Network analysis of metabolic enzyme evolution in Escherichia coli

BACKGROUND: The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc. RESULTS: Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL) between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1. CONCLUSIONS: The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution

Preferential attachment in the evolution of metabolic networks

BACKGROUND: Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. RESULTS: The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. CONCLUSION: Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate that E. coli has adjusted its metabolic network to a changing environment by replacing the relatively central enzymes for better adapted orthologs from other prokaryotic species

What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae?

BACKGROUND: Most proteins interact with only a few other proteins while a small number of proteins (hubs) have many interaction partners. Hub proteins and non-hub proteins differ in several respects; however, understanding is not complete about what properties characterize the hubs and set them apart from proteins of low connectivity. Therefore, we have investigated what differentiates hubs from non-hubs and static hubs (party hubs) from dynamic hubs (date hubs) in the protein-protein interaction network of Saccharomyces cerevisiae. RESULTS: The many interactions of hub proteins can only partly be explained by bindings to similar proteins or domains. It is evident that domain repeats, which are associated with binding, are enriched in hubs. Moreover, there is an over representation of multi-domain proteins and long proteins among the hubs. In addition, there are clear differences between party hubs and date hubs. Fewer of the party hubs contain long disordered regions compared to date hubs, indicating that these regions are important for flexible binding but less so for static interactions. Furthermore, party hubs interact to a large extent with each other, supporting the idea of party hubs as the cores of highly clustered functional modules. In addition, hub proteins, and in particular party hubs, are more often ancient. Finally, the more recent paralogs of party hubs are underrepresented. CONCLUSION: Our results indicate that multiple and repeated domains are enriched in hub proteins and, further, that long disordered regions, which are common in date hubs, are particularly important for flexible binding

Synthesis and properties of bis-porphyrin molecular tweezers: effects of spacer flexibility on binding and supramolecular chirogenesis

Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding constants Ka = 104–106 M?1 reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis

Selecting the Number and Labels of Topics in Topic Modeling: A Tutorial

13 pagesTopic modeling is a type of text analysis that identifies clusters of co-occurring words, or latent topics. A challenging step of topic modeling is determining the number of topics to extract. This tutorial describes tools researchers can use to identify the number and labels of topics in topic modeling. First, we outline the procedure for narrowing down a large range of models to a select number of candidate models. This procedure involves comparing the large set on fit metrics, including exclusivity, residuals, variational lower bound, and semantic coherence. Next, we describe the comparison of a small number of models using project goals as a guide and information about topic representative and solution congruence. Finally, we describe tools for labeling topics, including frequent and exclusive words, key examples, and correlations among topics

Enrollment and Assessment of a First-Year College Class Social Network for a Controlled Trial of the Indirect Effect of a Brief Motivational Intervention

Heavy drinking and its consequences among college students represent a serious public health problem, and peer social networks are a robust predictor of drinking-related risk behaviors. In a recent trial, we administered a Brief Motivational Intervention (BMI) to a small number of first-year college students to assess the indirect effects of the intervention on peers not receiving the intervention. Objectives: To present the research design, describe the methods used to successfully enroll a high proportion of a first-year college class network, and document participant characteristics. Methods: Prior to study enrollment, we consulted with a student advisory group and campus stakeholders to aid in the development of study-related procedures. Enrollment and baseline procedures were completed in the first six weeks of the academic semester. Surveys assessed demographics, alcohol use, and social network ties. Individuals were assigned to a BMI or control group according to their dormitory location. Results: The majority of incoming first-year students (1342/1660; 81%) were enrolled (55% female, 52% nonwhite, mean age 18.6 [SD = 0.51]). Differences between the intervention and control group were noted in alcohol use, but were in large part a function of there being more substance-free dormitory floors in the control group. Conclusions: The current study was successful in enrolling a large proportion of a first-year college class and can serve as a template for social network investigations

Building institutions for health and health systems in contexts of rapid change

Many Asian countries are in the midst of multiple interconnected social, economic, demographic, technological, institutional and environmental transitions. These changes are having important impacts on health and well-being and on the capacity of health systems to respond to health-related problems. This paper focuses on the creation of institutions to overcome information asymmetry and encourage the provision of safe, effective and affordable health services in this context of complexity and rapid change. It presents a review of literature on different approaches to the analysis of the management of system development and institution-building. There is a general agreement that the outcome of an intervention depends a great deal on the way that a large number of agents respond. Their response is influenced by the institutional arrangements that mediate relationships between health sector actors and also by their understandings and expectations of how other actors will respond. The impact of a policy or specific intervention is difficult to predict and there is a substantial risk of unintended outcomes. This creates the need for an iterative learning approach in which widespread experimentation is encouraged, good and bad experiences are evaluated and policies are formulated on the basis of the lessons learned. This enables actors to learn their roles and responsibilities and the appropriate responses to new incentive structures. The paper concludes with an outline of the information needs of managers of health system change in societies in the midst of rapid development.ESR

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

<p>Abstract</p> <p>Background</p> <p>PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity.</p> <p>Results</p> <p>We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls.</p> <p>Conclusion</p> <p>We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.</p

SCIPP: An Expanded Community of Practice - Community Publishing

SCIPP redefines and expands the existing notions about what makes for a vibrant and robust community of practice by partnering CSUSB students and professors with K-12 students, parents, and educators, along with committed community partners. SCIPP encourages curiosity in ways that leads to critical thinking, exploration, risk taking , confidence building, open-mindedness, and other personal traits that equip them with the softskills to be active, critical, and creative contributors to our communities. SCIPP pedagogy embraces our students\u27 collective wisdom and focuses on relational building where multi-directional communication is promoted and students are viewed as equal stakeholders in their own educations. SCIPP puts collaboration into action which in turn fosters community-based lifelong learning. SCIPP provides the open intellectual space for future university students (our K-12 students) to engage with existing university students in meaningful ways so as to sustain interconnected partnerships facilitating community engagement. It supports parents as experts in the education of their children and acknowledges parents as the first conduits to spark their children’s imagination while they actively participate in education enriching activities and programs. Everyone involved is committed to creating a secure and open atmosphere for dreaming, sharing, and learning. Together we explore the aspects of community publishing through collaborative learning in formal and informal settings relating to digital and printed medias