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

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Publications (100)


Supporting Information.docx
  • Data
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September 2021

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13 Reads

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Martin Ridout

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David L Roberts
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Sequence Identity (%ID) vs. Mass (kg) for myosin II motor domains
(A–D) Sequence Identity (%ID) vs. Mass (kg) for the motor domains of 4 myosin II isoforms: EMB, NMA, β-myosin, and IIx. Symbols indicate the clade that each species belongs to: grey squares (Euarchontoglires), black triangles (Laurasiatheria), and clear circles (Afrotheria and Metatheria). Each plot has been fitted with a robust linear regression. Sequence identity is pairwise to the mouse. The R² value and slope are shown on each plot. (E) The relationship between body mass and sequence divergence for the 13 myosin II motor domains. Values above the bar are the R² values. The error bars show the error of the gradient. Raw data files are available at Figshare. EMB, embryonic; NMA, non-muscle A; NMB, non-muscle B; NMC, non-muscle C.
Residue mass transition plots for 4 representative amino acid sites
(A) Species tree of organisms used in this analysis is shown, with the amino acids present in each species at the 4 sites and the mass of the organism displayed adjacent to it. Darker reds in the mass column are indicative of a greater mass value. In this tree, species from the Euarchontoglires clade are highlighted blue, and species from Laurasiatheria are highlighted pink. (B) Binomial regression mapping the transition of the most frequent amino acid at positions in the motor region of β-myosin to the second most frequent amino acid at that position. The residue numbering is that of the human β-cardiac myosin. The blue squares are Euarchontoglires, and the triangles are Laurasiatheria. The p-value with each plot arises from a test of the null hypothesis that amino acid type is unrelated to mass. Raw data files are available at Figshare.
Location of human variation, cardiomyopathy-associated variants, and non-conserved residues for the β isoform
Blue lines show the frequency of missense variation present in the gnomAD. Circles indicate the residue position of variants associated with cardiomyopathy (HCMs in orange, DCMs in magenta, and other in green [14]). Black lines show the frequency with which the consensus amino acid occurs at each residue position in the sequence. Red lines show the number of different amino acids occurring at that position in the sequence (minimum 1). The dashed grey lines indicate the position at which more than 10% of sequences contain an alternate amino acid. Key functional areas of the sequence as listed Motor domain: a. N-terminus 1–36, b. SH3 domain 37–75, c. Loop 1 201–215, d. Drosophila exon 7 region 300–335, e. Loop 4 368–372, f. Helix-O 426–440, g. Relay helix/loop, h. Loop 3 558–573, i. Loop 2 615–637, j. SH helices 680–707, k. Converter 710–778, l. IQ 781–810. B. Tail. S2, subfragment 2 coiled-coil; LMM, light meromyosin filament forming region. Raw data files are available at Figshare. DCM, dilated cardiomyopathy; gnomAD, Genome Aggregation Database; HCM, hypertrophic cardiomyopathy.
Residue mass change association with mass, clade, and each other
The association of each residue with clade (A), mass (B), and the association of the p-values of clade vs. mass (C) are plotted. Moreover, 1% and 5% significance thresholds are shown with the Bonferroni adjusted lines (blue and grey). The 3 groups of residues investigated are highlighted in orange, purple, and red and labelled with the human residue numbering in each plot. Raw data files are available at Figshare.
Location of residues switched in the chimera
Structure of human β-myosin (homology model based on Protein Databank ID 6FSA). The actin-binding site is highlighted in brown, exon 7 in blue, the nucleotide binding site in marine blue, and the converter region in yellow. The 3 groups of residues investigated are highlighted and labelled in orange (326, 343, 349, and 366), purple (421, 424, 430, and 434), and red (553, 569, 573, and 580) in each plot, and those that were switched are underlined. The structure shown represents one of the known conformations adopted by myosin during the turnover of ATP and is shown to illustrate the relative position of the residues of interest in relation to, e.g., actin- and ADP-binding sites. Since the residues highlighted are not directly coupled to ADP binding, it is likely that the stability of specific conformations and/or the transition (activation barrier) between conformations are affected by the sequence changes. For a review of the myosin motor domain structure, see [17,18], and for a broader discussion of activation barriers and conformational changes, see S1 Text and [19]. The table indicates the details about the 3 groups of variable residues, the adjusted probability (padj) of association with clade or mass, the log(mass) at the midpoint of the transition of the regression line between the 2 amino acids, and the range (10%–90%) over which the transition occurs.

