The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration

Sulfide: quinone oxidoreductase (SQR) is a flavoprotein with homologues in all domains of life except plants. It plays a physiological role both in sulfide detoxification and in energy transduction. We isolated the protein from native membranes of the hyperthermophilic bacterium Aquifex aeolicus, and we determined its X-ray structure in the "as-purified,'' substrate-bound, and inhibitor-bound forms at resolutions of 2.3, 2.0, and 2.9 angstrom, respectively. The structure is composed of 2 Rossmann domains and 1 attachment domain, with an overall monomeric architecture typical of disulfide oxidoreductase flavoproteins. A. aeolicus SQR is a surprisingly trimeric, periplasmic integral monotopic membrane protein that inserts about 12 angstrom into the lipidic bilayer through an amphipathic helix-turn-helix tripodal motif. The quinone is located in a channel that extends from the si side of the FAD to the membrane. The quinone ring is sandwiched between the conserved amino acids Phe-385 and Ile-346, and it is possibly protonated upon reduction via Glu-318 and/or neighboring water molecules. Sulfide polymerization occurs on the re side of FAD, where the invariant Cys-156 and Cys-347 appear to be covalently bound to polysulfur fragments. The structure suggests that FAD is covalently linked to the polypeptide in an unusual way, via a disulfide bridge between the 8-methyl group and Cys-124. The applicability of this disulfide bridge for transferring electrons from sulfide to FAD, 2 mechanisms for sulfide polymerization and channeling of the substrate, S2-, and of the product, S-n, in and out of the active site are discussed.

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximate to 20,000 microbial extracts, 12 hits were identified with broadspectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.

Prediction of Physical Properties of Yeast Cell Suspensions using Dielectric Spectroscopy

D.J. Currie, M.H. Lee and R.W. Todd, 'Prediction of Physical Properties of Yeast Cell Suspensions using Dielectric Spectroscopy', Conference on Electrical Insulation and Dielectric Phenomena, (CEIDP 2006), Annual Report, pp 672 ? 675, October 15th -18th 2006, Kansas City, Missouri, USA. Organised by IEEE Dielectrics and Electrical Insulation Society.

Regulation of yeast oscillatory dynamics

Douglas B. Murray, Manfred Beckmann, and Hiroaki Kitano. (2007). Regulation of yeast oscillatory dynamics. Proceedings of the National Academy of Sciences of the USA, 104 (7), 2241-2246 Sponsorship: Solution-Oriented Research for Science and Technology Agency to the Systems Biology Institute /21st Century Center of Excellence Program and Special Coordination Program of the Ministry of Education, Sports, Culture, Science, and Technology to Keio University RAE2008

Predicting interpretability of metabolome models based on behavior, putative identity, and biological relevance of explanatory signals

Enot, D. P., Beckmann, M., Overy, D., Draper, J. (2006). Predicting interpretability of metabolome models based on behavior, putative identity, and biological relevance of explanatory signals. Proceedings of the National Academy of Sciences of the USA, 103(40), 14865-14870. Sponsorship: BBSRC RAE2008

The why and how of foreign missions.

http://www.archive.org/details/whyandhowofforei014010mbp

The Practice and Understanding of the Eucharist in the United Church of Christ: A Practical Theological Study

