “to emerge victorious from that veritable ‘struggle for existence’ between various narrative forms that took place at the [End Page 18] turn of the eighteenth century” [10]. Modern Epic, in turn, uses the Darwinian model to plot the evolution of the hybrid genre announced in its title, while Atlas of the European Novel explains the morphological change novels undergo when they move from one space to another. But why Darwin? Or, since “Darwin” means many different things to many different Darwinists: why this punctuated, nongradualist, highly contingency-tolerant Gouldian Darwin? How much do we gain by applying the proliferation/lock-in sequence to the development of devices, texts, and genres? What motivates the optimism that the Darwinian paradigm may “help us to explain in a new—and better—way numerous questions that literary history has never succeeded in resolving satisfactorily”? [ME 5].But then why raise these arcane questions? Surely, Moretti’s books center on more relevant issues. Atlas is about space—and given the current critical focus on space, what more timely topic could there be? And what more obvious criticism than... (shrink)

The amdS gene of A. nidulans has proved extremely favourable for the isolation of mutations affecting gene regulation. Trans‐acting regulatory genes involved in amdS induction by small molecular weight effectors have been identified – amdR (ω‐amino acids) facB (acetate) and amdA (acetate). Another gene, the areA gene, has properties expected of a major activator gene involved in nitrogen metabolite repression of amdS. All of these regulatory genes are also involved in the control of various other functions encoded by structural (...) genes unlinked to amdS. Mutations in the 5′‐region adjacent to amdS have been isolated and allow the identification of independent cis‐acting sequences which are the target sites for the regulatory genes. The involvement of these sequences in regulatory product binding has been deduced from titration studies using transformants containing multiple copies of the 5′ sequences. A combination of genetics and molecular analysis is allowing a detailed characterization of this system. (shrink)

The expression “repressed memory” was introduced over 100 years ago as a theoretical term purportedly referring to an unobservable psychological entity postulated by Freud’s seduction theory. That theory, however, and its hypothesized cognitive architecture, have been thoroughly debunked—yet the term “repressed memory” seems to remain. In this paper I offer a philosophical evaluation of the meaning of this theoretical term as well as an argument to question its scientific status by comparing it to other cases of theoretical terms that have (...) either survived scientific change—such as “atom” or “gene”—or that have perished, such as “black bile”. Ultimately, I argue that “repressed memory” is more like “black bile” than “atom” or “gene” and, thus, recommend its demotion from our scientific vocabulary. (shrink)

This book argues that sometimes we have reasons to overcome repression and that these reasons are unlike any other reasons for action typically recognized by philosophers.

The origins of Axel Honneth's theory of recognition lie in his earlier project to correct the conceptual confusions and empirical shortcomings of historical materialism for the purpose of an adequate post-Habermasian critical social theory. Honneth proposed to accomplish this project, most strikingly, by reconnecting critical social theory with one of its repressed philosophical sources, namely anthropological materialism. In its mature shape, however, recognition theory operates on a narrow concept of interaction, which seems to lose sight of the material mediations with (...) which intersubjective relations are imbricated. The paper argues that a circumspect return to this twofold materialist heritage could substantively correct and enrich contemporary critical theory. The paper provides an illustration of this with the paradigmatic example of work. (shrink)

This title introduces the concepts of algorithms and sequencing in coding by using relatable real-world examples in the reader's everyday life. Vivid photographs and easy-to-read text aid comprehension for early readers. Features include a table of contents, an infographic, fun facts, Making Connections questions, a glossary, and an index. QR Codes in the book give readers access to book-specific resources to further their learning. Aligned to Common Core Standards and correlated to state standards. Cody Koala is an imprint of Pop!, (...) a division of ABDO. (shrink)

The notion of repression as active forgetfulness already found in Nietzsche and systematised by Freud and his successors is employed in a distinctive manner by Merleau-Ponty in Phenomenology of Perception. By showing how we appropriate our environment towards outcomes and respond to other people, he contends, we can unearth hidden modes of operative intentionality. Two such modes are the motor intentional projection of action and the anonymous intercorporeality that includes touching and being touched. Each of these is an aspect (...) of a past that was never a present. Merleau-Ponty does have something to say about pasts that were once present and that linger on in human life. Yet he shows little interest in the unconsciousness of psychoanalysis for its own sake. Psychoanalytic accounts of repression are assimilated into his theory of the body itself, serving merely as means for illustrating the latter. I suggest that this move follows on a conception of an integrated existent whose past acquisitions are remarkably enabling and untroubling. (shrink)

Erdelyi's dialectical repression theory attempts to reconcile what appear to be incompatible perspectives in the contentious area of memory for trauma. He partially succeeds and makes a strong case that repression is “an empirical fact,” but makes a weaker case that distortions and omissions are due to the same mechanism and that recovered memories are necessarily unreliable. Available data do not suggest that the return of the repressed is any less accurate than the return of the non-repressed.

