C.elegans as a Diabetes & Ischemia Model: Identification of Genetic and Cellular Changes that Modulate the Survival of Hyperglycemia and Oxygen-Deprivation

Diet represents an exogenous influence that often yields colossal effects on an individual’s phenotype, physiology, long-term health and disease risk. The overconsumption of dietary sugars for example, has contributed to significant increases in obesity and type 2 diabetes, health issues that are costly both in terms of dollars and human life. Additionally, individuals with these conditions have compromised oxygen delivery and thus, an increased vulnerability to other oxygen-deprivation related disease states, including cardiovascular disease, ischemic strokes, vascular and coronary diseases and myocardial infarction. While human and other mammalian studies have shown that individuals with type 2 diabetes have a worse prognosis and recovery after being challenged with an oxygen-deprivation related injury, mechanistic understanding regarding why this is the case is lacking. We are using C. elegans to identify genetic and cellular changes that modulate responses to the combinatory stress of hyperglycemia and oxygen-deprivation. We have determined that C. elegans fed a high glucose diet have increased cellular glucose (hyperglycemia), increased lipid content and increased sensitivity to oxygen-deprivation (anoxia) and ROS induction. We have determined that the insulin-like signaling pathway, via fatty acid and ceramide synthesis, modulates the increased sensitivity to anoxia. In mammalian systems, specific ceramide species increase after an ischemic event and are also linked to detrimental effects observed in diabetic patients, underscoring the potential role these molecules have in modulating oxygen-deprivation and hyperglycemia responses in individuals. Specific fatty acids also have known roles as both signaling molecules and as integral membrane components, thus, we hypothesize that a high-glucose diet disrupts fatty acid and ceramide homeostasis resulting in aberrations in metabolic processes and stress response pathways that are essential for the survival of oxygen-deprivation. Additionally, gene expression analysis (via RNAseq) on C. elegans fed either a standard or glucose-supplemented diet revealed that glucose impacts the expression of genes involved with multiple cellular processes, including lipid and carbohydrate metabolism, stress responses, cell division and extracellular functions. Several of the genes we identified are also differentially regulated in obese and type-2 diabetic human individuals, indicating a high degree of conserved gene expression changes between C. elegans fed a glucose-supplemented diet and in diabetic and/or obese human individuals. Together this work underscores how both diet and genotype impact stress responses and supports the use of C. elegans as a model for further elucidating the molecular mechanisms regulating dietary-induced metabolic diseases

Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

Measurement of the diffractive structure function in deep inelastic scattering at HERA

This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in $ep$ interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of \xpom, the momentum fraction lost by the proton, of $\beta$, the momentum fraction of the struck quark with respect to \xpom, and of $Q^2$. The \xpom dependence is consistent with the form \xpoma where $a~=~1.30~\pm~0.08~(stat)~^{+~0.08}_{-~0.14}~(sys)$ in all bins of $\beta$ and $Q^2$. In the measured $Q^2$ range, the diffractive structure function approximately scales with $Q^2$ at fixed $\beta$. In an Ingelman-Schlein type model, where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil

Spatial Orientation in Japanese Quails (Coturnix coturnix japonica)

Finding a given location can be based on a variety of strategies, for example on the estimation of spatial relations between landmarks, called spatial orientation. In galliform birds, spatial orientation has been demonstrated convincingly in very young domestic chicks. We wanted to know whether adult Japanese quails (Coturnix coturnix japonica) without food deprivation are also able to use spatial orientation. The quails had to learn the relation of a food location with four conspicuous landmarks which were placed in the corners of a square shaped arena. They were trained to find mealworms in three adjacent food cups in a circle of 20 such cups. The rewarded feeders were located during training between the same two landmarks each of which showed a distinct pattern. When the birds had learned the task, all landmarks were displaced clockwise by 90 degrees. When tested in the new situation, all birds redirected their choices with respect to the landmark shift. In subsequent tests, however, the previously correct position was also chosen. According to our results, quails are using conspicuous landmarks as a first choice for orientation. The orientation towards the previously rewarded location, however, indicates that the neuronal representation of space which is used by the birds also includes more fine grain, less conspicuous cues, which are probably also taken into account in uncertain situations. We also presume that the rare orientation towards never rewarded feeders may be due to a foraging strategy instead of being mistakes

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Observation of direct processes in photoproduction at HERA

Jets in photoproduction events have been studied with the ZEUS detector for gammap centre-of-mass energies ranging from 130 to 2 50 GeV. The inclusive jet distributions give evidence for the dominance of resolved photon interactions. In the di-jet sample the direct processes are for the first time clearly isolated. Di-jet cross sections for the resolved and direct processes are given in a restricted kinematic range

