Cyclin‐dependent kinases are Ser/Thr protein kinases best known for their cell cycle roles, where CDK1 triggers mitotic onset in all eukaryotes. CDKs are also involved in various other cellular processes, some of which, such as transcription and centrosome duplication, are coupled to cell cycle progression. A new study suggests that the mitotic CDK network is active at low levels in non‐dividing, differentiating precursors of multiciliated cells, and that it drives ciliogenesis. Manipulating the activity of CDK1 or PLK1 altered transitions between (...) the amplification, growth, and disengagement phases, in a manner analogous to the control of passage through different phases of mitosis. How the dynamics of the mitotic kinase network are controlled in these post‐mitotic cells, and whether other cell cycle regulators are also involved, remains unknown. In the present mini‐review we suggest that the redeployment of cell cycle regulators to control steps of differentiation in non‐dividing cells might be a more general, hitherto under‐recognized, feature of cell regulation. (shrink)

Behrendt & Young (B&Y) propose a useful theoretical framework for the study of processes underlying perception and hallucinations. It focuses on gamma oscillations in thalamocortical networks and the role of the reticular thalamic nucleus in modulating these oscillations. I suggest that their theoretical model might also be applied to the investigation of temporal encoding deficits in disorders such as dyslexia. I further suggest, however, that a role for slower rhythms, such as theta, might also be considered when investigating perceptual experience.

Transcription factor binding sites (TFBSs) on the DNA are generally accepted as the key nodes of gene control. However, the multitudes of TFBSs identified in genome‐wide studies, some of them seemingly unconstrained in evolution, have prompted the view that in many cases TF binding may serve no biological function. Yet, insights from transcriptional biochemistry, population genetics and functional genomics suggest that rather than segregating into ‘functional’ or ‘non‐functional’, TFBS inputs to their target genes may be generally cumulative, with varying (...) degrees of potency and redundancy. As TFBS redundancy can be diminished by mutations and environmental stress, some of the apparently ‘spurious’ sites may turn out to be important for maintaining adequate transcriptional regulation under these conditions. This has significant implications for interpreting the phenotypic effects of TFBS mutations, particularly in the context of genome‐wide association studies for complex traits. (shrink)

Relativistic geometrical action for a quantum particle in the superspace is analyzed from theoretical group point of view. To this end an alternative technique of quantization outlined by the authors in a previous work and that is based in the correct interpretation of the square root Hamiltonian, is used. The obtained spectrum of physical states and the Fock construction consist of Squeezed States which correspond to the representations with the lowest weights $\lambda=\frac{1}{4}$ and $\lambda=\frac{3}{4}$ with four possible (non-trivial) fractional representations (...) for the group decomposition of the spin structure. From the theory of semigroups the analytical representation of the radical operator in the superspace is constructed, the conserved currents are computed and a new relativistic wave equation is proposed and explicitly solved for the time-dependent case. The relation with the Relativistic Schrödinger equation and the Time-dependent Harmonic Oscillator is analyzed and discussed. (shrink)

The effects of the vacuum electromagnetic fluctuations and the radiation reaction fields on the time development of a simple microscopic system are identified using a new mathematical method. This is done by studying a charged mechanical oscillator (frequency Ω 0)within the realm of stochastic electrodynamics, where the vacuum plays the role of an energy reservoir. According to our approach, which may be regarded as a simple mathematical exercise, we show how the oscillator Liouville equation is transformed into a (...) Schrödinger-like stochastic equation with a free parameter h′ with dimensions of action. The role of the physical Planck's constant h is introduced only through the zero-point vacuum electromagnetic fields. The perturbative and the exact solutions of the stochastic Schrödinger-like equation are presented for h′>0. The exact solutions for which h′<h are called sub-Heisenberg states. These nonperturbative solutions appear in the form of Gaussian, non-Heisenberg states for which the initial classical uncertainty relation takes the form 〈(δx 2)〉〈(δp) 2 〉=(h′/2) 2,which includes the limit of zero indeterminacy (h → 0). We show how the radiation reaction and the vacuum fields govern the evolution of these non-Heisenberg states in phase space, guaranteeing their decay to the stationary state with average energy hΩ 0 /2 and 〈(δx) 2 〉〈(δp) 2 〉=h 2 /4 at zero temperature. Environmental and thermal effects-are briefly discussed and the connection with similar works within the realm of quantum electrodynamics is also presented. We suggest some other applications of the classical non-Heisenberg states introduced in this paper and we also indicate experiments which might give concrete evidence of these states. (shrink)

