Investigation of the role of Mg and Ca in the structure and durability of aluminoborosilicate glass

The structure and dissolution behaviour of Na 2 O·CaO·(15–x)Al 2 O 3 ·xB 2 O 3 ·SiO 2 and Na 2 O·MgO·(15–x)Al 2 O 3 ·xB 2 O 3 ·SiO 2 glasses, relevant to compositions of UK nuclear waste glass, have been investigated using nuclear magnetic resonance (NMR) spectroscopy and static dissolution experiments using the PCT protocol. Structural data from 11 B, 27 Al and 29 Si NMR analyses show that increasing the [B 2 O 3 ]/([Al 2 O 3 ] + [B 2 O 3 ]) ratio of the alkali-alkaline-earth aluminoborosilicate glasses led to an overall decrease in the proportion of non-silicate tetrahedral species ( IV Al + IV B) and a decrease in Si–O–X bonds (X[dbnd]B, Al). The Mg-containing glasses exhibited lower IV B fractions than their Ca-containing counterparts, which is thought to be due to the presence of IV Mg tetrahedra in the network. The measured corrosion rates were similar for both Ca and Mg-containing glasses although unexpectedly some Ca-containing glasses exhibited higher corrosion losses than the Mg-containing ones for time periods up to 112 d. However, there was evidence of a greater tendency to rate resumption in the Mg containing than the Ca containing ones. Alteration products were found to contain Ca, Si and Al with the Ca containing glasses and Ca, Mg, Si and Al with the Mg containing glasses; Na was not detected in the alteration products although its presence cannot be ruled out based on the data obtained

Sensory Deprivation as an Experimental Model of Psychosis

The development of novel experimental models of schizophrenia and psychosis are critical to developing a better understanding of these complex and poorly understood disorders. Existing approaches such as animal and drug models have major limitations to their use. An alternative approach to modelling psychosis is proposed, built upon the premise of continuum theory, focusing on ‘high risk’ hallucination prone individuals from within the healthy population. A systematic review considered existing non-pharmacological approaches for inducing psychosis-like experiences (PLE’s) in such individuals. The thesis then addressed how one such method, short-term sensory deprivation, can successfully induce transient psychosis-like experiences (PLE’s) in this population. The Revised Hallucinations Scale (RHS: Morrison et al. 2002) was found to accurately predict individuals most likely to experience PLE’s in sensory deprivation. Individual differences that may contribute to reports of PLE’s were explored: the most powerful predictor of PLE’s in sensory deprivation was verified to be hallucination proneness. Additional personality traits such as fantasy proneness and suggestibility were not implicated. A revised four factor structure for the RHS was also developed, using Exploratory Structural Equation Modelling (ESEM). This model showed improved fit to the original non-replicable factor structure. The ESEM approach is arguably more appropriate than traditional factor analysis for modelling data with high inter-factorial correlations. Quantitative Electroencephalogram (EEG) data was collected in order to establish whether this approach could provide a robust neurophysiological correlate for psychosis-like experiences. Initial pilot data suggested hallucination prone individuals may be characterised by reduced levels of theta, alpha and beta activity, alongside elevated levels of cortical hyper-excitability. These findings support weakened inhibitory processing theories of psychosis. Overall, sensory deprivation was found to have the potential to contribute significantly to our understanding of psychosis, and could be utilised effectively on a stand-alone basis, or as an adjunct to existing animal and drug models

