Biotechnology annual review最新文献

Sequencing of the human genome has opened the door to the most exciting new era for the holistic system description of human health. It is now possible to study the underlying mechanisms of human health in relation to diet and other environmental factors such as drugs and toxic pollutants. Technological advances make it feasible to envisage that in the future personalized drug treatment and dietary advice and possibly tailored food products can be used for promoting optimal health on an individual basis, in relation to genotype and lifestyle. Life-Science research has in the past very much focused on diseases and how to reestablish human health after illness. Today, the role of food and nutrition in human health and especially prevention of illness is gaining recognition. Diseases of modern civilization, such as diabetes, heart disease and cancer have been shown to be effected by dietary patterns. The risk of disease is often associated with genetic polymorphisms, but the effect is dependent on dietary intake and nutritional status. To understand the link between diet and health, nutritional-research must cover a broad range of areas, from the molecular level to whole body studies. Therefore it provides an excellent example of integrative biology requiring a systems biology approach. The current state and implications of systems biology in the understanding of human health are reviewed. It becomes clear that a complete mechanistic description of the human organism is not yet possible. However, recent advances in systems biology provide a trajectory for future research in order to improve health of individuals and populations. Disease prevention through personalized nutrition will become more important as the obvious avenue of research in life sciences and more focus will need to be put upon those natural ways of disease prevention. In particular, the new discipline of nutrigenomics, which investigates how nutrients interact with humans, taking predetermined genetic factors into account, will mediate new insights into human health that will finally have significant positive impact on our quality of life.

DNA or nucleic acid vaccines are being evaluated for efficacy against a range of parasitic diseases. Data from studies in rodent model systems have provided proof of principle that DNA vaccines are effective at inducing both humoral and T cell responses to a variety of candidate vaccine antigens. In particular, the induction of potent cellular responses often gives DNA vaccination an immunological advantage over subunit protein vaccination. Protection against parasite challenge has been demonstrated in a number of systems. However, application of parasite DNA vaccines in large animals including ruminants, primates and humans has been compromised by the relative lack of immune responsiveness to the vaccines, but the reasons for this hyporesponsiveness are not clear. Here, we review DNA vaccines against protozoan parasites, in particular vaccines for malaria, and the use of genomic approaches such as expression library immunization to generate novel vaccines. The application of DNA vaccines in ruminants is reviewed. We discuss some of the approaches being evaluated to improve responsiveness in large animals including the use of cytokines as adjuvants, targeting molecules as delivery ligands, electroporation and CpG oligonucleotides.

Papers reporting the results of clinical trials written by medical writers employed by the biotech and pharmaceutical industries have been criticized for possible bias in presentation and failure to adhere to authorship guidelines. Several groups have attempted to address the concerns of journal editors, academics, regulators, and the general public by issuing guidelines and policies for the preparation of such material.

The neurotrophin receptor p75(NTR) has long been known as a receptor for neurotrophins that promote survival and differentiation. Consistent with the role of neurotrophins, p75(NTR) is expressed during the developmental stages of the nervous system. However, p75(NTR) is re-expressed in various pathological conditions in the adult. We now know that p75(NTR) has the ability to elicit bi-directional signals, that result in the inhibition as well as the promotion of the neurite outgrowth. p75(NTR) is a key receptor for myelin-derived inhibitory cues that contribute to the lack of regeneration of the central nervous system.

Genetically Modified Organisms (GMOs) are a fact of modern agriculture and a major field of discussion in biotechnology. As science incessantly achieves innovative and unexpected breakthroughs, new medical, political, ethical and religious debates arise over the production and consumption of transgenic organisms. Despite no described medical condition being directly associated with a diet including approved GM crops in large exposed populations such as 300,000,000 Americans and a billion Chinese, public opinion seems to look at this new technology with either growing concern or even disapproval. It is generally recognized that a high level of vigilance is necessary and highly desirable, but it should also be considered that GMOs are a promising new challenge for the III Millennium societies, with remarkable impact on many disciplines and fields related to biotechnology. To acquire a basic knowledge on GMO production, GM-food consumption, GMO interaction with humans and environment is of primary importance for risk assessment. It requires availability of clear data and results from rigorous experiments. This review will focus on public health risks related with a GMO-containing diet. The objective is to summarize state of the art research, provide fundamental technical information, point out problems and perspectives, and make available essential tools for further research. Are GMO based industries and GMO-derived foods safe to human health? Can we consider both social, ethical and public health issues by means of a constant and effective monitoring of the food chain and by a clear, informative labeling of the products? Which are the so far characterized or alleged hazards of GMOs? And, most importantly, are these hazards actual, potential or merely contrived? Several questions remain open; answers and solutions belong to science, to politics and to the personal opinion of each social subject.

Zevalin (ibritumomab tiuxetan; IDEC Pharmaceuticals Corporation, San Diego, CA, USA) was approved by the United States Food and Drug Administration on February 19, 2002, following 9 years of clinical development. Six clinical studies supported the Zevalin Biologics License Application. The Zevalin regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), and for those with follicular NHL refractory to Rituxan (rituximab, MabThera; IDEC Pharmaceuticals Corporation, San Diego, CA and Genentech, South San Francisco, CA). In the year following FDA approval, approximately 1300 patients were treated in clinical trials or with the commercially available product.

Technological advances in miniaturization have found a niche in biology and signal the beginning of a new revolution. Most of the attention and advances have been made with DNA chips yet a lot of progress is being made in the use of other biomolecules and cells. A variety of reviews have covered only different aspects and technologies but leading to the shared terminology of "biochips." This review provides a basic introduction and an in-depth survey of the different technologies and applications involving the use of non-DNA molecules such as proteins and cells. The review focuses on microarrays and microfluidics, but also describes some cellular systems (studies involving patterning and sensor chips) and nanotechnology. The principles of each technology including parameters involved in biochip design and operation are outlined. A discussion of the different biological and biomedical applications illustrates the significance of biochips in biotechnology.

As the pharmaceutical and biotechnology industry enters the 21st century, the pressure on companies to maintain the level of productivity required for consistent year-on-year growth is increasing. Benchmarking has become a tool for obtaining the information needed to support continuous improvement and gain a competitive advantage. During the process of benchmarking, best practices can be identified while giving management the ability to improve on existing performance in an objective, well-informed manner. When used appropriately, benchmarking provides a new perspective on traditional methods while enabling companies to monitor their performance.

The molecular understanding of the initial interaction between a protein and, e.g., its substrate, a surface or an inhibitor is essentially an understanding of the role of electrostatics in intermolecular interactions. When studying biomolecules it is becoming increasingly evident that electrostatic interactions play a role in folding, conformational stability, enzyme activity and binding energies as well as in protein-protein interactions. In this chapter we present the key basic equations of electrostatics necessary to derive the equations used to model electrostatic interactions in biomolecules. We will also address how to solve such equations. This chapter is divided into two major sections. In the first part we will review the basic Maxwell equations of electrostatics equations called the Laws of Electrostatics that combined will result in the Poisson equation. This equation is the starting point of the Poisson-Boltzmann (PB) equation used to model electrostatic interactions in biomolecules. Concepts as electric field lines, equipotential surfaces, electrostatic energy and when can electrostatics be applied to study interactions between charges will be addressed. In the second part we will arrive at the electrostatic equations for dielectric media such as a protein. We will address the theory of dielectrics and arrive at the Poisson equation for dielectric media and at the PB equation, the main equation used to model electrostatic interactions in biomolecules (e.g., proteins, DNA). It will be shown how to compute forces and potentials in a dielectric medium. In order to solve the PB equation we will present the continuum electrostatic models, namely the Tanford-Kirkwood and the modified Tandord-Kirkwood methods. Priority will be given to finding the protonation state of proteins prior to solving the PB equation. We also present some methods that can be used to map and study the electrostatic potential distribution on the molecular surface of proteins. The combination of graphical visualisation of the electrostatic fields combined with knowledge about the location of key residues on the protein surface allows us to envision atomic models for enzyme function. Finally, we exemplify the use of some of these methods on the enzymes of the lipase family.

Many microbial peptide secondary metabolites possess important medicinal properties, of which the immunosuppressant cyclosporin A is an example. The enormous structural and functional diversity of these low-molecular weight peptides is attributable to their mode of biosynthesis. Peptide secondary metabolites are assembled non-ribosomally by multi-functional enzymes, termed non-ribosomal peptide synthetases. These systems consist of a multi-modular arrangement of the functional domains responsible for the catalysis of the partial reactions of peptide assembly. The extensive homology shared among NRPS systems allows for the generalisation of the knowledge garnered from studies of systems of diverse origins. In this review we shall focus the contemporary knowledge of non-ribosomal peptide biosynthesis on the structure and function of the cyclosporin biosynthetic system, with some emphasis on the re-direction of the biosynthetic potential of this system by combinatorial approaches.