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Showing papers in "Nature Methods in 2004"


Journal ArticleDOI
TL;DR: A new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscopy and combining this method with calcium indicator loading of cell populations demonstrated distinct calcium dynamics in astroglial and neuronal networks.
Abstract: Glial cells have been identified as key signaling components in the brain; however, methods to investigate their structure and function in vivo have been lacking. Here, we describe a new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscopy. The red fluorescent dye sulforhodamine 101 (SR101) was specifically taken up by protoplasmic astrocytes after brief exposure to the brain surface. Specificity was confirmed by immunohistochemistry. In addition, SR101 labeled enhanced green fluorescent protein (EGFP)-expressing astrocytes but not microglial cells in transgenic mice. We used SR101 labeling to quantify morphological characteristics of astrocytes and to visualize their close association with the cortical microvasculature. Furthermore, by combining this method with calcium indicator loading of cell populations, we demonstrated distinct calcium dynamics in astroglial and neuronal networks. We expect SR101 staining to become a principal tool for investigating astroglia in vivo.

793 citations


Journal ArticleDOI
TL;DR: Dual-channel microarrays are designed that monitor expression levels of 124 mammalian microRNAs and expression profiles of staged embryos demonstrate temporal regulation of a large class of micro RNAs, including members of the let-7 family.
Abstract: MicroRNAs are short, noncoding RNA transcripts that post-transcriptionally regulate gene expression. Several hundred microRNA genes have been identified in Caenorhabditis elegans, Drosophila, plants and mammals. MicroRNAs have been linked to developmental processes in C. elegans, plants and humans and to cell growth and apoptosis in Drosophila. A major impediment in the study of microRNA function is the lack of quantitative expression profiling methods. To close this technological gap, we have designed dual-channel microarrays that monitor expression levels of 124 mammalian microRNAs. Using these tools, we observed distinct patterns of expression among adult mouse tissues and embryonic stem cells. Expression profiles of staged embryos demonstrate temporal regulation of a large class of microRNAs, including members of the let-7 family. This microarray technology enables comprehensive investigation of microRNA expression, and furthers our understanding of this class of recently discovered noncoding RNAs.

791 citations


Journal ArticleDOI
TL;DR: The proposed method is based on the sequential isolation and fragmentation of precursor windows within the ion trap until a desired mass range has been covered, and showed improvements in signal-to-noise ratio over corresponding chromatograms generated from mass spectrometry scans.
Abstract: To take advantage of the potential quantitative benefits offered by tandem mass spectrometry, we have modified the method in which tandem mass spectrum data are acquired in 'shotgun' proteomic analyses. The proposed method is not data dependent and is based on the sequential isolation and fragmentation of precursor windows (of 10 m/z) within the ion trap until a desired mass range has been covered. We compared the quantitative figures of merit for this method to those for existing strategies by performing an analysis of the soluble fraction of whole-cell lysates from yeast metabolically labeled in vivo with 15N. To automate this analysis, we modified software (RelEx) previously written in the Yates lab to generate chromatograms directly from tandem mass spectra. These chromatograms showed improvements in signal-to-noise ratio of approximately three- to fivefold over corresponding chromatograms generated from mass spectrometry scans. In addition, to demonstrate the utility of the data-independent acquisition strategy coupled with chromatogram reconstruction from tandem mass spectra, we measured protein expression levels in two developmental stages of Caenorhabditis elegans.

696 citations


Journal ArticleDOI
TL;DR: It is demonstrated that miRNAs can be isolated and profiled from formalin-fixed paraffin-embedded tissue, which opens up new opportunities for analyses of small RNAs from archival human tissue.
Abstract: MicroRNAs (miRNAs) are small regulatory RNAs that serve fundamental biological roles across eukaryotic species. We describe a new method for high-throughput miRNA detection. The technique is termed the RNA-primed, array-based Klenow enzyme (RAKE) assay, because it involves on-slide application of the Klenow fragment of DNA polymerase I to extend unmodified miRNAs hybridized to immobilized DNA probes. We used RAKE to study human cell lines and brain tumors. We show that the RAKE assay is sensitive and specific for miRNAs and is ideally suited for rapid expression profiling of all known miRNAs. RAKE offers unique advantages for specificity over northern blots or other microarray-based expression profiling platforms. Furthermore, we demonstrate that miRNAs can be isolated and profiled from formalin-fixed paraffin-embedded tissue, which opens up new opportunities for analyses of small RNAs from archival human tissue. The RAKE assay is theoretically versatile and may be used for other applications, such as viral gene profiling.