Low-resolution structural studies of human Stanniocalcin-1

Background: Stanniocalcins (STCs) represent small glycoprotein hormones, found in all vertebrates, which have been functionally implicated in Calcium homeostasis. However, recent data from mammalian systems indicated that they may be also involved in embryogenesis, tumorigenesis and in the context of the latter especially in angiogenesis. Human STCI is a 247 amino acids protein with a predicted molecular mass of 27 kDa, but preliminary data suggested its di- or multimerization. The latter in conjunction with alternative splicing and/or post-translational modification gives rise to forms described as STC(50) and "big STC", which molecular weights range from 56 to 135 kDa. Results: In this study we performed a biochemical and structural analysis of STCI with the aim of obtaining low resolution structural information about the human STCI, since structural information in this protein family is scarce. We expressed STCI in both E. coli and insect cells using the baculo virus system with a C-terminal 6 x His fusion tag. From the latter we obtained reasonable amounts of soluble protein. Circular dichroism analysis showed STCI as a well structured protein with 52% of alpha-helical content. Mass spectroscopy analysis of the recombinant protein allowed to assign the five intramolecular disulfide bridges as well as the dimerization Cys202, thereby confirming the conservation of the disulfide pattern previously described for fish STCI. SAXS data also clearly demonstrated that STCI adopts a dimeric, slightly elongated structure in solution. Conclusion: Our data reveal the first low resolution, structural information for human STCI. Theoretical predictions and circular dichroism spectroscopy both suggested that STCI has a high content of alpha-helices and SAXS experiments revealed that STCI is a dimer of slightly elongated shape in solution. The dimerization was confirmed by mass spectrometry as was the highly conserved disulfide pattern, which is identical to that found in fish STCI

Health-related quality of life of Southern Chinese with chronic hepatitis B infection

<p>Abstract</p> <p>Background</p> <p>Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection.</p> <p>Aim</p> <p>To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL.</p> <p>Methods</p> <p>520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC) were interviewed with a structured questionnaire, the SF-36 Health Survey version 2 (SF-36v2), and the Chronic Liver Disease Questionnaire (CLDQ). The differences in SF-6D health preference values and SF-36v2 scores between each CHB group and Hong Kong population norms were assessed by t-test. ANOVA was used to compare the mean SF-6D health preference, SF-36v2 scores, and CLDQ scores among CHB groups. Multiple linear regressions were performed to identify determinants of HRQOL.</p> <p>Results</p> <p>CHB patients had significantly lower SF-36v2 scores than the population norm. The SF-6D values of CHB patients with uncomplicated disease, impaired liver function, HCC and cirrhosis were 0.755, 0.745, 0.720 and 0.701, respectively, all significantly lower than the population norm of 0.787. Advanced stage of CHB illness, anti-viral treatment, bilirubin level, psychological co-morbidity, younger age and female were associated with poorer HRQOL.</p> <p>Conclusion</p> <p>CHB infection had a negative impact on HRQOL. There was a progressive decrease in health preference values with CHB disease progression. The results can be used for the estimation of quality adjusted life years (QALYs) for CHB patients in cost effectiveness or cost utility studies.</p> <p>Trial Registration</p> <p><url>http://www.hkclinicaltrials.com</url>; HKCTR-151.</p

Structural constraints of pyocin S2 import through the ferripyoverdine receptor FpvAI

TonB-dependent transporters (TBDTs) mediate energized transport of essential nutrients into gram-negative bacteria. TBDTs are increasingly being exploited for the delivery of antibiotics to drug-resistant bacteria. While much is known about ground state complexes of TBDTs, few details have emerged about the transport process itself. In this study, we exploit bacteriocin parasitization of a TBDT to probe the mechanics of transport. Previous work has shown that the N-terminal domain of Pseudomonas aeruginosa–specific bacteriocin pyocin S2 (PyoS2NTD) is imported through the pyoverdine receptor FpvAI. PyoS2NTD transport follows the opening of a proton-motive force-dependent pore through FpvAI and the delivery of its own TonB box that engages TonB. We use molecular models and simulations to formulate a complete translocation pathway for PyoS2NTD that we validate using protein engineering and cytotoxicity measurements. We show that following partial removal of the FpvAI plug domain which occludes the channel, the pyocin's N-terminus enters the channel by electrostatic steering and ratchets to the periplasm. Application of force, mimicking that exerted by TonB, leads to unraveling of PyoS2NTD as it squeezes through the channel. Remarkably, while some parts of PyoS2NTD must unfold, complete unfolding is not required for transport, a result we confirmed by disulfide bond engineering. Moreover, the section of the FpvAI plug that remains embedded in the channel appears to serve as a buttress against which PyoS2NTD is pushed to destabilize the domain. Our study reveals the limits of structural deformation that accompanies import through a TBDT and the role the TBDT itself plays in accommodating transport

c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae.

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization