A contrario reasoning (or ‘a contrario argument’ or ‘argument a contrario’) is traditionally understood as an appeal to the deliberate silence of the legislator: because a legal rule does not mention case X specifically, the rule is not applicable to it. Modern perspectives on legal reasoning often apply this label to a broader concept of reasoning, namely the reasoning by which a legal rule is not applied because of the differences between the case at hand and the one(s) mentioned in (...) the legal rule. This article first explains how the broader concept could have come into being, and then argues that from an argumentation theoretical point of view the modern concept makes no sense as a category of argumentation. Furthermore it is shown under which conditions the traditional concept can be sound. (shrink)

Recent studies of early development in a number of ivertebrate and vertebrate species have suggested that growth factors and their receptors may play important roles in differentiation as well as cell proliferation. In the mouse embryo, the expression of the receptors for insulin and insulin‐like growth factors I and II (IGF‐I and ‐II) are temporally regulated. The ontogeny of receptor and ligand expression within the insulin and IGF gene family suggests that the very earliest stages of mammalian embryogenesis (...) may be subject to regulation by autocrine and paracrine factors from maternal and embryonic sources. (shrink)

The tendency for emotions to be predictable over time, labelled emotional inertia, has been linked to low well-being and is thought to reflect impaired emotion regulation. However, almost no studies have examined how emotion regulation relates to emotional inertia. We examined the effects of cognitive reappraisal and expressive suppression on the inertia of behavioural, subjective and physiological measures of emotion. In Study 1 (N = 111), trait suppression was associated with higher inertia of negative behaviours. We replicated this (...) finding experimentally in Study 2 (N = 186). Furthermore, in Study 2, instructed suppressors and reappraisers both showed higher inertia of positive behaviours, and reappraisers displayed higher inertia of heart rate. Neither suppression nor reappraisal were associated with the inertia of subjective feelings in either study. Thus, the effects of suppression and reappraisal on the temporal dynamics of emotions depend on the valence and emotional response component in question. (shrink)

Physiological concentrations of retinoic acid can induce acute alterations in the expression of the enzyme tissue transglutaminase in cultured macrophages. The induction of this enzyme offers a probe to study the mechanism of retinoid action in both normal and leukemic cells.

Pride expressions draw attention to one’s achievement, and therefore can enhance one’s status. However, such attention has been linked to negative interpersonal consequences (i.e. envy). Fortunately, people have been found to regulate their pride expressions accordingly. Specifically, pride expressions are lower when the domain of the achievement is of high relevance to observers. We set out to replicate this effect in a non-Western sample. Additionally, we extended the current finding by investigating the moderating role of self-monitoring, an individual’s ability and (...) willingness to adjust their behaviours under different social contexts to cultivate status. This allows us to explore the previously assumed underlying status motive in regulating pride expressions. Data from two preregistered studies (N1 = 913; N2 = 1081) replicated the effect that pride expressions are inhibited when the achievement domain is relevant. A significant main effect of self-monitoring was found, such that high self-monitors express more pride than low self-monitors, consistent with the conceptualisation of self-monitoring as rooted within a status-enhancement motive. The assumed interaction effect between domain relevance and self-monitoring was not significant. Our findings suggest that the effect of domain relevance on pride expression is robust and status driven. (shrink)

RNA polymerase II (RNAP II) non‐coding transcription is now known to cover almost the entire eukaryotic genome, a phenomenon referred to as pervasive transcription. As a consequence, regions previously thought to be non‐transcribed are subject to the passage of RNAP II and its associated proteins for histone modification. This is the case for the nucleosome‐depleted regions (NDRs), which provide key sites of entry into the chromatin for proteins required for the initiation of coding gene transcription and DNA replication. In this (...) review, recent data on the effects of pervasive transcription through NDRs are summarized and a model is proposed to explain how RNAP II‐driven transcription is able to modify the nucleosomes flanking the NDRs, leading to nucleosome repositioning and NDR closure. Even though much of the mechanistic detail underlying these events remains to be elucidated, such a model provides a basis to explain how non‐coding transcription through NDRs can regulate the initiation of coding gene expression and DNA replication. (shrink)

Phytochrome is known to regulate the expression of several major nuclearencoded polypeptides at the level of transcription. Both in vivo in vitro methods are currently being used to determine the step(s) between the light activation of phytochrome and changes in gene expression.

