Plagiarism and attribution: an academic literacies approach

In many Higher Education courses in the UK the ability to write extended academic prose is central to assessment and therefore to student success. One aspect of academic writing which students struggle with is incorporating the work and ideas of others, using appropriate attribution conventions. This can lead them to fall foul of àinstitutionsââ¬â¢ plagiarism policies. Advice on plagiarism often consists of discussions around what is or is not plagiaristic behaviour while advice on attribution has tended to focus on referencing. This paper explores what an academic literacies approach to plagiarism might look like. It discusses and illustrates how an academic literacies approach was used in the design, analysis and application of a small-scale ethnographic research which set out to explore international postgraduate students' understandings of and questions about plagiarism across the disciplines in one UK university. The intention of the research was to use the findings in developing more culturally and context sensitive explanations of our attribution practices.àààÃ

Antinociceptív neurotranszmitterek / modulátorok hatásmechanizmusa: homológ és heterológ receptor kölcsönhatások vizsgálata és új, endogén peptid-kötőhelyek azonosítása = Neurochemical studies on neurotransmitters in pain regulation: identification of novel peptide binding sites and investigation of homologous and heterologous receptor interactions

Az antinocicepcióban kulcsszerepet játszó mu opioid receptor endogén ligandumának tekintett endomorfinok (1 és 2) kötőhelyeit karakterizáltuk biokémiai és autoradiográfiás módszerekkel. Megállapítottuk, hogy az endomorfin 1 két kötőhelyet ismer fel, amelyek közül a kis affinitású a klasszikus mu receptortól részben eltérő lokalizációval, ligandspecificitással bír és regulációja nem követi az ismert reakció utakat. Új, konformációsan gátolt endomorfin analógok kifejlesztésével módosítható volt a peptidek affinitása, szelektivitása. Világossá vált, hogy akár kismértékű szerkezeti módosítások is jelentős funkcionális eltéréseket eredményezhetnek. Az opioid és kannabinoid rendszer összefüggéseit vizsgáltuk molekuláris biológiai és biokémiai módszerekkel in vitro és in vivo. A legmarkánsabb változásokat a mu opioid receptorok esetében kaptunk, legfőképpen az előagyi és az agytörzsi területeken. Mind endogén CB1 agonista, mind CB2 antagonista befolyásolta a mu opioid receptor expresszióját és regulációját. A kannabisz és opioid rendszer közötti interakciók pontos mechanizmusainak feltárásával új kapuk nyílhatnak meg a fájdalomcsillapítás terápiás alkalmazásában a távolabbi jvőben | The endomorphins (1 and 2) are putative endogenous ligands for mu opioid receptors, which play a major role in antinociception. It was found, that endomorphin1 labels two distinct sites with partially different localization, ligand selectivity profiles. The regulation of its binding is not identical to that of the classical opioid ligands. The recently developed endomorphin analogs with constrained structure show changes in affinity and selectivy. Relatively small chemical modifications might lead to major changes in functional consequences. We investigated the interaction of the opioid system with several others related to nociception/antinociception. Among them, the occurrence of possible changes in mRNA expression and in functional activity of opioid receptors after acute in vivo and in vitro treatments with cannabinoids were studied. Wild-type, CB1 knockout mice and CB2 receptor deficient animals were among the the subjects of the study. We examined the changes of opioid receptor?s mRNA levels by using real-time PCR, analyzed the capability of mu-, delta and kappa opioid agonists to activate G-proteins and investigated mu-opioid receptors binding properties by using competition assays. Our data show changes in the expression and functional integrity of mu opioid receptors in forebrain, cerebellum and brainstem after different cannabinoid treatments. A better knowledge of the observed interactions may lead to exciting therapeutic possibilities in a long term

Localization of Caveolin-1 and C-SRC in Mature and Differentiating Photoreceptors: Raft Proteins Co-Distribute With Rhodopsin During Development

Numerous biochemical and morphological studies have provided insight into the distribution pattern of caveolin-1 and the presence of membrane rafts in the vertebrate retina. To date however, studies have not addressed the localization profile of raft specific proteins during development. Therefore the purpose of our studies was to follow the localization pattern of caveolin-1, phosphocaveolin-1 and c-src in the developing retina and compare it to that observed in adults. Specific antibodies were used to visualize the distribution of caveolin-1, c-src, a kinase phosphorylating caveolin-1, and phospho-caveolin-1. The labeling pattern of this scaffolded complex was compared to those of rhodopsin and rhodopsin kinase. Samples were analyzed at various time points during postnatal development and compared to adult retinas. The immunocytochemical studies were complemented with immunoblots and immunoprecipitation studies. In the mature retina caveolin-1 and c-src localized mainly to the cell body and IS of photoreceptors, with only very weakly labeled OS. In contrast, phospho-caveolin-1 was only detectable in the OS of photoreceptors. During development we followed the expression and distribution profile of these proteins in a temporal sequence with special attention to the period when OS formation is most robust. Double labeling immunocytochemistry and immunoprecipitation showed rhodopsin to colocalize and co-immunoprecipitate with caveolin-1 and c-src. Individual punctate structures between the outer limiting membrane and the outer plexiform layer were seen at P10 to be labeled by both rhodopsin and caveolin-1 as well as by rhodopsin and c-src, respectively. These studies suggest that membrane raft specific proteins are co-distributed during development, thereby pointing to a role for such complexes in OS formation. In addition, the presence of small punctate structures containing caveolin-1, c-src and rhodopsin raise the possibility that these proteins may transport together to OS during development and that caveolin-1 exists predominantly in a phosphorylated form in the OS

A fotoreceptor-fejlődés sejt- és molekuláris biológiája = Cell and molecular biology of photoreceptor development

Az opszinváltás szabályozása fajonként eltérő, tiroxin és TRbéta2 nélkülözhetetlen a zöld csapfejlődéshez. A receptormegoszlás időbeli és térbeli mintázatával igazoltuk a tiroxint mediáló TRbéta2 szerepét. Tenyésztő módszerünkkel a fotoreceptor-differenciálódás szérummentes környezetben is végbemegy, a világon először definitív médiumban vizsgálható. Más faktorok (A- és E-vitamin, BDNF) is hatnak a pigment-expresszióra. Szelektív neurotrophin antagonisták az opszin és a TrkB receptor kapcsoltságára utalnak. Az erythropoietin retinális expressziója HIF1-α szabályozás alatt áll és időben változik a fejlődés korai szakaszában. Szemnyitás után a retinában lecsökken a transzdukciós molekulák szintje, kivéve a fotoreceptorokat. A sejttestben szintetizálódnak, közös lipid rafton kerülnek a kültagba és játszanak szerepet a fejlődésben. Az STK38L gén homozigóta mutációja befolyásolja a fotoreceptor-fejlődést. Sejthalál és proliferáció egyaránt jelen van. Hibrid sejtek jelennek meg pálcika-, kisebb mértékben S-opszin termeléssel. A differenciált, mutáns sejtek a degenerációs gén hatására megőrzik osztódóképességüket. A melatonin éjszaka termelődik, éjjeli világítás a hormontermelés gátlásával patológiás folyamatokat (emlő és colorectalis carcinoma) okozhat. A pineális szerv emlősben elvesztette fotoreceptor működését és szimpatikus rostokon a retinából kap információt. Mivel a pineális melatoninképzést rövidhullámú fény gátolja, éjjeli műszakban hosszúhullámú megvilágítást kell használni. | Regulation of opsin-switch varies across species. Thyroxin and TRß2 receptor is essential for green cone development. Spatial and temporal receptor distribution proved the role of TRß2 mediating thyroxin. Photoreceptor differentiation is completed in our culture method in serum-free medium, allowing its examination in a definitive paradigm. Other factors such as Vitamins A and E, BDNF) also influence visual pigment expression. Selective neurotrophin antagonists reveal the close connection of opsin and Trkß. Retinal expression of erythropoietin is under the regulation of HIF1-α, and changes during development. Transduction molecule levels decrease after eye opening, except for photoreceptors. They are synthesized in the cell body, located and transported in the outer segment on common lipid rafts and play a developmental role. Homozygotic mutation of STK38L influences photoreceptor development. Cell death and proliferation are equally present. Hybrid photoreceptors appear that express rod and, to a lesser extent, S-opsin. The degenerated, hybrid mutants retain their capacity to divide. Melatonin is produced at night. Nocturnal light exposition inhibiting hormone production may generate pathological processes (e.g.: carcinomas). The pineal organ in mammals has lost its photoreceptor function and receives information from the retina via sympathetic fibers. Since short wave light inhibits melatonin production, long-wave illumination is recommended during night-shift

Localization of Caveolin-1 and C-Src in Mature and Differentiating Photoreceptors: Raft Proteins Co-Distribute with Rhodopsin During Development

Numerous biochemical and morphological studies have provided insight into the distribution pattern of caveolin-1 and the presence of membrane rafts in the vertebrate retina. To date however, studies have not addressed the localization profile of raft specific proteins during development. Therefore the purpose of our studies was to follow the localization pattern of caveolin-1, phospho-caveolin-1 and c-src in the developing retina and compare it to that observed in adults. Specific antibodies were used to visualize the distribution of caveolin-1, c-src, a kinase phosphorylating caveolin-1, and phospho-caveolin-1. The labeling pattern of this scaffolded complex was compared to those of rhodopsin and rhodopsin kinase. Samples were analyzed at various time points during postnatal development and compared to adult retinas. The immunocytochemical studies were complemented with immunoblots and immunoprecipitation studies. In the mature retina caveolin-1 and c-src localized mainly to the cell body and IS of photoreceptors, with only very weakly labeled OS. In contrast, phospho-caveolin-1 was only detectable in the OS of photoreceptors. During development we followed the expression and distribution profile of these proteins in a temporal sequence with special attention to the period when OS formation is most robust. Double labeling immunocytochemistry and immunoprecipitation showed rhodopsin to colocalize and co-immunoprecipitate with caveolin-1 and c-src. Individual punctate structures between the outer limiting membrane and the outer plexiform layer were seen at P10 to be labeled by both rhodopsin and caveolin-1 as well as by rhodopsin and c-src, respectively. These studies suggest that membrane raft specific proteins are co-distributed during development, thereby pointing to a role for such complexes in OS formation. In addition, the presence of small punctate structures containing caveolin-1, c-src and rhodopsin raise the possibility that these proteins may transport together to OS during development and that caveolin-1 exists predominantly in a phosphorylated form in the OS. © 2011 Springer Science+Business Media B.V

In vitro binding and functional studies of Ac-RYYRIK-ol and its derivatives, novel partial agonists of the nociceptin/orphanin F/Q receptor.

Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NOP receptor affinity and selectivity were identified. On the basis of this information we developed a number of novel compounds. The detailed structure-activity studies on the partial agonist Ac-RYYRIK-NH(2) are reported in this communication. Besides the modifications on N- and C-terminal, Arg-Cit exchange was performed on the template structure. The novel hexapeptides were analyzed in radioligand binding, functional biochemical [(35)S]GTPgammaS binding assays by using membranes from rat brains and Chinese hamster ovary cells expressing human NOP receptor. The agonist/antagonist properties were also tested on in the mouse vas deferens bioassay. C-terminal modification yielded a high affinity, selective and potent NOP ligand (Ac-RYYRIK-ol) with a partial agonist property. Several analogs of this compound were synthesized. The presence of the positively charged arginine residue at the first position turned out to be crucial for the biological activity of the hexapeptide. The N-terminal modifications with various acyl groups (ClAc, pivaloyl, formyl, benzoyl, mesyl) decreased the affinity of the ligand towards the receptor and the intrinsic activity for stimulating the G-protein activation was also decreased. The structure-activity studies on the hexapeptide derivatives provided some basic information on the structural requirements for receptor binding and activation

The role of N- or C-terminal biotinylation in autoantibody recognition of citrullin containing filaggrin epitope peptides in Rheumatoid arthritis

Here, we report on the synthesis, conformational analysis and autoantibody binding properties of new sets of Rheumatoid arthritis (RA) specific biotin-peptide conjugates derived from filaggrin epitope peptides. The biotin with or without a linker was attached to the Cit or Arg containing epitope core (311TXGRS315) or epitope region (306SHQESTXGXSXGRSGRSGS324) peptide (where X = Cit), through an amide bond at the N- or C-terminal of the epitopes. Antibody binding was detected by indirect enzyme-linked immunosorbent assay (ELISA) using sera from RA, Systemic lupus erythematosus (SLE) patients as well as healthy individuals and the secondary structure of conjugates was investigated by electronic circular dichroism (ECD). We found that autoantibodies from RA patients recognize specifically both filaggrin epitope region (306SHQESTXGXSXGRSGRSGS324) and short epitope core (311TXGRS315) peptides. Our data also indicate that the positioning of the biotin label within a peptide sequence can markedly influence the antibody binding, but the length of the linker incorporated has essentially no effect on the recognition. ECD experiments demonstrate that the Arg/Cit change does not influence the solution conformation of the peptide conjugates. However, the presence and position of the biotin moiety has a pronounced effect on the conformation of the 5-mer epitope core peptides, while it doesn’t alter the secondary structure of the 19-mer epitope region peptides

Localization of Caveolin-1 and C-Src in Mature and Differentiating Photoreceptors: Raft Proteins Co-Distribute With Rhodopsin During Development

Numerous biochemical and morphological studies have provided insight into the distribution pattern of caveolin-1 and the presence of membrane rafts in the vertebrate retina. To date however, studies have not addressed the localization profile of raft specific proteins during development. Therefore the purpose of our studies was to follow the localization pattern of caveolin-1, phospho-caveolin-1 and c-src in the developing retina and compare it to that observed in adults. Specific antibodies were used to visualize the distribution of caveolin-1, c-src, a kinase phosphorylating caveolin-1, and phospho-caveolin-1. The labeling pattern of this scaffolded complex was compared to those of rhodopsin and rhodopsin kinase. Samples were analyzed at various time points during postnatal development and compared to adult retinas. The immunocytochemical studies were complemented with immunoblots and immunoprecipitation studies. In the mature retina caveolin-1 and c-src localized mainly to the cell body and IS of photoreceptors, with only very weakly labeled OS. In contrast, phospho-caveolin-1 was only detectable in the OS of photoreceptors. During development we followed the expression and distribution profile of these proteins in a temporal sequence with special attention to the period when OS formation is most robust. Double labeling immunocytochemistry and immunoprecipitation showed rhodopsin to colocalize and co-immunoprecipitate with caveolin-1 and c-src. Individual punctate structures between the outer limiting membrane and the outer plexiform layer were seen at P10 to be labeled by both rhodopsin and caveolin-1 as well as by rhodopsin and c-src, respectively. These studies suggest that membrane raft specific proteins are co-distributed during development, thereby pointing to a role for such complexes in OS formation. In addition, the presence of small punctate structures containing caveolin-1, c-src and rhodopsin raise the possibility that these proteins may transport together to OS during development and that caveolin-1 exists predominantly in a phosphorylated form in the OS. © 2011 Springer Science+Business Media B.V

Identifying new topoisomerase II poison scaffolds by combining publicly available toxicity data and 2D/3D-based virtual screening

Molecular descriptor (2D) and three dimensional (3D) shape based similarity methods are widely used in ligand based virtual drug design. In the present study pairwise structure comparisons among a set of 4858 DTP compounds tested in the NCI60 tumor cell line anticancer drug screen were computed using chemical hashed fingerprints and 3D molecule shapes to calculate 2D and 3D similarities, respectively. Additionally, pairwise biological activity similarities were calculated by correlating the 60 element vectors of pGI50 values corresponding to the cytotoxicity of the compounds across the NCI60 panel. Subsequently, we compared the power of 2D and 3D structural similarity metrics to predict the toxicity pattern of compounds. We found that while the positive predictive value and sensitivity of 3D and molecular descriptor based approaches to predict biological activity are similar, a subset of molecule pairs yielded contradictory results. By simultaneously requiring similarity of biological activities and 3D shapes, and dissimilarity of molecular descriptor based comparisons, we identify pairs of scaffold hopping candidates displaying characteristic core structural changes such as heteroatom/heterocycle change and ring closure. Attempts to discover scaffold hopping candidates of mitoxantrone recovered known Topoisomerase II (Top2) inhibitors, and also predicted new, previously unknown chemotypes possessing in vitro Top2 inhibitory activity