In this issue, Bolivar et al. take advantage of the fact that knockouts are typically generated using ES embryonic stem cells derived from 129 inbred strain and are often backcrossed to C57Bl6 (B6)animals when archived.

The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for “Kupffer cellevading” or long-circulating particles.In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs.

Lipopeptaibols are members of a novel group of naturally occurring, short peptides with antimicrobial activity, characterized by a lipophilic acyl chain at the Nterminus, a high content of the turn/helix forming a-aminoisobutyric acid and a 1,2-amino alcohol at the C-terminus.

In this article, I review recent progress in bent DNA research in eukaryotic transcription, and summarize the history of bent DNA research and several subjects relevant to this theme.

Once the individual sub-populations are defined and analyzed, we can then try to reconstruct the full organism by interrelating them, eventually allowing for a full and dynamic view of the cell.

Using an orthotopic intracerebral model, we investigated whether systemic treatment with DC101, a monoclonal antibody against vascular endothelial growth factor receptor (VEGFR)-2, could inhibit angiogenesis and the growth of human glioblastoma cells in severe combined immunodeficient mice.

We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually) to the structure of the receptor with the Internal Coordinates Mechanics (ICM) program. Thirty ligand candidates were tested in vitro.

The addition of a 20-base GC-clamp to a DNA fragment enabled mutations to be detected by denaturing highperformance liquid chromatography (DHPLC) in the higher melting domain of the two-domain fragment DYS271.

This paper discusses circadian output in terms of the signaling mechanisms used by circadian pacemaker neurons.

Several studies are starting to show the power of DNA microarrays to identify interactions between animal hosts and their pathogens, and have revealed interesting correlations between host responses to different infectious agents.

A special section consisting of proceedings from the Society for Endocrinology Symposium, Imperial College, London, UK, 4 September 2000

While exercise provides substantial health benefits, intensive exercise is also associated with a unique set of risks for the female athlete. Hypothalamic dysfunction associated with strenuous exercise, and the resulting disturbance of GnRH pulsatility, can result in delayed menarche and disruption of menstrual cyclicity.

Testosterone increases maximal voluntary strength in a dose-dependent manner and thus might improve performance in power-lifting events. However, testosterone has not been shown to improve performance in endurance events.

This review examines some interesting ‘new’ histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition.

This paper looks at the way in which rules on doping have evolved in an attempt to set out the ethical standards that should apply and to discuss how some sportsmen and sportswomen have worked around the rules, challenging them to the extent that the anti-doping system itself is questioned.

The role of the physician of today is to regain our position of impartiality and objectivity within both the sporting and general community. Only then will we be able to pursue a harm minimisation strategy designed to convince the public that it is better to be the best you can be naturally.

A person’s androgen level and his or her behaviour are mutually dependent; sex hormones can affect behaviour, and behaviour can alter sex hormone levels. Behaviour influencing androgen levels, especially testosterone, has been reported for sexual behaviour, alcohol consumption, nutrition, physical exercise and psychic and psychosomatic stress.

Histone acetylation is an important regulatory mechanism that controls transcription and diverse nuclear processes.

This guidance document represents the agency’s current thinking on the development and regulation of somatic cell therapy and gene therapy products. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public.

Development of an efficient method for introducing a therapeutic gene into target cells in vivo is the key issue in treating genetic and acquired diseases by gene therapy. To this end, various nonviral vectors have been designed and developed, and some of them are in clinical trials.

Cytokines are important pathophysiologic and pathogenic factors in cardiovascular disorders, including viral myocarditis. We attempted to treat viral myocarditis with cytokine gene therapy by transferring an inhibitory cytokine, IL-1 receptor antagonist (IL-1ra) or viral IL-10 (vIL-10), by in vivo electroporation, a new method for gene transfer into muscle.

Understanding the regulation of gene expression requires an analysis of gene-specific transcription factors. This review highlights recent work that uses protein-DNA crosslinking, immunoprecipitation and DNA microarrays to determine the binding sites for specific transcription factors throughout the yeast genome.

This review focuses on the use of gene deletion studies to evaluate the many physiological actions of the RAS.

Genetic forms of human hypertension

With a primary focus on the regulation of ENaC activity, this review will consider the recent advances in understanding the genetic forms of human hypertension.

Proteome-wide sampling of function can be used to shed light on complex biological systems. Protein microarrays have now been used to investigate the substrate specificities of essentially all the protein kinases encoded by the yeast genome.

Metal ions are essential nutrients, yet they can also be toxic if they over-accumulate. Homeostatic mechanisms and detoxification systems therefore precisely control their intracellular levels and distribution. The tools of functional genomics are rapidly accelerating understanding in this field, particularly in the yeast Saccharomyces cerevisiae.

It has recently been shown that the detection of gene fusion events across genomes can be used for predicting functional associations of proteins, including physical interaction or complex formation. To obtain such predictions we have made an exhaustive search for gene fusion events within 24 available completely sequenced genomes.

Completion of whole genome sequences and the use of differential gene expression technology will hasten the discovery of the clock output pathways that control diverse rhythmic phenomena.

This review addresses the following areas in which progress has been particularly rapid over the past 5–10 years in elucidating the mechanisms underlying Ca sensing.

The focus of this review is the current and evolving understanding of the contribution of GRKs, ß-arrestins, and endocytosis to GPCR-specific patterns of desensitization and resensitization.

March