Rigidity analysis of HIV-1 protease

We present a rigidity analysis on a large number of X-ray crystal structures of the enzyme HIV-1 protease using the 'pebble game' algorithm of the software FIRST. We find that although the rigidity profile remains similar across a comprehensive set of high resolution structures, the profile changes significantly in the presence of an inhibitor. Our study shows that the action of the inhibitors is to restrict the flexibility of the beta-hairpin flaps which allow access to the active site. The results are discussed in the context of full molecular dynamics simulations as well as data from NMR experiments.Comment: 4 pages, 3 figures. Conference proceedings for CMMP conference 2010 which was held at the University of Warwic

De novo protein design:How do we expand into the universe of possible protein structures?

Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do we build into protein-structure space where there are few, if any, natural structures to guide us? To what uses can the resulting proteins be put? And, what, if anything, does this pursuit tell us about how natural proteins fold, function and evolve? We describe the origins of this emerging area of fully de novo protein design, how it could be developed, where it might lead, and what challenges lie ahead

Why the idea of framework propositions cannot contribute to an understanding of delusions

One of the tasks that recent philosophy of psychiatry has taken upon itself is to extend the range of understanding to some of those aspects of psychopathology that Jaspers deemed beyond its limits. Given the fundamental difficulties of offering a literal interpretation of the contents of primary delusions, a number of alternative strategies have been put forward including regarding them as abnormal versions of framework propositions described by Wittgenstein in On Certainty. But although framework propositions share some of the apparent epistemic features of primary delusions, their role in partially constituting the sense of inquiry rules out their role in helping to understand delusions

Soil bacteria override speciation effects on zinc phytotoxicity in zinc-contaminated soils

The effects of zinc (Zn) speciation on plant growth in Zn-contaminated soil in the presence of bacteria are unknown but are critical to our understanding of metal biodynamics in the rhizosphere where bacteria are abundant. A 6-week pot experiment investigated the effects of two plant growth promoting bacteria (PGPB), <i>Rhizobium leguminosarum</i> and <i>Pseudomonas brassicacearum</i>, on Zn accumulation and speciation in <i>Brassica juncea</i> grown in soil amended with 600 mg kg^–1 elemental Zn as three Zn species: soluble ZnSO₄ and nanoparticles of ZnO and ZnS. Measures of plant growth were higher across all Zn treatments inoculated with PGPB compared to uninoculated controls, but Zn species effects were not significant. Transmission electron microscopy identified dense particles in the epidermis and intracellular spaces in roots, suggesting Zn uptake in both dissolved and particulate forms. X-ray absorption near-edge structure (XANES) analysis of roots revealed differences in Zn speciation between treatments. Uninoculated plants exposed to ZnSO₄ contained Zn predominantly in the form of Zn phytate (35%) and Zn polygalacturonate (30%), whereas Zn cysteine (57%) and Zn polygalacturonate (37%) dominated in roots exposed to ZnO nanoparticles. Inoculation with PGPB increased (>50%) the proportion of Zn cysteine under all Zn treatments, suggesting Zn coordination with cysteine as the predominant mechanism of Zn toxicity reduction by PGPB. Using this approach, we show, for the first time, that although speciation is important, the presence of rhizospheric bacteria completely overrides speciation effects such that most of the Zn in plant tissue exists as complexes other than the original form

Mixed planting with a leguminous plant outperforms bacteria in promoting growth of a metal remediating plant through histidine synthesis

<p>The effectiveness of plant growth promoting bacteria (PGPB) in improving metal phytoremediation is still limited by stunted plant growth under high soil metal concentrations. Meanwhile, mixed planting with leguminous plants is known to improve yield in nutrient deficient soils but the use of a metal tolerant legume to enhance metal tolerance of a phytoremediator has not been explored. We compared the use of <i>Pseudomonas brassicacearum, Rhizobium leguminosarum</i>, and the metal tolerant leguminous plant<i> Vicia sativa</i> to promote the growth of <i>Brassica juncea</i> in soil contaminated with 400 mg Zn kg^–1, and used synchrotron based microfocus X-ray absorption spectroscopy to probe Zn speciation in plant roots.<i> B. juncea </i>grew better when planted with <i>V. sativa</i> than when inoculated with PGPB. By combining PGPB with mixed planting,<i> B. juncea</i> recovered full growth while also achieving soil remediation efficiency of >75%, the maximum ever demonstrated for <i>B. juncea.</i> μXANES analysis of <i>V. sativa</i> suggested possible root exudation of the Zn chelates histidine and cysteine were responsible for reducing Zn toxicity. We propose the exploration of a legume-assisted-phytoremediation system as a more effective alternative to PGPB for Zn bioremediation.</p

Seasonal analysis of submicron aerosol in Old Delhi using high-resolution aerosol mass spectrometry: chemical characterisation, source apportionment and new marker identification

We present the first real-time composition of submicron particulate matter (PM1) in Old Delhi using high-resolution aerosol mass spectrometry (HR-AMS). Old Delhi is one of the most polluted locations in the world, and PM1 concentrations reached ∼ 750 µg m−3 during the most polluted period, the post-monsoon period, where PM1 increased by 188 % over the pre-monsoon period. Sulfate contributes the largest inorganic PM1 mass fraction during the pre-monsoon (24 %) and monsoon (24 %) periods, with nitrate contributing most during the post-monsoon period (8 %). The organics dominate the mass fraction (54 %–68 %) throughout the three periods, and, using positive matrix factorisation (PMF) to perform source apportionment analysis of organic mass, two burning-related factors were found to contribute the most (35 %) to the post-monsoon increase. The first PMF factor, semi-volatility biomass burning organic aerosol (SVBBOA), shows a high correlation with Earth observation fire counts in surrounding states, which links its origin to crop residue burning. The second is a solid fuel OA (SFOA) factor with links to local open burning due to its high composition of polyaromatic hydrocarbons (PAHs) and novel AMS-measured marker species for polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Two traffic factors were resolved: one hydrocarbon-like OA (HOA) factor and another nitrogen-rich HOA (NHOA) factor. The N compounds within NHOA were mainly nitrile species which have not previously been identified within AMS measurements. Their PAH composition suggests that NHOA is linked to diesel and HOA to compressed natural gas and petrol. These factors combined make the largest relative contribution to primary PM1 mass during the pre-monsoon and monsoon periods while contributing the second highest in the post-monsoon period. A cooking OA (COA) factor shows strong links to the secondary factor, semi-volatility oxygenated OA (SVOOA). Correlations with co-located volatile organic compound (VOC) measurements and AMS-measured organic nitrogen oxides (OrgNO) suggest SVOOA is formed from aged COA. It is also found that a significant increase in chloride concentrations (522 %) from pre-monsoon to post-monsoon correlates well with SVBBOA and SFOA, suggesting that crop residue burning and open waste burning are responsible. A reduction in traffic emissions would effectively reduce concentrations across most of the year. In order to reduce the post-monsoon peak, sources such as funeral pyres, solid waste burning and crop residue burning should be considered when developing new air quality policy