In Vivo Targeting of Organic Calcium Sensors via Genetically Selected Peptides

AbstractA library of constrained peptides that form stable folded structures was screened for aptamers that bind with high affinity to the fluorescent dye Texas red. Two selected clones had binding constants to Texas red of 25 and 80 pM as phage and binding had minimal effects on the fluorescence of Texas red. The peptides interact with distinct but overlapping regions of Texas red. One peptide bound to X-rhod calcium sensors, which share the same core fluorophore as Texas red. These dyes retained calcium sensitivity when bound to the peptide. This peptide was used to label a fusion protein with X-rhod-5F in vivo, and X-rhod sensed changes in calcium locally. Thus, minimal, constrained peptides can functionally bind to environmentally sensitive dyes or other organic agents in biological contexts, suggesting tools for in vivo imaging and analysis

Comparative Use of the Ages and Stages Questionnaires in Low‐ and Middle‐Income Countries

Aim: To map the breadth of use of the Ages and Stages Questionnaires (ASQ) in low‐ and middle‐income countries (LMICs) across world regions, and examine procedures for ASQ translation, adaptation, psychometric evaluation, and administration. Method: We conducted a review of all original, peer‐reviewed studies written in English referencing use of the ASQ in LMICs. We used a consensus rating procedure to classify each article into one of four categories: feasibility study, psychometric study, prevalence study, or research study. Results: We analysed 53 peer‐reviewed articles written in English detailing use of the ASQ in LMICs. We found evidence of ASQ use in 23 LMICs distributed across all world regions. The ASQ was translated into 16 languages. Just over half of the studies reported parent completion of the ASQ (50.9%). We identified eight feasibility studies, 12 psychometric studies, and nine prevalence studies. Study type varied by economy and region. Interpretation: Findings suggest broad global use of the ASQ in a range of countries and cultural and linguistic contexts. There is need for further validation studies across all cited regions and countries and in countries ready to begin to design systems for providing universal developmental screening services

Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells

BACKGROUND: Arachidonic acid metabolite, generated by cyclooxygenase (COX), is implicated in the colorectal cancer (CRC) pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. METHODS: Three colorectal cancer cell lines (HCA7, HT-29 & LoVo) expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor) and rofecoxib (COX-2 selective) on prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA) content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. RESULTS: COX inhibitors suppressed PGE(2) production but enhanced LTB(4) secretion in COX-2 expressing cell lines (P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to the shunting mechanism. CONCLUSIONS: This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors

School environment and mastery experience as predictors of teachers' self-efficacy beliefs towards inclusive teaching

Teacher self-efficacy plays a key role in the successful inclusion of children with intellectual disabilities in mainstream schools. But what influences self-efficacy and how can we support its growth? Drawing on Social Cognitive Theory, the study examined teachers’ mastery experiences, perceptions of the school environment, self-efficacy and reported inclusive teaching. The sample comprised 148 primary school teachers from Scottish mainstream schools. Participants completed questionnaires measuring mastery experiences, the school environment (collective efficacy and school climate perceptions), self-efficacy and reported inclusive teaching practices. Regression analyses demonstrated that school environment (collective efficacy and school climate), and mastery experiences were important in predicting teachers’ self-efficacy. Further, self-efficacy acted as a mediator between teachers’ perceptions of the school climate and reported inclusive behaviour. This brings us closer to understanding how teacher self-efficacy is fostered and the role of the school environment. Engaging with teacher belief systems may cultivate a school climate that promotes inclusion

The impact of explicit and implicit teacher beliefs on reports of inclusive teaching practices in Scotland

Successful inclusion is dependent upon teachers implementing classroom adaptations. Teacher beliefs can be expected to play a key role in their decision to make such adaptations. Using a cross-sectional survey, the purpose of the study was to examine mainstream school teachers’ explicit and implicit attitudes, self-efficacy and intentions towards children with intellectual disability and to assess their relationship to inclusive teaching. Primary school teachers working in Scotland were invited to take part. Eighty-seven participants completed a questionnaire measuring explicit attitudes, self-efficacy, intentions and inclusive teaching. Participants also completed a Single-Target Implicit Association Test assessing implicit attitudes. The results indicated that self-efficacy predicted reported inclusive behaviour and mediated the relationship between explicit attitudes and reported behaviour. Implicit attitudes did not relate to explicit beliefs (attitudes, self-efficacy, intentions) or behaviour

The impact of social cognitive and personality factors on teachers' reported inclusive behaviour

Background. Inclusive education of children with intellectual disabilities is intended to maximise their educational experience within the mainstream school setting. While policy mandates inclusion, it is classroom teachers’ behaviours that determine its success. Aims. This study provided a novel application of the Theory of Planned Behaviour (TPB) in this setting. It examined the effect of TPB variables and personality on reported inclusive teaching behaviours for learners with intellectual disabilities. Sample. The sample comprised 145 primary school teachers (85% female) from mainstream schools across Scotland. Method. Participants completed a TPB questionnaire assessing attitudes (instrumental and affective), subjective norms (injunctive and descriptive norms), perceptions of control (self-efficacy and controllability) and behavioural intentions towards using inclusive strategies. The Big Five Personality Index, measuring extraversion, conscientiousness, openness, neuroticism, and agreeableness, was also completed. Teaching practices were reported two weeks later. Results. Instrumental attitudes, descriptive norm, self-efficacy and neuroticism predicted teachers’ intentions to use inclusive strategies. Further, conscientiousness had indirect effects on intentions through TPB variables. These intentions, however, did not predict reported behaviour expected by TPB. Instead, self-efficacy was the only significant predictor of reported behaviour. Conclusions. This study demonstrates the application of TPB to an educational setting and contributes to the understanding of teachers’ reported use of inclusive strategies for children with intellectual disabilities