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131.
Mohammadi S Keller SS Glauche V Kugel H Jansen A Hutton C Flöel A Deppe M 《PloS one》2012,7(6):e36851
The sensitivity of diffusion tensor imaging (DTI) for detecting microstructural white matter alterations has motivated the application of voxel-based statistics (VBS) to fractional anisotropy (FA) images (FA-VBS). However, detected group differences may depend on the spatial registration method used. The objective of this study was to investigate the influence of spatial registration on detecting cerebral asymmetries in FA-VBS analyses with reference to data obtained using Tract-Based Spatial Statistics (TBSS). In the first part of this study we performed FA-VBS analyses using three single-contrast and one multi-contrast registration: (i) whole-brain registration based on T2 contrast, (ii) whole-brain registration based on FA contrast, (iii) individual-hemisphere registration based on FA contrast, and (iv) a combination of (i) and (iii). We then compared the FA-VBS results with those obtained from TBSS. We found that the FA-VBS results depended strongly on the employed registration approach, with the best correspondence between FA-VBS and TBSS results when approach (iv), the "multi-contrast individual-hemisphere" method was employed. In the second part of the study, we investigated the spatial distribution of residual misregistration for each registration approach and the effect on FA-VBS results. For the FA-VBS analyses using the three single-contrast registration methods, we identified FA asymmetries that were (a) located in regions prone to misregistrations, (b) not detected by TBSS, and (c) specific to the applied registration approach. These asymmetries were considered candidates for apparent FA asymmetries due to systematic misregistrations associated with the FA-VBS approach. Finally, we demonstrated that the "multi-contrast individual-hemisphere" approach showed the least residual spatial misregistrations and thus might be most appropriate for cerebral FA-VBS analyses. 相似文献
132.
Schizophrenia is a complex genetic disorder. Gene set-based analytic (GSA) methods have been widely applied for exploratory
analyses of large, high-throughput datasets, but less commonly employed for biological hypothesis testing. Our primary hypothesis
is that variation in ion channel genes contribute to the genetic susceptibility to schizophrenia. We applied Exploratory Visual
Analysis (EVA), one GSA application, to analyze European-American (EA) and African-American (AA) schizophrenia genome-wide
association study datasets for statistical enrichment of ion channel gene sets, comparing GSA results derived under three
SNP-to-gene mapping strategies: (1) GENIC; (2) 500-Kb; (3) 2.5-Mb and three complimentary SNP-to-gene statistical reduction
methods: (1) minimum p value (pMIN); (2) a novel method, proportion of SNPs per Gene with p values below a pre-defined α-threshold (PROP); and (3) the truncated product method (TPM). In the EA analyses, ion channel
gene set(s) were enriched under all mapping and statistical approaches. In the AA analysis, ion channel gene set(s) were significantly
enriched under pMIN for all mapping strategies and under PROP for broader mapping strategies. Less extensive enrichment in
the AA sample may reflect true ethnic differences in susceptibility, sampling or case ascertainment differences, or higher
dimensionality relative to sample size of the AA data. More consistent findings under broader mapping strategies may reflect
enhanced power due to increased SNP inclusion, enhanced capture of effects over extended haplotypes or significant contributions
from regulatory regions. While extensive pMIN findings may reflect gene size bias, the extent and significance of PROP and
TPM findings suggest that common variation at ion channel genes may capture some of the heritability of schizophrenia. 相似文献
133.
134.
Xu GW Mawji IA Macrae CJ Koch CA Datti A Wrana JL Dennis JW Schimmer AD 《Apoptosis : an international journal on programmed cell death》2008,13(3):413-422
p53 regulates apoptosis and the cell cycle through actions in the nucleus and cytoplasm. Altering the subcellular localization
of p53 can alter its biological function. Therefore, small molecules that change the localization of p53 would be useful chemical
probes to understand the influence of subcellular localization on the function of p53. To identify such molecules, a high-content
screen for compounds that increased the localization of p53 to the nucleus or cytoplasm was developed, automated, and conducted.
With this image-based assay, we identified ellipticine that increased the nuclear localization of GFP-mutant p53 protein but
not GFP alone in Saos-2 osteosarcoma cells. In addition, ellipticine increased the nuclear localization of endogenous p53
in HCT116 colon cancer cells with a resultant increase in the transactivation of the p21 promoter. Increased nuclear p53 after
ellipticine treatment was not associated with an increase in DNA double stranded breaks, indicating that ellipticine shifts
p53 to the nucleus through a mechanism independent of DNA damage. Thus, a chemical biology approach has identified a molecule
that shifts the localization of p53 and enhances its nuclear activity.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
G. Wei Xu and Imtiaz A. Mawji have contributed equally to this work. 相似文献
135.
Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding 总被引:1,自引:0,他引:1
Groppe J Hinck CS Samavarchi-Tehrani P Zubieta C Schuermann JP Taylor AB Schwarz PM Wrana JL Hinck AP 《Molecular cell》2008,29(2):157-168
Dimeric ligands of the transforming growth factor-beta (TGF-beta) superfamily signal across cell membranes in a distinctive manner by assembling heterotetrameric complexes of structurally related serine/threonine-kinase receptor pairs. Unlike complexes of the bone morphogenetic protein (BMP) branch that apparently form due to avidity from membrane localization, TGF-beta complexes assemble cooperatively through recruitment of the low-affinity (type I) receptor by the ligand-bound high-affinity (type II) pair. Here we report the crystal structure of TGF-beta3 in complex with the extracellular domains of both pairs of receptors, revealing that the type I docks and becomes tethered via unique extensions at a composite ligand-type II interface. Disrupting the receptor-receptor interactions conferred by these extensions abolishes assembly of the signaling complex and signal transduction (Smad activation). Although structurally similar, BMP and TGF-beta receptors bind in dramatically different modes, mediating graded and switch-like assembly mechanisms that may have coevolved with branch-specific groups of cytoplasmic effectors. 相似文献
136.
Insight into the population structure of hardhead silverside,Atherinomorus stipes (Teleostei: Atherinidae), in Belize and the Florida Keys using nd2
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Little is known about the natural history, biology, and population genetic structure of the Hardhead Silverside, Atherinomorus stipes, a small schooling fish found around islands throughout the Caribbean. Our field observations of A. stipes in the cays of Belize and the Florida Keys found that populations tend to be in close association with the shoreline in mangrove habitats. Due to this potential island‐based population structuring, A. stipes represents an ideal system to examine questions about gene flow and isolation by distance at different geographic scales. For this study, the mitochondrial gene nd2 was amplified from 394 individuals collected from seven different Belizean Cays (N = 175) and eight different Floridian Keys (N = 219). Results show surprisingly high haplotype diversity both within and between island‐groups, as well as a high prevalence of unique haplotypes within each island population. The results are consistent with models that require gene flow among populations as well as in situ evolution of rare haplotypes. There was no evidence for an isolation by distance model. The nd2 gene tree consists of two well‐supported monophyletic groups: a Belizean‐type clade and a Floridian‐type clade, indicating potential species‐level differentiation. 相似文献
137.
Eugene Christo-Foroux Tatiana Vallaeys Valentin Loux Elie Dassa Josef Deutscher Cécile Wandersman Aurélien Livernois Chloe Hot Alexis Criscuolo Catherine Dauga Dominique Clermont Olivier Chesneau 《Systematic and applied microbiology》2017,40(7):401-410
Staphylococcus sciuri is considered to be one of the most ancestral species in the natural history of the Staphylococcus genus that consists of 48 validly described species. It belongs to the basal group of oxidase-positive and novobiocin-resistant staphylococci that diverged from macrococci approximately 250 million years ago. Contrary to other groups, the S. sciuri species group has not developed host-specific colonization strategies. Genome analysis of S. sciuri ATCC 29059 provides here the first genetic basis for atypical traits that would support the switch between the free-living style and the infective state in animals and humans. From among the most remarkable features, it was noticed in this extensive study that there were a number of phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTS), almost twice as many as any other staphylococci, and the co-occurrence of mevalonate and non-mevalonate pathways for isoprenoid synthesis. The sequenced strain was devoid of the main virulence factors present in Staphylococcus aureus, although it exhibited numerous heme and iron acquisition systems, as well as crt and aldH genes necessary for gold pigment synthesis. The sensing and signaling networks, exemplified by a large and typical repertoire of two-component regulatory systems and a complete panel of master regulators, such as agr, rex, mgrA, rot, sarA and sarR genes, depict the background in which S. aureus virulence genes were later acquired. An additional sigma factor, a distinct set of electron transducer elements and many gene operons similar to those found in Bacillus spp. would constitute the most visible remnant links with Bacillaceae organisms. 相似文献
138.
Jelena uklina Chloe H Lee Evan G Williams Tatjana Sajic Ben C Collins María Rodríguez Martínez Varun S Sharma Fabian Wendt Sandra Goetze Gregory R Keele Bernd Wollscheid Ruedi Aebersold Patrick G A Pedrioli 《Molecular systems biology》2021,17(8)
Advancements in mass spectrometry‐based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much‐needed statistical power, handling them introduces technical variability known as batch effects. Here, we present a step‐by‐step protocol for the assessment, normalization, and batch correction of proteomic data. We review established methodologies from related fields and describe solutions specific to proteomic challenges, such as ion intensity drift and missing values in quantitative feature matrices. Finally, we compile a set of techniques that enable control of batch effect adjustment quality. We provide an R package, "proBatch", containing functions required for each step of the protocol. We demonstrate the utility of this methodology on five proteomic datasets each encompassing hundreds of samples and consisting of multiple experimental designs. In conclusion, we provide guidelines and tools to make the extraction of true biological signal from large proteomic studies more robust and transparent, ultimately facilitating reliable and reproducible research in clinical proteomics and systems biology. 相似文献
139.
