Receptors, sparks and waves in a fire-diffuse-fire framework for calcium release

Calcium ions are an important second messenger in living cells. Indeed calcium signals in the form of waves have been the subject of much recent experimental interest. It is now well established that these waves are composed of elementary stochastic release events (calcium puffs or sparks) from spatially localised calcium stores. The aim of this paper is to analyse how the stochastic nature of individual receptors within these stores combines to create stochastic behaviour on long timescales that may ultimately lead to waves of activity in a spatially extended cell model. Techniques from asymptotic analysis and stochastic phase-plane analysis are used to show that a large cluster of receptor channels leads to a release probability with a sigmoidal dependence on calcium density. This release probability is incorporated into a computationally inexpensive model of calcium release based upon a stochastic generalization of the Fire-Diffuse-Fire (FDF) threshold model. Numerical simulations of the model in one and two dimensions (with stores arranged on both regular and disordered lattices) illustrate that stochastic calcium release leads to the spontaneous production of calcium sparks that may merge to form saltatory waves. Illustrations of spreading circular waves, spirals and more irregular waves are presented. Furthermore, receptor noise is shown to generate a form of array enhanced coherence resonance whereby all calcium stores release periodically and simultaneously

Vermiculture: a potential role in the management of broiler litter in Australia?

With increasing human population, the demand for quality animal meat products is increasing, and intensive chicken meat (broiler) production is contributing to some of this demand. A major output from commercial farms is broiler litter (litter) which has relatively high plant nutrient concentrations compared to other animal manures. This makes litter valuable for plant production and hence it is mainly utilised and disposed of on land. However, the suitability of land within cost effective distances from growers is becoming an increasing problem worldwide, with reduced suitability due to potential environmental and bio-security risks. Therefore it is important to develop disposal mechanisms that can provide the industry with an alternative to the direct land application of litter. The present research was undertaken to gain an understanding of the potential role vermiculture could have in the management of litter in Australia. Vermiculture has the potential to produce both humic rich vermi-compost (vermicast) and meatmeal (vermimeal) from litter. Traditionally vermiculture has primarily been adopted to produce vermicast, a recognised valuable organic fertiliser. However, the production and processing of earthworms into vermimeal is becoming an increasingly viable component. Both of these outputs potentially render vermiculture a value-adding opportunity for the Australian poultry industry, whilst providing an alternative disposal option for litter. That being said vermiculturalists have tended to avoid nutrient rich or 'hot' wastes due the system becoming unstable, resulting in earthworm mortality. Uniquely, this research focused on using fresh litter as the sole food source for earthworms ('Eisenia andrei') in a batch flow system

Genetic parameters for Lamb Autopsy Traits

Heritabilities and genetic correlations were estimated between individual and composite autopsy traits for lambs autopsied in the Australian Sheep Cooperative Research Centre information nucleus flocks between 2008 and 2011 (n=3,224). In addition, correlations were estimated between autopsy categories and the production parameters, Greasy-fleece weight and Yearling weight and the potential survival indicator traits: Lamb ease, Thorax circumference and Crown-rump length. All autopsy trait heritability estimates were low (range 0.01 - 0.04). For all traits a higher proportion of the variance was partitioned into the maternal permanent environment when compared to the direct effects (range 0.01 - 0.12) suggesting that selection based on lamb autopsy results would impart little advantage over the lamb survival trait itself in improving lamb survival. Genetic correlations between Lamb ease and all autopsy traits were positive indicating that birth trauma is related to all causes of lamb deaths and that Lamb ease may be a useful selection criterion in seed-stock flocks to reduce overall mortality. There were also positive genetic correlations between Thorax circumference after adjusting for birth weight and 2 classes of dystocia as well as a positive correlation between Thorax circumference and incidences of Starvation-mismothering implying that Thorax circumference may be a useful indirect field measurement to reduce death from these causes. Of concern was the antagonistic genetic correlations estimated between Greasy-fleece weight and a composite trait of All Dystocia classes plus Starvation-mismothering (0.27 ± 0.15) implying that selection for increased fleece weight could be having a detrimental effect on overall lamb survival

Prospects for the future of pink salmon in three oceans: From the native Pacific to the novel Arctic and Atlantic

While populations of other migratory salmonids suffer in the Anthropocene, pink salmon (Oncorhynchus gorbusca Salmonidae) are thriving, and their distribution is expanding both within their natural range and in the Atlantic and Arctic following introduction of the species to the White Sea in the 1950s. Pink salmon are now rapidly spreading in Europe and even across the ocean to North America. Large numbers of pink salmon breed in Norwegian rivers and small numbers of individuals have been captured throughout the North Atlantic since 2017. Although little is known about the biology and ecology of the pink salmon in its novel distribution, the impacts of the species' introduction are potentially highly significant for native species and watershed productivity. Contrasts between pink salmon in the native and extended ranges will be key to navigating management strategies for Atlantic nations where the pink salmon is entrenching itself among the fish fauna, posing potential threats to native fish communities. One key conclusion of this paper is that the species' heritable traits are rapidly selected and drive local adaptation and evolution. Within the Atlantic region, this may facilitate further establishment and spread. The invasion of pink salmon in the Atlantic basin is ultimately a massive ecological experiment and one of the first examples of a major faunal change in the North Atlantic Ocean that is already undergoing rapid changes due to other anthropogenic stressors. New research is urgently needed to understand the role and potential future impacts of pink salmon in Atlantic ecosystems. Atlantification, biological invasions, climate adaptation, Pacific Ocean, regime shiftpublishedVersio

PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or \u27scaffold\u27) of haplotypes across each chromosome. We then phase the sequence data \u27onto\u27 this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models

The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-pharmaceutical interventions (e.g. lockdowns) to control the epidemic, making it difficult to estimate the relative transmissibility of variants. In this paper, we model the spatial spread of these variants in England using a meta-population agent-based model which correctly characterizes the regional variation in cases and distribution of variants. As a test of robustness, we additionally estimated the relative transmissibility of multiple variants using a statistical model based on the renewal equation, which simultaneously estimates the effective reproduction number R. Relative to earlier variants, the transmissibility of B.1.177 is estimated to have increased by 1.14 (1.12-1.16) and that of Alpha by 1.71 (1.65-1.77). The vaccination programme starting in December 2020 is also modelled. Counterfactual simulations demonstrate that the vaccination programme was essential for reopening in March 2021, and that if the January lockdown had started one month earlier, up to 30 k (24 k-38 k) deaths could have been prevented. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'

Using population admixture to help complete maps of the human genome

Tens of millions of base pairs of euchromatic human genome sequence, including many protein-coding genes, have no known location in the human genome. We describe an approach for localizing the human genome's missing pieces by utilizing the patterns of genome sequence variation created by population admixture. We mapped the locations of 70 scaffolds spanning four million base pairs of the human genome's unplaced euchromatic sequence, including more than a dozen protein-coding genes, and identified eight large novel inter-chromosomal segmental duplications. We find that most of these sequences are hidden in the genome's heterochromatin, particularly its pericentromeric regions. Many cryptic, pericentromeric genes are expressed in RNA and have been maintained intact for millions of years while their expression patterns diverged from those of paralogous genes elsewhere in the genome. We describe how knowledge of the locations of these sequences can inform disease association and genome biology studies