636 citations


Journal ArticleDOI
TL;DR: This work presents a genotyping method for simultaneously scoring 116,204 SNPs using oligonucleotide arrays with reproducibility and accuracy at call rates >99, and accuracy as measured by inheritance in trios and concordance with the HapMap Project.
Abstract: We present a genotyping method for simultaneously scoring 116,204 SNPs using oligonucleotide arrays. At call rates >99%, reproducibility is >99.97% and accuracy, as measured by inheritance in trios and concordance with the HapMap Project, is >99.7%. Average intermarker distance is 23.6 kb, and 92% of the genome is within 100 kb of a SNP marker. Average heterozygosity is 0.30, with 105,511 SNPs having minor allele frequencies >5%.

455 citations


Journal ArticleDOI
TL;DR: In this article, the authors used stable isotope labeling by amino acids in cell culture (SILAC) for quantitative comparison of proteomes, using antibodies targeted to methylated residues and analysis by liquid chromatography-tandem mass spectrometry.
Abstract: Protein methylation is a stable post-translational modification (PTM) with important biological functions. It occurs predominantly on arginine and lysine residues with varying numbers of methyl groups, such as mono-, di- or trimethyl lysine. Existing methods for identifying methylation sites are laborious, require large amounts of sample and cannot be applied to complex mixtures. We have previously described stable isotope labeling by amino acids in cell culture (SILAC) for quantitative comparison of proteomes. In heavy methyl SILAC, cells metabolically convert [(13)CD(3)]methionine to the sole biological methyl donor, [(13)CD(3)]S-adenosyl methionine. Heavy methyl groups are fully incorporated into in vivo methylation sites, directly labeling the PTM. This provides markedly increased confidence in identification and relative quantitation of protein methylation by mass spectrometry. Using antibodies targeted to methylated residues and analysis by liquid chromatography-tandem mass spectrometry, we identified 59 methylation sites, including previously unknown sites, considerably extending the number of in vivo methylation sites described in the literature.

449 citations


Journal ArticleDOI
TL;DR: This work reviews the basic concepts used by most search algorithms, the computational modeling of peptide identification and current challenges and limitations of this approach for protein identification.
Abstract: Database searching is an essential element of large-scale proteomics. Because these methods are widely used, it is important to understand the rationale of the algorithms. Most algorithms are based on concepts first developed in SEQUEST and PeptideSearch. Four basic approaches are used to determine a match between a spectrum and sequence: descriptive, interpretative, stochastic and probability–based matching. We review the basic concepts used by most search algorithms, the computational modeling of peptide identification and current challenges and limitations of this approach for protein identification.

427 citations


Journal ArticleDOI
TL;DR: A combinatorial peptide library method that allows rapid generation of phosphorylation motifs for serine/threonine kinases is described.
Abstract: Selection of target substrates by protein kinases is strongly influenced by the amino acid sequence surrounding the phosphoacceptor site. Identification of the preferred peptide phosphorylation motif for a given kinase permits the production of efficient peptide substrates and greatly simplifies the mapping of phosphorylation sites in protein substrates. Here we describe a combinatorial peptide library method that allows rapid generation of phosphorylation motifs for serine/threonine kinases.

362 citations


Journal ArticleDOI
TL;DR: An integrated series of reaction steps that allow individual nucleic acid molecules to be detected with excellent specificity are described and used to observe the distribution, within and among human cells, of individual normal and mutant mitochondrial genomes that differ at a single nucleotide position.
Abstract: Methods are needed to study single molecules to reveal variability, interactions and mechanisms that may go undetected at the level of populations of molecules. We describe here an integrated series of reaction steps that allow individual nucleic acid molecules to be detected with excellent specificity. Oligonucleotide probes are circularized after hybridization to target sequences that have been prepared so that localized amplification reactions can be initiated from the target molecules. The process results in strong, discrete detection signals anchored to the target molecules. We use the method to observe the distribution, within and among human cells, of individual normal and mutant mitochondrial genomes that differ at a single nucleotide position.

