Tetramerization reinforces the dimer interface of MnSOD.

Two yeast manganese superoxide dismutases (MnSOD), one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), have most biochemical and biophysical properties in common, yet ScMnSOD is a tetramer and CaMnSODc is a dimer or "loose tetramer" in solution. Although CaMnSODc was found to crystallize as a tetramer, there is no indication from the solution properties that the functionality of CaMnSODc in vivo depends upon the formation of the tetrameric structure. To elucidate further the functional significance of MnSOD quaternary structure, wild-type and mutant forms of ScMnSOD (K182R, A183P mutant) and CaMnSODc (K184R, L185P mutant) with the substitutions at dimer interfaces were analyzed with respect to their oligomeric states and resistance to pH, heat, and denaturant. Dimeric CaMnSODc was found to be significantly more subject to thermal or denaturant-induced unfolding than tetrameric ScMnSOD. The residue substitutions at dimer interfaces caused dimeric CaMnSODc but not tetrameric ScMnSOD to dissociate into monomers. We conclude that the tetrameric assembly strongly reinforces the dimer interface, which is critical for MnSOD activity

Analytic mode-matching for acoustic scattering in three dimensional waveguides with flexible walls: Application to a triangular duct

This is the post-print version of the Article. The official published version can be accessed from the links below - Copyright @ 2012 ElsevierAn analytic mode-matching method suitable for the solution of problems involving scattering in three-dimensional waveguides with flexible walls is presented. Prerequisite to the development of such methods is knowledge of closed form analytic expressions for the natural fluid–structure coupled waveforms that propagate in each duct section and the corresponding orthogonality relations. In this article recent theory [J.B. Lawrie, Orthogonality relations for fluid–structural waves in a 3-D rectangular duct with flexible walls, Proc. R. Soc. A. 465 (2009) 2347–2367] is extended to construct the non-separable eigenfunctions for acoustic propagation in a three-dimensional rectangular duct with four flexible walls. For the special case in which the duct cross-section is square, the symmetrical nature of the eigenfunctions enables the eigenmodes for a right-angled, isosceles triangular duct with flexible hypotenuse to be deduced. The partial orthogonality relation together with other important properties of the triangular modes are discussed. A mode-matching solution to the scattering of a fluid–structure coupled wave at the junction of two identical semi-infinite ducts of triangular cross-section is demonstrated for two different sets of “junction” conditions

Brief cognitive assessment in a UK population sample -- distributional properties and the relationship between the MMSE and an extended mental state examination.

BACKGROUND: Despite the MMSE's known flaws, it is still used extensively as both a screening instrument for dementia and a population measure of cognitive ability. The aim of this paper is to provide data on the distribution of MMSE scores in a representative sample from the UK population and to compare it with an extended cognitive assessment (EMSE) which covers a wider range of cognitive domains and provides a wider range of difficulty levels. METHODS: The MMSE and the EMSE were administered to over 12,000 participants at the screening stage of the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi-centre population-based study in England and Wales with respondents aged 65 years and older. RESULTS: Normative values on the MMSE and EMSE are presented by age group, sex and level of education. There are very large differences between age groups, with smaller differences seen between the sexes and by level of education. The EMSE extends the scores at the high end of the ability range, but is no better than the MMSE at differentiating between dementia and non-dementia. CONCLUSION: Population-derived norms are valuable for comparing an individual's score to the score that would be expected among the general population, given the individual's specific demographic characteristics.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Evaluation of recreational health risk in coastal waters based on enterococcus densities and bathing patterns.

We constructed a simulation model to compute the incidences of highly credible gastrointestinal illness (HCGI) in recreational bathers at two intermittently contaminated beaches of Orange County, California. Assumptions regarding spatial and temporal bathing patterns were used to determine exposure levels over a 31-month study period. Illness rates were calculated by applying previously reported relationships between enterococcus density and HCGI risk to the exposure data. Peak enterococcus concentrations occurred in late winter and early spring, but model results showed that most HCGI cases occurred during summer, attributable to elevated number of exposures. Approximately 99% of the 95,010 illness cases occurred when beaches were open. Model runs were insensitive to 0-10% swimming activity assumed during beach closure days. Comparable illness rates resulted under clustered and uniform bather distribution scenarios. HCGI attack rates were within federal guidelines of tolerable risk when averaged over the study period. However, tolerable risk thresholds were exceeded for 27 total days and periods of at least 6 consecutive days. Illness estimates were sensitive to the functional form and magnitude of the enterococcus density-HCGI relationships. The results of this study contribute to an understanding of recreational health risk in coastal waters

Conformational Dynamics of the Plug Domain of the SecYEG Protein-conducting Channel

The central pore of the SecYEG preprotein-conducting channel is closed at the periplasmic face of the membrane by a plug domain. To study its conformational dynamics, the plug was labeled site-specifically with an environment-sensitive fluorophore. In the presence of a stable preprotein translocation intermediate, the SecY plug showed an enhanced solvent exposure consistent with a displacement from the hydrophobic central pore region. In contrast, binding and insertion of a ribosome-bound nascent membrane protein did not alter the plug conformation. These data indicate different plug dynamics depending on the ligand bound state of the SecYEG channel.

