Using the CRISPR/Cas9 system to understand neuropeptide biology and regulation

Funding was provided by a Wellcome Trust ISSF starting grant (105625/Z/14/Z), Medical Research Scotland (PhD-719-2013), GW Pharmaceuticals (PhD-719-2013 - S.5242.001) and the BBSRC (BB/J012343/1).Peer reviewedPublisher PD

A reporter for amyloid precursor protein γ-secretase activity in Drosophila

A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as β-amyloid (Aβ) that is derived from the amyloid precursor protein (APP). A proteolytic activity called γ-secretase cleaves APP in the transmembrane domain and is required for Aβ generation. Aberrant γ-secretase cleavage of APP underlies the majority of early onset, familial AD. γ-Secretase resides in a large multi-protein complex, of which Presenilin, Nicastrin, APH-1 and PEN-2 are four essential components. Thus, identifying components and pathways by which the γ-secretase activity is regulated is crucial to understanding the mechanisms underlying AD pathogenesis, and may provide new diagnostic tools and therapeutic targets. Here we describe the generation of Drosophila that act as living reporters of γ-secretase activity in the fly eye. In these reporter flies the size of the eye correlates with the level of endogenous γ-secretase activity, and is very sensitive to the levels of three genes required for APP γ-secretase activity, presenilin, nicastrin and aph-1. Thus, these flies provide a sensitized system with which to identify other components of the γ-secretase complex and regulators of its activity. We have used these flies to carry out a screen for mutations that suppress γ-secretase activity and have identified a small chromosomal region that contains a gene or genes whose products may promote γ-secretase activity

Context-dependant enhancers as a reservoir of functional polymorphisms and epigenetic markers linked to alcohol use disorders and comorbidities

© 2022 The Authors. Acknowledgements AMcE was funded by BBSRC project grant (BB/N017544/1) and EH was funded by Medical Research Scotland (PhD-719–2013).Peer reviewedPublisher PD

Disease associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue specific activity of the cannabinoid‐1 receptor gene promoter; implications for cannabinoid pharmacogenetics

EH was funded by Medical Research Scotland (PhD-719-2013) and GW Pharmaceuticals. AMcE was funded by BBSRC project grant (BB/N017544/1). PB and DW are funded by the Scottish Government Rural and Environment Science and Analytical Services Division to the Rowett Institute. The authors declare no conflicts of interest.Peer reviewedPublisher PD

Exercise therapy after corticosteroid injection for moderate to severe shoulder pain: large pragmatic randomised trial

Objective To compare the effectiveness of subacromial corticosteroid injection combined with timely exercise and manual therapy (injection plus exercise) or exercise and manual therapy alone (exercise only) in patients with subacromial impingement syndrome

Health literacy and use and trust in health information

This is a post-print of an article whose final version has been published in Journal of Health Communication, Taylor and Francis, 2018.There is a need to investigate which health information sources are used and trusted by people with limited health literacy to help identify strategies for addressing knowledge gaps that can contribute to preventable illness. We examined whether health literacy was associated with people?s use of and trust in a range of potential health information sources. Six hundred participants from a GfK Internet survey panel completed an online survey. We assessed health literacy using the Newest Vital Sign, the sources participants used to get health information, and the extent to which participants trusted health information from these sources. We performed multivariable regressions, controlling for demographic characteristics. Lower health literacy was associated with lower odds of using medical websites for health information and with higher odds of using television, social media, and blogs or celebrity webpages. People with lower health literacy were less likely to trust health information from specialist doctors and dentists, but more likely to trust television, social media, blogs/celebrity webpages, friends, and pharmaceutical companies. People with limited health literacy had higher rates of using and trusting sources such as social media and blogs, which might contain lower quality health information compared to information from healthcare professionals. Thus, it might be necessary to enhance the public's ability to evaluate the quality of health information sources. The results of this study could be used to improve the reach of high quality health information among people with limited health literacy and thereby increase the effectiveness of health communication programs and campaigns.Peer reviewedCommunity Health Sciences, Counseling and Counseling Psycholog

The risks of malariainfection in Kenya in 2009

BACKGROUND: To design an effective strategy for the control of malaria requires a map of infection and disease risks to select appropriate suites of interventions. Advances in model based geo-statistics and malaria parasite prevalence data assemblies provide unique opportunities to redefine national Plasmodium falciparum risk distributions. Here we present a new map of malaria risk for Kenya in 2009. METHODS: Plasmodium falciparum parasite rate data were assembled from cross-sectional community based surveys undertaken from 1975 to 2009. Details recorded for each survey included the month and year of the survey, sample size, positivity and the age ranges of sampled population. Data were corrected to a standard age-range of two to less than 10 years (PfPR2-10) and each survey location was geo-positioned using national and on-line digital settlement maps. Ecological and climate covariates were matched to each PfPR2-10 survey location and examined separately and in combination for relationships to PfPR2-10. Significant covariates were then included in a Bayesian geostatistical spatial-temporal framework to predict continuous and categorical maps of mean PfPR2-10 at a 1 x 1 km resolution across Kenya for the year 2009. Model hold-out data were used to test the predictive accuracy of the mapped surfaces and distributions of the posterior uncertainty were mapped. RESULTS: A total of 2,682 estimates of PfPR2-10 from surveys undertaken at 2,095 sites between 1975 and 2009 were selected for inclusion in the geo-statistical modeling. The covariates selected for prediction were urbanization; maximum temperature; precipitation; enhanced vegetation index; and distance to main water bodies. The final Bayesian geo-statistical model had a high predictive accuracy with mean error of -0.15% PfPR2-10; mean absolute error of 0.38% PfPR2-10; and linear correlation between observed and predicted PfPR2-10 of 0.81. The majority of Kenya's 2009 population (35.2 million, 86.3%) reside in areas where predicted PfPR2-10 is less than 5%; conversely in 2009 only 4.3 million people (10.6%) lived in areas where PfPR2-10 was predicted to be > or =40% and were largely located around the shores of Lake Victoria. CONCLUSION: Model based geo-statistical methods can be used to interpolate malaria risks in Kenya with precision and our model shows that the majority of Kenyans live in areas of very low P. falciparum risk. As malaria interventions go to scale effectively tracking epidemiological changes of risk demands a rigorous effort to document infection prevalence in time and space to remodel risks and redefine intervention priorities over the next 10-15 years

The information needs of people living with ankylosing spondylitis: a questionnaire survey

<p>BACKGROUND:Today, health care is patient-centred with patients more involved in medical decision making and taking an active role in managing their disease. It is important that patients are appropriately informed about their condition and that their health care needs are met. We examine the information utilisation, sources and needs of people with ankylosing spondylitis (AS).</p> <p>METHODS: Participants in an existing AS cohort study were asked to complete a postal or online questionnaire containing closed and open-ended questions, regarding their information access and needs. Participants were stratified by age and descriptive statistics were performed using STATA 11, while thematic analysis was performed on open-ended question narratives. Qualitative data was handled in Microsoft Access and explored for emerging themes and patterns of experiences.</p> <p>RESULTS: Despite 73% of respondents having internet access, only 49% used the internet to access information regarding AS. Even then, this was only infrequently. Only 50% of respondents reported accessing written information about AS, which was obtained mainly in specialist clinics. Women were more likely than men to access information (63% (women) 46% (men)) regardless of the source, while younger patients were more likely to use online sources. The main source of non-written information was the rheumatologist. Overall, the respondents felt there was sufficient information available, but there was a perception that the tone was often too negative. The majority (95%) of people would like to receive a regular newsletter about AS, containing positive practical and local information. Suggestions were also made for more information about AS to be made available to non-specialist medical professionals and the general public.</p> <p>CONCLUSIONS: There appears to be sufficient information available for people with AS in the UK and this is mostly accessed by younger AS patients. Many patients, particularly men, choose not to access AS information and concerns were raised about its negative tone. Patients still rely on written and verbal information from their specialists. Future initiatives should focus on the delivery of more positive information, targeting younger participants in particular and increasing the awareness in the general population and wider non-specialist medical community.</p&gt

Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors

In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer's disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18-85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E epsilon 4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.Mueller Family Charitable Trust; Arizona Department of Health Services; National Institutes of Health [R01-AG041232, R01-AG049465-05]; Flinn FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]