Selection and characterization of Toxoplasma gondii mutants resistant to artemisinin

Toxoplasma gondii infection, like malaria, is sensitive to inhibition by artemisinin (ART). Mechanisms of action for ART in malaria treatment have been proposed, but little is known about its effects in T. gondii infection. To better understand its inhibitory effects on T. gondii, mutants resistant to ART were selected by progressive culture in permissive levels of the drug. Five clonal isolates were established and characterized. The isolates were approximately 65-fold less sensitive to ART than is the parental RH and showed cross-resistance to the ART derivatives dihydroartemisinin and artemether. In addition to ART resistance, 1 clone (C9) formed morphologically unusual parasitophorous vacuoles and another (A2) was avirulent for mice and protected mice from challenge with the wild type. These clonal T. gondii mutant isolates will be useful for the study of not only the mechanism of action of ART but also parasite vacuole biology and virulence factors.     

Gene therapy strategies for AIDS-related malignancies

AIDS-related malignancies (ARM) include AIDS-defining cancers such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma. In addition, certain other malignancies are also increased with human immunodeficiency virus (HIV) infection. New antiretroviral agents and better prophylaxis and treatment of HIV-related opportunistic infections are prolonging the lives of HIV-infected individuals. There will thus likely be a continued rise in the incidence and prevalence of ARM in the long term, even if effective antiretroviral and other AIDS-related therapies reduce their appearance in the short term. There are presently no curative regimens for the common ARM, with the possible exception of some lymphomas. Survival is shortened by most, and treatment is often toxic and poorly tolerated. Gene therapies may thus offer a useful adjunct to conventional treatment strategies for selected ARM. Although some gene therapy strategies may work well in the HIV setting, the chronic viral infection, immunodeficient status of the host, the tendency for HIV-infected individuals to have altered drug metabolism and an increased rate of adverse drug reactions will likely present special challenges. This review summarizes the state-of-the-art in the fledgling field of gene therapy for ARM, and explores areas for future research.     

Earthquake science research with a microsatellite

Reliable, repeatable earthquake forecast is a subject surrounded by controversy and scepticism. What is clear is that reliable forecast would be a critical tool for effective earthquake disaster management. It is proposed that satellites and ground-based facilities may detect earthquake precursors in the ionosphere a few hours or days before the main shock. A low-cost 100 kg class satellite carrying a topside sounder is proposed, to make systematic measurements over seismically active zones. The mission aims to confirm or refute the hypothesis of ionospheric earthquake precursors, define the reliability and reproducibility, and enable further scientific understanding of their mechanisms.     

Simultaneous degradation of atrazine and simazine by a binary culture of Stenotrophomonas maltophilia and Arthrobacter sp. in a two‐stage biofilm reactor

BACKGROUND: The impact of mixtures of chloro‐triazinic herbicides, such as atrazine and simazine, on aquatic ecosystems is of environmental concern. To study their biodegradation under various operational conditions, a binary community comprising Stenotrophomonas maltophilia and Arthrobacter sp. attached to the porous support of a packed bed reactor, was evaluated. RESULTS: The genetic analysis of the two atrazine‐degrading strains revealed that genes atzA, atzB, atzC are present in both bacteria, but only S. maltophilia possess atzD. Thus, by cultivating Arthrobacter sp. on these herbicides, cyanuric acid accumulation was observed. When the binary community was cultivated in the biofilm reactor, at all the loading rates probed, both herbicides were entirely removed. However, complete biodegradation of cyanuric acid was not achieved. CONCLUSIONS: Even with a two‐stage reactor, cyanuric acid was only partially removed. This fact could be attributed to the absence, in the second stage, of an easily degradable energy source, required by S. maltophilia for the uptake and cometabolic degradation of the recalcitrant heterocyclic ring. Responding to differences in nutritional conditions prevailing at each reactor stage, local differences in species' predominance were clearly detected by microbiological and molecular biology methods. Copyright © 2010 Society of Chemical Industry     

On balanced games and games with committee control

Summary A generalization of flow games, namely, flow games with committee control is considered, to obtain a representation of non-negative balanced games. The committee control is modeled with the aid of simple games. Linear production games with committee control are also studied and results on the balancedness of such games are obtained.