Pleiotropically acting eukaryotic corepressors such as retinoblastoma and SIN3 have been found to physically interact with many widely expressed “housekeeping” genes. Evidence suggests that their roles at these loci are not to provide binary on/off switches, as is observed at many highly cell‐type specific genes, but rather to serve as governors, directly modulating expression within certain bounds, while not shutting down gene expression. This sort of regulation is challenging to study, as the differential expression levels can be small. We hypothesize (...) that depending on context, corepressors mediate “soft repression,” attenuating expression in a less dramatic but physiologically appropriate manner. Emerging data indicate that such regulation is a pervasive characteristic of most eukaryotic systems, and may reflect the mechanistic differences between repressor action at promoter and enhancer locations. Soft repression may represent an essential component of the cybernetic systems underlying metabolic adaptations, enabling modest but critical adjustments on a continual basis. (shrink)

It is shown that the facts of behavior which Freud sought to encompass by his distinction of Primary and Secondary Process can be formulated in terms of Skinner's system of behavior. This is illustrated by considering the 'primary process' behavior in dreaming, some of whose characteristics according to Freud are: it is illogical and random; visual images predominate in primary process thinking; it is highly charged with affect compared to 'secondary process' thinking; it shows 'condensation' — the fusing together of (...) two or more images into a single image. It is shown that all of these properties can be derived from Skinner's account of behavior. It is then pointed out that both Freud and Skinner have pointed to similar controlling variables of behavior, utilized mainly similar processes, and drawn many of the same distinctions. Implications for contemporary criticisms of Skinner's account of 'thinking' are pointed out. The above is preceded by a preliminary argument that since both Freud and Skinner performed functional analyses of behavior, it should be possible to compare the two accounts if the 'superfluous' middle term — the intrapsychic apparatus — in Freud's account is ignored. It is pointed out that in extrapolating his system to human behavior, Skinner has described in terms of his own system some of the characteristically 'Freudian' facts of behavior, and his formulations on the phenomena of 'repression' are summarized. The Skinnerian formulation of the primary and secondary process distinction is then presented in support of the argument that other facts of behavior which have not been discussed by Skinner can nevertheless be represented within his system of behavior. (shrink)

Running head: Implicit sequence learning ABSTRACT Can we learn without awareness? Although this issue has been extensively explored through studies of implicit learning, there is currently no agreement about the extent to which knowledge can be acquired and projected onto performance in an unconscious way. The controversy, like that surrounding implicit memory, seems to be at least in part attributable to unquestioned acceptance of the unrealistic assumption that tasks are process-pure, that is, that a given task exclusively involves either (...) implicit or explicit knowledge. (shrink)

This paper uses the Process Dissociation Procedure to explore whether people can acquire unconscious knowledge in the serial reaction time task [Destrebecqz, A., & Cleeremans, A. . Can sequence learning be implicit? New evidence with the Process Dissociation Procedure. Psychonomic Bulletin & Review, 8, 343–350; Wilkinson, L., & Shanks, D. R. . Intentional control and implicit sequence learning. Journal of Experimental Psychology: Learning, Memory, and Cognition, 30, 354–369]. Experiment 1 showed that people generated legal sequences above baseline levels (...) under exclusion instructions. Reward moved exclusion performance towards baseline, indicating that the extent of motivation in the test phase influenced the expression of unconscious knowledge. Experiments 2 and 3 revealed that even with reward, adding noise to the sequences or shortening training led to above-baseline exclusion performance, suggesting that task difficulty and the amount of training also affected the expression of unconscious knowledge. The results help resolve some current debates about the role of conscious awareness in sequence learning. (shrink)

Over the past decade, sequence learning has gradually become a central paradigm through which to study implicit learning. In this chapter, we start by briefly summarizing the results obtained with different variants of the sequence learning paradigm. We distinguish three subparadigms in terms of whether the stimulus material is generated either by following a fixed and repeating sequence (e.g., Nissen & Bullemer, 1987), by relying on a complex set of rules from which one can produce several alternative (...) deterministic sequences (e.g., Lewicki, Hill & Bizot, 1988; Stadler, 1989), or by following the output of a probabilistic set of rules such as instantiated by noisy finite-state grammars (Cleeremans & McClelland, 1991; Jiménez, Mendéz & Cleeremans, 1996). Next, we focus on the processes involved in sequence representation and acquisition. We suggest that the sensitivity to the sequential structure observed in the probabilistic subparadigm can only be a result of the acquisition of a representation of the statistical constraints of the material, and that this sensitivity emerges through the operation of mechanisms that are well instantiated by connectionist models such as the Simple Recurrent Network (Elman, 1990; Cleeremans, 1993b). We present new simulation work meant to explore to what extent the model can also account for specific data obtained in a paradigmatic instance of deterministic, rule-based sequence learning task: Lewicki et al. (1988)'s situation. Finally, we report on the results of an experiment that compares learning on otherwise similar deterministic and probabilistic structures, and we show that learning of both types of structures is equivalent only under conditions that maximally hinder explicit acquisition. Taken together, these simulation and experimental data lend support to the claim that implicit learning in all three sequence learning subparadigms can amount to a form of statistical sequence learning. They also suggest that distinguishing among several theories of sequence representation and acquisition may require us to analize the data in great detail. Hopefully, however, some truth can be found in such details.. (shrink)