The effects of the vacuum electromagnetic fluctuations and the radiation reaction fields on the time development of a simple microscopic system are identified using a new mathematical method. This is done by studying a charged mechanical oscillator (frequency Ω 0)within the realm of stochastic electrodynamics, where the vacuum plays the role of an energy reservoir. According to our approach, which may be regarded as a simple mathematical exercise, we show how the oscillator Liouville equation is transformed into a (...) Schrödinger-like stochastic equation with a free parameter h′ with dimensions of action. The role of the physical Planck's constant h is introduced only through the zero-point vacuum electromagnetic fields. The perturbative and the exact solutions of the stochastic Schrödinger-like equation are presented for h′>0. The exact solutions for which h′shrink)

Relativistic geometrical action for a quantum particle in the superspace is analyzed from theoretical group point of view. To this end an alternative technique of quantization outlined by the authors in a previous work and, that is, based in the correct interpretation of the square root Hamiltonian, is used. The obtained spectrum of physical states and the Fock construction consist of Squeezed States which correspond to the representations with the lowest weights \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} (...) \begin{document}$${\lambda=\frac{1}{4}}$$\end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\frac{3}{4}}$$\end{document} with four possible fractional representations for the group decomposition of the spin structure. From the theory of semi-groups the analytical representation of the radical operator in the superspace is constructed, the conserved currents are computed and a new relativistic wave equation is proposed and explicitly solved for the time dependent case. The relation with the Relativistic Schrödinger equation and the Time-dependent Harmonic Oscillator is analyzed and discussed. (shrink)

A recently proposed approach to relativistic quantum mechanics is applied to the problem of a particle in a quadratic potential. The methods, both exact and approximate, allow one to obtain eigenstate energy levels and wavefunctions, using conventional numerical eigensolvers applied to Schrödinger-like equations. Results are obtained over a nine-order-of-magnitude variation of system parameters, ranging from the non-relativistic to the ultrarelativistic limits. Various trends are analyzed and discussed—some of which might have been easily predicted, others which may be a bit more (...) surprising. (shrink)

The physical meaning of the particularly simple non-degenerate supermetric, introduced in the previous part by the authors, is elucidated and the possible connection with processes of topological origin in high energy physics is analyzed and discussed. New possible mechanism of the localization of the fields in a particular sector of the supermanifold is proposed and the similarity and differences with a 5-dimensional warped model are shown. The relation with gauge theories of supergravity based in the OSP(1/4) group is explicitly given (...) and the possible original action is presented. We also show that in this non-degenerate super-model the physic states, in contrast with the basic states, are observables and can be interpreted as tomographic projections or generalized representations of operators belonging to the metaplectic group Mp(2). The advantage of geometrical formulations based on non-degenerate super-manifolds over degenerate ones is pointed out and the description and the analysis of some interesting aspects of the simplest Riemannian superspaces are presented from the point of view of the possible vacuum solutions. (shrink)

We explore the contribution made by oscillatory, synchronous neural activity to representation in the brain. We closely examine six prominent examples of brain function in which neural oscillations play a central role, and identify two levels of involvement that these oscillations take in the emergence of representations: enabling (when oscillations help to establish a communication channel between sender and receiver, or are causally involved in triggering a representation) and properly representational (when oscillations are a constitutive part of the representation). We (...) show that even an idealized informational sender–receiver account of representation makes the representational status of oscillations a non-trivial matter, which depends on rather minute empirical details. (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)

Approaches to induce tumor differentiation often result in manageable and therapy‐naïve cellular states in cancer cells. This transformation is achieved by activating pathways that drive tumor cells away from plasticity, a state that commonly correlates with enhanced aggression, metastasis and resistance to therapy. Here, we discuss signaling pathways, epigenetics and non‐coding RNAs as three main regulatory levels with the potential to drive tumor differentiation and hence as potential targets in differentiation therapy approaches. The success of an effective therapeutic regimen in (...) one cancer, however, does not necessarily sustain across cancer types; a phenomenon largely resulting from heterogeneity in the genetic and physiological landscapes of tumor types necessitating an approach designed for each cancer's unique genetic and phenotypic build‐up. (shrink)

I look at the ‘flavour-oscillation clocks’ proposed by D. V. Ahluwalia and two of his arguments suggesting that such clocks might behave in a way that threatens the geometricity of general relativity (GR). The first argument states that the behaviour of these clocks in the vicinity of a rotating gravitational source implies a non-geometrical element of gravity. I argue that the phenomenon is best seen as an instance of violation of the ‘clock hypothesis’ and therefore does not threaten the geometrical (...) nature of gravitation. Ahluwalia’s second argument, for the ‘incompleteness’ of general relativity, involves the idea that flavour-oscillation clocks can detect constant gravitational potentials. I argue that the purported ‘incompleteness-establishing’ result is in fact one that applies to all clocks. It is entirely derivable from general relativity, does not result in the observability of the potential, and is not at odds with any of general relativity’s foundations. (shrink)

