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101.
Dustin Nash Cammon B. Arrington Brett J. Kennedy Mark Yandell Wilfred Wu Wenying Zhang Stephanie Ware Lynn B. Jorde Peter J. Gruber H. Joseph Yost Neil E. Bowles Steven B. Bleyl 《PloS one》2015,10(6)
Most isolated congenital heart defects are thought to be sporadic and are often ascribed to multifactorial mechanisms with poorly understood genetics. Total Anomalous Pulmonary Venous Return (TAPVR) occurs in 1 in 15,000 live-born infants and occurs either in isolation or as part of a syndrome involving aberrant left-right development. Previously, we reported causative links between TAVPR and the PDGFRA gene. TAPVR has also been linked to the ANKRD1/CARP genes. However, these genes only explain a small fraction of the heritability of the condition. By examination of phased single nucleotide polymorphism genotype data from 5 distantly related TAPVR patients we identified a single 25 cM shared, Identical by Descent genomic segment on the short arm of chromosome 12 shared by 3 of the patients and their obligate-carrier parents. Whole genome sequence (WGS) analysis identified a non-synonymous variant within the shared segment in the retinol binding protein 5 (RBP5) gene. The RBP5 variant is predicted to be deleterious and is overrepresented in the TAPVR population. Gene expression and functional analysis of the zebrafish orthologue, rbp7, supports the notion that RBP5 is a TAPVR susceptibility gene. Additional sequence analysis also uncovered deleterious variants in genes associated with retinoic acid signaling, including NODAL and retinol dehydrogenase 10. These data indicate that genetic variation in the retinoic acid signaling pathway confers, in part, susceptibility to TAPVR. 相似文献
102.
Assessing biodiversity and endemism using phylogenetic methods across multiple taxonomic groups
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Carlos E. González‐Orozco Brent D. Mishler Joseph T. Miller Shawn W. Laffan Nunzio Knerr Peter Unmack Arthur Georges Andrew H. Thornhill Dan F. Rosauer Bernd Gruber 《Ecology and evolution》2015,5(22):5177-5192
Identifying geographical areas with the greatest representation of the tree of life is an important goal for the management and conservation of biodiversity. While there are methods available for using a single phylogenetic tree to assess spatial patterns of biodiversity, there has been limited exploration of how separate phylogenies from multiple taxonomic groups can be used jointly to map diversity and endemism. Here, we demonstrate how to apply different phylogenetic approaches to assess biodiversity across multiple taxonomic groups. We map spatial patterns of phylogenetic diversity/endemism to identify concordant areas with the greatest representation of biodiversity across multiple taxa and demonstrate the approach by applying it to the Murray–Darling basin region of southeastern Australia. The areas with significant centers of phylogenetic diversity and endemism were distributed differently for the five taxonomic groups studied (plant genera, fish, tree frogs, acacias, and eucalypts); no strong shared patterns across all five groups emerged. However, congruence was apparent between some groups in some parts of the basin. The northern region of the basin emerges from the analysis as a priority area for future conservation initiatives focused on eucalypts and tree frogs. The southern region is particularly important for conservation of the evolutionary heritage of plants and fishes. 相似文献
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To establish the mouse mutant, hairless (Hr), as a useful model for future analyses of target-ending interactions, we assessed the cutaneous innervation in the whisker pad after loss of primary hair targets. Postnatal (P) development of fur in Hr begins similarly to that of "normal" Swiss Webster (SW) mice. Around P10, hairs are shed and the follicles rendered permanently incompetent. Hair loss progresses rostrocaudally until the entire skin is denuded. Substantial alterations in the distribution and density of sensory and autonomic endings in the mystacial pad vibrissal and intervibrissal fur innervation were discovered. Pilo-neural complexes innervating fur hairs were dismantled in Hr. Epidermal innervation in SW was rich; only a few endings expressed growth-associated protein-43?kdal (GAP), suggesting limited changes in axonal elongation. Innervation in Hr formed a dense layer passing upward through the thickened epidermis, with substantial increases among all types of endings. Vibrissal follicle-sinus complexes were also hyperinnervated. Endings in Hr vibrissae and fur were strongly GAP-positive, suggesting reorganization of innervation. Dermal and vascular autonomic innervation in both strains co-localized tyrosine hydroxylase and neuropeptide Y, but only in Hr did neuropeptide Y co-localize calcitonin gene-related peptide (CGRP) and express GAP immunolabeling. Stereological quantitation of trigeminal ganglia revealed no differences in neuron number between Hr and SW, although there were small increases in cell volume in Hr trigeminal ganglion cells. These results suggested that a form of collateral sprouting was active in Hr mystacial pads, not in response to local injury, but as a result of loss of primary target tissues. 相似文献
105.
