Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity

Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise.Comment: 5 pages, 3 fiugres. Figure and text update

Transición política en Hungría. 1989 - 1990.

Sin resume

Structure and function of negative feedback loops at the interface of genetic and metabolic networks

The molecular network in an organism consists of transcription/translation regulation, protein-protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molecules that exist in its environment. A key part of this overall system of molecular regulation is therefore the interface between the genetic and the metabolic network. A motif that occurs very often at this interface is a negative feedback loop used to regulate the level of the signal molecules. In this work we use mathematical models to investigate the steady state and dynamical behaviour of different negative feedback loops. We show, in particular, that feedback loops where the signal molecule does not cause the dissociation of the transcription factor from the DNA respond faster than loops where the molecule acts by sequestering transcription factors off the DNA. We use three examples, the bet, mer and lac systems in E. coli, to illustrate the behaviour of such feedback loops.Comment: 8 pages, 4 figure

Oscillation patterns in negative feedback loops

Organisms are equipped with regulatory systems that display a variety of dynamical behaviours ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least one negative feedback loop in the regulatory network. Here we study the dynamics of a very general class of negative feedback loops. Our main result is that in these systems the sequence of maxima and minima of the concentrations is uniquely determined by the topology of the loop and the activating/repressing nature of the interaction between pairs of variables. This allows us to devise an algorithm to reconstruct the topology of oscillating negative feedback loops from their time series; this method applies even when some variables are missing from the data set, or if the time series shows transients, like damped oscillations. We illustrate the relevance and the limits of validity of our method with three examples: p53-Mdm2 oscillations, circadian gene expression in cyanobacteria, and cyclic binding of cofactors at the estrogen-sensitive pS2 promoter.Comment: 10 pages, 8 figure

A spiritualitás vizsgálata segítő foglalkozású diplomások és egyetemisták körében = Examining the spirituality among helping professionals and graduate students

Kutatásunk elméletalkotója, Ralph L. Piedmont megközelítésében a spiritualitás önálló személyiségdimenzióként jelenik meg. Projektünk során a Spiritualitási és Vallási Érzület Mérőskálából elsősorban az annak részét képező Spirituális Transzcendencia Skálát (STS) helyeztük előtérbe. Két, összesen 803 fős, segítő (hitéleti végzettségű, pszichoterapeuta és egyéb segítő) és nem segítő foglalkozású felnőttekből álló mintában a 23 tételes STS három alskálája, az ima/meditáció által érzett beteljesülés, az univerzalitás és az összekötöttség elfogadható pszichometriai jellemzőket mutatott. Javaslatot tettünk a teszt rövidített, 9 tételes magyar változatára, mely alskálánként 3 tételből áll. A vizsgálat során bebizonyosodott, hogy a skála magyar viszonyokra alkalmazható, megbízható és érvényes mérőeszköz, mely felhasználható további kutatásokra. Összességében eredményeink arra utalnak, hogy a Ralph L. Piedmont által leírt három spiritualitás-komponens léte az STS-H-val is kimutatható, és adataink jó illeszkedést mutattak a Piedmont által tapasztalt mintázattal. A Spirituális Transzcendencia Skála rövidített, 9 tételes magyar változata (STS-H-R) elérhető a Mentálhigiéné Intézet honlapján. A kérdőíves vizsgálatot kiegészítve mélyinterjúk segítségével kezdtük feltárni és elemezni, hogy a spiritualitás milyen szerepet játszik az egyes foglalkozások munkavégzésében. | The theorist of our research, Ralph L. Piedmont approaches the spirituality as an independent dimension of the personality. We primarily have brought into prominence the Spiritual Transcendence Scale (STS), as the part of the Assessment of Spirituality and Religious Sentiments. Three subscales, the prayer fulfilment, the universality and the connectedness has shown acceptable psychometric characteristics in two of our samples, which were consisted 803 adult helping professionals (religious professionals, psychotherapists and other helpers) and non helping professionals. We have made a proposal the shortened, 9-item Hungarian version of the test, which was composed of 3 items per subscale. The study has proved the adaptability of the scale to the Hungarian conditions, furthermore proved it is a reliable and valid measurement tool for the following researches. On the whole our results indicate the existence of the three spiritual components described by their author, Ralph L. Piedmont with the STS-H too, and the association of our data was proper with the pattern observed by Piedmont. The shortened, 9-item Hungarian version (STS-H-R) of the Spiritual Transcendence Scale is available on the Institute of Mental Health’s homepage. Expanding the questionnaire-related study we have begun exploring and analyzing the role of the spirituality in the various professions by using in-depth interviews

EXPERIMENTAL AND NUMERICAL INVESTIGATION INTO NON-ROLLING TYRE

Tyre vibration is an important reason of travell reduction safety when increasing the speed of a vehicle. The tyre circumference can be seen as a loop shaped chain of elastic parts which have their portion of the mass of the tyre. This model is suitable for computer aided investigation on tyre vibration phenomena such as steady waves when rolling. Such an investigation is presented in this article

A Mixed Incoherent Feed-Forward Loop Allows Conditional Regulation of Response Dynamics

Expression of the SodA superoxide dismutase (MnSOD) in Escherichia coli is regulated by superoxide concentration through the SoxRS system and also by Fur (Ferric uptake regulator) through a mixed incoherent feed forward loop (FFL) containing the RyhB small regulatory RNA. In this work I theoretically analyze the function of this feed forward loop as part of the network controlling expression of the two cytoplasmic superoxide dismutases, SodA and SodB. I find that feed forward regulation allows faster response to superoxide stress at low intracellular iron levels compared to iron rich conditions. That is, it can conditionally modulate the response time of a superimposed transcriptional control mechanism

Autoregulation of the Escherichia coli melR promoter: repression involves four molecules of MelR

The Escherichia coli MelR protein is a transcription activator that autoregulates its own promoter by repressing transcription initiation. Optimal repression requires MelR binding to a site that overlaps the melR transcription start point and to upstream sites. In this work, we have investigated the different determinants needed for optimal repression and their spatial requirements. We show that repression requires a complex involving four DNA-bound MelR molecules, and that the global CRP regulator plays little or no role

Comparative Network Analysis of Preterm vs. Full-Term Infant-Mother Interactions

Several studies have reported that interactions of mothers with preterm infants show differential characteristics compared to that of mothers with full-term infants. Interaction of preterm dyads is often reported as less harmonious. However, observations and explanations concerning the underlying mechanisms are inconsistent. In this work 30 preterm and 42 full-term mother-infant dyads were observed at one year of age. Free play interactions were videotaped and coded using a micro-analytic coding system. The video records were coded at one second resolution and studied by a novel approach using network analysis tools. The advantage of our approach is that it reveals the patterns of behavioral transitions in the interactions. We found that the most frequent behavioral transitions are the same in the two groups. However, we have identified several high and lower frequency transitions which occur significantly more often in the preterm or full-term group. Our analysis also suggests that the variability of behavioral transitions is significantly higher in the preterm group. This higher variability is mostly resulted from the diversity of transitions involving non-harmonious behaviors. We have identified a maladaptive pattern in the maternal behavior in the preterm group, involving intrusiveness and disengagement. Application of the approach reported in this paper to longitudinal data could elucidate whether these maladaptive maternal behavioral changes place the infant at risk for later emotional, cognitive and behavioral disturbance