The c‐myc proto‐oncogene is normally subject to complex regulation at the transcriptional and post‐transcriptional levels in proliferating and differentiating cells. It is activated in response to growth stimuli and generally, though not always, repressed in response to differentiation signals. Abnormal, deregulated c‐myc expression is a common feature of numerous malignancies and occurs by a variety of molecular mechanisms which probably reflect the existence of multiple factors responsible for its normal control. Here, I provide a detailed summary of recent (...) progress and current views on c‐myc gene regulation. (shrink)

Trypanosoma brucei mitochondria contain unusual small circular DNAs of unknown function. These are catenated with a long informational DNA sequence containing genes homologous to those found in other mitochondria. Although these genes are transcribed throughout the life cycle, differential production of the mitochondrial respiratory system during the life cycle is accompanied by differential abundance of specific transcripts and differential polyadenylation of mitochondrial gene transcripts. Multiple transcripts occur for most of the mitochondrial genes. Transcripts of the apocytochrome b gene possessing nucleotide (...) sequences at their 5′ ends which are not present in mitochondrial DNA are found at stages of the life cycle when the respiratory system is expressed. These results suggest the presence of post‐transcriptional mechanisms that regulate the expression of mitochondrial genes during the life cycle of T. brucei. (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)

Skin is one of the most thoroughly studied epithelia and can be used as a model for transcriptional control of epithelial differentiation. In particular, the stages of epidermal development and differentiation from a simple epithelium are well characterized. Temporal gene expression during development can be used to assign roles for transcription factors in epidermal differentiation. Approaches to understanding transcriptional regulation in epidermis include extensive promoter analysis and expression studies, in some cases coupled to functional studies. This work (...) has not produced any consensus about the importance of any particular factor or class of factors in epidermal specification. There is, as yet, nothing similar to the myo D family of tissue‐specific and cell‐type determining factors in epidermis. These studies, however, have revealed much about control of the differentiation process in epidermis. Most recently, there has been a suggestion that epithelial transcription can be influenced directly by the status of the adhesion complexes at the cell surface, providing a direct link between one of the distinguishing features of the epithelial state and gene transcription. (shrink)

It is often acknowledged that mindfulness facilitates emotion regulation on a long-term scale. Only few empirical studies support the hypothesis that even a brief mindfulness induction among subjects without previous experience of meditation allows an effective reduction of both positive and negative emotions. To the best of our knowledge, this hypothesis has never been tested when comparing mindfulness to other regulation strategies known to be effective. The current study investigates the effects of mindfulness, reappraisal and expressive suppression during (...) the regulation of positive emotions. Forty-five participants without previous meditation experience watched four positive video clips while applying a specific regulation strategy: mindful attention, reappraisal, expressive suppression or no strategy. Video clips were matched for intensity and positive emotions index. Each of them was evaluated on two dimensions, valence and arousal. Moreover, participants’ facial expressions were recorded during the presentation of the video clips. Results showed that participants report less positive affect in reappraisal and mindful attention conditions compared to expression suppression and a control condition; and the facialexpression – activation of AU12 and AU6 – varies with the regulation strategy applied. Results demonstrate the effectiveness of mindfulness in decreasing both the evaluative judgment of positive video clips and the related facial expression, among participants without previous mindfulness experience. (shrink)

The present study aimed to explore the effectiveness of two typical intrapersonal strategies (cognitive reappraisal, CR; expressive suppression, ES) on interpersonal emotion regulation (IER), and uncover the physiological synchrony pattern underlying this. A sample of 90 friend dyads (N = 180) was randomly assigned to the CR, the ES, or the control group. In each dyad, the target underwent a negative emotional task (induce sadness by recalling a negative event), and the regulator was assigned to implement the CR strategy, (...) the ES strategy, or no action to down-regulate the targets’ negative emotions. Self-reported results showed that compared to the control group, both CR and ES strategies decreased the targets’ negative emotions, and increased the targets’ positive emotions, indicating a successful IER effect. And the ECG results revealed that relative to the control condition, both CR and ES strategies evoked stronger physiological synchrony (heart rate synchrony and heart rate variation synchrony) during the emotion regulation stage of IER. Overall, these findings demonstrated the similar efficacy of reappraisal and suppression strategies implemented by the regulators to improve the targets’ negative emotions, and suggested that the physiological synchrony might have an important relational meaning during the IER process. (shrink)

