Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata

<b>BACKGROUND</b>: Little is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population. <b>RESULTS</b>: Strong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites. <b>CONCLUSIONS</b>: This analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response

Wills, Trusts, and Estates

Between legislative and judicial activity, there have been a number of noteworthy developments and changes to the rules governing trusts and estates. Several of these developments turn on questions related to the role of fiduciaries, what responsibilities they have with respect to reporting as well as asset management, and when they can be removed. These questions concerning fiduciaries implicitly address the rights of beneficiaries and the protections available to them. New developments also will have multiple repercussions for estate planners and wealth managers. New planning strategies in response to changes in the law of undue influence may become important to consider and recent judicial opinions may influence a planner’s drafting decisions, particularly with respect to no-contest and arbitration clauses. Overall, the developments clarify the balance of rights and responsibilities allocated between settlors, beneficiaries, and fiduciaries and, in many cases, bolster the rights of beneficiaries and those under legal guardianship

Core medicines for quality care of the dying

The proposal by Lindqvist and colleagues of four essential medicines for the control of terminal symptoms is commendable. Having a finite essential medication list facilitates prescribers to prescribe and pharmacies to stock and supply medications to support end-of-life care in the community. With this issue in mind, a recent collaboration of South Australian palliative care clinicians developed a core medicines list for the treatment of symptoms commonly seen at the end of life. As for Lindqvist’s model, we also involved widespread consultation with key palliative care stakeholders

Electroweak Corrections to the Top Quark Decay

We have calculated the one-loop electroweak corrections to the decay t-> bW+, including the counterterm for the CKM matrix elements V(tb). Previous calculations used an incorrect delta V(tb) that led to a gauge dependent amplitude. However, since the contribution stemming from delta V(tb) is small, those calculations only underestimate the width by roughly one part in 10^5.Comment: 7 pages, 2 figure

Measuring the W-t-b Interaction at the ILC

The large top quark mass suggests that the top plays a pivotal role in Electroweak symmetry-breaking dynamics and, as a result, may have modified couplings to Electroweak bosons. Hadron colliders can provide measurements of these couplings at the ~10% level, and one of the early expected triumphs of the International Linear Collider is to reduce these uncertainties to the per cent level. In this article, we propose the first direct measurement of the Standard Model W-t-b coupling at the ILC, from measurements of t tbar-like signals below the t tbar production threshold. We estimate that the ILC with 100 fb^{-1} can measure a combination of the coupling and top width to high precision, and when combined with a direct measurement of the top width from the above-threshold scan, results in a model-independent measurement of the W-t-b interaction of the order of ~ 3%

Proton Lifetime and Baryon Number Violating Signatures at the LHC in Gauge Extended Models

There exist a number of models in the literature in which the weak interactions are derived from a chiral gauge theory based on a larger group than SU(2)_L x U(1)_Y. Such theories can be constructed so as to be anomaly-free and consistent with precision electroweak measurements, and may be interpreted as a deconstruction of an extra dimension. They also provide interesting insights into the issues of flavor and dynamical electroweak symmetry breaking, and can help to raise the mass of the Higgs boson in supersymmetric theories. In this work we show that these theories can also give rise to baryon and lepton number violating processes, such as nucleon decay and spectacular multijet events at colliders, via the instanton transitions associated with the extended gauge group. For a particular model based on SU(2)_1 x SU(2)_2, we find that the $B+L$ violating scattering cross sections are too small to be observed at the LHC, but that the lower limit on the lifetime of the proton implies an upper bound on the gauge couplings.Comment: 36 page

Four Generations and Higgs Physics

In the light of the LHC, we revisit the implications of a fourth generation of chiral matter. We identify a specific ensemble of particle masses and mixings that are in agreement with all current experimental bounds as well as minimize the contributions to electroweak precision observables. Higgs masses between 115-315 (115-750) GeV are allowed by electroweak precision data at the 68% and 95% CL. Within this parameter space, there are dramatic effects on Higgs phenomenology: production rates are enhanced, weak-boson-fusion channels are suppressed, angular distributions are modified, and Higgs pairs can we observed. We also identify exotic signals, such as Higgs decay to same-sign dileptons. Finally, we estimate the upper bound on the cutoff scale from vacuum stability and triviality.Comment: 11 pages, 7 figures, REVTe

Geostatistical upscaling of rain gauge data to support uncertainty analysis of lumped urban hydrological models

In this study we develop a method to estimate the spatially averaged rainfall intensity together with associated level of uncertainty using geostatistical upscaling. Rainfall data collected from a cluster of eight paired rain gauges in a 400 × 200m urban catchment are used in combination with spatial stochastic simulation to obtain optimal predictions of the spatially averaged rainfall intensity at any point in time within the urban catchment. The uncertainty in the prediction of catchment average rainfall intensity is obtained for multiple combinations of intensity ranges and temporal averaging intervals. The two main challenges addressed in this study are scarcity of rainfall measurement locations and non-normality of rainfall data, both of which need to be considered when adopting a geostatistical approach. Scarcity of measurement points is dealt with by pooling sample variograms of repeated rainfall measurements with similar characteristics. Normality of rainfall data is achieved through the use of normal score transformation. Geostatistical models in the form of variograms are derived for transformed rainfall intensity. Next spatial stochastic simulation which is robust to nonlinear data transformation is applied to produce realisations of rainfall fields. These realisations in transformed space are first back-transformed and next spatially aggregated to derive a random sample of the spatially averaged rainfall intensity. Results show that the prediction uncertainty comes mainly from two sources: spatial variability of rainfall and measurement error. At smaller temporal averaging intervals both these effects are high, resulting in a relatively high uncertainty in prediction. With longer temporal averaging intervals the uncertainty becomes lower due to stronger spatial correlation of rainfall data and relatively smaller measurement error. Results also show that the measurement error increases with decreasing rainfall intensity resulting in a higher uncertainty at lower intensities. Results from this study can be used for uncertainty analyses of hydrologic and hydrodynamic modelling of similar-sized urban catchments as it provides information on uncertainty associated with rainfall estimation, which is arguably the most important input in these models. This will help to better interpret model results and avoid false calibration and force-fitting of model parameters