A stochastic movement simulator improves estimates of landscape connectivity.

Conservation actions often focus on restoration or creation of natural areas designed to facilitate the movements of organisms among populations. To be efficient, these actions need to be based on reliable estimates or predictions of landscape connectivity. While circuit theory and least-cost paths (LCPs) are increasingly being used to estimate connectivity, these methods also have proven limitations. We compared their performance in predicting genetic connectivity with that of an alternative approach based on a simple, individual-based "stochastic movement simulator" (SMS). SMS predicts dispersal of organisms using the same landscape representation as LCPs and circuit theory-based estimates (i.e., a cost surface), while relaxing key LCP assumptions, namely individual omniscience of the landscape (by incorporating perceptual range) and the optimality of individual movements (by including stochasticity in simulated movements). The performance of the three estimators was assessed by the degree to which they correlated with genetic estimates of connectivity in two species with contrasting movement abilities (Cabanis's Greenbul, an Afrotropical forest bird species, and natterjack toad, an amphibian restricted to European sandy and heathland areas). For both species, the correlation between dispersal model and genetic data was substantially higher when SMS was used. Importantly, the results also demonstrate that the improvement gained by using SMS is robust both to variation in spatial resolution of the landscape and to uncertainty in the perceptual range model parameter. Integration of this individual-based approach with other developing methods in the field of connectivity research, such as graph theory, can yield rapid progress towards more robust connectivity indices and more effective recommendations for land management.

Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10.

Neural tube defects (NTDs) are the second most common birth defects (1 in 1000 live births) in the world. Periconceptional maternal folate supplementation reduces NTD risk by 50-70%; however, studies of folate related and other developmental genes in humans have failed to definitively identify a major causal gene for NTD. The aetiology of NTDs remains unknown and both genetic and environmental factors are implicated. We present findings from a microsatellite based screen of 44 multiplex pedigrees ascertained through the NTD Collaborative Group. For the linkage analysis, we defined our phenotype narrowly by considering individuals with a lumbosacral level myelomeningocele as affected, then we expanded the phenotype to include all types of NTDs. Two point parametric analyses were performed using VITESSE and HOMOG. Multipoint parametric and nonparametric analyses were performed using ALLEGRO. Initial results identified chromosomes 7 and 10, both with maximum parametric multipoint lod scores (Mlod) >2.0. Chromosome 7 produced the highest score in the 24 cM interval between D7S3056 and D7S3051 (parametric Mlod 2.45; nonparametric Mlod 1.89). Further investigation demonstrated that results on chromosome 7 were being primarily driven by a single large pedigree (parametric Mlod 2.40). When this family was removed from analysis, chromosome 10 was the most interesting region, with a peak Mlod of 2.25 at D10S1731. Based on mouse human synteny, two candidate genes (Meox2, Twist1) were identified on chromosome 7. A review of public databases revealed three biologically plausible candidates (FGFR2, GFRA1, Pax2) on chromosome 10. The results from this screen provide valuable positional data for prioritisation of candidate gene assessment in future studies of NTDs.

Three-dimensional quantification of regional left-ventricular dyssynchrony by magnetic resonance imaging.

Heart failure accounts for over five million patients in the United States alone. Many of them present dyssynchronous left ventricular (LV) contraction, whose treatment by cardiac resynchronization therapy (CRT) is until now guided by electrocardiographic analysis. One third of the selected patients, however, does not respond to the therapy. Aiming at improving the response rate, recent studies showed the importance of left bundle branch block (LBBB) configurations. Therefore, in order to detect motion patterns that relate to LBBB, this paper presents a novel method for three-dimensional quantification of regional LV mechanical dyssynchrony. LV wall-motion analysis is performed on magnetic resonance imaging (MRI) cines segmented by commercial software. Mutual delays between endocardial wall motion in different LV regions are estimated by cross correlation followed by phase difference analysis in frequency domain, achieving unlimited time resolution. Rather than focusing on the systolic phase, the full cardiac cycle is used to estimate the contraction timing. The method was successfully validated against MRI tagging in five dogs before and after LBBB induction. Preliminary validation in humans with 10 LBBB patients and 7 healthy subjects showed the method feasibility and reproducibility, with sensitivity and specificity in LBBB detection equal to 95.1% and 99.4%, respectively.

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis.

Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

Genetic studies in neural tube defects. NTD Collaborative Group.

Neural tube defects (NTD) are one of the most common birth defects and are caused by both environmental and genetic factors. The approach to identifying the genes predisposing to NTD, through linkage analysis and candidate gene analysis, is reviewed along with characteristics of a large, nationally ascertained cohort of families. Results from specific assessments of p53, PAX3 and MTHFR failed to suggest that these genes play a major role in NTD development in these families. Advances in genetic laboratory and statistical techniques have made this a prime opportunity for investigation into the causes of complex disorders, such as NTD. However, traditional approaches may prove to be challenging due to the difficulty of ascertaining samplable multiplex families.