Filter Results
18915 results
A dataset consisting of 787 animals with high density SNP chip genotypes (346,774 SNP) and 939 animals with medium density SNP chip genotypes (33,828 SNP) from a total of 8 indigenous Swiss sheep breeds was analyzed to characterize population structures, quantify genomic inbreeding based on runs of homozygosity and identify selection signatures. In concordance with the recent known history of these breeds, the highest genetic diversity was observed in Engadine Red sheep and the lowest in Valais Blacknose sheep. Correlation between FPED and FROH was around 0.50 and thereby lower than that found in similar studies in cattle. Mean FROH estimates from medium density data and HD data were highly correlated (0.95). Signatures of selection and candidate gene analysis revealed that the most prominent signatures of selection were found in the proximity of genes associated with body size (NCAPG, LCORL, LAP3, SPP1, PLAG1, ALOX12, TP53), litter size (SPP1), milk production (ABCG2, SPP1), coat color (KIT, ASIP, TBX3) and horn status (RXFP2). For the Valais Blacknose sheep the private signatures in proximity of genes/QTL influencing body size, coat color and fatty acid composition were confirmed based on runs of homozygosity analysis. These private signatures underline the genetic uniqueness of the Valais Blacknose sheep breed. In conclusion we identified differences in the genetic make-up of Swiss sheep breeds and we present relevant candidate genes responsible for breed differentiation in locally adapted breeds.
Data Types:
  • Other
  • Dataset
Context: Childhood cancer survivors experience chronic health conditions that impact health related quality of life (HRQOL) and participation in optimal physical activity. Objective: The study aimed to determine independent effects of endocrine and metabolic disorders on HRQOL and physical activity. Design, Setting, and Patients: Retrospective cohort with longitudinal follow-up of survivors of childhood cancer enrolled in the North American Childhood Cancer Survivor Study. Main Outcome Measures: Medical Outcomes Short Form-36 estimated HRQOL while participation in physical activity was dichotomized as meeting or not meeting recommendations from the Center for Disease Control and Prevention. Log binomial regression evaluated the association of each endocrine/metabolic disorder with HRQOL scales and physical activity. Results: Of 7,287 survivors, median age 32 years (18-54) at their last follow-up survey, 4,884 (67%) reported one or more endocrine/metabolic disorders. Survivors with either disorder were significantly more likely to be male, older, received radiation treatment, and experience other chronic health conditions. After controlling for covariates, survivors with any endocrine/metabolic disorder were more likely to report poor physical function risk ratio ([RR] 1.25; 95% confidence interval [CI] 1.05-1.48), increased bodily pain (RR 1.27; CI 1.12-1.44), poor general health (RR 1.49; CI 1.32-1.68) and lower vitality (RR 1.21; CI 1.09-1.34) compared to survivors without. The likelihood of meeting recommended physical activity was lower among survivors with growth disorders (RR 0.90; CI=0.83-0.97), osteoporosis (RR 0.87; CI=0.76-0.99), and overweight/obesity (RR 0.92; CI 0.88-0.96). Conclusion: Endocrine and metabolic disorders are independently associated with poor HRQOL and sub-optimal physical activity among childhood cancer survivors.
Data Types:
  • Other
  • Dataset
Predictions of airborne allergenic pollen concentrations at fine spatial scales require information on source plant location and pollen production. Such data are lacking at the urban scale, largely because manually mapping allergenic pollen producing plants across large areas is infeasible. However, modest-sized field surveys paired with allometric equations, remote sensing, and habitat distribution models can predict where these plants occur and how much pollen they produce. In this study, common ragweed (Ambrosia artemisiifolia) was mapped in a field survey in Detroit, MI, USA. The relationship between ragweed presence and habitat-related variables derived from aerial imagery, LiDAR, and municipal data were used to create a habitat distribution model, which was then used to predict ragweed presence across the study area (392 km2). The relationship between inflorescence length and pollen production was used to predict pollen production in the city. Ragweed occurs in 1.7% of Detroit and total pollen production is 312 × 1012 pollen grains annually, but ragweed presence was highly heterogeneous across the city. Ragweed was predominantly found in in vacant lots (75%) and near demolished structures (48%), and had varying associations with land cover types (e.g., sparse vegetation, trees, pavement) detected by remote sensing. These findings also suggest several management strategies that could help reduce levels of allergenic pollen, including appropriate post-demolition management practices. Spatially-resolved predictions for pollen production will allow mechanistic modeling of airborne allergenic pollen and improved exposure estimates for use in epidemiological and other applications.
Data Types:
  • Other
  • Image
  • Dataset
  • File Set
Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TF) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the gene-regulatory activity of Pnt, an ETS transcriptional activator. Directly knocking down Pnt recapitulates aspects of the Aop/Foxo transcriptional programme and is sufficient to extend lifespan. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines expression of metabolic genes, and where Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are often conserved amongst ETS TFs, prompting us to examine whether other Drosophila ETS-coding genes may also affect ageing. We show that five out of eight Drosophila ETS TFs play a role in fly ageing, acting from a range of organs and cells including the intestine, adipose and neurons. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing and revealing that the roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species.
