Optimized alkylated cyclodextrin polysulphates with reduced risks on thromboembolic accidents improve osteoarthritic chondrocyte metabolism

Objectives. To compare the ability of different cyclodextrin polysulphate (CDPS) derivatives to affect human articular cartilage cell metabolism in vitro

Aharonov-Bohm interference in the presence of metallic mesoscopic cylinders

This work studies the interference of electrons in the presence of a line of magnetic flux surrounded by a normal-conducting mesoscopic cylinder at low temperature. It is found that, while there is a supplementary phase contribution from each electron of the mesoscopic cylinder, the sum of these individual supplementary phases is equal to zero, so that the presence of a normal-conducting mesoscopic ring at low temperature does not change the Aharonov-Bohm interference pattern of the incident electron. It is shown that it is not possible to ascertain by experimental observation that the shielding electrons have responded to the field of an incident electron, and at the same time to preserve the interference pattern of the incident electron. It is also shown that the measuring of the transient magnetic field in the region between the two paths of an electron interference experiment with an accuracy at least equal to the magnetic field of the incident electron generates a phase uncertainty which destroys the interference pattern.Comment: 15 pages, 5 Postscript figure

Cross-cultural adaptation of the Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) and a study on its construct validity

SummaryObjectiveTo validate a cross-culturally translated and adapted Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) in patients with osteoarthritis (OA) of the hands and to evaluate its construct validity by comparing with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN).MethodsThe FIHOA was translated into Dutch and cross-culturally adapted. The questionnaire was administered to 72 patients with hand OA (female/male ratio: 64/8, handedness: right: 62/left: 7/both: 3). A visual analogue scale (VAS) pain scale (100mm) and the AUSCAN questionnaire were also recorded. An item–item analysis was performed. Test–retest reliability (time interval: 5 days) was assessed in 21 patients with intraclass correlation coefficient (ICC) and Bland and Altman graphical method. Construct validity was assessed by Spearman rank correlation coefficient between the FIHOA and AUSCAN.ResultsInternal consistency was high (Cronbach's alpha=0.89). All items, except for one (‘Are you able to clench the fist?’), and the mean total FIHOA scores were statistically different between the subgroups based on the VAS (mean total score=7.46 and 14.19, in a-/mild symptomatic and symptomatic group, respectively (P<0.001)).The Spearman's correlation between all subscales of the AUSCAN (pain, stiffness, functionality) and the FIHOA was good, especially with the subscale functionality (r=0.81, P<0.01). Test–retest reliability was excellent with an ICC of 0.96 for the total score and the Bland and Altman plot showing a homogeneous distribution of the differences.ConclusionThe psychometric properties of the Dutch version of the FIHOA are excellent. There is a good correlation between the FIHOA and all subscales of the AUSCAN, especially the subscale functionality

The rhythm of life: the perfect rhythm of morse code

Morse code is a unique exemplar of the inherent complexities of rhythm. Learning Morse code in wartime presented challenges to expedite skill acquisition. This thesis explored the strategies used to teach and learn Morse code in the second World War and investigated the resourceful techniques used by the WRANS in an empirical study. The first study investigated the teaching and learning strategies of wartime telegraphists to learn Morse code. Five WRANS described a series of techniques to learn Morse code, including rote learning and repetition, visualisation and pattern recognition, intoning and mnemonics, and music. Music provided effective training for the fundamental teaching and learning of Morse code by matching the rhythmical properties of Morse code to music. Music equipped Morse code operators with a unique approach to Morse code instruction. Learning Morse code with music was described as a way of making sense of the ‘rhythm’ and ‘shape’ of the Morse code letters and proved an invaluable aid to learning and teaching Morse code. The second study examined the effectiveness of learning Morse code with the aid of music. Novices formed two groups, Control Group (no music aid) and Music Group (with music aid). Results confirmed the effectiveness of music training in three Morse code letters, Q V, and A in two experiments, the first with known Morse code letters (Q V A) and the second with unknown letters. The Music Group accurately identified 90% of known and unknown Morse code letters compared to the Control Group who identified less then 50% of known and unknown Morse code letters. This thesis explored the transferable attributes of rhythm perception in music as a teaching and learning mechanism for Morse code. There is extensive research on the complex learning and retention of Morse code but the studies in this thesis have indicated that the ground-breaking wartime strategy of music and Morse code is a powerful duo. The investigation of learning and teaching strategies of the WRANS showed that musical rhythm influenced the skill acquisition of Morse code and the perceptual test suggests that current work in rhythm perception extends beyond music pedagogy and has further implications for all cognitive function

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments.