In our everyday interaction with the environment, we often perceive objects and spaces as opportunities to feel, maintain, enhance, and change our affective states and processes. The concept of affective affordance was coined to accommodate this aspect of ordinary perception and the many ways in which we rely on the material environment to regulate our emo- tions. One natural way to think of affective affordances in emotion regulation is to interpret them as tools for regulating felt affective states. We (...) argue that this way of conceiving of affective affordances is too restrictive. By analyzing the role of expressive properties of objects and spaces in emotion regulation, we show that our environment does not need to elicit felt affective states to regulate our emotions. Thus, we revise the concept of affective affordance to accommodate these cases. This revised concept explains more with less. Hence, it should be preferred in wide-reaching philosophical projects that aim to explain human affectivity as a situated phenomenon. (shrink)

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (...) (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. (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)

Many common human traits are believed to be a composite reflection of multiple genetic and non‐genetic factors and the genetic contribution is consequently often difficult to characterise. Recent advances suggest that subtle variation in the regulation of gene expression may contribute to complex human traits. In two reports,1,2 Cheung and colleagues scale up human genetics analysis to an impressive level in a genome‐wide search for the regulators of gene expression. They perform linkage analysis on expression profiles (...) for over 3,500 genes and then employ the HapMap resource3 to take positive findings through to association studies at the genome‐wide level. This work gives new insights into the complexities of gene regulation and the plausibility of genome‐wide study design. BioEssays 28: 968–972, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional (...) significance. The so‐called “ectopic” expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by‐product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities. BioEssays 27:592–601, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

A key characteristic of an animal's nervous system is that it can respond to brief environmental stimuli with lasting changes in its structure and function. These changes are triggered by specific patterns of neuronal electrical activity and are manifested as changes in the strength and patterns of synaptic connectivity between activated neurons. The biochemical mechanisms that control these changes are unclear, but cytoplasmic rises in Ca2+ levels may play a critical role, especially in regulating neuronal gene expression for making (...) activity‐induced synaptic changes permanent. Recently, two reports have explored the spatial features by which activity‐induced rises in Ca2+ levels activate transcription factors and gene expression(1,2). The reports suggest that Ca2+ influx acts both locally at the synapse and distantly within the nucleus to regulate transcription factors and gene expression. The results also show that regulatory elements within genes can respond differentially, depending on spatial differences in intracellular Ca2+ rises. These reports suggest new spatial mechanisms by which Ca2+‐dependent gene expression could contribute to activity‐dependent synaptic changes. (shrink)

Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its (...) regulation. Dissection of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)

The tenascins are a growing family of extracellular matrix proteins of typical multidomain structure. The prototype to be discovered was tenascin‐C. It shows a highly regulated expression pattern during embryonic development and is often transiently associated with morphogenetic tissue interactions during organogenesis. In the adult organism reexpression of tenascin‐C occurs in tumors and many other pathological conditions. Tenascin‐C expression can be regulated by many different growth factors and hormones. Furthermore, mechanical strain exerted by fibroblasts seems to induce the (...) expression of tenascin‐C. This could represent a mechanism of translating mechanical forces into protein patterns, a step of potential relevance in the organization of embryogenesis. Tenascin‐C as well as tenascin‐R are believed to counteract the cell adhesion and spreading activity of fibronectin, thereby facilitating cell movement. (shrink)

A gene's “expression profile” denotes the number of transcripts present relative to all other transcripts. The overall rate of transcript production is determined by transcription and RNA processing rates. While the speed of elongating RNA polymerase II has been characterized for many different genes and organisms, gene‐architectural features – primarily the number and length of exons and introns – have recently emerged as important regulatory players. Several new studies indicate that rapidly cycling cells constrain gene‐architecture toward short genes with (...) a few introns, allowing efficient expression during short cell cycles. In contrast, longer genes with long introns exhibit delayed expression, which can serve as timing mechanisms for patterning processes. These findings indicate that cell cycle constraints drive the evolution of gene‐architecture and shape the transcriptome of a given cell type. Furthermore, a tendency for short genes to be evolutionarily young hints at links between cellular constraints and the evolution of animal ontogeny. (shrink)

