Nonhuman primate transgenesis: progress and prospects

The nonhuman primate is used extensively in biomedical research owing to its close similarities to human physiology and human disease pathophysiology. Recently, several groups have initiated efforts to genetically manipulate nonhuman primates to address complex questions concerning primate-specific development and physiological adaptation. Primates pose unique challenges to transgenesis and, although this field is still in its infancy, the potential for obtaining new insights into primate physiology and gene function is unprecedented. This review focuses on the methods and potential applications of genetically altered nonhuman primates in biomedical research.     

Mesenchymal stem cells: progress toward promise

Despite having access to embryonic stem cells, many laboratories choose to study adult stem cells, not because of philosophical reasons but because of the practical aspects and day-to-day progress necessary for developing cellular therapeutics. There is certainly the ethical desire and responsibility to provide patients with therapies where few options exist. Multipotential cells have been isolated from adult tissues in many laboratories, characterized and their multipotentiality examined. Mesenchymal stem cells (MSC) can be isolated from several tissues but easily accessible BM seems to be the most common source. These adult stem cells may not be as 'powerful' or diverse as embryonic stem cells may one day become, but at present they offer many advantages for developing cellular therapeutics: ease of isolation, expansion potential, stable phenotype, shippability, and compatibility with different delivery methods and formulations. Their potential use as cellular therapeutics has prompted the investigation of interactions of allogeneic MSC with the immune response. The great importance of cardiovascular medicine has demanded that MSC also be tested in this discipline. We believe MSC continue to provide a substantial scientific and therapeutic opportunity, and have reviewed some of the recent developments in the field.     

Molecular evolution study in China: progress and future promise

China has a large land area with highly diverse topography, climate and vegetation, and animal resources and is ranked eighth in the world and first in the Northern Hemisphere on richness of biodiversity. Even though little work on molecular evolution had been reported a decade ago, studies on both the evolution of macromolecules and the molecular phylogeny have become active in China in recent years. This review highlights some of the interesting and important developments in molecular evolution study in China. Chinese scientists have made significant contribution on the methods inferring phylogeny and biogeography of animals and plants in East Asia using molecular data. Studies on population and conservation genetics of animals and plants, such as Golden monkey and Chinese sturgeon, provided useful information for conserving the endangered species. East and South Asia has been demonstrated to be one of the centres of domestication. Origin and evolution of genes and gene families have been explored, which shed new insight on the genetic mechanism of adaptation. In the genomic era, Chinese researchers also made a transition from single-gene to a genomic investigation approach. Considering the fact that amazing progress has been made in the past few years, and more and more talented young scientists are entering field, the future of molecular evolution study in China holds much promise.     

Dynamic imaging of the immune system: progress, pitfalls and promise

Both innate and adaptive immunity are dependent on the migratory capacity of myeloid and lymphoid cells. Effector cells of the innate immune system rapidly enter infected tissues, whereas sentinel dendritic cells in these sites mobilize and transit to lymph nodes. In these and other secondary lymphoid tissues, interactions among various cell types promote adaptive humoral and cell-mediated immune responses. Recent advances in light microscopy have allowed direct visualization of these events in living animals and tissue explants, which allows a new appreciation of the dynamics of immune-cell behaviour. In this article, we review the basic techniques and the tools used for in situ imaging, as well as the limitations and potential artefacts of these methods.     

Studies of threespine stickleback developmental evolution: progress and promise

A promising route for understanding the origin and diversification of organismal form is through studies at the intersection of evolution and development (evo-devo). While much has been learned over the last two decades concerning macroevolutionary patterns of developmental change, a fundamental gap in the evo-devo synthesis is the integration of mathematical population and quantitative genetics with studies of how genetic variation in natural populations affects developmental processes. This micro-evo-devo synthesis requires model organisms with which to ask empirical questions. Threespine stickleback fish (Gasterosteus aculeatus), long a model for studying behavior, ecology and evolution, is emerging as a prominent model micro-evo-devo system. Research on stickleback over the last decade has begun to address the genetic basis of morphological variation and sex determination, and much of this work has important implications for understanding the genetics of speciation. In this paper we review recent threespine stickleback micro-evo-devo results, and outline the resources that have been developed to make this synthesis possible. The prospects for stickleback research to speed the micro-(and macro-) evo-devo syntheses are great, and this workhorse model system is well situated to continue contributing to our understanding of the generation of diversity in organismal form for many more decades.     

Genetic susceptibility to coronary artery disease: from promise to progress

Family history is an important independent risk factor for coronary artery disease (CAD), and identification of susceptibility genes for this common, complex disease is a vital goal. Although there has been considerable success in identifying genetic variants that influence well-known risk factors, such as cholesterol levels, progress in unearthing novel CAD genes has been slow. However, advances are now being made through the application of large-scale, systematic, genome-wide approaches. Recent findings particularly highlight the link between CAD and inflammation and immunity, and highlight the biological insights to be gained from a genetic understanding of the world's biggest killer.     

Cardiovascular genomics: recent progress, current challenges, future promise

A report from the second Annual Cardiovascular Genomics Meeting, Sponsored by Cambridge Healthtech, Inc., Miami, January 31-February 1, 2000.     

Tomatoes,lycopene, and prostate cancer: progress and promise

Prostate cancer has emerged as a major public health problem in nations that have an affluent culture with an aging population. The search for etiologic risk factors and an emphasis on the development of chemopreventive agents has gained momentum over the last decade. Among the landmark epidemiologic findings during this period has been the association between the consumption of tomato products and a lower risk of prostate cancer. The traditional reductionist scientific approach has led many investigators to propose that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Thus, many laboratory and clinical studies are now underway with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate and other malignancies. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound could possibly reduce prostate cancer risk. In contrast to the pharmacologic approach with pure lycopene, many nutritional scientists direct their attention upon the diverse array of tomato products as a complex mixture of biologically active phytochemicals that together may have anti-prostate cancer benefits beyond those of any single constituent. These contrasting approaches will continue to be explored in clinical, laboratory and epidemiologic studies in the near future, providing hope that the next generation will benefit from this knowledge and experience a lower risk of prostate cancer.     

