Assessing cellular response to functionalized α-helical peptide hydrogels

α-Helical peptide hydrogels are decorated with a cell-binding peptide motif (RGDS), which is shown to promote adhesion, proliferation, and differentiation of PC12 cells. Gel structure and integrity are maintained after functionalization. This opens possibilities for the bottom-up design and engineering of complex functional scaffolds for 2D and 3D cell cultures.</p

An update on the mosquito species composition and diversity in western and North Western Uganda

Although the west and north western parts of Uganda are historically known homes to a number of mosquito species and arboviruses associated with morbidity and mortality, early studies were highly focal and limited to specific collection methods. We aimed to update mosquito species composition in areas where a febrile illness study had shown evidence of arboviruses circulating. Adult mosquito sampling was done outside and inside houses using light traps baited with solid carbon dioxide and pyrethrum spray respectively. All collected mosquitoes were identified using appropriate morphological identification keys. A total of 22,455 mosquitoes from 89 species, 22 sub species and 11 genera were collected from Arua and Kasese districts. Overall abundance was found to be higher in Kasese (n=13446, 59.9%) than Arua district (n = 9009, 40.1%), though no significant differences were observed across villages in Arua and Kasese districts (Kruskal Wallis, X2 = 2, df = 3, p&gt;0.05). Collection numbers were highest for genus Coquillettidia (n = 7942, 35.4%), followed by Culex (n = 7642, 34.03%), Mansonia (n = 3414, 15.2%), Anopheles (n = 1970, 8.8%) and Aedes (n = 1349, 6.01%). Other species were across 6 genera Eretmopodites (n = 59, 0.26%), Uranoteania (n = 36, 0.16%), Lutzia (n = 26, 0.12%), Mimomyia (n = 13, 0.06%), Aediomyia (n = 3, 0.01%) and Toxorhynchites (n = 1, 0.004%) appeared low in both districts. Species richness was comparatively higher in Kasese than Arua district, however across villages, it was evenly distributed with no significant differences observed, and species diversity was significantly higher in Arua than Kasese (Mann Whitney U test, p&lt;0.05). A number of species identified here have been implied in arbovirus transmission. Moreover, we show the first description of Culex (Culex) litwakae Harbach mosquito in Uganda, a species previously described in the coastal regions of Kenya. The existence of a mosquito species previously not documented in Uganda suggests a likelihood of many invasive species whose potential to transmit viruses to humans and animals remains largely unknown

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase

This work was supported by the Medical Research Council and the Scottish Funding Council.Influenza virus sialidase has an essential role in the virus’ life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the ‘150-loop’, providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.Publisher PDFPeer reviewe

Use of Remote Sensing for Monitoring Climate Variability for Integrated Early Warning Systems: Applications for Human Diseases and Desert Locust Management

A number of the major human infectious diseases (like malaria and dengue) and Desert Locusts that still plague the developing world are sensitive to inter-seasonal and inter-decadal changes in environment and climate. Monitoring variations in environmental conditions such as rainfall and vegetation helps decision-makers at Ministries of Agriculture and Ministries of Health to assess the risk levels of Desert Locust outbreaks or malaria epidemics. The International research institute for climate and society (IRI) has developed products based on remotely sensed data to monitor those changes and provide the information directly to the decision-makers. This paper presents recent developments which use remote sensing to monitor climate variability, environmental conditions and their impacts on the dynamics of infectious diseases (malaria) and Desert Locust outbreaks

Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population

Acknowledgements Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. For the Lothian Birth Cohorts (LBC1921 and LBC1936), we thank Paul Redmond for database management assistance; Alan Gow, Martha Whiteman, Alison Pattie, Michelle Taylor, Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry; nurses and staff at the Wellcome Trust Clinical Research Facility, where blood extraction and genotyping was performed; staff at the Lothian Health Board; and the staff at the SCRE Centre, University of Glasgow. The research was supported by a program grant from Age UK (Disconnected Mind) and by grants from the Biotechnology and Biological Sciences Research Council (BBSRC). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Medical Research Council (MRC) and BBSRC is gratefully acknowledged. DJM is an NRS Career Research Fellow funded by the CSO. BATS were funded by the Australian Research Council (A79600334, A79906588, A79801419, DP0212016, DP0664638, and DP1093900) and the National Health and Medical Research Council (389875) Australia. MKL is supported by a Perpetual Foundation Wilson Fellowship. SEM is supported by a Future Fellowship (FT110100548) from the Australian Research Council. GWM is supported by a National Health and Medical Research Council (NHMRC), Australia, Fellowship (619667). We thank the twins and siblings for their participation, Marlene Grace, Ann Eldridge and Natalie Garden for cognitive assessments, Kerrie McAloney, Daniel Park, David Smyth and Harry Beeby for research support, Anjali Henders and staff in the Molecular Epidemiology Laboratory for DNA sample processing and preparation and Scott Gordon for quality control and management of the genotypes. This work is supported by a Stragetic Award from the Wellcome Trust, reference 104036/Z/14/Z.Peer reviewedPublisher PD

Embodied Knowledge: Writing Researchers’ Bodies Into Qualitative Health Research

After more than a decade of postpositivist health care research and an increase in narrative writing practices, social scientific, qualitative health research remains largely disembodied. The erasure of researchers’ bodies from conventional accounts of research obscures the complexities of knowledge production and yields deceptively tidy accounts of research. Qualitative health research could benefit significantly from embodied writing that explores the discursive relationship between the body and the self and the semantic challenges of writing the body by incorporating bodily details and experiences into research accounts. Researchers can represent their bodies by incorporating autoethnographic narratives, drawing on all of their senses, interrogating the connections between their bodily signifiers and research processes, and experimenting with the semantics of self and body. The author illustrates opportunities for embodiment with excerpts from an ethnography of a geriatric oncology team and explores implications of embodied writing for the practice of qualitative health research

Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis

OBJECTIVES: Methotrexate (MTX) is the mainstay treatment for juvenile idiopathic arthritis (JIA), however approximately 30% of children will fail to respond to the drug. Identification of genetic predictors of response to MTX would be invaluable in developing optimal treatment strategies for JIA. Using a candidate gene approach, single nucleotide polymorphisms (SNPs) within genes in the metabolic pathway of MTX, were investigated for association with response to treatment in JIA cases. METHODS: Tagging SNPs were selected across 13 MTX metabolic pathway genes and were genotyped using Sequenom genotyping technology in subjects recruited from the Sparks Childhood Arthritis Response to Medication Study. Response to MTX was defined using the American College of Rheumatology (ACR) paediatric response criteria and SNP genotype frequencies were compared between the worst and best responders (ACR-Ped70) to MTX. An independent cohort of US JIA cases was available for validation of initial findings. RESULTS: One SNP within the inosine triphosphate pyrophosphatase gene (ITPA) and two SNPs within 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) were significantly associated with a poor response to MTX. One of the ATIC SNPs showed a trend towards association with MTX response in an independent cohort of US JIA cases. Meta-analysis of the two studies strengthened this association (combined p value=0.002). CONCLUSIONS: This study presents association of a SNP in the ATIC gene with response to MTX in JIA. There is now growing evidence to support a role of the ATIC gene with response to MTX treatment. These results could contribute towards a better understanding of and ability to predict MTX response in JIA

Patient preferences for topical treatment of actinic keratoses:a discrete-choice experiment

Funding: This study was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit programme (PB-PG-0110-21244), Department of Health, UK. The funder was not involved in the study design. Acknowledgments: The authors gratefully acknowledge support from the Cancer Research UK Clinical Trials Unit, the UK Dermatology Clinical Trials Network, the NIHR Clinical Studies Group, and support for investigators from the British Skin Foundation and Cancer Research UK. We would also like to thank Martin Jones, Daniel Rigby and Ariel Bergmann for constructive comments on the design of the DCE.Peer reviewedPostprin

The maximally entangled symmetric state in terms of the geometric measure

The geometric measure of entanglement is investigated for permutation symmetric pure states of multipartite qubit systems, in particular the question of maximum entanglement. This is done with the help of the Majorana representation, which maps an n qubit symmetric state to n points on the unit sphere. It is shown how symmetries of the point distribution can be exploited to simplify the calculation of entanglement and also help find the maximally entangled symmetric state. Using a combination of analytical and numerical results, the most entangled symmetric states for up to 12 qubits are explored and discussed. The optimization problem on the sphere presented here is then compared with two classical optimization problems on the S^2 sphere, namely Toth's problem and Thomson's problem, and it is observed that, in general, they are different problems.Comment: 18 pages, 15 figures, small corrections and additions to contents and reference

"Engaging with birth stories in pregnancy: a hermeneutic phenomenological study of women's experiences across two generations"

BACKGROUND: The birth story has been widely understood as a crucial source of knowledge about childbirth. What has not been reported is the effect that birth stories may have on primigravid women's understandings of birth. Findings are presented from a qualitative study exploring how two generations of women came to understand birth in the milieu of other's stories. The prior assumption was that birth stories must surely have a positive or negative influence on listeners, steering them towards either medical or midwifery-led models of care. METHODS: A Heideggerian hermeneutic phenomenological approach was used. Twenty UK participants were purposively selected and interviewed. Findings from the initial sample of 10 women who were pregnant in 2012 indicated that virtual media was a primary source of birth stories. This led to recruitment of a second sample of 10 women who gave birth in the 1970s-1980s, to determine whether they were more able to translate information into knowledge via stories told through personal contact and not through virtual technologies RESULTS: Findings revealed the experience of 'being-in-the-world' of birth and of stories in that world. From a Heideggerian perspective, the birth story was constructed through 'idle talk' (the taken for granted assumptions of things, which come into being through language). Both oral stories and those told through technology were described as the 'modern birth story'. The first theme 'Stories are difficult like that', examines the birth story as problematic and considers how stories shape meaning. The second 'It's a generational thing', considers how women from two generations came to understand what their experience might be. The third 'Birth in the twilight of certainty,' examines women's experience of Being in a system of birth as constructed, portrayed and sustained in the stories being shared. CONCLUSIONS: The women pregnant in 2012 framed their expectations in the language of choice, whilst the women who birthed in the 1970s-1980s framed their experience in the language of safety. For both, however, the world of birth was the same; saturated with, and only legitimised by the birth of a healthy baby. Rather than creating meaningful understanding, the 'idle talk' of birth made both cohorts fearful of leaving the relative comfort of the 'system', and of claiming an alternative birth