Host-parasite dynamics in Chagas disease from systemic to hyper-local scales

Trypanosoma cruzi is a remarkably versatile parasite. It can parasitize almost any nucleated cell type and naturally infects hundreds of mammal species across much of the Americas. In humans it is the cause of Chagas disease, a set of mainly chronic conditions predominantly affecting the heart and gastrointestinal tract that can progress to become life threatening. Yet around two thirds of infected people are long-term asymptomatic carriers. Clinical outcomes depend on many factors, but the central determinant is the nature of the host-parasite interactions that play out over the years of chronic infection in diverse tissue environments. In this review, we aim to integrate recent developments in the understanding of the spatial and temporal dynamics of T. cruzi infections with established and emerging concepts in host immune responses in the corresponding phases and tissues

Possible Applications of Surface Electromagnetic Waves to Measure Absorption Coefficients

We Show that Surface Electromagnetic Waves Can Probably Be Used to Measure the Absorption Coefficients of Materials overlaying Metals. the Proposed Experimental Method is Illustrated in the Infrared Frequency Range using Water, Teflon, and Polyethylene as Sample Materials

Hidden Symmetries and Integrable Hierarchy of the N=4 Supersymmetric Yang-Mills Equations

We describe an infinite-dimensional algebra of hidden symmetries of N=4 supersymmetric Yang-Mills (SYM) theory. Our derivation is based on a generalization of the supertwistor correspondence. Using the latter, we construct an infinite sequence of flows on the solution space of the N=4 SYM equations. The dependence of the SYM fields on the parameters along the flows can be recovered by solving the equations of the hierarchy. We embed the N=4 SYM equations in the infinite system of the hierarchy equations and show that this SYM hierarchy is associated with an infinite set of graded symmetries recursively generated from supertranslations. Presumably, the existence of such nonlocal symmetries underlies the observed integrable structures in quantum N=4 SYM theory.Comment: 24 page

Exploiting Genetically Modified Dual-Reporter Strains to Monitor Experimental Trypanosoma cruzi Infections and Host-Parasite Interactions.

Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. Despite a global research effort, there have been no significant treatment advances for at least 40 years. Gaps in our knowledge of T. cruzi biology and pathogenesis have been major factors in limiting progress. In addition, the extremely low parasite burden during chronic infections has complicated the monitoring of both disease progression and drug efficacy, even in predictive animal models. To address these problems, we genetically modified T. cruzi to express a red-shifted luciferase. Mice infected with these highly bioluminescent parasites can be monitored by in vivo imaging, with exquisite sensitivity. However, a major drawback of bioluminescence imaging is that it does not allow visualization of host-parasite interactions at a cellular level. To facilitate this, we generated T. cruzi strains that express a chimeric protein that is both bioluminescent and fluorescent. Bioluminescence allows the tissue location of infection foci to be identified, and fluorescence can then be exploited to detect parasites in histological sections derived from excised tissue. In this article, we describe in detail the in vivo imaging and confocal microscopy protocols that we have developed for visualizing T. cruzi parasites expressing these dual-reporter fusion proteins. The approaches make it feasible to locate individual parasites within chronically infected murine tissues, to assess their replicative status, to resolve the nature of host cells, and to characterize their immunological context

X-ray Bright Optically Inactive Galaxies (XBONG) in XMM-Newton/SDSS fields: more diluted than absorbed?

We explore the properties of X-ray Bright Optically Inactive Galaxies (XBONG) detected in the 0.5-8 keV spectral band in 20 public XMM fields overlapping with the SDSS. We constrain our sample to optically extended systems with log (f_X/f_o > -2) that have spectroscopic identifications available from the SDSS (r<19.2 mag). The resulting sample contains 12 objects with L_X (0.5-8keV)= 5 x 10^41 - 2x10^44 erg s-1 in the redshift range 0.06 < z < 0.45. The X-ray emission in four cases is extended suggesting the presence of hot gas associated with a cluster or group of galaxies. The X-ray spectral fits show that two additional sources are best fit with a thermal component emission (kT \~ 1 keV). Three sources aremost likely associated with AGN: their X-ray spectrum is described by a steep photon index ~ 1.9 typical of unobscured AGN while, they are very luminous in X-rays (L_X (0.5-8 keV) ~ 10^43 - 10^44 erg s-1.) Finally, three more sources could be associated with either normal galaxies or unobscured Low Luminosity AGN (L_X < 10^42 erg s-1). We find no evidence for significant X-ray absorbing columns in any of our XBONGs. The above suggest that XBONGs, selected in the total 0.5-8 keV band, comprise a mixed bag of objects primarily including normal elliptical galaxies and type-1 AGN whose optical nuclear spectrum is probably diluted by the strong stellar continuum. Nevertheless, as our sample is not statistically complete we cannot exclude the possibility that a fraction of optically fainter XBONG may be associated with heavily obscured AGN.Comment: 8 pages to appear in MNRA

In Vivo Analysis of Trypanosoma cruzi Persistence Foci at Single-Cell Resolution.

Infections with Trypanosoma cruzi are usually lifelong despite generating a strong adaptive immune response. Identifying the sites of parasite persistence is therefore crucial to understanding how T. cruzi avoids immune-mediated destruction. However, this is a major technical challenge, because the parasite burden during chronic infections is extremely low. Here, we describe an integrated approach involving comprehensive tissue processing, ex vivo imaging, and confocal microscopy, which allowed us to visualize infected host cells in murine tissue with exquisite sensitivity. Using bioluminescence-guided tissue sampling, with a detection level of 200 parasites, which we term mega-nests. In contrast, during the acute stage, when the total parasite burden is considerably higher and many cells are infected, nests containing >50 parasites are rarely found. In C3H/HeN mice, but not BALB/c mice, we identified skeletal muscle as a major site of persistence during the chronic stage, with most parasites being found in large mega-nests within the muscle fibers. Finally, we report that parasites are also frequently found in the skin during chronic murine infections, often in multiple infection foci. In addition to being a site of parasite persistence, this anatomical reservoir could play an important role in insect-mediated transmission and have implications for drug development.IMPORTANCE Trypanosoma cruzi causes Chagas disease, the most important parasitic infection in Latin America. Major pathologies include severe damage to the heart and digestive tract, although symptoms do not usually appear until decades after infection. Research has been hampered by the complex nature of the disease and technical difficulties in locating the extremely low number of parasites. Here, using highly sensitive imaging technology, we reveal the sites of parasite persistence during chronic-stage infections of experimental mice at single-cell resolution. We show that parasites are frequently located in smooth muscle cells in the circular muscle layer of the colon and that skeletal muscle cells and the skin can also be important reservoirs. This information provides a framework for investigating how the parasite is able to survive as a lifelong infection, despite a vigorous immune response. It also informs drug development strategies by identifying tissue sites that must be accessed to achieve a curative outcome

Incomplete Recruitment of Protective T Cells Is Associated with Trypanosoma cruzi Persistence in the Mouse Colon.

Trypanosoma cruzi is the etiological agent of Chagas disease. Following T cell-mediated suppression of acute-phase infection, this intracellular eukaryotic pathogen persists long-term in a limited subset of tissues at extremely low levels. The reasons for this tissue-specific chronicity are not understood. Using a dual bioluminescent-fluorescent reporter strain and highly sensitive tissue imaging that allows experimental infections to be monitored at single-cell resolution, we undertook a systematic analysis of the immunological microenvironments of rare parasitized cells in the mouse colon, a key site of persistence. We demonstrate that incomplete recruitment of T cells to a subset of colonic infection foci permits the occurrence of repeated cycles of intracellular parasite replication and differentiation to motile trypomastigotes at a frequency sufficient to perpetuate chronic infections. The lifelong persistence of parasites in this tissue site continues despite the presence, at a systemic level, of a highly effective T cell response. Overcoming this low-level dynamic host-parasite equilibrium represents a major challenge for vaccine development

Trypanosoma cruzi amastigotes that persist in the colon during chronic stage murine infections have a reduced replication rate.

Chronic Trypanosoma cruzi infections are typically lifelong, with small numbers of parasites surviving in restricted tissue sites, which include the gastrointestinal tract. There is considerable debate about the replicative status of these persistent parasites and whether there is a role for dormancy in long-term infection. Here, we investigated T. cruzi proliferation in the colon of chronically infected mice using 5-ethynyl-2'deoxyuridine incorporation into DNA to provide 'snapshots' of parasite replication status. Highly sensitive imaging of the extremely rare infection foci, at single-cell resolution, revealed that parasites are three times more likely to be in S-phase during the acute stage than during the chronic stage. By implication, chronic infections of the colon are associated with a reduced rate of parasite replication. Despite this, very few host cells survived infection for more than 14 days, suggesting that T. cruzi persistence continues to involve regular cycles of replication, host cell lysis and re-infection. We could find no evidence for wide-spread dormancy in parasites that persist in this tissue reservoir

The role of AGN in the migration of early-type galaxies from the blue cloud to the red sequence

We present a general picture of the ongoing formation and evolution of early-type galaxies via a specific evolutionary sequence starting in the blue cloud and ending in the low-mass end of the red sequence. This evolutionary sequence includes a Seyfert AGN phase in the green valley, but this phase occurs too late after the shutdown of star formation to be responsible for it. Thus, the bulk of black hole accretion in low-redshift early-type galaxies occurs in post-starburst objects, and not concurrent with star formation. On the other hand, a low-luminosity AGN phase switching on at an earlier stage when some star formation activity remains may be responsible for destroying the molecular gas reservoir fueling star formation.Comment: 4 pages, 2 figures. To appear in proceedings of "The Monster's Fiery Breath", Madison, Wisconsin, 1-5 June 2009, Ed. Sebastian Heinz & Eric Wilcot