Control of DNA topology during thermal stress in hyperthermophilic archaea: DNA topoisomerase levels, activities and induced thermotolerance during heat and cold shock in Sulfolobus

Plasmid topology varies transiently in hyperthermophilic archaea during thermal stress. As in mesophilic bacteria, DNA linking number (Lk) increases during heat shock and decreases during cold shock. Despite this correspondence, plasmid DNA topology and proteins presumably involved in DNA topological control in each case are different. Plasmid DNA in hyperthermophilic archaea is found in a topological form from relaxed to positively supercoiled in contrast to the negatively supercoiled state typical of bacteria, eukaryotes and mesophilic archaea. We have analysed the regulation of DNA topological changes during thermal stress in Sulfolobus islandicus (kingdom Crenarchaeota), which harbours two plasmids, pRN1 and pRN2. In parallel with plasmid topological variations, we analysed levels of reverse gyrase, topoisomerase VI (Topo VI) and the small DNA-binding protein Sis7, as well as topoisomerase activities in crude extracts during heat shock from 80 degrees C to 85-87 degrees C, and cold shock from 80 degrees C to 65 degrees C. Quantitative changes in reverse gyrase, Topo VI and Sis7 were not significant. In support of this, inhibition of protein synthesis in S. islandicus during shocks did not alter plasmid topological dynamics, suggesting that an increase in topoisomerase levels is not needed for control of DNA topology during thermal stress. A reverse gyrase activity was detected in crude extracts, which was strongly dependent on the assay temperature. It was inhibited at 65 degrees C, but was greatly enhanced at 85 degrees C. However, the intrinsic reverse gyrase activity did not vary with heat or cold shock. These results suggest that the control of DNA topology during stress in Sulfolobus relies primarily on the physical effect of temperature on topoisomerase activities and on the geometry of DNA itself. Additionally, we have detected an enhanced thermoresistance of reverse gyrase activities in cultures subject to prolonged heat shock (but not cold shock). This acquired thermotolerance at the enzymatic level is abolished when cultures are treated with puromycin, suggesting a requirement for protein synthesis.     

The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics

It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins (“hubs”). As a complementary notion, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many “shortest paths” going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, betweenness (i.e., “bottleneck-ness”) is a much more significant indicator of essentiality than degree (i.e., “hub-ness”). Furthermore, bottlenecks correspond to the dynamic components of the interaction network—they are significantly less well coexpressed with their neighbors than nonbottlenecks, implying that expression dynamics is wired into the network topology.     

DebtRank: A Microscopic Foundation for Shock Propagation

The DebtRank algorithm has been increasingly investigated as a method to estimate the impact of shocks in financial networks, as it overcomes the limitations of the traditional default-cascade approaches. Here we formulate a dynamical “microscopic” theory of instability for financial networks by iterating balance sheet identities of individual banks and by assuming a simple rule for the transfer of shocks from borrowers to lenders. By doing so, we generalise the DebtRank formulation, both providing an interpretation of the effective dynamics in terms of basic accounting principles and preventing the underestimation of losses on certain network topologies. Depending on the structure of the interbank leverage matrix the dynamics is either stable, in which case the asymptotic state can be computed analytically, or unstable, meaning that at least one bank will default. We apply this framework to a dataset of the top listed European banks in the period 2008–2013. We find that network effects can generate an amplification of exogenous shocks of a factor ranging between three (in normal periods) and six (during the crisis) when we stress the system with a 0.5% shock on external (i.e. non-interbank) assets for all banks.     