Recent progress towards understanding the synaptic ribbon

Neurons of the visual, auditory and vestibular systems that signal through graded changes in membrane potential rely upon synaptic ribbons for the exquisite control of neurotransmitter release. Although clearly important for tonic neurotransmission, the precise role of synaptic ribbons remains elusive. In recent years, several genetic, biochemical, electrophysiological and optical approaches have begun to shed light on the functions of these enigmatic organelles.     

A cardiovascular EST repertoire: progress and promise for understanding cardiovascular disease

The application of expressed sequence tag (EST) technology has proven to be an effective tool for gene discovery and the generation of gene expression profiles. The generation of an EST resource for the cardiovascular system has revealed significant insights into the changes in gene expression that guide heart development and disease. Furthermore, an important genetic resource has been developed for cardiovascular biology that is valuable for data mining and disease gene discovery.     

Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise

Green tea's active ingredient, epigallocatechin 3-gallate (EGCG), has gained significant attention among scientists and has been one of the leading plant-derived molecules studied for its potential health benefits. In the present review I summarize the findings from some of the most significant preclinical studies with EGCG in arthritic diseases. The review also addresses the limitations of the dose, pharmacokinetics, and bioavailability of EGCG in experimental animals and findings related to the EGCG-drug interaction. Although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases.     

Genetic progress towards the molecular basis of autoimmunity

The past few years have seen the identification of PTPN22 and the confirmation of CTLA-4 as common autoimmune disease genes. Together with MHC and INS, these developments have increased the collection of confirmed susceptibility loci for autoimmunity. In this article, the latest developments related to these genes and to other recently studied candidate autoimmune susceptibility loci (PDCD1, FCRL3, SUMO4, CD25, PADI4 and SLC22A4) are reviewed. Collectively, these genes strongly indicate that aberrant inhibition of the signalling cascade initiated by activation of the T-cell receptor is involved in the aetiology of autoimmune disease. However, much basic genetic, molecular and clinical research is still needed to help us fully understand the underlying mechanisms of autoimmunity and how these translate into prognosis or therapy.     

Analysis of N-linked oligosaccharides: progress towards the characterisation of glycoprotein-linked carbohydrates

The covalent attachment of carbohydrate to proteins is a very common co- or post-translational event in the biosynthesis of glycoproteins. The type and heterogeneity of these oligosaccharides can affect a range of physico-chemical and biological properties of a glycoprotein. Thus the development of sensitive, reliable and robust analytical methods for carbohydrate analysis is important in the pharmaceutical industry, especially in the recombinant production of experimental and therapeutic glycoproteins. In this report we have reviewed methodology for the in-gel enzymatic release of N-linked oligosaccharides from glycoproteins separated by electrophoresis. These oligosaccharides are derivatised by reductive amination using 3-acetamido-6-aminoacridine (AA-Ac), a novel, highly fluorescent probe. A major advantage of this technique is that glycan derivatives are amenable to analysis by an array of chromatographic and mass spectrometric methods, allowing the resolution and characterisation of a wide variety of glycan structures. It is hoped that in due course the methodology described will be applied to proteomics studies, especially in identifying the role of carbohydrate in protein function and disease.     

Unraveling the enigma: progress towards understanding the coronin family of actin regulators

Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for 20 years, substantial progress has been made in the past 5 years towards their understanding. In this review, we examine this progress, place it into the context of what was already known, and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading-edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge.     

Innovations: applications of insect transgenesis

The recent establishment of broadly applicable genetic transformation systems will allow the analysis of gene function in diverse insect species. This will increase our understanding of developmental and evolutionary biology. Furthermore, insect transgenesis will provide new strategies for insect pest management and methods to impair the transmission of pathogens by human disease vectors. However, these powerful techniques must be applied with great care to avoid harm to our environment.     

Animal transgenesis: state of the art and applications

There is a constant expectation for fast improvement of livestock production and human health care products. The advent of DNA recombinant technology and the possibility of gene transfer between organisms of distinct species, or even distinct phylogenic kingdoms, has opened a wide range of possibilities. Nowadays we can produce human insulin in bacteria or human coagulation factors in cattle milk. The recent advances in gene transfer, animal cloning, and assisted reproductive techniques have partly fulfilled the expectation in the field of livestock transgenesis. This paper reviews the recent advances and applications of transgenesis in livestock and their derivative products. At first, the state of art and the techniques that enhance the efficiency of livestock transgenesis are presented. The consequent reduction in the cost and time necessary to reach a final product has enabled the multiplication of transgenic prototypes around the world. We also analyze here some emerging applications of livestock transgenesis in the field of pharmacology, meat and dairy industry, xenotransplantation, and human disease modeling. Finally, some bioethical and commercial concerns raised by the transgenesis applications are discussed.     

Sperm cell mediated transgenesis: A review

Abstract

Transgenesis would be greatly streamlined if sperm cells could be used as transgene vectors. Attempts to ‘force’ sperm cells to take up transgenes may be more worthy of further study than ‘autouptake’ attempts. However, thorough proof of its effectiveness will be required if sperm cell‐mediated gene transfer is to be accepted, given the evolutionary implications associated with the possibility of sperm cells being able to transfer exogenous DNA.