345 citations


Journal ArticleDOI
TL;DR: Fluorescent quantum dots provide a useful alternative for studies that require long-term and multicolor imaging of cellular and molecular interactions.
Abstract: . Despite their considerable advantages in live cell imaging, organic fluorophores are subject to certain limitations. Fluorescent quantum dots (QDs) are inorganic fluorescent nanocrystals that overcome many of these limitations and provide a useful alternative for studies that require long-term and multicolor imaging of cellular and molecular interactions

325 citations


Journal ArticleDOI
TL;DR: A microscope-based instrument capable of simultaneous, spatially coincident optical trapping and single-molecule fluorescence is constructed and the distance to the thermodynamic transition state and the thermal off rates in the absence of load for both processes are determined.
Abstract: We constructed a microscope-based instrument capable of simultaneous, spatially coincident optical trapping and single-molecule fluorescence. The capabilities of this apparatus were demonstrated by studying the force-induced strand separation of a dye-labeled, 15-base-pair region of double-stranded DNA (dsDNA), with force applied either parallel ('unzipping' mode) or perpendicular ('shearing' mode) to the long axis of the region. Mechanical transitions corresponding to DNA hybrid rupture occurred simultaneously with discontinuous changes in the fluorescence emission. The rupture force was strongly dependent on the direction of applied force, indicating the existence of distinct unbinding pathways for the two force-loading modes. From the rupture force histograms, we determined the distance to the thermodynamic transition state and the thermal off rates in the absence of load for both processes.

Journal ArticleDOI
TL;DR: Both theoretical and experimental approaches that discriminate the parallel versus the sequential energy transfer processes in the 3-FRET system are described, which highlight the potential of 3- FRET microscopy in studies of spatial and temporal regulation of signaling processes in living cells.
Abstract: Nearly every major process in a cell is carried out by assemblies of multiple dynamically interacting protein molecules. To study multi-protein interactions within such molecular machineries, we have developed a fluorescence microscopy method called three-chromophore fluorescence resonance energy transfer (3-FRET). This method allows analysis of three mutually dependent energy transfer processes between the fluorescent labels, such as cyan, yellow and monomeric red fluorescent proteins. Here, we describe both theoretical and experimental approaches that discriminate the parallel versus the sequential energy transfer processes in the 3-FRET system. These approaches were established in vitro and in cultured mammalian cells, using chimeric proteins consisting of two or three fluorescent proteins linked together. The 3-FRET microscopy was further applied to the analysis of three-protein interactions in the constitutive and activation-dependent complexes in single endosomal compartments. These data highlight the potential of 3-FRET microscopy in studies of spatial and temporal regulation of signaling processes in living cells.

Journal ArticleDOI
TL;DR: This work has developed a system to drive expression of shRNAs by placing them under the control of the human RNA polymerase III U6 small nuclear RNA (snRNA) promoter, which normally controls expression of small RNAs in cells.
Abstract: We and others have chosen to explore the shRNAs for several reasons: first, the considerable cost of chemically synthesized siRNAs; second, the possibility of enforceable and stable expression of shRNAs; and third, the availability of applications of expression constructs in primary cell types (for example, using retroviruses) and in whole organisms (for example, in mouse) We have developed a system to drive expression of shRNAs by placing them under the control of the human RNA polymerase III U6 small nuclear RNA (snRNA) promoter, which normally controls expression of small RNAs in cells This system has now been demonstrated to be effective both in

Journal ArticleDOI
TL;DR: Preparation, isolation and characterization of stage-specific spermatogenic cells for cellular and molecular analysis and its applications in medicine and nano-pharmaceuticals.
Abstract: Preparation, isolation and characterization of stage-specific spermatogenic cells for cellular and molecular analysis

Journal ArticleDOI
TL;DR: The approach uses in situ microarray DNA synthesis for generation of complex oligonucleotide populations that can be recovered and either used directly or immortalized by cloning, and achieves high-fidelity clone retrieval with a uniform representation of intended library sequences.
Abstract: Generation of complex libraries of defined nucleic acid sequences can greatly aid the functional analysis of protein and gene function. Previously, such studies relied either on individually synthesized oligonucleotides or on cellular nucleic acids as the starting material. As each method has disadvantages, we have developed a rapid and cost-effective alternative for construction of small-fragment DNA libraries of defined sequences. This approach uses in situ microarray DNA synthesis for generation of complex oligonucleotide populations. These populations can be recovered and either used directly or immortalized by cloning. From a single microarray, a library containing thousands of unique sequences can be generated. As an example of the potential applications of this technology, we have tested the approach for the production of plasmids encoding short hairpin RNAs (shRNAs) targeting numerous human and mouse genes. We achieved high-fidelity clone retrieval with a uniform representation of intended library sequences.

