Bayesian methods outperform parsimony but at the expense of precision in the estimation of phylogeny from discrete morphological data

Different analytical methods can yield competing interpretations of evolutionary history and, currently, there is no definitive method for phylogenetic reconstruction using morphological data. Parsimony has been the primary method for analysing morphological data, but there has been a resurgence of interest in the likelihood-based Mk-model. Here, we test the performance of the Bayesian implementation of the Mk-model relative to both equal and implied-weight implementations of parsimony. Using simulated morphological data, we demonstrate that the Mk-model outperforms equal-weights parsimony in terms of topological accuracy, and implied-weights performs the most poorly. However, the Mk-model produces phylogenies that have less resolution than parsimony methods. This difference in the accuracy and precision of parsimony and Bayesian approaches to topology estimation needs to be considered when selecting a method for phylogeny reconstruction

Uncertain-tree:Discriminating among competing approaches to the phylogenetic analysis of phenotype data

Morphological data provide the only means of classifying the majority of life's history, but the choice between competing phylogenetic methods for the analysis of morphology is unclear. Traditionally, parsimony methods have been favoured but recent studies have shown that these approaches are less accurate than the Bayesian implementation of the Mk model. Here we expand on these findings in several ways: we assess the impact of tree shape and maximum-likelihood estimation using the Mk model, as well as analysing data composed of both binary and multistate characters. We find that all methods struggle to correctly resolve deep clades within asymmetric trees, and when analysing small character matrices. The Bayesian Mk model is the most accurate method for estimating topology, but with lower resolution than other methods. Equal weights parsimony is more accurate than implied weights parsimony, and maximum-likelihood estimation using the Mk model is the least accurate method. We conclude that the Bayesian implementation of the Mk model should be the default method for phylogenetic estimation from phenotype datasets, and we explore the implications of our simulations in reanalysing several empirical morphological character matrices. A consequence of our finding is that high levels of resolution or the ability to classify species or groups with much confidence should not be expected when using small datasets. It is now necessary to depart from the traditional parsimony paradigms of constructing character matrices, towards datasets constructed explicitly for Bayesian methods.This research was funded by NERC (NE/L501554/1 to J.E.O.R. and L.A.P.; NE/K500823/1 to M.N.P.; NE/L002434/1 to J.F.; NE/N003438/1 to P.C.J.D.), BBSRC (BB/N000919/1 to P.C.J.D.), the University of Bristol (STaR scholarship to A.R.T.), Royal Society Wolfson Research Merit Award (P.C.J.D.) and the John Templeton Foundation (43915 to D.P. and L.H.).N

Evolving boolean functions with conjunctions and disjunctions via genetic programming

Recently it has been proved that simple GP systems can efficiently evolve the conjunction of n variables if they are equipped with the minimal required components. In this paper, we make a considerable step forward by analysing the behaviour and performance of a GP system for evolving a Boolean function with unknown components, i.e. the target function may consist of both conjunctions and disjunctions. We rigorously prove that if the target function is the conjunction of n variables, then a GP system using the complete truth table to evaluate program quality evolves the exact target function in O(ℓ n log2 n) iterations in expectation, where ℓ ≥ n is a limit on the size of any accepted tree. Additionally, we show that when a polynomial sample of possible inputs is used to evaluate solution quality, conjunctions with any polynomially small generalisation error can be evolved with probability 1 - O(log2(n)/n). To produce our results we introduce a super-multiplicative drift theorem that gives significantly stronger runtime bounds when the expected progress is only slightly super-linear in the distance from the optimum

Environmental forcing by submarine canyons: Evidence between two closely situated cold-water coral mounds (Porcupine Bank Canyon and Western Porcupine Bank, NE Atlantic)

Within the Porcupine Bank Canyon (NE Atlantic), cold-water coral (CWC) mounds are mostly found clustered along the canyon lip, with individual disconnected mounds occurring nearby on the western Porcupine Bank. Remotely operated vehicle-mounted vibrocoring was utilized to acquire cores from both of these sites. This study is the first to employ this novel method when aiming to precisely sample two closely situated areas. Radiometric ages constrain the records from the early to mid-Holocene (9.1 to 5.6 ka BP). The cores were then subjected to 3D segmented computer tomography to capture mound formation stages. The cores were then further examined using stable isotopes and benthic foraminiferal assemblages, to constrain the paleoenvironmental variation that influenced CWC mound formation of each site. In total, mound aggradation rate in the Porcupine Bank Canyon and western Porcupine Bank was comparable to other Holocene CWC mounds situated off western Ireland. Results derived from multiproxy analysis, show that regional climatic shifts define the environmental conditions that allow positive coral mound formation. In addition, the aggradation rate of coral mounds is higher adjacent to the Porcupine Bank Canyon than on the western Porcupine Bank. Benthic foraminifera assemblages and planktic foraminiferal δ13C reveal that higher quality organic matter is more readily available closer to the canyon lip. As such, we hypothesize that coral mound formation in the region is likely controlled by an interplay between enhanced shelf currents and the existence of the Eastern North Atlantic Water-Mediterranean Outflow Water-Transition Zone. The geomorphology of the canyon promotes upwelling of these water masses that are enriched in particles, including food and sediment supply. The higher availability of these particles support the development and succession of ecological hotspots along the canyon lip and adjacent areas of the seafloor. These observations provide a glimpse into the role that submarine canyons play in influencing macro and micro benthic fauna distributions and highlights the importance of their conservation

