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Evolution of Embryonic Developmental Period in the Marine Bird Families Alcidae and Spheniscidae: Roles for Nutrition and Predation?

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Nutrition and predation have been considered two primary agents of selection important in theevolution of avian life history traits. The relative importance of these natural selective forces in the evolution of avianembryonic developmental period (EDP) remain poorly resolved, perhaps in part because research has tended to focuson a single, high taxonomic-level group of birds: Order Passeriformes. The marine bird families Alcidae (auks) andSpheniscidae (penguins) exhibit marked variation in EDP, as well as behavioural and ecological traits ultimately linkedto EDP. Therefore, auks and penguins provide a unique opportunity to assess the natural selective basis of variation in akey life-history trait at a low taxonomic-level. We used phylogenetic comparative methods to investigate the relativeimportance of behavioural and ecological factors related to nutrition and predation in the evolution of avian EDP.Results: Three behavioural and ecological variables related to nutrition and predation risk (i.e., clutch size, activitypattern, and nesting habits) were significant predictors of residual variation in auk and penguin EDP based on modelspredicting EDP from egg mass. Species with larger clutch sizes, diurnal activity patterns, and open nests hadsignificantly shorter EDPs. Further, EDP was found to be longer among birds which forage in distant offshore waters,relative to those that foraged in near shore waters, in line with our predictions, but not significantly so.Conclusion: Current debate has emphasized predation as the primary agent of selection driving avian life historydiversification. Our results suggest that both nutrition and predation have been important selective forces in theevolution of auk and penguin EDP, and highlight the importance of considering these questions at lower taxonomicscales. We suggest that further comparative studies on lower taxonomic-level groups will continue to constructivelyinform the debate on evolutionary determinants of avian EDP, as well as other life history parameters.

Document type: 
Article

Structural and Micro-Anatomical Changes in Vertebrae Associated with Idiopathic-Type Spinal Curvature in the Curveback Guppy Model

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population.

Document type: 
Article

A Major QTL Controls Susceptibility to Spinal Curvature in the Curveback Guppy

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2011
Abstract: 

Background: Understanding the genetic basis of heritable spinal curvature would benefit medicine andaquaculture. Heritable spinal curvature among otherwise healthy children (i.e. Idiopathic Scoliosis and Scheuermannkyphosis) accounts for more than 80% of all spinal curvatures and imposes a substantial healthcare cost throughbracing, hospitalizations, surgery, and chronic back pain. In aquaculture, the prevalence of heritable spinal curvaturecan reach as high as 80% of a stock, and thus imposes a substantial cost through production losses. The geneticbasis of heritable spinal curvature is unknown and so the objective of this work is to identify quantitative trait loci(QTL) affecting heritable spinal curvature in the curveback guppy. Prior work with curveback has demonstratedphenotypic parallels to human idiopathic-type scoliosis, suggesting shared biological pathways for the deformity.Results: A major effect QTL that acts in a recessive manner and accounts for curve susceptibility was detected inan initial mapping cross on LG 14. In a second cross, we confirmed this susceptibility locus and fine mapped it toa 5 cM region that explains 82.6% of the total phenotypic variance.Conclusions: We identify a major QTL that controls susceptibility to curvature. This locus contains over 100 genes,including MTNR1B, a candidate gene for human idiopathic scoliosis. The identification of genes associated withheritable spinal curvature in the curveback guppy has the potential to elucidate the biological basis of spinalcurvature among humans and economically important teleosts.

Document type: 
Article

Functional Genomics of Human Bronchial Epithelial Cells Directly Interacting with Conidia of Aspergillus Fumigatus