Numerous accessory factors modulate RNA polymerase response to regulatory signals and cellular cues and establish communications with co‐transcriptional RNA processing. Transcription regulators are astonishingly diverse, with similar mechanisms arising via convergent evolution. NusG/Spt5 elongation factors comprise the only universally conserved and ancient family of regulators. They bind to the conserved clamp helices domain of RNA polymerase, which also interacts with non‐homologous initiation factors in all domains of life, and reach across the DNA channel to form processivity clamps that enable (...) uninterrupted RNA chain synthesis. In addition to this ubiquitous function, NusG homologs exert diverse, and sometimes opposite, effects on gene expression by competing with each other and other regulators for binding to the clamp helices and by recruiting auxiliary factors that facilitate termination, antitermination, splicing, translation, etc. This surprisingly diverse range of activities and the underlying unprecedented structural changes make studies of these “transformer” proteins both challenging and rewarding. (shrink)

Homeotic genes are subject to transcriptional silencing, which prevents their expression in inappropriate body regions. Here, we shall focus on Drosophila, as little is known about this process in other organisms. Evidence is accumulating that silencing of Drosophila homeotic genes is conferred by two types of cis‐regulatory sequences: initiation (SIL‐I) and maintenance (SIL‐M) elements. The former contain target sites for transient repressors with a highly localised distribution in the early embryo and the latter for constitutive repressors that are likely (...) to be present in all cells. We discuss how SIL‐I elements may cooperate with SIL‐M elements to promote formation of a silencing complex. We propose that this complex consists of specific non‐histone proteins, the so‐called Polycomb group proteins, and that it is anchored at SIL‐M elements and at the promoter. (shrink)

Transcription factors (TFs) have to find their binding sites, which are distributed throughout the genome. Facilitated diffusion is currently the most widely accepted model for this search process. Based on this model the TF alternates between one‐dimensional sliding along the DNA, and three‐dimensional bulk diffusion. In this view, the non‐specific associations between the proteins and the DNA play a major role in the search dynamics. However, little is known about how the DNA properties around the motif contribute to the search. (...) Accumulating evidence showing that TF binding sites are embedded within a unique environment, specific to each TF, leads to the hypothesis that the search process is facilitated by favorable DNA features that help to improve the search efficiency. Here, we review the field and present the hypothesis that TF‐DNA recognition is dictated not only by the motif, but is also influenced by the environment in which the motif resides. (shrink)

Two mechanisms are available for the repair of DNA double‐strand breaks (DSBs) in eukaryotic cells: homology directed repair (HDR) and non‐homologous end‐joining (NHEJ). While NHEJ is not restricted to a particular phase of the cell cycle, it is incapable of accurately repairing DBSs that have suffered a loss or gain of nucleotide sequence information. In contrast, HDR achieves accurate repair of such DSBs by use of a sister chromatid as a DNA template, but is restricted to cell cycle phases (S/G2) (...) when such templates are available. In this scheme, G1 cells appear to lack a mechanism for the accurate repair of certain DSBs, and an ability to use alternative templates would be highly advantageous. Considered here, therefore, is the possibility that RNA transcripts are used as templates for HDR. Potential mechanisms for transcript‐templated HDR, and ways in which it might be detected, are presented. BioEssays 28:78–83, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

Non‐genetic forms of antimicrobial (drug) resistance can result from cell‐to‐cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non‐genetic mechanisms can facilitate the development of genetic drug resistance. We speculate on how the interplay between non‐genetic and genetic mechanisms may affect microbial adaptation and evolution during drug treatment. We argue that cellular heterogeneity arising from fluctuations in gene expression, epigenetic modifications, as well as genetic changes contribute to drug resistance at different timescales, (...) and that the interplay between these mechanisms enhance pathogen resistance. Accordingly, developing a better understanding of the role of non‐genetic mechanisms in drug resistance and how they interact with genetic mechanisms will enhance our ability to combat antimicrobial resistance. Also see the video abstract here: https://youtu.be/aefGpdh-bgU. (shrink)

Two groups of plant viruses have DNA in their genomes. One group, the caulimoviruses, are non‐integrating retroviruses that package dsDNA in virions. The other group, the geminiviruses, package small circular ssDNA and include the only DNA viruses known with bipartite genomes. The regulation of transcription of these viruses is not well characterized, but recent work is beginning to yield interesting results. Regulatory sequences from these viruses function in cells of species that are not hosts of the virus and are finding (...) use in constitutive expression of chimeric genes in transformed plants. Development of vectors based on plant viruses requires further characterization at the molecular level of viral life cycles. (shrink)

