Traveling and Pinned Fronts in Bistable Reaction-Diffusion Systems on Networks

Traveling fronts and stationary localized patterns in bistable reaction-diffusion systems have been broadly studied for classical continuous media and regular lattices. Analogs of such non-equilibrium patterns are also possible in networks. Here, we consider traveling and stationary patterns in bistable one-component systems on random Erdös-Rényi, scale-free and hierarchical tree networks. As revealed through numerical simulations, traveling fronts exist in network-organized systems. They represent waves of transition from one stable state into another, spreading over the entire network. The fronts can furthermore be pinned, thus forming stationary structures. While pinning of fronts has previously been considered for chains of diffusively coupled bistable elements, the network architecture brings about significant differences. An important role is played by the degree (the number of connections) of a node. For regular trees with a fixed branching factor, the pinning conditions are analytically determined. For large Erdös-Rényi and scale-free networks, the mean-field theory for stationary patterns is constructed.     

Thermodynamics of Random Reaction Networks

Reaction networks are useful for analyzing reaction systems occurring in chemistry, systems biology, or Earth system science. Despite the importance of thermodynamic disequilibrium for many of those systems, the general thermodynamic properties of reaction networks are poorly understood. To circumvent the problem of sparse thermodynamic data, we generate artificial reaction networks and investigate their non-equilibrium steady state for various boundary fluxes. We generate linear and nonlinear networks using four different complex network models (Erdős-Rényi, Barabási-Albert, Watts-Strogatz, Pan-Sinha) and compare their topological properties with real reaction networks. For similar boundary conditions the steady state flow through the linear networks is about one order of magnitude higher than the flow through comparable nonlinear networks. In all networks, the flow decreases with the distance between the inflow and outflow boundary species, with Watts-Strogatz networks showing a significantly smaller slope compared to the three other network types. The distribution of entropy production of the individual reactions inside the network follows a power law in the intermediate region with an exponent of circa −1.5 for linear and −1.66 for nonlinear networks. An elevated entropy production rate is found in reactions associated with weakly connected species. This effect is stronger in nonlinear networks than in the linear ones. Increasing the flow through the nonlinear networks also increases the number of cycles and leads to a narrower distribution of chemical potentials. We conclude that the relation between distribution of dissipation, network topology and strength of disequilibrium is nontrivial and can be studied systematically by artificial reaction networks.     

Interplay between Graph Topology and Correlations of Third Order in Spiking Neuronal Networks

The study of processes evolving on networks has recently become a very popular research field, not only because of the rich mathematical theory that underpins it, but also because of its many possible applications, a number of them in the field of biology. Indeed, molecular signaling pathways, gene regulation, predator-prey interactions and the communication between neurons in the brain can be seen as examples of networks with complex dynamics. The properties of such dynamics depend largely on the topology of the underlying network graph. In this work, we want to answer the following question: Knowing network connectivity, what can be said about the level of third-order correlations that will characterize the network dynamics? We consider a linear point process as a model for pulse-coded, or spiking activity in a neuronal network. Using recent results from theory of such processes, we study third-order correlations between spike trains in such a system and explain which features of the network graph (i.e. which topological motifs) are responsible for their emergence. Comparing two different models of network topology—random networks of Erdős-Rényi type and networks with highly interconnected hubs—we find that, in random networks, the average measure of third-order correlations does not depend on the local connectivity properties, but rather on global parameters, such as the connection probability. This, however, ceases to be the case in networks with a geometric out-degree distribution, where topological specificities have a strong impact on average correlations.     

A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models

We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.     

Immunization of Epidemics in Multiplex Networks

Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks.     

