Enhanced CD8+ T-cell response in mice immunized with NS1-truncated influenza virus

Influenza viruses with truncated NS1 protein stimulate a more intensive innate immune response compared to their wild type counterparts. Here, we investigate how the shortening of the NS1 protein influence the immunogenicity of the conserved T-cellular epitopes of influenza virus. Using flow cytometry, we showed that the intraperitoneal immunization of mice with influenza virus encoding 124 N-terminal amino acid residues of the NS1 protein (A/PR8/NS124) induced higher levels of CD8+ T-cells recognizing immunodominant (NP366-374) and sub-immunodominant (NP161-175, NP196-210, HA323-337, HA474-483, NA427-433) epitopes compared to immunization with the virus expressing full-length NS1 (A/PR8/full NS). It is noteworthy that the response to the immunodominant influenza epitope NP366-374 was achieved with the lower immunization dose of A/PR8/NS124 virus compared to the reference wild type strain. Despite the fact that polyfunctional CD8+ effector memory T-lymphocytes simultaneously producing two (IFNγ and TNFα) or three (IFNγ, IL2, and TNFα) cytokines prevailed in the immune response to both viruses, the relative number of such T-cells was higher in A/PR8/NS124-immunized mice. Furthermore, we have found that polyfunctional populations of lymphocytes generated upon the immunization of mice with the mutant virus demonstrated an increased capacity to produce IFNγ compared to the corresponding populations derived from the A/PR8/full NS-immunized mice. Therefore, immunization with the attenuated influenza virus encoding truncated NS1 protein ensures a more potent CD8+ T-cell immune response.Influenza viruses with truncated NS1 protein stimulate a more intensive innate immune response compared to their wild type counterparts. Here, we investigate how the shortening of the NS1 protein influence the immunogenicity of the conserved T-cellular epitopes of influenza virus. Using flow cytometry, we showed that the intraperitoneal immunization of mice with influenza virus encoding 124 N-terminal amino acid residues of the NS1 protein (A/PR8/NS124) induced higher levels of CD8+ T-cells recognizing immunodominant (NP366-374) and sub-immunodominant (NP161-175, NP196-210, HA323-337, HA474-483, NA427-433) epitopes compared to immunization with the virus expressing full-length NS1 (A/PR8/full NS). It is noteworthy that the response to the immunodominant influenza epitope NP366-374 was achieved with the lower immunization dose of A/PR8/NS124 virus compared to the reference wild type strain. Despite the fact that polyfunctional CD8+ effector memory T-lymphocytes simultaneously producing two (IFNγ and TNFα) or three (IFNγ, IL2, and TNFα) cytokines prevailed in the immune response to both viruses, the relative number of such T-cells was higher in A/PR8/NS124-immunized mice. Furthermore, we have found that polyfunctional populations of lymphocytes generated upon the immunization of mice with the mutant virus demonstrated an increased capacity to produce IFNγ compared to the corresponding populations derived from the A/PR8/full NS-immunized mice. Therefore, immunization with the attenuated influenza virus encoding truncated NS1 protein ensures a more potent CD8+ T-cell immune response

Search for Sterile Neutrinos with a Radioactive Source at Daya Bay

The far site detector complex of the Daya Bay reactor experiment is proposed as a location to search for sterile neutrinos with > eV mass. Antineutrinos from a 500 kCi 144Ce-144Pr beta-decay source (DeltaQ=2.996 MeV) would be detected by four identical 20-ton antineutrino targets. The site layout allows flexible source placement; several specific source locations are discussed. In one year, the 3+1 sterile neutrino hypothesis can be tested at essentially the full suggested range of the parameters Delta m^2_{new} and sin^22theta_{new} (90% C.L.). The backgrounds from six nuclear reactors at >1.6 km distance are shown to be manageable. Advantages of performing the experiment at the Daya Bay far site are described

Observation of microbial carbonate build-ups growing at methane seeps near the upper boundary of the gas-hydrate stability zone in the Black Sea

Extensive dredge sampling carried out in May-June 2004 in the deeper part of the Dnepr paleo-delta area (NW Black Sea) yielded for the first time chimney-shaped carbonate microbial build-ups, which occur at methane seeps close to upper boundary of the gas-hydrate stability zone (~ 700 m). Carbonate samples taken with a benthic trawl represent fragments of the uppermost, middle and lowest parts of the build-up; they are similar morphologically to those found previously at the shallower and deeper methane seeps in the Black Sea. At the same time, the perforated, plate-like carbonates in the lowest parts of the build-up provide first indications that gas channels are formed during the earliest growth phase of these microbial structures. Stable carbon isotope analyses of the carbonates from the uppermost fragments gave the 5I3C values ranging from -33.7 to -36.6 %o, while the 813C values of the lowest fragments are significantly lighter, varying between -42.0 and -44.6 %o. Oxygen isotopic values also show differences between the samples from the uppermost part of the build-ups, which are composed of a mixture of aragonite and Mg-calcite (5180 = 0.7 to 0.94 %o), and the only Mg-calcite cemented thin slabs of lowest carbonates (5180 = 1.35 to 1.57 96o). The isotope data for carbon and oxygen suggests that carbonates formed as a result of anaerobic microbiological oxi­dation of methane supplied as a shallower-sourced fluid component from below. The difference in 513C and 5I80 values found in the upper and lowest parts of the build-ups may indicate that more carbon derived from seawater and less hydrate water are involved to the chimney formation during its growth, but this may be also a record of the long-term changes in the near-bottom environments related to evolution of salinity, temperature and anoxic conditions in the Black Sea