High-frequency oscillations (HFO) are a promising biomarker for the identification of epileptogenic tissue. While HFO rates have been shown to predict seizure outcome, it is not yet clear whether their morphological features might improve this prediction. We validated HFO rates against seizure outcome and delineated the distribution of HFO morphological features. We collected stereo-EEG recordings from 20 patients (231 electrodes; 1,943 contacts). We computed HFO rates (the co-occurrence of ripples and fast ripples) through a validated automated detector during non-rapid eye (...) movement sleep. Applying machine learning, we delineated HFO morphological features within and outside epileptogenic tissue across mesial temporal lobe (MTL) and Neocortex. HFO rates predicted seizure outcome with 85% accuracy, 79% specificity, 100% sensitivity, 100% negative predictive value, and 67% positive predictive value. The analysis of HFO features showed larger amplitude in the epileptogenic tissue, similar morphology for epileptogenic HFO in MTL and Neocortex, and larger amplitude for physiological HFO in MTL. We confirmed HFO rates as a reliable biomarker for epilepsy surgery and characterized the potential clinical relevance of HFO morphological features. Our results support the prospective use of HFO in epilepsy surgery and contribute to the anatomical mapping of HFO morphology. (shrink)

The resting-state human electroencephalogram power spectrum is dominated by alpha and theta oscillations, and also includes non-oscillatory broadband activity inversely related to frequency. Gratton proposed that alpha and theta oscillations are both related to cognitive control function, though in a complementary manner. Alpha activity is hypothesized to facilitate the maintenance of representations, such as task sets in preparation for expected task conditions. In contrast, theta activity would facilitate changes in representations, such as the updating of task sets in response to (...) unpredicted task demands. Therefore, theta should be related to reactive control, while alpha may be more relevant to proactive control. Less is known about the possible relationship between 1/f activity and cognitive control, which was analyzed here in an exploratory fashion. To investigate these hypothesized relationships, we recorded eyes-open and eyes-closed resting-state EEG from younger and older adults and subsequently tested their performance on a cued flanker task, expected to elicit both proactive and reactive control processes. Results showed that alpha power and 1/f offset were smaller in older than younger adults, whereas theta power did not show age-related reductions. Resting alpha power and 1/f offset were associated with proactive control processes, whereas theta power was related to reactive control as measured by the cued flanker task. All associations were present over and above the effect of age, suggesting that these resting-state EEG correlates could be indicative of trait-like individual differences in cognitive control performance, which may be already evident in younger adults, and are still similarly present in healthy older adults. (shrink)

Metazoan genomes contain thousands of protein‐coding and non‐coding RNA genes, most of which are differentially expressed, i.e., at different locations, at different times during development, or in response to environmental signals. Differential gene expression is achieved through complex regulatory networks that are controlled in part by two types of trans‐regulators: transcription factors (TFs) and microRNAs (miRNAs). TFs bind to cis‐regulatory DNA elements that are often located in or near their target genes, while miRNAs hybridize to cis‐regulatory RNA elements mostly located (...) in the 3′ untranslated region of their target mRNAs. Here, we describe how these trans‐regulators interact with each other in the context of gene regulatory networks to coordinate gene expression at the genome‐scale level, and discuss future challenges of integrating these networks with other types of functional networks. (shrink)