SOCIAL CAUSES OF CORRELATIONAL SELECTION AND THE RESOLUTION OF A HERITABLE THROAT COLOR POLYMORPHISM IN A LIZARD 总被引:6,自引:0,他引:6
Barry Sinervo Colin Bleay Chloe Adamopoulou 《Evolution; international journal of organic evolution》2001,55(10):2040-2052
Abstract When selection acts on social or behavioral traits, the fitness of an individual depends on the phenotypes of its competitors. Here, we describe methods and statistical inference for measuring natural selection in small social groups. We measured selection on throat color alleles that arises from microgeographic variation in allele frequency at natal sites of side‐blotched lizards (Uta stansburiana). Previous game‐theoretic analysis indicates that two color morphs of female side‐blotched lizards are engaged in an offspring quantity‐quality game that promotes a density‐and frequency‐dependent cycle. Orange‐throated females are r‐strategists. They lay large clutches of small progeny, which have poor survival at high density, but good survival at low density. In contrast, yellow‐throated females are K‐strategists. They lay small clutches of large progeny, which have good survival at high density. We tested three predictions of the female game: (1) orange progeny should have a fitness advantage at low density; (2) correlational selection acts to couple color alleles and progeny size; and (3) this correlational selection arises from frequency‐dependent selection in which large hatchling size confers an advantage, but only when yellow alleles are rare. We also confirmed the heritability of color, and therefore its genetic basis, by producing progeny from controlled matings. A parsimonious cause of the high heritability is that three alleles (o, b, y) segregate as one genetic factor. We review the physiology of color formation to explain the possible genetic architecture of the throat color trait. Heritability of color was nearly additive in our breeding study, allowing us to compute a genotypic value for each individual and thus predict the frequency of progeny alleles released on 116 plots. Rather than study the fitness of individual progeny, we studied how the fitness of their color alleles varied with allele frequency on plots. We confirmed prediction 1: When orange alleles are present in female progeny, they have higher fitness at low density when compared to other alleles. Even though the difference in egg size of the female morphs was small (0.02 g), it led to knife‐edged survival effects for their progeny depending on local social context. Selection on hatchling survival was not only dependent on color alleles, but on a fitness interaction between color alleles and hatchling size, which confirmed prediction 2. Sire effects, which are not confounded by maternal phenotype, allowed us to resolve the frequency dependence of correlational selection on egg size and color alleles and thereby confirmed prediction 3. Selection favored large size when yellow sire alleles were rare, but small size when they were common. Correlational selection promotes the formation of a self‐reinforcing genetic correlation between the morphs and life‐history variation, which causes selection in the next density and frequency cycle to be exacerbated. We discuss general conditions for the evolution of self‐reinforcing genetic correlations that arise from social selection associated with frequency‐dependent sexual and natural selection. 相似文献
140.
Elissa E. Epel Anne E. Moyer Chloe D. Martin Susan Macary Nancy Cummings Judith Rodin Marielle Rebuffe-Scrive 《Obesity (Silver Spring, Md.)》1999,7(1):9-15
EPEL, ELISSA A., ANNE E. MOYER, CHLOE D. MARTIN, SUSAN MACARY, NANCY CUMMINGS, JUDITH RODIN, AND MARIELLE REBUFFE-SCRIVE. Stress-induced Cortisol, mood, and fat distribution in men. Obes Res. 1999;7:9–15. Objective : A previous study in our laboratory (Moyer et al., Obes Res. 1994;2:255-62 found that, in response to uncontrollable laboratory stress, women with a high waist-to-hip ratio (WHR) had higher Cortisol reactivity, poorer coping skills, and lower anger responses than women with low WHR. We aimed to compare high WHR men's stress responses to these women. Research Methods and Procedures : The current study examined Cortisol reactivity and psychological data of 27 healthy high WHR men exposed to the same laboratory challenges as the women from our previous study. Men's data are discussed in relation to that of the high and low WHR women. Results : Men responded to the stress with increases in both Cortisol and blood pressure. In comparison with the high and low WHR women, men had significantly higher total cortisof on the stress day. However, when comparing a sub-sample of men and women matched in WHR's, differences in Cortisol secretion were greatly diminished and no longer significant. In addition, men had higher desire for control than both high and low WHR women, and lower mood reactivity than low WHR women. Despite the lower mood reactivity of high WHR groups, the high mood reactors among the high WHR women, and to a lesser extent, men, tended to have higher Cortisol reactivity. Discussion: These results suggest that the psychological differences and greater exposure to Cortisol observed amon; the high WHR men and women may have played a role ii contributing to their greater abdominal fat depots. Discussion : These results suggest that the psychological differences and greater exposure to cortisol observed among the high WHR men and women may have played a role contributing to their greater abdominal fat depots. 相似文献