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Identification of sequence changes in myosin II that adjust muscle contraction velocity

June 2021

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140 Reads

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11 Citations

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.


Modified Glasgow Prognostic Score (mGPS) for Prognostication of Adult Oncology Patients With Palliative Intent in a Regional Victorian Hospital, Australia

September 2020

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21 Reads

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3 Citations

American Journal of Hospice and Palliative Medicine

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.


Figure 1 Sequence Identity (%ID) vs Mass (kg) for the motor domains of six myosin II isoforms; embryonic (EMB), non-muscle A (NMA), non-muscle B (NMB), β-myosin, 2A and 2B. Symbols indicate the clade that each species belongs to grey squares (Euarchontoglires), black triangles (Laurasiatheria) and clear circles (Afrotheria and Metatheria). Each plot has been fitted with a robust linear regression. Sequence identity is pairwise to the mouse. The R 2 value and slope are shown on each plot.
Figure 3. Phylogenetic Tree for the coding DNA sequences of the β-myosin (MyHC 7) motor domain. The Maximum likelihood tree is shown. Black circles indicate positions where the Bayesian tree differed. The tree is coloured according to clade: Blue lines are Euarchontoglires (blue lines), Laurasiatheria (orange) and the few species in other groups are coloured black. The species mass is shown in brackets with the corresponding species name; all have the unit kg.
II Isoforms considered
Adaptation of mammalian myosin II sequences to body mass

June 2019

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28 Reads

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.


Figure 2. Distribution of sequence variations for the β-myosin sequences listed
Figure 4. Residue mass change association with mass, clade, and each other.
Figure 7. Stopped-flow analysis of the chimera, rat and human β-S1 proteins. A.
Cardiac contraction velocity has evolved to match heart rate with body size through variation in β-cardiac myosin sequence

June 2019

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119 Reads

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3 Citations

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.


Prognosis prediction with two calculations of Palliative Prognostic Index: Further prospective validation in hospice cancer patients with multicentre study

March 2018

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18 Reads

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15 Citations

Supportive and Palliative Care

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.




Figure 1. Estimated occupancy (ψ) and detection (p) probabilities for 2015 monthly dataset using site only, varying with months (February to May), altitudinal zone (high, medium and low) and season (dry and wet). Vertical lines are 95% confidence intervals. 
Figure 2. Distribution of the maximum likelihood estimates (MLE) for 2014 dataset (ψ = 0.3, p = 0.56, 10000 iterations) with varying number of visits according to predicted number of occasions (2, 3 and 4 visits; previous calculations) and with a constant number of sites (S = 123). 
Figure 3. Statistical power for different changes in occupancy (effect sizes of 0.3, 0.2 and 0.15) with respect to species detectability (p), number of sampling occasions (K) and number of sampling sites (S). 
Figure 4. Statistical power as function of change in occupancy (effect size) under different sampling designs, based on estimates of best model psi(alt)p(obs) for 2015 dataset (ψ = 0.49; p = 0.61; α = 0.1). S = number of sites surveyed. 
The power of monitoring: Optimizing survey designs to detect occupancy changes in a rare amphibian population

November 2017

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421 Reads

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65 Citations

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.


Increased conservation marketing effort has major fundraising benefits for even the least popular species

July 2017

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579 Reads

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112 Citations

Biological Conservation

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.


Citations (78)


... With sheep atrial myosin, Tmod1 reduced the Ca 2+ sensitivity of the velocities of thin filaments with both Tpm1.1 and Tpm1.2 ( Figure 5 and Table 2). Table 2. Table 2. Myosins of large and small animals differ in their mechanical and kinetic properties [53,54] and in their effects on the activation of the thin filament [40]. Therefore, we compared the effects of Tmod1 on the calcium regulation of the actin-myosin interaction with sheep and rat myosin. ...

Reference:

Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments
Identification of sequence changes in myosin II that adjust muscle contraction velocity

... To address the differences due only to the myosin isoform, we next performed simulations of the human twitch for the 100% α-myosin isoform. Deacon et al. generated a set of crossbridge parameters for human α-myosin [38], which were used by Johnson et al. [51] to model the complete crossbridge cycle for human αand β-myosins. This work was consistent, with little change in the rate constants for crossbridge attachment (k +A ) to and detachment (k −A ) from the A.M.D.Pi state between αand β-myosin. ...