The term functional domain is often used to describe the region containing the cis acting sequences that regulate a gene locus. “Strong” domain models propose that the domain is a spatially isolated entity consisting of a region of extended accessible chromatin bordered by insulators that have evolved to act as functional boundaries. However, the observation that independently regulated loci can overlap partially or completely raises questions about functional requirements for physically isolated domain structures. An alternative model, the “weak” domain model, (...) proposes that domain structure is determined by the distribution of binding sites for positively acting factors, without a requirement for functional boundaries. The domain would effectively be the region that contains these factor-binding sites. Specificity of promoter-enhancer interactions would play a major role in maintaining the functional autonomy of adjacent genes. Sequences that interfere with these interactions (frequently characterised as insulators) would be selected against if they occurred within the domain but not at the edges, or in the interdomain regions. As a result, insulators would often be found near the borders of domains without necessarily being selected to act as boundaries. BioEssays 22:657–665, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Zeins are a group of alcohol‐soluble proteins that are synthesized in the endosperm of developing maize seeds. These proteins are encoded by a large number of genes located on several chromosomes; based upon the number of mutants that have been isolated, zein gene regulation is complex. Comparisons of gene flanking regions reveal conserved sequences that may be important for their regulation. Studies of transformed plant tissues support the assertion that cis‐acting elements with the 5′ flanking regions of zein (...) genes are required for accurate transcription. Although the genes are transcribed in transgenic tobacco and petunia plants, they are not properly regulated. This appears to be due to transcriptional effects rather than protein or mRNA instability. (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)

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels in (...) the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

The explosion in sequencing technologies has provided us with an instrument to describe mammalian transcriptomes at unprecedented depths. This has revealed that alternative splicing is used extensively not only to generate protein diversity, but also as a means to regulate gene expression post‐transcriptionally. Intron retention (IR) is overwhelmingly perceived as an aberrant splicing event with little or no functional consequence. However, recent work has now shown that IR is used to regulate a specific differentiation event within the haematopoietic system (...) by coupling it to nonsense‐mediated mRNA decay (NMD). Here, we highlight how IR and, more broadly, alternative splicing coupled to NMD (AS‐NMD) can be used to regulate gene expression and how this is deregulated in disease. We suggest that the importance of AS‐NMD is not restricted to the haematopoietic system but that it plays a prominent role in other normal and aberrant biological settings. (shrink)

In our everyday interaction with the environment, we often perceive objects and spaces as opportunities to feel, maintain, enhance, and change our affective states and processes. The concept of affective affordance was coined to accommodate this aspect of ordinary perception and the many ways in which we rely on the material environment to regulate our emotions. One natural way to think of affective affordances in emotion regulation is to interpret them as tools for regulating felt affective states. We argue (...) that this way of conceiving of affective affordances is too restrictive. By analyzing the role of expressive properties of objects and spaces in emotion regulation, we show that our environment does not need to elicit felt affective states to regulate our emotions. Thus, we revise the concept of affective affordance to accommodate these cases. This revised concept explains more with less. Hence, it should be preferred in wide-reaching philosophical projects that aim to explain human affectivity as a situated phenomenon. (shrink)

Depression is a disorder of impaired emotion regulation. Consequently, examining individual differences in the habitual use of emotion-regulation strategies has considerable potential to inform models of this debilitating disorder. The aim of the current study was to identify cognitive processes that may be associated with the use of emotion-regulation strategies and to elucidate their relation to depression. Depression has been found to be associated with difficulties in cognitive control and, more specifically, with difficulties inhibiting the processing of (...) negative material. We used a negative affective priming task to assess the relations among inhibition and individual differences in the habitual use of rumination, reappraisal, and expressive suppression in clinically depressed, formerly depressed, and never-depressed participants. We found that depressed participants exhibited the predicted lack of inhibition when processing negative material. Moreover, within the group of depressed participants, reduced inhibition of negative material was associated with greater rumination. Across the entire sample, reduced inhibition of negative material was related to less use of reappraisal and more use of expressive suppression. Finally, within the formerly depressed group, less use of reappraisal, more use of rumination, and greater expressive suppression were related to higher levels of depressive symptoms. These findings suggest that individual differences in the use of emotion-regulation strategies play an important role in depression, and that deficits in cognitive control are related to the use of maladaptive emotion-regulation strategies in this disorder. (shrink)