Data Types:
  • Other
  • Dataset
Background: Myotonic dystrophy type 1 (DM1) is caused by expansion of an unstable CTG repeat in the DMPK gene. The average number of repeats reported in routine diagnostics is broadly correlated with disease severity, but with limited predictive value and is not provided to patients in genetic counselling. OPTIMISTIC is a large international randomised trial of the efficacy of personalised cognitive behavioural therapy and graded exercise in DM1. Objective: Evaluate the genetic basis of symptomatic diversity in 250 adult, ambulant DM1 patients recruited through OPTIMISTIC. Methods: We used small pool PCR to correct age at sampling biases and estimate the progenitor allele CTG repeat length and somatic mutational dynamics, and AciI digests and repeat primed-PCR to test for the presence of variant repeats. Results: We confirmed disease severity is driven by progenitor allele length, is further modified by sex and that patients with faster expansion rate develop symptoms earlier than predicted. We quantified the critical role of variant repeats in delaying age at onset by approximately 13.2 years (95% CI = 5.7 to 20.7, two-tailed t-test, t = 3.7, p = 0.0019). Conclusions: Careful characterisation of the DMPK CTG repeat to define progenitor allele length and presence of variant repeats has increased utility in understanding clinical variability in a trial cohort and provides a genetic route for defining the basis of treatment response and stratification in DM1 trials. We suggest to re-evaluate the recommended diagnostic criteria for DM1 and the potential value of reporting more informative prognostic information to families.
Data Types:
  • Other
  • Dataset
Motivation: Quality of gene expression analyses using de novo assembled transcripts in species that experienced recent polyploidization remains unexplored. Results: Differential gene expression (DGE) analyses using putative genes inferred by Trinity, Corset and Grouper performed slightly differently across five plant species that experienced various poly-ploidy histories. In species that lack recent polyploidy events that occurred in the past several millions of years, DGE analyses using de novo assembled transcriptomes identified 54–82% of the differen-tially expressed genes recovered by mapping reads to the reference genes. However, in species that experienced more recent polyploidy events, the percentage decreased to 21–65%. Gene co-expression network analyses using de novo assemblies vs. mapping to the reference genes recov-ered the same module that significantly correlated with treatment in one species that lacks recent polyploidization.
Data Types:
  • Other
  • Dataset
  • File Set
Offspring produced by older parents often have reduced longevity, termed the Lansing Effect. Because adults usually have similar aged-mates, it is difficult to separate effects of maternal and paternal age, and environmental circumstances are also likely to influence offspring outcomes. The mechanisms underlying the Lansing Effect are poorly understood. Variation in telomere length and loss, particularly in early life, is linked to longevity in many vertebrates and therefore changes in offspring telomere dynamics could be very important in this context. We examined the effect of maternal age and environment on offspring telomere length in zebra finches. We kept mothers under either control (ad lib food) or more challenging (unpredictable food) circumstances and experimentally minimised paternal age and mate choice effects. Irrespective of the maternal environment, there was a substantial negative effect of maternal age on offspring telomere length, evident in longitudinal and cross sectional comparisons (average of 39% shorter). Furthermore, in young mothers, sons reared by challenged mothers had significantly shorter telomere lengths than sons reared by control mothers. This effect disappeared when the mothers were old, and was absent in daughters. These findings highlight the importance of telomere dynamics as inter-generational mediators of the evolutionary processes determining optimal age-specific reproductive effort and sex allocation.
Data Types:
  • Other
  • Dataset
Ocean acidification and ocean warming (OAW) are simultaneously occurring and could pose ecological challenges to marine life, particularly early life stages of fish that, although they are internal calcifiers, have poorly developed acid-base regulation. This study assessed the effect of projected OAW on key fitness traits (growth, development and swimming ability) in European sea bass (Dicentrarchus labrax) larvae and juveniles. Starting at 2 days post-hatch (dph), larvae were exposed to one of three levels of PCO₂ (650, 1150, 1700 µatm; pH 8.0, 7.8, 7.6) at either a cold (15°C) or warm (20°C) temperature. Growth rate, development stage and critical swimming speed (Ucrit) were repeatedly measured as sea bass grew from 0.6 to ~10.0 (cold) or ~14.0 (warm) cm body length. Exposure to different levels of PCO₂ had no significant effect on growth, development or Ucrit of larvae and juveniles. At the warmer temperature, larvae displayed faster growth and deeper bodies. Notochord flexion occurred at 0.8 and 1.2 cm and metamorphosis was completed at an age of ~45 and ~60 days post-hatch for sea bass in the warm and cold treatments, respectively. Swimming performance increased rapidly with larval development but better swimmers were observed in the cold treatment, reflecting a potential trade-off between fast grow and swimming ability. A comparison of the results of this and other studies on marine fish indicates that the effects of OAW on the growth, development and swimming ability of early life stages are species-specific and that generalizing the impacts of climate-driven warming or ocean acidification is not warranted.
Data Types:
  • Other
  • Dataset
1. Most studies on the evolution of migration focus on food, mates and/or climate as factors influencing these movements, whereas negative species interactions such as predators, parasites and pathogens are often ignored. Although infection and its associated costs clearly have the potential to influence migration, thoroughly studying these interactions is challenging without a solid theoretical framework from which to develop testable predictions in natural systems. 2. Here, we aim to understand when parasites favour the evolution of migration. 3. We develop a general model which enables us to explore a broad range of biological conditions and to capture population and infection dynamics over both ecological and evolutionary time scales. 4. We show that when migration evolves depends on whether the costs of migration and infection are paid in reduced fecundity or survival. Also important are the parasite transmission mode and spatiotemporal dynamics of infection and recovery (if it occurs). Finally, we find that partial migration (where only a fraction of the population migrates) can evolve but only when parasite transmission is density-dependent. 5. Our results highlight the critical, if overlooked, role of parasites in shaping long-distance movement patterns, and suggest that infection should be considered alongside more traditional drivers of migration in both empirical and theoretical studies.
Data Types:
  • Other
  • Dataset
  • File Set
Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling "high throughput" fluorescence mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.
Data Types:
  • Dataset
  • File Set
6