Between Treewidth and Clique-width

Many hard graph problems can be solved efficiently when restricted to graphs of bounded treewidth, and more generally to graphs of bounded clique-width. But there is a price to be paid for this generality, exemplified by the four problems MaxCut, Graph Coloring, Hamiltonian Cycle and Edge Dominating Set that are all FPT parameterized by treewidth but none of which can be FPT parameterized by clique-width unless FPT = W[1], as shown by Fomin et al [7, 8]. We therefore seek a structural graph parameter that shares some of the generality of clique-width without paying this price. Based on splits, branch decompositions and the work of Vatshelle [18] on Maximum Matching-width, we consider the graph parameter sm-width which lies between treewidth and clique-width. Some graph classes of unbounded treewidth, like distance-hereditary graphs, have bounded sm-width. We show that MaxCut, Graph Coloring, Hamiltonian Cycle and Edge Dominating Set are all FPT parameterized by sm-width

A Midbrain Circuit that Mediates Headache Aversiveness in Rats.

Migraines are a major health burden, but treatment is limited because of inadequate understanding of neural mechanisms underlying headache. Imaging studies of migraine patients demonstrate changes in both pain-modulatory circuits and reward-processing regions, but whether these changes contribute to the experience of headache is unknown. Here, we demonstrate a direct connection between the ventrolateral periaqueductal gray (vlPAG) and the ventral tegmental area (VTA) that contributes to headache aversiveness in rats. Many VTA neurons receive monosynaptic input from the vlPAG, and cranial nociceptive input increases Fos expression in VTA-projecting vlPAG neurons. Activation of PAG inputs to the VTA induces avoidance behavior, while inactivation of these projections induces a place preference only in animals with headache. This work identifies a distinct pathway that mediates cranial nociceptive aversiveness

Last interglacial temperature evolution – a model inter-comparison

Abstract. There is a growing number of proxy-based reconstructions detailing the climatic changes during the Last Interglacial period. This period is of special interest because large parts of the globe were characterized by a warmer-than-present-day climate, making this period an interesting test bed for climate models in the light of projected global warming. However, mainly because synchronizing the different records is difficult, there is no consensus on a global picture of Last Interglacial temperature changes. Here we present the first model inter-comparison of transient simulations covering the Last Interglacial period. By comparing the different simulations we aim at investigating the robustness of the simulated surface air temperature evolution. The model inter-comparison shows a robust Northern Hemisphere July temperature evolution characterized by a maximum between 130–122 ka BP with temperatures 0.4 to 6.8 K above pre-industrial values. This temperature evolution is in line with the changes in June insolation and greenhouse-gas concentrations. For the evolution of July temperatures in the Southern Hemisphere, the picture emerging from the inter-comparison is less clear. However, it does show that including greenhouse-gas concentration changes is critical. The simulations that include this forcing show an early, 128 ka BP July temperature anomaly maximum of 0.5 to 2.6 K. The robustness of simulated January temperatures is large in the Southern Hemisphere and the mid-latitudes of the Northern Hemisphere. In these latitudes maximum January temperature anomalies of respectively −2.5 to 2 K and 0 to 2 K are simulated for the period after 118 ka BP. The inter-comparison is inconclusive on the evolution of January temperatures in the high-latitudes of the Northern Hemisphere. Further investigation of regional anomalous patterns and inter-model differences indicate that in specific regions, feedbacks within the climate system are important for the simulated temperature evolution. Firstly in the Arctic region, changes in the summer sea-ice cover control the evolution of Last Interglacial winter temperatures. Secondly, for the Atlantic region, the Southern Ocean and the North Pacific, possible changes in the characteristics of the Atlantic meridional overturning circulation are critical. The third important feedback, having an impact on the temperature evolution of the Northern Hemisphere, is shown to be the presence of remnant continental ice from the preceding glacial period. Another important feedback are changes in the monsoon regime which controls the evolution of temperatures over parts of Africa and India. Finally, the simulations reveal an important land-sea contrast, with temperature changes over the oceans lagging continental temperatures by up to several thousand years. The aforementioned feedback mechanisms tend to be highly model-dependent, indicating that specific proxy-data is needed to constrain future climate simulations and to further enhance our understanding of the evolution of the climate during the Last Interglacial period

