Recent, independent and anthropogenic origins of Trypanosoma cruzi hybrids.

The single celled eukaryote Trypanosoma cruzi, a parasite transmitted by numerous species of triatomine bug in the Americas, causes Chagas disease in humans. T. cruzi generally reproduces asexually and appears to have a clonal population structure. However, two of the six major circulating genetic lineages, TcV and TcVI, are TcII-TcIII inter-lineage hybrids that are frequently isolated from humans in regions where chronic Chagas disease is particularly severe. Nevertheless, a prevalent view is that hybridisation events in T. cruzi were evolutionarily ancient and that active recombination is of little epidemiological importance. We analysed genotypes of hybrid and non-hybrid T. cruzi strains for markers representing three distinct evolutionary rates: nuclear GPI sequences (n = 88), mitochondrial COII-ND1 sequences (n = 107) and 28 polymorphic microsatellite loci (n = 35). Using Maximum Likelihood and Bayesian phylogenetic approaches we dated key evolutionary events in the T. cruzi clade including the emergence of hybrid lineages TcV and TcVI, which we estimated to have occurred within the last 60,000 years. We also found evidence for recent genetic exchange between TcIII and TcIV and between TcI and TcIV. These findings show that evolution of novel recombinants remains a potential epidemiological risk. The clearly distinguishable microsatellite genotypes of TcV and TcVI were highly heterozygous and displayed minimal intra-lineage diversity indicative of even earlier origins than sequence-based estimates. Natural hybrid genotypes resembled typical meiotic F1 progeny, however, evidence for mitochondrial introgression, absence of haploid forms and previous experimental crosses indicate that sexual reproduction in T. cruzi may involve alternatives to canonical meiosis. Overall, the data support two independent hybridisation events between TcII and TcIII and a recent, rapid spread of the hybrid progeny in domestic transmission cycles concomitant with, or as a result of, disruption of natural transmission cycles by human activities

Chagas disease reactivation in a heart transplant patient infected by domestic Trypanosoma cruzi discrete typing unit I (TcIDOM)

Background Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC). Findings In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcI DOM ). Conclusions Our results constitute compelling evidence in support of TcI DTU’s ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally

Wild Trypanosoma cruzi I genetic diversity in Brazil suggests admixture and disturbance in parasite populations from the Atlantic Forest region

Background Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae) infection is an ancient and widespread zoonosis distributed throughout the Americas. Ecologically, Brazil comprises several distinct biomes: Amazonia, Cerrado, Caatinga, Pantanal and the Atlantic Forest. Sylvatic T. cruzi transmission is known to occur throughout these biomes, with multiple hosts and vectors involved. Parasite species-level genetic diversity can be a useful marker for ecosystem health. Our aims were to: investigate sylvatic T. cruzi genetic diversity across different biomes, detect instances of genetic exchange, and explore the possible impact of ecological disturbance on parasite diversity at an intra-species level. Methods We characterised 107 isolates of T. cruzi I (TcI; discrete typing unit, DTU I) from different major Brazilian biomes with twenty-seven nuclear microsatellite loci. A representative subset of biologically cloned isolates was further characterised using ten mitochondrial gene loci. We compared these data generated from Brazilian TcI isolates from around America. Results Genetic diversity was remarkably high, including one divergent cluster that branched outside the known genetic diversity of TcI in the Americas. We detected evidence for mitochondrial introgression and genetic exchange between the eastern Amazon and Caatinga. Finally, we found strong signatures of admixture among isolates from the Atlantic Forest region by comparison to parasites from other study sites. Conclusions Atlantic Forest sylvatic TcI populations are highly fragmented and admixed by comparison to others around Brazil. We speculate on: the possible causes of Atlantic Forest admixture; the role of T. cruzi as a sentinel for ecosystem health, and the impact disrupted sylvatic transmission cycles might have on accurate source attribution in oral outbreaks

Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by Maxicircle MLST and next generation sequencing

Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear-mitochondrial phylogenetic incongruence indicate that genetic recombination is geographically widespread and continues to influence the natural population structure of TcI, a conclusion which challenges the traditional paradigm of clonality in T. cruzi

Neutral processes dominate microbial community assembly in Atlantic salmon, Salmo salar

In recent years a wealth of studies have examined the relationships between a host and its microbiome across diverse taxa. Many studies characterise the host microbiome without considering the ecological processes that underpin microbiome assembly. In this study, the intestinal microbiota of Atlantic salmon, Salmo salar, sampled from farmed and wild environments was first characterised using 16s rDNA MiSeq sequencing analysis. We used neutral community models to determine the balance of stochastic and deterministic processes that underpin microbial community assembly and transfer across lifecycle stage and between gut compartments. Across gut compartments in farmed fish, neutral models suggest that most microbes are transient with no evidence of adaptation to their environment. In wild fish, we find declining taxonomic and functional microbial community richness as fish mature through different lifecycle stages. Alongside neutral community models applied to wild fish, we suggest declining richness demonstrates an increasing role for the host in filtering microbial communities that is correlated with age. We find a limited subset of gut microflora adapted to the farmed and wild host environment among which Mycoplasma sp. are prominent. Our study reveals the ecological drivers underpinning community assembly in both farmed and wild Atlantic salmon and underlines the importance of understanding the role of stochastic processes such as random drift and small migration rates in microbial community assembly, before considering any functional role of the gut microbes encountered

Unitary Standard Model from Spontaneous Dimensional Reduction and Weak Boson Scattering at the LHC