Using novel methods to track British and Irish Ice Sheet dynamics since the Late Pleistocene, along the west Porcupine Bank, NE Atlantic

Extensive research has been undertaken to elucidate the glacial history of the British Irish Ice Sheet (BIIS) in the NE Atlantic. BRITICE-CHRONO has compiled terrestrial and marine based evidence, to provide an empirical reconstruction of ice sheet expansion and retreat during the Late Pleistocene. Across the Irish margin, particular focus has been given to seafloor sediments which contain ice-rafted debris (IRD). However, there are few publications on IRD from areas proximal to the maximum extent of the BIIS, which would offer further insights on the behaviour of the ice sheet during (de)glacial events. Previous exploratory surveys of the west Porcupine Bank (wPB) visually identified IRD on the seafloor and these present a new study site to investigate the extent of the BIIS and the course of its icebergs. Moreover, there are uncertainties about the effects of icebergs on the marine life and cold-water corals occupying the nearby Porcupine Bank Canyon. Assessing a sediment core containing an IRD analogue for the wPB would thus, have a dual purpose. In the past however, coring missions of the wPB using traditional coring methods (i.e. piston and gravity cores) were unsuccessful. Here, we utilized a novel ROV-mounted vibrocoring procedure to capture a 0.75 m IRD-bearing sediment core from the wPB. Then further novel analytical methods (computed tomography-based IRD-detection) were used to quantify IRD every 0.02 cm to provide the highest resolution record of BIIS related IRD to date. From this, several fluxes of IRD deposition onto the wPB between 31.6 and 9 ka BP were revealed and corroborated by other published records from across the NE Atlantic. It was shown that the wPB IRD fluxes occur simultaneously with other parts of the margin. The IRD signal also shows that iceberg calving occurred on the wPB during the Younger Dryas. Grain-size analysis of the core allowed for a reconstruction and interpretation of the palaeoenvironmental conditions during these IRD flux events and shows that BIIS-derived glaciers had a major impact on hydrodynamic conditions in the wPB. Subsequently, intensive scouring led to a major hiatus in the core during 27.3â 17.2 ka BP. These results are a useful addition to BIIS literature on this part of the shelf. Furthermore, it shows that bottom currents were influenced by (de)glacial events, an important finding when considering the presence of nearby current-dependant benthos

Monitoring changes in submarine canyon coral habitats - Leg 1 (MoCha_SCan)

This survey focused on the maiden deployment of a number of novel, ROV-adapted lander systems in the Porcupine Bank Canyon (PBC) coral habitats, NE Atlantic. Cold water corals (CWCs) flourish on the Irish-Atlantic margin between 600 and 100 m water depth, where they form a number of structural habitat types (coral reefs, mounds and gardens). Recent research shows that deep water habitats, including CWC habitats on the Irish margin, may be impacted by recent environmental change. The main objectives of this survey are: a) to deploy 8 new lander systems within a range of coral habitats throughout the PBC; b) to complete mapping coverage within the PBC; c) to sample the coral, sediment and ambient watermass around the lander sites and; d) to sample particulate organic matter around key coral habitats. Data recorded via landers from each habitat will allow to determine the controls on habitat variability. Furthermore, this data can be used as a baseline to which later deployments at this site will be used to compare against. Completed canyon coverage will feed into a number of multiscale mapping projects including the H2020 project â Integrated Assessment of Atlantic Marine Ecosystems in Space & Timeâ (iATLANTIC) and the SFI-, GSI- and MI-funded â Mapping, Modelling and Monitoring Key Processes and Controls on Cold Water Coral Habitats in Submarine Canyonsâ (MMMonKey_Pro) programme. Video data will be used to characterise key coral habitat within the canyon and subsequesntly, HD DEMâ s will be generated as a central dataset for the multiscale projects listed above

Deficient and null variants of SERPINA1 are proteotoxic in a Caenorhabditis elegans model of α1-antitrypsin deficiency

