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21.
Background
The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies. 相似文献22.
SMM?VerstappenEmail author AR?Poole M?Ionescu LE?King M?Abrahamowicz DM?Hofman JWJ?Bijlsma FPJG?Lafeber the Utrecht Rheumatoid Arthritis Cohort Study group 《Arthritis research & therapy》2005,8(1):R31
Introduction
The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). 相似文献23.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)
Background
To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.Results
Here, we present a method that allows for the identification of differential gene expression associated with DNA copy number changes over time. The temporal variation in gene expression is described by a generalized linear mixed model employing low-rank thin-plate splines. Model parameters are estimated with an empirical Bayes procedure, which exploits integrated nested Laplace approximation for fast computation. Iteratively, posteriors of hyperparameters and model parameters are estimated. The empirical Bayes procedure shrinks multiple dispersion-related parameters. Shrinkage leads to more stable estimates of the model parameters, better control of false positives and improvement of reproducibility. In addition, to make estimates of the DNA copy number more stable, model parameters are also estimated in a multivariate way using triplets of features, imposing a spatial prior for the copy number effect.Conclusion
With the proposed method for analysis of time-course multilevel molecular data, more profound insight may be gained through the identification of temporal differential expression induced by DNA copy number abnormalities. In particular, in the analysis of an integrative oncogenomics study with a time-course set-up our method finds genes previously reported to be involved in cervical carcinogenesis. Furthermore, the proposed method yields improvements in sensitivity, specificity and reproducibility compared to existing methods. Finally, the proposed method is able to handle count (RNAseq) data from time course experiments as is shown on a real data set.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-327) contains supplementary material, which is available to authorized users. 相似文献24.
Patr��cia F N Fa��sca Ana Nunes Rui DM Travasso Eugene I Shakhnovich 《Protein science : a publication of the Protein Society》2010,19(11):2196-2209
Systematic Monte Carlo simulations of simple lattice models show that the final stage of protein folding is an ordered process where native contacts get locked (i.e., the residues come into contact and remain in contact for the duration of the folding process) in a well‐defined order. The detailed study of the folding dynamics of protein‐like sequences designed as to exhibit different contact energy distributions, as well as different degrees of sequence optimization (i.e., participation of non‐native interactions in the folding process), reveals significant differences in the corresponding locking scenarios—the collection of native contacts and their average locking times, which are largely ascribable to the dynamics of non‐native contacts. Furthermore, strong evidence for a positive role played by non‐native contacts at an early folding stage was also found. Interestingly, for topologically simple target structures, a positive interplay between native and non‐native contacts is observed also toward the end of the folding process, suggesting that non‐native contacts may indeed affect the overall folding process. For target models exhibiting clear two‐state kinetics, the relation between the nucleation mechanism of folding and the locking scenario is investigated. Our results suggest that the stabilization of the folding transition state can be achieved through the establishment of a very small network of native contacts that are the first to lock during the folding process. 相似文献
25.
X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family 总被引:8,自引:0,他引:8 下载免费PDF全文
Laumonnier F Bonnet-Brilhault F Gomot M Blanc R David A Moizard MP Raynaud M Ronce N Lemonnier E Calvas P Laudier B Chelly J Fryns JP Ropers HH Hamel BC Andres C Barthélémy C Moraine C Briault S 《American journal of human genetics》2004,74(3):552-557
A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins. 相似文献
26.