Significant strides have been made in recent years towards understanding the molecular basis of cell cycle progression in the model bacterium Caulobacter crescentus. At the heart of cell cycle regulation is a multicomponent transcriptional feedback loop, governing the production of successive regulatory waves or pulses of at least three master regulatory proteins. These oscillating master regulators direct the execution of phase‐specific events and, importantly, through intrinsic genetic switches not only determine the length of a given phase, but also provide (...) the driving force that catapults the cell into the next stage of the cell cycle. The genetic switches act as fail safe mechanisms that prevent the cell cycle from relapsing and thus govern the ordered production and the periodicity of these regulatory waves. Here, we detail how the master regulators CtrA, GcrA and DnaA coordinate cell cycle progression and polar development in Caulobacter. BioEssays 28: 355–361, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Non‐coding centromeres, which dictate kinetochore formation for proper chromosome segregation, are extremely divergent in DNA sequences across species but are under active transcription carried out by RNA polymerase (RNAP) II. The RNAP II‐mediated centromeric transcription has been shown to facilitate the deposition of the centromere protein A (CENP‐A) to centromeres, establishing a conserved and critical role of centromeric transcription in centromere maintenance. Our recent work revealed another role of centromeric transcription in chromosome segregation: maintaining centromeric cohesion during mitosis. Interestingly, this (...) role appears to be fulfilled through ongoing centromeric transcription rather than centromeric transcripts. In addition, we found that centromeric transcription may not require some of the traditional transcription initiation factors, suggestive of “uniqueness” in its regulation. In this review, we discuss the novel role and regulation of centromeric transcription as well as the potential underlying mechanisms. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:GAUGUIN: THE OSCILLATING STRUCTURE OF DISGUISE Ralph Hajj University ofMontreal In this essay we will examine Gauguin's self-portraits as ritualistic activity. Through them we will attempt to determine the formal and iconographical consequences ofhis extensive use ofdisguise and how this use can illuminate the nature ofart in general. The ritualistic function of disguise Within the framework ofa given social order, disguise functions as a ritualistic activity. Ritual is aframed (...) event where concepts—which in a non-ritualistic context are strictly differentiated and which take their meaning from this very differentiation—become undifferentiated.In Violence andthe Sacred, René Girard studied the function ofmask in ritual activity: he concluded that within the function of ritual, which is to reinforce the cultural differentiation through a repetition of its undifferentiated origins, the mask introduces undifferentiation between the self, (the human being wearing the mask), and the other (who or what the mask represents): Masks stand at that equivocal frontier between the human and the "divine," between a differentiated order in the process of disintegration and its final undifferentiated state—the point where all differences, all monstrosities are concentrated, and from which a new order will emerge. There is no point in trying to determine the "nature" ofmasks, because it is in their nature not to have a nature but to encompass all natures. (168). Disguise as a form of ritual activity is the representation of undifferentiation or non-representability. It is then a fundamentally paradoxical 168Ralph Hajj activity; an actofundifferentiating which has its condition ofpossibility in differentiated meaning. In turn differentiated meaning has its condition of possibility in a transcendental undifferentiation which the disguise represents. The mutual determination of the two, the totality of meaning and its negation, which is the condition ofpossibility ofmeaning as such, is represented through disguise both as a synchronic state and as a diachronic process. Thus, disguise is one of the forms of synchronic condensation leading to diachronic oscillation. This structure/process of condensation/oscillation is posited here as the universal underlying principle ofritual and in extension ofart in general. The structure/process of condensations/oscillations are seen most clearly in Gauguin's letters and the self-representations put forward inthem where he liked to call himselfa "savage." It is also seen in his self-portraits of 1888-1890, were he alternatively disguises himself as Jean Valjean, as Jesus Christ, and as a Breton priest, among other roles. A study of the paintings were these disguises occur will allow us to make the connection between his self-representation, as seen through his letters, and its consequences on the formal and iconographical level of these and other paintings. This in turn, will allow us to see how the structure/process of condensation/oscillation affects the form and iconography ofhis two most complex works; La Vision après le sermon [Fig. 1], and Van Goghpeignant des tournesols [Fig. 2], both ofwhich were painted in 1888. This choice of paintings will allow us to examine some fundamental generative aspects of Paul Gauguin's work during that period. Self-Portraits as tropes In 1888 Van Gogh, who was interested in creating a colony ofartists, and as a means ofpreserving his ties with the painters ofPont-Aven whom he considered as likely candidates, wanted to exchange his self-portrait with a portrait painted by Paul Gauguin representing Émile Bernard and one by Gauguin representing Bernard (Sugana 94). Gauguin, who had trouble painting Bernard (Correspondence No. 165, 230), painted a selfportrait instead with an outline of Bernard's profile on the background, entitling it Les Misérables [Fig.3] after Victor Hugo's novel. Simultaneously, Bernard painted a self-portrait with Gauguin's profile. Gauguin'sLesMisérables [Fig. 3] is typical ofhis self-portraits, where he is usually disguised, in this case as Jean Valjean. The picture shows Gauguin looking straight at the viewer, his prominent arced nose—which he considered as a sign ofhis "primitive" origins—emphasized. The Gauguin: The Oscillating Structure ofDisguise171 background is painted yellow with decorative designs vaguely reminiscent ofPersian carpets, exceptforagreen areaonthetop rightofthe canvasthat contains a linear portrait of Emile Bernard. In a letter written to Shuffenecker in October 1888, he describesthispaintingand its intentions:...I did a portrait... (shrink)