Mechanistic inquiry into decrease in probability of defibrillation success with increase in complexity of preshock reentrant activity

Energy requirements for successful antiarrhythmia shocks are arrhythmia specific. However, it remains unclear why the probability of shock success decreases with increasing arrhythmia complexity. The goal of this research was to determine whether a diminished probability of shock success results from an increased number of functional reentrant circuits in the myocardium, and if so, to identify the responsible mechanisms. To achieve this goal, we assessed shock efficacy in a bidomain defibrillation model of a 4-mm-thick slice of canine ventricles. Shocks were applied between a right ventricular cathode and a distant anode to terminate either a single scroll wave (SSW) or multiple scroll waves (MSWs). From the 160 simulations conducted, dose-response curves were constructed for shocks given to SSWs and MSWs. The shock strength that yielded a 50% probability of success (ED(50)) for SSWs was found to be 13% less than that for MSWs, which indicates that a larger number of functional reentries results in an increased defibrillation threshold. The results also demonstrate that an isoelectric window exists after both failed and successful shocks; however, shocks of strength near the ED(50) value that were given to SSWs resulted in 16.3% longer isoelectric window durations than the same shocks delivered to MSWs. Mechanistic inquiry into these findings reveals that the two main factors underlying the observed relationships are 1) smaller virtual electrode polarizations in the tissue depth, and 2) differences in preshock tissue state. As a result of these factors, intramural excitable pathways leading to delayed breakthrough on the surface were formed earlier after shocks given to MSWs compared with SSWs and thus resulted in a lower defibrillation threshold for shocks given to SSWs.     

Convergence of Molecular,Modeling, and Systems Approaches for an Understanding of the Escherichia coli Heat Shock Response

Summary: The heat shock response (HSR) is a homeostatic response that maintains the proper protein-folding environment in the cell. This response is universal, and many of its components are well conserved from bacteria to humans. In this review, we focus on the regulation of one of the most well-characterized HSRs, that of Escherichia coli. We show that even for this simple model organism, we still do not fully understand the central component of heat shock regulation, a chaperone-mediated negative feedback loop. In addition, we review other components that contribute to the regulation of the HSR in E. coli and discuss how these additional components contribute to regulation. Finally, we discuss recent genomic experiments that reveal additional functional aspects of the HSR.     

Biological effects of two successive shock waves focused on liver tissues and melanoma cells

A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes.     

Reverse engineering: the architecture of biological networks

We adopt a control theory approach to reverse engineer the complexity of a known system--the bacterial heat shock response. Using a computational dynamic model, we explore the organization of the heat shock system and elucidate its various regulation strategies. We show that these strategies are behind much of the complexity of the network. We propose that complexity is a necessary outcome of robustness and performance requirements that are achieved by the heat shock system's exquisite regulation modules. The techniques we use rely on dynamic computational models and principles from the field of control theory.     

Exploring the Morphospace of Communication Efficiency in Complex Networks

Graph theoretical analysis has played a key role in characterizing global features of the topology of complex networks, describing diverse systems such as protein interactions, food webs, social relations and brain connectivity. How system elements communicate with each other depends not only on the structure of the network, but also on the nature of the system''s dynamics which are constrained by the amount of knowledge and resources available for communication processes. Complementing widely used measures that capture efficiency under the assumption that communication preferentially follows shortest paths across the network (“routing”), we define analytic measures directed at characterizing network communication when signals flow in a random walk process (“diffusion”). The two dimensions of routing and diffusion efficiency define a morphospace for complex networks, with different network topologies characterized by different combinations of efficiency measures and thus occupying different regions of this space. We explore the relation of network topologies and efficiency measures by examining canonical network models, by evolving networks using a multi-objective optimization strategy, and by investigating real-world network data sets. Within the efficiency morphospace, specific aspects of network topology that differentially favor efficient communication for routing and diffusion processes are identified. Charting regions of the morphospace that are occupied by canonical, evolved or real networks allows inferences about the limits of communication efficiency imposed by connectivity and dynamics, as well as the underlying selection pressures that have shaped network topology.     

On the Origins and Control of Community Types in the Human Microbiome

Microbiome-based stratification of healthy individuals into compositional categories, referred to as “enterotypes” or “community types”, holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems approach and found that heterogeneity in the interspecific interactions or the presence of strongly interacting species is sufficient to explain community types, independent of the topology of the underlying ecological network. By controlling the presence or absence of these strongly interacting species we can steer the microbial ecosystem to any desired community type. This open-loop control strategy still holds even when the community types are not distinct but appear as dense regions within a continuous gradient. This finding can be used to develop viable therapeutic strategies for shifting the microbial composition to a healthy configuration.     

