The recombinant maize ribosome-inactivating protein transiently reduces viral load in SHIV89.6 infected Chinese Rhesus Macaques.

Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.

Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum.

Gametocyte maturation in Plasmodium falciparum is a critical step in the transmission of malaria. While the majority of parasites proliferate asexually in red blood cells, a small fraction of parasites undergo sexual conversion and mature over 2 weeks to become competent for transmission to a mosquito vector. Immature gametocytes sequester in deep tissues while mature stages must be able to circulate, pass the spleen and present themselves to the mosquito vector in order to complete transmission. Sequestration of asexual red blood cell stage parasites has been investigated in great detail. These studies have demonstrated that induction of cytoadherence properties through specific receptor-ligand interactions coincides with a significant increase in host cell stiffness. In contrast, the adherence and biophysical properties of gametocyte-infected red blood cells have not been studied systematically. Utilizing a transgenic line for 3D live imaging, in vitro capillary assays and 3D finite element whole cell modelling, we studied the role of cellular deformability in determining the circulatory characteristics of gametocytes. Our analysis shows that the red blood cell deformability of immature gametocytes displays an overall decrease followed by rapid restoration in mature gametocytes. Intriguingly, simulations suggest that along with deformability variations, the morphological changes of the parasite may play an important role in tissue distribution in vivo. Taken together, we present a model, which suggests that mature but not immature gametocytes circulate in the peripheral blood for uptake in the mosquito blood meal and transmission to another human host thus ensuring long-term survival of the parasite.

Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.).

Tripterygium wilfordii Hook.f., known as Leigongteng (Thunder God Vine) in traditional Chinese medicine, has attracted much attention for its applications in relieving autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, and for treating cancer. Molecular analyses of the ITS and 5S rDNA sequences indicate that T. hypoglaucum and T. doianum are not distinct from T. wilfordii, while T. regelii should be recognized as a separate species. The results also demonstrate potential value of rDNA sequence data in forensic detection of adulterants derived from Celastrus angulatus in commercial samples of Leigongteng.

A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells.

Maize ribosome-inactivating protein (RIP) is a plant toxin that inactivates eukaryotic ribosomes by depurinating a specific adenine residue at the α-sarcin/ricin loop of 28S rRNA. Maize RIP is first produced as a proenzyme with a 25-amino acid internal inactivation region on the protein surface. During germination, proteolytic removal of this internal inactivation region generates the active heterodimeric maize RIP with full N-glycosidase activity. This naturally occurring switch-on mechanism provides an opportunity for targeting the cytotoxin to pathogen-infected cells. Here, we report the addition of HIV-1 protease recognition sequences to the internal inactivation region and the activation of the maize RIP variants by HIV-1 protease in vitro and in HIV-infected cells. Among the variants generated, two were cleaved efficiently by HIV-1 protease. The HIV-1 protease-activated variants showed enhanced N-glycosidase activity in vivo as compared to their un-activated counterparts. They also possessed potent inhibitory effect on p24 antigen production in human T cells infected by two HIV-1 strains. This switch-on strategy for activating the enzymatic activity of maize RIP in target cells provides a platform for combating pathogens with a specific protease.

Laser ultrasonic surface wave dispersion technique for non-destructive evaluation of human dental enamel.

This paper describes a novel optical system for clinical diagnosis of dental enamel based on its elasticity. Current examination techniques are typically destructive, and frequently impractical for in-vivo inspection. This paper describes the first application of a laser ultrasonic non-destructive evaluation (NDE) method for clinical dental diagnosis. It performs remote elasticity evaluation on small dimension samples. A focused laser line-source generates broadband surface acoustic wave (SAW) impulses which are detected with a simplified optical fibre interferometer. The measured SAW velocity dispersion spectrum was in turn used to characterise the elasticity of the specimen. Different metal structures were measured to verify the system performance. The results agree well with theoretical values and confirm the reliability and accuracy of the laser NDE system. This technique was then applied to evaluate the surface of sound natural human dental enamel. The measured dispersion spectra match theoretical expectations and the influences of both the enamel and the underlying dentin on the surface wave propagation were observed. This is the first time, to the best of our knowledge, that a laser based SAW velocity dispersion technique has been successfully applied on human dental enamel. As a remote, non-destructive technique it is applicable in-vivo and opens the way for early diagnosis of dental caries.

Cerenkov light spectrum in an optical fiber exposed to a photon or electron radiation therapy beam.

A Cerenkov signal is generated when energetic charged particles enter the core of an optical fiber. The Cerenkov intensity can be large enough to interfere with signals transmitted through the fiber. We determine the spectrum of the Cerenkov background signal generated in a poly(methyl methacrylate) optical fiber exposed to photon and electron therapeutic beams from a linear accelerator. This spectral measurement is relevant to discrimination of the signal from the background, as in scintillation dosimetry using optical fiber readouts. We find that the spectrum is approximated by the theoretical curve after correction for the wavelength dependent attenuation of the fiber. The spectrum does not depend significantly on the angle between the radiation beam and the axis of the fiber optic but is dependent on the depth in water at which the fiber is exposed to the beam.

In vivo dosimeters for HDR brachytherapy: a comparison of a diamond detector, MOSFET, TLD, and scintillation detector.

The large dose gradients in brachytherapy necessitate a detector with a small active volume for accurate dosimetry. The dosimetric performance of a novel scintillation detector (BrachyFOD) is evaluated and compared to three commercially available detectors, a diamond detector, a MOSFET, and LiF TLDs. An 192Ir HDR brachytherapy source is used to measure the depth dependence, angular dependence, and temperature dependence of the detectors. Of the commercially available detectors, the diamond detector was found to be the most accurate, but has a large physical size. The TLDs cannot provide real time readings and have depth dependent sensitivity. The MOSFET used in this study was accurate to within 5% for distances of 20 to 50 mm from the 192Ir source in water but gave errors of 30%-40% for distances greater than 50 mm from the source. The BrachyFOD was found to be accurate to within 3% for distances of 10 to 100 mm from an HDR 192Ir brachytherapy source in water. It has an angular dependence of less than 2% and the background signal created by Cerenkov radiation and fluorescence of the plastic optical fiber is insignificant compared to the signal generated in the scintillator. Of the four detectors compared in this study the BrachyFOD has the most favorable combination of characteristics for dosimetry in HDR brachytherapy.

Optimal coupling of light from a cylindrical scintillator into an optical fiber.

Radiation dose measurements based on scintillator detection are conveniently made by coupling the light from the scintillator into an optical fiber. The low light levels involved typically require sensitive photodetectors, so it is advantageous to increase the available signal by optimizing the optical coupling efficiency between the scintillator and optical fiber. We model this process using geometric optics and finite-element ray tracing to determine the features that maximize the amount of light coupled to an optical fiber from a cylindrical scintillator. We also address whether the coupling can be improved by using an intermediate optical element such as a lens, and we provide a means for calculating its required optical properties for a given geometry.