Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703

Long-term remission of myopic choroidal neovascular membrane after treatment with ranibizumab: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myopia has become a big public health problem in certain parts of the world. Sight-threatening complications like choroidal neovascularisation membranes occur in up to 10% of pathological myopia, and natural history studies show a trend towards progressive visual loss. There are long-term financial and quality-of-life implications in this group of patients, and treatment strategies should aim for long-term preservation of vision.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian woman presented with a best-corrected visual acuity of 6/6-1 in her right eye and 6/24 in her left. Fundal examination revealed pathological myopia in both eyes and an elevated lesion associated with pre-retinal haemorrhage in the left macula. Ocular coherence tomography and fundus fluorescein angiogram confirmed a subfoveal classic choroidal neovascularisation membrane. The patient decided to proceed with intravitreal ranibizumab (0.5 mg) therapy. One month after treatment, best-corrected visual acuity improved to 6/12 in her left eye, with complete resolution subretinal fluid on ocular coherence tomography. After three months, best-corrected visual acuity further improved to 6/9, which was maintained up to 16 months post-treatment.</p> <p>Conclusion</p> <p>We suggest intravitreal ranibizumab as an alternative treatment for long-term remission of myopic choroidal neovascular membrane. It also suggests that myopic choroidal neovascularisation membranes may require fewer treatments to achieve sustained remission. Furthermore, this could serve as a feasible long-term management option if used in conjunction with ocular coherence tomography.</p

Ab initio atomistic thermodynamics and statistical mechanics of surface properties and functions

Previous and present "academic" research aiming at atomic scale understanding is mainly concerned with the study of individual molecular processes possibly underlying materials science applications. Appealing properties of an individual process are then frequently discussed in terms of their direct importance for the envisioned material function, or reciprocally, the function of materials is somehow believed to be understandable by essentially one prominent elementary process only. What is often overlooked in this approach is that in macroscopic systems of technological relevance typically a large number of distinct atomic scale processes take place. Which of them are decisive for observable system properties and functions is then not only determined by the detailed individual properties of each process alone, but in many, if not most cases also the interplay of all processes, i.e. how they act together, plays a crucial role. For a "predictive materials science modeling with microscopic understanding", a description that treats the statistical interplay of a large number of microscopically well-described elementary processes must therefore be applied. Modern electronic structure theory methods such as DFT have become a standard tool for the accurate description of individual molecular processes. Here, we discuss the present status of emerging methodologies which attempt to achieve a (hopefully seamless) match of DFT with concepts from statistical mechanics or thermodynamics, in order to also address the interplay of the various molecular processes. The new quality of, and the novel insights that can be gained by, such techniques is illustrated by how they allow the description of crystal surfaces in contact with realistic gas-phase environments.Comment: 24 pages including 17 figures, related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Tailoring the oxidation state of cobalt through halide functionality in sol-gel silica

The functionality or oxidation state of cobalt within a silica matrix can be tailored through the use of cationic surfactants and their halide counter ions during the sol-gel synthesis. Simply by adding surfactant we could significantly increase the amount of cobalt existing as Co3O4 within the silica from 44% to 77%, without varying the cobalt precursor concentration. However, once the surfactant to cobalt ratio exceeded 1, further addition resulted in an inhibitory mechanism whereby the altered pyrolysis of the surfactant decreased Co3O4 production. These findings have significant implications for the production of cobalt/silica composites where maximizing the functional Co3O4 phase remains the goal for a broad range of catalytic, sensing and materials applications

How South Pacific mangroves may respond to predicted climate change and sea level rise