Journal ArticleDOI
TL;DR: A new method to study this dynamic post-translational modification in intact human embryonic kidney cells using bioluminescence resonance energy transfer (BRET) and allowing the detection of basal and GPCR-regulated ubiquitination of β-arrestin 2 in living cells.
Abstract: Ubiquitin has emerged as an important regulator of protein stability and function in organisms ranging from yeast to mammals. The ability to detect in situ changes in protein ubiquitination without perturbing the physiological environment of cells would be a major step forward in understanding the ubiquitination process and its consequences. Here, we describe a new method to study this dynamic post-translational modification in intact human embryonic kidney cells. Using bioluminescence resonance energy transfer (BRET), we measured the ubiquitination of beta-arrestin 2, a regulatory protein implicated in the modulation of G protein-coupled receptors. In addition to allowing the detection of basal and GPCR-regulated ubiquitination of beta-arrestin 2 in living cells, real-time BRET measurements permitted the recording of distinct ubiquitination kinetics that are dictated by the identity of the activated receptor. The ubiquitination BRET assay should prove to be a useful tool for studying the dynamic ubiquitination of proteins and for understanding which cellular functions are regulated by this post-translational event.

Journal ArticleDOI
TL;DR: A generic approach, quantitative chromatin profiling, that uses quantitative analysis of in vivo chromatin structure over entire gene loci to rapidly and precisely localize cis-regulatory sequences and other functional modalities encoded by DNase I hypersensitive sites is described.
Abstract: Identification of functional, noncoding elements that regulate transcription in the context of complex genomes is a major goal of modern biology. Localization of functionality to specific sequences is a requirement for genetic and computational studies. Here, we describe a generic approach, quantitative chromatin profiling, that uses quantitative analysis of in vivo chromatin structure over entire gene loci to rapidly and precisely localize cis-regulatory sequences and other functional modalities encoded by DNase I hypersensitive sites. To demonstrate the accuracy of this approach, we analyzed approximately 300 kilobases of human genome sequence from diverse gene loci and cleanly delineated functional elements corresponding to a spectrum of classical cis-regulatory activities including enhancers, promoters, locus control regions and insulators as well as novel elements. Systematic, high-throughput identification of functional elements coinciding with DNase I hypersensitive sites will substantially expand our knowledge of transcriptional regulation and should simplify the search for noncoding genetic variation with phenotypic consequences.

Journal ArticleDOI
TL;DR: The development of living-cell microarrays for screening large collections of RNAi-inducing double-stranded RNAs (dsRNAs) in Drosophila cells are described and previously unknown genes that affect cell proliferation and morphology are identified.
Abstract: RNA interference (RNAi)-mediated loss-of-function screening in Drosophila melanogaster tissue culture cells is a powerful method for identifying the genes underlying cell biological functions and for annotating the fly genome. Here we describe the development of living-cell microarrays for screening large collections of RNAi-inducing double-stranded RNAs (dsRNAs) in Drosophila cells. The features of the microarrays consist of clusters of cells 200 μm in diameter, each with an RNAi-mediated depletion of a specific gene product. Because of the small size of the features, thousands of distinct dsRNAs can be screened on a single chip. The microarrays are suitable for quantitative and high-content cellular phenotyping and, in combination screens, for the identification of genetic suppressors, enhancers and synthetic lethal interactions. We used a prototype cell microarray with 384 different dsRNAs to identify previously unknown genes that affect cell proliferation and morphology, and, in a combination screen, that regulate dAkt/dPKB phosphorylation in the absence of dPTEN expression.

