Gene repair and mutagenesis mediated by chimeric RNA–DNA oligonucleotides

The use of chimeric RNA–DNA oligonucleotides (chimeraplasts), in which a mutated allele that already exists in an affected individual can be corrected，has been observed that intracellular delivery of oligonucleotides is likely to be more efficient than that of plasmid DNA or viral vectors.

Magic bullets hit the target

After decades of disappointment, antibodies are finally emerging as viable — if expensive — drugs. Trisha Gura finds biotech start-ups and pharmaceutical giants rushing to claim a piece of the action.

Aquaporin water channels: atomic structure and molecular dynamics meet clinical medicine

Aquaporins are exquisitely selective for the transport of water — even repelling hydronium ions. The importance of the latter is emphasized by the normal function of mammalian renal tubules, which reabsorb 99% of the water from glomerular filtrate at the same time that acid is secreted by intercalated cells.

Corticosteroids and cardioprotection

New findings in mice suggest that corticosteroids mediate nitric oxide production in the endothelium, which in turn protects the heart against damage when deprived of oxygen. The mechanism explains, at least in part, the cardioprotective effects of these anti-inflammatory agents.

Signalling & Adhesion across the Internet

As this focus issue of Nature Cell Biology homes in on the increased crosstalk between signalling and adhesion, we felt it was time to highlight specific websites in this area.We draw attention to reviews from the Encylopedia of Life Sciences, homepages of various laboratories and educational tools.

Viral Oncolysis

As more is learned about the functions of viral gene products in controlling the mammalian cell cycle and in disabling cellular defense mechanisms, specific viral functions can be augmented or eliminated to enhance antineoplastic efficacy. In this article, general mechanisms by which oncolytic viruses achieve their antitumor efficacy and specificity are reviewed.

Cytotoxic T Lymphocytes: All Roads Lead To Death

Cytotoxic T lymphocytes (CTLs) provide potent defences against virus infection and intracellular pathogens. However, CTLs have a dark side — their lytic machinery can be directed against selftissues in autoimmune disorders, transplanted cells during graft rejection and host tissues to cause graft-versus-host disease, which is one of the most serious diseases related to CTL function.

IAP Proteins:Blocking the Road To the Death's Door

The ‘inhibitor of apoptosis’ (IAP) gene family encodes a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions. Here, we review the functional and structural properties of this fascinating group of proteins, and of several recently identified IAP-binding factors that regulate IAP function.

Cardiac sodium and calcium channels: a history of excitatory currents

Na and Ca channels are the basis of excitability, and in the heart they generate the rhythm, coordinating and controling cardiac contraction. Dysfunction of ion channels results in arrhythmias that underlie 20–25% of deaths in the developed world, and some arrhythmias result directly from gene defects in ion channels.

Teamed up for transcription

In bacterial genomes, functionally related genes are often clustered and controlled as a unit. Such ‘operons’ are not normally found in animals －so why are they so abundant in one class of worm?

Antibody Design by Man and Nature

Sixteen years ago, Lerner and Schultz independently reported that probing the natural repertoire of antibodies with transition state analogs enables new catalysts to be identified on the evolutionary time scale of the immune response (2 to 3 weeks), and they demonstrated that the antibody molecule can mediate chemistry more complex than simple binding.

Germline Stem Cell Transplantation and Transgenesis

The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals.

Suppressors of Cytokine Signalling (SOCS) in the Immune System

The suppressors of cytokine signalling (SOCS) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine responses, including those that regulate the immune system. The SOCS proteins seem to regulate signal transduction by combining direct inhibitory interactions with cytokine receptors and signalling proteins with a generic mechanism of targeting associated proteins for degradation.

Cellular Roles of DNA Topoisomerases: A Molecular Perspective

Extensive biochemical and structural studies over the past three decades have provided molecular models of how the various subfamilies of DNA topoisomerase manipulate DNA. In this review, the cellular roles of these enzymes are examined from a molecular point of view.

Targeting Death and Decoy Receptors of the Tumornecrosis Factor Superfamily

Death receptors — members of the tumour-necrosis factor receptor (TNFR) superfamily — signal apoptosis independently of p53. Decoy receptors, by contrast, are a nonsignalling subset of the TNFR superfamily that attenuate death-receptor function. Agents that are designed to activate death receptors (or block decoy receptors) might therefore be used to kill tumour cells that are resistant to conventional cancer therapies.