Mechanisms involved in the regulation of development and its genetic control are receiving ever‐increasing attention in studies of mammalian developmental genetics. The potential success of such studies is strongly enhanced by the availability of suitable systems of analysis. Such a system was identified in a series of radiation‐induced chromosomal deletions at and around the albino (c) locus of the mouse associated with cell type‐specific effects on liver differentiation. Their detailed study has aided the analysis of possible machanisms of cell (...) type‐specific gene expression. As summarized in this review, the experimental results strongly suggest that specific trans‐acting developmental regulatory genes are concerned with the differentiation of hormone‐inducible expression of a cluster of hepatocyte specific structural genes mapping in different parts of the genome. (shrink)

Fundamental problems in developmental biology, such as the generation of asymmetry, differential transcription, and the execution of positional information, are all exhibited by a prokaryotic system, the Caulobacter cell cycle. Progeny cells resulting from each cell division have different developmental programs with respect to patterns of transcription and the initiation of DNA replication. The binary fission that yields dissimilar progeny results from asymmetry generated in the parent cell. An aspect of this fundamental developmental event is the temporally‐controlled biogenesis of a (...) polar flagellum. Several flagellar promoters require the histone‐like protein, integration host factor (IHF) for transcription activation. IHF introduces bends in DNA resulting in the reorganization of the higher‐order structure of the promoter region. These promoters appear to be transcribed from the chromosome in the swarmer pole of the predivisional cell. The newly replicated chromosomes in the predivisional cell differ in sedimentation coefficient and in the ability to initiate replication in the progeny cell. We hypothesize that the differential higher order structure of the two chromosomes contributes to both replication potential and transcription specificity. (shrink)

How should we regulate genome editing in the face of persistent substantive disagreement about the moral status of this technology and its applications? In this paper, we aim to contribute to resolving this question. We first present two diametrically opposed possible approaches to the regulation of genome editing. A first approach, which we refer to as “elitist,” is inspired by Joshua Greene’s work in moral psychology. It aims to derive at an abstract theoretical level what preferences people would have (...) if they were committed to implementing public policies regulating genome editing in a context of ethical pluralism. The second approach, which we refer to as the democratic approach, defended by Francoise Baylis and Sheila Jasanoff et al., emphasizes the importance of including the public’s expressed attitudes in the regulation of genome editing. After pointing out a serious shortcoming with each of these approaches, we propose our own favored approach—the “enlightened democracy” approach—which attempts to combine the strengths of the elitist and democratic approaches while avoiding their weaknesses. (shrink)

The transcriptional profile of the entire Caulobacter crescentus genome over a synchronous cell cycle was recently described.(1) The analysis reveals a stunning 553 cell-cycle-regulated genes or orfs, nearly 19% of the genome, including putative functions in virtually all biological activities. Over a quarter of these genes/orfs respond to the Caulobacter master regulator, CtrA, most of them apparently indirectly. The analysis confirms and extends earlier observations showing that many proteins involved in cell cycle functions are expressed at the cell age when (...) they are needed. Conversely, the data suggest that proteins specifically expressed at a particular age may be involved in a process taking place then. BioEssays 23:563–565, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

What are rules? In this paper I develop a view of regulative rules which takes them to be a distinctive normative kind occupying a middle ground between orders and normative truths. The paradigmatic cases of regulative rules that I’m interested in are social rules like rules of etiquette and legal rules like traffic rules. On the view I’ll propose, a rule is a general normative content that is in force due to human activity: enactment by an authority or acceptance by (...) a community. Rules are unlike orders in being not necessarily communicative, not an expression’s of the giver’s will, not evaluable for sincerity, and in that they have propositional content. And they’re unlike normative truths in that they’re themselves not even truth-evaluable (though their contents are). This is because rules qua things that are in force are not like constatives which have a mind to world direction of fit, but more like performatives. Furthermore, they differ from normative truths in that their normativity is isolated from their background justification and is therefore not dependent on contributory notions like reasons coming together in a weighing explanation. As such, they occupy a middle ground between orders and normative truths, much like in H. L. A. Hart’s opinion law occupies a middle ground between “coercion” and “morality” (Hart 1961/1994). I also illustrate the virtues of this understanding of rules by showing how proper appreciation of how they differ from normative truths helps us defuse a common objection to Hart’s practice theory of rules. (shrink)