Spontaneous dimensional reduction (SDR) is a striking phenomenon predicted by a number of quantum gravity approaches which all indicate that the spacetime dimensions get reduced at high energies. In this work, we formulate an effective theory of electroweak interactions based upon the standard model, incorporating the spontaneous reduction of space-dimensions at TeV scale. The electroweak gauge symmetry is nonlinearly realized with or without a Higgs boson. We demonstrate that the SDR ensures good high energy behavior and predicts unitary weak boson scattering. For a light Higgs boson of mass 125GeV, the TeV-scale SDR gives a natural solution to the hierarchy problem. Such a light Higgs boson can have induced anomalous gauge couplings from the TeV-scale SDR. We find that the corresponding WW scattering cross sections become unitary at TeV scale, but exhibit different behaviors from that of the 4d standard model. These can be discriminated by the WW scattering experiments at the LHC.Comment: 38pp, Eur.Phys.J.(in Press); extended discussions for testing non-SM Higgs boson(125GeV) via WW scattering; minor clarifications added; references added; a concise companion is given in the short PLB letter arXiv:1301.457

Masses of ground and excited-state hadrons

We present the first Dyson-Schwinger equation calculation of the light hadron spectrum that simultaneously correlates the masses of meson and baryon ground- and excited-states within a single framework. At the core of our analysis is a symmetry-preserving treatment of a vector-vector contact interaction. In comparison with relevant quantities the root-mean-square-relative-error/degree-of freedom is 13%. Notable amongst our results is agreement between the computed baryon masses and the bare masses employed in modern dynamical coupled-channels models of pion-nucleon reactions. Our analysis provides insight into numerous aspects of baryon structure; e.g., relationships between the nucleon and Delta masses and those of the dressed-quark and diquark correlations they contain.Comment: 25 pages, 7 figures, 4 table

The NuTeV Anomaly, Neutrino Mixing, and a Heavy Higgs Boson

Recent results from the NuTeV experiment at Fermilab and the deviation of the Z invisible width, measured at LEP/SLC, from its Standard Model (SM) prediction suggest the suppression of neutrino-Z couplings. Such suppressions occur naturally in models which mix the neutrinos with heavy gauge singlet states. We postulate a universal suppression of the Z-nu-nu couplings by a factor of (1-epsilon) and perform a fit to the Z-pole and NuTeV observables with epsilon and the oblique correction parameters S and T. Compared to a fit with S and T only, inclusion of epsilon leads to a dramatic improvement in the quality of the fit. The values of S and T preferred by the fit can be obtained within the SM by a simple increase in the Higgs boson mass. However, if the W mass is also included in the fit, a non-zero U parameter becomes necessary which cannot be supplied within the SM. The preferred value of epsilon suggests that the seesaw mechanism may not be the reason why neutrinos are so light.Comment: 19 pages, REVTeX4, 8 postscript figures. Updated references. Typos correcte

Scale of fermion mass generation

Unitarity of longitudinal weak vector boson scattering implies an upper bound on the scale of electroweak symmetry breaking, $\Lambda_{EWSB}\equiv \sqrt{8\pi}v\approx$ 1 TeV. Appelquist and Chanowitz have derived an analogous upper bound on the scale of fermion mass generation, proportional to $v^2/m_f$, by considering the scattering of same-helicity fermions into pairs of longitudinal weak vector bosons in a theory without a standard Higgs boson. We show that there is no upper bound, beyond that on the scale of electroweak symmetry breaking, in such a theory. This result is obtained by considering the same process, but with a large number of longitudinal weak vector bosons in the final state. We further argue that there is no scale of (Dirac) fermion mass generation in the standard model. In contrast, there is an upper bound on the scale of Majorana-neutrino mass generation, given by $\Lambda_{Maj}\equiv 4\pi v^2/m_\nu$. In general, the upper bound on the scale of fermion mass generation depends on the dimensionality of the interaction responsible for generating the fermion mass. We explore the scale of fermion mass generation in a variety of excursions from the standard model: models with fermions in nonstandard representations, a theory with higher-dimension interactions, a two-Higgs-doublet model, and models without a Higgs boson.Comment: 31 pages, 9 figures; version accepted for publication in Phys. Rev.

Genome erosion and evidence for an intracellular niche – exploring the biology of mycoplasmas in Atlantic salmon

Mycoplasmas are the smallest autonomously self-replicating life form on the planet. Members of this bacterial genus are known to parasitise a wide array of metazoans including vertebrates. Whilst much research has been significant targeted at parasitic mammalian mycoplasmas, very little is known about their role in other vertebrates. In the current study, we aim to explore the biology of mycoplasmas in Atlantic Salmon, a species of major significance for aquaculture, including cellular niche, genome size structure and gene content. Using fluorescent in-situ hybridisation (FISH), mycoplasmas were targeted in epithelial tissues across the digestive tract (stomach, pyloric caecum and midgut) from different development stages (eggs, parr, subadult) of farmed Atlantic salmon (Salmo salar), and we present evidence for an intracellular niche for some of the microbes visualised. Via shotgun metagenomic sequencing, a nearly complete, albeit small, genome (~0.57 MB) as assembled from a farmed Atlantic salmon subadult. Phylogenetic analysis of the recovered genome revealed taxonomic proximity to other salmon derived mycoplasmas, as well as to the human pathogen Mycoplasma penetrans (~1.36 Mb). We annotated coding sequences and identified riboflavin pathway encoding genes and sugar transporters, the former potentially consistent with micronutrient provisioning in salmonid development. Our study provides insights into mucosal adherence, the cellular niche and gene catalog of Mycoplasma in the gut ecosystem of the Atlantic salmon, suggesting a high dependency of this minimalist bacterium on its host. Further study is required to explore and functional role of Mycoplasma in the nutrition and development of its salmonid host