Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

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A Stratabound Zinc-Lead Deposit in Meguma Group Metasediments at Eastville, Nova Scotia

The Eastville zinc-lead deposit, discovered by soil sampling in 1976, occurs near the contact of the Goldenvllle and Halifax Formations, the two divisions of the Cambro-Ordovician Meguma Group. The stratigraphic succession in the contact zone comprises an assemblage of quartz metawacke, calcareous quartz metawacke and slate. Quartz metawacke is predominant in the Goldenvllle Formation and slate is the dominant lithology in the overlying Halifax Formation. These rocks are interpreted as the middle to outer fan and basin plain deposits of a submarine fan complex. Pyrrhotite and pyrite, the predominant Bulphide minerals in all lithologles in the contact zone, were deposited by reduction of iron in the sediments, independent of the mineralizing process. Sphalerite and galena occur in rocks over a 10 km strike length in elongate blebs, 2 to 5 mm long, distributed parallel to bedding and in cross-cutting fractures. The deposit is stratabound and generally occurs in black slate beds near the Goldenvllle-Halifax contact. Geochemical analyses of the rocks have indicated a concentration of Mn in the calcareous quartzite member, the upper unit of the Goldenville Formation. A relationship between the Mn enrichment and the abundance of sphalerite and galena in the section has not been established. The sulphide mineralogy, laterally continuous stratigraphy and lack of metal zonation and underlying feeder structures indicate the sphalerite and galena were syngenetically deposited from metal-rich brines at a site distant from where the brines entered the basin of deposition- RÉSUMÉ Le dépôt de plomb at de zinc de Eastville, qui a été découvert par des prises d'échantillons de terre en 1976, est situé pré du contact des formations Goldenville et Halifax (les deux unités du groupe Meguma). La succession stratigraphique dans la zone de contact est constitué d'un assemblage de métagrauwacke de quartz, de métagrauvacke calcaire de quartz, et d'ardoise. Le métagrauwacke de quartz est prédominant dans la formation Goldenville et l'ardoise est la lithologie dominate de la formation de Halifax, qui est superposé sur la première. Ces roches sont expllquées comme étant le cône central ou extérieur et des dépôts de la plaine d'un basin d'un compiexe de cône. La pyrrhotite et la pyrite, les minéraux sulfides principalis dans toutes les lithologles de la zone de contact, ont été déposés par une réduction de fer dans les sédiments, indépendement des processus de minéralisation. La sphalérite et la galène se trouvent dans les roches sur une longueur de 10 kilomètres le long de la couche en temps que soufflures de 2 à 5 mm de longueur, réparties paralèllement à la couche et dans les fractures à trafers banc. Le dépôt est limite aux strates et se crouve en général dans de l'ardoise noire près du contact Goldenville-Halifax. Des analyses géochimiques des roches ont indiqué une concentration de Mn dans les quartzites calcaires, l'unité la plus é1evé de la formation Goldenville. Un rapport entre l'enrichiasement en Mn et l'abondance de la sphalerite et de la galène dans la section, n'a pas été établie. La minéralogie des sulfides, la stratigraphie laterale continue, et le manque de zonation de métaux et de structures de conduite d'alimentation, indique que la sphalerite et la galène ont été déposées sygénétiquement à partir de saumures riches en métaux dans un site éloigné de l'endroit où les saumures pénétrent le basin de dépôt. [Traduit par le journal

Smoothing in linear multicompartment biological processes subject to stochastic input

Many physical and biological systems rely on the progression of material through multiple independent stages. In viral replication, for example, virions enter a cell to undergo a complex process comprising several disparate stages before the eventual accumulation and release of replicated virions. While such systems may have some control over the internal dynamics that make up this progression, a challenge for many is to regulate behaviour under what are often highly variable external environments acting as system inputs. In this work, we study a simple analogue of this problem through a linear multicompartment model subject to a stochastic input in the form of a mean-reverting Ornstein-Uhlenbeck process, a type of Gaussian process. By expressing the system as a multidimensional Gaussian process, we derive several closed-form analytical results relating to the covariances and autocorrelations of the system, quantifying the smoothing effect discrete compartments afford multicompartment systems. Semi-analytical results demonstrate that feedback and feedforward loops can enhance system robustness, and simulation results probe the intractable problem of the first passage time distribution, which has specific relevance to eventual cell lysis in the viral replication cycle. Finally, we demonstrate that the smoothing seen in the process is a consequence of the discreteness of the system, and does not manifest in an equivalent continuum limit description. While we make progress through analysis of a simple linear problem, many of our insights are applicable more generally, and our work enables future analysis into multicompartment processes subject to stochastic inputs

