1,949 research outputs found
Terminal Reassortment Drives the Quantum Evolution of Type III Effectors in Bacterial Pathogens
Many bacterial pathogens employ a type III secretion system to deliver type III secreted effectors (T3SEs) into host cells, where they interact directly with host substrates to modulate defense pathways and promote disease. This interaction creates intense selective pressures on these secreted effectors, necessitating rapid evolution to overcome host surveillance systems and defenses. Using computational and evolutionary approaches, we have identified numerous mosaic and truncated T3SEs among animal and plant pathogens. We propose that these secreted virulence genes have evolved through a shuffling process we have called âterminal reassortment.â In terminal reassortment, existing T3SE termini are mobilized within the genome, creating random genetic fusions that result in chimeric genes. Up to 32% of T3SE families in species with relatively large and well-characterized T3SE repertoires show evidence of terminal reassortment, as compared to only 7% of non-T3SE families. Terminal reassortment may permit the near instantaneous evolution of new T3SEs and appears responsible for major modifications to effector activity and function. Because this process plays a more significant role in the evolution of T3SEs than non-effectors, it provides insight into the evolutionary origins of T3SEs and may also help explain the rapid emergence of new infectious agents
Critical exponents predicted by grouping of Feynman diagrams in phi^4 model
Different perturbation theory treatments of the Ginzburg-Landau phase
transition model are discussed. This includes a criticism of the perturbative
renormalization group (RG) approach and a proposal of a novel method providing
critical exponents consistent with the known exact solutions in two dimensions.
The usual perturbation theory is reorganized by appropriate grouping of Feynman
diagrams of phi^4 model with O(n) symmetry. As a result, equations for
calculation of the two-point correlation function are obtained which allow to
predict possible exact values of critical exponents in two and three dimensions
by proving relevant scaling properties of the asymptotic solution at (and near)
the criticality. The new values of critical exponents are discussed and
compared to the results of numerical simulations and experiments.Comment: 34 pages, 6 figure
Type III Effector Diversification via Both Pathoadaptation and Horizontal Transfer in Response to a Coevolutionary Arms Race
The concept of the coevolutionary arms race holds a central position in our understanding of pathogenâhost interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among âŒ45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteineâprotease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range
Nanoscale phase-engineering of thermal transport with a Josephson heat modulator
Macroscopic quantum phase coherence has one of its pivotal expressions in the
Josephson effect [1], which manifests itself both in charge [2] and energy
transport [3-5]. The ability to master the amount of heat transferred through
two tunnel-coupled superconductors by tuning their phase difference is the core
of coherent caloritronics [4-6], and is expected to be a key tool in a number
of nanoscience fields, including solid state cooling [7], thermal isolation [8,
9], radiation detection [7], quantum information [10, 11] and thermal logic
[12]. Here we show the realization of the first balanced Josephson heat
modulator [13] designed to offer full control at the nanoscale over the
phase-coherent component of thermal currents. Our device provides
magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a
maximum of the flux-to-temperature transfer coefficient reaching 200 mK per
flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the
exact correspondence in the phase-engineering of charge and heat currents,
breaking ground for advanced caloritronic nanodevices such as thermal splitters
[14], heat pumps [15] and time-dependent electronic engines [16-19].Comment: 6+ pages, 4 color figure
Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument
We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents
A formally verified compiler back-end
This article describes the development and formal verification (proof of
semantic preservation) of a compiler back-end from Cminor (a simple imperative
intermediate language) to PowerPC assembly code, using the Coq proof assistant
both for programming the compiler and for proving its correctness. Such a
verified compiler is useful in the context of formal methods applied to the
certification of critical software: the verification of the compiler guarantees
that the safety properties proved on the source code hold for the executable
compiled code as well
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