This dissertation explores the complexity of the understanding and practice of the Eucharist in the United Church of Christ as revealed in a textual analysis of the UCC Book of Worship (1986) and a qualitative study of five representative UCC congregations. Little has been written on this topic, save for several brief articles on the history of the theology of the sacrament in the two bodies that merged to form the UCC in 1957: the Congregational Christian Churches (CC) and the Evangelical and Reformed Church (E&R). This dissertation advances the topic through a practical-theological study that brings into critical conversation contemporary eucharistic practices in five congregations and a historical theological analysis of liturgical traditions in the UCC and antecedent denominations. Through this conversation, the study articulates common themes of a UCC eucharistic theology and explores implications for ongoing theology and practice in the denomination. The introduction explicates the methodology employed in this study, guided by Don Browning's work. The first two chapters present the findings of the focus group interviews and an interpretation of those results respectively. Chapter three analyzes the eucharistic liturgies in three historic books of worship used in the E&R heritage. In chapter four, two of the antecedent resources utilized in the CC tradition are analyzed. The short-lived Hymnal of the United Church of Christ, published in 1974, includes liturgies that would find fuller expression in the 1986 Book of Worship. That hymnal is examined in chapter five. Chapter six interprets the two services of "Word and Sacrament" found in the Book of Worship. Chapter seven offers a comparative analysis of the focus group findings and the theology inherent in the Book of Worship. The final chapter offers strategic recommendations for revised theory and practice. The conclusion points toward areas for further research: it propels a critical conversation around the notion of covenant, Christ's presence in the meal, and who can receive and officiate at the Eucharist. This dissertation concludes that the UCC lives within a balance of multiple, complementary theologies and challenges the denomination to make stronger connections between the meal and mission, reconciliation, and tradition.

Towards a new model of criminal justice system in the era of globalised criminality: the biggest challenges for criminal process legislation

The main objective of this thesis is the critical analysis of the evolution of the criminal justice systems throughout the past decade, with special attention to the fight against transnational terrorism. It is evident – for any observer - that such threats and the associated risk that terrorism entails, has changed significantly throughout the past decade. This perception has generated answers – many times radical ones – by States, as they have committed themselves to warrant the safety of their populations and to ease a growing sentiment of social panic. This thesis seeks to analyse the characteristics of this new threat and the responses that States have developed in the fight against terrorism since 9/11, which have questioned some of the essential principles and values in place in their own legal systems. In such sense, freedom and security are placed into perspective throughout the analysis of the specific antiterrorist legal reforms of five different States: Israel, Portugal, Spain, the United Kingdom and the United States of America. On the other hand, in light of those antiterrorist reforms, it will be questioned if it is possible to speak of the emergence of a new system of criminal justice (and of a process of a convergence between common law and civil law systems), built upon a control and preventive security framework, significantly different from traditional models. Finally, this research project has the fundamental objective to contribute to a better understanding on the economic, social and civilization costs of those legal reforms regarding human rights, the rule of law and democracy in modern States.

Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain

P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATPBinding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse Pgp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.

Acid gas hazards in the crater of Villarrica volcano (Chile)

The atmospheric concentrations of the acid gases SO2, HCl, and HF were measured during austral summer 2001 in the summit crater area of Villarrica volcano using 'filter packs'. These data were collected in order to assess the acid gas hazards to tourists who ascend the volcano. The authors compared their acid gas concentration results with exposure limits outlined by the National Institute of Occupational Safety and Health (NIOSH-United States of America). The authors conclude that tourists who visit the summit crater of Villarrica may be exposed to non-lethal concentrations of SO2 and HCl that exceed the recommended exposure limits defined by NIOSH, while atmospheric concentrations of HF do not exceed the recommended exposure limits.

Ontogeny of mouse B lymphocytes and inactivation by antigen of early B lymphocytes

Taking advantage of recent findings about membrane fluidity, the authors studied and compared the biosynthetic capacities of fetal or neonatal mouse B (bone marrow derived) lymphocytes (until 10 days after birth) and adult B lymphocytes. Although both early and adult lymphocytes can synthesize surface immunoglobulins, they have a different physiological behavior after interaction with a ligand (anti immunoglobulin sera or antigen), either in vivo or in vitro. Fetal and neonatal lymphocytes bearing surface immunoglobulins do not reexpress their membrane receptors after capping and endocytosis promoted by anti immunoglobulin sera. On the other hand, adult lymphocytes resynthesize completely their receptors after the same treatment. Furthermore, intrafetal injections of hemocyanin in pregnant mice lead to a striking decrease in the number of hemocyanin binding cells. It seems plausible that this non reexpression of surface immunoglobulins could be the first step in tolerance establishment.

Current scenario of scientific publications related to weeds in Argentina : comparison with some countries of America

p.131-140

Current scenario of scientific publications related to weeds in Argentina : comparison with some countries of America

p.131-140