Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons

In many strongly-interacting models of electroweak symmetry breaking the lowest-lying observable particle is a pseudo-Goldstone boson of approximate scale symmetry, the pseudo-dilaton. Its interactions with Standard Model particles can be described using a low-energy effective nonlinear chiral Lagrangian supplemented by terms that restore approximate scale symmetry, yielding couplings of the pseudo-dilaton that differ from those of a Standard Model Higgs boson by fixed factors. We review the experimental constraints on such a pseudo-dilaton in light of new data from the LHC and elsewhere. The effective nonlinear chiral Lagrangian has Skyrmion solutions that may be identified with the `electroweak baryons' of the underlying strongly-interacting theory, whose nature may be revealed by the properties of the Skyrmions. We discuss the finite-temperature electroweak phase transition in the low-energy effective theory, finding that the possibility of a first-order electroweak phase transition is resurrected. We discuss the evolution of the Universe during this transition and derive an order-of-magnitude lower limit on the abundance of electroweak baryons in the absence of a cosmological asymmetry, which suggests that such an asymmetry would be necessary if the electroweak baryons are to provide the cosmological density of dark matter. We revisit estimates of the corresponding spin-independent dark matter scattering cross section, with a view to direct detection experiments.Comment: 34 pages, 4 figures, additional references adde

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

The A-B transition in superfluid helium-3 under confinement in a thin slab geometry

The influence of confinement on the topological phases of superfluid 3He is studied using the torsional pendulum method. We focus on the phase transition between the chiral A-phase and the time-reversal-invariant B-phase, motivated by the prediction of a spatiallymodulated (stripe) phase at the A-B phase boundary. We confine superfluid 3He to a single 1.08 {\mu}m thick nanofluidic cavity incorporated into a high-precision torsion pendulum, and map the phase diagram between 0.1 and 5.6 bar. We observe only small supercooling of the A-phase, in comparison to bulk or when confined in aerogel. This has a non-monotonic pressure dependence, suggesting that a new intrinsic B-phase nucleation mechanism operates under confinement, mediated by the putative stripe phase. Both the phase diagram and the relative superfluid fraction of the A and B phases, show that strong coupling is present at all pressures, with implications for the stability of the stripe phase.Comment: 6 figures, 1 table + supplemental informatio

On the importance of the 1-loop finite corrections to seesaw neutrino masses

In the standard seesaw mechanism, finite corrections to the neutrino mass matrix arise from 1-loop self-energy diagrams mediated by a heavy neutrino. We study in detail these corrections and demonstrate that they can be very significant, exceeding in several cases the tree-level result. We consider the normal and inverted hierarchy spectra for light neutrinos and compute the finite corrections to the different elements of the neutrino mass matrix. Special attention is paid to their dependence with the parameters of the seesaw model. Among the cases in which the corrections can be large, we identify the fine-tuned models considered previously in the literature, where a strong cancellation between the different parameters is required to achieve compatibility with the experimental data. As a particular example, we also analyze how these corrections modify the tribimaximal mixing pattern and find that the deviations may be sizable, in particular for $\theta_{13}$. Finally, we emphasize that due to their large size, the finite corrections to neutrino masses have to be taken into account if one wants to properly scan the parameter space of seesaw models.Comment: 24 pages, 11 figure

Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria

<p>Abstract</p> <p>Background</p> <p>Many pathogens use a type III secretion system to translocate virulence proteins (called effectors) in order to adapt to the host environment. To date, many prediction tools for effector identification have been developed. However, these tools are insufficiently accurate for producing a list of putative effectors that can be applied directly for labor-intensive experimental verification. This also suggests that important features of effectors have yet to be fully characterized.</p> <p>Results</p> <p>In this study, we have constructed an accurate approach to predicting secreted virulence effectors from Gram-negative bacteria. This consists of a support vector machine-based discriminant analysis followed by a simple criteria-based filtering. The accuracy was assessed by estimating the average number of true positives in the top-20 ranking in the genome-wide screening. In the validation, 10 sets of 20 training and 20 testing examples were randomly selected from 40 known effectors of <it>Salmonella enterica </it>serovar Typhimurium LT2. On average, the SVM portion of our system predicted 9.7 true positives from 20 testing examples in the top-20 of the prediction. Removal of the N-terminal instability, codon adaptation index and ProtParam indices decreased the score to 7.6, 8.9 and 7.9, respectively. These discrimination features suggested that the following characteristics of effectors had been uncovered: unstable N-terminus, non-optimal codon usage, hydrophilic, and less aliphathic. The secondary filtering process represented by coexpression analysis and domain distribution analysis further refined the average true positive counts to 12.3. We further confirmed that our system can correctly predict known effectors of <it>P. syringae </it>DC3000, strongly indicating its feasibility.</p> <p>Conclusions</p> <p>We have successfully developed an accurate prediction system for screening effectors on a genome-wide scale. We confirmed the accuracy of our system by external validation using known effectors of <it>Salmonella </it>and obtained the accurate list of putative effectors of the organism. The level of accuracy was sufficient to yield candidates for gene-directed experimental verification. Furthermore, new features of effectors were revealed: non-optimal codon usage and instability of the N-terminal region. From these findings, a new working hypothesis is proposed regarding mechanisms controlling the translocation of virulence effectors and determining the substrate specificity encoded in the secretion system.</p

