How to work the crowd : a snapshot of barriers and motivations to crowdfunding

Introduction This study is a snapshot of Australian donor motivations and donor barriers to crowdfunding, and provides some indicative recommendations on ways the uptake of crowdfunding in the creative industries might increase. It is based upon a literature review and semi-structured interviews with 17 stakeholders who have used crowdfunding in Australia, including: creative producers seeking funds; financial crowdfunding donors; Artsupport Australia mentors of artists who are using crowdfunding; and crowdfunding site stakeholders. About the report Artsupport Australia commissioned the Queensland University of Technology Creative Industries team to produce a report on trends related to crowdfunding, particularly identifying barriers and motivations that might be associated with it. Artsupport Australia suggested a list of interview candidates, based on those individuals’ knowledge or experience with crowdfunding, to provide a better understanding of perceptions of this emerging practice, and to inform discussions on whether it is a useful revenue generating mechanism for the cultural sector.

Listening skill requires a further look into second/foreign language learning

Current English-as-a-second and foreign-language (ESL/EFL) research has encouraged to treat each communicative macroskill separately due to space constraint, but the interrelationship among these skills (listening, speaking, reading, and writing) is not paid due attention. This study attempts to examine first the existing relationship among the four dominant skills, second the potential impact of reading background on the overall language proficiency, and finally the relationship between listening and overall language proficiency as listening is considered an overlooked/passive skill in the pedagogy of the second/foreign language classroom. However, the literature in language learning has revealed that listening skill has salient importance in both first and second language learning. The purpose of this study is to investigate the role of each of four skills in EFL learning and their existing interrelationships in an EFL setting. The outcome of 701 Iranian applicants undertaking International English Language Testing System (IELTS) in Tehran demonstrates that all communicative macroskills have varied correlations from moderate (reading and writing) to high (listening and reading). The findings also show that the applicants’ reading history assisted them in better performing at high stakes tests, and what is more, listening skill was strongly correlated with the overall language proficiency.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Metacognitive strategy instruction in English as a Foreign Language (EFL) listening skill

Listening skill is allocated inadequate consideration in English language instruction and learning in Iran. At the school level, listening skill is not taught but reading and writing skills are taught traditionally. At the college level, reading skill is emphasised. For students seeking IELTS certification, institutes teach listening skill within the framework of a Communicative Language Teaching (CLT) approach. Nonetheless, despite the official syllabus, many teachers tend to test rather than teach listening skill. Currently, listening skill in the curriculum is embedded in an oral comprehension teaching approach through multiple choice written responses in the institutes. Therefore, the process of explicitly teaching listening is overlooked with a strong emphasis on the post hoc assessment of the products of listening. This study used a mixed methods approach to investigate the relationship between metacognitive strategy instruction and listening performance, metacognitive awareness and use of metacognitive strategies in listening. Three research questions were addressed in this study: - Is there a relationship between metacognitive strategy instruction (planning, monitoring and evaluation) and Iranian High Intermediate students¡¦ listening? „ - Is there a relationship between metacognitive strategy instruction and Iranian High Intermediate students¡¦ metacognitive awareness of listening? - Does metacognitive strategy instruction help Iranian High Intermediate students¡¦ use of metacognitive strategies during listening? A single group (N = 30) of High Intermediate level tertiary students in Iran were guided through a metacognitive strategy instruction over one semester (10 weeks). The first research question was measured through IELTS listening tests, which tracked any change of students’ listening performance. The second research question was analysed through results of a Metacognitive Awareness Listening Questionnaire (MALQ) to survey students’ awareness of metacognitive strategies in listening. Finally, the third research question was analysed through interviews, which explored students’ use of metacognitive strategies in listening. Results indicate that High Intermediate students developed listening performance, but there were no significant changes in metacognitive awareness in listening. Students reported in the interviews that they used multiple strategies (cognitive and metacognitive) to approach listening. Implications for English teaching in Iran and other contexts are discussed.