Osteological and Biomolecular Evidence of a 7000-Year-Old Case of Hypertrophic Pulmonary Osteopathy Secondary to Tuberculosis from Neolithic Hungary

Seventy-one individuals from the late Neolithic population of the 7000-year-old site of Hódmezővásárhely-Gorzsa were examined for their skeletal palaeopathology. This revealed numerous cases of infections and non-specific stress indicators in juveniles and adults, metabolic diseases in juveniles, and evidence of trauma and mechanical changes in adults. Several cases showed potential signs of tuberculosis, particularly the remains of the individual HGO-53. This is an important finding that has significant implications for our understanding of this community. The aim of the present study was to seek biomolecular evidence to confirm this diagnosis. HGO-53 was a young male with a striking case of hypertrophic pulmonary osteopathy (HPO), revealing rib changes and cavitations in the vertebral bodies. The initial macroscopic diagnosis of HPO secondary to tuberculosis was confirmed by analysis of Mycobacterium tuberculosis complex specific cell wall lipid biomarkers and corroborated by ancient DNA (aDNA) analysis. This case is the earliest known classical case of HPO on an adult human skeleton and is one of the oldest palaeopathological and palaeomicrobiological tuberculosis cases to date.     

Recent Developments in Nematode Steroid Biochemistry

Current knowledge of steroid nutrition, metabolism, and function in free-living, plant-parasitic and animal-parasitic nematodes is reviewed, with emphasis upon recent investigation of Caenorhabditis elegans. A number of 4-desmethylsterols with a trans-A/B ring configuration can satisfy the steroid nutritional requirement in C. elegans, but sterols with a cis-A/B ring configuration or trans-A/B sterols with a 4-methyl group cannot. C. elegans removes methyl or ethyl substituents at C-24 of the plant sterols sitosterol, campesterol, stigmasterol, stigmastanol, and 24-methylene-cholesterol to produce various sterols with structures partially dependent upon that of the dietary sterol. Additional metabolic steps in C. elegans include reduction of Δ²²- and Δ⁵-bonds, C-7 dehydrogenation, isomerization of a Δ⁷-bond to a Δ⁸⁽¹⁴⁾-bond, and 4α-methylation. An azasteroid and several long-chain alkyl amines interfere with the dealkylation pathway in C. elegans by inhibiting the Δ²⁴-sterol reductase; these compounds also inhibit growth and reproduction in various plant-parasitic and animal-parasitic nematodes. A possible hormonal role for various steroids identified in nematodes is discussed.     

Synaptic polarity and sign-balance prediction using gene expression data in the Caenorhabditis elegans chemical synapse neuronal connectome network

Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The chemical synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the ionotropic chemical synapse connectome of C. elegans (3,638 connections and 20,589 synapses total), incorporating available presynaptic neurotransmitter and postsynaptic receptor gene expression data for three major neurotransmitter systems. We made predictions for more than two-thirds of these chemical synapses and observed an excitatory-inhibitory (E:I) ratio close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.     

Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling

Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin''s high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method''s sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism.     

Computer Assisted Assembly of Connectomes from Electron Micrographs: Application to Caenorhabditis elegans

A rate-limiting step in determining a connectome, the set of all synaptic connections in a nervous system, is extraction of the relevant information from serial electron micrographs. Here we introduce a software application, Elegance, that speeds acquisition of the minimal dataset necessary, allowing the discovery of new connectomes. We have used Elegance to obtain new connectivity data in the nematode worm Caenorhabditis elegans. We analyze the accuracy that can be obtained, which is limited by unresolvable ambiguities at some locations in electron microscopic images. Elegance is useful for reconstructing connectivity in any region of neuropil of sufficiently small size.     

Dynamic functional connectivity in the static connectome of Caenorhabditis elegans

A hallmark of adaptive behavior is the ability to flexibly respond to sensory cues. To understand how neural circuits implement this flexibility, it is critical to resolve how a static anatomical connectome can be modulated such that functional connectivity in the network can be dynamically regulated. Here, we review recent work in the roundworm Caenorhabditis elegans on this topic. EM studies have mapped anatomical connectomes of many C. elegans animals, highlighting the level of stereotypy in the anatomical network. Brain-wide calcium imaging and studies of specified neural circuits have uncovered striking flexibility in the functional coupling of neurons. The coupling between neurons is controlled by neuromodulators that act over long timescales. This gives rise to persistent behavioral states that animals switch between, allowing them to generate adaptive behavioral responses across environmental conditions. Thus, the dynamic coupling of neurons enables multiple behavioral states to be encoded in a physically stereotyped connectome.     

