A latent ability to persist: differentiation in Toxoplasma gondii

A critical factor in the transmission and pathogenesis of Toxoplasma gondii is the ability to convert from an acute disease-causing, proliferative stage (tachyzoite), to a chronic, dormant stage (bradyzoite). The conversion of the tachyzoite-containing parasitophorous vacuole membrane into the less permeable bradyzoite cyst wall allows the parasite to persist for years within the host to maximize transmissibility to both primary (felids) and secondary (virtually all other warm-blooded vertebrates) hosts. This review presents our current understanding of the latent stage, including the factors that are important in bradyzoite induction and maintenance. Also discussed are the recent studies that have begun to unravel the mechanisms behind stage switching

The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time

In Drosophila cells cyclin B is normally degraded in two phases: (a) destruction of the spindle-associated cyclin B initiates at centrosomes and spreads to the spindle equator; and (b) any remaining cytoplasmic cyclin B is degraded slightly later in mitosis. We show that the APC/C regulators Fizzy (Fzy)/Cdc20 and Fzy-related (Fzr)/Cdh1 bind to microtubules in vitro and associate with spindles in vivo. Fzy/Cdc20 is concentrated at kinetochores and centrosomes early in mitosis, whereas Fzr/Cdh1 is concentrated at centrosomes throughout the cell cycle. In syncytial embryos, only Fzy/Cdc20 is present, and only the spindle-associated cyclin B is degraded at the end of mitosis. A destruction box–mutated form of cyclin B (cyclin B triple-point mutant [CBTPM]–GFP) that cannot be targeted for destruction by Fzy/Cdc20, is no longer degraded on spindles in syncytial embryos. However, CBTPM–GFP can be targeted for destruction by Fzr/Cdh1. In cellularized embryos, which normally express Fzr/Cdh1, CBTPM–GFP is degraded throughout the cell but with slowed kinetics. These findings suggest that Fzy/Cdc20 is responsible for catalyzing the first phase of cyclin B destruction that occurs on the mitotic spindle, whereas Fzr/Cdh1 is responsible for catalyzing the second phase of cyclin B destruction that occurs throughout the cell. These observations have important implications for the mechanisms of the spindle checkpoint

Fiber beam model for fire response simulation of axially loaded concrete filled tubular columns

This paper presents a fiber beam model for the fire response simulation of concrete filled tubular columns of circular section under concentric axial load. The model consists of two parallel components, one with a circular tubular steel section, and the other with a solid circular concrete section. The components interact with nonlinear longitudinal and transverse links at the end nodes. The element is formulated on a system without rigid body modes and accounts for large displacement geometry through the co-rotational formulation connected both longitudinally and transversely at their nodes by link elements. The model is capable of representing different types of concrete infill of the steel tubes: plain, reinforced and steel fiber reinforced concrete of normal or high strength. It is validated against experimental data from column specimens under fire. The results are also compared against a three-dimensional finite element model characterized by its accuracy of fire response simulation.The authors express their sincere gratitude to Prof. Filip C. Filippou for his comments to the paper. Also to the Spanish "Ministerio de Ciencia e Innovacion" for the help provided through the Project BIA2009-9411; to the Valencian autonomous community institution "Generalitat Valenciana" for the support given by means of the ACIF/2010/219 Program; and to the European Union for its collaboration through the FEDER funds.Ibáñez Usach, C.; Romero, ML.; Hospitaler Pérez, A. (2013). Fiber beam model for fire response simulation of axially loaded concrete filled tubular columns. Engineering Structures. 56:182-193. https://doi.org/10.1016/j.engstruct.2013.05.004S1821935

Puma strikes Bax

The commitment to programmed cell death via apoptosis is largely made upon activation of the proapoptotic mitochondrial proteins Bax or Bak. In this issue, Gallenne et al. (Gallenne, C., F. Gautier, L. Oliver, E. Hervouet, B. Noël, J.A. Hickman, O. Geneste, P.-F. Cartron, F.M. Vallette, S. Manon, and P. Juin. 2009. J. Cell Biol. 185:279–290) provide evidence that the p53 up-regulated modulator of apoptosis (Puma) protein can directly activate Bax

Propagation of Nonclassical Radiation through a Semiconductor Slab

Based on a microscopic derivation of the emission spectra of a bulk semiconductor we arrive at a clear physical interpretation of the noise current operators in macroscopic quantum electrodynamics. This opens the possibility to study medium effects on nonclassical radiation propagating through an absorbing or amplifying semiconductor. As an example, the propagation of an incident squeezed vacuum is analyzed.Comment: 4 pages, 2 figure

Associations between serum lipids and hepatitis C antiviral treatment efficacy

Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naÏve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR. Conclusion: Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication. (Hepatology 2010)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78060/1/23796_ftp.pd

An Overview on Principles for Energy Efficient Robot Locomotion

Despite enhancements in the development of robotic systems, the energy economy of today's robots lags far behind that of biological systems. This is in particular critical for untethered legged robot locomotion. To elucidate the current stage of energy efficiency in legged robotic systems, this paper provides an overview on recent advancements in development of such platforms. The covered different perspectives include actuation, leg structure, control and locomotion principles. We review various robotic actuators exploiting compliance in series and in parallel with the drive-train to permit energy recycling during locomotion. We discuss the importance of limb segmentation under efficiency aspects and with respect to design, dynamics analysis and control of legged robots. This paper also reviews a number of control approaches allowing for energy efficient locomotion of robots by exploiting the natural dynamics of the system, and by utilizing optimal control approaches targeting locomotion expenditure. To this end, a set of locomotion principles elaborating on models for energetics, dynamics, and of the systems is studied

DNA Damage–Induced Bcl-x(L) Deamidation Is Mediated by NHE-1 Antiport Regulated Intracellular pH

The pro-survival protein Bcl-x(L) is critical for the resistance of tumour cells to DNA damage. We have previously demonstrated, using a mouse cancer model, that oncogenic tyrosine kinase inhibition of DNA damage–induced Bcl-x(L) deamidation tightly correlates with T cell transformation in vivo, although the pathway to Bcl-x(L) deamidation remains unknown and its functional consequences unclear. We show here that rBcl-x(L) deamidation generates an iso-Asp(52)/iso-Asp(66) species that is unable to sequester pro-apoptotic BH3-only proteins such as Bim and Puma. DNA damage in thymocytes results in increased expression of the NHE-1 Na/H antiport, an event both necessary and sufficient for subsequent intracellular alkalinisation, Bcl-x(L) deamidation, and apoptosis. In murine thymocytes and tumour cells expressing an oncogenic tyrosine kinase, this DNA damage–induced cascade is blocked. Enforced intracellular alkalinisation mimics the effects of DNA damage in murine tumour cells and human B-lineage chronic lymphocytic leukaemia cells, thereby causing Bcl-x(L) deamidation and increased apoptosis. Our results define a signalling pathway leading from DNA damage to up-regulation of the NHE-1 antiport, to intracellular alkalanisation to Bcl-x(L) deamidation, to apoptosis, representing the first example, to our knowledge, of how deamidation of internal asparagine residues can be regulated in a protein in vivo. Our findings also suggest novel approaches to cancer therapy

Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival