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81.

Introduction

Modern omics experiments pertain not only to the measurement of many variables but also follow complex experimental designs where many factors are manipulated at the same time. This data can be conveniently analyzed using multivariate tools like ANOVA-simultaneous component analysis (ASCA) which allows interpretation of the variation induced by the different factors in a principal component analysis fashion. However, while in general only a subset of the measured variables may be related to the problem studied, all variables contribute to the final model and this may hamper interpretation.

Objectives

We introduce here a sparse implementation of ASCA termed group-wise ANOVA-simultaneous component analysis (GASCA) with the aim of obtaining models that are easier to interpret.

Methods

GASCA is based on the concept of group-wise sparsity introduced in group-wise principal components analysis where structure to impose sparsity is defined in terms of groups of correlated variables found in the correlation matrices calculated from the effect matrices.

Results

The GASCA model, containing only selected subsets of the original variables, is easier to interpret and describes relevant biological processes.

Conclusions

GASCA is applicable to any kind of omics data obtained through designed experiments such as, but not limited to, metabolomic, proteomic and gene expression data.
  相似文献   
82.
Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1+/+), hemizygous (Pin1+/?) or knock-out (Pin1?/?) background for Pin1 were experimentally infected with RML prions. The study indicates that, neither the total depletion nor reduced levels of Pin1 significantly altered the clinical and neuropathological features of the disease.  相似文献   
83.
The occurrence of coprophilous fungi on samples of antelope, buffalo, zebra and hippopotamus dung collected from the Marula Estates in Kenya was recorded. A hundred and seventy three fungal isolates representative of 40 genera and 59 species were identified. Among these species, 23 were Ascomycetes (39%), 30 Deuteromycetes (50.8%), 5 Zygomycetes (8.5%) and 1 Basidiomycete (1.7%). Ascobolus immersus, Coprotus niveus, Iodophanus carneus, Lasiobolus lasioboloides, Podospora anserina, P. australis and Sporormiella minima were the dominant species occurring in the dung of these animals. Notes on infrequent or interesting Ascomycetes include Kernia nitida, Saccobolus versicolor, Sordaria fimicola and others. The interdependence of the vegetation of this area with the fungi occurring on the dung of these animals is discussed. This revised version was published online in June 2006 with corrections to the Cover Date.  相似文献   
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Kim HD  Puglisi JD  Chu S 《Biophysical journal》2007,93(10):3575-3582
Adjacent transfer RNAs (tRNAs) in the A- and P-sites of the ribosome are in dynamic equilibrium between two different conformations called classical and hybrid states before translocation. Here, we have used single-molecule fluorescence resonance energy transfer to study the effect of Mg(2+) on tRNA dynamics with and without an acetyl group on the A-site tRNA. When the A-site tRNA is not acetylated, tRNA dynamics do not depend on [Mg(2+)], indicating that the relative positions of the substrates for peptide-bond formation are not affected by Mg(2+). In sharp contrast, when the A-site tRNA is acetylated, Mg(2+) lengthens the lifetime of the classical state but does not change the lifetime of the hybrid state. Based on these findings, the classical state resembles a state with direct stabilization of tertiary structure by Mg(2+) ions whereas the hybrid state resembles a state with little Mg(2+)-assisted stabilization. The antibiotic viomycin, a translocation inhibitor, suppresses tRNA dynamics, suggesting that the enhanced fluctuations of tRNAs after peptide-bond formation drive spontaneous attempts at translocation by the ribosome.  相似文献   
87.
M I Recht  S Douthwaite    J D Puglisi 《The EMBO journal》1999,18(11):3133-3138
The aminoglycosides, a group of structurally related antibiotics, bind to rRNA in the small subunit of the prokaryotic ribosome. Most aminoglycosides are inactive or weakly active against eukaryotic ribosomes. A major difference in the binding site for these antibiotics between prokaryotic and eukaryotic ribosomes is the identity of the nucleotide at position 1408 (Escherichia coli numbering), which is an adenosine in prokaryotic ribosomes and a guanosine in eukaryotic ribosomes. Expression in E.coli of plasmid-encoded 16S rRNA containing an A1408 to G substitution confers resistance to a subclass of the aminoglycoside antibiotics that contain a 6' amino group on ring I. Chemical footprinting experiments indicate that resistance arises from the lower affinity of the drug for the eukaryotic rRNA sequence. The 1408G ribosomes are resistant to the same subclass of aminoglycosides as previously observed both for eukaryotic ribosomes and bacterial ribosomes containing a methylation at the N1 position of A1408. The results indicate that the identity of the nucleotide at position 1408 is a major determinant of specificity of aminoglycoside action, and agree with prior structural studies of aminoglycoside-rRNA complexes.  相似文献   
88.
Herbaceous plants endemic to native Kenyan grassland on the Marula Estate were assessed for their phylloplane fungal occurrence using leaf cultures on tap water agar. From 26 sampled plants, 261 fungal isolates representative of 58 genera and 92 taxa were identified. The principal filamentous fungi were of the genera: Alternaria, Bipolaris, Curvularia, Epicoccum, Fusarium, Nigrospora, Periconia, Phoma and Pithomyces. The fungal species that occurred most frequently were: Alternaria alternata aggreate (73%), Pithomyces chartarum (73%) Nigrospora sphaerica (42%), Torula herbarum (30%) and Microsphaeropsis olivacea (27%). Fungi of limited occurrence were: Didymosphaeria oblitescens, Doliomyces mysoriensis, Endophragmiella dimorphospora, Parapericonia angusii, Podospora minicaudata, Spegazzinia tessarthra, Sporormiella minima, Stagonospora vitensis, Stigmella effigurata and Truncatella conorum-piceae. It is postulated that the phylloplane of these endemic plants provides a niche for endemic fungi. This revised version was published online in June 2006 with corrections to the Cover Date.  相似文献   
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A great effort has recently been made to obtain human stem cells able to differentiate into cholinergic neurons, as a number of diseases are associated to the cholinergic neuron loss, degeneration or incorrect function (Alzheimer's disease and motor neuron disease). A stem cell population (i.e. pre-adipocytes) is present in the adipose stromal compartment. Pre-adipocytes, like the mesodermic derivative cells, retain high plasticity and potentiality to convert in vitro from one phenotype into many others, and they can be isolated from adult adipose tissue. Pre-adipocytes committed in vitro to neural differentiation were followed up to the acquisition of neural morphology. Acetylcholinesterase and choline acetyltransferase are expressed from the native cell stage, with different localisations and roles during neural commitment. Western blots show the beginning of a new synthesis of these enzymes at 4 weeks of culture of neurogenic pre-adipocytes, in parallel with neural morphology. The passage of the choline-acetyltransferase immunoreactivity from cytoplasmic to membrane localisation shows the possible onset of catalytic activity and the histochemical reaction confirms the activity of acetylcholinesterase. This explains the possibility of obtaining cholinergic-like phenotype from pre-adipocytes.  相似文献   
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