ESI-MS and thermal melting studies of nanoscale platinum(ii) metallomacrocycles with DNA

The hydrophilic, long-chain diamine PEGda (O,O′-bis(2-aminoethyl)octadeca(ethylene glycol)), when complexed with cis-protected Pt(II) ions afforded water-soluble complexes of the type [Pt(N,N)(PEGda)](NO3)2 (N,N = N,N,N′,N′-tetramethyl-1,2-diaminoethane (tmeda), 1,2-diaminoethane (en), and 2,2′-bipyridine (2,2′-bipy)) featuring unusual 62-membered chelate rings. Equimolar mixtures containing either the 16-mer duplex DNA D2 or the single-stranded D2a and [Pt(N,N)(PEGda)]2+ were analyzed by negative-ion ESI-MS. Analysis of D2-Pt(II) mixtures showed the formation of 1:1 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and the previously-described metallomacrocycle [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ with D2; the dinuclear species bound to D2 most strongly, consistent with its greater charge and aromatic surface area. D2 formed 1:2 complexes with the acyclic species [Pt(2,2′-bipy)(Mebipy)2]4+ and [Pt(2,2′-bipy)(NH3)2]2+. Analyses of D2a-Pt(II) mixtures gave results similar to those obtained with D2, although fragmentation was more pronounced, indicating that the nucleobases in D2a play more significant roles in mediating the decomposition of complexes than those in D2, in which they are paired in a complementary manner. Investigations were also conducted into the effects of selected platinum(II) complexes on the thermal denaturation of calf thymus DNA (CT-DNA) in buffered solution. Both [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)64,4′-bipy}2]8+ and [Pt(2,2′-bipy)(Mebipy)2]4+ stabilized CT-DNA. In contrast, [Pt(tmeda)(PEGda)]2+ and [Pt(en)(PEGda)]2+ (as well as free PEGda) caused negligible changes in melting temperature (ΔTm), suggesting that these species interact weakly with CT-DNA

Preventing sexism and sexual harassment in medical schools by using Theater of the Oppressed as an interactive and reflexive tool.

Among the measures taken to combat sexism and sexual harassment, prevention courses for medical students are one possibility. We aimed to describe the process of implementing a training course on the prevention of sexism and sexual harassment for medical students in two Swiss medical schools by using the Theater of the Oppressed as an interactive and reflexive tool within the course. The purpose of this theater was to give the students the opportunity to express themselves and to collectively look for and discuss ways to combat and escape from oppressive situations. This collaborative, innovative, and interactive implementation showed that different forms of a training course can be implemented with similar objectives in an adaptable and transferable manner. The interactive and reflexive Theater of the Oppressed was an appropriate option to reach the objectives. Courses were based on identifying and acting on concrete problematic situations by focusing on individual, collective, and institutional resources. Students reported a high level of satisfaction

The mediating effect of task presentation on collaboration and children's acquisition of scientific reasoning

There has been considerable research concerning peer interaction and the acquisition of children's scientific reasoning. This study investigated differences in collaborative activity between pairs of children working around a computer with pairs of children working with physical apparatus and related any differences to the development of children's scientific reasoning. Children aged between 9 and 10 years old (48 boys and 48 girls) were placed into either same ability or mixed ability pairs according to their individual, pre-test performance on a scientific reasoning task. These pairs then worked on either a computer version or a physical version of Inhelder and Piaget's (1958) chemical combination task. Type of presentation was found to mediate the nature and type of collaborative activity. The mixed-ability pairs working around the computer talked proportionally more about the task and management of the task; had proportionally more transactive discussions and used the record more productively than children working with the physical apparatus. Type of presentation was also found to mediated children's learning. Children in same ability pairs who worked with the physical apparatus improved significantly more than same ability pairs who worked around the computer. These findings were partially predicted from a socio-cultural theory and show the importance of tools for mediating collaborative activity and collaborative learning

Matrix Modulation of the Bioactivation of Estragole by Constituents of Different Alkenylbenzene-containing Herbs and Spices and Physiologically Based Biokinetic Modeling of Possible In Vivo Effects

The alkenylbenzene estragole is a constituent of several herbs and spices. It induces hepatomas in rodents at high doses following bioactivation by cytochrome P450s and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from different alkenylbenzene-containing herbs and spices were able to inhibit SULT activity. Flavonoids including quercetin, kaempferol, myricetin, apigenin, and nevadensin were the major constituents responsible for this inhibition with Ki values in the nano to micromolar range. In human HepG2 cells exposed to the proximate carcinogen 1ʹ-hydroxyestragole, the various flavonoids were able to inhibit estragole DNA adduct formation and shift metabolism in favor of glucuronidation which is a detoxification pathway for 1ʹ-hydroxyestragole. In a next step, the kinetics for SULT inhibition were incorporated in physiologically based biokinetic (PBBK) models for estragole in rat and human to predict the effect of co-exposure to estragole and (mixtures of) the different flavonoids on the bioactivation in vivo. The PBBK-model-based predictions indicate that the reduction of estragole bioactivation in rat and human by co-administration of the flavonoids is dependent on whether the intracellular liver concentrations of the flavonoids can reach their Ki values. It is expected that this is most easily achieved for nevadensin which has a Ki value in the nanomolar range and is, due to its methyl ation, more metabolically stable than the other flavonoid

Targeting of Pseudorabies Virus Structural Proteins to Axons Requires Association of the Viral Us9 Protein with Lipid Rafts

The pseudorabies virus (PRV) Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF). In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs). Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system

Toxicological aspects of the use of phenolic compounds in disease prevention

The consumption of a diet low in fat and enhanced by fruits and vegetables, especially rich in phenolic compounds, may reduce risks of many civilization diseases. The use of traditional medicines, mainly derived from plant sources, has become an attractive segment in the management of many lifestyle diseases. Concerning the application of dietary supplements (based on phenolic compounds) in common practice, the ongoing debate over possible adverse effects of certain nutrients and dosage levels is of great importance. Since dietary supplements are not classified as drugs, their potential toxicities and interactions have not been thoroughly evaluated. First, this review will introduce phenolic compounds as natural substances beneficial for human health. Second, the potential dual mode of action of flavonoids will be outlined. Third, potential deleterious impacts of phenolic compounds utilization will be discussed: pro-oxidant and estrogenic activities, cancerogenic potential, cytotoxic effects, apoptosis induction and flavonoid-drug interaction. Finally, future trends within the research field will be indicated