Engineering the vaccinia virus L1 protein for increased neutralizing antibody response after DNA immunization

<p>Abstract</p> <p>Background</p> <p>The licensed smallpox vaccine, comprised of infectious vaccinia virus, has associated adverse effects, particularly for immunocompromised individuals. Therefore, safer DNA and protein vaccines are being investigated. The L1 protein, a component of the mature virion membrane that is conserved in all sequenced poxviruses, is required for vaccinia virus entry into host cells and is a target for neutralizing antibody. When expressed by vaccinia virus, the unglycosylated, myristoylated L1 protein attaches to the viral membrane via a C-terminal transmembrane anchor without traversing the secretory pathway. The purpose of the present study was to investigate modifications of the gene expressing the L1 protein that would increase immunogenicity in mice when delivered by a gene gun.</p> <p>Results</p> <p>The L1 gene was codon modified for optimal expression in mammalian cells and potential N-glycosylation sites removed. Addition of a signal sequence to the N-terminus of L1 increased cell surface expression as shown by confocal microscopy and flow cytometry of transfected cells. Removal of the transmembrane domain led to secretion of L1 into the medium. Induction of binding and neutralizing antibodies in mice was enhanced by gene gun delivery of L1 containing the signal sequence with or without the transmembrane domain. Each L1 construct partially protected mice against weight loss caused by intranasal administration of vaccinia virus.</p> <p>Conclusion</p> <p>Modifications of the vaccinia virus L1 gene including codon optimization and addition of a signal sequence with or without deletion of the transmembrane domain can enhance the neutralizing antibody response of a DNA vaccine.</p

General relativistic effects on neutrino-driven wind from young, hot neutron star and the r-process nucleosynthesis

Neutrino-driven wind from young hot neutron star, which is formed by supernova explosion, is the most promising candidate site for r-process nucleosynthesis. We study general relativistic effects on this wind in Schwarzschild geometry in order to look for suitable conditions for a successful r-process nucleosynthesis. It is quantitatively discussed that the general relativistic effects play a significant role in increasing entropy and decreasing dynamic time scale of the neutrino-driven wind. Exploring wide parameter region which determines the expansion dynamics of the wind, we find interesting physical conditions which lead to successful r-process nucleosynthesis. The conditions which we found realize in the neutrino-driven wind with very short dynamic time scale $\tau_{\rm dyn} \sim 6$ ms and relatively low entropy $S \sim 140$. We carry out the $\alpha$-process and r-process nucleosynthesis calculation on these conditions by the use of our single network code including over 3000 isotopes, and confirm quantitatively that the second and third r-process abundance peaks are produced in the neutrino-driven wind.Comment: Accepted for publication in Ap

Neurite imaging reveals microstructural variations in human cerebral cortical gray matter

We present distinct patterns of neurite distribution in the human cerebral cortex using diffusion magnetic resonance imaging (MRI). We analyzed both high-resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects from the Human Connectome Project. Neurite distributions were evaluated using the neurite orientation dispersion and density imaging (NODDI) model, optimized for gray matter, and mapped onto the cortical surface using a method weighted towards the cortical mid-thickness to reduce partial volume effects. The estimated neurite density was high in both somatosensory and motor areas, early visual and auditory areas, and middle temporal area (MT), showing a strikingly similar distribution to myelin maps estimated from the T1w/T2w ratio. The estimated neurite orientation dispersion was particularly high in early sensory areas, which are known for dense tangential fibers and are classified as granular cortex by classical anatomists. Spatial gradients of these cortical neurite properties revealed transitions that colocalize with some areal boundaries in a recent multi-modal parcellation of the human cerebral cortex, providing mutually supportive evidence. Our findings indicate that analyzing the cortical gray matter neurite morphology using diffusion MRI and NODDI provides valuable information regarding cortical microstructure that is related to but complementary to myeloarchitecture

Terahertz spectroscopy of N18^{18}O and isotopic invariant fit of several nitric oxide isotopologs

A tunable far-infrared laser sideband spectrometer was used to investigate a nitric oxide sample enriched in 18O between 0.99 and 4.75 THz. Regular, electric dipole transitions were recorded between 0.99 and 2.52 THz, while magnetic dipole transitions between the 2Pi(1/2) and 2Pi(3/2) spin-ladders were recorded between 3.71 and 4.75 THz. These data were combined with lower frequency data of N(18)$O (unlabeled atoms refer to (14)N and (16)O, respectively), with rotational data of NO, (15)NO, N(17)O, and (15)N(18)O, and with heterodyne infrared data of NO to be subjected to one isotopic invariant fit. Rotational, fine and hyperfine structure parameters were determined along with vibrational, rotational, and Born-Oppenheimer breakdown corrections. The resulting spectroscopic parameters permit prediction of rotational spectra suitable for the identification of various nitric oxide isotopologs especially in the interstellar medium by means of rotational spectroscopy.Comment: 8 pages, 1 figure; part of the Marilyn Jacox special issue of the Journal of Molecular Spectroscopy, in pres