The Structure and Evolution of Buyer-Supplier Networks

In this paper, we investigate the structure and evolution of customer-supplier networks in Japan using a unique dataset that contains information on customer and supplier linkages for more than 500,000 incorporated non-financial firms for the five years from 2008 to 2012. We find, first, that the number of customer links is unequal across firms; the customer link distribution has a power-law tail with an exponent of unity (i.e., it follows Zipf''s law). We interpret this as implying that competition among firms to acquire new customers yields winners with a large number of customers, as well as losers with fewer customers. We also show that the shortest path length for any pair of firms is, on average, 4.3 links. Second, we find that link switching is relatively rare. Our estimates indicate that the survival rate per year for customer links is 92 percent and for supplier links 93 percent. Third and finally, we find that firm growth rates tend to be more highly correlated the closer two firms are to each other in a customer-supplier network (i.e., the smaller is the shortest path length for the two firms). This suggests that a non-negligible portion of fluctuations in firm growth stems from the propagation of microeconomic shocks – shocks affecting only a particular firm – through customer-supplier chains.     

Performance of Single and Concatenated Sets of Mitochondrial Genes at Inferring Metazoan Relationships Relative to Full Mitogenome Data

Mitochondrial (mt) genes are some of the most popular and widely-utilized genetic loci in phylogenetic studies of metazoan taxa. However, their linked nature has raised questions on whether using the entire mitogenome for phylogenetics is overkill (at best) or pseudoreplication (at worst). Moreover, no studies have addressed the comparative phylogenetic utility of mitochondrial genes across individual lineages within the entire Metazoa. To comment on the phylogenetic utility of individual mt genes as well as concatenated subsets of genes, we analyzed mitogenomic data from 1865 metazoan taxa in 372 separate lineages spanning genera to subphyla. Specifically, phylogenies inferred from these datasets were statistically compared to ones generated from all 13 mt protein-coding (PC) genes (i.e., the “supergene” set) to determine which single genes performed “best” at, and the minimum number of genes required to, recover the “supergene” topology. Surprisingly, the popular marker COX1 performed poorest, while ND5, ND4, and ND2 were most likely to reproduce the “supergene” topology. Averaged across all lineages, the longest ∼2 mt PC genes were sufficient to recreate the “supergene” topology, although this average increased to ∼5 genes for datasets with 40 or more taxa. Furthermore, concatenation of the three “best” performing mt PC genes outperformed that of the three longest mt PC genes (i.e, ND5, COX1, and ND4). Taken together, while not all mt PC genes are equally interchangeable in phylogenetic studies of the metazoans, some subset can serve as a proxy for the 13 mt PC genes. However, the exact number and identity of these genes is specific to the lineage in question and cannot be applied indiscriminately across the Metazoa.     

Entrepreneurial Regions: Do Macro-Psychological Cultural Characteristics of Regions Help Solve the “Knowledge Paradox” of Economics?

In recent years, modern economies have shifted away from being based on physical capital and towards being based on new knowledge (e.g., new ideas and inventions). Consequently, contemporary economic theorizing and key public policies have been based on the assumption that resources for generating knowledge (e.g., education, diversity of industries) are essential for regional economic vitality. However, policy makers and scholars have discovered that, contrary to expectations, the mere presence of, and investments in, new knowledge does not guarantee a high level of regional economic performance (e.g., high entrepreneurship rates). To date, this “knowledge paradox” has resisted resolution. We take an interdisciplinary perspective to offer a new explanation, hypothesizing that “hidden” regional culture differences serve as a crucial factor that is missing from conventional economic analyses and public policy strategies. Focusing on entrepreneurial activity, we hypothesize that the statistical relation between knowledge resources and entrepreneurial vitality (i.e., high entrepreneurship rates) in a region will depend on “hidden” regional differences in entrepreneurial culture. To capture such “hidden” regional differences, we derive measures of entrepreneurship-prone culture from two large personality datasets from the United States (N = 935,858) and Great Britain (N = 417,217). In both countries, the findings were consistent with the knowledge-culture-interaction hypothesis. A series of nine additional robustness checks underscored the robustness of these results. Naturally, these purely correlational findings cannot provide direct evidence for causal processes, but the results nonetheless yield a remarkably consistent and robust picture in the two countries. In doing so, the findings raise the idea of regional culture serving as a new causal candidate, potentially driving the knowledge paradox; such an explanation would be consistent with research on the psychological characteristics of entrepreneurs.     

