APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination

ANTI-DIABETIC ACTIVITY OF EPIPREMNUM AUREUM.L IN NORMAL AND ALLOXAN-INDUCED DIABETIC RATS

ABSTRACTObjective: The study was carried out with the objective of phytochemical screening and to evaluate the anti-diabetic activity of aqueous and alcoholicextract of E. aureum.Methods: The anti-diabetic activity was determined alloxan-induced diabetic rats. A total of 24 albino Wistar rats of either sex weighing 200-250 gwere divided into 4 groups consisting of 4 rats in each group. Group-1 served as control, Group-2 received standard drug, Group-3 received test drugaqueous extract of E. aureum, and Group-4 received test drug alcoholic extract of E. aureum.Results: Phytochemical investigation of aqueous and alcoholic extracts of E. aureum revealed the presence of alkaloids, tannins, saponins, terpenoids,and flavonoids as secondary metabolites. The both aqueous and alcoholic extracts of E. aureum showed a significant reduction in blood glucose levelsdue to the presence of phytochemicals such as flavonoids, terpenoids, and alkaloids in both extracts of E. aureum. The administration of drug (IP) wascontinued upto 15 days.Conclusion: Extracts of E. aureum have shown the great potential of anti-diabetic activity in normal and alloxan-induced rats. Flavonoids might beproducing hypoglycemic effect by a mechanism independent from insulin secretion, e.g. by the inhibition of endogenous glucose production or bythe inhibition of intestinal glucose absorption. This study E. aureum of both aqueous and alcoholic extracts was showed significant effect on alloxaninducedrats.Keywords: Epipremnum aureum, Anti-diabetic activity, Alloxan-induced diabetic rats, Glucometer

A CASE REPORT ON WILSON’S DISEASE: A RARE CLINICAL CONDITION OF COPPER DEPOSITION IN LIVER

Wilson’s disease is a rare inherited disorder and is characterized by the accumulation of copper in various tissues and also in organs like the liver, brain, kidneys and cornea. Symptoms in paediatrics characteristically appear with hepatic involvement. In this case we have discussed about an eleven-year-old male child, who was presented to the Paediatric department in a tertiary care hospital with chief complaints of yellowish discoloration of eyes, dark coloured urine and high grade fever. Due to the accumulation of copper there were decreased levels of ceruloplasmin and there was an increased 24 hour urinary copper, which confirms the Wilson’s disease in this child. Child was treated with Cephalosporin antibiotics, vitamins, laxative, and bile acid sequestrants. Child showed gradual improvement in clinical symptoms and got discharged without any further event. Quality of evidence was assessed according to the GRADE system. Early diagnosis and management helped to prevent serious complications

Cosmo-dynamics and dark energy with a quadratic EoS: anisotropic models, large-scale perturbations and cosmological singularities

In general relativity, for fluids with a linear equation of state (EoS) or scalar fields, the high isotropy of the universe requires special initial conditions, and singularities are anisotropic in general. In the brane world scenario anisotropy at the singularity is suppressed by an effective quadratic equation of state. There is no reason why the effective EoS of matter should be linear at the highest energies, and a non-linear EoS may describe dark energy or unified dark matter (Paper I, astro-ph/0512224). In view of this, here we study the effects of a quadratic EoS in homogenous and inhomogeneous cosmological models in general relativity, in order to understand if in this context the quadratic EoS can isotropize the universe at early times. With respect to Paper I, here we use the simplified EoS P=alpha rho + rho^2/rho_c, which still allows for an effective cosmological constant and phantom behavior, and is general enough to analyze the dynamics at high energies. We first study anisotropic Bianchi I and V models, focusing on singularities. Using dynamical systems methods, we find the fixed points of the system and study their stability. We find that models with standard non-phantom behavior are in general asymptotic in the past to an isotropic fixed point IS, i.e. in these models even an arbitrarily large anisotropy is suppressed in the past: the singularity is matter dominated. Using covariant and gauge invariant variables, we then study linear perturbations about the homogenous and isotropic spatially flat models with a quadratic EoS. We find that, in the large scale limit, all perturbations decay asymptotically in the past, indicating that the isotropic fixed point IS is the general asymptotic past attractor for non phantom inhomogeneous models with a quadratic EoS. (Abridged)Comment: 16 pages, 6 figure

Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)This study was funded by the British Heart Foundation (RG/09/002/2642 to F.M.M.-B.) and the Medical Research Council of the UK (G0901084 to F.M.M.-B.). ImageStream X was funded by the Wellcome Trust (101604/Z/13/Z). This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research

Meteor radar measurements of MLT winds near the equatorial electro jet region over Thumba (8.5° N, 77° E): comparison with TIDI observations

The All-Sky interferometric meteor (SKYiMET) radar (MR) derived winds in the vicinity of the equatorial electrojet (EEJ) are discussed. As Thumba (8.5° N, 77° E; dip lat. 0.5° N) is under the EEJ belt, there has been some debate on the reliability of the meteor radar derived winds near the EEJ height region. In this regard, the composite diurnal variations of zonal wind profiles in the mesosphere-lower thermosphere (MLT) region derived from TIMED Doppler Interferometer (TIDI) and ground based meteor radar at Thumba are compared. In this study, emphasis is given to verify the meteor radar observations at 98 km height region, especially during the EEJ peaking time (11:00 to 14:00 LT). The composite diurnal cycles of zonal winds over Thumba are constructed during four seasons of the year 2006 using TIDI and meteor radar observations, which showed good agreement especially during the peak EEJ hours, thus assuring the reliability of meteor radar measurements of neutral winds close to the EEJ height region. It is evident from the present study that on seasonal scales, the radar measurements are not biased by the EEJ. The day-time variations of HF radar measured E-region drifts at the EEJ region are also compared with MR measurements to show there are large differences between ionospheric drifts and MR measurements. The significance of the present study lies in validating the meteor radar technique over Thumba located at magnetic equator by comparing with other than the radio technique for the first time

Effects of the Nearest-Neighbour Coulomb Interactions on the Ground State of the Periodic Anderson Model

The magnetic and non-magnetic ground states of the periodic Anderson model with Coulomb interaction between $f$-electrons on the nearest-neighbour(NN) sites are investigated using a variational method, which gives exact calculation of the expectation values in the limit of infinite dimensions. It is shown that for a critical value of NN Coulomb interactions the magnetic ground state of the periodic Anderson model in the Kondo regime is unstable. Factors in terms of the physical processes responsible for instability of the magnetic ground state are also discussed. Our study indicates the importance of the NN Coulomb interactions for correlated two band models.Comment: RevTeX, 6 pages, 5 figures, to appear in Phys. Rev.