This daily diary study examined the within-person coupling between four emotion regulation strategies and both subjective well-being and perceived stress in daily life of geriatric nurses. Participants ( N = 89) described how they regulated their emotions in terms of cognitive reappraisal and suppression. They also indicated their subjective well-being and level of perceived stress each day over 3 weeks. At the within-person level, cognitive reappraisal intended to increase positive emotions was positively associated with higher subjective well-being and negatively (...) associated with perceived stress. Suppression of the expression of positive emotions was negatively associated with subjective well-being and positively associated with perceived stress. However, cognitive reappraisal intended to down-regulate negative emotions and suppression as a strategy to inhibit the expression of negative emotions were not associated with daily well-being or perceived stress. Off-days were rated as days with higher subjective well-being and lower perceived stress in contrast to working days. At the between-person level, individuals who reported more daily negative affect reported increased suppression of positive emotions, corroborating the within-person findings. Moreover, findings indicated that nurses with more years of experience in the job reported higher subjective well-being and less perceived stress. These results provide insights into important daily emotional processes of geriatric nurses, both at workdays and in their leisure time. (shrink)

Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3′ untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for (...) their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms. BioEssays 24:119–129, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

In mice, dosage compensation of X‐linked gene expression is achieved through the inactivation of one of the two X‐chromosomes in XX female cells. The complex epigenetic process leading to X‐inactivation is largely controlled by Xist and Tsix, two non‐coding genes of opposing function. Xist RNA triggers X‐inactivation by coating the inactive X, while Tsix is critical for the designation of the active X‐chromosome through cis‐repression of Xist RNA accumulation. Recently, a plethora of trans‐acting factors and cis‐regulating elements have been (...) suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X‐linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. (shrink)

Mammalian oocytes exhibit a series of cell cycle transitions that coordinate the penultimate events of meiosis with the onset of embryogenesis at fertilization. The execution of these cell cycle transitions, at G2/M of meiosis‐I and metaphase/anaphase of meiosis I and II, involve both biosynthetic and post‐translational modifications that directly modulate centrosome and microtubule behavior. Specifically, somatic cells alter the signal transduction pathways in the oocyte and influence the expression of maturation promoting factor (MPF) and cytostatic factor (CSF) activity through (...) a microtubule‐dependent mechanism. The regulation of the oocytes' cell cycle machinery by hormone‐mediated somatic cell signals, involving both positive and negative stimuli, ensures that meiotic cell cycle progression is synchronized with the earliest pivotal events of mammalian reproduction. (shrink)

The form of higher plants is largely dependent upon cell division and expansion patterns. Taking a genetic approach, Takahashi et al.(1) have identified a regulatory molecule in Arabidopsis thaliana called DIMINUTO (DIM), which is involved in determining the degree and direction of plant cell expansion. Their extensive characterization of a dim mutant suggested a direct involvement of the DIM gene in regulating cell elongation, perhaps by modulating the expression of structural genes which determine the orientation and elasticity of the (...) cell wall. (shrink)

Pre‐existing but untranslated or ‘poised’ mRNA exists as a means to rapidly induce the production of specific proteins in response to stimuli and as a safeguard to limit the actions of these proteins. The translation of poised mRNA enables immune cells to express quickly genes that enhance immune responses. The molecular mechanisms that repress the translation of poised mRNA and, upon stimulation, enable translation have yet to be elucidated. They likely reflect intrinsic properties of the mRNAs and their interactions with (...) trans‐acting factors that direct poised mRNAs away from or into the ribosome. Here, I discuss mechanisms by which this might be regulated. (shrink)

