Studies on the Development of Resistance in Experimental Murine Schistosomiasis

Experiments were performed in mice on resistance to challenge with Schistosoma mansoni and S. mattheei cercariae following previous bisexual, single sex or irradiated infections. Resistance to reinfection was demonstrated following bisexual infection with S. mansoni using out-bred T.O. mice and it appeared that such resistance was not stimulated by cercarial transformation products. T. O. mice from three different suppliers exhibited markedly different levels of resistance and mortality. Bisexual infection with S. mattheei resulted in resistance to both homologous challenge and heterologous challenge with S. mansoni. Infections with S.mansoni worms of one sex only, stimulated significantly lower resistance than light bisexual infections. Injection of eggs alone failed to stimulate resistance, suggesting that both worms and eggs may be required. Studies on irradiation of S. mansoni and S. mattheei showed that the minimum radiation doses required to produce sterile infections were 2.3 kr and 2.7 kr respectively, due predominantly to sterilization of the female worms. Radiation-induced death of 2.3 kr-irradiated para sites occurred mainly in the liver. but higher doses resulted in death earlier in the migration pathway. with parasites exposed to 40 kr dying at the site of infection. Varying levels of resistance followed percutaneous or intramuscular infection with larvae irradiated with 2.3-160 kr. This resistance was demonstrated by significantly reduced worm and egg burdens and by longer survival of the vaccinated mice. Maximal resistance was demonstrated earlier following vaccination with highly irradiated parasites (20-40 kr) than with 2.3 kr-irradiated parasites, although comparable levels were eventually reached. The resistance was not transient, being demonstrated 17 weeks post-infection. Neither unirradiated male parasites alone nor dead irradiated parasites could confer resistance suggesting that, in the absence of eggs, death of the parasites within the host is necessary for the induction of resistance. Resistance was not increased by varying the number of irradiated larvae, the number of vaccinations, the route of vaccination or by the simultaneous administration of B.C.G. Irradiated S. mattheei infections conferred only weak resistance to homologous challenge and vaccination with irradiated S.mansoni or S. mattheei failed to confer significant resistance to heterologous challenge

Structure of HsdS Subunit from Thermoanaerobacter tengcongensis Sheds Lights on Mechanism of Dynamic Opening and Closing of Type I Methyltransferase

Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 Å crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase

The Role of Galectin-1 and Galectin-3 in the Mucosal Immune Response to Citrobacter rodentium Infection

Despite their abundance at gastrointestinal sites, little is known about the role of galectins in gut immune responses. We have therefore investigated the Citrobacter rodentium model of colonic infection and inflammation in Galectin-1 or Galectin-3 null mice. Gal-3 null mice showed a slight delay in colonisation after inoculation with C. rodentium and a slight delay in resolution of infection, associated with delayed T cell, macrophage and dendritic cell infiltration into the gut mucosa. However, Gal-1 null mice also demonstrated reduced T cell and macrophage responses to infection. Despite the reduced T cell and macrophage response in Gal-1 null mice, there was no effect on C. rodentium infection kinetics and pathology. Overall, Gal-1 and Gal-3 play only a minor role in immunity to a gut bacterial pathogen

The Geomechanics of CO2 Storage in Deep Sedimentary Formations

This paper provides a review of the geomechanics and modeling of geomechanics associated with geologic carbon storage (GCS), focusing on storage in deep sedimentary formations, in particular saline aquifers. The paper first introduces the concept of storage in deep sedimentary formations, the geomechanical processes and issues related with such an operation, and the relevant geomechanical modeling tools. This is followed by a more detailed review of geomechanical aspects, including reservoir stress-strain and microseismicity, well integrity, caprock sealing performance, and the potential for fault reactivation and notable (felt) seismic events. Geomechanical observations at current GCS field deployments, mainly at the In Salah CO2 storage project in Algeria, are also integrated into the review. The In Salah project, with its injection into a relatively thin, low-permeability sandstone is an excellent analogue to the saline aquifers that might be used for large scale GCS in parts of Northwest Europe, the U.S. Midwest, and China. Some of the lessons learned at In Salah related to geomechanics are discussed, including how monitoring of geomechanical responses is used for detecting subsurface geomechanical changes and tracking fluid movements, and how such monitoring and geomechanical analyses have led to preventative changes in the injection parameters. Recently, the importance of geomechanics has become more widely recognized among GCS stakeholders, especially with respect to the potential for triggering notable (felt) seismic events and how such events could impact the long-term integrity of a CO{sub 2} repository (as well as how it could impact the public perception of GCS). As described in the paper, to date, no notable seismic event has been reported from any of the current CO{sub 2} storage projects, although some unfelt microseismic activities have been detected by geophones. However, potential future commercial GCS operations from large power plants will require injection at a much larger scale. For such largescale injections, a staged, learn-as-you-go approach is recommended, involving a gradual increase of injection rates combined with continuous monitoring of geomechanical changes, as well as siting beneath a multiple layered overburden for multiple flow barrier protection, should an unexpected deep fault reactivation occur