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December 31,2002 The Poly(A) Tail of mRNAs:Bodyguard in Eukaryotes, Scavenger in Bacteria
  In eukaryotes, poly(A) tails usually act as stabilizers of intact mRNAs, whereas in E. coli they serve to accelerate the destruction of fragments. The mechanisms underlying these contrasting effects of the same RNA modification are discussed.
December 30,2002 Single Protein Molecules Visualized and Tracked in the Interior of Eukaryotic Cells
  In the last few years the visualization and tracking of single fluorescent proteins, nanometer-sized RNP particles and viruses within the cellular interior was accomplished. This became feasible by use of photostable fluorescent dyes, extremely low probe concentrations, and wide-field fluorescence microscopic setups equipped with sensitive slow-scan or intensified CCD cameras. This paper reviews the results of the studies performed so far, discusses potential problems and gives an outlook on future applications.
December 29,2002 Clinical Trial Design for Target-Based Therapy
  The clinical development of target-based anticancer drugs will require fundamental changes to the traditional clinical trial design and end points that have been used for conventional cytotoxic drugs.As our understanding of the complex pathways and networks controlling cell signaling, proliferation, and cell death expands, we must learn how and when to use agents to target specific steps in malignant transformation and proliferation, and we must adapt clinical trial design to test the clinical utility of this promising new class of anticancer drugs.
December 28,2002 Short constrained peptides that inhibit HIV-1 entry
  Peptides corresponding to the C-terminal heptad repeat of HIV-1 gp41 (C-peptides) are potent inhibitors of HIV-1 entry into cells.Their mechanism of inhibition involves binding in a helical conformation to the central coiled coil of HIV-1 gp41 in a dominant–negative manner.In this study, the shortlinear peptide shows no significant inhibitory activity, but a constrained peptide (C14linkmid) inhibits cell– cell fusion at micromolar potency.
December 27,2002 Changes in gene expression in atherosclerotic plaques analyzed using DNA array
  A better understanding of atherogenesis at the level of gene expression could lead to the identification of new therapeutic strategies for vascular diseases. With DNA array technology, it is possible to identify multiple, simultaneous changes in gene expression in small tissue samples from atherosclerotic arteries.
December 26,2002 Finding important sites in protein sequences
  By using sequence information from an aligned protein family, a procedure is exhibited for finding sites that may be functionally or structurally critical to the protein. Features based on sequence conservation within subfamilies in the alignment and associations between sites are used to select the sites. The sites are subject to statistical evaluation correcting for phylogenetic bias in the collection of sequences.
December 25,2002 Decoding NF-κB Signaling
  The ability of NF-κB to regulate gene expression is controlled by chemical modifications such as the addition of phosphate groups, and by interactions with other proteins notably members of the IκB family (inhibitors of NF-κB). The binding of NF-κB to IκB helps to localize NF-κB in the cytoplasm. Upon activation of the NF-κB signaling pathway by tumor necrosis factor (TNF), IκB kinases target IκBs for degradation. This allows NF-κB to accumulate in the nucleus, where it binds to DNA, resulting in the expression of target genes.
December 24,2002 High throughput screening of human subtelomeric DNA for copy number changes using MAPH
  Subtelomeric regions of the human genome are gene rich, with a high level of sequence polymorphism. A number of clinical conditions, including learning disability, have been attributed to subtelomeric deletions or duplications, but screening for deletion in these regions using conventional cytogenetic methods and fluorescence in situ hybridisation (FISH) is laborious. Here we report that a new method, multiplex amplifiable probe hybridisation (MAPH), can be used to screen for copy number at subtelomeric regions.
December 23,2002 Emotion, Cognition, and Behavior
  The neurobiological substrates of human emotion are now attracting increasing interest within the neurosciences motivated, to a considerable extent, by advances in functional neuroimaging techniques. An emerging theme is the question of how emotion interacts with and in.uences other domains of cognition, in particular attention, memory, and reasoning. The psychological consequences and mechanisms underlying the emotional modulation of cognition provide the focus of this article.
December 19/20,2002 Nature 2002 Context & Science 2002 Breakthrough
December 18,2002 Immunologic and Genetic Factors in Type 1 Diabetes
  Over the last few years, evidence has accumulated that type 1 diabetes is an autoimmune disease or at least has a major autoimmune component. The purpose of this article on type 1 diabetes is to review some of this evidence with emphasis on the immunological and genetic factors involved in prediction of disease and destruction of beta cells.
December 17,2002 Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions
  For many decades, clinicians have been aware of the formation of insoluble protein aggregates in particular diseases.Here, the author offer an overview of the molecular mechanisms of both protein folding and misfolding, particularly in the formation of aggregates.