This volume seeks to explain how American society, which had been capable of noble aspirations such as those in the Declaration of Independence and the Constitution, was capable of adopting one of the most widely deplored statutes of our history, the Sedition Act of 1798. It examines how the political ideals of the American Revolution were undermined by the adoption of repressive doctrines of the English monarchial system - the criminalization of criticism against the king, the Parliament, the judiciary, and (...) Christianity. Freedom of speech was dramatically confined, and this law remained unchallenged until well into the twentieth century. This book will be of keen interest to all concerned with the early Republic, freedom of speech, and evolution of American constitutional jurisprudence. Because it addresses the much-criticized Sedition Act of 1798, one of the most dramatic illustrations of this repressive jurisprudence, the book will also be of interest to Americans concerned about preserving free speech in wartime. (shrink)

The aim of this paper is to highlight an interdependence between procedural and agential norms that undermines their neat separation when appraising argumentation. Drawing on the munāẓara tradition, we carve a space for sequencing in argumentation scholarship. Focusing on the antagonist’s sequencing of critical moves, we identify each sequence’s corresponding values of argumentation: coalescence, reliability, and efficacy. These values arise through the mediation of virtues and simultaneously underpin procedural as well as agential norms. Consequently, an ambiguity between procedure and (...) agent becomes apparent. This ambiguity hints at the potential for a virtue theory of argumentation that draws on procedural norms. (shrink)

A major weakness in Erdelyi's account concerns the claim that repression can become conscious. A relational account of cognition demonstrates that if repression is successful, then the repressive act cannot become known. Additionally, “resistance” further distinguishes “repression” from “suppression.” Rather than blurring the distinction between these processes, it is possible to recognise a series of defences. Suggestions are provided for alternative research avenues.

ABSTRACT There are two tenets about free agency that have proven difficult to combine: free agency is grounded in an agent’s possession or exercise of their reasons-responsiveness, only actual sequence features can ground free agency. This paper argues that and can only be reconciled if we recognise that their clash is just the particular manifestation of a wider conflict between two approaches to the notion of non-accidentality. According to modalism, p is non-accidentally connected to q iff p modally tracks (...) q. According to explanationism, p is non-accidentally connected to q iff q explains p in the right way. The conflict between these two approaches becomes manifest in Frankfurt-like cases for many notions, in which p and q are intuitively non-accidentally connected even though there is no modal tracking between them. Thus, and can’t be combined because the Frankfurt-cases upon which rests track explanationist intuitions, while the non-accidentality requirement of reasons-responsiveness in is usually spelled out in modalist terms. Hence, the possibility of an actual sequence reasons-responsiveness account depends on finding an explanationist approach to the non-accidentality requirement of reasons-responsiveness. (shrink)

Fredric Jameson's exacting essay, "The Symbolic Interference; or, Kenneth Burke and Ideological Analysis" Critical Inquiry 4 [Spring 1978]: 507-23) moves me to comment. I shall apply one of my charges of my title to him, he applies the other to me. The matter is further complicated by the fact that there is a distance at which they are hard to tell apart. For any expression of something implies a repression of something else, and any statement that goes only so (...) far is analyzable as serving to forestall a statement that goes farther. And I can't go as far as I think if I share with Jameson what I take to be his over-investment in the term "ideology." . . . the line between the implicit and the explicit being so wavering, there are many cases where the distinctions between conscious and unconscious become correspondingly blurred. But the kind of methodological repression that is implicit in Jameson's hermeneutic model can be wasteful beyond necessity. For it encourages him to be so precociously prompt in his "rereading" of a text that he doesn't allow his readers to read a single sentence of it. He doesn't tell them what Sinn, in its own terms, my text has on the subject of "ideology," "mystification," and the "unconscious." Instead, he cuts corners and settles for a report of the Bedeutung that it has for him. In this case the procedure is particularly wasteful because Jameson is highly intelligent, and if it weren't for the bad leads of his models he's the last man in the world who would have to be so bluntly inaccurate as he is on this occasion. I believe that he could put me through quite a trying ordeal if he could have but kept on the subject and pursued me accordingly. Kenneth Burke's previous contributions to Critical Inquiry are "Dancing with Tears in My Eyes" , "Post-Poesque Derivation of a Terministic Cluster" , " Motion/ Action" , and a hermeneutic fantasy, "A Critical Load . . ." . He would like us to mention that William Willeford, the interlocutor of a section in " Motion/ Action," is a professor of English at the University of Washington. (shrink)

Transitional justice scholars are increasingly concerned with measuring the impact of transitional justice initiatives. Scholars often assume that TJ mechanisms must be properly designed and ordered to achieve lasting effect, but the impact of TJ timing and sequencing has attracted relatively little theoretical or empirical attention. Focusing on Latin America, this article explores variation within the region as to when TJ occurs and the order in which mechanisms are implemented. We utilize qualitative comparative analysis to assess the impact of TJ (...) timing and sequencing on democratic development. We find little evidence for path dependency owing to the chronological order of mechanisms. We do find, however, that amnesties and trials approach a sufficient condition for democratic consolidation in Latin America; trials, however, come closest to being a necessary condition for successful democratic consolidation. (shrink)