A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis

Signaling networks are designed to sense an environmental stimulus and adapt to it. We propose and study a minimal model of signaling network that can sense and respond to external stimuli of varying strength in an adaptive manner. The structure of this minimal network is derived based on some simple assumptions on its differential response to external stimuli. We employ stochastic differential equations and probability distributions obtained from stochastic simulations to characterize differential signaling response in our minimal network model. We show that the proposed minimal signaling network displays two distinct types of response as the strength of the stimulus is decreased. The signaling network has a deterministic part that undergoes rapid activation by a strong stimulus in which case cell-to-cell fluctuations can be ignored. As the strength of the stimulus decreases, the stochastic part of the network begins dominating the signaling response where slow activation is observed with characteristic large cell-to-cell stochastic variability. Interestingly, this proposed stochastic signaling network can capture some of the essential signaling behaviors of a complex apoptotic cell death signaling network that has been studied through experiments and large-scale computer simulations. Thus we claim that the proposed signaling network is an appropriate minimal model of apoptosis signaling. Elucidating the fundamental design principles of complex cellular signaling pathways such as apoptosis signaling remains a challenging task. We demonstrate how our proposed minimal model can help elucidate the effect of a specific apoptotic inhibitor Bcl-2 on apoptotic signaling in a cell-type independent manner. We also discuss the implications of our study in elucidating the adaptive strategy of cell death signaling pathways.Comment: 9 pages, 6 figure

The influence of implicit theories and offender characteristics on judgements of sexual offenders: a moderated mediation analysis

The psychological factors underpinning responses to sexual offenders are beginning to receive increased empirical scrutiny. One such factor is offender representativeness, which refers to the extent to which a given offender example matches a stereotype of those who are typically labelled as 'sexual offenders'. Using a sample of 252 community members, we examined the role of implicit theories about sexual offenders (i.e., whether sexual offending is seen as fixed or malleable) in mediating the relationship between affective responses to sexual offenders and policy outcome judgements. We found support for this mediating effect, although this was eliminated when participants were presented with a 'non-representative' offender vignette. We argue that the relationship between affective responses and policy judgements is contingent on the activation of a sexual offender stereotype, and that this link can be disrupted via the increased presentation of non-stereotypical case examples. Implications for public debate and professional practice are discussed

Implicit theories and offender representativeness in judgments about sexual crime

Implicit theories structure the way people understand and respond to various human actions. Typically, people believe attributes are either fixed (entitists) or malleable (incrementalists). The present study aimed to examine: (a) whether attitudes towards sexual offenders differ depending upon one’s implicit theory about human nature and sexual offenders, and (b) whether implicit theories are associated with judgments made about different types of child abuser. A sample of 252 community participants was recruited. Their attitudes, implicit theories, and political orientation were assessed via self-report. One of three vignettes describing an incidence of child sexual abuse was then presented. The cases were identical except the perpetrator was either an adult male, an adult female, or a male juvenile. Participants then made judgments about the offender's deserved sentence and moral character. Entitists (across both domains) held more negative attitudes than incrementalists, although the magnitude of the difference was greatest when examining implicit theories about sexual offenders. Compared to those with an incremental theory of sexual offenders, entity theorists judged sexual offending to be more: (a) indicative of the perpetrator’s moral character, and (b) deserving of punishment. However, scores were greater towards the adult male relative to the adult female and juvenile. The findings suggest that implicit theories about sexual offenders are domain-specific. They also indicate that judgments made by those with an entity theory (about sexual offenders) are affected by whether a case is representative of a stereotypical sexual offender. Implications of the findings are discussed, along with limitations and future research

Radically Rethinking Agriculture for the 21st Century

Population growth, arable land and fresh water limits, and climate change have profound implications for the ability of agriculture to meet this century’s demands for food, feed, fiber, and fuel while reducing the environmental impact of their production. Success depends on the acceptance and use of contemporary molecular techniques, as well as the increasing development of farming systems that use saline water and integrate nutrient flows

A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

Safe uses of Hill's model: an exact comparison with the Adair-Klotz model

<p>Abstract</p> <p>Background</p> <p>The Hill function and the related Hill model are used frequently to study processes in the living cell. There are very few studies investigating the situations in which the model can be safely used. For example, it has been shown, at the mean field level, that the dose response curve obtained from a Hill model agrees well with the dose response curves obtained from a more complicated Adair-Klotz model, provided that the parameters of the Adair-Klotz model describe strongly cooperative binding. However, it has not been established whether such findings can be extended to other properties and non-mean field (stochastic) versions of the same, or other, models.</p> <p>Results</p> <p>In this work a rather generic quantitative framework for approaching such a problem is suggested. The main idea is to focus on comparing the particle number distribution functions for Hill's and Adair-Klotz's models instead of investigating a particular property (e.g. the dose response curve). The approach is valid for any model that can be mathematically related to the Hill model. The Adair-Klotz model is used to illustrate the technique. One main and two auxiliary similarity measures were introduced to compare the distributions in a quantitative way. Both time dependent and the equilibrium properties of the similarity measures were studied.</p> <p>Conclusions</p> <p>A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same. The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.</p

Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

YesThere are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences

Goal Priming in Dieters: Recent Insights and Applications

What are the psychological mechanisms that make dieting so challenging in our food-rich living environment? Social psychological research on goal priming provides a useful framework for answering this question, as well as implications for how to enhance dieting success. This review presents and discusses recent research which shows that attractive food cues prime the hedonic eating goal in dieters, and thus facilitate overeating. However, external cues priming the goal of weight control can be used to offset these effects and thus to facilitate dieting success, as is demonstrated in both field and laboratory experiments. In addition, recent strategies to prevent hedonic effects of attractive food, such as mindful attention, can facilitate self-regulation. These recent advances in our understanding of dieting behavior have theoretical and practical implications for how successful dieting can be facilitated, both by means of individual strategies, as well as by environmental changes

Genomic repeat abundances contain phylogenetic signal

A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution