α-Synuclein Aggregation Inhibitory Prunolides and a Dibrominated β-Carboline Sulfamate from the Ascidian Synoicum prunum

Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D–I (4–9) and cis-prunolide C (10), a new dibrominated β-carboline sulfamate named pityriacitrin C (11), alongside the known prunolides A–C (1–3) were isolated from the Australian colonial ascidian Synoicum prunum. The prunolides D–G (4–7) represent the first asymmetrically brominated prunolides, while cis-prunolide C (10) is the first reported with a cis-configuration about the prunolide’s bis-spiroketal core. The prunolides displayed binding activities with the Parkinson’s disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (1–5 and 10) were found to significantly inhibit the aggregation (>89.0%) of α-synuclein in a ThT amyloid dye assay. The prunolides A–C (1–3) were also tested for inhibition of pSyn aggregate formation in a primary embryonic mouse midbrain dopamine neuron model with prunolide B (2) displaying statistically significant inhibitory activity at 0.5 μM. The antiplasmodial and antibacterial activities of the isolates were also examined with prunolide C (3) displaying only weak activity against the 3D7 parasite strain of Plasmodium falciparum. Our findings reported herein suggest that the prunolides could provide a novel scaffold for the exploration of future therapeutics aimed at inhibiting amyloid protein aggregation and the treatment of numerous neurodegenerative diseases.Peer reviewe

Plotting the motivation of student volunteers in sports-based outreach work in the North East of England

This paper examines the evolution of student volunteers’ motivation during their participation in a sports-based outreach project and how their experiences during the programme serve to influence their commitment and retention to it. The Sport Universities North East England (SUNEE) project is a university-led community outreach initiative that provides the region's student volunteers with vast opportunities to gain both experience and qualifications as sports coaches, mentors and leaders by working with a range of hard-to-reach groups. This work draws on qualitative data generated from semi-structured interviews (n = 40) and describes a sequence of motivational transitions undergone by student volunteers over the course of their involvement in the project. In order to illustrate this, the paper applies the socio-psychological framework of Self-Determination Theory (SDT) to not only index the type of motivations that compel students to volunteer on the SUNEE project, but to also track motivational adaptation and reveal the features occurring within the project, which serve to either facilitate volunteer motivation or retention (Deci & Ryan, 1985, 2000). By using the example of the SUNEE project, this research demonstrates how students’ motivation to volunteer changes from the extrinsic (i.e., instrumental reasons such as enhancing one's employability profile) to the intrinsic (i.e., enjoying the experience) motivations the longer the person has taken part in the project. The findings demonstrate the utility of the SDT as a framework with which to understand student motivation to volunteer within a university-led sports-based community outreach setting. The theoretical contributions of the study to the literature on student volunteering are outlined, and implications are drawn for practice and future research

Bioavailability of prednisolone tablets

Two fourtreatment crossover studies were performed using 12 adult male volunteers in each with seven different commercially available prednisolone tablets. Plasma samples were assayed for prednisolone by a radioimmunoassay method. Statisacal analyses of the data, by analysis of variance for crossover design (ANOVA), showed no significant differences among the treatment averages at any of the sampling times except at 0.25 and 4 hr in one of the studies. There were also no significant differences among the treatment averages for peak plasma level, time of peak plasma level, area 0–12 hr, area 0–24 hr, and the halflife of elimination of prednisolone. We conclude that the average plasma concentrations of prednisolone are superimposable in a statistical sense and that the tablets tested are bioequivalent. Results of dissolution studies of six tablets of each of the seven lots of prednisolone tablets, using deaerated water in the spin filter apparatus, are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45072/1/10928_2005_Article_BF01065399.pd

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and ‘hard-to-reach’ patients

Background Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. Methods/design A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60–75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led ‘lung health check’ hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. Discussion If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. Trial registration This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number : ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015

