Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P<0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.

Nitrone [2]rotaxanes: Simultaneous chemical protection and electrochemical activation of a functional group

We report on the use of the hydrogen bond accepting properties of neutral nitrone moieties to prepare benzylic-amide-macrocycle-containing [2]rotaxanes in yields as high as 70 %. X-Ray crystallography shows the presence of up to four intercomponent hydrogen bonds between the amide groups of the macrocycle and the two nitrone groups of the thread. Dynamic 1H NMR studies of the rates of macrocycle pirouetting in nonpolar solutions indicate that amide-nitrone hydrogen bonds are particularly strong, ~1.3 and ~0.2 kcal mol-1 stronger than similar amide-ester and amide-amide interactions, respectively. In addition to polarizing the N-O bond through hydrogen bonding, the rotaxane structure affects the chemistry of the nitrone groups in two significant ways: The intercomponent hydrogen bonding activates the nitrone groups to electrochemical reduction, a one electron reduction of the rotaxane being stablized by a remarkable 400 mV (8.1 kcal mol-1) with respect to the same process in the thread; encapsulation, however, protects the same functional groups from chemical reduction with an external reagent (and slows down electron transfer to and from the electroactive groups in cyclicvoltammetry experiments). Mechanical interlocking with a hydrogen bonding molecular sheath thus provides a route to an encapsulated polarized functional group and radical anions of significant kinetic and thermodynamic stability.

Photoinduced conjugation of Dithioester- and Trithiocarbonate-Functional RAFT polymers with alkenes

We report the photoinduced conjugation of polymers synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization with a number of low molecular weight (functional) olefins. Upon irradiation of a solution of an aliphatic alkene and the benzyl dithioacetic acid ester (CPDA) or dodecyl trithiocarbonate (DoPAT) functional poly(alkyl acrylate) at the absorption wavelength of the thiocarbonyl group (315 nm), incorporation of the alkene at the polymer chain-end occurred. The most efficient systems identified with regard to the rate of reaction and yield were poly(butyl acrylate)/CPDA/ethyl vinyl ether (78% monoinsertion product after 1 h) and poly(butyl acrylate)/CPDA/1-pentene (73% insertion product after 7 h) at ambient temperature. An in-depth analysis of the reaction mechanism by 1H NMR and online size-exclusion chromatography-electrospray ionization tandem mass spectrometry (SEC/ESI−MSn) revealed that a possible [2 + 2] photoaddition mechanism of conjugation does not take place. Instead, fast β-cleavage of the photoexcited RAFT-end group with subsequent radical addition of an alkene was observed for all employed systems. The presented reaction thus provides a means of spatial and temporal control for the conjugation of alkenes to thiocarbonyl thio-capped macromolecules via the use of UV radiation.

Mapping the language of science and science teaching practices : a case study of early childhood school science

Concerns raised in educational reports about school science in terms of students. outcomes and attitudes, as well as science teaching practices prompted investigation into science learning and teaching practices at the foundational level of school science. Without science content and process knowledge, understanding issues of modern society and active participation in decision-making is difficult. This study contended that a focus on the development of the language of science could enable learners to engage more effectively in learning science and enhance their interest and attitudes towards science. Furthermore, it argued that explicit teaching practices where science language is modelled and scaffolded would facilitate the learning of science by young children at the beginning of their formal schooling. This study aimed to investigate science language development at the foundational level of school science learning in the preparatory-school with students aged five and six years. It focussed on the language of science and science teaching practices in early childhood. In particular, the study focussed on the capacity for young students to engage with and understand science language. Previous research suggests that students have difficulty with the language of science most likely because of the complexities and ambiguities of science language. Furthermore, literature indicates that tensions transpire between traditional science teaching practices and accepted early childhood teaching practices. This contention prompted investigation into means and models of pedagogy for learning foundational science language, knowledge and processes in early childhood. This study was positioned within qualitative assumptions of research and reported via descriptive case study. It was located in a preparatory-school classroom with the class teacher, teacher-aide, and nineteen students aged four and five years who participated with the researcher in the study. Basil Bernstein.s pedagogical theory coupled with Halliday.s Systemic Functional Linguistics (SFL) framed an examination of science pedagogical practices for early childhood science learning. Students. science learning outcomes were gauged by focussing a Hallydayan lens on their oral and reflective language during 12 science-focussed episodes of teaching. Data were collected throughout the 12 episodes. Data included video and audio-taped science activities, student artefacts, journal and anecdotal records, semi-structured interviews and photographs. Data were analysed according to Bernstein.s visible and invisible pedagogies and performance and competence models. Additionally, Halliday.s SFL provided the resource to examine teacher and student language to determine teacher/student interpersonal relationships as well as specialised science and everyday language used in teacher and student science talk. Their analysis established the socio-linguistic characteristics that promoted science competencies in young children. An analysis of the data identified those teaching practices that facilitate young children.s acquisition of science meanings. Positive indications for modelling science language and science text types to young children have emerged. Teaching within the studied setting diverged from perceived notions of common early childhood practices and the benefits of dynamic shifting pedagogies were validated. Significantly, young students demonstrated use of particular specialised components of school-science language in terms of science language features and vocabulary. As well, their use of language demonstrated the students. knowledge of science concepts, processes and text types. The young students made sense of science phenomena through their incorporation of a variety of science language and text-types in explanations during both teacher-directed and independent situations. The study informs early childhood science practices as well as practices for foundational school science teaching and learning. It has exposed implications for science education policy, curriculum and practices. It supports other findings in relation to the capabilities of young students. The study contributes to Systemic Functional Linguistic theory through the development of a specific resource to determine the technicality of teacher language used in teaching young students. Furthermore, the study contributes to methodology practices relating to Bernsteinian theoretical perspectives and has demonstrated new ways of depicting and reporting teaching practices. It provides an analytical tool which couples Bernsteinian and Hallidayan theoretical perspectives. Ultimately, it defines directions for further research in terms of foundation science language learning, ongoing learning of the language of science and learning science, science teaching and learning practices, specifically in foundational school science, and relationships between home and school science language experiences.

Functional fixation : experimental evidence on the presentation of financial information through different digital formats

This study examines whether, in the presentation of financial information, digital formats address the concern over users’ functional fixation. The accounting literature indicates that the presentation of financial information either within the financial statements or in the notes to the financial statements often creates functional fixation where users of financial statements fail to adjust for differences in accounting policy. This leads users to judge what would otherwise be identical financial situations as being different due to the different accounting policies and methods adopted. It has been suggested that the use of digital formats in presenting financial reports may overcome functional fixation. Using an experimental design involving accountants in public practice, the results indicate that the use of digital formats to present financial reports does not fully overcome the issue of functional fixation in the processing of financial information. Although the participants were able to identify and extract relevant information, irrespective of whether or not the information was presented within the financial statements or in the notes to the accounts, the evidence indicates that functional fixation remained when the participants made final decisions based on available information. This suggests that functional fixation may not be caused by access to or extraction of information but by the level of perceived significance based on where the information is reported in the financial statements. In general, the results indicate that current technology may not be able to fully reduce functional fixation in the evaluation of financial information prepared in accordance with different accounting policies and methods.