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

Measurement of the F2 structure function in deep inelastic e+^{+}p scattering using 1994 data from the ZEUS detector at HERA

We present measurements of the structure function \Ft\ in e^+p scattering at HERA in the range 3.5\;\Gevsq < \qsd < 5000\;\Gevsq. A new reconstruction method has allowed a significant improvement in the resolution of the kinematic variables and an extension of the kinematic region covered by the experiment. At \qsd < 35 \;\Gevsq the range in x now spans 6.3\cdot 10^{-5} < x < 0.08 providing overlap with measurements from fixed target experiments. At values of Q^2 above 1000 GeV^2 the x range extends to 0.5. Systematic errors below 5\perc\ have been achieved for most of the kinematic urray, W

Measurement of Elastic ϕ\phi Photoproduction at HERA

The production of $\phi$ mesons in the reaction $e^{+}p \rightarrow e^{+} \phi p$ ($\phi \rightarrow K^{+}K^{-}$) at a median $Q^{2}$ of $10^{-4} \ \rm{GeV^2}$has been studied with the ZEUS detector at HERA. The differential$\phi$photoproduction cross section$d\sigma/dt$has an exponential shape and has been determined in the kinematic range$0.1<|t|<0.5 \ \rm{GeV^2}$and$60 < W < 80 \ \rm{GeV}$. An integrated cross section of$\sigma_{\gamma p \rightarrow \phi p} = 0.96 \pm 0.19^{+0.21}_{-0.18}$$\rm{\mu b}$has been obtained by extrapolating to {\it t} = 0. When compared to lower energy data, the results show a weak energy dependence of both$\sigma_{\gamma p \rightarrow \phi p}$and the slope of the$t$distribution. The$\phi$decay angular distributions are consistent with$s$-channel helicity conservation. From lower energies to HERA energies, the features of$\phi$ photoproduction are compatible with those of a soft diffractive process.Comment: 23 pages, including 6 post script figure

Ecological networks: Pursuing the shortest path, however narrow and crooked

International audienceRepresenting data as networks cuts across all sub-disciplines in ecology and evolutionary biology. Besides providing a compact representation of the interconnections between agents, network analysis allows the identification of especially important nodes, according to various metrics that often rely on the calculation of the shortest paths connecting any two nodes. While the interpretation of a shortest paths is straightforward in binary, unweighted networks, whenever weights are reported, the calculation could yield unexpected results. We analyzed 129 studies of ecological networks published in the last decade that use shortest paths, and discovered a methodological inaccuracy related to the edge weights used to calculate shortest paths (and related centrality measures), particularly in interaction networks. Specifically, 49% of the studies do not report sufficient information on the calculation to allow their replication, and 61% of the studies on weighted networks may contain errors in how shortest paths are calculated. Using toy models and empirical ecological data, we show how to transform the data prior to calculation and illustrate the pitfalls that need to be avoided. We conclude by proposing a five-point checklist to foster best-practices in the calculation and reporting of centrality measures in ecology and evolution studies. The last two decades have witnessed an exponential increase in the use of graph analysis in ecological and conservation studies (see refs. 1,2 for recent introductions to network theory in ecology and evolution). Networks (graphs) represent agents as nodes linked by edges representing pairwise relationships. For instance, a food web can be represented as a network of species (nodes) and their feeding relationships (edges) 3. Similarly, the spatial dynamics of a metapopulation can be analyzed by connecting the patches of suitable habitat (nodes) with edges measuring dispersal between patches 4. Data might either simply report the presence/absence of an edge (binary, unweighted networks), or provide a strength for each edge (weighted networks). In turn, these weights can represent a variety of ecologically-relevant quantities, depending on the system being described. For instance, edge weights can quantify interaction frequency (e.g., visitation networks 5), interaction strength (e.g., per-capita effect of one species on the growth rate of another 3), carbon-flow between trophic levels 6 , genetic similarity 7 , niche overlap (e.g., number of shared resources between two species 8), affinity 9 , dispersal probabilities (e.g., the rate at which individuals of a population move between patches 10), cost of dispersal between patches (e.g., resistance 11), etc. Despite such large variety of ecological network representations, a common task is the identification of nodes of high importance, such as keystone species in a food web, patches acting as stepping stones in a dispersal network , or genes with pleiotropic effects. The identification of important nodes is typically accomplished through centrality measures 5,12. Many centrality measures has been proposed, each probing complementary aspects of node-to-node relationships 13. For instance, Closeness centrality 14,15 highlights nodes that are "near" to all othe