Introducing the JMBE themed issue on science communication

No Abstrac

Differential Gene Expression Regulated by Oscillatory Transcription Factors

Cells respond to changes in the internal and external environment by a complex regulatory system whose end-point is the activation of transcription factors controlling the expression of a pool of ad-hoc genes. Recent experiments have shown that certain stimuli may trigger oscillations in the concentration of transcription factors such as NF-B and p53 influencing the final outcome of the genetic response. In this study we investigate the role of oscillations in the case of three different well known gene regulatory mechanisms using mathematical models based on ordinary differential equations and numerical simulations. We considered the cases of direct regulation, two-step regulation and feed-forward loops, and characterized their response to oscillatory input signals both analytically and numerically. We show that in the case of indirect two-step regulation the expression of genes can be turned on or off in a frequency dependent manner, and that feed-forward loops are also able to selectively respond to the temporal profile of oscillating transcription factors

Identification of a Topological Characteristic Responsible for the Biological Robustness of Regulatory Networks

Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed ‘regulation entropy’, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks

Management of Acute Traumatic Central Cord Syndrome: A Narrative Review.

Study Design Narrative review. Objectives To provide an updated overview of the management of acute traumatic central cord syndrome (ATCCS). Methods A comprehensive narrative review of the literature was done to identify evidence-based treatment strategies for patients diagnosed with ATCCS. Results ATCCS is the most commonly encountered subtype of incomplete spinal cord injury and is characterized by worse sensory and motor function in the upper extremities compared with the lower extremities. It is most commonly seen in the setting of trauma such as motor vehicles or falls in elderly patients. The operative management of this injury has been historically variable as it can be seen in the setting of mechanical instability or preexisting cervical stenosis alone. While each patient should be evaluated on an individual basis, based on the current literature, the authors' preferred treatment is to perform early decompression and stabilization in patients that have any instability or significant neurologic deficit. Surgical intervention, in the appropriate patient, is associated with an earlier improvement in neurologic status, shorter hospital stay, and shorter intensive care unit stay. Conclusions While there is limited evidence regarding management of ATCCS, in the presence of mechanical instability or ongoing cord compression, surgical management is the treatment of choice. Further research needs to be conducted regarding treatment strategies and patient outcomes

Liana Abundance, Diversity, and Distribution on Barro Colorado Island, Panama

Lianas are a key component of tropical forests; however, most surveys are too small to accurately quantify liana community composition, diversity, abundance, and spatial distribution – critical components for measuring the contribution of lianas to forest processes. In 2007, we tagged, mapped, measured the diameter, and identified all lianas ≥1 cm rooted in a 50-ha plot on Barro Colorado Island, Panama (BCI). We calculated liana density, basal area, and species richness for both independently rooted lianas and all rooted liana stems (genets plus clones). We compared spatial aggregation patterns of liana and tree species, and among liana species that varied in the amount of clonal reproduction. We also tested whether liana and tree densities have increased on BCI compared to surveys conducted 30-years earlier. This study represents the most comprehensive spatially contiguous sampling of lianas ever conducted and, over the 50 ha area, we found 67,447 rooted liana stems comprising 162 species. Rooted lianas composed nearly 25% of the woody stems (trees and lianas), 35% of woody species richness, and 3% of woody basal area. Lianas were spatially aggregated within the 50-ha plot and the liana species with the highest proportion of clonal stems more spatially aggregated than the least clonal species, possibly indicating clonal stem recruitment following canopy disturbance. Over the past 30 years, liana density increased by 75% for stems ≥1 cm diameter and nearly 140% for stems ≥5 cm diameter, while tree density on BCI decreased 11.5%; a finding consistent with other neotropical forests. Our data confirm that lianas contribute substantially to tropical forest stem density and diversity, they have highly clumped distributions that appear to be driven by clonal stem recruitment into treefall gaps, and they are increasing relative to trees, thus indicating that lianas will play a greater role in the future dynamics of BCI and other neotropical forests

The political process of constructing a sustainable London Olympics sports development legacy

This study attempts to develop a research agenda for understanding the process of constructing a sustainable Olympic sports development legacy. The research uses a social constructivist perspective to examine the link between the 2012 London Olympic Games and sustainable sports development. The first part of the paper provides justification for the study of sport policy processes using a constructivist lens. This is followed by a section which critically unpacks sustainable sports development drawing on Mosse’s (1998) ideas of process-oriented research and Searle’s conceptualisation of the construction of social reality. Searle’s (1995) concepts of the assignment of function, collective intentionality, collective rules, and human capacity to cope with the environment are considered in relation to the events and discourses emerging from the legacy vision(s) associated with the 2012 London Olympic Games. The paper concludes by proposing a framework for engaging in process oriented research and highlights key elements, research questions, and methodological issues. The proposed constructivist approach can be used to inform policy, practice, and research on sustainable Olympic sports development legacy

Stochastic Delay Accelerates Signaling in Gene Networks

The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, the time it takes to create a single protein depends on the number of steps in the reaction chain and the nature of each step. One way to account for these reactions in models of gene regulatory networks is to incorporate dynamical delay. However, the stochastic nature of the reactions necessary to produce protein leads to a waiting time that is randomly distributed. Here, we use queueing theory to examine the effects of such distributed delay on the propagation of information through transcriptionally regulated genetic networks. In an analytically tractable model we find that increasing the randomness in protein production delay can increase signaling speed in transcriptional networks. The effect is confirmed in stochastic simulations, and we demonstrate its impact in several common transcriptional motifs. In particular, we show that in feedforward loops signaling time and magnitude are significantly affected by distributed delay. In addition, delay has previously been shown to cause stable oscillations in circuits with negative feedback. We show that the period and the amplitude of the oscillations monotonically decrease as the variability of the delay time increases

Exploring and challenging the network of angiogenesis

Angiogenesis is one of the hallmarks of cancer and, as such, one of the alternative general targets for anticancer therapy. Since angiogenesis is a complex process involving a high number of interconnected components, a network approach would be a convenient systemic way to analyse responses to directed drug attacks. Herein we show that, although the angiogenic network is easily broken by short combinations of directed attacks, it still remains essentially functional by keeping the global patterns and local efficiency essentially unaltered after these attacks. This is a clear sign of its high robustness and resilience and stresses the need of directed, combined attacks for an effective blockade of the process. The results of this theoretical study could be relevant for the design of new antiangiogenic therapies and the selection of their targets

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments