Flagellar membrane association via interaction with lipid rafts

The eukaryotic flagellar membrane has a distinct composition from other domains of the plasmalemma. Our work shows that the specialized composition of the trypanosome flagellar membrane reflects increased concentrations of sterols and saturated fatty acids, correlating with direct observation of high liquid order by laurdan fluorescence microscopy. These findings indicate that the trypanosome flagellar membrane possesses high concentrations of lipid rafts: discrete regions of lateral heterogeneity in plasma membranes that serve to sequester and organize specialized protein complexes. Consistent with this, a dually acylated Ca(2+) sensor that is concentrated in the flagellum is found in detergent-resistant membranes and mislocalizes if the lipid rafts are disrupted. Detergent-extracted cells have discrete membrane patches localized on the surface of the flagellar axoneme, suggestive of intraflagellar transport particles. Together, these results provide biophysical and biochemical evidence to indicate that lipid rafts are enriched in the trypanosome flagellar membrane, providing a unique mechanism for flagellar protein localization and illustrating a novel means by which specialized cellular functions may be partitioned to discrete membrane domains

Spacetime Slices and Surfaces of Revolution

Under certain conditions, a $(1+1)$-dimensional slice $\hat{g}$ of a spherically symmetric black hole spacetime can be equivariantly embedded in $(2+1)$-dimensional Minkowski space. The embedding depends on a real parameter that corresponds physically to the surface gravity $\kappa$ of the black hole horizon. Under conditions that turn out to be closely related, a real surface that possesses rotational symmetry can be equivariantly embedded in 3-dimensional Euclidean space. The embedding does not obviously depend on a parameter. However, the Gaussian curvature is given by a simple formula: If the metric is written $g = \phi(r)^{-1} dr^2 + \phi(r) d\theta^2$, then \K_g=-{1/2}\phi''(r). This note shows that metrics $g$ and $\hat{g}$ occur in dual pairs, and that the embeddings described above are orthogonal facets of a single phenomenon. In particular, the metrics and their respective embeddings differ by a Wick rotation that preserves the ambient symmetry. Consequently, the embedding of $g$ depends on a real parameter. The ambient space is not smooth, and $\kappa$ is inversely proportional to the cone angle at the axis of rotation. Further, the Gaussian curvature of $\hat{g}$ is given by a simple formula that seems not to be widely known.Comment: 15 pages, added reference

Precision Health for Chagas Disease: Integrating Parasite and Host Factors to Predict Outcome of Infection and Response to Therapy

Chagas disease, caused by the infection with the protozoan parasite Trypanosoma cruzi, is clinically manifested in approximately one-third of infected people by inflammatory heart disease (cardiomyopathy) and, to a minor degree, gastrointestinal tract disorders (megaesophagus or megacolon). Chagas disease is a zoonosis transmitted among animals and people through the contact with triatomine bugs, which are found in much of the western hemisphere, including most countries of North, Central and South America, between parallels 45° north (Minneapolis, USA) and south (Chubut Province, Argentina). Despite much research on drug discovery for T. cruzi, there remain only two related agents in widespread use. Likewise, treatment is not always indicated due to the serious side effects of these drugs. On the other hand, the epidemiology and pathogenesis of Chagas disease are both highly complex, and much is known about both. However, it is still impossible to predict what will happen in an individual person infected with T. cruzi, because of the highly variability of parasite virulence and human susceptibility to infection, with no definitive molecular predictors of outcome from either side of the host-parasite equation. In this Minireview we briefly discuss the current state of T. cruzi infection and prognosis and look forward to the day when it will be possible to employ precision health to predict disease outcome and determine whether and when treatment of infection may be necessary.Fil: Martinez, Santiago Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Romano, Patricia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Engman, David M.. Cedars Sinai Medical Center; Estados Unidos. Northwestern University; Estados Unidos. University of California at Los Angeles; Estados Unido

Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months; 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0·73/10000 (95% CI 0·15–2·14) (3/40978). The incidence of primary infection during pregnancy was 5·1/10000 (95% CI 2·6–8·9) susceptible pregnant women. The seroprevalence in the southern part was 25·7% and in the Stockholm area 14·0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility

Assessment of SERS-active nanosensors as a tool for pH measurements within living cells

Intracellular and intraorganellar pH is an essential aspect of the maintenance of proper cellular functions. Measurement of pH within cells could therefore elucidate crucial information regarding cell behaviour and pathology. Surface Enhanced Raman spectroscopy (SERS) is a method which has shown great potential as a method for pH measurement. SERS in combination with gold nanoparticles (AuNP) covalently bound to a pH sensitive molecule, 4-mercaptobenzoic acid (MBA), was assessed as a method to measure pH within live mammalian cells. The protonation states of MBA can be detected via the change of pH sensitive peaks within its Raman spectrum, and this information can be used to determine the pH. Within this thesis the MBA-AuNP were characterised in terms of cytotoxicity, reversibility, intracellular localisation, and capability of the MBA-AuNPs to measure pH within healthy and disease model mammalian cells, specifically human embryonic stem cells and primary sheep subventricular zone (SVZ) cells from Batten Disease affected and unaffected animals, respectively. The sensor was shown to cause no decrease in cell viability or proliferation and were able to respond to pH changes in a reversible manner. Large numbers of MBA-AuNP were shown to accumulate in perinuclear regions in close association with vesicles positive for the lysosomal marker LAMP1, but not LAMP2. Furthermore, assessment of pH perturbations in a cell model for the lysosomal storage disorder, Batten Disease, showed that the sensors are capable of discrimination of slight physiological pH changes within lysosomes

Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice

The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of preexisting interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells. © 2014 Di Caro et al

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity.

Modulating PI3K at different stages of dendritic cells (DC) generation could be a novel means to balance the generation of immunosuppressive versus immunostimulatory DC. We show that PI3K inhibition during mouse DC generation in vitro results in cells that are potently immunosuppressive and characteristic of CD8alpha- CD11c+ CD11b+ DC. These DC exhibited low surface class I and class II MHC, CD40, and CD86 and did not produce TNF-alpha. In allogeneic MLR, these DC were suppressive. Although in these mixed cultures, there was no increase in the frequency of CD4+ CD25+ Foxp3+ cells, the Foxp3 content on a per cell basis was significantly increased. Sustained TLR9 signaling in the presence of PI3K inhibition during DC generation overrode the cells' suppressive phenotype

Total angular momentum from Dirac eigenspinors

The eigenvalue problem for Dirac operators, constructed from two connections on the spinor bundle over closed spacelike 2-surfaces, is investigated. A class of divergence free vector fields, built from the eigenspinors, are found, which, for the lowest eigenvalue, reproduce the rotation Killing vectors of metric spheres, and provide rotation BMS vector fields at future null infinity. This makes it possible to introduce a well defined, gauge invariant spatial angular momentum at null infinity, which reduces to the standard expression in stationary spacetimes. The general formula for the angular momentum flux carried away be the gravitational radiation is also derived.Comment: 34 pages, typos corrected, four references added, appearing in Class. Quantum Gra