December 16,2002 PKB Binding Proteins: Getting in on the Akt
  Protein kinase B(PKB)has emerged as the focal point for many signal transduction pathways,regulating multiple cellular processes such as glucose metabolism,transcription,apoptosis,cell proliferation,angiogenesis,and cell motility.In this review,we discuss the implication of these data in understanding the mulitude of functions predicted for PKB in cells.
December 15,2002 Transcription Factors as Targets for Cancer Therapy
  A limited list of transcription factors are overactive in most human cancer cells, which makes them targets for the development of anticancer drugs. That they are the most direct and hopeful targets for treating cancer is proposed, and this is supported by the fact that there are many more human oncogenes in signalling pathways than there are oncogenic transcription factors. But how could specific transcription-factor activity be inhibited?
December 14,2002 Predicting three-dimensional genome structure from transcriptional activity
  We would like to be able to predict how genomes are folded in the cell from the primary DNA sequence. A model for the three-dimensional structure of all genomes is presented; it is based on the structure of the bacterial nucleoid, where RNA polymerases cluster and loop the DNA.
December 13,2002 New hope for Alzheimer disease vaccine
  Unfortunately,We are all born with the seeds of Alzheimer Disease. This is because we all continuously produce the neurotoxic amyloid β peptide, which is known to be the central player in AD pathology. In this issue,the author provide new hope for a spectacular and unexpected AD treatment strategy.
December 12,2002 New careers for antioxidants
  Chemopreventive antioxidants are usually considered in terms of radical scavenging, but Some research present evidence that selenium up-regulates DNA excision repair via P53. These preventive roles are complemented by other recent studies, indicating a corrective activity of antioxidants: inducing apoptosis selectively in transformed cells.
December 11,2002 Single Molecule Microscopy in Living Cells: Subtraction of Autofluorescence Based on Two Color Recording
  A significant limitation of ultra-sensitive microscopy on living cells is set by background signal arising from cellular autofluorescence.In this article, we present a new strategy to identify and eliminate signal arising from autofluorescence to circumvent this limitation.
December 10,2002 Functional proteomics: The goalposts are moving
  Proteomics offers physiologically enriched insights to protein function, and ongoing advances are enabling proteome analyses to proceed with increased depth and efficiency.Thousands more proteins of uncertain function will be unveiled in the near future. Consequently, the goalposts aremoving for proteomics both through increasing demand for high-value functional information and improving capacity to deliver.
December 09,2002 Correlated Mutation Analyses on Very Large Sequence Families
  Thanks to genome sequencing projects, large numbers of sequence families with more than a thousand members each are now available. Novel analytical techniques are needed to deal with this avalanche of sequence data.The combination of entropy,variability and correlation is a powerful tool to convert sequence data into useful information.
December 07,2002 Initial sequencing and comparative analysis of the mouse genome
  The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences.
December 06,2002 Drug Design Strategies for Targeting G-Protein-Coupled Receptors
  The increasing knowledge of GPCRs (biological target space) and their ligands (chemical ligand space) enables novel drug design strategies to accelerate the finding and optimization of GPCR leads.The linking of chemical and biological spaces will aid in generating lead-finding libraries, which are tailor-made for their respective receptor.
December 05,2002 Molecular control of lymphangiogenesis
  The lymphatic vasculature plays a critical role in the regulation of body fluid volume and immune function. Extensive research into the molecular mechanisms that control blood vessel growth has led to identification of molecules that also regulate development and growth of the lymphatic vessels. This is generating a great deal of interest in the molecular control of the lymphatics in the context of embryogenesis, lymphatic disorders and tumor metastasis.
December 04,2002 Chaperonins in disease: mechanisms, models, and treatments
  Chaperonins are oligomeric proteins that assist in the folding of nascent or denatured proteins.This review focuses on the current knowledge of the roles of Chaperonins 60 in the pathology of infectious and immune diseases, and discusses models for the actions of this molecule. Some potential therapeutic strategies will also be reviewed.
December 03,2002 Angiotensin-Converting Enzyme 2 - A New Cardiac Regulator
  Crackower and colleagues have now made it clear that the renin–angiotensin system is much more complicated than previous research suggested. Their experiments indicate that a recently identified enzyme, angiotensin-converting enzyme 2 (ACE2), has direct effects on cardiac function. This new chapter in the story of the renin–angiotensin system began in 2000, with the discovery of ACE2 and its identification as an enzyme similar to ACE.
December 02,2002 Biomechanical Signaling in Cardiac Hypertrophy
  Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.
December 01,2002 Apoptosis in myocardial ischaemia and infarction
  Recent studies indicate that, in addition to necrosis,apoptosis also plays a role in the process of tissue damage after myocardial infarction, which has pathological and therapeutic implications. This review article will discuss studies in which the role and mechanisms of apoptosis in myocardial infarction were analysed in vivo and in vitro in humans and in animals.