In the Pacific islands the total mangrove area is about 343,735 ha, with largest areas in Papua New Guinea, Solomon Islands, Fiji and New Caledonia. A total of 34 species of mangroves occur, as well as 3 hybrids. These are of the Indo-Malayan assemblage (with one exception), and decline in diversity from west to east across the Pacific, reaching a limit at American Samoa. Mangrove resources are traditionally exploited in the Pacific islands, for construction and fuel wood, herbal medicines, and the gathering of crabs and fish. There are two main environmental settings for mangroves in the Pacific, deltaic and estuarine mangroves of high islands, and embayment, lagoon and reef flat mangroves of low islands. It is indicated from past analogues that their close relationship with sea-level height renders these mangrove swamps particularly vulnerable to disruption by sea-level rise. Stratigraphic records of Pacific island mangrove ecosystems during sea-level changes of the Holocene Period demonstrate that low islands mangroves can keep up with a sea-level rise of up to 12 cm per 100 years. Mangroves of high islands can keep up with rates of sea-level rates of up to 45 cm per 100 years, according to the supply of fluvial sediment. When the rate of sea-level rise exceeds the rate of accretion, mangroves experience problems of substrate erosion, inundation stress and increased salinity. Rise in temperature and the direct effects of increased CO2 levels are likely to increase mangrove productivity, change phenological patterns (such as the timing of flowering and fruiting), and expand the ranges of mangroves into higher latitudes. Pacific island mangroves are expected to demonstrate a sensitive response to the predicted rise in sea-level. A regional monitoring system is needed to provide data on ecosystem changes in productivity, species composition and sedimentation. This has been the intention of a number of programs, but none has yet been implemented

Metagenomic analysis of the turkey gut RNA virus community

Viral enteric disease is an ongoing economic burden to poultry producers worldwide, and despite considerable research, no single virus has emerged as a likely causative agent and target for prevention and control efforts. Historically, electron microscopy has been used to identify suspect viruses, with many small, round viruses eluding classification based solely on morphology. National and regional surveys using molecular diagnostics have revealed that suspect viruses continuously circulate in United States poultry, with many viruses appearing concomitantly and in healthy birds. High-throughput nucleic acid pyrosequencing is a powerful diagnostic technology capable of determining the full genomic repertoire present in a complex environmental sample. We utilized the Roche/454 Life Sciences GS-FLX platform to compile an RNA virus metagenome from turkey flocks experiencing enteric disease. This approach yielded numerous sequences homologous to viruses in the BLAST nr protein database, many of which have not been described in turkeys. Our analysis of this turkey gut RNA metagenome focuses in particular on the turkey-origin members of the Picornavirales, the Caliciviridae, and the turkey Picobirnaviruses

Nutrient Enrichment Increases Mortality of Mangroves

Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients

Evidence and morality in harm-reduction debates: can we use value-neutral arguments to achieve value-driven goals?

It is common to argue that politicians make selective use of evidence to tacitly reinforce their moral positions, but all stakeholders combine facts and values to produce and use research for policy. The drug policy debate has largely been framed in terms of an opposition between evidence and politics. Focusing on harm reduction provides useful ground to discuss a further opposition proposed by evidence advocates, that between evidence and morality. Can evidence sway individuals from their existing moral positions, so as to “neutralise” morality? And if not, then should evidence advocates change the way in which they frame their arguments? To address these questions, analysis of N=27 interviews with stakeholders involved in drug policy and harm reduction research, advocacy, lobbying, implementation and decision-making in England, UK and New South Wales, Australia, was conducted. Participants’ accounts suggest that although evidence can help focus discussions away from values and principles, exposure to evidence does not necessarily change deeply held views. Whether stakeholders decide to go with the evidence or not seems contingent on whether they embrace a view of evidence as secular faith; a view that is shaped by experience, politics, training, and role. And yet, morality, values, and emotions underpin all stakeholders’ views, motivating their commitment to drug policy and harm reduction. Evidence advocates might thus benefit from morally and emotionally engaging audiences. This paper aims to develop better tools for analysing the role of morality in decision-making, starting with moral foundations theory. Using tools from disciplines such as moral psychology is relevant to the study of the politics of evidence-based policymaking