Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture

1 Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) have structural similarities, interact with each others receptors (calcitonin receptor-like receptor (CLR)/receptor-activity-modifying proteins (RAMPs)) and show overlapping biological activities. AM and CGRP receptors are chiefly coupled to cAMP production. In this study, a method of primary dissociated cell culture was used to investigate the presence of AM and CGRP receptors and their effects on cAMP production in embryonic spinal cord cells. 2 Both neuronal and non-neuronal CLR immunopositive cells were present in our model. 3 High affinity, specific [ 125I]-AM binding sites (K(d) 79±9 pM and B(max) 571±34 fmol mg -1 protein) were more abundant than specific [ 125I]-CGRP binding sites (K(d) 12±0.7 pM and B(max) 32±2 fmol mg -1 protein) in embryonic spinal cord cells. 4 Specific [ 125I]-AM binding was competed by related molecules with a ligand selectivity profile of rAM>hAM(22-52)>rCGRPα>CGRP(8-37) ≫[r-(r*,s*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide (BIBN4096BS). 5 Specific [ 125I]-CGRP binding was competed by rCGRPα>rAM≥ CGRP(8-37)≥BIBN4096BS>hAM(22-52). 6 Cellular levels of cAMP were increased by AM (pEC"5"0 10.2±0.2) and less potently by rCGRPα (pEC"5"0 8.9±0.4). rCGRPα-induced cAMP accumulation was effectively inhibited by CGRP(8-37) (pA"2 7.63±0.44) and hAM(22-52) (pA"2 6.18±0.21) while AM-stimulation of cAMP levels was inhibited by CGRP(8-37) (pA"2 7.41±0.15) and AM(22-52) (pA"2 7.26±0.18). BIBN4096BS only antagonized the effects of CGRP (pA"2 8.40±0.30) on cAMP accumulation. 7 These pharmacological profiles suggest that effects of CGRP are mediated by the CGRP"1 (CLR/RAMP1) receptor in our model while those of AM are related to the activation of the AM"1 (CLR/RAMP2) receptor subtype. © 2006 Nature Publishing Group All rights reserved.

Conflicts and online community social capital:the influence of conflict management practices

Conflicts are part and parcel of online community dynamics (De Valck 2007; Harrison and Jenkins 1996; Kozinets 2001) – from flames about publishing inappropriate content (De Zwart and Lindsay 2009) to battles to win high status positions (Campbell, Fletcher and Greenhill 2009) and stigmatization of illegitimate insiders (Tikkanen, Hietanen, Henttonen, and Rokka 2009) up to bashing and smearing campaigns (Bocij 2002). As the concept of community presumes unity, marketers may be inclined to suppress any dissonance in their online brand communities thinking that it may hurt brand image or community attractiveness. However, Fournier and Lee (2009) advise marketers to embrace the conflicts that make communities thrive. As tensions and conflict cannot be avoided this seems logical advice. Nevertheless, are all tensions and conflicts created equally? Are some not more constructive (or destructive) than others? Thus, should all tensions and conflicts really be embraced, and what can be done to channel tensions and conflicts such that they do not become destructive? These questions form the starting point of this paper.

ALEX:mobile language assistant for low-literacy adults

Basic literacy skills are fundamental building blocks of education, yet for a very large number of adults tasks such as understanding and using everyday items is a challenge. While research, industry, and policy-making is looking at improving access to textual information for low-literacy adults, the literacy-based demands of today's society are continually increasing. Although many community-based organizations offer resources and support to adults with limited literacy skills, current programs have difficulties reaching and retaining those that would benefit most from them. To address these challenges, the National Research Council of Canada is proposing a technological solution to support literacy programs and to assist low-literacy adults in today's information-centric society: ALEX© – Adult Literacy support application for EXperiential learning. ALEX© has been created together with low-literacy adults, following guidelines for inclusive design of mobile assistive tools. It is a mobile language assistant that is designed to be used both in the classroom and in daily life, in order to help low-literacy adults become increasingly literate and independent.

Hidden in plain sight:low-literacy adults in a developed country overcoming social and educational challenges through mobile learning support tools

Illiteracy is often associated with people in developing countries. However, an estimated 50 % of adults in a developed country such as Canada lack the literacy skills required to cope with the challenges of today's society; for them, tasks such as reading, understanding, basic arithmetic, and using everyday items are a challenge. Many community-based organizations offer resources and support for these adults, yet overall functional literacy rates are not improving. This is due to a wide range of factors, such as poor retention of adult learners in literacy programs, obstacles in transferring the acquired skills from the classroom to the real life, personal attitudes toward learning, and the stigma of functional illiteracy. In our research we examined the opportunities afforded by personal mobile devices in providing learning and functional support to low-literacy adults. We present the findings of an exploratory study aimed at investigating the reception and adoption of a technological solution for adult learners. ALEX© is a mobile application designed for use both in the classroom and in daily life in order to help low-literacy adults become increasingly literate and independent. Such a solution complements literacy programs by increasing users' motivation and interest in learning, and raising their confidence levels both in their education pursuits and in facing the challenges of their daily lives. We also reflect on the challenges we faced in designing and conducting our research with two user groups (adults enrolled in literacy classes and in an essential skills program) and contrast the educational impact and attitudes toward such technology between these. Our conclusions present the lessons learned from our evaluations and the impact of the studies' specific challenges on the outcome and uptake of such mobile assistive technologies in providing practical support to low-literacy adults in conjunction with literacy and essential skills training. © 2013 Her Majesty the Queen in Right of Canada.

“Showing off” your mobile device:adult literacy learning in the classroom and beyond

For a very large number of adults, tasks such as reading. understanding, and using everyday items are a challenge. Although many community-based organizations offer resources and support for adults with limited literacy skills. current programs have difficulty reaching and retaining those that would benefit most. In this paper we present the findings of an exploratory study aimed at investigating how a technological solution that addresses these challenges is received and adopted by adult learners. For this, we have developed a mobile application to support literacy programs and to assist low-literacy adults in today's information-centric society. ALEX© (Adult Literacy support application for Experiential learning) is a mobile language assistant that is designed to be used both in the classroom and in daily life in order to help low-literacy adults become increasingly literate and independent. Through a long-term study with adult learners we show that such a solution complements literacy programs by increasing users' motivation and interest in learning, and raising their confidence levels both in their education pursuits and in facing the challenges of their daily lives.

Tale of two studies:challenges in field research with low-literacy adult learners in a developed country

Efforts to address the problems of literacy are often focused on developing countries. However, functional illiteracy is a challenge encountered by up to 50% of adults in developed countries. In this paper we reflect on the challenges we faced in trying to design and study the use of a mobile application to support adult literacy with two user groups: adults enrolled in literacy classes and carpenters without a high school education enrolled in an essential skills program. We also elaborate on aspects of the evaluations that are specific to a marginalized, functionally illiterate, group in a developed country - aspects that are less frequently present in similar studies of mobile literacy support technologies in developing countries. We conclude with presenting the lessons learnt from our evaluations and the impact of the studies' specific challenges on the outcome and uptake of such mobile assistive technologies in providing practical support to low-literacy adults in conjunction with literacy and essential skills training.

Relationship between sunlight and the age of onset of bipolar disorder:an international multisite study

Background - The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Methods - Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. Results - There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Limitations - Recall bias for onset and family history data. Conclusions - A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Evaluation of the antimicrobial activities of plant oxylipins supports their involvement in defense against pathogens

Plant oxylipins are a large family of metabolites derived from polyunsaturated fatty acids. The characterization of mutants or transgenic plants affected in the biosynthesis or perception of oxylipins has recently emphasized the role of the so-called oxylipin pathway in plant defense against pests and pathogens. In this context, presumed functions of oxylipins include direct antimicrobial effect, stimulation of plant defense gene expression, and regulation of plant cell death. However, the precise contribution of individual oxylipins to plant defense remains essentially unknown. To get a better insight into the biological activities of oxylipins, in vitro growth inhibition assays were used to investigate the direct antimicrobial activities of 43 natural oxylipins against a set of 13 plant pathogenic microorganisms including bacteria, oomycetes, and fungi. This study showed unequivocally that most oxylipins are able to impair growth of some plant microbial pathogens, with only two out of 43 oxylipins being completely inactive against all the tested organisms, and 26 oxylipins showing inhibitory activity toward at least three different microbes. Six oxylipins strongly inhibited mycelial growth and spore germination of eukaryotic microbes, including compounds that had not previously been ascribed an antimicrobial activity such as 13-keto-9(Z),11(Z),15(Z)- octadecatrienoic acid and 12-oxo-10,15(Z)-phytodienoic acid. Interestingly this first large-scale comparative assessment of the antimicrobial effects of oxylipins reveals that regulators of plant defense responses are also the most active oxylipins against eukaryotic microorganisms, suggesting that such oxylipins might contribute to plant defense through their effects both on the plant and on pathogens, possibly through related mechanisms. © 2005 American Society of Plant Biologists.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Influence of light exposure during early life on the age of onset of bipolar disorder

Background: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4N and 70.7N, and 1.2S and 41.3S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. Results: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.