Embryonic stem cells are derived from the preimplantation embryo and can differentiate into virtually any other cell type, which is governed by lineage specific transcriptions factors binding to cis regulatory elements to mediate changes in gene expression. The reliance on transcriptional regulation to maintain pluripotency makes ESCs a valuable model to study the role of distal CREs such as enhancers in modulating gene expression to affect cell fate decisions. This review will highlight recent advance on transcriptional enhancers, (...) focusing on studies performed in ESCs. In addition, we argue that the Nanog locus, which encodes for an ESC-critical TF, is particularly informative because it contains multiple co-regulated genes and enhancers in close proximity to one another. The unique landscape at Nanog permits the study of ongoing questions including whether multiple enhancers function additively versus synergistically, determinants of gene specificity, and cell-to-cell variability in gene expression. Nanog encodes a transcription factor required to maintain ESC pluripotency. The Nanog locus is an ideal model to study enhancers because it contains multiple highly potent super-enhancers within a small region. Nanog and three super-enhancers are in close physical proximity but only two SEs are required for Nanog expression. (shrink)

Dimorphism in the yeast Candida albicans provides an unusually simple model system for investigating the mechanisms which regulate cellular differentiation, or cell divergence. Under the regime of pH‐regulated dimorphism, it has been demonstrated that the programs of protein synthesis accompanying bud and hypha formation are strikingly similar. Instead of dramatic differences in the repertoire of gene products possessed by bud‐ and hypha‐forming cells, subtle temporal, spatial and quantitative differences in the same architectural events appear to be basic to the genesis (...) of alternative phenotypes. This emerging story of phenotypic regulation does not exclude differential gene expression, but rather de‐emphasizes its role and underscores other mechanisms which are not generally considered. (shrink)

Emotions are foremost self-regulating processes that permit rapid responses and adaptations to situations of personal concern. They have biological bases and are shaped ontogenetically via learning and experience. Many situations and events of personal concern are social in nature. Thus, social exchanges play an important role in learning about rules and norms that shape regulation processes. I argue that (a) emotions often are actively auto-regulating—the behavior implied by the emotional reaction bias to the eliciting event or situation modifies or (...) terminates the situation; (b) certain emotion components are likely to habituate dynamically, modifying the emotional states; (c) emotions are typically intra- and interpersonal processes at the same time, and modulating forces at these different levels interact; (d) emotions are not just regulated—they regulate. Important conclusions of my arguments are that the scientific analysis of emotion should not exclude regulatory processes, and that effortful emotion regulation should be seen relative to a backdrop of auto-regulation and habituation, and not the ideal notion of a neutral baseline. For all practical purposes unregulated emotion is not a realistic concept. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

The study of Attention Deficit Hyperactivity Disorder addresses variables related to three core symptoms: inattention, hyperactivity, and impulsivity. However, it has been suggested that in recent years emotional difficulties and subsequent social challenges have not received sufficient attention. This study had two objectives: 1) to compare the performance of participants (age range: 8-14 years) on facial emotion recognition tasks using the Affect Recognition subtest of the Children Neuropsychological Battery II; and 2) to assess the perceptions of family members in relation (...) to variables associated with emotional problems, difficulty in regulating emotions, and anger management using the Spanish Assessment System for Children and Adolescents. Assessments were conducted before and after applying an emotion regulation intervention designed for this study. Following the intervention, there was a significant decrease in scores associated with emotional regulation, and an improvement in the identification of affect on facial recognition tasks. The results suggest that despite Attention Deficit Hyperactivity Disorder children and adolescents having social and emotional deficits secondary to the core symptom triad, emotional regulation in this group can be improved by the application of socio-emotional intervention programs. (shrink)

Introduction of human plasma protein genes into the mouse genome to produce transgenic mice furnishes an in vivo model for correlating chromosomal DNA sequences with developmental and tissue‐specific expression. The liver produces an array of plasma proteins that circulate throughout the body contributing to homeostasis. Non‐hepatic tissue sites of synthesis have been identified where a local provision of plasma proteins in needed. Analysis of expression of human plasma protein genes in ageing transgenic mice appears especialy promising in identifying (...) DNA sequences that respond to environmental adversities such as inflammatory factors, hormonal changes and metal toxicity. The results indicate that human genes encoding and controlling liver plasma proteins serve as useful models for studying genetic regulation in the background of development and ageing. (shrink)