1,610 research outputs found
Stochastic model of transcription factor-regulated gene expression
We consider a stochastic model of transcription factor (TF)-regulated gene
expression. The model describes two genes: Gene A and Gene B which synthesize
the TFs and the target gene proteins respectively. We show through analytic
calculations that the TF fluctuations have a significant effect on the
distribution of the target gene protein levels when the mean TF level falls in
the highest sensitive region of the dose-response curve. We further study the
effect of reducing the copy number of Gene A from two to one. The enhanced TF
fluctuations yield results different from those in the deterministic case. The
probability that the target gene protein level exceeds a threshold value is
calculated with a knowledge of the probability density functions associated
with the TF and target gene protein levels. Numerical simulation results for a
more detailed stochastic model are shown to be in agreement with those obtained
through analytic calculations. The relevance of these results in the context of
the genetic disorder haploinsufficiency is pointed out. Some experimental
observations on the haploinsufficiency of the tumour suppressor gene, Nkx3.1,
are explained with the help of the stochastic model of TF-regulated gene
expression.Comment: 17 pages, 11 figures. Accepted for publication in Physical Biolog
Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes
The receptor for macrophage colony stimulating factor (CSF-1), the c- fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c- ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c- myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c- myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c- myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c- fms during myeloid differentiation
A functional-cognitive framework for attitude research
In attitude research, behaviours are often used as proxies for attitudes and attitudinal processes. This practice is problematic because it conflates the behaviours that need to be explained (explanandum) with the mental constructs that are used to explain these behaviours (explanans). In the current chapter we propose a meta-theoretical framework that resolves this problem by distinguishing between two levels of analysis. According to the proposed framework, attitude research can be conceptualised as the scientific study of evaluation. Evaluation is defined not in terms of mental constructs but in terms of elements in the environment, more specifically, as the effect of stimuli on evaluative responses. From this perspective, attitude research provides answers to two questions: (1) Which elements in the environment moderate evaluation? (2) What mental processes and representations mediate evaluation? Research on the first question provides explanations of evaluative responses in terms of elements in the environment (functional level of analysis); research on the second question offers explanations of evaluation in terms of mental processes and representations (cognitive level of analysis). These two levels of analysis are mutually supportive, in that better explanations at one level lead to better explanations at the other level. However, their mutually supportive relation requires a clear distinction between the concepts of their explanans and explanandum, which are conflated if behaviours are treated as proxies for mental constructs. The value of this functional-cognitive framework is illustrated by applying it to four central questions of attitude research
The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine
Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT.
Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine.
Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists.
Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum.
Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions.
Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal
Graded and Binary Responses in Stochastic Gene Expression
Recently, several theoretical and experimental studies have been undertaken
to probe the effect of stochasticity on gene expression (GE). In experiments,
the GE response to an inducing signal in a cell, measured by the amount of
mRNAs/proteins synthesized, is found to be either graded or binary. The latter
type of response gives rise to a bimodal distribution in protein levels in an
ensemble of cells. One possible origin of binary response is cellular
bistability achieved through positive feedback or autoregulation. In this
paper, we study a simple, stochastic model of GE and show that the origin of
binary response lies exclusively in stochasticity. The transitions between the
active and inactive states of the gene are random in nature. Graded and binary
responses occur in the model depending on the relative stability of the
activated and deactivated gene states with respect to that of
mRNAs/proteins.The theoretical results on binary response provide a good
description of the ``all-or-none'' phenomenon observed in an eukaryotic system.Comment: to be published in Physical Biolog
Additivity and non-additivity of multipartite entanglement measures
We study the additivity property of three multipartite entanglement measures,
i.e. the geometric measure of entanglement (GM), the relative entropy of
entanglement and the logarithmic global robustness. First, we show the
additivity of GM of multipartite states with real and non-negative entries in
the computational basis. Many states of experimental and theoretical interests
have this property, e.g. Bell diagonal states, maximally correlated generalized
Bell diagonal states, generalized Dicke states, the Smolin state, and the
generalization of D\"{u}r's multipartite bound entangled states. We also prove
the additivity of other two measures for some of these examples. Second, we
show the non-additivity of GM of all antisymmetric states of three or more
parties, and provide a unified explanation of the non-additivity of the three
measures of the antisymmetric projector states. In particular, we derive
analytical formulae of the three measures of one copy and two copies of the
antisymmetric projector states respectively. Third, we show, with a statistical
approach, that almost all multipartite pure states with sufficiently large
number of parties are nearly maximally entangled with respect to GM and
relative entropy of entanglement. However, their GM is not strong additive;
what's more surprising, for generic pure states with real entries in the
computational basis, GM of one copy and two copies, respectively, are almost
equal. Hence, more states may be suitable for universal quantum computation, if
measurements can be performed on two copies of the resource states. We also
show that almost all multipartite pure states cannot be produced reversibly
with the combination multipartite GHZ states under asymptotic LOCC, unless
relative entropy of entanglement is non-additive for generic multipartite pure
states.Comment: 45 pages, 4 figures. Proposition 23 and Theorem 24 are revised by
correcting a minor error from Eq. (A.2), (A.3) and (A.4) in the published
version. The abstract, introduction, and summary are also revised. All other
conclusions are unchange
- …