Sequence-Based Prediction of Type III Secreted Proteins

The type III secretion system (TTSS) is a key mechanism for host cell interaction used by a variety of bacterial pathogens and symbionts of plants and animals including humans. The TTSS represents a molecular syringe with which the bacteria deliver effector proteins directly into the host cell cytosol. Despite the importance of the TTSS for bacterial pathogenesis, recognition and targeting of type III secreted proteins has up until now been poorly understood. Several hypotheses are discussed, including an mRNA-based signal, a chaperon-mediated process, or an N-terminal signal peptide. In this study, we systematically analyzed the amino acid composition and secondary structure of N-termini of 100 experimentally verified effector proteins. Based on this, we developed a machine-learning approach for the prediction of TTSS effector proteins, taking into account N-terminal sequence features such as frequencies of amino acids, short peptides, or residues with certain physico-chemical properties. The resulting computational model revealed a strong type III secretion signal in the N-terminus that can be used to detect effectors with sensitivity of ∼71% and selectivity of ∼85%. This signal seems to be taxonomically universal and conserved among animal pathogens and plant symbionts, since we could successfully detect effector proteins if the respective group was excluded from training. The application of our prediction approach to 739 complete bacterial and archaeal genome sequences resulted in the identification of between 0% and 12% putative TTSS effector proteins. Comparison of effector proteins with orthologs that are not secreted by the TTSS showed no clear pattern of signal acquisition by fusion, suggesting convergent evolutionary processes shaping the type III secretion signal. The newly developed program EffectiveT3 (http://www.chlamydiaedb.org) is the first universal in silico prediction program for the identification of novel TTSS effectors. Our findings will facilitate further studies on and improve our understanding of type III secretion and its role in pathogen–host interactions

How to find simple and accurate rules for viral protease cleavage specificities

<p>Abstract</p> <p>Background</p> <p>Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way.</p> <p>Results</p> <p>A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods.</p> <p>Conclusion</p> <p>A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.</p

Deletions in the Repertoire of Pseudomonas syringae pv. tomato DC3000 Type III Secretion Effector Genes Reveal Functional Overlap among Effectors

The γ-proteobacterial plant pathogen Pseudomonas syringae pv. tomato DC3000 uses the type III secretion system to inject ca. 28 Avr/Hop effector proteins into plants, which enables the bacterium to grow from low inoculum levels to produce bacterial speck symptoms in tomato, Arabidopsis thaliana, and (when lacking hopQ1-1) Nicotiana benthamiana. The effectors are collectively essential but individually dispensable for the ability of the bacteria to defeat defenses, grow, and produce symptoms in plants. Eighteen of the effector genes are clustered in six genomic islands/islets. Combinatorial deletions involving these clusters and two of the remaining effector genes revealed a redundancy-based structure in the effector repertoire, such that some deletions diminished growth in N. benthamiana only in combination with other deletions. Much of the ability of DC3000 to grow in N. benthamiana was found to be due to five effectors in two redundant-effector groups (REGs), which appear to separately target two high-level processes in plant defense: perception of external pathogen signals (AvrPto and AvrPtoB) and deployment of antimicrobial factors (AvrE, HopM1, HopR1). Further support for the membership of HopR1 in the same REG as AvrE was gained through bioinformatic analysis, revealing the existence of an AvrE/DspA/E/HopR effector superfamily, which has representatives in virtually all groups of proteobacterial plant pathogens that deploy type III effectors

Genome Sequence Analyses of Pseudomonas savastanoi pv. glycinea and Subtractive Hybridization-Based Comparative Genomics with Nine Pseudomonads

Bacterial blight, caused by Pseudomonas savastanoi pv. glycinea (Psg), is a common disease of soybean. In an effort to compare a current field isolate with one isolated in the early 1960s, the genomes of two Psg strains, race 4 and B076, were sequenced using 454 pyrosequencing. The genomes of both Psg strains share more than 4,900 highly conserved genes, indicating very low genetic diversity between Psg genomes. Though conserved, genome rearrangements and recombination events occur commonly within the two Psg genomes. When compared to each other, 437 and 163 specific genes were identified in B076 and race 4, respectively. Most specific genes are plasmid-borne, indicating that acquisition and maintenance of plasmids may represent a major mechanism to change the genetic composition of the genome and even acquire new virulence factors. Type three secretion gene clusters of Psg strains are near identical with that of P. savastanoi pv. phaseolicola (Pph) strain 1448A and they shared 20 common effector genes. Furthermore, the coronatine biosynthetic cluster is present on a large plasmid in strain B076, but not in race 4. In silico subtractive hybridization-based comparative genomic analyses with nine sequenced phytopathogenic pseudomonads identified dozens of specific islands (SIs), and revealed that the genomes of Psg strains are more similar to those belonging to the same genomospecies such as Pph 1448A than to other phytopathogenic pseudomonads. The number of highly conserved genes (core genome) among them decreased dramatically when more genomes were included in the subtraction, suggesting the diversification of pseudomonads, and further indicating the genome heterogeneity among pseudomonads. However, the number of specific genes did not change significantly, suggesting these genes are indeed specific in Psg genomes. These results reinforce the idea of a species complex of P. syringae and support the reclassification of P. syringae into different species

The Extended Cleavage Specificity of Human Thrombin

Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1′-Ser/Ala/Gly/Thr, P2′-not acidic and P3′-Arg. Our analysis also identifies an important role for a P3′-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3′-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200–400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1–30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times