A concrete example of the collaborative double-robust targeted likelihood estimator (C-TMLE) introduced in a companion article in this issue is presented, and applied to the estimation of causal effects and variable importance parameters in genomic data. The focus is on non-parametric estimation in a point treatment data structure. Simulations illustrate the performance of C-TMLE relative to current competitors such as the augmented inverse probability of treatment weighted estimator that relies on an external non-collaborative estimator of the treatment mechanism, and inefficient estimation procedures including propensity score matching and standard inverse probability of treatment weighting. C-TMLE is also applied to the estimation of the covariate-adjusted marginal effect of individual HIV mutations on resistance to the anti-retroviral drug lopinavir. The influence curve of the C-TMLE is used to establish asymptotically valid statistical inference. The list of mutations found to have a statistically significant association with resistance is in excellent agreement with mutation scores provided by the Stanford HIVdb mutation scores database. 相似文献
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108.
Yubo Sun David R Mauerhan Patrick R Honeycutt Jeffrey S Kneisl H James Norton Natalia Zinchenko Edward N HanleyJr Helen E Gruber 《Arthritis research & therapy》2010,12(2):R56
Introduction
Calcium crystals exist in the knee joint fluid of up to 65% of osteoarthritis (OA) patients and the presence of these calcium crystals correlates with the radiographic evidence of hyaline cartilaginous degeneration. This study sought to examine calcium deposition in OA meniscus and to investigate OA meniscal cell-mediated calcium deposition. The hypothesis was that OA meniscal cells may play a role in pathological meniscal calcification. 相似文献109.
Abstract. 1. Clark and Evans' nearest-neighbour method was used to evaluate the distribution pattern of Acacia oswaldii and Oncothrips tepperi populations.
2. A random distribution pattern was supported statistically for both the host trees and trees that were parasitised by O. tepperi .
3. It is therefore likely that dispersal distances of colonising thrips are large enough to be able to traverse the 1 km2 study site. 相似文献
2. A random distribution pattern was supported statistically for both the host trees and trees that were parasitised by O. tepperi .
3. It is therefore likely that dispersal distances of colonising thrips are large enough to be able to traverse the 1 km
110.
Plastids of diatoms and related algae evolved by secondary endocytobiosis, the uptake of a eukaryotic alga into a eukaryotic
host cell and its subsequent reduction into an organelle. As a result diatom plastids are surrounded by four membranes. Protein
targeting of nucleus encoded plastid proteins across these membranes depends on N-terminal bipartite presequences consisting
of a signal and a transit peptide-like domain. Diatoms and cryptophytes share a conserved amino acid motif of unknown function
at the cleavage site of the signal peptides (ASAFAP), which is particularly important for successful plastid targeting. Screening
genomic databases we found that in rare cases the very conserved phenylalanine within the motif may be replaced by tryptophan,
tyrosine or leucine. To test such unusual presequences for functionality and to better understand the role of the motif and
putative receptor proteins involved in targeting, we constructed presequence:GFP fusion proteins with or without modifications
of the “ASAFAP”-motif and expressed them in the diatom Phaeodactylum tricornutum. In this comprehensive mutational analysis we found that only the aromatic amino acids phenylalanine, tryptophan, tyrosine
and the bulky amino acid leucine at the +1 position of the predicted signal peptidase cleavage site allow plastid import,
as expected from the sequence comparison of native plastid targeting presequences of P. tricornutum and the cryptophyte Guillardia theta. Deletions within the signal peptide domains also impaired plastid import, showing that the presence of F at the N-terminus
of the transit peptide together with a cleavable signal peptide is crucial for plastid import.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
A. Gruber and S. Vugrinec contributed equally to this work. 相似文献