Explanation Based Generalisation = Partial Evaluation

We argue that explanation-based generalisation as recently proposed in the machine learning literature is essentially equivalent to partial evaluation, a well known technique in the functional and logic programming literature. We show this equivalence by analysing the definitions and underlying algorithms of both techniques, and by giving a Prolog program which can be interpreted as doing either explanation-based generalisation or partial evaluation

A simple rule for axon outgrowth and synaptic competition generates realistic connection lengths and filling fractions

Neural connectivity at the cellular and mesoscopic level appears very specific and is presumed to arise from highly specific developmental mechanisms. However, there are general shared features of connectivity in systems as different as the networks formed by individual neurons in Caenorhabditis elegans or in rat visual cortex and the mesoscopic circuitry of cortical areas in the mouse, macaque, and human brain. In all these systems, connection length distributions have very similar shapes, with an initial large peak and a long flat tail representing the admixture of long-distance connections to mostly short-distance connections. Furthermore, not all potentially possible synapses are formed, and only a fraction of axons (called filling fraction) establish synapses with spatially neighboring neurons. We explored what aspects of these connectivity patterns can be explained simply by random axonal outgrowth. We found that random axonal growth away from the soma can already reproduce the known distance distribution of connections. We also observed that experimentally observed filling fractions can be generated by competition for available space at the target neurons--a model markedly different from previous explanations. These findings may serve as a baseline model for the development of connectivity that can be further refined by more specific mechanisms.Comment: 31 pages (incl. supplementary information); Cerebral Cortex Advance Access published online on May 12, 200

Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations

We describe how the James Webb Space Telescope (JWST) Near-Infrared Spectrograph's (NIRSpec's) detectors will be read out, and present a model of how noise scales with the number of multiple non-destructive reads sampling-up-the-ramp. We believe that this noise model, which is validated using real and simulated test data, is applicable to most astronomical near-infrared instruments. We describe some non-ideal behaviors that have been observed in engineering grade NIRSpec detectors, and demonstrate that they are unlikely to affect NIRSpec sensitivity, operations, or calibration. These include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real test data, we show that the reset anomaly is: (1) very nearly noiseless and (2) can be easily calibrated out. Likewise, we show that large-amplitude RTN affects only a small and fixed population of pixels. It can therefore be tracked using standard pixel operability maps.Comment: 55 pages, 10 figure

Elevated Bathing-Associated Disease Risks Despite Certified Water Quality: A Cohort Study

Bacteriological water quality criteria have been recommended to ensure bathers’ health. However, this risk-assessment approach is based mainly on routine measurements of fecal pollution indicator bacteria in seawater, and may not be adequate to protect bathers effectively. The aim of this study was to assess the risks of symptoms related to infectious diseases among bathers after exposure to seawater which was of excellent quality according to EU guidelines. This study is a cohort study recruiting bathers and non-bathers. Water samples were collected for estimating bacterial indicators. Univariable and multivariable analysis was performed to compare the risks of developing symptoms/diseases between bathers and non-bathers. A total of 3805 bathers and 572 non-bathers were included in the study. Water analysis results demonstrated excellent quality of bathing water. Significantly increased risks of symptoms related to gastrointestinal infections (OR = 3.60, 95% CI 1.28–10.13), respiratory infections (OR = 1.92, 95% CI 1.00–3.67), eye infections (OR = 2.43, 95% CI 1.27–4.63) and ear infections (OR = 17.21, 95% CI 2.42–122.34) were observed among bathers compared with non-bathers. Increased rates of medical consultation and medication use were also observed among bathers. There was evidence that bathers experienced increased morbidity compared with non-bathers though the bathing waters met bacteriological water quality criteria. These results suggest that risk assessments of recreational seawaters should not only focus on bacteriological water quality criteria

Pro-BDNF–induced synaptic depression and retraction at developing neuromuscular synapses

Postsynaptic cells generate positive and negative signals that retrogradely modulate presynaptic function. At developing neuromuscular synapses, prolonged stimulation of muscle cells induces sustained synaptic depression. We provide evidence that pro–brain-derived neurotrophic factor (BDNF) is a negative retrograde signal that can be converted into a positive signal by metalloproteases at the synaptic junctions. Application of pro-BDNF induces a dramatic decrease in synaptic efficacy followed by a retraction of presynaptic terminals, and these effects are mediated by presynaptic pan-neurotrophin receptor p75 (p75NTR), the pro-BDNF receptor. A brief stimulation of myocytes expressing cleavable or uncleavable pro-BDNF elicits synaptic potentiation or depression, respectively. Extracellular application of metalloprotease inhibitors, which inhibits the cleavage of endogenous pro-BDNF, facilitates the muscle stimulation–induced synaptic depression. Inhibition of presynaptic p75NTR or postsynaptic BDNF expression also blocks the activity-dependent synaptic depression and retraction. These results support a model in which postsynaptic secretion of a single molecule, pro-BDNF, may stabilize or eliminate presynaptic terminals depending on its proteolytic conversion at the synapses