Modelling disease spread in real landscapes: Squirrelpox spread in southern Scotland as a case study

PublishedJournal ArticleThis is the author accepted manuscript. The final version is available from Associazione Teriologica Italiana via the DOI in this record.© 2016 Associazione Teriologica Italiana.There is increasing evidence that invading species can gain an advantage over native species by introducing novel disease. A clear understanding of the role of disease in the expansion of introduced and invading species is therefore essential for the conservation of native species. In this study we focus on the case study system of the UK red and grey squirrel system in which disease-mediated competition has facilitated the replacement of red squirrels by greys. We modify a deterministic model of the squirrel system in which the competition and infection dynamics are well understood to produce a stochastic model which includes a realistic representation of the heterogeneous habitat in Southern Scotland. The model is used to examine the potential spread of infection (squirrelpox virus) through the squirrel system and to examine the impact of conservation measures that control grey squirrel numbers in an attempt to contain disease spread. The results have direct implications for conservation management and we discuss how they have helped shape current and future policy for red squirrel conservation in Scotland. The methods in this study can be readily adapted to represent different systems and since the stochastic population and disease dynamics are underpinned by classical deterministic modelling frameworks the results are applicable in general.AW and PL were supported in part by SNH. AW, MB and PL were supported in part by a NERC Innovations grant NE/M021319/1

Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis

Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9-deficient mice are born with complex cardiovascular malformations that affect the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system

The essential role of Cited2, a negative regulator for HIF-1α, in heart development and neurulation

Cited2 is a cAMP-responsive element-binding protein (CBP)/p300 interacting transcriptional modulator and a proposed negative regulator for hypoxia-inducible factor (HIF)-1α through its competitive binding with HIF-1α to CBP/p300. Disruption of the gene encoding Cited2 is embryonic lethal because of defects in the development of heart and neural tube. Morphological and Doppler echocardiographic analyses of Cited2(−/−) embryos reveal severe cardiovascular abnormalities, including pulmonic arterial stenosis and ventricular septal defects accompanied by high peak outflow velocities, features of the human congenital cardiac defect termed tetralogy of Fallot. The mRNA levels of several HIF-1α-responsive genes, such as vascular endothelial growth factor (VEGF), Glut1, and phosphoglycerate kinase 1, increased in the Cited2(−/−) hearts. The increase of VEGF levels is significant, because defects in the Cited2(−/−) embryos closely resemble the major defects observed in the VEGF transgenic embryos. Finally, compared with wild-type, cultured fibroblasts from Cited2(−/−) embryos demonstrate an enhanced expression of HIF-1α-responsive genes under hypoxic conditions. These observations suggest that functional loss of Cited2 is responsible for defects in heart and neural tube development, in part because of the modulation of HIF-1 transcriptional activities in the absence of Cited2. These findings demonstrate that Cited2 is an indispensable regulatory gene during prenatal development

Regulation and Function of Cardiac Neural Crest Cells ☆

The cardiac neural crest cells (NCCs), also known as circumpharyngeal NCCs, make an essential contribution to cardiovascular development in vertebrates. These cells delaminate from the developing neural tube to migrate into the pharyngeal arches (PAs) of the embryo, where they induce the remodeling of the pharyngeal arch arteries (PAAs) into the great vessels that distribute blood from the heart into the lung and systemic vasculature. A subset of cardiac NCCs continues to migrate into the cardiac outflow tract (OFT) to induce its septation into the arterial and pulmonary trunks that connect to the remodeled PAAs. Owing to their essential role in cardiovascular development, cardiac NCC defects cause congenital heart disease. In this article, we describe current knowledge of the molecular and cellular mechanisms that underlie cardiac NCC function