Notable

M.B. Yaffe et al., "A motif-based profile scanning approach for genome-wide prediction of signaling pathways," Nature Biotechnology, 19:348-53, April 2001. F1000 Rating: Recommended "This paper describes a powerful fusion of experimental and computational methods to predict binding motifs in signal transduction pathways. Functional screens of degenerate peptide libraries are used to determine experimentally verified sequence preferences (motifs) that are the basis for a pattern matching approach to finding protein-protein binding sites, phosphorylation sites and other linear sequence motifs. The novelty of the paper and the utility of its method lies in the fusion of computational and experimental methods; the algorithm is available over the web." —Peter Sorger, Massachusetts Institute of Technology, Cambridge, Mass., US Neurology E. Yeh et al., "neuralized functions as an E3 ubiquitin ligase during Drosophila development," Current Biology, 11:1675-9, Oct. 30, 2001. E.C. Lai et al., "Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of Delta," Developmental Cell, 1:783-94, December 2001. G.A. Deblandre et al., "Xenopus neuralized is a ubiquitin ligase that interacts with XDelta1 and regulates Notch signaling," Developmental Cell, 1:795-806, December 2001. E. Pavlopoulos et al., "neuralized encodes a peripheral membrane protein involved in Delta signaling and endocytosis," Developmental Cell, 1:807-16, December 2001. F1000 Recommendation: Must Read "neuralized was identified as a 'neurogenic' gene almost two decades ago and yet its precise function in the Notch signaling pathway has remained elusive. Four new papers now each provide evidence that neuralized encodes a Ubiquitin ligase that promotes the internalization and degradation of Delta, the Notch ligand. Pavlopoulos et al., Lai et al., and Yeh et al. focus on neuralized in Drosophila melanogaster, whereas Deblandre et al. focus on the Xenopus laevis homologue. Together these papers reveal that the neuralized-encoded Ubiquitin ligase plays an evolutionarily conserved role in Notch signaling by targeting Delta for degradation and thus regulating the level of cell surface Delta." —Judith S. Eisen, University of Oregon, US Genomics & Genetics A.S. Weinmann et al., "Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis," Genes & Development, 16:235-44, Jan. 15, 2002. F1000 Recommendation: Must Read "Powerful and elegant new high throughput approach for identifying many direct targets for a transcription factor. To identify direct targets of the transcription factor, E2F4, the authors employ a clever combination of approaches: first, chromatin immunoprecipitation with E2F4 antibodies was used to enrich bound promoter sequences; in the second step, the immunoprecipitated DNA is used to screen a genomic library enriched in promoters; that is, the CpG island library prepared originally by Sally Cross and Adrian Bird. In addition to known or suspected targets, a further 68 unique new targets for E2F4 were identified. These not only include genes involved in replication, but also some involved in recombination and repair, pinpointing new functions for E2F4." —Nicholas Hastie, Western General Hospital, UK Structural Biology S. Hu et al., "Capillary sodium dodecyl sulfate-DALT electrophoresis of proteins in a single human cancer cell," Electrophoresis, 22:3677-82, October 2001. F1000 Recommendation: Exceptional "This exciting paper presents for the first time the size-based separation of proteins from a single human cancer cell. Application of capillary sodium dodlecyl sulfate (SDS) Dalton electrophoresis provided a one-dimensional separation capable of resolving about 30 protein components in single HT29 cells with molecular masses from 10 to 100 kDa. Laser-induced fluorescence (LIF) detection with this electrophoresis system produces a wide dynamic range that is important when analyzing protein samples with a wide range of protein expression. The next step is to apply two-dimensional single-cell analysis." —Deirdre Meldrum, University of Washington, US Developmental Biology W. Dean et al., "Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos," Proceedings of the National Academy of Sciences (PNAS), 98:13734-8, Nov. 20, 2001. F1000 Recommendation: Must Read "This is the first study to identify a possible biochemical cause to the varied and widespread abnormal gene expression observed during the development of nuclear transfer-produced embryos. Understanding the biochemical mechanisms that are responsible for abnormal gene expression patterns in cloned embryos may provide useful information that can be used to modify the protocols used for cloning animals and improve the efficiency of the technology." —Mark Westhusin, Texas A & M University, US Biochemistry M.C. Morris et al., "A peptide carrier for the delivery of biologically active proteins into mammalian cells," Nature Biotechnology, 19:1173-6, December 2001. F1000 Recommendation: Must Read "This paper describes de novo design of a 21-residue peptide designed to bind noncovalently to other proteins and transport these proteins into living cells with high efficiency. The system was tested using GFP and several different antibodies. While other peptides have been demonstrated as allowing efficient transport into cells when covalently attached to other proteins, none of these has allowed simple add and mix approaches with native proteins as this method promises." —Andrew Belmont, University of Illinois at Urbana-Champaign, US Signal Transduction J. Zhang et al., "Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering," PNAS, 98:14997-5002, Dec. 18, 2001. A.Y. Ting et al., "Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells," PNAS, 98:15003-8, Dec. 18, 2001. F1000 Recommendation: Must Read "In [these papers] Roger Tsien and colleagues have developed the means to assay protein kinase activity in living cells using FRET (fluorescence resonance energy transfer). This advance makes it possible to determine both when and where specific protein kinases are activated in living cells." —Jonathon Pines, University of Cambridge, UK

Notable

Neurology

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