En 1893, « physicien-ingénieur » André Blondel invente l’oscillographe bifilaire permettant de visualiser les tensions et courants variables. À l’aide de ce puissant moyen d’investigation, il entreprend tout d’abord l’étude des phénomènes de l’arc électrique alors utilisé pour l’éclairage côtier et urbain puis de l’arc chantant employé comme émetteur d’ondes radioélectriques en T.S.F. En 1905, il met en évidence un nouveau type d’oscillations non-sinusoïdales au sein de l’arc chantant. Vingt ans plus tard, Balthasar Van der Pol reconnaitra qu’il s’agissait en (...) réalité d’oscillations de relaxation. Pour expliquer ce phénomène, il fait appel à une representation dans le plan de phase et montre que son évolution prend la forme de petits cycles. Pendant le premier conflit mondial la triode remplace peu à peu l’arc chantant dans les systèmes de transmission. Au sortir de la guerre, Blondel transpose à la triode la plupart de ses résultats par analogie avec l’arc chantant. En avril 1919, il publie un long mémoire dans lequel il introduit la terminologie « oscillations auto- entretenues » et propose d’illustrer ce concept à partir de l’exemple du vase de Tantale qui sera ensuite repris par Van der Pol et par Philippe Le Corbeiller. Il fournit alors une définition d’un système auto-entretenu assez proche de celles qui seront données par la suite par Aleksandr’ Andronov et Van der Pol. Pour étudier la stabilité des oscillations entretenues par la triode et par l’arc chantant il utilise cette fois une représentation dans le plan complexe et explicite l’amplitude en coordonnées polaires. Il justifie alors l’entretien des oscillations par l’existence de cycles qui présentent presque toutes les caractéristiques des cycles limites de Poincaré. Enfin, en novembre 1919, Blondel réalise, un an avant Van der Pol, la mise en équation des oscillations d’une triode. En mars 1926, Blondel établit l’équation différentielle caractérisant les oscillations de l’arc chantant, en tous points similaire à celle qu’obtient concomitamment Van der Pol pour la triode. Ainsi, tout au long de sa carrière, Blondel, a apporté une contribution fondamentale et relativement méconnue à l’élaboration de la théorie des oscillations non linéaires. L’objet de cet article est donc d’analyser ses principaux travaux dans ce domaine et de mesurer leur importance, voire leur influence en les replaçant dans la perspective du développement de cette théorie. (shrink)

This commentary addresses the complexities of representation in sociolinguistic transcripts, considering the meaning potentials of different representational choices at the level of both ideology and identity. It considers the kinds of authenticity and evidence that are indexed by simplified versus more detailed transcripts, suggesting that a simplified transcript may give more direct access to elements of the original speaker's voice. Second, it discusses the role of transcripts as scholarly texts, and questions their use as sociolinguistic records suitable for reinterpretation by (...) scholars who do not have access to the original recordings. Third, it emphasizes that the use of non-standard orthographies is an unreliable source of data on sociolinguistic variation, because few authors use non-standard forms in consistent and principled ways. Fourth, it proposes that translations may take different forms depending on whether they are efforts to be `faithful' to `authentic' speech in the target versus the source language. Finally, it reflects on the act of transcription as part of professional practice and identity among linguists. (shrink)

The proteasome is a proteolytic complex that is known to degrade proteins marked by the attachment of ubiquitin. Recently, it has become apparent that the proteasome has non-proteolytic roles. Several studies have implicated the proteasome in the regulation of transcription. A new study now shows that the proteasome facilitates the interaction of a histone acetyltransferase complex with transcriptional activators at active promoters.1 Bioessays 28:235–239, 2006. © 2006 Wiley Periodicals, Inc.

L'analogie chez Rahner tente d'agir en médiateur entre les positions de Barth et de Przywara radicalement différentes à ce sujet. Une analogie objective de l'émanation et du retour à toute réalité de et vers Dieu correspond à l'analogie subjective de la sensibilité, de l'abstraction et du jugement. Pour réaliser cette jointure entre les analogies objective et subjective, Rahner a développé une relation complexe entre l'esse commune et connu dans le jugement, le concept d'esse, le concept d'ens commune, et l'esse absolutum, (...) qui se trouve à la fois à l'horizon de l'esse commune tout en le remplissant. Pour mettre ensemble tous ces éléments divers, Rahner met en œuvre une analogie dialectique qui joint dynamiqueemnt, tout en les distinguant conceptuellement, matière et esprit, non-être et être, objectivité et subjectivité, concept et jugement, monde et homme, Dieu et homme. (shrink)

The target article raises the question of whether transcription-based evidence is sufficient to support assumptions relating to patterns of mandibular activity in young children. Studies on the perception of both adult and infant speech indicate that the argument needs to be reexamined on the basis of acoustic and articulatory data.