Smoothing in linear multicompartment biological processes subject to stochastic input

Many physical and biological systems rely on the progression of material through multiple independent stages. In viral replication, for example, virions enter a cell to undergo a complex process comprising several disparate stages before the eventual accumulation and release of replicated virions. While such systems may have some control over the internal dynamics that make up this progression, a challenge for many is to regulate behaviour under what are often highly variable external environments acting as system inputs. In this work, we study a simple analogue of this problem through a linear multicompartment model subject to a stochastic input in the form of a mean-reverting Ornstein-Uhlenbeck process, a type of Gaussian process. By expressing the system as a multidimensional Gaussian process, we derive several closed-form analytical results relating to the covariances and autocorrelations of the system, quantifying the smoothing effect discrete compartments afford multicompartment systems. Semi-analytical results demonstrate that feedback and feedforward loops can enhance system robustness, and simulation results probe the intractable problem of the first passage time distribution, which has specific relevance to eventual cell lysis in the viral replication cycle. Finally, we demonstrate that the smoothing seen in the process is a consequence of the discreteness of the system, and does not manifest in system with continuous transport. While we make progress through analysis of a simple linear problem, many of our insights are applicable more generally, and our work enables future analysis into multicompartment processes subject to stochastic inputs.Comment: 6 figures, includes supplementary documen

Mathematical modelling of the interaction between cancer cells and an oncolytic virus: insights into the effects of treatment protocols

Oncolytic virotherapy is an experimental cancer treatment that uses genetically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. While PEG modification appeared to improve plasma retention and initial infectivity it also increased the virus particle arrival time. We derive a mathematical model that describes the interaction between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy is explored.Comment: 15 pages, 6 figure

High lability of sexual system over 250 million years of evolution in morphologically conservative tadpole shrimps

Background Sexual system is a key factor affecting the genetic diversity, population structure, genome structure and the evolutionary potential of species. The sexual system androdioecy – where males and hermaphrodites coexist in populations – is extremely rare, yet is found in three crustacean groups, barnacles, a genus of clam shrimps Eulimnadia, and in the order Notostraca, the tadpole shrimps. In the ancient crustacean order Notostraca, high morphological conservatism contrasts with a wide diversity of sexual systems, including androdioecy. An understanding of the evolution of sexual systems in this group has been hampered by poor phylogenetic resolution and confounded by the widespread occurrence of cryptic species. Here we use a multigene supermatrix for 30 taxa to produce a comprehensive phylogenetic reconstruction of Notostraca. Based on this phylogenetic reconstruction we use character mapping techniques to investigate the evolution of sexual systems. We also tested the hypothesis that reproductive assurance has driven the evolution of androdioecy in Notostraca. Results Character mapping analysis showed that sexual system is an extremely flexible trait within Notostraca, with repeated shifts between gonochorism and androdioecy, the latter having evolved a minimum of five times. In agreement with the reproductive assurance hypothesis androdioecious notostracans are found at significantly higher latitudes than gonochoric ones indicating that post glacial re-colonisation may have selected for the higher colonisation ability conferred by androdioecy. Conclusions In contrast to their conserved morphology, sexual system in Notostraca is highly labile and the rare reproductive mode androdioecy has evolved repeatedly within the order. Furthermore, we conclude that this lability of sexual system has been maintained for at least 250 million years and may have contributed to the long term evolutionary persistence of Notostraca. Our results further our understanding of the evolution of androdioecy and indicate that reproductive assurance is a recurrent theme involved in the evolution of this sexual system

Efficient inference and identifiability analysis for differential equation models with random parameters

Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.Comment: Minor changes to text. Additional results in supplementary material. Additional statistics regarding results given in main and supplementary materia

Binge-watching: Video-on-demand, quality TV and mainstreaming fandom

This article explores the concept of the binge as viewing protocol associated with fan practices, industry practice and linked to ‘cult’ and ‘quality’ serialised content. Viewing binge-watching as an intersection of discourses of industry, audience and text, the concept is analysed here as shaped by a range of issues that dominate the contemporary media landscape. In this, factors like technological developments, fan discourses and practices being adopted as ‘mainstream’ media practice, changes in the discursive construction of ‘television’ and an emerging Video-on-Demand industry contribute to the construction of binge-watching as deliberate, self-scheduled alternative to ‘watching TV’