Martin S. Ridout’s research while affiliated with University of Kent and other places

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj < 0.05) but not with the clade (padj > 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat–human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin–myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate.

Background: Accurate prognostication is essential in caring for palliative patients. Various prognostication tools have been validated in many settings in the past few years. Biomarkers of inflammation (albumin and C-reactive protein) are combined to calculate the modified Glasgow prognostic score (mGPS), which has been found to be a simple prognostic tool in this population. Objective: This retrospective cohort study was to evaluate mGPS as a prognostication tool for cancer patients admitted to an acute hospital in regional Australia. Methods: Adult cancer patients admitted to an acute Australian regional hospital during 2017 who had albumin and C-reactive protein (CRP) tested were included. The mGPS was calculated based on their admission values and discharge values. Based on their score (0-2), groups were compared using univariate and multivariate Cox regression analysis for prognostication. Kaplan-Meier survival plots and median survival time from admission and discharge were constructed. Results: A total of 170 patient records were reviewed of which 95 had admission and discharge mGPS scores available for analysis. Of those, 86 had died at the time of data analysis. The median survival for admission mGPS 0, 1, 2 was 168,156 and 74 days. For discharge mGPS 0, 1, 2 medians were 168,119 and 70 days. On multi variate analysis admission mGPS 2 showed Hazard ratio of 2.29 (95% CI 1.16-4.56, p -0.02) and discharge mGPS 2 of 2.07 (95% CI 0.95-4.50, p value 0.07). Conclusions: In this study, mGPS was able to differentiate cancer patients into various prognostic groups. Further studies in regional acute hospitals could validate this prospectively with a multi-center larger sample size.

The speed of muscle contraction is related to body size; muscles in larger species contract at a slower rate. We investigated the evolution of twelve myosin II isoforms to identify any adapted to increasing body mass in mammals. We identified a correlation between body mass and sequence divergence for the motor domain of three adult myosin II isoforms (β, 2A, 2B) suggesting that these isoforms have adapted to increasing body mass. In contrast the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass, while the sarcomeric myosin 7b, extraocular and 2X isoforms showed a divergence intermediate between these two groups. The 2B and β-myosin motor domain showed the greatest rate of sequence divergence (−0.84 and −0.69 % per ten-fold increase in mass respectively). β-myosin is abundant in cardiac ventricle and slow skeletal muscle. We propose that β-myosin has adapted to enable slower heart beating and contraction of slow skeletal muscle as body mass increased.

Heart rate and the maximum velocity of contraction of striated muscle are inversely related to species size. As mammals evolve to different sizes, adaptations are required such as slower contracting heart and skeletal muscles. Analysis of the motor domain of β-myosin from 67 mammals from two clades identifies 14 sites, out of 800, strongly associated with body mass (p<0.01) but not with the clade (p>0.05). Nine of these sites were mutated in the human β-myosin to make it resemble the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a two fold increase in both motility and in the rate of ADP release from the actin.myosin cross-bridge (the step that limits contraction velocity). Both clades use the same small set of amino acids to adjust contraction velocity, suggesting a limited number of ways in which velocity can be manipulated.

Objectives In palliative care settings, predicting prognosis is important for patients and clinicians. The Palliative Prognostic Index (PPI), a prognostic tool calculated using clinical indices alone has been validated within cancer population. This study was to further test the discriminatory ability of the PPI (ie, its ability to determine whether a subject will live more or less than a certain amount of time) in a larger sample but with a palliative care context and to compare predictions at two different points in time. Methods Multicentre, prospective, observational study in 10 inpatient hospices in the UK. The PPI score was calculated on the day of admission (PPI1) and again once on days 3–5 of inpatient stay (PPI2). Patients were followed up for 6 weeks or until death, whichever was earlier. Results Of the 1164 patients included in the study, 962 had both scores available. The results from PPI2 showed improved sensitivity, specificity, positive predictive value and negative predictive value compared with PPI1. For PPI1versus PPI2, area under receiver operator character curve (ROC) for <21 days were 0.73 versus 0.82 and for ≥42 days prediction 0.72 versus 0.80. The median survival days for patients with PPI1 ≤4, 4.5–6 and >6 were 38 (31 to 44), 17 (14 to 19) and 5 (4 to 7). Conclusion This study showed improved discriminatory ability using the PPI score calculated between day 3and day5 of admission compared with that calculated on admission. This study further validated PPI as a prognostic tool within a palliative care population and showed recording at two time points improved accuracy.

Biodiversity conservation requires reliable species assessments and rigorously designed surveys. However, determining the survey effort required to reliably detect population change can be challenging for rare, cryptic and elusive species. We used a tropical bromeliad-dwelling frog as a model system to explore a cost-effective sampling design that optimizes the chances of detecting a population decline. Relatively few sampling visits were needed to estimate occupancy and detectability with good precision, and to detect a 30% change in occupancy with 80% power. Detectability was influenced by observer expertise, which therefore also had an effect on the sampling design – less experienced observers require more sampling visits to detect the species. Even when the sampling design provides precise parameter estimates, only moderate to large changes in occupancy will be detected with reliable power. Detecting a population change of 15% or less requires a large number of sites to be surveyed, which might be unachievable for range-restricted species occurring at relatively few sites. Unless there is high initial occupancy, rare and cryptic species will be particularly challenging when it comes to detecting small population changes. This may be a particular issue for long-term monitoring of amphibians which often display low detectability and wide natural fluctuations.

Conservationists often complain that their study species are ignored by donors. However, marketing theory could help understand and increase the profile and fundraising potential of these neglected species. We used linear regression with multimodel inference to analyse data on online behaviour from the websites of the World Wildlife Fund-US (WWF-US) and the Zoological Society of London's EDGE of Existence programme (EDGE), in order to understand how species traits and marketing campaign characteristics influenced flagship-based fundraising efforts. Our analysis accounted for species traits through variables such as appeal and familiarity, and marketing campaign characteristics through measuring the order in which the species were presented and the amount of information provided. We found that species traits were key for the WWF-US website, with appealing and threatened non-mammal species the most popular with donors. This was probably because WWF-US used well-known flagship species and so marketing had little impact. The EDGE website used a wider variety of species and in this case both species traits and the marketing campaign characteristics were important, so that appealing species and well-promoted species did best. We then predicted outcomes for a hypothetical EDGE fundraising campaign with varying degrees of marketing effort. We showed that additional marketing can have a large impact on donor behaviour, potentially increasing the interest of potential donors towards unappealing species by up to 26 times. This increase would more than equal the amount raised by campaigns using appealing species without additional promotion. Our results show marketing can have a large impact on donor behaviour and suggest there is scope for successful marketing campaigns based on a much wider range of species.