Binets: fundamental building blocks for phylogenetic networks

Phylogenetic networks are a generalization of evolutionary trees that are used by biologists to represent the evolution of organisms which have undergone reticulate evolution. Essentially, a phylogenetic network is a directed acyclic graph having a unique root in which the leaves are labelled by a given set of species. Recently, some approaches have been developed to construct phylogenetic networks from collections of networks on 2- and 3-leaved networks, which are known as binets and trinets, respectively. Here we study in more depth properties of collections of binets, one of the simplest possible types of networks into which a phylogenetic network can be decomposed. More speci_cally, we show that if a collection of level-1 binets is compatible with some binary network, then it is also compatible with a binary level-1 network. Our proofs are based on useful structural results concerning lowest stable ancestors in networks. In addition, we show that, although the binets do not determine the topology of the network, they do determine the number of reticulations in the network, which is one of its most important parameters. We also consider algorithmic questions concerning binets. We show that deciding whether an arbitrary set of binets is compatible with some network is at least as hard as the well-known Graph Isomorphism problem. However, if we restrict to level-1 binets, it is possible to decide in polynomial time whether there exists a binary network that displays all the binets. We also show that to _nd a network that displays a maximum number of the binets is NP-hard, but that there exists a simple polynomial-time 1/3-approximation algorithm for this problem. It is hoped that these results will eventually assist in the development of new methods for constructing phylogenetic networks from collections of smaller networks

Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

<p>Abstract</p> <p>Background</p> <p>Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart.</p> <p>Methods</p> <p>The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects.</p> <p>Results</p> <p>Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC₅₀values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine.</p> <p>Conclusions</p> <p>In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity.</p

Nucleolin, a Shuttle Protein Promoting Infection of Human Monocytes by Francisella tularensis

International audienceWe herein confirm the importance of nucleolin expression for LVS binding and its specificity as nucleolin is not involved in binding of another intracellular pathogen as L. monocytogenes or an inert particle. Association of nucleolin with F. tularensis during infection continues intracellularly after endocytosis of the bacteria. The present work therefore unravels for the first time the presence of nucleolin in the phagosomal compartment of macrophages

A Putative P-Type ATPase Required for Virulence and Resistance to Haem Toxicity in Listeria monocytogenes

Regulation of iron homeostasis in many pathogens is principally mediated by the ferric uptake regulator, Fur. Since acquisition of iron from the host is essential for the intracellular pathogen Listeria monocytogenes, we predicted the existence of Fur-regulated systems that support infection. We examined the contribution of nine Fur-regulated loci to the pathogenicity of L. monocytogenes in a murine model of infection. While mutating the majority of the genes failed to affect virulence, three mutants exhibited a significantly compromised virulence potential. Most striking was the role of the membrane protein we designate FrvA (Fur regulated virulence factor A; encoded by frvA [lmo0641]), which is absolutely required for the systemic phase of infection in mice and also for virulence in an alternative infection model, the Wax Moth Galleria mellonella. Further analysis of the ΔfrvA mutant revealed poor growth in iron deficient media and inhibition of growth by micromolar concentrations of haem or haemoglobin, a phenotype which may contribute to the attenuated growth of this mutant during infection. Uptake studies indicated that the ΔfrvA mutant is unaffected in the uptake of ferric citrate but demonstrates a significant increase in uptake of haem and haemin. The data suggest a potential role for FrvA as a haem exporter that functions, at least in part, to protect the cell against the potential toxicity of free haem

Glutathione Provides a Source of Cysteine Essential for Intracellular Multiplication of Francisella tularensis

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative γ-glutamyl transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, γ-glutamyl-cysteinyl-glycine) and γ-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria–host adaptation