Use of 16S rRNA and rpoB Genes as Molecular Markers for Microbial Ecology Studies

Several characteristics of the 16S rRNA gene, such as its essential function, ubiquity, and evolutionary properties, have allowed it to become the most commonly used molecular marker in microbial ecology. However, one fact that has been overlooked is that multiple copies of this gene are often present in a given bacterium. These intragenomic copies can differ in sequence, leading to identification of multiple ribotypes for a single organism. To evaluate the impact of such intragenomic heterogeneity on the performance of the 16S rRNA gene as a molecular marker, we compared its phylogenetic and evolutionary characteristics to those of the single-copy gene rpoB. Full-length gene sequences and gene fragments commonly used for denaturing gradient gel electrophoresis were compared at various taxonomic levels. Heterogeneity found between intragenomic 16S rRNA gene copies was concentrated in specific regions of rRNA secondary structure. Such “heterogeneity hot spots” occurred within all gene fragments commonly used in molecular microbial ecology. This intragenomic heterogeneity influenced 16S rRNA gene tree topology, phylogenetic resolution, and operational taxonomic unit estimates at the species level or below. rpoB provided comparable phylogenetic resolution to that of the 16S rRNA gene at all taxonomic levels, except between closely related organisms (species and subspecies levels), for which it provided better resolution. This is particularly relevant in the context of a growing number of studies focusing on subspecies diversity, in which single-copy protein-encoding genes such as rpoB could complement the information provided by the 16S rRNA gene.     

Functions and Regulation of Circular Dorsal Ruffles

Cells construct a number of plasma membrane structures to meet a range of physiological demands. Driven by juxtamembrane actin machinery, these actin-based membrane protrusions are essential for the operation and maintenance of cellular life. They are required for diverse cellular functions, such as directed cell motility, cell spreading, adhesion, and substrate/matrix degradation. Circular dorsal ruffles (CDRs) are one class of such structures characterized as F-actin-rich membrane projections on the apical cell surface. CDRs commence their formation minutes after stimulation as flat, open, and immature ruffles and progressively develop into fully enclosed circular ruffles. These “rings” then mature and contract centrifugally before subsiding. Serving a critical function in receptor internalization and cell migration, CDRs are thus highly dynamic but transient formations. Here, we review the current state of knowledge concerning the regulation of circular dorsal ruffles. We focus specifically on the biochemical pathways leading to CDR formation in order to better define the roles and functions of these enigmatic structures.     

Green Niche Market Development

This article introduces a multiagent simulation framework for investigating the emergence of niche markets for environmentally innovative products. It clarifies how consumer preferences, business strategy, and government policy interact during market development. The framework allows investigation of the effects of uncertainty and agents' corresponding coping strategies. We describe the model, illustrate how it works when applied to the case of hybrid cars, and analyze results spanning several policy cases and a range of scenarios that make different assumptions about the heterogeneity of agents. Heterogeneity within each agent class strongly influences aggregate outcomes. Innovative firms can create green products in response to or in anticipation of government regulation, but true green niche markets do not emerge unless there are also green consumers. Niche markets do not go mainstream unless scale economies drive costs down to parity with conventional products. Preferred environmental innovation policies change with heterogeneity assumptions.     