Two ACEs and a heart

Cardiovascular diseases are some of the biggest killers in the developedworld. The discovery of a new enzyme that affects cardiac function might provide fresh insight into heart disease.

The Subcellular Destinations of APC Protein

Adenomatous polyposis coli (APC) is an important tumour suppressor in the human colon, and is conserved in various organisms. Its best understood function is the destabilization of β-catenin, a key effector of the Wnt signalling pathway.

The 3′–5′ Exonucleases

Over the past few years, several new 3′–5′ exonucleases have been identified. Here, we look at not only the newly discovered enzymes,but also at the roles of other 3′–5′ exonucleases in the quality control of DNA synthesis,where they act as proofreading exonucleases for DNA polymerases during DNA replication,repair and recombination.

The rise of computational biology

The year 2001 saw a remarkable burst of interest in biological simulation, with several international meetings on the subject, and the inclusion, by journals, of web site references from which published models can be downloaded. So, why has all this happened so suddenly?

The Fundamental Role of Epigenetic Events in Cancer

The recent explosion in our knowledge of how chromatin organization modulates gene transcription has further highlighted the importance of epigenetic mechanisms in the initiation and progression of human cancer.Here we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.

With a little help from your friends: cells don’t die alone

A series of results now challenge the traditional view of phagocytes as simply scavengers, ‘cleaning up’ after apoptosis to prevent inflammatory responses, and hence tissue damage. Instead, they suggest that phagocytes are active in the induction and/or execution of apoptosis in target cells.

Modulating T-cell Immunity to Tumours: New Strategies For Monitoring T-cell Response

Novel immunological tools can be used not only to quantify the antigen-specific response, but also to analyse the phenotype and function of individual effector cells. Application of these tools to dissect the antitumour responses will lead to a greater understanding of the principles that underlie successful immunotherapeutic strategies and potential mechanisms of tumour immune evasion.

New directions in vaccine research

There is an urgent need to maintain and improve vaccinations against circulating agents, to develop vaccines against emerging diseases, and to hone our ability to respond to novel biological threats, whether of natural or unnatural origins.

Protein-interaction networks: from experiments to analysis

Here, we review recent techniques for the construction and prediction of large-scale protein-interaction networks, with a particular emphasis on computational processing steps and comparative assessment of the reliability and completeness of the various approaches.

Germline Stem Cell Transplantation and Transgenesis

The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals.

Diabetes and Atherosclerosis - Epidemiology, Pathophysiology, and Management

This review of Diabetes and Atherosclerosis considers 3 main topics: epidemiology of atherosclerosis in diabetes, the pathophysiology of the diabetic blood vessel,medical and invasive treatment for atherosclerosis complications for diabetes.

Brain mechanisms of pain affect and pain modulation

Recent animal studies reveal ascending nociceptive and descending modulatory pathways that may contribute to the affective–motivational aspects of pain and play a critical role in the modulation of pain.

The T cell as a bridge between innate and adaptive immune systems: Implications for the kidney

recent data from experimental models in kidney as well as liver, intestine, brain and heart implicate T cells as important mediators of ischemia reperfusion injury. These data reveal new insights into the pathogenesis of ischemic acute renal failure and demonstrates that the functional capacity of T cells spreads beyond adaptive immunity into the realm of the innate immune response.

Advances in human artificial chromosome technology

Recent reports show that Human Artificial Chromosomes are useful gene transfer vectorsin expression studies and important tools for determining human chromosome function.HACs have been used to complement gene deficiencies in human cultured cells by transfer of large genomic loci also containing the regulatory elements for appropriate expression.

Genotype to phenotype: associations, errors and complexity

There is a lot of ground between genotype and phenotype, but most of it was touched on at some point during The Keystone Symposium on Genotype to Phenotype: Focus on Disease was held in Santa Fe, New Mexico, USA, from 19 to 24 February 2002.

A new source for cardiovascular tissue engineering: human bone marrow stromal cells

Marrow stromal cells (MSC) demonstrate the ability to differentiate into multiple mesenchymal cell lineages and would offer an alternative cell source for tissue engineering involving a less invasive harvesting technique.