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Zusammenfassung Eine Verallgemeinerung von Fluß-spielen, nämlich solchen mit Komitee-Kontrolle, wird in der vorliegenden Arbeit betrachtet, um eine Darstellung nicht-negativer ausgewogener Spiele zu erhalten. Die Komitee-Kontrolle wird mit Hilfe einfacher Spiele modelliert. Ebenso werden lineare Produktionsspiele mit Komitee-Kontrolle untersucht, und Ergebnisse zur Ausgewogenheit solcher Spiele werden hergeleitet.

     

A carcinoembryonic antigen polynucleotide vaccine for human clinical use

Congenital cataract, type Volkmann (McKusick no 115665, gene symbol CCV) is an autosomal dominant eye disease. The disease is characterized by a progressive, central and zonular cataract, with opacities both in the embryonic, fetal and juvenile nucleus and around the anterior and posterior Y-suture. We examined blood samples from 91 members of a Danish pedigree comprising 426 members, by using highly informative short tandem repeat polymorphisms and found the closest linkage of the disease gene (CCV) to a (CA)n dinucleotide repeat polymorphism at locus D1S243 (Zmax = 14.04 at theta M = 0.025 theta F = 0.000), at a penetrance of 0.90. Using two additional chromosome 1 markers, we were able to map the CCV gene in the sequence 1pter-(CCV, D1S243)-D1S468-D1S214. The (enolase 1) gene has been mapped to this area; however, a mutation described in this gene did not give eye disease.     

Production of biogenic amines by lactic acid bacteria and enterobacteria isolated from fresh pork sausages packaged in different atmospheres and kept under refrigeration

The occurrence of in vitro amino acid activity in bacterial strains associated with fresh pork sausages packaged in different atmospheres and kept in refrigeration was studied. The presence of biogenic amines in decarboxylase broth was confirmed by ion-exchange chromatography and by the presence of the corresponding decarboxylase genes by PCR. From the 93 lactic acid bacteria and 100 enterobacteria strains analysed, the decarboxylase medium underestimates the number of biogenic amine-producer strains. 28% of the lactic acid bacteria produced tyramine and presented the tdc gene. All the tyramine-producer strains were molecularly identified as Carnobacterium divergens. Differences on the relative abundance of C. divergens were observed among the different packaging atmospheres assayed. After 28 days of storage, the presence of argon seems to inhibit C. divergens growth, while packing under vacuum seems to favour it. Among enterobacteria, putrescine was the amine more frequently produced (87%), followed by cadaverine (85%); agmatine and tyramine were only produced by 13 and 1%, respectively, of the strains analysed. Packing under vacuum or in an atmosphere containing nitrogen seems to inhibit the growth of enterobacteria which produce simultaneously putrescine, cadaverine, and agmatine. Contrarily, over-wrapping or packing in an atmosphere containing argon seems to favour the growth of agmatine producer-enterobacteria. The production of putrescine and cadaverine was associated with the presence of the corresponding amino acid decarboxylase genes. The biogenic amine-producer strains were included in a wide range of enterobacterial species, including Kluyvera intermedia, Enterobacter aerogenes, Yersinia kristensenii, Serratia grimesii, Serratia ficaria, Yersinia rodhei, Providencia vermicola and Obesumbacterium proteus.     

Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate

Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.     

Mental organization of maps.

Previous studies deconfounding spatial and temporal proximity during map learning have found a temporal influence on mental map organization. The authors explored whether this observed priming effect reflected the manner in which a map was learned by having people either name objects or point to them during learning. Naming objects resulted in temporal organization but pointing to objects resulted in spatial organization, suggesting that mental map organization is sensitive to emphasizing different types of map information during learning. The authors also explored whether the temporal organization observed in the naming group was influenced by the ease of using spatial information during learning, such as when the expectancy to use spatial information was made explicit or when a consistent temporal order was absent. When naming map objects, evidence for a spatial organization was weak, whereas a temporal organization was observed when a consistent temporal order was present. (PsycINFO Database Record (c) 2010 APA, all rights reserved)