Polarity reversal lowers activation time during diastolic field stimulation of the rabbit ventricles: insights into mechanisms

To fully characterize the mechanisms of defibrillation, it is necessary to understand the response, within the three-dimensional (3D) volume of the ventricles, to shocks given in diastole. Studies that have examined diastolic responses conducted measurements on the epicardium or on a transmural surface of the left ventricular (LV) wall only. The goal of this study was to use optical imaging experiments and 3D bidomain simulations, including a model of optical mapping, to ascertain the shock-induced virtual electrode and activation patterns throughout the rabbit ventricles following diastolic shocks. We tested the hypothesis that the locations of shock-induced regions of hyperpolarization govern the different diastolic activation patterns for shocks of reversed polarity. In model and experiment, uniform-field monophasic shocks of reversed polarities (cathode over the right ventricle is RV-, reverse polarity is LV-) were applied to the ventricles in diastole. Experiments and simulations revealed that RV- shocks resulted in longer activation times compared with LV- shocks of the same strength. 3D simulations demonstrated that RV- shocks induced a greater volume of hyperpolarization at shock end compared with LV- shocks; most of these hyperpolarized regions were located in the LV. The results of this study indicate that ventricular geometry plays an important role in both the location and size of the shock-induced virtual anodes that determine activation delay during the shock and subsequently affect shock-induced propagation. If regions of hyperpolarization that develop during the shock are sufficiently large, activation delay may persist until shock end.     

Immediate effects of thermal shocks on the plasma level of various components in the Rainbow trout: compounds indicating stress and protein fraction]

Rainbow trout were subjected to thermal shocks (9 degrees water temperature increase, 1 hr stay at 21 degrees and return to initial temperature) at the rate of 2 shocks a day during 1 day or 3 successive days. The observed changes only show a moderate reaction. cAMP does not vary; lactate slightly increases at 17 hr after the end of the shocks. Glucose seems to be the most reliable stress indicator; it increases at 2 hr and remains again above control value at 17 hr after a 3 day shock time. Fibrinogen increases after a 3 day shock time. Lastly, a strong decrease in low density lipoprotein level is seen at 17 hr following both shock duration times and from 2 hr in case of a 3 day shock time.     

Urbanization promotes the loss of seasonal dynamics in the semi-natural grasslands of an East Asian megacity

The biodiversity of agricultural landscapes has been noticeably affected by rapid urbanization. Although many studies have examined species diversity per unit area (alpha diversity), knowledge about the patterns of species turnover (beta diversity) in urban areas remains limited. Furthermore, most beta diversity studies have focused on spatial heterogeneity; however, losses of temporal heterogeneity resulting from urbanization remain limited. In this study, we examined how urbanization is associated with decreases in the seasonal heterogeneity of species composition, which could be used as an indicator of the loss of seasonality by ecologists and policy makers aiming to conserve biodiversity. We investigated (1) changes in species richness based on seasonal averages (alpha diversity) and (2) the seasonal turnover of species composition (beta diversity) for flowering plants and butterflies along a rural-urban gradient in semi-natural grasslands. The response variables were alpha and beta diversity for flowering plants and butterflies, and the explanatory variables were urban areas within a 1-km radius of the center of each site. Increasing urban area caused both the seasonal alpha and beta diversity of flowering plants and butterflies to decline. These results supported the homogenization hypothesis for the seasonality of plants and butterflies in semi-natural grasslands of dominant urban areas in East Asia. Future studies should focus on investigating how urbanization is causing both declines in seasonality and changes in the spatial heterogeneity of species composition and associated biodiversity loss. Ecologists and policy makers should focus on developing strategies to halt the loss of temporal biological heterogeneity to maintain biodiversity.     

系统理论指导下辩证思维模式与抗休克决策

休克是由于有效循环血量不足引发的微循环障碍而表现一系列症候群,作为一种系统性疾病,病因十分复杂多样,诊疗过程中的临床决策应全面而富有针对性,并充分考虑到救治措施的协调一致和互相配合。系统论主张整体大于部分之和强调的就是措施之间的整体化效果,充分考虑到患者个体间差异,辩证分析不同类型休克、不同个体间不同表现,在系统理论指导下的富有针对性措施间协调一致的决策模式才是较为完整的休克救治临床决策模式。