Diatoms and Other Epibionts Associated with Olive Ridley (Lepidochelys olivacea) Sea Turtles from the Pacific Coast of Costa Rica

Although the sea turtles have long been familiar and even iconic to marine biologists, many aspects of their ecology remain unaddressed. The present study is the first of the epizoic diatom community covering the olive ridley turtle’s (Lepidochelys olivacea) carapace and the first describing diatoms living on sea turtles in general, with the primary objective of providing detailed information on turtle epibiotic associations. Samples of turtle carapace including the associated diatom biofilm and epizoic macro-fauna were collected from Ostional beach (9° 59´ 23.7´´ N 85° 41´ 52.6´´ W), Costa Rica, during the arribada event in October 2013. A complex diatom community was present in every sample. In total, 11 macro-faunal and 21 diatom taxa were recorded. Amongst diatoms, the most numerous were erect (Achnanthes spp., Tripterion spp.) and motile (Haslea sp., Navicula spp., Nitzschia spp., Proschkinia sp.) forms, followed by adnate Amphora spp., while the most common macro-faunal species was Stomatolepas elegans (Cirripedia). Diatom densities ranged from 8179 ± 750 to 27685 ± 4885 cells mm^-2. Epizoic microalgae were either partly immersed or entirely encapsulated within an exopolymeric coat. The relatively low diatom species number, stable species composition and low inter-sample dissimilarities (14.4% on average) may indicate a mutualistic relationship between the epibiont and the basibiont. Dispersal of sea turtle diatoms is probably highly restricted and similar studies will help to understand both diatom diversity, evolution and biogeography, and sea turtle ecology and foraging strategies.     

Truffle Br?lés Have an Impact on the Diversity of Soil Bacterial Communities

Background

The development of Tuber melanosporum mycorrhizal symbiosis is associated with the production of an area devoid of vegetation (commonly referred to by the French word ‘brûlé’) around the symbiotic plants and where the fruiting bodies of T. melanosporum are usually collected. The extent of the ecological impact of such an area is still being discovered. While the relationship between T. melanosporum and the other fungi present in the brûlé has been assessed, no data are available on the relationship between this fungus and the bacteria inhabiting the brûlé.

Methodology/Principal Findings

We used DGGE and DNA microarrays of 16S rRNA gene fragments to compare the bacterial and archaeal communities inside and outside of truffle brûlés. Soil samples were collected in 2008 from four productive T. melanosporum/Quercus pubescens truffle-grounds located in Cahors, France, showing characteristic truffle brûlé. All the samples were analyzed by DGGE and one truffle-ground was analyzed also using phylogenetic microarrays. DGGE profiles showed differences in the bacterial community composition, and the microarrays revealed a few differences in relative richness between the brûlé interior and exterior zones, as well as differences in the relative abundance of several taxa.

Conclusions/Significance

The different signal intensities we have measured for members of bacteria and archaea inside versus outside the brûlé are the first demonstration, to our knowledge, that not only fungal communities, but also other microorganisms are affected by T. melanosporum. Firmicutes (e.g., Bacillus), several genera of Actinobacteria, and a few Cyanobacteria had greater representation inside the brûlé compared with outside, whereas Pseudomonas and several genera within the class Flavobacteriaceae had higher relative abundances outside the brûlé. The findings from this study may contribute to future searches for microbial bio-indicators of brûlés.     

Ecdysteroids in Axenically Propagated Caenorhabditis elegans and Culture Medium

Ecdysteroids (insect molting hormones) from Caenorhabditis elegans were chromatographically purified and quantified by radioimmunoassay. Nematodes from semidefined medium contained the immunoreactive equivalent of 460 pg ecdysone per gram dry weight. Culture medium, however, contained the immunoreactive equivalent of 68 times the quantity within the nematodes. In a defined medium lacking immunoreactivity, C. elegans contained 520 pg ecdysone equivalents per gram dry weight but reproduced slowly. Reproduction of C. elegans in defined medium was enhanced by formulation in agar. Propagation of C. elegans in either agar-based or aqueous defined medium supplemented with [¹⁴C]cholesterol of high specific activity failed to result in production of radiolabeled free ecdysteroids or polar or apolar ecdysteroid conjugates. Failure to demonstrate ecdysteroid biosynthesis in C. elegans raises questions about the ecdysteroids identified previously in nematodes being products of endogenous biosynthesis, a necessary condition for these compounds to be nematode hormones.     