Bivalent chromatin with active H3K4me3 and repressive H3K27me3 was initially identified in embryonic stem cells (ESCs) to poise expression of developmental genes upon lineage commitment. Since then, many more different bivalent modifications have been demonstrated in both ESCs and fully differentiated cells. Bivalency not only spatiotemporally controls gene transcription but also acts to fine‐tune the level of transcription during development. Although increasing number of studies demonstrated the functional significance of bivalent chromatin, the molecular connection of bivalent chromatin and transcriptional (...) regulation remains largely elusive. Recently, we showed Spindlin1/C11orf84 complex prefers to recognize the non‐canonical histone H3K4me3K9me3 bivalent mark, which is required for timely ribosomal RNA transcription. Here, we hypothesize the recognition of K4me3 and K9me3 at the same histone tail by Spindlin1/C11orf84 complex may serve as a general mechanism of conversion from a repressed to an active chromatin structure for transcriptional activation. (shrink)

A widely accepted tenet of evolutionary biology is that spontaneous mutations occur randomly with regard to their fitness effect. However, since the mutation rate varies along a genome and this variation can be subject to selection, organisms might evolve lower mutation rates at loci where mutations are most deleterious or increased rates where mutations are most needed. In fact, mechanisms of targeted hypermutation are known in organisms ranging from bacteria to humans. Here we review the main forces driving the evolution (...) of local mutation rates and identify the main limiting factors. Both targeted hyper‐ and hypomutation can evolve, although the former is restricted to loci under very frequent positive selection and the latter is severely limited by genetic drift. Nevertheless, we show how an association of repair with transcription or chromatin‐associated proteins could overcome the drift limit and lead to non‐random hypomutation along the genome in most organisms.Editor's suggested further reading in BioEssays Stress‐induced mutation via DNA breaks in Escherichia coli: A molecular mechanism with implications for evolution and medicine Abstract. (shrink)

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non‐protein coding, or non‐coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is “junk”, a term still championed by some geneticists and evolutionary biologists. In contrast, (...) molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome “junk” often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their bases, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields. (shrink)

This article discusses the status of transcripts in Conversation Analysis. Repeatedly, the function and the epistemic state of transcripts have been the subject of discussions and reflections in Conversation Analysis. Drawing on a range of empirical examples taken from various authors, this article discusses the question of how present forms of visuality and multi-modality in the data material or the handling of artifacts can be captured in transcripts and how the problem of ‘representation’ of complex and interactive situations can be (...) solved. It turns out that the evolution of recording media along with the medium shift in Conversation Analysis has altered the status of transcripts, effecting a twofold ‘in-between-ness’: transcripts inhabit the conceptual space between orality and literacy on the one hand and between artwork and figure on the other hand. This oscillating hybrid nature proves to be the central property of transcripts in present-day Conversation Analysis. Transcripts are described as scientific ‘objects of knowledge’ and discussed with respect to their methodological and epistemic status. (shrink)

We study the deviations from the exponential decay law, both in quantum field theory (QFT) and quantum mechanics (QM), for an unstable particle which can decay in (at least) two decay channels. After a review of general properties of non-exponential decay in QFT and QM, we evaluate in both cases the decay probability that the unstable particle decays in a given channel in the time interval between t and t+dt. An important quantity is the ratio of the probability of decay (...) into the first and the second channel: this ratio is constant in the Breit-Wigner limit (in which the decay law is exponential) and equals the quantity Γ1/Γ2, where Γ1 and Γ2 are the respective tree-level decay widths. However, in the full treatment (both for QFT and QM) it is an oscillating function around the mean value Γ1/Γ2 and the deviations from this mean value can be sizable. Technically, we study the decay properties in QFT in the context of a superrenormalizable Lagrangian with scalar particles and in QM in the context of Lee Hamiltonians, which deliver formally analogous expressions to the QFT case. (shrink)

Deletions, duplications, insertions, inversions, and translocations, collectively called structural variations (SVs), affect more base pairs of the genome than any other sequence variant. The recent technological advancements in genome sequencing have enabled the discovery of tens of thousands of SVs per human genome. These SVs primarily affect non‐coding DNA sequences, but the difficulties in interpreting their impact limit our understanding of human disease etiology. The functional annotation of non‐coding DNA sequences and methodologies to characterize their three‐dimensional (3D) organization in the (...) nucleus have greatly expanded our understanding of the basic mechanisms underlying gene regulation, thereby improving the interpretation of SVs for their pathogenic impact. Here, we discuss the various mechanisms by which SVs can result in altered gene regulation and how these mechanisms can result in rare genetic disorders. Beyond changing gene expression, SVs can produce novel gene‐intergenic fusion transcripts at the SV breakpoints. (shrink)