Journal ArticleDOI
TL;DR: The system, presented in the protocol that follows, consists of two plasmid vectors for the independent expression of fusions with N- and C-terminal fragments of GFP, and allows for simple visual detection of protein-protein interactions with a K D as weak as 1 mM.
Abstract: The detection of protein-protein interactions in vivo is of critical importance to our understanding of biological processes. The classic library approach has been to use the yeast two-hybrid screen, where an interaction between known bait and unknown prey proteins leads to restoration of transcription factor activity 1 . However, its use is limited by host organism and nuclear localization requirements, and a tendency to detect indirect interactions (false positives). Bacterial two-hybrid screens have eliminated localization requirements and simplified many technical aspects of the procedure 2 . An innovative approach has been the reassembly of protein fragments, which then directly report interactions. A suitable reporter protein is dissected at the genetic level, and the fragments are fused to bait and prey, which are then coexpressed in vivo. Bait and prey interaction brings the reporter fragments together, facilitating reassembly of the active reporter protein, giving a direct readout of the association. This method has been demonstrated for dihydrofolate reductase 3,4 , ubiquitin 5 and the green fluorescent protein6 (GFP) from Aequorea victoria. We recently described improvements to the original screen based on the reassembly of the GFP enhancedstability mutant sg100 in Escherichia coli 7 . Our system, presented in the protocol that follows, consists of two plasmid vectors for the independent expression of fusions with N- and C-terminal fragments of GFP, and allows for simple visual detection of protein-protein interactions with a K D as weak as 1 mM.

Journal ArticleDOI
TL;DR: In this paper, two oligonucleotides are hybridized adjacently to a DNA template, and if the target sequence is present, they are ligated together and detected using real-time PCR.
Abstract: We developed the LigAmp assay for sensitive detection and accurate quantification of viruses and cells with single-base mutations. In LigAmp, two oligonucleotides are hybridized adjacently to a DNA template. One oligonucleotide matches the target sequence and contains a probe sequence. If the target sequence is present, the oligonucleotides are ligated together and detected using real-time PCR. LigAmp detected KRAS2 mutant DNA at 0.01% in mixtures of different cell lines. KRAS2 mutations were also detected in pancreatic duct juice from patients with pancreatic cancer. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at approximately 0.1% in DNA amplified from plasma HIV-1. Detection in both systems is linear over a broad dynamic range. Preliminary evidence indicates that reactions can be multiplexed. This assay may find applications in the diagnosis of genetic disorders and the management of patients with cancer and infectious diseases.

Journal ArticleDOI
TL;DR: Here, strategies and techniques for the reconstitution of chromatin in vitro are described and a variety of methods by which a nonspecialist can prepare chromatin of high quality are described.
Abstract: In eukaryotes, chromatin is the natural form of DNA in the nucleus. For hundreds of millions of years, DNA-binding factors have evolved with chromatin. It is therefore more desirable to study the molecular mechanisms of DNA-directed processes with chromatin than with naked DNA templates. To this end, it is necessary to reconstitute DNA and histones into chromatin. Fortunately, there are a variety of methods by which a nonspecialist can prepare chromatin of high quality. Here, we describe strategies and techniques for the reconstitution of chromatin in vitro.

Journal ArticleDOI
TL;DR: A wheat germ cell-free platform for protein production that supports efficient NMR structural studies of eukaryotic proteins and offers advantages over cell-based methods is described.
Abstract: Structural proteomics requires robust, scalable methods. Here we describe a wheat germ cell-free platform for protein production that supports efficient NMR structural studies of eukaryotic proteins and offers advantages over cell-based methods. To illustrate this platform, we describe its application to a specific target (At3g01050.1) from Arabidopsis thaliana. After cloning the target gene into a specialized plasmid, we carry out a small-scale (50 μl) in vitro sequential transcription and translation trial to ascertain the level of protein production and solubility. Next, we prepare mRNA for use in a 4-ml semicontinuous cell-free translation reaction to incorporate 15N-labeled amino acids into a protein sample that we purify and test for suitability for NMR structural analysis. We then repeat the cell-free approach with 13C,15N-labeled amino acids to prepare a doubly labeled sample. The three-dimensional (3D) structure of At3g01050.1 shows that this protein is an unusual member of the β-grasp protein family.

Journal ArticleDOI
TL;DR: A new technique, based on a chain reaction of recognition and hybridization events between two sets of DNA hairpin molecules, offers an enzyme-free alternative for the rapid detection of specific DNA sequences.
Abstract: A new technique, based on a chain reaction of recognition and hybridization events between two sets of DNA hairpin molecules, offers an enzyme-free alternative for the rapid detection of specific DNA sequences.