Enhancement of the immunogenicity of influenza A virus by the inhibition of immunosuppressive function of NS1 protein

The truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response.The truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response

REFINED MODEL OF THE OPTICAL SYSTEM FOR SPACE MINI-VEHICLES WITH LASER PROPULSION

Simulation results for on-board optical system of a space mini-vehicle with laser propulsion are presented. This system gives the possibility for receiving theremote laser radiation power independently of a system telescope mutual orientation to the vehicle orbiting direction. The on-board optical system is designed with the use of such optical elements as optical hinges and turrets. The system incorporates the optical switch that is a special optical system adapting optically both receiving telescope and laser propulsion engines. Modeling and numerical simulation of the system have been performed with the use of ZEMAX software (Radiant Ltd). The object matter of calculations lied in size definition of system optical elements, requirements to accuracy of their manufacturing and reciprocal adjusting to achieve an efficient radiation energy delivery to laser propulsion engine. Calculations have been performed with account to the limitations on the mini-vehicle mass, its overall dimensions, and radiation threshold density of the optical elements utilized. The requirements to the laser beam quality at the entrance aperture of laser propulsion engine have been considered too. State-of-the-art optical technologies make it possible to manufacture space reflectors made of CO-115M glassceramics with weight-reducing coefficient of 0.72 and the radiation threshold of 5 J/cm2 for the radiation with a 1.064 microns wavelength at 10-20 ns pulse duration. The optimal diameter of a receiving telescope primary mirror has been 0.5 m when a coordinated transmitting telescope diameter is equal to 1 m. This provides the reception of at least 84% of laser energy. The main losses of radiation energy are caused by improper installation of receiving telescope mirrors and by in-process errors arising at manufacturing the telescope mirrors with a parabolic surface. It is shown that requirements to the in-process admissible errors for the on-board optical system elements and to their mutual adjustment accuracy are enhanced, but they are feasible at the same time. The proposed onboard optical system are usable both for space mini-vehicle with laser propulsion and for wireless technology of energy delivery through space with the use of lasers

Effect of Copper Doping on Charge Ordering in La 1/3 Ca 2/3 Mn 1 - y Cu y O 3 (0 ≤ y ≤ 0.07)

Electron microscope studies have shown that the presence of copper suppresses the formation of a regular superstructure, which is characteristic of the undoped starting compound, beginning already from low concentrations (y=0.01). Differential scanning calorimetry revealed a substantial decrease in the transition entropy at the onset of charge ordering in copper-doped samples as compared to the starting compound. Doping with copper destroys long-range charge-orbital ordering and retains apparently only short-range orderyesBelgorod State Universit

Structures of Malcev Bialgebras on a simple non-Lie Malcev algebra

Lie bialgebras were introduced by Drinfeld in studying the solutions to the classical Yang-Baxter equation. The definition of a bialgebra in the sense of Drinfeld (D-bialgebra), related with any variety of algebras, was given by Zhelyabin. In this work, we consider Malcev bialgebras. We describe all structures of a Malcev bialgebra on a simple non-Lie Malcev algebra

Spin light of neutrino in gravitational fields

We predict a new mechanism for the spin light of neutrino ($SL\nu$) that can be emitted by a neutrino moving in gravitational fields. This effect is studied on the basis of the quasiclassical equation for the neutrino spin evolution in a gravitational field. It is shown that the gravitational field of a rotating object, in the weak-field limit, can be considered as an axial vector external field which induces the neutrino spin procession. The corresponding probability of the neutrino spin oscillations in the gravitational field has been derived for the first time. The considered in this paper $SL\nu$ can be produced in the neutrino spin-flip transitions in gravitational fields. It is shown that the total power of this radiation is proportional to the neutrino gamma factor to the fourth power, and the emitted photon energy, for the case of an ultra relativistic neutrino, could span up to gamma-rays. We investigate the $SL\nu$ caused by both gravitational and electromagnetic fields, also accounting for effects of arbitrary moving and polarized matter, in various astrophysical environments. In particular, we discuss the $SL\nu$ emitted by a neutrino moving in the vicinity of a rotating neutron star, black hole surrounded by dense matter, as well as by a neutrino propagating in the relativistic jet from a quasar.Comment: 14 pages in LaTex with 1 eps figure; derivation of the neutrino spin oscillations probability in gravitational fields and several clarifying notes are added, typos correcte