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Aspergillus fumigatus (A. fumigatus) is a ubiquitous fungus which reproduces asexually by releasingabundant airborne conidia (spores), which are easily respirable. In allergic and immunocompromised individuals A.fumigatus can cause a wide spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma andinvasive aspergillosis. Previous studies have demonstrated that A. fumigatus conidia are internalized by macrophagesand lung epithelial cells; however the exact transcriptional responses of airway epithelial cells to conidia are currentlyunknown. Thus, the aim of this study was to determine the transcriptomic response of the human bronchial epithelialcell line (16HBE14o-) following interaction with A. fumigatus conidia. We used fluorescence-activated cell sorting (FACS)to separate 16HBE14o- cells having bound and/or internalized A. fumigatus conidia expressing green fluorescentprotein from cells without spores. Total RNA was then isolated and the transcriptome of 16HBE14o- cells was evaluatedusing Agilent Whole Human Genome microarrays.Results: Immunofluorescent staining and nystatin protection assays demonstrated that 16HBE14o- cells internalized30-50% of bound conidia within six hrs of co-incubation. After FAC-sorting of the same cell culture to separate cellsassociated with conidia from those without conidia, genome-wide analysis revealed a set of 889 genes showingdifferential expression in cells with conidia. Specifically, these 16HBE14o- cells had increased levels of transcripts fromgenes associated with repair and inflammatory processes (e.g., matrix metalloproteinases, chemokines, andglutathione S-transferase). In addition, the differentially expressed genes were significantly enriched for Gene Ontologyterms including: chromatin assembly, G-protein-coupled receptor binding, chemokine activity, and glutathionemetabolic process (up-regulated); cell cycle phase, mitosis, and intracellular organelle (down-regulated).Conclusions: We demonstrate a methodology using FACs for analyzing the transcriptome of infected and uninfectedcells from the same cell population that will provide a framework for future characterization of the specific interactionsbetween pathogens such as A. fumigatus with human cells derived from individuals with or without underlying diseasesusceptibility.

Document type: 
Article

A Glycine Zipper Motif Mediates the Formation of Toxic Beta-Amyloid Oligomers in Vitro and in Vivo

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2011
Abstract: 

Background: The b-amyloid peptide (Ab) contains a Gly-XXX-Gly-XXX-Gly motif in its C-terminal region that hasbeen proposed to form a “glycine zipper” that drives the formation of toxic Ab oligomers. We have tested thishypothesis by examining the toxicity of Ab variants containing substitutions in this motif using a neuronal cell line,primary neurons, and a transgenic C. elegans model.Results: We found that a Gly37Leu substitution dramatically reduced Ab toxicity in all models tested, as measuredby cell dysfunction, cell death, synaptic alteration, or tau phosphorylation. We also demonstrated in multiplemodels that Ab Gly37Leu is actually anti-toxic, thereby supporting the hypothesis that interference with glycinezipper formation blocks assembly of toxic Ab oligomers. To test this model rigorously, we engineered second sitesubstitutions in Ab predicted by the glycine zipper model to compensate for the Gly37Leu substitution andexpressed these in C. elegans. We show that these second site substitutions restore in vivo Abtoxicity, furthersupporting the glycine zipper model.Conclusions: Our structure/function studies support the view that the glycine zipper motif present in the Cterminalportion of Ab plays an important role in the formation of toxic Ab oligomers. Compounds designed tointerfere specifically with formation of the glycine zipper could have therapeutic potential.

Document type: 
Article

Association Testing Of Copy Number Variants in Schizophrenia and Autism Spectrum Disorders

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

Background: Autism spectrum disorders and schizophrenia have been associated with an overlapping set of copynumber variant loci, but the nature and degree of overlap in copy number variants (deletions compared toduplications) between these two disorders remains unclear.Methods: We systematically evaluated three lines of evidence: (1) the statistical bases for associations of autismspectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies;(2) data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially amongchildren, and (3) data on the extent to which the CNVs were associated with intellectual disability anddevelopmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs inautism by pooling data from seven case control studies.Results: Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clearstatistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors forschizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as riskfactors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal fortests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but werenot statistically associated with autism, a notable number of children with the CNVs have been diagnosed withautism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability anddevelopmental, speech, or language delays.Conclusions: These findings suggest that although CNV loci notably overlap between autism and schizophrenia,the degree of strongly statistically supported overlap in specific CNVs at these loci remains limited. These analysesalso suggest that relatively severe premorbidity to CNV-associated schizophrenia in children may sometimes bediagnosed as autism spectrum disorder.

Document type: 
Article