Journal ArticleDOI
TL;DR: The results presented here show how a wide range of biotechnological applications can be developed starting from the insertion of selenocysteine into proteins.
Abstract: Selenium is essential to human life and occurs in selenoproteins as selenocysteine (Sec), the 21st amino acid. The selenium atom endows selenocysteine with unique biochemical properties, including a low pK(a) and a high reactivity with many electrophilic agents. Here we describe the introduction of selenocysteine into recombinant non-selenoproteins produced in Escherichia coli, as part of a small tetrapeptide motif at the C terminus. This selenocysteine-containing motif could subsequently be used as a protein tag for purification of the recombinant protein, selenolate-targeted labeling with fluorescent compounds or radiolabeling with either gamma-emitting (75)Se or short-lived positron emitters such as (11)C. The results presented here thus show how a wide range of biotechnological applications can be developed starting from the insertion of selenocysteine into proteins.

Journal ArticleDOI
TL;DR: The potent combination of this SNP linkage panel with the multiplexed assay system provides a previously unattainable level of performance for linkage studies, and the relative information content of this panel was higher than those of commonly used STR marker panels.
Abstract: We have developed a highly informative set of single-nucleotide polymorphism (SNP) assays designed for linkage mapping of the human genome. These assays were developed on a robust multiplexed assay system to provide a combination of very high accuracy and data completeness with high throughput for linkage studies. The linkage panel is comprised of approximately 4,700 SNPs with 0.39 average minor allele frequency and 624-kb average spacing. Based on almost 2 million genotypes, data quality was shown to be extremely high, with a 99.94% call rate, >99.99% reproducibility and 99.995% genotypes consistent with mendelian inheritance. We constructed a genetic map with an average 1.5-cM resolution using series of 28 CEPH pedigrees. The relative information content of this panel was higher than those of commonly used STR marker panels. The potent combination of this SNP linkage panel with the multiplexed assay system provides a previously unattainable level of performance for linkage studies.

Journal ArticleDOI
TL;DR: The ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development.
Abstract: It is becoming increasingly clear that alternative splicing enables the complex development and homeostasis of higher organisms. To gain a better understanding of how splicing contributes to regulatory pathways, we have developed an alternative splicing library approach for the identification of alternatively spliced exons and their flanking regions by alternative splicing sequence enriched tags sequencing. Here, we have applied our approach to mouse melan-c melanocyte and B16-F10Y melanoma cell lines, in which 5,401 genes were found to be alternatively spliced. These genes include those encoding important regulatory factors such as cyclin D2, Ilk, MAPK12, MAPK14, RAB4, melastatin 1 and previously unidentified splicing events for 436 genes. Real-time PCR further identified cell line-specific exons for Tmc6, Abi1, Sorbs1, Ndel1 and Snx16. Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development.

Journal ArticleDOI
TL;DR: The DNA marketplace is changing: the technology is maturing, whole human genome arrays, as well as those of model organisms, are beginning to make it onto the market, and researchers have more choices of commercial platform than ever before as mentioned in this paper.
Abstract: The DNA marketplace is changing: the technology is maturing, whole human genome arrays, as well as those of model organisms, are beginning to make it onto the market, and researchers have more choices of commercial platform than ever before. Diane Gershon takes a closer look at what's on offer.

Journal ArticleDOI
TL;DR: The ability to trigger RNA interference in mammalian cells provides unprecedented opportunities for probing the functions of genes, and many products and resources are there to help.
Abstract: The ability to trigger RNA interference in mammalian cells provides unprecedented opportunities for probing the functions of genes. Many products and resources are there to help. Laura Bonetta reports.

Journal ArticleDOI
TL;DR: New advancements in microarray technology offer a stepping-stone to the biological function of microRNAs and help scientists understand more fully the role of these molecules in human health.
Abstract: New advancements in microarray technology offer a stepping-stone to the biological function of microRNAs.

Journal ArticleDOI
TL;DR: A new scanning approach to data acquisition in tandem mass spectrometry promises to increase sensitivity and accuracy of proteomic analysis.
Abstract: A new scanning approach to data acquisition in tandem mass spectrometry promises to increase sensitivity and accuracy of proteomic analysis.