Common themes are emerging in the molecular mechanisms of long non‐coding RNA‐mediated gene repression. Long non‐coding RNAs (lncRNAs) participate in targeted gene silencing through chromatin remodelling, nuclear reorganisation, formation of a silencing domain and precise control over the entry of genes into silent compartments. The similarities suggest that these are fundamental processes of transcription regulation governed by lncRNAs. These findings have paved the way for analogous investigations on other lncRNAs and chromatin remodelling enzymes. Here we discuss these common mechanisms and (...) provide our view on other molecules that warrant similar investigations. We also present our concepts on the possible mechanisms that may facilitate the exit of genes from the silencing domains and their potential therapeutic applications. Finally, we point to future areas of research and put forward our recommendations for improvements in resources and applications of existing technologies towards targeted outcomes in this active area of research. (shrink)

Transcriptional repression and silencing have been strongly associated with hypoacetylation of histones. Accordingly, histone deacetylases, which remove acetyl groups from histones, have been shown to participate in mechanisms of transcriptional repression. Therefore, current models of the role of acetylation in transcriptional regulation focus on the acetylation status of histones and designate histone acetyltransferases, which add acetyl groups to histones, as transcriptional coactivators and histone deacetylases as corepressors. In recent years, an accumulation of studies have shown that (...) these enzymes also target non‐histone proteins and that histone deacetylases have clear roles as coactivators at a variety of genes, some of which are key regulators of cell growth and survival. This review summarizes the evidence for histone deacetylases as coactivators and provides models of coactivation mechanisms, some of which integrate roles of acetylated histones and non‐histone proteins in transcription. BioEssays 30:15–24, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

New DNA sequencing technologies have provided novel insights into eukaryotic genomes, epigenomes, and the transcriptome, including the identification of new non‐coding RNA (ncRNA) classes such as promoter‐associated RNAs and long RNAs. Moreover, it is now clear that up to 90% of eukaryotic genomes are transcribed, generating an extraordinary range of RNAs with no coding capacity. Taken together, these new discoveries are modifying the status quo in genomic science by demonstrating that the eukaryotic gene pool is divided into two distinct categories (...) of transcripts: protein‐coding and non‐coding. The function of the majority of ncRNAs produced by the transcriptome is largely unknown; however, it is probable that many are associated with epigenetic mechanisms. The purpose of this review is to describe the most recent discoveries in the ncRNA field that implicate these molecules as key players in the epigenome. (shrink)

SummaryMutations in human genes encoding transcription factors are often dominant because one active allele cannot ensure a normal phenotype (haploinsufficiency). In other instances, heterozygous mutations of two genes are required for a phenotype to appear (combined haploinsufficiency). Here, we explore with models (i) the basis of haploinsufficiency and combined haploinsufficiency owing to mutations in transcription activators, and (ii) how the effects of such mutations can be amplified or buffered by subsequent steps in a transcription cascade. We propose that the non‐linear (...) (sigmoidal) response of transcription to the concentration of activators can explain haploinsufficiency. We further show that the sigmoidal character of the output of a cascade increases with the number of steps involved, the settings of which will determine the buffering or enhancement of the effects of a decreased concentration of an upstream activator. This exploration provides insights into the bases of compensatory mutations and on interloci interactions underlying oligogenic inheritance patterns. (shrink)

This paper presents a numerical study of the reaction A ↔ B in the presence of an intermediate and destabilizing step in its dynamics. After introducing a direct autocatalytic destabilizing process, namely quadratic autocatalysis ) and cubic autocatalysis ), a thermodynamic analysis of the evolution of the reaction in closed and open systems was performed. In addition, the Gibbs free energy, the thermodynamic affinity, and the entropy generation of the overall reaction were evaluated for each of the autocatalytic steps, in (...) order to analyze the behavior of these thermodynamic quantities when the system moved towards equilibrium or towards oscillatory non-equilibrium states. (shrink)

Electron micrographs of active ribosomal genes from many species show a similar picture in which gene regions covered with nascent transcripts alternate with apparently non‐transcribed spacers. Since the gradients of visible nascent transcripts stop near the 3′ end of the 28S sequence it has often been assumed that transcription by RNA polymerase I also terminates at that point. Recent biochemical studies have shown however, that transcription continues far beyond the 3′ end of the 28S and in some species continues across (...) the entire spacer. In this article we review the evidence for spacer transcription in Xenopus, mouse and Drosophila and discuss possible reasons for its invisibility in the electron microscope. (shrink)