Cellular hypersensitivity in Guillain-Barré syndrome

The Guillain-Barré syndrome is hypothesized to be secondary to cellular hypersensitivity to peripheral nerve antigens. To test this theory lymphocytes from 100 subjects were studied using the macrophage-migration-inhibition factor (MIF) assay. Thirty-four normal controls gave a mean migration of 100.4 ± 9%. Of 34 patients with peripheral nervous system disease, only those with the Guillain-Barré syndrome showed hypersensitivity with a mean migration of 72 ± 11%. Of 34 patients with central nervous system disease only three with multiple sclerosis and two with stroke gave similar results. Positive results in the Guillain-Barré syndrome were found only in patients presenting with classical disease and who were ill at the time of study.     

Investigating the Role of Assessment Method on Reports of Déjà Vu and Tip-of-the-Tongue States during Standard Recognition Tests

Déjà vu and tip-of-the-tongue (TOT) are retrieval-related subjective experiences whose study relies on participant self-report. In four experiments (ns = 224, 273, 123 and 154), we explored the effect of questioning method on reported occurrence of déjà vu and TOT in experimental settings. All participants carried out a continuous recognition task, which was not expected to induce déjà vu or TOT, but were asked about their experiences of these subjective states. When presented with contemporary definitions, between 32% and 58% of participants nonetheless reported experiencing déjà vu or TOT. Changing the definition of déjà vu or asking participants to bring to mind a real-life instance of déjà vu or TOT before completing the recognition task had no impact on reporting rates. However, there was an indication that changing the method of requesting subjective reports impacted reporting of both experiences. More specifically, moving from the commonly used retrospective questioning (e.g. “Have you experienced déjà vu?”) to free report instructions (e.g. “Indicate whenever you experience déjà vu.”) reduced the total number of reported déjà vu and TOT occurrences. We suggest that research on subjective experiences should move toward free report assessments. Such a shift would potentially reduce the presence of false alarms in experimental work, thereby reducing the overestimation of subjective experiences prevalent in this area of research.     

Limited microsynteny between the genomes of Pristionchus pacificus and Caenorhabditis elegans

Nematodes are an attractive group of organisms for studying the evolution of developmental processes. Pristionchus pacificus was established as a satellite organism for comparing vulva development and other processes to Caenorhabditis elegans. The generation of a genetic linkage map of P.pacificus has provided a first insight into the structure and organization of the genome of this species. Pristionchus pacificus and C.elegans are separated from one another by >100 000 000 years such that the structure of the genomes of these two nematodes might differ substantially. To evaluate the amount of synteny between the two genomes, we have obtained 126 kb of continuous genomic sequence of P.pacificus, flanking the developmental patterning gene pal-1. Of the 20 predicted open reading frames in this interval, 11 have C.elegans orthologs. Ten of these 11 orthologs are located on C.elegans chromosome III, indicating the existence of synteny. However, most of these genes are distributed over a 12 Mb interval of the C.elegans genome and only three pairs of genes show microsynteny. Thus, intrachromosomal rearrange ments occur frequently in nematodes, limiting the likelihood of identifying orthologous genes of P.pacificus and C.elegans based on positional information within the two genomes.     

Effect of Temperature Pre-Exposure on the Locomotion and Chemotaxis of C. elegans

The effect of temperature pre-exposure on locomotion and chemotaxis of the soil-dwelling nematode Caenorhabditis elegans has been extensively studied. The behavior of C. elegans was quantified using a simple harmonic curvature-based model. Animals showed increased levels of activity, compared to control worms, immediately after pre-exposure to 30°C. This high level of activity in C. elegans translated into frequent turns by making ‘complex’ shapes, higher velocity of locomotion, and higher chemotaxis index () in presence of a gradient of chemoattractant. The effect of pre-exposure was observed to be persistent for about 20 minutes after which the behavior (including velocity and ) appeared to be comparable to that of control animals (maintained at 20°C). Surprisingly, after 30 minutes of recovery, the behavior of C. elegans continued to deteriorate further below that of control worms with a drastic reduction in the curvature of the worms'' body. A majority of these worms also showed negative chemotaxis index indicating a loss in their chemotaxis ability.