WIDGET: System Performance and GRB Prompt Optical Observations

The WIDeField telescope for Gamma-ray burst Early Timing (WIDGET) is used for a fully automated, ultra-wide-field survey aimed at detecting the prompt optical emission associated with Gamma-ray Bursts (GRBs). WIDGET surveys the HETE-2 and Swift/BAT pointing directions covering a total field of view of 62 degree x 62 degree every 10 secounds using an unfiltered system. This monitoring survey allows exploration of the optical emission before the gamma-ray trigger. The unfiltered magnitude is well converted to the SDSS r' system at a 0.1 mag level. Since 2004, WIDGET has made a total of ten simultaneous and one pre-trigger GRB observations. The efficiency of synchronized observation with HETE-2 is four times better than that of Swift. There has been no bright optical emission similar to that from GRB 080319B. The statistical analysis implies that GRB080319B is a rare event. This paper summarizes the design and operation of the WIDGET system and the simultaneous GRB observations obtained with this instrument.Comment: 19 pages, 11 figures, Accepted to appear in PAS

Classical and Quantum Solutions and the Problem of Time in R2R^2 Cosmology

We have studied various classical solutions in $R^2$ cosmology. Especially we have obtained general classical solutions in pure $R^2$\ cosmology. Even in the quantum theory, we can solve the Wheeler-DeWitt equation in pure $R^2$\ cosmology exactly. Comparing these classical and quantum solutions in $R^2$\ cosmology, we have studied the problem of time in general relativity.Comment: 17 pages, latex, no figure, one reference is correcte

Pressure-Induced Antiferromagnetic Bulk Superconductor EuFe2_2As2_2

We present the magnetic and superconducting phase diagram of EuFe$_2$As$_2$ for $B \parallel c$ and $B \parallel ab$. The antiferromagnetic phase of the Eu$^{2+}$ moments is completely enclosed in the superconducting phase. The upper critical field vs. temperature curves exhibit strong concave curvatures, which can be explained by the Jaccarino-Peter compensation effect due to the antiferromagnetic exchange interaction between the Eu$^{2+}$ moments and conduction electrons.Comment: submitted to the proceedings of the M2S-IX Toky

Systematic Center-To-Limb Variation in Measured Helioseismic Travel Times and Its Effect on Inferences of Solar Interior Meridional Flows

We report on a systematic center-to-limb variation in measured helioseismic travel times, which must be taken into account for an accurate determination of solar interior meridional flows. The systematic variation, found in time-distance helioseismology analysis using SDO/HMI and SDO/AIA observations, is different in both travel-time magnitude and variation trend for different observables. It is not clear what causes this systematic effect. Subtracting the longitude-dependent east-west travel times, obtained along the equatorial area, from the latitude-dependent north-south travel times, obtained along the central meridian area, gives remarkably similar results for different observables. We suggest this as an effective procedure for removing the systematic center-to-limb variation. The subsurface meridional flows obtained from inversion of the corrected travel times are approximately 10 m s1 slower than those obtained without removing the systematic effect. The detected center-to-limb variation may have important implications in the derivation of meridional flows in the deep interior and needs to be better understood

Development of Simple Sequence Repeat (SSR) Markers and Their Use to Assess Genetic Diversity in Apomictic Guineagrass (\u3cem\u3ePanicum Maximum\u3c/em\u3e Jacq.)

Guineagrass is an important and widely grown tropical forage grass. Despite its importance and increasing popularity, only little is known about its genetic diversity (Ebina et al., 2001). Such information is useful for the selection of diverse parents in breeding programmes. Moreover, no simple sequence repeat (SSR) markers have been reported in any apomixis species. In this study SSR markers were developed and used to investigate genetic diversity in germplasm of apomictic guineagrass

Circadian factors BMAL1 and RORα control HIF-1α transcriptional activity in nucleus pulposus cells: implications in maintenance of intervertebral disc health.

BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or RORα binding to HIF-1α in NP cells. Noteworthy, stable silencing of BMAL1 as well as inhibition of RORα decreased expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To delineate if BMAL1 plays a role in maintenance of disc health, we studied the spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced decreased height, and several parameters associated with vertebral trabecular bone quality were also affected in nulls. In addition, null animals showed a higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus fibrosus. Taken together, our results indicate that BMAL1 and RORα form a regulatory loop in the NP and control HIF-1 activity without direct interaction. Importantly, activities of these circadian rhythm molecules may play a role in the adaptation of NP cells to their unique niche