Published onlineJournal ArticleReviewSince its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host-pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host-pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.This work was funded by the Open Innovation Platform at the University of Exeter (Open Innovation Fund Initiative PHSW029) and by the Centre for Environment, Fisheries and Aquaculture Science (Cefas) (under seedcorn project DP318 to GDS) under the Strategic Alliance partnership between the University of Exeter and Cefas

ECOdrug: A database connecting drugs and conservation of their targets across species

This is the author accepted manuscriptPharmaceuticals are designed to interact with specific molecular targets in humans and these targets generally have orthologs in other species. This provides opportunities for the drug discovery community to use alternative model species for drug development. It also means, however, there is potential for mode of action related effects in non-target wildlife species as many pharmaceuticals reach the environment through patient use and manufacturing wastes. Acquiring insight in drug target ortholog predictions across species and taxonomic groups has proven difficult because of the lack of an optimal strategy and because necessary information is spread across multiple and diverse sources and platforms. We introduce a new research platform tool, ECOdrug, that reliably connects drugs to their protein targets across divergent species. It harmonizes ortholog predictions from multiple sources via a simple user interface underpinning critical applications for a wide range of studies in pharmacology, ecotoxicology and comparative evolutionary biology. ECOdrug can be used to identify species with drug targets and identify drugs that interact with those targets. As such, it can be applied to support intelligent targeted drug safety testing by ensuring appropriate and relevant species are selected in ecological risk assessments. ECOdrug is freely accessible and available at: Http://www.ecodrug.org.Innovative Medicines Initiative Joint Undertaking under Intelligent Assessment of PharmaceuticalsEuropean Union’s Seventh Framework ProgrammeAstraZenecaNC3Rs funded projec

De novo assembly of the Carcinus maenas transcriptome and characterization of innate immune system pathways.

Journal ArticleCopyright © 2015 Verbruggen et al.BACKGROUND: The European shore crab, Carcinus maenas, is used widely in biomonitoring, ecotoxicology and for studies into host-pathogen interactions. It is also an important invasive species in numerous global locations. However, the genomic resources for this organism are still sparse, limiting research progress in these fields. To address this resource shortfall we produced a C. maenas transcriptome, enabled by the progress in next-generation sequencing technologies, and applied this to assemble information on the innate immune system in this species. RESULTS: We isolated and pooled RNA for twelve different tissues and organs from C. maenas individuals and sequenced the RNA using next generation sequencing on an Illumina HiSeq 2500 platform. After de novo assembly a transcriptome was generated encompassing 212,427 transcripts (153,699 loci). The transcripts were filtered, annotated and characterised using a variety of tools (including BLAST, MEGAN and RSEM) and databases (including NCBI, Gene Ontology and KEGG). There were differential patterns of expression for between 1,223 and 2,741 transcripts across tissues and organs with over-represented Gene Ontology terms relating to their specific function. Based on sequence homology to immune system components in other organisms, we show both the presence of transcripts for a series of known pathogen recognition receptors and response proteins that form part of the innate immune system, and transcripts representing the RNAi, Toll-like receptor signalling, IMD and JAK/STAT pathways. CONCLUSIONS: We have produced an assembled transcriptome for C. maenas that provides a significant molecular resource for wide ranging studies in this species. Analysis of the transcriptome has revealed the presence of a series of known targets and functional pathways that form part of their innate immune system and illustrate tissue specific differences in their expression patterns.Cefas Seedcorn Contract #DP318University of Exeter’s Open Innovation PlatformWellcome Trust Institutional Strategic Support Awar

European Society of Biomechanics S.M. Perren Award 2018: Altered biomechanical stimulation of the developing hip joint in presence of hip dysplasia risk factors

Fetal kicking and movements generate biomechanical stimulation in the fetal skeleton, which is important for prenatal musculoskeletal development, particularly joint shape. Developmental dysplasia of the hip (DDH) is the most common joint shape abnormality at birth, with many risk factors for the condition being associated with restricted fetal movement. In this study, we investigate the biomechanics of fetal movements in such situations, namely fetal breech position, oligohydramnios and primiparity (firstborn pregnancy). We also investigate twin pregnancies, which are not at greater risk of DDH incidence, despite the more restricted intra-uterine environment. We track fetal movements for each of these situations using cine-MRI technology, quantify the kick and muscle forces, and characterise the resulting stress and strain in the hip joint, testing the hypothesis that altered biomechanical stimuli may explain the link between certain intra-uterine conditions and risk of DDH. Kick force, stress and strain were found to be significantly lower in cases of breech position and oligohydramnios. Similarly, firstborn fetuses were found to generate significantly lower kick forces than non-firstborns. Interestingly, no significant difference was observed in twins compared to singletons. This research represents the first evidence of a link between the biomechanics of fetal movements and the risk of DDH, potentially informing the development of future preventative measures and enhanced diagnosis. Our results emphasise the importance of ultrasound screening for breech position and oligohydramnios, particularly later in pregnancy, and suggest that earlier intervention to correct breech position through external cephalic version could reduce the risk of hip dysplasia

Why decision making may not require awareness

Newell & Shanks (N&S) argue against the idea that any significant role for unconscious influences on decision making has been established by research to date. Inasmuch as this conclusion applies to the idea of an "intelligent cognitive unconscious," we would agree. Our concern is that the article could lead the unwary to conclude that there are no unconscious influences on decision making - and never could be. We give reasons why this may not be the case