α1-antitrypsin deficiency (ATD) predisposes patients to both loss-of-function (emphysema) and gain-of-function (liver cirrhosis) phenotypes depending on the type of mutation. Although the Z mutation (ATZ) is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels) or null (<1% normal levels) alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype) induced by the aggregationprone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS), showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gainoffunction proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of different AT variants using a transgenic approach

The association of polypharmacy and high-risk drug classes with adverse health outcomes in the Scottish population with type 1 diabetes

This study was supported by funding from the Diabetes UK (17/0005627). The funder had no role in designing the study or in analysing and interpreting data and results.Aims/hypothesis The aim of this work was to map the number of prescribed drugs over age, sex and area-based socioeconomic deprivation, and to examine the association between the number of drugs and particular high-risk drug classes with adverse health outcomes among a national cohort of individuals with type 1 diabetes. Methods Utilising linked healthcare records from the population-based diabetes register of Scotland, we identified 28,245 individuals with a diagnosis of type 1 diabetes on 1 January 2017. For this population, we obtained information on health status, predominantly reflecting diabetes-related complications, and information on the total number of drugs and particular high-risk drug classes prescribed. We then studied the association of these baseline-level features with hospital admissions for falls, diabetic ketoacidosis (DKA), and hypoglycaemia or death within the subsequent year using multivariate Cox proportional hazards models. Results Not considering insulin and treatment for hypoglycaemia, the mean number of prescribed drugs was 4.00 (SD 4.35). The proportion of individuals being prescribed five or more drugs at baseline consistently increased with age (proportion [95% CI]: 0–19 years 2.04% [1.60, 2.49]; 40–49 years 28.50% [27.08, 29.93]; 80+ years 76.04% [67.73, 84.84]). Controlling for age, sex, area-based socioeconomic deprivation and health status, each additional drug at baseline was associated with an increase in the hazard for hospitalisation for falls, hypoglycaemia and death but not for DKA admissions (HR [95% CI]: falls 1.03 [1.01, 1.06]; DKA 1.01 [1.00, 1.03]; hypoglycaemia 1.05 [1.02, 1.07]; death 1.04 [1.02, 1.06]). We found a number of drug classes to be associated with an increased hazard of one or more of these adverse health outcomes, including antithrombotic/anticoagulant agents, corticosteroids, opioids, antiepileptics, antipsychotics, hypnotics and sedatives, and antidepressants. Conclusions Polypharmacy is common among the Scottish population with type 1 diabetes and is strongly patterned by sociodemographic factors. The number of prescribed drugs and the prescription of particular high-risk drug classes are strong markers of an increased risk of adverse health outcomes, including acute complications of diabetes.Publisher PDFPeer reviewe

Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with Type 1 Diabetes in Scotland:a retrospective nationwide observational study

Funding Information: This study was supported by funding from the Diabetes UK (17/0005627) and the Chief Scientist Office (Ref. ETM/47).Peer reviewedPublisher PD

Environmental forcing by submarine canyons: evidence between two closely situated cold-water coral mounds (Porcupine Bank Canyon and Western Porcupine Bank, NE Atlantic)

Within the Porcupine Bank Canyon (NE Atlantic), cold-water coral (CWC) mounds are mostly found clustered along the canyon lip, with individual disconnected mounds occurring nearby on the western Porcupine Bank. Remotely operated vehicle-mounted vibrocoring was utilized to acquire cores from both of these sites. This study is the first to employ this novel method when aiming to precisely sample two closely situated areas. Radiometric ages constrain the records from the early to mid-Holocene (9.1 to 5.6 ka BP). The cores were then subjected to 3D segmented computer tomography to capture mound formation stages. The cores were then further examined using stable isotopes and benthic foraminiferal assemblages, to constrain the paleoenvironmental variation that influenced CWC mound formation of each site. In total, mound aggradation rate in the Porcupine Bank Canyon and western Porcupine Bank was comparable to other Holocene CWC mounds situated off western Ireland. Results derived from multiproxy analysis, show that regional climatic shifts define the environmental conditions that allow positive coral mound formation. In addition, the aggradation rate of coral mounds is higher adjacent to the Porcupine Bank Canyon than on the western Porcupine Bank. Benthic foraminifera assemblages and planktic foraminiferal d13C reveal that higher quality organic matter is more readily available closer to the canyon lip. As such, we hypothesize that coral mound formation in the region is likely controlled by an interplay between enhanced shelf currents and the existence of the Eastern North Atlantic Water-Mediterranean Outflow Water-Transition Zone. The geomorphology of the canyon promotes upwelling of these water masses that are enriched in particles, including food and sediment supply. The higher availability of these particles support the development and succession of ecological hotspots along the canyon lip and adjacent areas of the seafloor. These observations provide a glimpse into the role that submarine canyons play in influencing macro and micro benthic fauna distributions and highlights the importance of their conservation