Cardiac contraction velocity has evolved to match heart rate with body size through variation in β-cardiac myosin sequence

... The Model combining the initial PPI score with changes in the score proved to be a better predictor of 30-day survival than using the initial score, Week 1 PPI score or score change individually. Another study found that a second PPI assessment conducted on Days 3-5 in hospice residents had better discriminative performance than the first assessment at admission (Subramaniam et al. 2019). The studies (Arai et al. 2014;Hung et al. 2014;Kao et al. 2014) included employed different methods for calculating PPI. ...

Prognosis prediction with two calculations of Palliative Prognostic Index: Further prospective validation in hospice cancer patients with multicentre study
  • Citing Article
  • March 2018

Supportive and Palliative Care

... We constructed models to examine the impact of site-and survey-specific characteristics on the occupancy probability (Ψ)-likelihood that a salamander occupies a boardand detection probability (p)-likelihood of detecting a salamander given that the board is occupied-within the salamander community (MacKenzie et al. 2002;Kéry and Royle 2015;Barata et al. 2017). The models assume that individuals are not detected when absent, sites are closed during the study, observations are independent, and sites are correctly identified (Kéry and Royle 2015). ...

The power of monitoring: Optimizing survey designs to detect occupancy changes in a rare amphibian population

... Conservation and tourism complement each other, particularly for tourists who value destinations with preserved nature and culture. Global trends have shown that the efforts can significantly impact funding opportunities, positioning conservation as appealing to an innovative aspect of tourism (Veríssimo et al., 2017). In this case, Ewa Barbara (2019) implies that a social marketing approach involving all parties in landscape conservation is necessary to succeed. ...

Increased conservation marketing effort has major fundraising benefits for even the least popular species
  • Citing Article
  • July 2017

Biological Conservation

... Considering the potential biases, modelling approaches that do not account for the effort should be avoided when using opportunistic citizen science data to estimate species distributions and their potential changes (Isaac et al. 2014;Johnston et al. 2021). Opportunistic citizen science data has been used to determine changes and trends in population and distribution of several animal groups under different scenarios and employing different modelling approaches, therefore having varying data inputs and degrees of complexity (van Strien et al. 2013;Kamp et al. 2016;Dennis et al. 2017;Walker and Taylor 2017;Horns et al. 2018;Johnston et al. 2021;Hernández-Brito et al. 2022). However, documenting early detection of establishment and invasion by alien birds and estimating distribution trends using opportunistic citizen science data can present additional challenges. ...

Efficient occupancy model-fitting for extensive citizen-science data

... The first component handles the zero count and the other part deals with the positive counts which is referred to as the zero truncated Poisson or NB [17]. In Eqs (8) and (9) below, (1 − π) is the likelihood of overcoming the "hurdle" and generating a non-zero count [26]. The hurdle Poisson model is expressed as ...

Models for count data with many zeros. International Biomeric Conference

... Neglecting to consider the values and circumstances of key stakeholders can jeopardize the perceived legitimacy and effectiveness of ecologically sound solutions to conservation challenges, including wildlife trade controls (Challender et al. 2025;Weizman et al. 2023). For example, negative perceptions of CITES in terms of its legitimacy and benefit for conservation are associated with greater noncompliance in the orchid trade (Hinsley et al. 2017). To address present deficiencies, CITES could seek to establish systematic, collaborative processes mandating that key stakeholders be identified and given the opportunity to be represented in decision-making. ...

Estimating the Extent of CITES Noncompliance among Traders and End-Consumers; Lessons from the Global Orchid Trade

... They analysed all synthesisable compounds within a drug family involved in inflammatory diseases such as asthma. Aspects of design were discussed in Brown and Ridout [42]. The data have subsequently been re-expressed in terms of the presence or absence of fragments or functional complexes of atoms-see [3,28,43]-with p = 3149 attributes or fragments. ...

Level-screening designs for factors with many levels
  • Citing Article
  • June 2016

The Annals of Applied Statistics

... However, single species data with low survey detection probabilities (p < 0.15) and/or limited detection histories (i.e., few survey replicates) may lead to highly uncertain occupancy parameters that provide poor foundations on which to make inferences[7,12,27,28]. Probabilities of survey detection > 0.40 are generally more thanCamera arrays increase detection probabilities adequate for occupancy or abundance estimation[12,29]. For opossum and bobcat, two species with lower numbers of detections, increasing array sizes to ten still did not reach a survey detection probability of 0.40. ...

Design of occupancy studies with imperfect detection (vol 1, pg 131, 2010)
  • Citing Article
  • March 2016

Methods in Ecology and Evolution