Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox

The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.     

Adenosine-induced slow ionic currents in the Xenopus oocyte

Adenosine and its 5'-phosphorylated congeners evoke specific membrane-mediated responses in excitable tissues. Available data suggest that inhibition of the target cell occurs due to hyperpolarization, and in some preparations a compound effect of ATP (excitation and inhibition) has been found. However, the ionic mechanism of the purinergic-mediated response has not been studied by standard intracellular voltage-clamping techniques. Recently, we have discovered purinergic receptors in the Xenopus oocyte, a well defined giant cell amenable to rigorous electrophysiological and biochemical studies. We report here that in these cells, adenosine-induced slow membrane responses consisted of an early depolarizing (D) transient current carried by Cl ions, followed by a steady hyperpolarizing (H) current involving K+ ions. The relative potency sequence for the D current was ATP congruent to ADP greater than AMP congruent to adenosine; this order was reversed for the H current.     

The origin of the anomalous superconducting properties of MgB(2)

Magnesium diboride differs from ordinary metallic superconductors in several important ways, including the failure of conventional models to predict accurately its unusually high transition temperature, the effects of isotope substitution on the critical transition temperature, and its anomalous specific heat. A detailed examination of the energy associated with the formation of charge-carrying pairs, referred to as the 'superconducting energy gap', should clarify why MgB(2) is different. Some early experimental studies have indicated that MgB(2) has multiple gaps, but past theoretical studies have not explained from first principles the origin of these gaps and their effects. Here we report an ab initio calculation of the superconducting gaps in MgB(2) and their effects on measurable quantities. An important feature is that the electronic states dominated by orbitals in the boron plane couple strongly to specific phonon modes, making pair formation favourable. This explains the high transition temperature, the anomalous structure in the specific heat, and the existence of multiple gaps in this material. Our analysis suggests comparable or higher transition temperatures may result in layered materials based on B, C and N with partially filled planar orbitals.     

Enhancement of the high-magnetic-field critical current density of superconducting MgB2 by proton irradiation

Magnesium diboride, MgB2, has a relatively high superconducting transition temperature, placing it between the families of low- and high-temperature (copper oxide based) superconductors. Supercurrent flow in MgB2 is unhindered by grain boundaries, making it potentially attractive for technological applications in the temperature range 20-30 K. But in the bulk material, the critical current density (Jc) drops rapidly with increasing magnetic field strength. The magnitude and field dependence of the critical current are related to the presence of structural defects that can 'pin' the quantized magnetic vortices that permeate the material, and a lack of natural defects in MgB2 may be responsible for the rapid decline of Jc with increasing field strength. Here we show that modest levels of atomic disorder induced by proton irradiation enhance the pinning of vortices, thereby significantly increasing Jc at high field strengths. We anticipate that either chemical doping or mechanical processing should generate similar levels of disorder, and so achieve performance that is technologically attractive in an economically viable way.     

Phagocytosis and clearance of apoptotic cells is mediated by MER

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.