排序方式: 共有127条查询结果,搜索用时 109 毫秒
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Jorma J. de Ronde Guillem Rigaill Sven Rottenberg Sjoerd Rodenhuis Lodewyk F. A. Wessels 《Nucleic acids research》2013,41(21):e200
Traditional methods that aim to identify biomarkers that distinguish between two groups, like Significance Analysis of Microarrays or the t-test, perform optimally when such biomarkers show homogeneous behavior within each group and differential behavior between the groups. However, in many applications, this is not the case. Instead, a subgroup of samples in one group shows differential behavior with respect to all other samples. To successfully detect markers showing such imbalanced patterns of differential signal, a different approach is required. We propose a novel method, specifically designed for the Detection of Imbalanced Differential Signal (DIDS). We use an artificial dataset and a human breast cancer dataset to measure its performance and compare it with three traditional methods and four approaches that take imbalanced signal into account. Supported by extensive experimental results, we show that DIDS outperforms all other approaches in terms of power and positive predictive value. In a mouse breast cancer dataset, DIDS is the only approach that detects a functionally validated marker of chemotherapy resistance. DIDS can be applied to any continuous value data, including gene expression data, and in any context where imbalanced differential signal is manifested. 相似文献
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Guillem Prats-Ejarque Jose A. Blanco Vivian A. Salazar Victòria M. Nogués Mohammed Moussaoui Ester Boix 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):105-117
Background
Human RNase6 is a small cationic antimicrobial protein that belongs to the vertebrate RNaseA superfamily. All members share a common catalytic mechanism, which involves a conserved catalytic triad, constituted by two histidines and a lysine (His15/His122/Lys38 in RNase6 corresponding to His12/His119/Lys41 in RNaseA). Recently, our first crystal structure of human RNase6 identified an additional His pair (His36/His39) and suggested the presence of a secondary active site.Methods
In this work we have explored RNase6 and RNaseA subsite architecture by X-ray crystallography, site-directed mutagenesis and kinetic characterization.Results
The analysis of two novel crystal structures of RNase6 in complex with phosphate anions at atomic resolution locates a total of nine binding sites and reveals the contribution of Lys87 to phosphate-binding at the secondary active center. Contribution of the second catalytic triad residues to the enzyme activity is confirmed by mutagenesis. RNase6 catalytic site architecture has been compared with an RNaseA engineered variant where a phosphate-binding subsite is converted into a secondary catalytic center (RNaseA-K7H/R10H).Conclusions
We have identified the residues that participate in RNase6 second catalytic triad (His36/His39/Lys87) and secondary phosphate-binding sites. To note, residues His39 and Lys87 are unique within higher primates. The RNaseA/RNase6 side-by-side comparison correlates the presence of a dual active site in RNase6 with a favored endonuclease-type cleavage pattern.General significance
An RNase dual catalytic and extended binding site arrangement facilitates the cleavage of polymeric substrates. This is the first report of the presence of two catalytic centers in a single monomer within the RNaseA superfamily. 相似文献4.
Guillem VM Tormo M Revert F Benet I García-Conde J Crespo A Aliño SF 《The journal of gene medicine》2002,4(2):170-182
Background
Specific and efficient delivery of genes into targeted cells is a priority objective in non‐viral gene therapy. Polyethyleneimine‐based polyplexes have been reported to be good non‐viral transfection reagents. However, polyplex‐mediated DNA delivery occurs through a non‐specific mechanism. This article reports the construction of an immunopolyplex, a targeted non‐viral vector based on a polyplex backbone, and its application in gene transfer over human lymphoma cell lines.Methods
Targeting elements (biotin‐labeled antibodies), which should recognize a specific element of the target cell membrane and promote nucleic acid entry into the cell, were attached to the polyplex backbone through a bridge protein (streptavidin). Immunopolyplex transfection activity was studied in several hematological cell lines [Jurkat (CD3+/CD19?), Granta 519 (CD3?/ CD19+), and J.RT3‐T3.5 (CD3?/CD19?)] using the EGFP gene as a reporter gene and anti‐CD3 and anti‐CD19 antibodies as targeting elements. Transfection activity was evaluated via green fluorescence per cell and the percentage of positive cells determined by flow cytometry.Results
A significant selectivity of gene delivery was observed, since the anti‐CD3 immunopolyplex worked only in Jurkat cells while the anti‐CD19 immunopolyplex worked only in the Granta cell line. Moreover, transfection of a CD3+/CD3? cell mixture with anti‐CD3 immunopolyplexes showed up to 16‐fold more transfection in CD3+ than in CD3? cells. Several non‐specific transfection reagents showed poor or no transfection activity.Conclusion
It is concluded that immunopolyplex is a good non‐viral vector for specific and selective nucleic acid delivery. Immunopolyplex design allows easy replacement of the targeting element (antibody) – the streptavidin–polyplex backbone remaining intact – thereby conferring high versatility. Copyright © 2002 John Wiley & Sons, Ltd.5.
Guillem A Alegría A Barberá R Farré R Lagarda MJ Clemente G 《Biological trace element research》2000,75(1-3):11-19
Seven zinc salts—acetate, chloride, lactate, sulfate, citrate, gluconate, and oxide—were added to milk—and soy-based infant
formulas to estimate possible differences in zinc availability depending on the type of salt used. For this purpose, an in
vitro method that estimates the dialyzability of the element (i.e., the fraction available for absorption) was applied. Zinc
dialyzability is always higher in milk-based products than in soy products, even when the total zinc contents are higher in
the latter.
The salts can be classified according to the zinc dialyzability in the two types of formulas as follows: oxide>gluconate=chloride=lactate>citrate=acetate>sulfate.
Therefore, according to the dialysis percentage, oxide and gluconate are the compounds of choice for zinc supplementation
of infant formulas. 相似文献
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Carey Philip G. Sargent Angela J. Taberner Antoni Martínez Ramón Guillem Moyà Gabriel 《Hydrobiologia》2001,448(1-3):193-201
On the island of Mallorca, anchihaline lagoons, meromictic in character, are common in the flooded coastal karst. These subterranean lagoons, containing important populations of crustacea, maintain a connection, albeit tenuous, to the sea. Thus, the first truly quantitative study of marine ciliates inhabiting anchihaline lagoons was undertaken between April 1996 and April 1997. Physical and chemical measurements were taken in-situ, together with water samples for faunal analysis in each of four stratified lakes. These lagoons typically displayed a temperature inversion, an increase in conductivity and a decrease in dissolved oxygen concentration with depth. Ciliates were present in all lagoons studied, with a total of nine species recorded. All were assigned to known taxa. Spatial distribution of the trophic cells was noteworthy with populations clearly stratified within the water column, most being found at the waters surface, sometimes in association with rafts of floating calcite crystals, or in the sediment. Only on one occasion were ciliates recorded in mid-water. Abundance was very low, typically <1 ciliate cm–3. The floating calcite crystals may form a delimitable biotope for ciliate populations. The role of the cyst in maintaining populations of ciliates in these cave waters is discussed. 相似文献
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Revilla-López G Rodríguez-Ropero F Curcó D Torras J Isabel Calaza M Zanuy D Jiménez AI Cativiela C Nussinov R Alemán C 《Proteins》2011,79(6):1841-1852
Recently, we reported a database (Noncoded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of nonproteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally established conformational propensities, and applications (Revilla-López et al., J Phys Chem B 2010;114:7413-7422). The database initially contained the information available for α-tetrasubstituted α-amino acids. In this work, we extend NCAD to three families of compounds, which can be used to engineer peptides and proteins incorporating modifications at the--NHCO--peptide bond. Such families are: N-substituted α-amino acids, thio-α-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 3(10)-helix with respect to the α-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database. 相似文献
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Picard F Lebarbier E Hoebeke M Rigaill G Thiam B Robin S 《Biostatistics (Oxford, England)》2011,12(3):413-428
The statistical analysis of array comparative genomic hybridization (CGH) data has now shifted to the joint assessment of copy number variations at the cohort level. Considering multiple profiles gives the opportunity to correct for systematic biases observed on single profiles, such as probe GC content or the so-called "wave effect." In this article, we extend the segmentation model developed in the univariate case to the joint analysis of multiple CGH profiles. Our contribution is multiple: we propose an integrated model to perform joint segmentation, normalization, and calling for multiple array CGH profiles. This model shows great flexibility, especially in the modeling of the wave effect that gives a likelihood framework to approaches proposed by others. We propose a new dynamic programming algorithm for break point positioning, as well as a model selection criterion based on a modified bayesian information criterion proposed in the univariate case. The performance of our method is assessed using simulated and real data sets. Our method is implemented in the R package cghseg. 相似文献