An EGF-like Protein Forms a Complex with PfRh5 and Is Required for Invasion of Human Erythrocytes by Plasmodium falciparum

Invasion of erythrocytes by Plasmodium falciparum involves a complex cascade of protein-protein interactions between parasite ligands and host receptors. The reticulocyte binding-like homologue (PfRh) protein family is involved in binding to and initiating entry of the invasive merozoite into erythrocytes. An important member of this family is PfRh5. Using ion-exchange chromatography, immunoprecipitation and mass spectroscopy, we have identified a novel cysteine-rich protein we have called P. falciparum Rh5 interacting protein (PfRipr) (PFC1045c), which forms a complex with PfRh5 in merozoites. Mature PfRipr has a molecular weight of 123 kDa with 10 epidermal growth factor-like domains and 87 cysteine residues distributed along the protein. In mature schizont stages this protein is processed into two polypeptides that associate and form a complex with PfRh5. The PfRipr protein localises to the apical end of the merozoites in micronemes whilst PfRh5 is contained within rhoptries and both are released during invasion when they form a complex that is shed into the culture supernatant. Antibodies to PfRipr1 potently inhibit merozoite attachment and invasion into human red blood cells consistent with this complex playing an essential role in this process

Myth or Memory? Recollections of Penal Times in Irish Folklore

Stories of priests being hunted down and murdered at Mass Rocks by priest catchers and soldiers during the Penal era in Ireland persist to the present day. Using Ó Ciosáin’s (2004) tripartite taxonomy of memory this paper explores the reasons why these images continue to dominate and reflect persecuted nature of Catholicism

Cabinet Bed

Patent for "a cheap and simple construction of bed of this class, adapted to be readily folded or unfolded and to provide means for automatically folding and unfolding the legs for supporting the foot of the bed-frame when said frame is raised or lowered" (lines 9-15

Traumatic Extensor Hood Rupture

We report a traumatic rupture of the extensor hood of the dominant middle finger in an elite boxer. Surgical repair of the extensor hood with the metacarpophalangeal joint (MCPJ) in 90° of flexion and immobilisation of the MCPJ in flexion for 4 weeks allowed successful return of function to an international level

'Rhetorical Style and Issue Emphasis within the Conference Speeches of UKIP’s Nigel Farage 2010-2014'

This paper makes a distinctive contribution to the academic literature on the United Kingdom Independence Party (UKIP) by focusing in on a new area of research – i.e. the political rhetoric of Nigel Farage in relation to his Conference speeches. Our first research question asks how his Conference speeches are constructed and delivered and identifies what rhetorical techniques are deployed to maximise their impact. In methodological terms we address this question through rhetorical political analysis (RPA). Our second research question examines the extent to which his Conference speeches are changing. We ask whether there is evidence that Farage is broadening the range of issue appeals within his rhetoric (as one would expect if UKIP were making that transition from an anti-establishment to a mainstream party). Our method for this involves the use of N-Vivo – a computer coding programme – which quantifies which policies and issues are being used within speeches

Exploring the relationship between social class and sport event volunteering

There is a dearth of research that examines the relationship between sport event volunteering and social class. This article contributes to this gap by exploring the social class of volunteers involved in the running of a series of major international field hockey events held between 2015 and 2017 at the Queen Elizabeth Olympic Park, London. The authors draw upon longitudinal research that utilises demographic information and qualitative data from semi-structured interviews with 46 event volunteers. To gauge the social composition of this volunteer pool, the authors first discern the social class categories of the study’s participants. Following analysis of the qualitative data, the authors then examine how the interplay between social class and Pierre Bourdieu’s principal forms of cultural, economic and social capital shapes the volunteer workforce, and how they might operate to inhibit under-represented groups from volunteering. In parallel to the class analysis of the participants, the authors provide novel insights into the organisational amassing of an event volunteer workforce. The article concludes by considering the implications of the nexus between social class, capitals, and inclusion within event volunteering and its management