Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells

We describe new T cell receptor (TCR) transgenic mice (relapsing-remitting [RR] mice) carrying a TCR specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92–106 in the context of I-As. Backcrossed to the SJL/J background, most RR mice spontaneously develop RR experimental autoimmune encephalomyelitis (EAE) with episodes often altering between different central nervous system tissues like the cerebellum, optic nerve, and spinal cord. Development of spontaneous EAE depends on the presence of an intact B cell compartment and on the expression of MOG autoantigen. There is no spontaneous EAE development in B cell–depleted mice or in transgenic mice lacking MOG. Transgenic T cells seem to expand MOG autoreactive B cells from the endogenous repertoire. The expanded autoreactive B cells produce autoantibodies binding to a conformational epitope on the native MOG protein while ignoring the T cell target peptide. The secreted autoantibodies are pathogenic, enhancing demyelinating EAE episodes. RR mice constitute the first spontaneous animal model for the most common form of multiple sclerosis (MS), RR MS

Phenotype Enhancement Screen of a Regulatory spx Mutant Unveils a Role for the ytpQ Gene in the Control of Iron Homeostasis

Spx is a global regulator of genes that are induced by disulfide stress in Bacillus subtilis. The regulon that it governs is comprised of over 120 genes based on microarray analysis, although it is not known how many of these are under direct Spx control. Most of the Spx-regulated genes (SRGs) are of unknown function, but many encode products that are conserved in low %GC Gram-positive bacteria. Using a gene-disruption library of B. subtilis genomic mutations, the SRGs were screened for phenotypes related to Spx-controlled activities, such as poor growth in minimal medium and sensitivity to methyglyoxal, but nearly all of the SRG mutations showed little if any phenotype. To uncover SRG function, the mutations were rescreened in an spx mutant background to determine which mutant SRG allele would enhance the spx mutant phenotype. One of the SRGs, ytpQ was the site of a mutation that, when combined with an spx null mutation, elevated the severity of the Spx mutant phenotype, as shown by reduced growth in a minimal medium and by hypersensitivity to methyglyoxal. The ytpQ mutant showed elevated oxidative protein damage when exposed to methylglyoxal, and reduced growth rate in liquid culture. Proteomic and transcriptomic data indicated that the ytpQ mutation caused the derepression of the Fur and PerR regulons of B. subtilis. Our study suggests that the ytpQ gene, encoding a conserved DUF1444 protein, functions directly or indirectly in iron homeostasis. The ytpQ mutant phenotype mimics that of a fur mutation, suggesting a condition of low cellular iron. In vitro transcription analysis indicated that Spx stimulates transcription from the ytpPQR operon within which the ytpQ gene resides. The work uncovers a link between Spx and control of iron homeostasis

Experimental methodology to assess contaminant diffusion in rock mass

Monitoring changes in electrical conductivity (EC) of aqueous phase, due to contaminant diffusion through porous media, is one of the techniques followed by researchers to understand the migration mechanism. However, the contaminant diffusion in the rock mass is a slow process and hence detecting small changes in conductivity with the help of conventional laboratory conductivity meters is quite difficult. With this in view, an experimental methodology to monitor diffusion of contaminant(s) through the intact and fractured rock mass, with the help of a USDTS (Ultra-Sensitive Devices and Technical Services) conductivity meter, has been developed. Results have been validated with those obtained from the ion chromatograph (IC) technique and a good agreement has been noted. The study demonstrates usefulness of the proposed methodology for online monitoring of contaminant migration through the porous media

Diffusion of iodide, cesium and strontium in charnockite rock mass

Experiments have been conducted to study the diffusion of iodide, cesium and strontium ions through intact and fractured rock samples of charnockite rock formation present at Kalpakkam, India. The diffusion coefficient (D-i) of these ions for the intact and fractured rock samples has been evaluated and is found to be ranging from 0.76.10(-14) to 6.25 . 10(-14) m(2)/s and 0.67 . 10(-9) to 84.6 . 10(-9) m(2)/s, respectively. The study reveals that despite the sorbing nature of Cs and Sr, these ions diffuse comparatively faster than the iodide ion (non-sorbing) through the intact and fractured rock mass. The results have been validated vis-A-vis those reported in the literature and a good agreement has been noticed. This paper deals with details of the testing methodology developed to assess the radionuclide migration as well as the rock mass suitability for safe disposal of the radioactive waste

Centrifuge Modeling of diffusion through rock mass

A geotechnical centrifuge has been employed to model diffusion of contaminants through fractured and intact rock mass. This paper deals with the details of the test setups used for this purpose. The obtained results have been compared with those obtained from the conventional diffusion tests and the validity of the modeling of models has been demonstrated. The study demonstrates the usefulness of the geotechnical centrifuge for modeling the diffusion of contaminants through rock mass in a short time