Devina Purmessur Clare C Guterl Samuel K Cho Marisa C Cornejo Ying W Lam Bryan A Ballif Damien M Laudier James C Iatridis 《Arthritis research & therapy》2013,15(5):R122
Introduction
Notochordal cells (NCs) pattern aneural and avascular intervertebral discs (IVDs), and their disappearance, is associated with onset of IVD degeneration. This study induced and characterized the maturation of nucleus pulposus (NP) tissue from a gelatinous NC-rich structure to a matrix-rich structure populated by small NP cells using dynamic pressurization in an ex vivo culture model, and also identified soluble factors from NCs with therapeutic potential.Methods
Porcine NC-rich NP tissue was cultured and loaded with hydrostatic pressure (0.5 to 2 MPa at 0.1 Hz for 2 hours) either Daily, for 1 Dose, or Control (no pressurization) groups for up to eight days. Cell phenotype and tissue maturation was characterized with measurements of cell viability, cytomorphology, nitric oxide, metabolic activity, matrix composition, gene expression, and proteomics.Results
Daily pressurization induced transition of NCs to small NP cells with 73.8%, 44%, and 28% NCs for Control, 1 Dose and Daily groups, respectively (P < 0.0002) and no relevant cell death. Dynamic loading matured NP tissue by significantly increasing metabolic activity and accumulating Safranin-O-stained matrix. Load-induced maturation was also apparent from the significantly decreased glycolytic, cytoskeletal (Vimentin) and stress-inducible (HSP70) proteins assessed with proteomics. Loading increased the production of bioactive proteins Sonic Hedgehog (SHH) and Noggin, and maintained Semaphorin3A (Sema3A).Discussion
NP tissue maturation was induced from dynamic hydrostatic pressurization in a controlled ex vivo environment without influence from systemic effects or surrounding structures. NCs transitioned into small nonvacuolated NP cells probably via differentiation as evidenced by high cell viability, lack of nitric oxide and downregulation of stress-inducible and cytoskeletal proteins. SHH, Sema3A, and Noggin, which have patterning and neurovascular-inhibiting properties, were produced in both notochordal and matured porcine NP. Results therefore provide an important piece of evidence suggesting the transition of NCs to small NP cells is a natural part of aging and not the initiation of degeneration. Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain. 相似文献27.
28.
The complexity of genetic pathways for hearing is beginning to be amenable to unraveling by systematic functional genomic analysis. Genome-wide mutagenesis studies in the mouse are beginning to shed further light on the structure and regulation of the machinery of hearing. 相似文献
29.
Clara Correia‐Melo Francisco DM Marques Rhys Anderson Graeme Hewitt Rachael Hewitt John Cole Bernadette M Carroll Satomi Miwa Jodie Birch Alina Merz Michael D Rushton Michelle Charles Diana Jurk Stephen WG Tait Rafal Czapiewski Laura Greaves Glyn Nelson Mohammad Bohlooly‐Y Sergio Rodriguez‐Cuenca Antonio Vidal‐Puig Derek Mann Gabriele Saretzki Giovanni Quarato Douglas R Green Peter D Adams Thomas von Zglinicki Viktor I Korolchuk João F Passos 《The EMBO journal》2016,35(7):724-742
30.
Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis 总被引:6,自引:0,他引:6
Using sequence data from the 28S ribosomal RNA (rRNA) genes of selected
vertebrates, we investigated the effects that constraints imposed by
secondary structure have on the phylogenetic analysis of rRNA sequence
data. Our analysis indicates that characters from both base-pairing regions
(stems) and non-base-pairing regions (loops) contain phylogenetic
information, as judged by the level of support of the phylogenetic results
compared with a well-established tree based on both morphological and
molecular data. The best results (the greatest level of support of
well-accepted nodes) were obtained when the complete data set was used.
However, some previously supported nodes were resolved using either the
stem or loop bases alone. Stem bases sustain a greater number of
compensatory mutations than would be expected at random, but the number is
< 40% of that expected under a hypothesis of perfect compensation to
maintain secondary structure. Therefore, we suggest that in phylogenetic
analyses, the weighting of stem characters be reduced by no more than 20%,
relative to that of loop characters. In contrast to previous suggestions,
we do not recommend weighting of stem positions by one-half, compared with
that of loop positions, because this overcompensates for the constraints
that selection imposes on the secondary structure of rRNA.
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